They list the following vegetables as good sources of vitamin C:. Another review suggests that consuming fewer than five servings of fruit or vegetables per day increases the risk of hip fractures. Calcium is the primary nutrient for bone health.

As the bones break down and grow each day, it is essential to get enough calcium. The best way to absorb calcium is to consume foods containing calcium every day.

Getting calcium through the diet is best unless a doctor advises otherwise. Vitamin K2 is essential to bone health. It reduces calcium loss and helps minerals bind to the bones. Vitamin D helps the body absorb calcium. People with vitamin D deficiencies have a higher risk of losing bone mass.

A person can absorb vitamin D through moderate sun exposure. Without sufficient vitamin D, a person has a higher risk of developing bone disease, such as osteoporosis or osteopenia. A moderate weight is essential for bone density. People with underweight have a higher risk of developing bone disease.

Overweight and obesity put additional stress on the bones. Doctors recommend people avoid rapid weight loss and cycling between gaining and losing weight.

As a person loses weight, they can lose bone density, but gaining back the weight will not restore bone density. This reduction in density can lead to weaker bones. Super low calorie diets can lead to health problems, including bone density loss. Before restricting calories, discuss calorie needs with a qualified healthcare professional, such as a primary care doctor or registered dietitian, to determine a safe target number of calories to consume.

Protein plays an essential role in bone health and density. A cross-sectional study examined bone mass and dietary protein intake in 1, older adults. Researchers associated higher bone mass density with higher intakes of total and animal protein.

However, they associated lower bone mass density with plant protein intake. Researchers call for further studies, particularly into how a plant-based diet may affect bone health and density.

Research suggests that omega-3 fatty acids play a role in maintaining bone density and overall bone health. Like calcium, magnesium and zinc are minerals that support bone health and density.

Magnesium helps activate vitamin D so it can promote calcium absorption. Zinc exists in the bones. It promotes bone growth and helps prevent the bones from breaking down.

Many people associate smoking with lung cancer and breathing issues, but smoking can also increase the risk of conditions such as osteoporosis and bone fractures.

To support healthy bone density, a person can avoid or quit smoking , especially during their teens and young adulthood.

However, long-term heavy drinking can lead to poor calcium absorption, a decrease in bone density, and the development of osteoporosis later in life.

Moderate alcohol consumption is considered two drinks or fewer per day for males and one drink or fewer per day for females. Although the best time to influence peak bone mass and build bone density is from childhood to early adulthood, people can take steps at every age to improve bone health and reduce bone density loss.

Strength training exercises can increase bone density in specific parts of the body in the short and medium term. However, people need to continue exercising regularly to maintain bone health in the long term. Bone mass peaks in young adults, usually between 25 and 30 years old.

After 40 years old, people start to lose bone mass. However, they can reduce this loss by exercising regularly and eating a balanced, nutrient-dense diet.

Dietary intake of calcium and vitamin D is vital for bone health. Foods that contain these nutrients include:.

To support healthy bone density, it is important to consume plenty of calcium, vitamin D, protein, and vegetables. It is also important to avoid smoking and heavy alcohol use.

Taking these steps can help support bone density throughout adulthood. Read this article in Spanish. A Z-score compares a person's bone density with the average bone density of those of the same age, sex, and body size.

A low score can indicate…. Bone density tests help a doctor see how strong a person's bones are. Learn more, including what happens during a bone density test, in this article. Femoral neck osteoporosis refers to a low bone density at the top of the thigh bone, and it puts people at a high risk of fractures.

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These factors increase the fracture risk of obese elderly at certain anatomical sites and significantly contribute to the disability and financial toll of musculoskeletal diseases among elderly [ 5, 6 ]. Intentional weight loss achieved through lifestyle modifications in obese elderly persons is a controversially discussed subject.

Intentional weight loss improves physical function as well as metabolic and cardiovascular outcomes in obese elderly [ 3, 7 ]. Conversely, observational studies suggest an association between weight loss whether intentional or unintentional and higher mortality rates, although this negative effect is not supported by randomized controlled weight loss trials [ 3, 7 ].

Importantly, weight loss is potentially harmful for musculoskeletal health. The evidence in this age group is, however, limited and conclusions are frequently extrapolated from studies in younger individuals [ 8, 9 ]. We further address mechanical and non-mechanical factors that link weight loss to bone loss in this age group.

Finally, given the research avenues arising from matching animal models with clinical scenarios, we identify current or potentially usable age-related animal models for osteoporosis and obesity.

We believe that this review will guide the design of future research to explore the pathophysiology and management of skeletal changes attributed to weight reduction in obese elderly.

Previous prospective epidemiological studies have shown that weight loss in older adults is associated with a greater loss of BMD at weight-bearing skeletal sites such as the hip or the lumbar spine [ ]. The impact of weight loss on non-weight-bearing skeletal sites such as the radius or the forearm is not as clear [ 11, 19 ].

These sites are less affected by mechanical unloading due to weight loss. Importantly, the associations between weight loss and BMD loss are consistent across BMI categories in older men [ 18 ] and women [ 12, 19 ]. The same is true for intentional or unintentional weight loss [ 12, 18 ].

Several epidemiological studies indicate negative associations between weight loss and bone microarchitecture and strength in older individuals [ ]. Men with weight loss had lower bone strength, total body BMD, cortical BMD and thickness assessed by high-resolution peripheral quantitative computed tomography at the distal radius and tibia compared to those with stable weight over a 7-year follow-up [ 24 ].

These findings remained unchanged after adjustments for age and BMI [ 24 ]. In a retrospective analysis, recent 6 years and long-term 40 years weight loss were associated with a lower cortical BMD and deterioration of the cortical microarchitecture at the tibia [ 22 ].

Interestingly, total bone area was increased in weight losers compared to weight gainers, with the between-group differences being more pronounced in long-term weight loss [ 22 ].

Periosteal apposition may represent a compensatory response to maintain bone strength, which, eventually, declines with weight loss [ 22 ].

Taken together, these studies largely support weight-loss-related changes in the microstructure of cortical bone and the loss of bone strength.

Trabecular microarchitecture appears to be affected by weight loss in the elderly, although current evidence on this aspect is less consistent. Weight loss was not associated with altered trabecular parameters in older men followed up for 7 years [ 24 ]. Reductions in trabecular BMD and alterations in trabecular microarchitecture have also been associated with long-term over 40 years weight loss [ 22 ].

These conflicting findings may be at least partially explained by differences in study design, follow-up period, cohort characteristics, and bone assessment methods. Large epidemiological studies have consistently shown associations between weight loss and a greater risk of fractures in the central part of the body e.

Data concerning older men not only are scarce but also suggest that weight loss is a risk factor for hip fracture [ 30 ].

A limitation of many of these studies is their failure to distinguish between intentional and unintentional weight loss. Unintentional weight loss is frequently associated with comorbidities and poor health, which may affect bone loss, fall patterns, and the risk of fractures in independent ways.

Conversely, intentional weight loss may involve practices such as exercise , which have some bone-sparing effects even among older adults [ 31 ]. Of the few studies addressing intentional weight loss [ 12, 28 ], one showed that both intentional and unintentional weight loss were associated with an approximately doubled risk of hip fracture in older women [ 12 ].

Another study revealed different fracture risks by anatomical site, depending on the intention to lose weight [ 28 ]. An elevated fracture risk has been associated with both short-term a few years [ 29 ] and long-term a few decades weight loss [ 25, 26 ].

This raises concerns about the impact of weight loss in old age, as well as during early and mid-adulthood. Weight changes have been commonly assessed as the difference between baseline and a single follow-up. However, during this period, individuals may experience repeated episodes of weight loss and subsequent weight gain or weight cycling.

These weight variations have been associated with negative effects on skeletal health in younger individuals [ 32, 33 ]. The few available studies in the elderly suggest that weight cycling increases their risk of fracture [ 34, 35 ].

These findings were closely related to the extent of variability in weight [ 34 ] and the number of weight cycling episodes between the ages of 25 and 50 years [ 35 ]. This section addresses the findings of interventional studies focused on lifestyle changes resulting in weight loss.

Interventional studies that explored the effects of weight loss through lifestyle modification on skeletal health outcomes in obese older adults. A month randomized controlled trial RCT comprised obese and frail older adults [ 36, 37 ]. They also experienced synchronous increases in osteocalcin bone formation and C-telopeptide of type I collagen or CTX bone resorption levels and decreases in hip BMD at 6 and 12 months compared to baseline [ 36, 37 ].

Hip structure analysis based on DXA-acquired BMD images revealed decreases in cross-sectional area and cortical thickness and increases in buckling ratio at the hip in the weight loss group at 12 months [ 31 ]. Collectively, these changes suggest bone degradation secondary to weight loss achieved by diet rather than a normalization of BMD relative to weight loss.

Importantly, the prescribed diet in this arm was characterized by a moderate energy deficit, while providing sufficient quantities of protein, calcium, and vitamin D [ 36 ].

These data suggest that even well-planned weight loss diets may not suffice to maintain skeletal health in the elderly. In contrast to hip BMD, lumbar spine and total body BMD appear to be unaffected by weight loss in this age group [ 36, 38, 39 ].

It is uncertain whether these findings were actual treatment effects or were flawed by measurement error. In the presence of obesity or during aging, calcifications originating from atherosclerotic lesions within the aorta or osteophytes may artificially mask bone reduction [ 9 ].

Nevertheless, these findings in obese elderly individuals are consistent with those of a meta-analysis of diet-induced weight loss studies [ 9 ]. The majority of the studies was conducted in younger adults and indicated similar skeletal responses to this weight loss approach with age [ 9 ].

Several studies have addressed the combined effects of exercise and caloric restriction on bone health [ 31, 36, 37, ]. In an earlier investigation, older women were offered counseling on diet and physical activity to induce weight loss [ 40 ]. Weight loss was a significant predictor of total body BMD, but not spine or hip BMD [ 40 ].

Interestingly, total body and hip BMD declined not only in the weight loss group but also in controls [ 40 ]. The study was not informative about the individual contributions of diet and exercise to weight loss and bone loss, and the participants did not follow a specific exercise program under supervision.

However, the data revealed the importance of including a control group with no weight loss, given that aging itself is associated with bone deterioration.

Haywood et al. Total body BMD was assessed by DXA as the sole skeletal health outcome at baseline and at 12 weeks follow-up.

The exercise plus very low-calorie diet group experienced greatest weight loss, accompanied by a small, but significant, reduction in total body BMD; no significant changes were observed in the other study arms [ 41 ].

Additional evidence on the effects of exercise added to weight loss were obtained from 2 further RCTs [ 36, 42 ]. In a first small cohort, the effects of a lifestyle intervention consisting of caloric restriction, calcium and vitamin D supplementation, and a combined aerobic and resistance training program were compared to no treatment.

The reductions in hip BMD were correlated with elevations in CTX ~fold and osteocalcin ~fold , indicating that the bone loss was mediated by an uncoupling of bone formation from resorption, favoring the latter.

BMD was maintained at the lumbar spine, which was suggested to be a bone-protective effect of exercise [ 42 ]. In a subsequent study by the same group, obese and frail older adults were randomized to no treatment, caloric restriction, exercise without weight loss, or caloric restriction combined with exercise [ 36 ].

The group that was randomized to caloric restriction combined with exercise experienced less hip bone loss than those who followed caloric restriction alone. Unlike the group subjected to caloric restriction, the combined exercise and caloric restriction group did not experience changes in bone turnover markers or bone structure cross-sectional area, cortical thickness, and volumetric BMD at the 1-year follow-up, although trabecular microarchitecture was not assessed [ 31, 37 ].

These results suggest that a combination of resistance and aerobic training added to a weight loss program can lessen the bone loss induced by weight reduction. More recent studies have focused on the exercise type that would be most beneficial for weight loss in obese older individuals [ 39, 44, 45 ].

In a 6-month RCT, Villareal et al. Beaver et al. Volumetric BMD and cortical thickness estimates at the hip and femoral neck assessed by CT scans were significantly declined in all groups, with the most pronounced changes seen in the diet-induced weight loss group [ 39 ].

In a pooled analysis of the 3 treatment groups, bone strength estimated with subject-specific finite-element models based on CT-derived parameters was reduced by 6.

Although this sub-analysis was not powered to detect between-group differences, finite-element models can be used to provide better predictions of bone strength and fracture risk in future weight loss interventions.

Taken together, these findings suggest that resistance training exerts bone-sparing effects in weight loss interventions which, however, may not always be captured by BMD assessed by DXA. The discrepant results between the studies may be explained by differences in exercise regimens and the baseline characteristics of the study populations.

Frail and obese individuals are possibly more responsive to the effects of exercise training. In a month follow-up of a 1-year weight loss intervention [ 36 ], Waters et al. Similarly, Beavers et al. Both studies support unfavorable changes in skeletal health due to long-term weight loss.

These studies were subject to reporting bias because they were based on subsets of the initial groups and did not include individuals with no weight loss. Nevertheless, they underpin the need for follow-up studies to evaluate weight management approaches in the elderly and characterize skeletal health outcomes associated with sustained weight loss or multiple weight loss attempts.

