Smoking Cessation and Mental Health: A briefing for front-line staff. Smoking cessation and smokefree policies: Good practice for mental health services. Smoking cessation and cannabis use.

Stopping Smoking in Pregnancy: A briefing for maternity care providers. Stop smoking aids. Stop smoking aids resources. Stop smoking aids quick reference sheet. Vaping resources. Vaping: a guide for health and social care professionals.

Information for specialist stop-smoking services that are considering providing e-cigarette starter packs: recommendations from the Trial of Ecigarettes TEC.

Nicotine Replacement Therapy. Nicotine Gum. Unlicensed varenicline. Secondary care resources. How were these factsheets put together? Interventions in Secondary Care - Orthopedic Patients Factsheet NHS Smokefree, Inpatient Tobacco Dependence Treatment Resources.

Inpatient Tobacco Dependence Treatment: Best Practices and Key Messages. NHS Acute Inpatient Tobacco Dependence Advisor Training Resources. NHS Mental Health Inpatient Tobacco Dependence Advisor Training Resources.

Communicating with high-risk individuals about lung cancer screening. Communicating with high-risk individuals about lung cancer screening training module. NHSE Competency frameworks for tobacco dependence treatment in secondary care.

Appendix A: NHSE Competency Frameworks Overview. In a review , researchers summarized the latest research into the way smoking causes osteoporosis. They found that smoking may, directly and indirectly, induce osteoporosis in several different ways.

The researchers also noted that there are currently no effective ways to stop smoking-induced osteoporosis because scientists do not fully understand the specific mechanisms through which smoking affects bone metabolism.

In the study mentioned above, researchers found that smoking may cause other bone-related conditions, such as:. Smoking may also :. People can manage their osteoporosis symptoms. Stopping smoking at any stage of life may help limit smoking-related bone loss, which helps manage osteoporosis.

Other tips for managing osteoporosis can help people slow bone loss and reduce their risk of fractures. These tips include :. Healthcare professionals can help people quit smoking.

Doctors may prescribe treatments to help people quit, such as:. The CDC has a free quitline to help people stop smoking. The helpline provides confidential free coaching with a trained quit coach.

A person can access the helpline by calling in the U. Doctors can also find out if someone may be at risk of osteoporosis and help them reduce their risk of developing the condition.

If a person does have osteoporosis, a healthcare professional can help them manage the condition. Scientists have linked smoking to osteoporosis in several studies. While people who smoke tend to have an increased risk of developing osteoporosis, this may be due to them having other risk factors for the condition, as well.

People can also manage osteoporosis by eating a balanced diet, avoiding activities that may cause fractures, limiting alcohol consumption, and preventing falls. A person should speak with a doctor for further information about quitting smoking and managing osteoporosis on an individual basis.

Estrogen plays an important role in maintaining bone structure. Here, learn how having low estrogen, possibly due to menopause, can lead to…. Secondary osteoporosis occurs as a result of a medical condition or medication rather than because of age. Learn more about the causes.

There is not one type of doctor that treats osteoporosis, as professionals of different medical disciplines can help manage the condition. HIF1alpha is required for osteoclast activation by estrogen deficiency in postmenopausal osteoporosis. USA , — Article ADS PubMed Google Scholar.

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FEBS Lett. Peng, G. Genomics 17 , — Hoshi, H. Aldehyde-stress resulting from Aldh2 mutation promotes osteoporosis due to impaired osteoblastogenesis.

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Download references. Miyamoto was supported by a grant-in-aid for Scientific Research in Japan and a grant from the Japan Agency for Medical Research and Development. Sato and K. Sato were supported by a grant-in-aid for Scientific Research in Japan.

Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, , Japan. Department of Advanced Therapy for Musculoskeletal Disorders II, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, , Japan.

Department of Musculoskeletal Reconstruction and Regeneration Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, , Japan. Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, , Japan.

Institute for Integrated Sports Medicine, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, , Japan. Chuo Naika Clinic, Nihon-bashi Ningyou-chou, Chuo-ku, Tokyo, , Japan.

Department of Orthopedic Surgery, Kumamoto University, Honjo, Chuo-ku, Kumamoto, , Japan. You can also search for this author in PubMed Google Scholar. analyzed human data and performed animal experiments.

and H. collected human samples. and T. prepared animals for experiments. analyzed data. designed the study. wrote the manuscript. All authors discussed the results and commented on the manuscript.

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Skip to main content Thank you for visiting nature. nature scientific reports articles article. Download PDF. Subjects Calcium and phosphate metabolic disorders Metabolic disorders Osteoporosis. Abstract Smoking is thought to be a risk factor for osteoporosis development; however, the consequences of stopping smoking for bone homeostasis remain unknown.

Introduction Bone homeostasis is regulated by a delicate balance between osteoclastic bone resorption and osteoblastic bone formation; failure to maintain that balance promotes changes in bone mass 1.

Results Bone mineral density is significantly lower in smokers than in non-smokers among post-menopausal females For this analysis, we invited women over 40 years of age Fig. Figure 1. Full size image.

Table 1 Basic characteristics of pre- and post-menopausal subjects. Full size table. Figure 2. Figure 3. Figure 4. Table 2 Comparison of factors relevant to bone metabolism before and after smoking cessation.

It is important to note that different ways of nicotine administration could interfere in its systemic absorption, altering bone turnover impact. The inhalation of nicotine induces higher levels of this substance compared with subcutaneously administration. Thus, clinical studies have been showed that the interruption of smoking habit before the elective surgeries diminishes the time required for bone healing as well the complications after surgery Lower levels of nicotine and cotinine, that is a compound of nicotine, are detected in serum and urine of patients after smoking cessation Probably, part of these benefits could be attributed to the decreased systemic levels of nicotine and a consequent oxidative stress reduction after a smoking cessation.

Osteoporosis is characterized by low BMD and weakening of bone tissue, which leads to gradual bone fragility and can causes fractures. Among all the treatable causes of osteoporosis, smoking has been established as an important contributing risk factor.

It affects the balance of the naturally occurring processes of bone resorption and bone formation, resulting in low BMD as the amount resorbed is not totally replaced Few studies are available regarding the pathophysiological mechanisms by which smoking would lead to bone loss and the assessment of the clinical association of them.

Smoking is thought to cause low bone density through numerous pathways. Among the currently available studies, there is the fact that, in general, smokers have lower weight and body mass index BMI , which is postulated to provide an osteogenic stimulus and it is linked to higher BMD 6 , They also found lower serum levels of vitamin D in smokers, which is required for good bone health.

Furthermore, there is an impaired intestinal calcium absorption associated with changes in the metabolism of calciotropic hormones. Smoking has been linked to changes in hormone household, leading to a decrease in parathyroid hormone i.

Those changes have been linked to an increased risk of osteoporosis. It is imperative to reassure that woman who smoke have alterations in the metabolism of sex hormones leading to a lower level of estradiol and menopause at an earlier age when compared to non-smokers When men are evaluated, the studies are conflicting, but some have shown inhibition of aromatase similar to that found in women and, consequently, reduced production of estradiol from testosterone.

In addition, there is a negative impact on the angiogenesis required for bone metabolism Smokers are more likely to suffer from peripheral vascular disease, reducing the bone blood supply.

As smokers are weaker with less lean mass, they have poorer balance and impaired neuromuscular performance, which may also increase the risk of falls Few studies are available regarding the effect of smoking cessation on bone health.

One study found an intermediate risk of fracture in ex-smokers. And another one discovered that the effect of smoking on bone density was reversible, and the bone density of ex-smokers improved in less than 10 years i.