We investigated the available evidence on the mechanistic links between weight loss and bone loss in obese older individuals or relevant aged animal models.

We also discuss speculative contributors to bone loss during weight loss which, however, have been poorly investigated in obese elderly under weight loss and require further elucidation. The effects of weight loss on skeletal outcomes during aging are likely multifactorial and may be mediated by i mechanical unloading, ii changes in body composition, iii restriction of important nutrients for bone metabolism and health, iv alterations in gonadal hormones and endocrine factors that co-regulate energy and bone metabolism, and v changes in inflammatory factors.

These factors appear to affect the balance between bone formation and resorption. This, in turn, mediates changes in the macro- and microstructure of bone as well as bone material, which determine bone strength and, ultimately, the risk of fractures Fig. They also influence other geriatric outcomes such as physical function or falls, which are known to modify the risk of fracture [ 37, 44, 48 ] Fig.

Bone adapts its mass, structure, and strength to the loads applied by muscle contractions as a result of physical activity or gravitational forces i.

Several lines of evidence support mechanical unloading as a mediator of the effects of weight loss on bone.

First, diet-induced weight loss consistently results in bone loss at the weight-bearing hip rather than total body [ 36, 37, 39 ]. Second, changes in muscle mass and strength are correlated with bone changes in the hip in older individuals; these effects are largely explained by the gravitational forces exerted by muscles on bone [ 37 ].

Third, exercise and especially resistance training incorporated in weight loss programs can preserve fat-free mass and reduce the negative skeletal effects of weight loss [ 31, 37 ].

At the molecular level, the skeletal effects of mechanical unloading during diet-induced weight loss are supported by elevations in sclerostin levels [ 31 ]. Sclerostin is produced by osteocytes, the bone mechanosensors, and acts on bone formation through inhibition of the canonical Wnt signaling pathway.

The latter regulates osteoblastic differentiation, proliferation, and activity. Despite the significant role of mechanical unloading on bone responses to weight loss, it cannot explain the skeletal changes that occur at non-weight-bearing sites [ ], or continued bone loss after a weight loss plateau [ 47 ].

Obese older individuals have been shown to lose fat-free mass not only during single weight loss interventions but also during weight cycling [ 36, 41, 42 ]. In the latter, weight regain is predominantly accompanied by the acquisition of fat mass rather than fat-free mass [ 50 ].

In addition to the aforementioned mechanical link between muscle and bone, these tissues are connected through bidirectional signaling. Muscle mass also affects skeletal health through its role in physical performance and fall prevention; this emphasizes the need for strategies aimed at the maintenance of muscle mass during weight loss.

A recent systematic review of weight loss RCTs in obese elderly person provided a summary of current evidence on the subject. The review showed that caloric restrictions combined with exercise attenuated the reductions in muscle and bone mass seen in diet-only study arms and resulted in greatest improvements in physical performance [ 48 ].

The relationship between bone and adipose tissue during weight loss appears to be particularly strong during aging. For example, in a population-based prospective study in older men, fat loss — and not loss of lean body mass — was strongly associated with hip bone loss in older men who lost weight over 2 years [ 16 ].

These results likely reflect the actions of fat mass in modulating bone health above and beyond its effects on skeletal loading.

Several endocrine factors that link bone and adipose tissue have been identified [ 52 ]; these appear to mediate skeletal responses to weight loss during aging see below. The current published literature supports the role of bone marrow adipose tissue in bone and energy metabolism and osteogenesis [ 53 ].

Marrow adipocytes have a common origin with osteoblasts, both arising from mesenchymal stem cells. Alterations in the mesenchymal stem cells lineage allocation may contribute to the associations between increased marrow adipose tissue and the elevated risk of fracture in osteoporosis, anorexia nervosa, and diabetes [ 53 ].

Limited animal and human data suggest that marrow fat is reduced during weight loss [ 54, 55 ]; these reductions may also attenuate bone loss.

Given the age-related increase in marrow adipose tissue [ 56 ], it would be interesting to explore changes in bone marrow and their contribution to skeletal outcomes during weight loss in obese elderly.

Macro- and micronutrient deficiencies are common among elderly individuals, due to altered lifestyle or metabolism. These may be exacerbated by energy-deficient diets, which frequently lack key nutrients for skeletal health including protein, vitamin D, and calcium.

This suggests that higher doses of these nutrients or other combined strategies might be needed to mitigate the undesirable weight-loss-induced effects on the skeletal system. The contribution of endocrine factors such as estrogens, insulin-like-growth-factor-1 IGF-1 , leptin, and adiponectin to bone loss observed after weight loss has been detailed elsewhere [ 8 ].

Hereby, we summarize the key findings in older obese individuals. Although reductions in estradiol levels have been reported in obese older women and men during weight loss, possibly due to the reduction of fat mass, these were not correlated with bone loss.

Thus, estradiol probably exerts indirect rather than direct effects on bone responses to weight loss [ 37, 42, 56 ]. IGF-1 reductions have been inconsistently reported in older adults under energy or protein restriction [ 37, 42 ]. However, it is unclear whether the absence of changes reflects true effects of the intervention or whether IGF-1 reductions are masked by increases in its binding proteins [ 60 ].

A reduction in leptin, an adipokine significantly involved in the regulation of energy metabolism and with established central and peripheral effects on bone [ 56 ], is a consistent finding among obese elderly weight losers [ 37, 42 ].

In contrast, the role of adiponectin, another adipokine with potential action on bone [ 61 ], in skeletal changes in obese elderly under weight loss remains poorly understood. Inflammation also contributes to sarcopenia by accelerating protein degradation and slowing down protein synthesis in the muscle [ 56 ].

It is widely accepted that aging, obesity, and exercise are characterized by chronic low-grade inflammation, and weight loss reduces inflammatory markers [ ]. However, the effects of weight loss and exercise on inflammatory molecules and processes in relation to skeletal health outcomes in older obese individuals require further elucidation.

Besides, a complex interplay exists between bone and inflammatory factors derived from muscle, adipose tissue, brain, the immune system, and host — gut microbiota interactions, which might be further modified by weight loss and exercise during aging [ 66 ]. Animal studies complement and extend research in humans by allowing a detailed examination of caloric restriction, exercise, or nutrient manipulation under standardized conditions and by addressing mechanistic aspects.

One of the strengths of animal studies is the existence of similarities in age-related bone loss and obesity among animals and humans. Further advantages of animal studies include the accurate control of diet and exercise, the employment of many study arms, and the ability to analyze changes at different levels [ ].

These advantages are contrasted by a significant diversity among different animal models. The use of animal models requires knowledge of the respective bone anatomy, physiology, energy homeostasis, and the differences between these parameters in animals and humans [ ].

Despite the differences, meticulously designed experimental studies in animals, accompanied by critical data interpretation, have great potential to enhance our knowledge in this area.

Surprisingly, we found no previous study on the effects of caloric restriction on skeletal health in obese aged animals, underpinning a significant literature gap in this age group.

Current evidence is derived from research in lean aged animals [ 57, ] or obese mature animals [ ], which cannot be extrapolated to obese aged animals. As such, we hereby present available animal models that capture age-related bone loss and obesity. We also propose potentially relevant models, which, however, require validation prior to their use in future weight loss interventions Fig.

Advantages and disadvantages of small e. Excellent reviews have described animal models of senile osteoporosis [ 67, 79 ] and obesity [ 68, 80 ]; however, models including both phenotypes are scarce [ 81 ]. A simple and useful model may be the application of a diet-induced obesity DIO paradigm in young, mature, or aged animals.

In the DIO paradigm, animals are provided ad libitum access to energy-dense diets, and the progression of obesity and its metabolic consequences are monitored [ 76, 81 ]. Despite its validity and relevance to human obesity, the DIO paradigm is influenced by animal characteristics e.

Similarly, aged Sprague-Dawley rats have severe abnormalities in trabecular bone and imbalanced bone turnover favoring bone resorption [ 87 ]. Furthermore, progressive increases in body fat percentage and body fat to lean mass ratio have been reported in Sprague-Dawley rats monitored from the age of 8 to 24 months [ 88 ].

Dietary manipulations and characterization of the body composition of animals with senile osteoporosis may provide new alleys of investigation. The same is true for the determination of skeletal features in established animal models of obesity.

For instance, senescence-accelerated mouse-P lines are featured by an accelerated aging phenotype and a short lifespan [ 89 ].

The senescence-accelerated mouse-P6 mice have been established as a model of senile osteoporosis: they exhibit low peak bone mass due to low bone formation and are prone to spontaneous fractures [ 90 ].

Nevertheless, these mice have not been used in diet-induced weight loss interventions. Finally, the use of larger animal models such as dogs, sheep, and pigs might be promising for future research because they offer significant advantages compared to smaller animals [ 79 ].

These include their greater phenotypical similarities to humans and the possibility to collect larger blood volumes over time for biochemical analyses Fig. Nevertheless, their use in age-related research is hampered by their long life span, high costs, handling, housing requirements, and ethical implications.

The effects of intentional weight loss in obese older individuals are of clinical significance because this population is susceptible to poor musculoskeletal health even prior to weight reduction. Prospective studies suggest that weight loss is associated with bone loss, impaired bone microstructure, and a higher risk of fractures in elderly.

However, these associations often reflect the negative impact of unintentional weight loss in underweight older individuals rather than the effects of intentional weight loss in their obese counterparts.

Interventional studies support the worsening of musculoskeletal health outcomes. Nevertheless, these effects appear to be relatively small following a single weight loss attempt and their contribution to the risk of fractures is unknown.

The limited body of data from weight maintenance studies is a cause of concern. These show that bone loss persists during this phase.

Given the long-term implications of intentional weight loss or repeated weight reduction efforts, strategies to attenuate the harmful effects of weight loss on bone are clinically relevant but remain understudied in this group.

The most compelling evidence for such strategies is derived from studies that combined caloric restriction with resistance training. Some older individuals cannot or do not wish to perform exercise training. Thus, future work should be focused on alternative approaches that may counteract, if not prevent, bone loss during active weight loss and weight maintenance.

Simultaneously, the assessment of other geriatric outcomes and biochemical markers could provide mechanistic links between weight loss and bone loss. To this end, the use of relevant animal models serves as a unique opportunity to understand the pathophysiology of weight-loss-associated bone alterations, as well as develop and test potential counteracting strategies for obese elderly.

The discrepant results between the studies may be explained by differences in exercise regimens and the baseline characteristics of the study populations. Frail and obese individuals are possibly more responsive to the effects of exercise training.

In a month follow-up of a 1-year weight loss intervention [ 36 ], Waters et al. Similarly, Beavers et al. Both studies support unfavorable changes in skeletal health due to long-term weight loss.

These studies were subject to reporting bias because they were based on subsets of the initial groups and did not include individuals with no weight loss. Nevertheless, they underpin the need for follow-up studies to evaluate weight management approaches in the elderly and characterize skeletal health outcomes associated with sustained weight loss or multiple weight loss attempts.

We investigated the available evidence on the mechanistic links between weight loss and bone loss in obese older individuals or relevant aged animal models. We also discuss speculative contributors to bone loss during weight loss which, however, have been poorly investigated in obese elderly under weight loss and require further elucidation.

The effects of weight loss on skeletal outcomes during aging are likely multifactorial and may be mediated by i mechanical unloading, ii changes in body composition, iii restriction of important nutrients for bone metabolism and health, iv alterations in gonadal hormones and endocrine factors that co-regulate energy and bone metabolism, and v changes in inflammatory factors.

These factors appear to affect the balance between bone formation and resorption. This, in turn, mediates changes in the macro- and microstructure of bone as well as bone material, which determine bone strength and, ultimately, the risk of fractures Fig.

They also influence other geriatric outcomes such as physical function or falls, which are known to modify the risk of fracture [ 37, 44, 48 ] Fig. Bone adapts its mass, structure, and strength to the loads applied by muscle contractions as a result of physical activity or gravitational forces i.

Several lines of evidence support mechanical unloading as a mediator of the effects of weight loss on bone. First, diet-induced weight loss consistently results in bone loss at the weight-bearing hip rather than total body [ 36, 37, 39 ].

Second, changes in muscle mass and strength are correlated with bone changes in the hip in older individuals; these effects are largely explained by the gravitational forces exerted by muscles on bone [ 37 ]. Third, exercise and especially resistance training incorporated in weight loss programs can preserve fat-free mass and reduce the negative skeletal effects of weight loss [ 31, 37 ].

At the molecular level, the skeletal effects of mechanical unloading during diet-induced weight loss are supported by elevations in sclerostin levels [ 31 ].

Sclerostin is produced by osteocytes, the bone mechanosensors, and acts on bone formation through inhibition of the canonical Wnt signaling pathway. The latter regulates osteoblastic differentiation, proliferation, and activity.

Despite the significant role of mechanical unloading on bone responses to weight loss, it cannot explain the skeletal changes that occur at non-weight-bearing sites [ ], or continued bone loss after a weight loss plateau [ 47 ].

Obese older individuals have been shown to lose fat-free mass not only during single weight loss interventions but also during weight cycling [ 36, 41, 42 ].

In the latter, weight regain is predominantly accompanied by the acquisition of fat mass rather than fat-free mass [ 50 ]. In addition to the aforementioned mechanical link between muscle and bone, these tissues are connected through bidirectional signaling.

Muscle mass also affects skeletal health through its role in physical performance and fall prevention; this emphasizes the need for strategies aimed at the maintenance of muscle mass during weight loss.

A recent systematic review of weight loss RCTs in obese elderly person provided a summary of current evidence on the subject. The review showed that caloric restrictions combined with exercise attenuated the reductions in muscle and bone mass seen in diet-only study arms and resulted in greatest improvements in physical performance [ 48 ].

The relationship between bone and adipose tissue during weight loss appears to be particularly strong during aging. For example, in a population-based prospective study in older men, fat loss — and not loss of lean body mass — was strongly associated with hip bone loss in older men who lost weight over 2 years [ 16 ].

These results likely reflect the actions of fat mass in modulating bone health above and beyond its effects on skeletal loading. Several endocrine factors that link bone and adipose tissue have been identified [ 52 ]; these appear to mediate skeletal responses to weight loss during aging see below.

The current published literature supports the role of bone marrow adipose tissue in bone and energy metabolism and osteogenesis [ 53 ]. Marrow adipocytes have a common origin with osteoblasts, both arising from mesenchymal stem cells.

Alterations in the mesenchymal stem cells lineage allocation may contribute to the associations between increased marrow adipose tissue and the elevated risk of fracture in osteoporosis, anorexia nervosa, and diabetes [ 53 ]. Limited animal and human data suggest that marrow fat is reduced during weight loss [ 54, 55 ]; these reductions may also attenuate bone loss.

Given the age-related increase in marrow adipose tissue [ 56 ], it would be interesting to explore changes in bone marrow and their contribution to skeletal outcomes during weight loss in obese elderly. Macro- and micronutrient deficiencies are common among elderly individuals, due to altered lifestyle or metabolism.

These may be exacerbated by energy-deficient diets, which frequently lack key nutrients for skeletal health including protein, vitamin D, and calcium.

This suggests that higher doses of these nutrients or other combined strategies might be needed to mitigate the undesirable weight-loss-induced effects on the skeletal system. The contribution of endocrine factors such as estrogens, insulin-like-growth-factor-1 IGF-1 , leptin, and adiponectin to bone loss observed after weight loss has been detailed elsewhere [ 8 ].

Hereby, we summarize the key findings in older obese individuals. Although reductions in estradiol levels have been reported in obese older women and men during weight loss, possibly due to the reduction of fat mass, these were not correlated with bone loss.

Thus, estradiol probably exerts indirect rather than direct effects on bone responses to weight loss [ 37, 42, 56 ]. IGF-1 reductions have been inconsistently reported in older adults under energy or protein restriction [ 37, 42 ]. However, it is unclear whether the absence of changes reflects true effects of the intervention or whether IGF-1 reductions are masked by increases in its binding proteins [ 60 ].

A reduction in leptin, an adipokine significantly involved in the regulation of energy metabolism and with established central and peripheral effects on bone [ 56 ], is a consistent finding among obese elderly weight losers [ 37, 42 ].

In contrast, the role of adiponectin, another adipokine with potential action on bone [ 61 ], in skeletal changes in obese elderly under weight loss remains poorly understood.

Inflammation also contributes to sarcopenia by accelerating protein degradation and slowing down protein synthesis in the muscle [ 56 ]. It is widely accepted that aging, obesity, and exercise are characterized by chronic low-grade inflammation, and weight loss reduces inflammatory markers [ ].

However, the effects of weight loss and exercise on inflammatory molecules and processes in relation to skeletal health outcomes in older obese individuals require further elucidation.

Besides, a complex interplay exists between bone and inflammatory factors derived from muscle, adipose tissue, brain, the immune system, and host — gut microbiota interactions, which might be further modified by weight loss and exercise during aging [ 66 ].

Animal studies complement and extend research in humans by allowing a detailed examination of caloric restriction, exercise, or nutrient manipulation under standardized conditions and by addressing mechanistic aspects. One of the strengths of animal studies is the existence of similarities in age-related bone loss and obesity among animals and humans.

Further advantages of animal studies include the accurate control of diet and exercise, the employment of many study arms, and the ability to analyze changes at different levels [ ]. These advantages are contrasted by a significant diversity among different animal models.

The use of animal models requires knowledge of the respective bone anatomy, physiology, energy homeostasis, and the differences between these parameters in animals and humans [ ]. Despite the differences, meticulously designed experimental studies in animals, accompanied by critical data interpretation, have great potential to enhance our knowledge in this area.

Surprisingly, we found no previous study on the effects of caloric restriction on skeletal health in obese aged animals, underpinning a significant literature gap in this age group.

Current evidence is derived from research in lean aged animals [ 57, ] or obese mature animals [ ], which cannot be extrapolated to obese aged animals. As such, we hereby present available animal models that capture age-related bone loss and obesity.

We also propose potentially relevant models, which, however, require validation prior to their use in future weight loss interventions Fig.

Advantages and disadvantages of small e. Excellent reviews have described animal models of senile osteoporosis [ 67, 79 ] and obesity [ 68, 80 ]; however, models including both phenotypes are scarce [ 81 ].

A simple and useful model may be the application of a diet-induced obesity DIO paradigm in young, mature, or aged animals. In the DIO paradigm, animals are provided ad libitum access to energy-dense diets, and the progression of obesity and its metabolic consequences are monitored [ 76, 81 ].

Despite its validity and relevance to human obesity, the DIO paradigm is influenced by animal characteristics e. Similarly, aged Sprague-Dawley rats have severe abnormalities in trabecular bone and imbalanced bone turnover favoring bone resorption [ 87 ].

Furthermore, progressive increases in body fat percentage and body fat to lean mass ratio have been reported in Sprague-Dawley rats monitored from the age of 8 to 24 months [ 88 ]. Dietary manipulations and characterization of the body composition of animals with senile osteoporosis may provide new alleys of investigation.

The same is true for the determination of skeletal features in established animal models of obesity. For instance, senescence-accelerated mouse-P lines are featured by an accelerated aging phenotype and a short lifespan [ 89 ].

The senescence-accelerated mouse-P6 mice have been established as a model of senile osteoporosis: they exhibit low peak bone mass due to low bone formation and are prone to spontaneous fractures [ 90 ].

Nevertheless, these mice have not been used in diet-induced weight loss interventions. Finally, the use of larger animal models such as dogs, sheep, and pigs might be promising for future research because they offer significant advantages compared to smaller animals [ 79 ].

These include their greater phenotypical similarities to humans and the possibility to collect larger blood volumes over time for biochemical analyses Fig.

Nevertheless, their use in age-related research is hampered by their long life span, high costs, handling, housing requirements, and ethical implications. The effects of intentional weight loss in obese older individuals are of clinical significance because this population is susceptible to poor musculoskeletal health even prior to weight reduction.

Prospective studies suggest that weight loss is associated with bone loss, impaired bone microstructure, and a higher risk of fractures in elderly.

However, these associations often reflect the negative impact of unintentional weight loss in underweight older individuals rather than the effects of intentional weight loss in their obese counterparts. Interventional studies support the worsening of musculoskeletal health outcomes.

Nevertheless, these effects appear to be relatively small following a single weight loss attempt and their contribution to the risk of fractures is unknown. The limited body of data from weight maintenance studies is a cause of concern.

These show that bone loss persists during this phase. Given the long-term implications of intentional weight loss or repeated weight reduction efforts, strategies to attenuate the harmful effects of weight loss on bone are clinically relevant but remain understudied in this group.

The most compelling evidence for such strategies is derived from studies that combined caloric restriction with resistance training. Some older individuals cannot or do not wish to perform exercise training. Thus, future work should be focused on alternative approaches that may counteract, if not prevent, bone loss during active weight loss and weight maintenance.

Simultaneously, the assessment of other geriatric outcomes and biochemical markers could provide mechanistic links between weight loss and bone loss.

To this end, the use of relevant animal models serves as a unique opportunity to understand the pathophysiology of weight-loss-associated bone alterations, as well as develop and test potential counteracting strategies for obese elderly.

All other authors have no conflicts of interest to declare. All authors reviewed and approved the final manuscript. Sign In or Create an Account. Search Dropdown Menu. header search search input Search input auto suggest.

filter your search All Content All Journals Gerontology. Advanced Search. Skip Nav Destination Close navigation menu Article navigation. Volume 66, Issue 1. Epidemiological Studies. Interventional Studies. Animal Studies. Statement of Ethics. Disclosure Statement. Funding Sources. Author Contributions.

Article Navigation. Review Articles June 28 Is Weight Loss Harmful for Skeletal Health in Obese Older Adults? Subject Area: Geriatrics and Gerontology. Maria Papageorgiou ; Maria Papageorgiou. a Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, Vienna, Austria.

b Department of Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School, University of Hull, Hull, United Kingdom. This Site.

Google Scholar. Katharina Kerschan-Schindl ; Katharina Kerschan-Schindl. c Department of Physical Medicine, Rehabilitation and Occupational Therapy, Medical University of Vienna, Vienna, Austria. Thozhukat Sathyapalan ; Thozhukat Sathyapalan. Peter Pietschmann Peter Pietschmann.

pietschmann meduniwien. Gerontology 66 1 : 2— Article history Received:. Cite Icon Cite. toolbar search Search Dropdown Menu. toolbar search search input Search input auto suggest. Table 1. View large. View Large. Table 2. View large Download slide. Proposed mechanisms underlying bone loss during intentional weight loss in obese older adults.

is the recipient of a postdoctoral Ernst Mach Fellowship. The authors have no ethical conflicts to disclose. No funding was granted for this work. Prevalence of adult overweight and obesity in 20 European countries, Search ADS.

Prevalence of obesity among adults and youth: United States, — NCHS data brief, no Obesity Management Task Force of the European Association for the Study of Obesity. Prevalence, pathophysiology, health consequences and treatment options of obesity in the elderly: a guideline.

Osteosarcopenic obesity syndrome: what is it and how can it be identified and diagnosed? Intentional weight loss in older adults: useful or wasting disease generating strategy? Does diet-Induced weight loss lead to bone loss in overweight or obese adults? A systematic review and meta-analysis of clinical trials.

Bone loss, physical activity, and weight change in elderly women: the Dubbo Osteoporosis Epidemiology Study. Risk factors for longitudinal bone loss in elderly men and women: the Framingham Osteoporosis Study.

Intentional and unintentional weight loss increase bone loss and hip fracture risk in older women. Weight loss: a determinant of hip bone loss in older men and women.

The Rancho Bernardo Study. Body weight change since menopause and percentage body fat mass are predictors of subsequent bone mineral density change of the proximal femur in women aged 75 years and older: results of a 5 year prospective study. Risk factors for bone loss in the hip of year-old women: a 4-year follow-up study.

The role of fat and lean mass in bone loss in older men: findings from the CHAMP study. Weight change over three decades and the risk of osteoporosis in men: the Norwegian Epidemiological Osteoporosis Studies NOREPOS.

Voluntary weight reduction in older men increases hip bone loss: the osteoporotic fractures in men study. What is the influence of weight change on forearm bone mineral density in peri- and postmenopausal women? The health study of Nord-Trondelag, Norway.

Predictors of change of trabecular bone score TBS in older men: results from the Osteoporotic Fractures in Men MrOS Study. Long-Term and Recent Weight Change Are Associated With Reduced Peripheral Bone Density, Deficits in Bone Microarchitecture, and Decreased Bone Strength: The Framingham Osteoporosis Study.

Osteoporotic Fractures in Men MrOS Research Group. Accelerated bone loss in older men: effects on bone microarchitecture and strength. Weight loss in men in late life and bone strength and microarchitecture: a prospective study. Weight change between age 50 years and old age is associated with risk of hip fracture in white women aged 67 years and older.

Weight loss from maximum body weight among middle-aged and older white women and the risk of hip fracture: the NHANES I epidemiologic follow-up study. Weight loss and distal forearm fractures in postmenopausal women: the Nord-Trøndelag health study, Norway.

Increase in Fracture Risk Following Unintentional Weight Loss in Postmenopausal Women: The Global Longitudinal Study of Osteoporosis in Women.

Risk factors for hip fracture in white men: the NHANES I Epidemiologic Follow-up Study. Share your thoughts in the comments below for other readers to try!

Save my name, email, and website in this browser for the next time I comment. Previous Next. Tips for eating better while losing weight to combat osteoporosis. They may not optimize for a calcium dense diet, which is beneficial for your bone health , but rather focus on rapid weight loss.

Skipping breakfast: some diets promote intermittent fasting or skipping breakfast to cut calories. Dipping below calories per day: losing weight is a long-term process that has dangerous consequences when done improperly.

Women should consume at least 1, calories per day, while men have a little more wiggle room at 1, Focus on eating whole foods to promote optimal bone health. Fresh fruit and dark leafy vegetables like kale or broccoli. These foods are packed full of essential nutrients, including calcium. Plenty of Vitamin D.

You can get this by walking in the sun for minutes or through beverages like soy milk or orange juice. Lean protein and dairy. Exercise tips while losing weight to combat osteoporosis.