Another two studies reported that subjects exposed to secondhand smoke had significantly lower phalangeal BMD and higher risk for femoral neck osteoporosis than unexposed subjects 29, 97, OS is generated as a result of insufficient activity of the endogenous antioxidant defense system against reactive oxygen species ROS The results have been further shown by cross-sectional and case-control studies, in which OS was characterized by a high level of F2-isoprostanes in urine and a low level of antioxidant enzymes in blood, along with a reduced bone mineral density and an increased risk of osteoporosis , Studies suggested that homocysteine Hcy played an important role in bone metabolism and had been involved in osteoporotic facture incidence The results of a meta-analysis showed increased Hcy and nitric oxide NO in the postmenopausal osteoporosis PO subjects, while it showed decreased levels of folate and total antioxidant power TAP , along with lower activity of superoxide dismutase SOD and glutathione peroxidase GPx in these subjects.

The imbalance of ROS and antioxidant system may contribute to functional and structural remodeling that favors the occurrence of PO Despite of clinical evidence of increased incidence of bone diseases amongst smokers as well as worsening recovery in orthopedic surgeries, it is still unclear which pathological mechanisms are induced by CS and how these events impair bone turnover.

To describe these pathological mechanisms, animal models and in vitro studies have been performed to describe different bone cells activities and signaling pathways regulating cells interactions.

Part of these findings pointed out the CS-induced oxidative stress importance in the impairment of bone turnover resulting in damage of mineral and organic bone matrix which corroborate with clinical studies that have extensively showed lower BMD and increased bone fragility in smokers.

Although it is difficult to perform measurement of ROS due to its short half-life, there are some clinical studies that showed increased levels of F2 isoprostanes as well as 8-isoprostanes in urine samples form smokers compared with non-smokers and in patients with osteoporosis, revealing the oxidative stress occurrence.

However, until now, the majority of experimental and clinical studies have evaluated levels of vitamins, or antioxidant enzymes, which are informative; but they only reflect one side of the redox homeostasis, leaving the question of whether decreased levels are actually indicative of increased oxidative stress occurrence In this context, the administration of antioxidant compounds showed a reduction in ROS production in experimental studies and beneficial results in smokers with periodontal diseases, revealing this therapeutic approach as promisor to ameliorate bone healing even under smoking conditions.

Clinical management are still mainly based in radiographic images. X-Rays and CT-Scans reveal only the final result of bone structural changes. It is not possible to investigate the different cell types and not even the components of bone matrix separately.

Moreover, the majority of these exams detect structural changes only after the establishment of bone diseases that are worsening by smoking. The association between radiographic images and specific biomarkers in serum could be useful to facilitate the clinical management.

These measurements could be performed in tissue as well in serum or urine samples to evaluate the impact of smoking cessation in the diminishment of oxidative stress markers and how it impacts bone turnover, revealing the best moment for elective orthopedic surgeries.

Also, it will be useful to evaluate the efficacy of different treatments, such as antioxidants, in different bone diseases that are worsening by smoking. Smoking Bone loss Bone turnover Bone matrix Oxidative stress Bone fragility. Home Articles Article Details.

Highlights We present the newest findings in understanding the impact of smoking in bone matrix composition. Introduction Smoking effects on bone: Epidemiological evidence Cigarette smoking is recognized as an important risk factor for several diseases, such as chronic obstructive pulmonary disease, cancer, heart attack and vascular diseases Increased Reactive Oxygen Species production: Oxidative Stress Oxidative stress is a physiological mechanism characterized by an imbalance between oxidants and antioxidants components.

ROS: Reactive Oxygen Species; RANK: Receptor Activator of Nuclear Factor κ B; RANKL: Receptor Activator of Nuclear Factor kB ligand; MSCs Mesenchymal stromal cells Figure 2 : The effects of the CS-induced oxidative stress showed in experimental and clinical studies in bone mineral A and organic B matrix.