This could include: Walking or a light jog. Weight-bearing exercises such as squats, push-ups, and weight lifting. Yoga and pilates. Muh Ihsan Hadi Prabowo T February 1st, Bone Health. Share This Story, Choose Your Platform!

Facebook Twitter LinkedIn Pinterest Email. Related Posts. February 1st, 0 Comments.

Adipose tissue has been shown to regulate inflammatory immune responses in cartilage People and animals affected by obesity exhibit higher serum levels of TNF-α, IL-1 and IL-6, all from macrophages in adipose tissue Park et al.

In parallel, the levels of TNF-α, IL-1 and IL-6 in synovial fluid, synovial membrane, subchondral bone and cartilage in patients with OA were increased, confirming their important roles in the pathogenesis of OA TNF-α, IL-6, and IL-1 are the cytokines produced by adipose tissue to directly and negatively regulate cartilage.

In addition, TNF-α, IL-1, and IL-6 can promote the formation of other factors, matrix metalloproteinases MMPs and prostaglandins, while restrain the synthesis of proteoglycans and type II collagen. Therefore, they play an important role in OA cartilage matrix degradation and bone resorption.

Moreover, TNF-α, IL-1, and IL-6 may indirectly cause OA by regulating adiponectin and leptin secreted by fat cells Koskinen et al. Reyes et al. Overweight, class I obesity and class II obesity increased the risk of knee OA by 2-, 3. Adipokines represent a new class of compounds that are currently considered to be key molecules involved in the pathogenesis of rheumatic diseases Felson and Chaisson, ; Scotece et al.

Resistin is an adipokines closely related to obesity, local low-level inflammation and MS Rong et al. Alissa et al. In addition, elevated serum resistin levels were positively correlated with indicators of obesity, markers of inflammation, and WOMAC Index an indicator of the severity of OA symptoms Alissa et al.

Furthermore, Koskinen et al. The effect of leptin on MMP-1, MMP-3, and MMP was mediated by transcription factor NF-κβ, and protein kinase C and MAP kinase pathways. Leptin concentration in synovial fluid was also positively correlated with MMP-1 and MMP-3 levels in patients with OA Koskinen et al.

The results showed that leptin had catabolic effect on OA joints by increasing the production of MMP in cartilage Bao et al. In addition, adiponectin has been reported to be involved in the pathophysiological process of OA.

Kang et al. NO is one of the main mediators of pro-inflammatory cytokines acting on chondrocytes and also regulates different cartilage functions, including chondrocyte phenotypic loss, apoptosis, and extracellular matrix degradation Otero et al.

In this study, adiponectin increased the expression of MMPs and iNOS in human OA chondrocytes through AMPK and JNK pathways, leading to the degradation of OA cartilage matrix Kang et al.

In summary, obesity not only increases the incidence of OA, especially in weight-bearing joints such as knee joints, but also is related to non-weight-bearing joints such as finger joints and wrist OA, suggesting that these metabolic mediators lead to an increase in the incidence of OA in obese patients.

This may be because obesity increases the mechanical load of articular cartilage, leading to its degradation, and fatty tissue secretes metabolic factors such as IL-1, TNF-A, adiponectin, and leptin , leading to an increased prevalence of OA in obese people Oliveria et al. Rheumatoid arthritis RA , the most common form of inflammatory arthritis, is a chronic systemic autoimmune disease characterized by aggressive symmetrical inflammation of multiple joints Kobayashi et al.

Therefore, RA has brought a heavy burden and great pain to affected families, patients and even the whole society Nam et al. There is evidence that an increase in BMI is associated with an increased risk of RA Feng et al.

As mentioned above, adipokines such as adiponectin and visfatin have also been reported to play a key role in the pathophysiology of autoimmune diseases Coelho et al.

It has now been well established that patients with RA show higher plasma adiponectin, leptin, and visfatin levels compared with healthy controls Otero et al.

Visfatin is a proinflammatory mediator that induces the production of TNF-α, IL-1, IL-6, IL-8, and MMPs, which are typical manifestations of RA joint inflammation Brentano et al. Similarly, adiponectin stimulated fibroblast-like synoviocytes FLS in patients with RA to produce IL-6, IL-8, and PGE2 Choi et al.

In addition, adiponectin increased the production of VEGF and MMPs in RA FLS, which may induce inflammation and joint destruction Lee et al.

Figure 1. Changes of various factors caused by obesity on the regulation of bone disease. Obesity can increase mechanical load, visceral fat and bone marrow fat. In addition, obesity is associated with increased adipokines, increased TNF — or, IL-1, IL- 6, decreased vitamin D, and accompanied by hypertension, dyslipidemia, and dysglycemia.

They regulate bone disease by affecting bone formation, bone resorption, and cartilage. Previous studies have shown that the frequency of circulating T follicular helper cells Tfh is significantly increased in RA patients, which is positively correlated with disease activity and anti-CCP autoantibody levels Liu et al.

RA FLSs stimulated by AD adiponectin promoted the production of Tfh cells. In addition, intra-articular injection of AD aggravated synovitis and increased the frequency of Tfh cells in CIA mice treated with AD Nurieva et al.

Obesity is not only prevalent in RA patients, but also associated with disease activity. Obesity reduces the chance of RA remission and negatively affects disease activity and outcomes reported by patients during treatment Liu et al.

Lee and Bae observed that the levels of circulating adiponectin and visfatin in RA patients were significantly higher than those in the control group. The levels of visfatin in 28 joints were positively correlated with disease activity score and CRP level Lee and Bae, On the one hand, obesity is divided into peripheral obesity and abdominal obesity according to the distribution of fat in the body.

Abdominal fat is made up of abdominal wall fat SAT and abdominal fat VAT , also known as central obesity, visceral obesity. Previous studies have shown that adipokins are associated with bone metabolism, and that central obesity can lead to osteopenia or OP because bone density decreases with an increase in waist-to-hip ratio, an index of central obesity Mitsuyo et al.

In one study, whole body bone mineral content was positively correlated with HOMA-IR and negatively correlated with the percentage of trunk fat, which is a good representative of visceral fat, suggesting that abdominal obesity may have an adverse effect on systemic bone parameters Krishnan et al.

Local fat is increasingly recognized as a determinant of bone density, and this association may be mediated by adipocytokines Vicente et al. Russell et al. Consequently, VAT is an independent negative determining factor of bone density in obesity Jurimae et al. On the other hand, according to the different obesity phenotypes, it can be divided into normal metabolic healthy BMI, metabolic healthy obesity and metabolic abnormal obesity Karelis et al.

Marques Loureiro et al. In summary, the MUHO phenotype presents a higher risk of bone metabolism-related changes, which may contribute to the development of metabolic bone disease Marques Loureiro et al. Figure 2. Effects of factors secreted by adipose tissue on bone metabolism.

Adipose tissue can secrete leptin, adiponectin, visfatin, TNF- a , IL-6, and IL-1 These factors act on chondrocytes, osteoblasts, osteoclasts, respectively, to regulate bone formation and resorption, as well as cartilage degradation. While childhood obesity has always been a major health problem, its prevalence has been on the rise.

In addition, childhood obesity may be associated with multiple complications, such as hyperinsulinemia, hypertension, MS, and non-alcoholic fatty liver disease NAFLD; Oh et al. Childhood obesity may affect the growth patterns of children and adolescents, according to several studies Children influenced by obesity may develop accelerated skeletal maturity and advanced bone age beyond their actual age Johnson et al.

A study of children aged 6—15 years found that the prevalence of advanced bone age increased significantly with increased body weight, height, BMI, and waist circumference percentiles Oh et al. Instead, a study of young people with an average age of 10—17 confirmed that obese children and adolescents had higher bone mass and density than their normal-weight peers Chaplais et al.

Notably, Zhao et al. The BMD gradually increased in the range within As noted above, although there have been several studies on the effects of fat mass on skeletal health in normal weight and obese adolescents, the results remain controversial.

Osteoporosis is considered a major public health problem for postmenopausal women. Low estrogen levels lead to rapid bone loss in women five to seven years after menopause Kanis et al.

Actually, some evidences, indicated that age and BMI were important factors influencing BMD. The BMD of obese postmenopausal women was higher than that of normal size women, and the reduction of BMD of obese women can be delayed by weight bearing Méndez et al.

At the same time, Cherif et al. also observed that the left femur, right femur, total hip joint, and overall bone density were higher in obese women Cherif et al. In addition, adipokines secreted by fat are considered as potential pathophysiological factors of OP.

Several studies have shown that leptin has significant effects on bone growth and bone metabolism through central and peripheral pathways, and may be involved in the occurrence of various bone diseases Chen and Yang, Studies have shown a positive correlation between leptin levels and BMI.

And higher BMI is associated with higher bone density. However, obesity had no effect on adiponectin and resistin secretion in postmenopausal women with OP, so leptin was the only one of the adipokines studied to be considered as a protective factor for bone tissue in postmenopausal women Pasco et al.

Thus, the above results indicate that, adiposity may be beneficial to bone density in postmenopausal women. The protective effect of high body weight and BMI may be due to hormonal influences in the body.

Postmenopausal women affected by obesity have more adipose tissue and more estrogen conversion, resulting in higher estrogen levels in their bodies.

Obesity, sarcopenia, and OP are common chronic diseases in the elderly. Sarcopenia is a newly discovered age-related disease related to lipid metabolism and insulin resistance.

The main diagnostic criteria for sarcopenia are reduced skeletal muscle mass, muscle strength, and function. Older people continue to lose muscle mass as they age, while body fat, especially visceral fat, tends to rise, known as "sarcopenic obesity" SO; Stenholm et al.

A recent study found that women with SO were more easy to show elevated blood glucose, while men with SO were more likely to present with OP and dyslipidemia Du et al.

On the other hand, muscles secrete a set of cytokines called myokines, thereby regulating bone metabolism. Myostatin, as a key myokine, has been reported for its effect on bone. Myostatin can inhibit osteogenic differentiation of BMSCs, as well as osteoblast differentiation and mineralization Hamrick et al.

Likewise, myostatin may inhibit osteogenesis by activating the RANKL signaling pathway, thus showing an adverse impact on bone mass Saad, Thus, inhibition or blocking of the myostatin signaling pathway may provide potential therapeutic targets for a number of diseases, particularly in sarcopenia and OP.

Several studies have reported the links between BMD and body fat and lean mass. When body weight was stratified into lean body mass and fat mass, the increase in BMD was more pronounced for lean body mass, whereas fat mass was only beneficial for men and premenopausal women.

Santos et al. also observed a more direct relationship between lean body mass and bone density total bone density, femur, and spine , while sarcopenia was associated with OP.

Obesity was more likely to be a protective factor for OP in old subjects aged 80 and over Santos et al. At the same time, Barrera et al. demonstrated the beneficial effects of high BMI on femoral neck bone density in older adults.

In particular, obese people were reported to have higher bone density, but they also showed damaged bone microstructures and different fall patterns Compston, ; Ilich et al.

Conclusions about the relationship between obesity and bone in humans rely on statistical correlations or models, rather than controlled trials. Therefore, the establishment of obesity mouse model is helpful to study the effect of high-fat diet HFD -induced obesity on bone metabolism.

Studies have shown that obese animals burn the same amount of energy, no matter how much fat is in their diet Brown et al. The mice provided a model for studying the relationship between body size, obesity and skeletal characteristics.

High fat intake in rodents leads to obesity, and several studies have shown a strong link between bone size, strength and body size. However, mice are not always reliable indicators of human pathophysiology. Human can enjoy more colorful life style, more abundant food and more complicated living environment.

Moreover, patients with obesity often have multiple complications, not just weight gain. These factors make the relationship between obesity and bone more complex in humans than in mice. The effects of a high-fat diet on cancellous bone in rodents have been shown to be harmful.

In addition, in obese mice, serum leptin levels were associated with bone trabeculae, but not cortical bone density, while adiponectin and total cholesterol levels were not associated with bone mass Fujita et al.

Scheller et al. In addition, Inzana et al. A recent study conducted by Tian et al. In other words, after short-term feeding, HFD may show a positive effect on bone mass, however, after long-term feeding, bone mass was significantly decreased in HFD mice.

However, the effects of diet induced obesity on cortical bone in rodents are less clear, with positive, negative, and neutral results reported.

The femoral cortical thickness and cross-sectional area of 4-week old male mice were increased after feeding HFD-DAG Diacylglycerol. HFD-DAG had obvious promoting effect on bone and bone metabolism Choi et al. In addition, Silva et al.

recently suggested that a high-fat diet had beneficial effects on most femoral size and skeletal mechanical properties, as well as radius size and stiffness Silva et al. However, Ionova-Martin et al. found that femur strength, hardness, and toughness were significantly lower in both young and adult mice fed HFD than in the control group Ionova-Martin et al.

In contrast, Cao et al. concluded that feeding mice HFD for 14 weeks reduced proximal tibial cancellous bone mass in young mice, but had no effect on cortical bone mass Cao et al. Halade et al. To sum up, in the above studies, the effect of HFD on cortical bone was not as significant as that on cancellous bone.

It is generally believed that age-related OP has three main processes. The first and most important process is reduction of trabecular bone, the second is continuous bone resorption on the cortical surface, and the third is cortical bone loss Chen et al.