ROS: Reactive Oxygen Species; RANKL: Receptor Activator of Nuclear Factor kB ligand Enzymatic reactions such as those involved in respiratory chain, cytochrome P system, phagocytosis, and prostaglandin synthesis are recognized by oxidants generation The smoking-induced oxidative stress effects in bone turn over Oxidative stress effects in bone mineral matrix Inorganic and organic components are present in bone matrix.

Oxidative stress effects in bone organic matrix The organic components of bone tissue include collagen fiber types I and V, proteoglycans, growth factors and cytokines. Clinical aspects of smoking and bone health Osteoporosis is characterized by low BMD and weakening of bone tissue, which leads to gradual bone fragility and can causes fractures.

Final considerations and new directions Despite of clinical evidence of increased incidence of bone diseases amongst smokers as well as worsening recovery in orthopedic surgeries, it is still unclear which pathological mechanisms are induced by CS and how these events impair bone turnover.

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For the second study, we invited current smokers who had visited smoking cessation clinics as outpatients Fig. Among them, and 36 were male and female, respectively Fig.

Among that , 54 males and 22 females reported success in stopping smoking Fig. Among that 76, we performed blood tests in 64 subjects immediately before and then approximately days after smoking cessation to evaluate cotinine levels Fig. Blood cotinine levels significantly decreased after smoking cessation in 47 of 64 subjects Fig.

Based on this analysis, we concluded that these 47 subjects successfully quit smoking. Blood cotinine levels decrease in subjects who successfully quit smoking. a Flow chart of subjects participating in a smoking cessation program.

Informed consent was obtained from all subjects enrolled, and their progression is shown as indicated. We then monitored changes in various biochemical parameters in individuals who had successfully stopped smoking Fig. S1 and Table 2. First, we focused on bone markers and found that parameters associated with bone resorption, namely, urinary NTX and deoxypyridinoline and serum TRACP5b levels, were unchanged after smoking cessation Fig.

However, serum levels of some parameters associated with bone formation, namely osteocalcin and ucOC, significantly increased after subjects quit smoking, although levels of other bone formation factors such as total type 1 procollagen-N-propeptide P1NP and bone specific alkaline phosphatase BAP did not Fig.

To identify potential regulators of osteocalcin and ucOC levels, we assessed other factors associated with bone metabolism Table 2. However, serum levels of pentosidine, homocysteine, parathyroid hormone PTH , 25 OH D, and estradiol E2 , all implicated in regulating bone homeostasis, were comparable in these subjects before and after they stopped smoking Table 2.

Changes in bone parameters after smoking cessation. a Analysis of bone-resorption parameters such as urinary NTX and deoxypyridinoline, and serum TRACP5b before Before and after After smoking cessation.

E after relative to before smoking cessation of NTX, deoxypyridinoline, and TRACP5b. b Analysis of bone formation markers evaluated in sera before Before and after After smoking cessation.

Dotted lines indicate baselines. Finally, we asked whether bone homeostasis would improve in nicotine-treated mice once drug was withdrawn Fig. To do so, first we conducted bone mineral density analysis, and TRAP and toluidine blue staining of femoral bone and tibial bone sections, respectively, in mice that had been treated with and without nicotine cross sectionally Fig.

These data indicated that daily subcutaneous administration of nicotine to wild-type mice over a 3-week period starting at 8 weeks of age reduced bone mass relative to untreated controls, but those changes were not significant Fig.

However, when we examined bone sections from these mice, nicotine-administered mice showed a significant increase in the number of osteoclasts relative to controls Fig. We then examined bone mass longitudinally in nicotine-administered mice 2 weeks after nicotine withdrawal, when mice were 13 weeks of age Fig.

These mice showed significantly elevated bone mineral density compared to mice evaluated immediately after 3 weeks of nicotine treatment Fig.