Similarly, the above studies indicate that the most significant change in obesity-related bone loss is the reduction of femoral trabecular bone Combined, these results suggest that HFD could regulate the changes of trabecular and cortical bone in different ways.

This may be due to the fact that cancellous bone generally responds more strongly to diet or drug therapy, physiological conditions, or aging than cortical bone, because cancellous bone is more active in remodeling because of its larger surface to volume ratio than cortical bone Morgan et al.

On the other hand, bearing capacity and mechanical stress are important factors in determining cortical bone mass, while trabecular bone density is affected by sex maturation related hormones Mora et al.

In addition to affecting bone structure, HFD can also have significant effects on cell function. Bone mass reflects the balance between bone formation and bone resorption and is involved in the coordination and regulation of the number and activity of osteoblasts and osteoclasts at the cellular level.

A previous study showed that the expression of RANKL, the ratio of RANKL to OPG, and the level of serum TRAP in osteoblasts from HFD mice were increased, suggesting that HFD can promote osteoclast activity and bone resorption Cao et al. Notably, Halade et al. reported that in mice fed HFD, the accumulation of bone marrow adipocytes resulted in significantly higher levels of pro-inflammatory factors, leading to increased bone resorption.

Furthermore, Shu et al. The elevated osteoclast precursor frequency, increased osteoclast formation, and bone resorption activity, along with increased osteoclastogenic regulators such as RANKL, TNF, and PPARγ were seen in bone marrow cells from HFD-fed mice.

But, osteoblast function was also increased after 12 weeks of HFD Shu et al. A possible explanation is that mechanical load of body weight stimulates bone formation, reduces apoptosis, and enhances proliferation and differentiation of osteoblasts and osteocytes.

Therefore, it was not surprising that bone formation rates and osteoblast numbers increased in this study, since HFD mice were significantly heavier than the control group Bonewald and Johnson, In conclusion, it is reasonable to believe that the bone loss caused by HFD is mainly related to the promotion of osteoclast differentiation and activity by changing the bone marrow microenvironment.

Obesity initially has a beneficial effect on bones, possibly due to anabolic effects that increase mechanical load. However, due to the development of metabolic complications including systemic inflammation, the second stage is followed by a reduction in bone formation Lecka-Czernik et al.

As mentioned above, these results may support the idea that as obesity rises, the benefits for bone health are diminishing. In conclusion, obesity or overweight is strictly related to bone metabolism, although the correlation has not yet been fully unified.

Adipose tissue interacts with bone by secreting various cytokines, so as to regulate bone health. Meanwhile BMAT also exerts a crucial impact on bone density and bone microstructure.

In addition, human obesity is a complex problem that involves not only excessive fat intake but also other nutrient consumption imbalances such as vitamin D, calcium and phosphorus, which are known to affect bone metabolism, further making it difficult to determine the impact of obesity on human bone health.

Moreover, while BMI is closely related to the gold standard of body fat, it does not distinguish between lean and fat mass, nor does it provide an indication of the distribution of body fat. The loss of muscle mass in the elderly means that BMI is also less accurate at predicting body fat in this group.

Therefore, determining whether obesity causes changes in bone mass based on BMI is less accurate. Central obesity measures, including waist circumference, waist-to-height ratio and waist-to-hip ratio, are better predictors of visceral obesity, bone-related disease and mortality than BMI.

Simply put, all of these findings indicate that skeletal response to obesity has either a positive or negative effect on bone, suggesting that the influence of obesity on bone metabolism is intricate and depend on diverse factors, such as mechanical load by the weight, obesity type, the location of adipose tissue, gender, age, and bone sites, along with secreted cytokines, these factors may play a major function for bone health.

The effects of obesity on bone metabolism and bone microstructure involve these multiple factors, which may exert different regulatory mechanisms and ultimately affect the skeletal health.

The investigation of the relationship between obesity and bone is conducive to finding new targets for the treatment of bone-related diseases, including OP, fractures, RA, and OA. JH wrote the manuscript. CH, WH, and MY revised the manuscript. CL and XL were responsible for the guidance and supervision.

All authors contributed to the article and approved the submitted version. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Agbaht, K. Circulating adiponectin represents a biomarker of the association between adiposity and bone mineral density.

Endocrine 35, — doi: PubMed Abstract CrossRef Full Text Google Scholar. Al Saedi, A. Rapamycin affects palmitate-induced lipotoxicity in osteoblasts by modulating apoptosis and autophagy.

A Biol. Alissa, E. Relationship between serum resistin, body fat and inflammatory markers in females with clinical knee osteoarthritis.

Knee 27, 45— Arango-Lopera, V. Mortality as an adverse outcome of sarcopenia. Health Aging 17, — Ardawi, M. Increased serum sclerostin and decreased serum IGF-1 are associated with vertebral fractures among postmenopausal women with type-2 diabetes. Bone 56, — Astudillo, P.

Baggio, L. Biology of incretins: GLP-1 and GIP. Gastroenterology , — Bao, J. Leptin plays a catabolic role on articular cartilage. Barba, C. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet , — CrossRef Full Text Google Scholar.

Barrera, G. A high body mass index protects against femoral neck osteoporosis in healthy elderly subjects. Nutrition 20, — Bartell, S. Bone Miner. Beekman, K. Google Scholar. Bijlsma, J. Osteoarthritis: an update with relevance for clinical practice.

Bonewald, L. Osteocytes, mechanosensing and Wnt signaling. Bone 42, — Boon, M. BMP7 activates brown adipose tissue and reduces diet-induced obesity only at subthermoneutrality.

PLoS One 8:e Borges, J. Diabetes Obes. Brandt, K. Yet more evidence that osteoarthritis is not a cartilage disease. Bredella, M. Increased bone marrow fat in anorexia nervosa. Determinants of bone mineral density in obese premenopausal women.

Bone 48, — Vertebral bone marrow fat is positively associated with visceral fat and inversely associated with IGF-1 in obese women. Obesity Silver Spring 19, 49— Brentano, F. Arthritis Rheum. Brown, J. Effect of high-fat diet on body composition and hormone responses to glucose tolerance tests.

Endocrine 19, — Brun, J. Diabetes 66, — Burguera, B. Leptin reduces ovariectomy-induced bone loss in rats. Endocrinology , — Cao, J.

Involuntary wheel running improves but does not fully reverse the deterioration of bone structure of obese rats despite decreasing adiposity. Tissue Int. High-fat diet decreases cancellous bone mass but has no effect on cortical bone mass in the tibia in mice. Bone 44, — Carobbio, S. Adipose tissue function and expandability as determinants of lipotoxicity and the metabolic syndrome.

Chaplais, E. Effects of interventions with a physical activity component on bone health in obese children and adolescents: a systematic review and meta-analysis. Chen, H. Site-specific bone loss in senescence-accelerated mouse SAMP6 : a murine model for senile osteoporosis.

Chen, X. Roles of leptin in bone metabolism and bone diseases. Chen, Y. GDF8 inhibits bone formation and promotes bone resorption in mice. Cherif, R. Positive Association of Obesity and insulin resistance with bone mineral density in Tunisian postmenopausal women.

Choi, H. Multifaceted physiological roles of adiponectin in inflammation and diseases. Adiponectin may contribute to synovitis and joint destruction in rheumatoid arthritis by stimulating vascular endothelial growth factor, matrix metalloproteinase-1, and matrix metalloproteinase expression in fibroblast-like synoviocytes more than proinflammatory mediators.

Arthritis Res. Yonsei Med. Coelho, M. Biochemistry of adipose tissue: an endocrine organ. Compston, J. Obesity and fractures. Joint Bone Spine 80, 8— Type 2 diabetes mellitus and bone. Obesity is not protective against fracture in postmenopausal women: GLOW.

Conde, J. Adipokines and osteoarthritis: novel molecules involved in the pathogenesis and progression of disease. Arthritis Cui, Y. Molecular basis and therapeutic potential of myostatin on bone formation and metabolism in orthopedic disease. Biofactors 71, — Dalamaga, M.

Adiponectin as a biomarker linking obesity and adiposopathy to hematologic malignancies. de Araujo, I. Marrow adipose tissue spectrum in obesity and type 2 diabetes mellitus. De Laet, C. Body mass index as a predictor of fracture risk: a meta-analysis. Del Mar Gonzalez-Barroso, M. Di Angelantonio, E.

Body-mass index and all-cause mortality: individual-participant-data meta-analysis of prospective studies in four continents. Ding, C. Metabolic triggered inflammation in osteoarthritis. Osteoarthritis Cartilage 41, 90— Dobson, R. Metabolically healthy and unhealthy obesity: differential effects on myocardial function according to metabolic syndrome, rather than obesity.

Dormuth, C. Thiazolidinediones and fractures in men and women. Du, Y. Sex differences in the prevalence and adverse outcomes of sarcopenia and sarcopenic obesity in community dwelling elderly in East China using the AWGS criteria.

BMC Endocr. Ducy, P. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell , — Elbaz, A. Inhibition of fatty acid biosynthesis prevents adipocyte lipotoxicity on human osteoblasts in vitro.

Fassio, A. The obesity paradox and osteoporosis. Weight Disord. Fazeli, P. Marrow fat and preadipocyte factor-1 levels decrease with recovery in women with anorexia nervosa.

Changes in marrow adipose tissue with short-term changes in weight in premenopausal women with anorexia nervosa. Serum FGF levels are associated with worsened radial trabecular bone microarchitecture and decreased radial bone strength in women with anorexia nervosa.

Bone 77, 6— Marrow fat and bone—new perspectives. Felson, D. Understanding the relationship between body weight and osteoarthritis.

Baillieres Clin. Hamilton KC, Fisher G, Roy JL, Gower BA, Hunter GR. The effects of weight loss on relative bone mineral density in premenopausal women.

Villareal DT, Fontana L, Das SK, Redman L, Smith SR, Saltzman E, Bales C, Rochon J, Pieper C, Huang M, Lewis M, Schwartz AV, Group CS. Effect of two-year caloric restriction on bone metabolism and bone mineral density in non-obese younger adults: a randomized clinical trial.

Meyer HE, Tverdal A, Selmer R. Weight variability, weight change and the incidence of hip fracture: a prospective study of 39, middle-aged Norwegians. Osteoporos Int. Zibellini J, Seimon RV, Lee CM, Gibson AA, Hsu MS, Shapses SA, Nguyen TV, Sainsbury A.

Does diet-induced weight loss lead to bone loss in overweight or obese adults? A systematic review and meta-analysis of clinical trials.

Johnson KC, Bray GA, Cheskin LJ, Clark JM, Egan CM, Foreyt JP, Garcia KR, Glasser S, Greenway FL, Gregg EW, Hazuda HP, Hergenroeder A, Hill JO, Horton ES, Jakicic JM, Jeffery RW, Kahn SE, Knowler WC, Lewis CE, Miller M, Montez MG, Nathan DM, Patricio JL, Peters AL, Pi-Sunyer X, Pownall HJ, Reboussin D, Redmon JB, Steinberg H, Wadden TA, Wagenknecht LE, Wing RR, Womack CR, Yanovski SZ, Zhang P, Schwartz AV.

The effect of intentional weight loss on fracture risk in persons with diabetes: results from the Look AHEAD randomized clinical trial. Ensrud KE, Ewing SK, Stone KL, Cauley JA, Bowman PJ, Cummings SR.

Intentional and unintentional weight loss increase bone loss and hip fracture risk in older women. J Am Geriatr Soc.

Sogaard AJ, Meyer HE, Ahmed LA, Jorgensen L, Bjornerem A, Joakimsen RM, Emaus N. Does recalled dieting increase the risk of non-vertebral osteoporotic fractures? The Tromso study. Redman LM, Rood J, Anton SD, Champagne C, Smith SR, Ravussin E. Calorie restriction and bone health in young, overweight individuals.

Carrasco F, Ruz M, Rojas P, et al. Changes in bone mineral density, body composition and adiponectin levels in morbidly obese patients after bariatric surgery. Obese Surg — Coates PS, Fernstrom JD, Fernstrom MH, Schauer PR, Greenspan SL.

Gastric bypass surgery for morbid obesity leads to an increase in bone turnover and a decrease in bone mass. Vilarrasa N, San José P, Garcia I, et al.

Evaluation of bone mineral density loss in morbidly obese women after gastric bypass: 3-year follow-up. Obes Surg. von Mach MA, Stoeckli R, Bilz S, Kraenzlin M, Langer I, Keller U.

Changes in bone mineral content after surgical treatment of morbid obesity. Rodríguez-Carmona Y, López-Alavez FJ, González-Garay AG, Solís-Galicia C, Meléndez G, Serralde-Zúñiga AE. Bone mineral density after bariatric surgery. A systematic review.

Int J Surg. Fleischer J, Stein EM, Bessler M, Della Badia M, Restuccia N, Olivero-Rivera L, McMahon DJ, Silverberg SJ. The decline in hip bone density after gastric bypass surgery is associated with extent of weight loss.

Article PubMed PubMed Central CAS Google Scholar. Nogues X, Goday A, Pena MJ, Benaiges D, de Ramon M, Crous X, Vial M, Pera M, Grande L, Diez-Perez A, Ramon JM. Bone mass loss after sleeve gastrectomy: a prospective comparative study with gastric bypass.

Cir Esp. Cifuentes M, López-Alavez FJ, Lewis RD et al. Bone turnover and body weight relationships differ in normal-weight compared to heavier postmenopausal women. Ostrowska Z, Zwirska-Korczala K, Bunter B et al. Assessment of bone metabolism in obese women.

Endocr Regul ; Balsa JA, Botella-Carretero JI, Peromingo R, Caballero C, Munoz-Malo T, Villafruela JJ, Arrieta F, Zamarron I, Vazquez C. Chronic increase of bone turnover markers after biliopancreatic diversion is related to secondary hyperparathyroidism and weight loss.

Relation with bone mineral density. Graat-Verboom L, Spruit MA, van den Borne BE, Smeenk FW, Wouters EF. Whole-body versus local DXA-scan for the diagnosis of osteoporosis in COPD patients.

J Osteoporos. Yu EW, Thomas BJ, Brown JK, Finkelstein JS. Simulated increases in body fat and errors in bone mineral density measurements by DXA and QCT.

Download references. The authors would like to acknowledge the University of Michigan Nutrition Obesity Research Center MNORC: Grant Number DK and the Michigan Center for Diabetes Translational Research MCDTR: Grant Number P30DK from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.

Additional support was provided by the A. Alfred Taubman Medical Institute and the Robert C. and Veronica Atkins Foundation. The funders had no role in the design and conduct of the study; the collection, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript.

Department of Internal Medicine, University of Michigan, 24 Frank Lloyd Wright Dr, Ann Arbor, MI, , USA. Molecular and Integrative Physiology, University of Michigan, Ann Arbor, USA. Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, USA.

Department of Nutritional Sciences, University of Michigan, Ann Arbor, USA. You can also search for this author in PubMed Google Scholar. PC: participated in study concept, design, statistical analysis and drafting the manuscript.

AR: participated in study concept, design, statistical analysis and drafting the manuscript. AK: Helped in drafting the manuscript. NM and KZ: participated with data collection and reviewed the manuscript. CB and CVP: participated in its design and coordination and helped to draft the manuscript.

MP: participated in study concept, design, statistical analysis and drafting the manuscript. All authors read and approved the final manuscript. Correspondence to Palak Choksi. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Choksi, P. et al. Weight loss and bone mineral density in obese adults: a longitudinal analysis of the influence of very low energy diets. Clin Diabetes Endocrinol 4 , 14 Download citation.

Received : 01 March Accepted : 30 May Published : 19 June Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. Research article Open access Published: 19 June Weight loss and bone mineral density in obese adults: a longitudinal analysis of the influence of very low energy diets Palak Choksi ORCID: orcid.

Abstract Background The long-term effect of weight reduction on skeletal health is not well understood. Methods We examined the impact of VLED-induced weight loss on BMD and FFM Fat-free Mass after 3—6 months and again while in weight maintenance at 2 years in 49 subjects.

Results At the end of 2 years, the average weight loss was greater for men weight: Conclusions Despite significant weight loss with VLED, there was only a small loss is BMD. Methods Design We included adults who were enrolled in and completed a 2-year weight management program.

Statistical analysis Descriptive statistics were used to explore the distribution, central tendency, and variation of each measurement, with an emphasis on graphical methods such as histograms, scatterplots, and boxplots. Results Forty-nine participants completed both the induction and maintenance phase and had complete DXA scans available at baseline, at 3—6 months and at the end of 2 years.

Table 1 Morphological characteristics for men and women at baseline and at 2-years Full size table. Table 2 Multiple regression showing the associations between changes in body weight primary predictor and BMD and FFM at 2-years dependent variable , after adjustment for age, sex, and baseline values ANCOVA Full size table.

Full size image. Limitations In this study, DXA imaging at one year was not available. Conclusion Obesity has negative effects on bone metabolism and is associated with a number of cardio-metabolic conditions that pose threats to bone health.

Abbreviations BMD: Bone Mineral Density BMI: Body Mass Index CTX: Serum cross-linked C-Telopeptide DXA: Dual X-Ray Absorptiometry FFM: Fat-Free Mass FM: Fat Mass VLED: Very Low Energy Diets.

References Flegal KM, Carroll MD, Kit BK, Ogden CL. Article PubMed Google Scholar Wang CY, McPherson K, Marsh T, Gortmaker SL, Brown M.

Article PubMed Google Scholar Heaney RPAS, Dawson-Highes B. Article CAS Google Scholar Iqbal J, Zaidi M. Epidemiological Studies. Interventional Studies.

Animal Studies. Statement of Ethics. Disclosure Statement. Funding Sources. Author Contributions. Article Navigation. Review Articles June 28 Is Weight Loss Harmful for Skeletal Health in Obese Older Adults? Subject Area: Geriatrics and Gerontology.

Maria Papageorgiou ; Maria Papageorgiou. a Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, Vienna, Austria.

b Department of Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School, University of Hull, Hull, United Kingdom. This Site. Google Scholar. Katharina Kerschan-Schindl ; Katharina Kerschan-Schindl.

c Department of Physical Medicine, Rehabilitation and Occupational Therapy, Medical University of Vienna, Vienna, Austria.

Thozhukat Sathyapalan ; Thozhukat Sathyapalan. Peter Pietschmann Peter Pietschmann. pietschmann meduniwien. Gerontology 66 1 : 2— Article history Received:. Cite Icon Cite. toolbar search Search Dropdown Menu. toolbar search search input Search input auto suggest.

Table 1. View large. View Large. Table 2. View large Download slide. Proposed mechanisms underlying bone loss during intentional weight loss in obese older adults.

is the recipient of a postdoctoral Ernst Mach Fellowship. The authors have no ethical conflicts to disclose. No funding was granted for this work. Prevalence of adult overweight and obesity in 20 European countries, Search ADS.

Prevalence of obesity among adults and youth: United States, — NCHS data brief, no Obesity Management Task Force of the European Association for the Study of Obesity.

Prevalence, pathophysiology, health consequences and treatment options of obesity in the elderly: a guideline. Osteosarcopenic obesity syndrome: what is it and how can it be identified and diagnosed? Intentional weight loss in older adults: useful or wasting disease generating strategy?

Does diet-Induced weight loss lead to bone loss in overweight or obese adults? A systematic review and meta-analysis of clinical trials. Bone loss, physical activity, and weight change in elderly women: the Dubbo Osteoporosis Epidemiology Study.

Risk factors for longitudinal bone loss in elderly men and women: the Framingham Osteoporosis Study. Intentional and unintentional weight loss increase bone loss and hip fracture risk in older women.

Weight loss: a determinant of hip bone loss in older men and women. The Rancho Bernardo Study. Body weight change since menopause and percentage body fat mass are predictors of subsequent bone mineral density change of the proximal femur in women aged 75 years and older: results of a 5 year prospective study.

Risk factors for bone loss in the hip of year-old women: a 4-year follow-up study. The role of fat and lean mass in bone loss in older men: findings from the CHAMP study. Weight change over three decades and the risk of osteoporosis in men: the Norwegian Epidemiological Osteoporosis Studies NOREPOS.

Voluntary weight reduction in older men increases hip bone loss: the osteoporotic fractures in men study. What is the influence of weight change on forearm bone mineral density in peri- and postmenopausal women?

The health study of Nord-Trondelag, Norway. Predictors of change of trabecular bone score TBS in older men: results from the Osteoporotic Fractures in Men MrOS Study.

Long-Term and Recent Weight Change Are Associated With Reduced Peripheral Bone Density, Deficits in Bone Microarchitecture, and Decreased Bone Strength: The Framingham Osteoporosis Study.

Osteoporotic Fractures in Men MrOS Research Group. Accelerated bone loss in older men: effects on bone microarchitecture and strength. Weight loss in men in late life and bone strength and microarchitecture: a prospective study. Weight change between age 50 years and old age is associated with risk of hip fracture in white women aged 67 years and older.

Weight loss from maximum body weight among middle-aged and older white women and the risk of hip fracture: the NHANES I epidemiologic follow-up study. Weight loss and distal forearm fractures in postmenopausal women: the Nord-Trøndelag health study, Norway.

Increase in Fracture Risk Following Unintentional Weight Loss in Postmenopausal Women: The Global Longitudinal Study of Osteoporosis in Women. Risk factors for hip fracture in white men: the NHANES I Epidemiologic Follow-up Study.

Weight loss in obese older adults increases serum sclerostin and impairs hip geometry but both are prevented by exercise training. Association between weight cycling history and bone mineral density in premenopausal women. Does recalled dieting increase the risk of non-vertebral osteoporotic fractures?

The Tromsø Study. Weight cycling and risk of forearm fractures: a year follow-up of men in the Oslo Study. Weight loss, exercise, or both and physical function in obese older adults. Exercise training in obese older adults prevents increase in bone turnover and attenuates decrease in hip bone mineral density induced by weight loss despite decline in bone-active hormones.

Weighted vest use during dietary weight loss on bone health in older adults with obesity. Effect of exercise modality during weight loss on bone health in older adults with obesity and cardiovascular disease or metabolic syndrome: a randomized controlled trial.

Effect of voluntary weight loss on bone mineral density in older overweight women. Very low calorie diets for weight loss in obese older adults-a randomized trial.

Effect of weight loss and exercise therapy on bone metabolism and mass in obese older adults: a one-year randomized controlled trial. Does high-intensity resistance training maintain bone mass during moderate weight loss in older overweight adults with type 2 diabetes?

Armamento-Villareal R1, Qualls C. Aerobic or resistance exercise, or both, in dieting obese older adults. Change in bone mineral density during weight loss with resistance versus aerobic exercise training in older adults.

Prediction of lumbar vertebral body compressive strength of overweight and obese older adults using morphed subject-specific finite-element models to evaluate the effects of weight loss.

Long-term maintenance of weight loss after lifestyle intervention in frail, obese older adults. Weight loss interventions in older adults with obesity: a systematic review of randomized controlled trials since Why the ISMNI and the Utah paradigm?

Their role in skeletal and extraskeletal disorders. Weight loss and regain and effects on body composition: the Health, Aging, and Body Composition Study. Changes in skeletal integrity and marrow adiposity during high-fat diet and after weight loss.

Bone marrow fat changes after gastric bypass surgery are associated with loss of bone mass. Interaction between bone and muscle in older persons with mobility limitations. Energy restriction reduces bone density and biomechanical properties in aged female rats.

Calcium supplementation suppresses bone turnover during weight reduction in postmenopausal women. A diet high in protein, dairy, and calcium attenuates bone loss over twelve months of weight loss and maintenance relative to a conventional high-carbohydrate diet in adults. Effects of 2-year calorie restriction on circulating levels of IGF-1, IGF-binding proteins and cortisol in nonobese men and women: a randomized clinical trial.

Influence of adipokines and ghrelin on bone mineral density and fracture risk: a systematic review and meta-analysis. Health relevance of the modification of low grade inflammation in ageing inflammageing and the role of nutrition.

Running has a negative effect on bone metabolism and proinflammatory status in male aged rats. Weight loss in obese adults 65years and older: a review of the controversy.

The relevance of mouse models for investigating age-related bone loss in humans. Influence of fat intake and caloric restriction on bone in aging male rats. Effects of aging and caloric restriction on bone structure and mechanical properties.

Impact of energy and casein or whey protein intake on bone status in a rat model of age-related bone loss. Energy-restricted diet benefits body composition but degrades bone integrity in middle-aged obese female rats.

A well-balanced diet combined or not with exercise induces fat mass loss without any decrease of bone mass despite bone micro-architecture alterations in obese rat. Effects of a moderately high-protein diet and interval aerobic training combined with strength-endurance exercise on markers of bone metabolism, microarchitecture and turnover in obese Zucker rats.

Energy restriction is associated with lower bone mineral density of the tibia and femur in lean but not obese female rats. High fat diet-induced animal model of age-associated obesity and osteoporosis. Effects of parathyroid hormone on bone mass, bone strength, and bone regeneration in male rats with type 2 diabetes mellitus.

Bone structure and metabolism in a rodent model of male senile osteoporosis.

Article history Received:. Cite Icon Cite. toolbar search Search Dropdown Menu. toolbar search search input Search input auto suggest. Table 1. View large.

View Large. Table 2. View large Download slide. Proposed mechanisms underlying bone loss during intentional weight loss in obese older adults. is the recipient of a postdoctoral Ernst Mach Fellowship. The authors have no ethical conflicts to disclose.

No funding was granted for this work. Prevalence of adult overweight and obesity in 20 European countries, Search ADS. Prevalence of obesity among adults and youth: United States, — NCHS data brief, no Obesity Management Task Force of the European Association for the Study of Obesity.

Prevalence, pathophysiology, health consequences and treatment options of obesity in the elderly: a guideline. Osteosarcopenic obesity syndrome: what is it and how can it be identified and diagnosed? Intentional weight loss in older adults: useful or wasting disease generating strategy?

Does diet-Induced weight loss lead to bone loss in overweight or obese adults? A systematic review and meta-analysis of clinical trials. Bone loss, physical activity, and weight change in elderly women: the Dubbo Osteoporosis Epidemiology Study.