Twelve-week-old mice that had undergone 1 week of nicotine withdrawal also showed decreased levels of serum TRACP5b than did control mice treated with nicotine for 3 weeks Fig. Nicotine administration stimulates osteoclastogenesis in mice.

a , b Eight-week-old wild-type female mice were administered nicotine or PBS vehicle control for 3 weeks and then bone mineral density of femurs divided equally longitudinally was evaluated.

c — f Eight-week-old wild-type female mice were administered nicotine or PBS vehicle control for 3 weeks and then tibial bone sections were stained with TRAP c or toluidine blue e. The number of osteoclasts per bone perimeter N. Pm d or the number of osteoblasts per bone perimeter N.

Pm f were then evaluated. Data represent mean N. Pm or N. Representative data of two independent experiments are shown. Bone mineral density increases following cessation of nicotine administration in mice.

a , b Eight-week-old wild-type female mice were administered nicotine for 3 weeks. Then, nicotine administration was stopped and mice were maintained for two more weeks without nicotine administration.

Bone mineral density of femurs divided equally longitudinally was evaluated serially from distal to proximal points in mice representing two time points: 1 after nicotine had been administered for 3 weeks nicotine , and 2 2 weeks after nicotine withdrawal nicotine cessation.

Mice in group 1 were 11 weeks old, and those in group 2 were 13 weeks old. c Eight-week-old wild-type female mice were administered nicotine for 3 weeks. Then, nicotine administration was stopped and mice were maintained for seven more days without nicotine administration. Serum TRAP5b levels were evaluated by ELISA after nicotine had been administered for 3 weeks day 0 , and 7 days after nicotine withdrawal day 7.

Osteoporosis is a multifactorial disease brought on by various risk factors or their combination 2 , 3 , 4. Among them, aging, menopause and genetic factors cannot be controlled as a means to antagonize osteoporosis development; however, lifestyle-related factors such as excessive alcohol consumption and smoking are manageable.

In this study, we addressed effects of smoking and smoking cessation in two human studies. In the first, we assessed BMD differences in female pre- and post-menopausal smokers versus comparable non-smokers. That analysis revealed BMD to be significantly lower in post-menopausal smokers compared to non-smokers.

In a second study, we evaluated male and female smokers before and after they quit smoking and found that levels of bone formation markers significantly increased within days of smoking cessation. This analysis indicates that the negative effects of smoking on bone homeostasis can be reversed within a short period following smoking cessation, conferring a significant benefit for bone health.

Also, mouse studies reported here show that BMD increases within a short period after nicotine discontinuation accompanied by significantly reduced serum levels of TRAP5b, a marker of bone resorption.

Nicotine promotes various effects in smokers. Among them, euphoria and decreased heart rate are due to vagal nerve stimulation. Nicotine intake reportedly promotes peripheral vessel vasoconstriction, which is associated with osteoporosis development or delayed fracture healing In mice, nicotine administration was demonstrated to elevate RANKL and to decrease OPG levels in sera to stimulate osteoclastogenesis In this study, we demonstrated that interrupting administration of nicotine to mice increased bone mass and decreased levels of the bone resorption marker TRACP5b.

We also observed increased levels of some markers of bone formation in humans who had stopped smoking. Thus, although we currently do not understand the reasons for differences in effects of smoking cessation on bone metabolism between humans and mice, it is clear that stopping smoking is a way to decrease the risk of osteoporosis development.

At present, we do not know precisely why only osteocalcin and ucOC levels changed after smoking cessation in human subjects. Nonetheless, these findings suggest that osteocalcin and ucOC respond more rapidly to smoking cessation than TRACP5b, making them potentially more appropriate markers of bone effects of smoking cessation.

The osteocalcin-ucOC axis reportedly plays a role in regulating glucose metabolism 21 ; however, since hemoglobin A1c HgbA1c levels were unchanged after smoking cessation Table 2 , we do not attribute changes in ucOC to improved glycemic control.

Relevant to study limitations, we did not collect BMD data from subjects who had stopped smoking, as most stopped smoking within days, a period too short to observe significant changes in BMD.