Risk factors for longitudinal bone loss in elderly men and women: the Framingham Osteoporosis Study. Intentional and unintentional weight loss increase bone loss and hip fracture risk in older women. Weight loss: a determinant of hip bone loss in older men and women.

The Rancho Bernardo Study. Body weight change since menopause and percentage body fat mass are predictors of subsequent bone mineral density change of the proximal femur in women aged 75 years and older: results of a 5 year prospective study.

Risk factors for bone loss in the hip of year-old women: a 4-year follow-up study. The role of fat and lean mass in bone loss in older men: findings from the CHAMP study. Weight change over three decades and the risk of osteoporosis in men: the Norwegian Epidemiological Osteoporosis Studies NOREPOS.

Voluntary weight reduction in older men increases hip bone loss: the osteoporotic fractures in men study. What is the influence of weight change on forearm bone mineral density in peri- and postmenopausal women? The health study of Nord-Trondelag, Norway. Predictors of change of trabecular bone score TBS in older men: results from the Osteoporotic Fractures in Men MrOS Study.

Long-Term and Recent Weight Change Are Associated With Reduced Peripheral Bone Density, Deficits in Bone Microarchitecture, and Decreased Bone Strength: The Framingham Osteoporosis Study.

Osteoporotic Fractures in Men MrOS Research Group. Accelerated bone loss in older men: effects on bone microarchitecture and strength. Weight loss in men in late life and bone strength and microarchitecture: a prospective study.

Weight change between age 50 years and old age is associated with risk of hip fracture in white women aged 67 years and older. Weight loss from maximum body weight among middle-aged and older white women and the risk of hip fracture: the NHANES I epidemiologic follow-up study.

Weight loss and distal forearm fractures in postmenopausal women: the Nord-Trøndelag health study, Norway. Increase in Fracture Risk Following Unintentional Weight Loss in Postmenopausal Women: The Global Longitudinal Study of Osteoporosis in Women.

Risk factors for hip fracture in white men: the NHANES I Epidemiologic Follow-up Study. Weight loss in obese older adults increases serum sclerostin and impairs hip geometry but both are prevented by exercise training.

Association between weight cycling history and bone mineral density in premenopausal women. Does recalled dieting increase the risk of non-vertebral osteoporotic fractures? The Tromsø Study. Weight cycling and risk of forearm fractures: a year follow-up of men in the Oslo Study.

Weight loss, exercise, or both and physical function in obese older adults. Exercise training in obese older adults prevents increase in bone turnover and attenuates decrease in hip bone mineral density induced by weight loss despite decline in bone-active hormones.

Weighted vest use during dietary weight loss on bone health in older adults with obesity. Effect of exercise modality during weight loss on bone health in older adults with obesity and cardiovascular disease or metabolic syndrome: a randomized controlled trial.

Effect of voluntary weight loss on bone mineral density in older overweight women. Very low calorie diets for weight loss in obese older adults-a randomized trial.

Effect of weight loss and exercise therapy on bone metabolism and mass in obese older adults: a one-year randomized controlled trial. Does high-intensity resistance training maintain bone mass during moderate weight loss in older overweight adults with type 2 diabetes?

Armamento-Villareal R1, Qualls C. Aerobic or resistance exercise, or both, in dieting obese older adults. Change in bone mineral density during weight loss with resistance versus aerobic exercise training in older adults.

Prediction of lumbar vertebral body compressive strength of overweight and obese older adults using morphed subject-specific finite-element models to evaluate the effects of weight loss.

Long-term maintenance of weight loss after lifestyle intervention in frail, obese older adults. Weight loss interventions in older adults with obesity: a systematic review of randomized controlled trials since Why the ISMNI and the Utah paradigm? Their role in skeletal and extraskeletal disorders.

Weight loss and regain and effects on body composition: the Health, Aging, and Body Composition Study. Changes in skeletal integrity and marrow adiposity during high-fat diet and after weight loss.

Bone marrow fat changes after gastric bypass surgery are associated with loss of bone mass. Interaction between bone and muscle in older persons with mobility limitations.

Energy restriction reduces bone density and biomechanical properties in aged female rats. Calcium supplementation suppresses bone turnover during weight reduction in postmenopausal women.

A diet high in protein, dairy, and calcium attenuates bone loss over twelve months of weight loss and maintenance relative to a conventional high-carbohydrate diet in adults. Effects of 2-year calorie restriction on circulating levels of IGF-1, IGF-binding proteins and cortisol in nonobese men and women: a randomized clinical trial.

Influence of adipokines and ghrelin on bone mineral density and fracture risk: a systematic review and meta-analysis. Health relevance of the modification of low grade inflammation in ageing inflammageing and the role of nutrition. Running has a negative effect on bone metabolism and proinflammatory status in male aged rats.

Weight loss in obese adults 65years and older: a review of the controversy. The relevance of mouse models for investigating age-related bone loss in humans. Influence of fat intake and caloric restriction on bone in aging male rats. Effects of aging and caloric restriction on bone structure and mechanical properties.

Impact of energy and casein or whey protein intake on bone status in a rat model of age-related bone loss. Energy-restricted diet benefits body composition but degrades bone integrity in middle-aged obese female rats.

A well-balanced diet combined or not with exercise induces fat mass loss without any decrease of bone mass despite bone micro-architecture alterations in obese rat.

Effects of a moderately high-protein diet and interval aerobic training combined with strength-endurance exercise on markers of bone metabolism, microarchitecture and turnover in obese Zucker rats. Energy restriction is associated with lower bone mineral density of the tibia and femur in lean but not obese female rats.

High fat diet-induced animal model of age-associated obesity and osteoporosis. Effects of parathyroid hormone on bone mass, bone strength, and bone regeneration in male rats with type 2 diabetes mellitus.

Bone structure and metabolism in a rodent model of male senile osteoporosis. Effect of genetic strain and gender on age-related changes in body composition of the laboratory rat.

Long bones from the senescence accelerated mouse SAMP6 have increased size but reduced whole-bone strength and resistance to fracture. Karger AG, Basel. Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.

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View Metrics. Email alerts Online First Alert. Latest Issue Alert. Citing articles via Web Of Science CrossRef Latest Most Read Most Cited Examining a healthy lifestyle as a moderator of the relationship between psychological distress and cognitive decline among older adults in the NuAge study.

Erratum - Association of Multi-Dimensional Factors with Accelerating Age and Constructing a Healthy Lifestyle Index: Guangzhou Biobank Cohort Study.

The Trajectory of Successful Aging: Insights from Metagenome and Cytokine Profiling. Sertraline Promotes Health and Longevity in Caenorhabditis elegans. Harnessing Speech-Derived Digital Biomarkers to Detect and Quantify Cognitive Decline Severity in Older Adults.

Suggested Reading The Role of Parathyroid Hormone in the Management of Osteoporosis Hormone Research November, Assessment of Bone Architecture with Ultrasonometry: Experimental and Clinical Experience Hormone Research November, Lead Accumulation in the Bones of Aging Male Mice Gerontology April, A recent study found that women with SO were more easy to show elevated blood glucose, while men with SO were more likely to present with OP and dyslipidemia Du et al.

On the other hand, muscles secrete a set of cytokines called myokines, thereby regulating bone metabolism. Myostatin, as a key myokine, has been reported for its effect on bone. Myostatin can inhibit osteogenic differentiation of BMSCs, as well as osteoblast differentiation and mineralization Hamrick et al.

Likewise, myostatin may inhibit osteogenesis by activating the RANKL signaling pathway, thus showing an adverse impact on bone mass Saad, Thus, inhibition or blocking of the myostatin signaling pathway may provide potential therapeutic targets for a number of diseases, particularly in sarcopenia and OP.

Several studies have reported the links between BMD and body fat and lean mass. When body weight was stratified into lean body mass and fat mass, the increase in BMD was more pronounced for lean body mass, whereas fat mass was only beneficial for men and premenopausal women.

Santos et al. also observed a more direct relationship between lean body mass and bone density total bone density, femur, and spine , while sarcopenia was associated with OP. Obesity was more likely to be a protective factor for OP in old subjects aged 80 and over Santos et al.

At the same time, Barrera et al. demonstrated the beneficial effects of high BMI on femoral neck bone density in older adults. In particular, obese people were reported to have higher bone density, but they also showed damaged bone microstructures and different fall patterns Compston, ; Ilich et al.

Conclusions about the relationship between obesity and bone in humans rely on statistical correlations or models, rather than controlled trials. Therefore, the establishment of obesity mouse model is helpful to study the effect of high-fat diet HFD -induced obesity on bone metabolism.

Studies have shown that obese animals burn the same amount of energy, no matter how much fat is in their diet Brown et al. The mice provided a model for studying the relationship between body size, obesity and skeletal characteristics.

High fat intake in rodents leads to obesity, and several studies have shown a strong link between bone size, strength and body size. However, mice are not always reliable indicators of human pathophysiology.

Human can enjoy more colorful life style, more abundant food and more complicated living environment. Moreover, patients with obesity often have multiple complications, not just weight gain. These factors make the relationship between obesity and bone more complex in humans than in mice.

The effects of a high-fat diet on cancellous bone in rodents have been shown to be harmful. In addition, in obese mice, serum leptin levels were associated with bone trabeculae, but not cortical bone density, while adiponectin and total cholesterol levels were not associated with bone mass Fujita et al.

Scheller et al. In addition, Inzana et al. A recent study conducted by Tian et al. In other words, after short-term feeding, HFD may show a positive effect on bone mass, however, after long-term feeding, bone mass was significantly decreased in HFD mice. However, the effects of diet induced obesity on cortical bone in rodents are less clear, with positive, negative, and neutral results reported.

The femoral cortical thickness and cross-sectional area of 4-week old male mice were increased after feeding HFD-DAG Diacylglycerol. HFD-DAG had obvious promoting effect on bone and bone metabolism Choi et al.

In addition, Silva et al. recently suggested that a high-fat diet had beneficial effects on most femoral size and skeletal mechanical properties, as well as radius size and stiffness Silva et al. However, Ionova-Martin et al. found that femur strength, hardness, and toughness were significantly lower in both young and adult mice fed HFD than in the control group Ionova-Martin et al.

In contrast, Cao et al. concluded that feeding mice HFD for 14 weeks reduced proximal tibial cancellous bone mass in young mice, but had no effect on cortical bone mass Cao et al. Halade et al.

To sum up, in the above studies, the effect of HFD on cortical bone was not as significant as that on cancellous bone. It is generally believed that age-related OP has three main processes. The first and most important process is reduction of trabecular bone, the second is continuous bone resorption on the cortical surface, and the third is cortical bone loss Chen et al.

Similarly, the above studies indicate that the most significant change in obesity-related bone loss is the reduction of femoral trabecular bone Combined, these results suggest that HFD could regulate the changes of trabecular and cortical bone in different ways.

This may be due to the fact that cancellous bone generally responds more strongly to diet or drug therapy, physiological conditions, or aging than cortical bone, because cancellous bone is more active in remodeling because of its larger surface to volume ratio than cortical bone Morgan et al.

On the other hand, bearing capacity and mechanical stress are important factors in determining cortical bone mass, while trabecular bone density is affected by sex maturation related hormones Mora et al.

In addition to affecting bone structure, HFD can also have significant effects on cell function. Bone mass reflects the balance between bone formation and bone resorption and is involved in the coordination and regulation of the number and activity of osteoblasts and osteoclasts at the cellular level.

A previous study showed that the expression of RANKL, the ratio of RANKL to OPG, and the level of serum TRAP in osteoblasts from HFD mice were increased, suggesting that HFD can promote osteoclast activity and bone resorption Cao et al.

Notably, Halade et al. reported that in mice fed HFD, the accumulation of bone marrow adipocytes resulted in significantly higher levels of pro-inflammatory factors, leading to increased bone resorption. Furthermore, Shu et al. The elevated osteoclast precursor frequency, increased osteoclast formation, and bone resorption activity, along with increased osteoclastogenic regulators such as RANKL, TNF, and PPARγ were seen in bone marrow cells from HFD-fed mice.

But, osteoblast function was also increased after 12 weeks of HFD Shu et al. A possible explanation is that mechanical load of body weight stimulates bone formation, reduces apoptosis, and enhances proliferation and differentiation of osteoblasts and osteocytes.

Therefore, it was not surprising that bone formation rates and osteoblast numbers increased in this study, since HFD mice were significantly heavier than the control group Bonewald and Johnson, In conclusion, it is reasonable to believe that the bone loss caused by HFD is mainly related to the promotion of osteoclast differentiation and activity by changing the bone marrow microenvironment.

Obesity initially has a beneficial effect on bones, possibly due to anabolic effects that increase mechanical load. However, due to the development of metabolic complications including systemic inflammation, the second stage is followed by a reduction in bone formation Lecka-Czernik et al.

As mentioned above, these results may support the idea that as obesity rises, the benefits for bone health are diminishing. In conclusion, obesity or overweight is strictly related to bone metabolism, although the correlation has not yet been fully unified.

Adipose tissue interacts with bone by secreting various cytokines, so as to regulate bone health. Meanwhile BMAT also exerts a crucial impact on bone density and bone microstructure.

In addition, human obesity is a complex problem that involves not only excessive fat intake but also other nutrient consumption imbalances such as vitamin D, calcium and phosphorus, which are known to affect bone metabolism, further making it difficult to determine the impact of obesity on human bone health.

Moreover, while BMI is closely related to the gold standard of body fat, it does not distinguish between lean and fat mass, nor does it provide an indication of the distribution of body fat. The loss of muscle mass in the elderly means that BMI is also less accurate at predicting body fat in this group.

Therefore, determining whether obesity causes changes in bone mass based on BMI is less accurate. Central obesity measures, including waist circumference, waist-to-height ratio and waist-to-hip ratio, are better predictors of visceral obesity, bone-related disease and mortality than BMI.

Simply put, all of these findings indicate that skeletal response to obesity has either a positive or negative effect on bone, suggesting that the influence of obesity on bone metabolism is intricate and depend on diverse factors, such as mechanical load by the weight, obesity type, the location of adipose tissue, gender, age, and bone sites, along with secreted cytokines, these factors may play a major function for bone health.

The effects of obesity on bone metabolism and bone microstructure involve these multiple factors, which may exert different regulatory mechanisms and ultimately affect the skeletal health. The investigation of the relationship between obesity and bone is conducive to finding new targets for the treatment of bone-related diseases, including OP, fractures, RA, and OA.

JH wrote the manuscript. CH, WH, and MY revised the manuscript. CL and XL were responsible for the guidance and supervision. All authors contributed to the article and approved the submitted version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Agbaht, K. Circulating adiponectin represents a biomarker of the association between adiposity and bone mineral density.

Endocrine 35, — doi: PubMed Abstract CrossRef Full Text Google Scholar. Al Saedi, A. Rapamycin affects palmitate-induced lipotoxicity in osteoblasts by modulating apoptosis and autophagy. A Biol. Alissa, E. Relationship between serum resistin, body fat and inflammatory markers in females with clinical knee osteoarthritis.

Knee 27, 45— Arango-Lopera, V. Mortality as an adverse outcome of sarcopenia. Health Aging 17, — Ardawi, M. Increased serum sclerostin and decreased serum IGF-1 are associated with vertebral fractures among postmenopausal women with type-2 diabetes. Bone 56, — Astudillo, P. Baggio, L.

Biology of incretins: GLP-1 and GIP. Gastroenterology , — Bao, J. Leptin plays a catabolic role on articular cartilage. Barba, C. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies.

Lancet , — CrossRef Full Text Google Scholar. Barrera, G. A high body mass index protects against femoral neck osteoporosis in healthy elderly subjects. Nutrition 20, — Bartell, S. Bone Miner. Beekman, K. Google Scholar. Bijlsma, J.

Osteoarthritis: an update with relevance for clinical practice. Bonewald, L. Osteocytes, mechanosensing and Wnt signaling. Bone 42, — Boon, M. BMP7 activates brown adipose tissue and reduces diet-induced obesity only at subthermoneutrality.

PLoS One 8:e Borges, J. Diabetes Obes. Brandt, K. Yet more evidence that osteoarthritis is not a cartilage disease. Bredella, M. Increased bone marrow fat in anorexia nervosa. Determinants of bone mineral density in obese premenopausal women.

Bone 48, — Vertebral bone marrow fat is positively associated with visceral fat and inversely associated with IGF-1 in obese women. Obesity Silver Spring 19, 49— Brentano, F.

Arthritis Rheum. Brown, J. Effect of high-fat diet on body composition and hormone responses to glucose tolerance tests. Endocrine 19, — Brun, J. Diabetes 66, — Burguera, B. Leptin reduces ovariectomy-induced bone loss in rats. Endocrinology , — Cao, J.

Involuntary wheel running improves but does not fully reverse the deterioration of bone structure of obese rats despite decreasing adiposity. Tissue Int. High-fat diet decreases cancellous bone mass but has no effect on cortical bone mass in the tibia in mice.

Bone 44, — Carobbio, S. Adipose tissue function and expandability as determinants of lipotoxicity and the metabolic syndrome. Chaplais, E.

Effects of interventions with a physical activity component on bone health in obese children and adolescents: a systematic review and meta-analysis. Chen, H. Site-specific bone loss in senescence-accelerated mouse SAMP6 : a murine model for senile osteoporosis. Chen, X. Roles of leptin in bone metabolism and bone diseases.

Chen, Y. GDF8 inhibits bone formation and promotes bone resorption in mice. Cherif, R. Positive Association of Obesity and insulin resistance with bone mineral density in Tunisian postmenopausal women.

Choi, H. Multifaceted physiological roles of adiponectin in inflammation and diseases. Adiponectin may contribute to synovitis and joint destruction in rheumatoid arthritis by stimulating vascular endothelial growth factor, matrix metalloproteinase-1, and matrix metalloproteinase expression in fibroblast-like synoviocytes more than proinflammatory mediators.

Arthritis Res. Yonsei Med. Coelho, M. Biochemistry of adipose tissue: an endocrine organ. Compston, J. Obesity and fractures. Joint Bone Spine 80, 8— Type 2 diabetes mellitus and bone. Obesity is not protective against fracture in postmenopausal women: GLOW.

Conde, J. Adipokines and osteoarthritis: novel molecules involved in the pathogenesis and progression of disease. Arthritis Cui, Y. Molecular basis and therapeutic potential of myostatin on bone formation and metabolism in orthopedic disease. Biofactors 71, — Dalamaga, M. Adiponectin as a biomarker linking obesity and adiposopathy to hematologic malignancies.

de Araujo, I. Marrow adipose tissue spectrum in obesity and type 2 diabetes mellitus. De Laet, C. Body mass index as a predictor of fracture risk: a meta-analysis. Del Mar Gonzalez-Barroso, M.

Di Angelantonio, E. Body-mass index and all-cause mortality: individual-participant-data meta-analysis of prospective studies in four continents. Ding, C.

Metabolic triggered inflammation in osteoarthritis. Osteoarthritis Cartilage 41, 90— Dobson, R. Metabolically healthy and unhealthy obesity: differential effects on myocardial function according to metabolic syndrome, rather than obesity. Dormuth, C. Thiazolidinediones and fractures in men and women.

Du, Y. Sex differences in the prevalence and adverse outcomes of sarcopenia and sarcopenic obesity in community dwelling elderly in East China using the AWGS criteria. BMC Endocr. Ducy, P.

Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell , — Elbaz, A. Inhibition of fatty acid biosynthesis prevents adipocyte lipotoxicity on human osteoblasts in vitro.

Fassio, A. The obesity paradox and osteoporosis. Weight Disord. Fazeli, P. Marrow fat and preadipocyte factor-1 levels decrease with recovery in women with anorexia nervosa.

Changes in marrow adipose tissue with short-term changes in weight in premenopausal women with anorexia nervosa. Serum FGF levels are associated with worsened radial trabecular bone microarchitecture and decreased radial bone strength in women with anorexia nervosa.

Bone 77, 6— Marrow fat and bone—new perspectives. Felson, D. Understanding the relationship between body weight and osteoarthritis. Baillieres Clin. Felson, T. Effect of weight and body mass index on bone mineral density in men and women: the Framingham study.

Feng, X. Body mass index and the risk of rheumatoid arthritis: an updated dose-response meta-analysis. Ferron, M. Del, DePinho, R.

Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Frontini, A. Distribution and development of brown adipocytes in the murine and human adipose organ.

Cell Metab. Fruhbeck, G. The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation. Fujita, Y. Serum leptin levels negatively correlate with trabecular bone mineral density in high-fat diet-induced obesity mice.

Neuronal Interact. Gimble, J. Peroxisome proliferator-activated receptor-gamma activation by thiazolidinediones induces adipogenesis in bone marrow stromal cells. Glogowska-Szelag, J. Assessment of selected adipocytokines in obese women with postmenopausal osteoporosis.

Gordeladze, J. Leptin stimulates human osteoblastic cell proliferation, de novo collagen synthesis, and mineralization: impact on differentiation markers, apoptosis, and osteoclastic signaling.

Gremese, E. Obesity as a risk and severity factor in rheumatic diseases autoimmune chronic inflammatory diseases. Grotle, M. BMC Musculoskelet. Halade, G. El, Williams, P. Obesity-mediated inflammatory microenvironment stimulates osteoclastogenesis and bone loss in mice.

Hamrick, M. Leptin deficiency produces contrasting phenotypes in bones of the limb and spine. Bone 34, — Loss of myostatin GDF8 function increases osteogenic differentiation of bone marrow-derived mesenchymal stem cells but the osteogenic effect is ablated with unloading.

Bone 40, — Hao, R. Association between fibroblast growth factor 21 and bone mineral density in adults. Endocrine 59, — Hardouin, P. Bone marrow adipose tissue: to be or not to be a typical adipose tissue? Lausanne Holloway, W. Leptin inhibits osteoclast generation. Horowitz, M. Bone marrow adipocytes.

Adipocyte 6, — Huang, C. Adiponectin increases BMP-2 expression in osteoblasts via AdipoR receptor signaling pathway. Huang, Y. MicroRNA regulates aging-associated metabolic phenotype. Aging Cell e Hunter, D.

Ilich, J. Osteosarcopenic obesity syndrome: what is it and how can it be identified and diagnosed? Interrelationship among muscle, fat, and bone: connecting the dots on cellular, hormonal, and whole body levels.

Ageing Res. Inzana, J. Immature mice are more susceptible to the detrimental effects of high fat diet on cancellous bone in the distal femur. Bone 57, — Ionova-Martin, S. III, Lane, N. Changes in cortical bone response to high-fat diet from adolescence to adulthood in mice.

Johansson, A. Insulin-like growth factor I stimulates bone turnover in osteoporosis. Lancet Johnson, W. Patterns of linear growth and skeletal maturation from birth to 18 years of age in overweight young adults.

Jurimae, J. The influence of ghrelin, adiponectin, and leptin on bone mineral density in healthy postmenopausal women. Justesen, J. Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis.

Biogerontology 2, — Kahn, S. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. Kalichman, L. Hand osteoarthritis in Chuvashian population: prevalence and determinants. Kanazawa, I. Assessment using serum insulin-like growth factor-I and bone mineral density is useful for detecting prevalent vertebral fractures in patients with type 2 diabetes mellitus.

Serum insulin-like growth factor-I is a marker for assessing the severity of vertebral fractures in postmenopausal women with type 2 diabetes mellitus. Effects of intensive glycemic control on serum levels of insulin-like growth factor-I and dehydroepiandrosterone sulfate in type 2 diabetes mellitus.

Kang, D. Association of body composition with bone mineral density in northern Chinese men by different criteria for obesity. Research in a review highlights a positive association between bone mass density and fruit and vegetable consumption, which may be due to vitamin intake.

The authors also highlight research suggesting vitamin C intake may improve bone health and protect against osteoporosis. They list the following vegetables as good sources of vitamin C:. Another review suggests that consuming fewer than five servings of fruit or vegetables per day increases the risk of hip fractures.

Calcium is the primary nutrient for bone health. As the bones break down and grow each day, it is essential to get enough calcium. The best way to absorb calcium is to consume foods containing calcium every day.

Getting calcium through the diet is best unless a doctor advises otherwise. Vitamin K2 is essential to bone health. It reduces calcium loss and helps minerals bind to the bones. Vitamin D helps the body absorb calcium. People with vitamin D deficiencies have a higher risk of losing bone mass.

A person can absorb vitamin D through moderate sun exposure. Without sufficient vitamin D, a person has a higher risk of developing bone disease, such as osteoporosis or osteopenia.

A moderate weight is essential for bone density. People with underweight have a higher risk of developing bone disease. Overweight and obesity put additional stress on the bones. Doctors recommend people avoid rapid weight loss and cycling between gaining and losing weight.

As a person loses weight, they can lose bone density, but gaining back the weight will not restore bone density. This reduction in density can lead to weaker bones. Super low calorie diets can lead to health problems, including bone density loss.

Before restricting calories, discuss calorie needs with a qualified healthcare professional, such as a primary care doctor or registered dietitian, to determine a safe target number of calories to consume. Protein plays an essential role in bone health and density.

A cross-sectional study examined bone mass and dietary protein intake in 1, older adults. Researchers associated higher bone mass density with higher intakes of total and animal protein. However, they associated lower bone mass density with plant protein intake. Researchers call for further studies, particularly into how a plant-based diet may affect bone health and density.

Research suggests that omega-3 fatty acids play a role in maintaining bone density and overall bone health. Like calcium, magnesium and zinc are minerals that support bone health and density. Magnesium helps activate vitamin D so it can promote calcium absorption.

Zinc exists in the bones. It promotes bone growth and helps prevent the bones from breaking down. Many people associate smoking with lung cancer and breathing issues, but smoking can also increase the risk of conditions such as osteoporosis and bone fractures.

To support healthy bone density, a person can avoid or quit smoking , especially during their teens and young adulthood. However, long-term heavy drinking can lead to poor calcium absorption, a decrease in bone density, and the development of osteoporosis later in life.

Moderate alcohol consumption is considered two drinks or fewer per day for males and one drink or fewer per day for females.