Also, samples were collected at fasting but at various times of day. We note, however, that TRACP5b levels are reportedly unaffected by circadian rhythm and feeding Also, we did not follow up with subjects after successful smoking cessation, and samples were not collected before or after days.

Finally, the number of non-smokers evaluated exceeded the number of smokers: the proportion of smokers in our subjects was Nonetheless, we feel that conclusions relevant to reported changes in bone density are valid and that our study makes a significant contribution to the field.

In summary, we conclude that based on our findings, deleterious changes in bone homeostasis associated with smoking can be rescued by smoking cessation.

Such changes in smoking behaviors should be encouraged as a potential means to improve bone metabolism and reduce risk of osteoporosis development.

This study protocol was approved by an ethics committee at Keio University School of Medicine and carried out in accordance with guidelines of that committee.

Informed consent was taken from all subjects prior to the study. We conducted two separate human studies. In the first, we invited female medical workers in our university hospital, aged 39 to 64 years of age, and obtained informed consent from The second study included current smokers who intended to stop smoking.

Of them, 76 reported they had stopped smoking, and 47 of those were blood cotinine-negative. In that group of 47 subjects, we evaluated levels of bone markers and other parameters in sera before and after smoking cessation. In the first study, body height, weight, and serum levels of tartrate resistant acid phosphatase 5b TRACP5b , N-terminal telopeptide of type 1 collagen NTX , osteocalcin and undercarboxylated osteocalcin ucOC were assessed in all subjects, and body mass index BMI was calculated based on body height and weight data.

TRACP5b Nittobo, Fukushima, Japan and NTX Abbott Diagnostics Medical Co. Osteocalcin Roche, Basel, Switzerland and ucOC Sekisui Medical, Tokyo, Japan were analyzed by an electrochemiluminescent immunoassay ECLIA. BMD was analyzed using an AOS system Aloka, Tokyo, Japan , as described In the second study, parameters associated with bone resorption, namely, urinary NTX and deoxypyridinoline and serum TRACP5b were assessed in all subjects as well as bone formation parameters including serum osteocalcin, uncarboxylated osteocalcin ucOC , total type 1 procollagen-N-propeptide P1NP , and bone specific alkaline phosphatase BAP , as were pentosidine, homocystein, intact parathyroid hormone PTH , 25 OH VitD, estradiol E2 , and cotinine levels.

TRACP5b Nittobo, Fukushima, Japan , pentosidine FSK, Kagawa, Japan and deoxypyridinoline SB Bioscience Co. PTH Roche Diagnostics, Tokyo, Japan , osteocalcin Roche , total P1NP Roche , E2 Roche , and ucOC Sekisui Medical, Tokyo, Japan were analyzed by ECLIA. BAP Beckman Coulter, Pasadena, CA and uNTX Alere Medical Co.

Homocysteine YMC CO. Eight-week-old wild-type female mice were randomly assigned to each treatment group. In the first examination, mice were administered nicotine or PBS vehicle control for 3 weeks. We then evaluated bone mineral density of femurs divided equally longitudinally.

Tibial bone sections were stained with TRAP or toluidine blue, and the number of osteoclasts per bone perimeter N.

Pm and the number of osteoblasts per bone perimeter N. In the second examination, mice were administered nicotine for 3 weeks. Then, nicotine administration was stopped, and mice were maintained for two more weeks without nicotine administration.

In the third examination, mice were administered nicotine for 3 weeks. Nicotine administration was then stopped, and mice were maintained seven more days without drug. Ltd, Tokyo, Japan.

Bone morphometric analysis and tartrate-resistant acid phosphatase TRAP staining were performed in tibiae, as described All animals were maintained under specific pathogen-free conditions in animal facilities certified by the Keio University animal care committee.

Water and food were available ad libitum. All animal studies were performed in accordance with the guidelines of the Keio University animal care committee, as described Sera were collected from nicotine-administered mice before and 7 days after nicotine cessation.

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