In this article, learn about how to prevent the condition by losing weight…. A person can manage their diabetes by making healthful changes to their diet, exercising frequently, and regularly taking the necessary medications…. A low-carb diet is one strategy to help manage diabetes symptoms and reduce the risk of complications.

In this article, learn why a low-carb diet…. Researchers said baricitinib, a drug used to treat rheumatoid arthritis, showed promise in a clinical trial in helping slow the progression of type 1….

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Medical News Today. Health Conditions Health Products Discover Tools Connect. How can diabetes cause joint pain? Medically reviewed by Soo Rhee, MD — By Jenna Fletcher — Updated on May 19, Diabetes and joint pain Treatment Prediabetes Summary Diabetes can cause pain in the joints in various ways.

How does diabetes cause joint pain? Share on Pinterest Image credit: J. Terrence Jose Jerome. Treatment and management. Prediabetes and joint pain.

Diabetes Type 1 Type 2 Rheumatology. How we reviewed this article: Sources. Medical News Today has strict sourcing guidelines and draws only from peer-reviewed studies, academic research institutions, and medical journals and associations. We avoid using tertiary references. We link primary sources — including studies, scientific references, and statistics — within each article and also list them in the resources section at the bottom of our articles.

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Latest news Ovarian tissue freezing may help delay, and even prevent menopause. RSV vaccine errors in babies, pregnant people: Should you be worried? Scientists discover biological mechanism of hearing loss caused by loud noise — and find a way to prevent it. How gastric bypass surgery can help with type 2 diabetes remission.

Atlantic diet may help prevent metabolic syndrome. Related Coverage. How do you prevent type 2 diabetes? Medically reviewed by Deborah Weatherspoon, Ph. How to manage diabetes. People with type 1 diabetes have been found to have a lower bone mineral density and a higher incidence of osteoporosis.

People with type 2 diabetes have a higher bone mineral density, yet they have a higher risk of fractures. It is not known why type 2 diabetes affects bone strength regardless of the bone mineral density. Bone fractures , especially hip fractures, are common in people who have either osteoarthritis or osteoporosis.

Charcot joint , a rare but serious condition in people with diabetes who have neuropathy. It initially causes redness, swelling and feels warm to the touch.

Eventually, it can lead to weakness or breaks in the bones and dislocation of the joints of the foot and ankle. What can be done to reduce the risk of bone disease?

The four main things you can do are: 1. Read also about Target blood glucose levels. Blood glucose levels change across the course of a day, and can vary depending on the foods you eat and physical activity levels.

Read also about Exercise with joint pain or leg pain. Read this article to learn about the benefits of exercise with joint pain or leg pain.

Read also about Diabetes and arthritis. There are many types of arthritis, but the two most common ones are osteoarthritis which involves wear and tear on cartilage and joints and rheumatoid arthritis an autoimmune disease.

Footer Living Well with Diabetes Healthy eating, management, exercise, medication and other diabetes information Subscriber Type Diabetes Digest Healthcare Professionals Better Management. Better Control Learn About Diabetes Living Well with Diabetes.

Diabetes Care Community Inc 16 Dominion St. This is accomplished by limiting weight bearing activities and the guided use of assistive devices. The disorder of diabetic hand syndrome, or cheiroarthropathy, involves a thickening of the skin on the hands and fingers. Symptoms: Flesh may become waxy, and the stiffness makes it difficult or impossible to move fingers or lay palms flat.

Better management can help stop the disorder from getting worse and possibly prevent it. Osteoporosis is a loss of bone mass and density that leads to bones becoming brittle and easily broken.

They may suggest a bone density test, or offer medication designed to help reduce bone loss. Treatment: Diet and exercise are key to maintaining healthy bone mass, and in treating osteoporosis.

Make sure you are eating lots of calcium and vitamin D, getting some exposure to sunlight, and exercising regularly. Those with type 2 diabetes are at increased risk for osteoarthritis, a disorder that causes joint cartilage to break down.

The degeneration of joint cartilage often means pain and loss of function in affected joints. Osteoarthritis can affect any joint. Symptoms: Joints may become painful, inflamed, and stiff, and become less flexible and functional.

Treatment: Exercising and maintaining a healthy weight is key to staving off and slowing down this condition. Resting the affected area, medication to control the pain, and other treatments such as acupuncture and therapeutic massage are the primary modes of treatment, though in rare or very advanced cases, surgery may also be advised.

Forestier disease is also known as diffuse idiopathic skeletal hyperostosis DISH. Type 2 diabetics are particularly vulnerable.

Symptoms: The affected part of the body may become stiff or sore, and will usually have a decreased range of motion. Back and neck pain and stiffness is common in cases affecting the spine.

Treatment: Steroid injections are sometimes used to treat pain. Diabetes is a risk factor for this condition, where shoulders usually just one become sore, stiff, and lose functionality.

Symptoms: Pain and stiffness in the shoulder are primary symptoms of this condition. Treatment: As long as the condition is detected early, targeted physical therapy can help keep the joint functional. If you are diabetic, and concerned about treating existing bone and joint issues or taking action to preserve your mobility, call to speak with our experts!

So happy we found him. I highly recommend Michael Grelller if you are experiencing any problem with your knees. Visit the Patient Portal.

Charcot Joint Charcot joint, otherwise known as neuropathic arthropathy, is a condition where a joint degenerates because of nerve damage. Diabetic Hand Syndrome The disorder of diabetic hand syndrome, or cheiroarthropathy, involves a thickening of the skin on the hands and fingers.

Osteoarthritis Those with type 2 diabetes are at increased risk for osteoarthritis, a disorder that causes joint cartilage to break down.

Forestier Disease Forestier disease is also known as diffuse idiopathic skeletal hyperostosis DISH. Dupuytren contracture This deformity causes fingers to bend in toward the palm due to thickened, scarred connective tissues in the hand and fingers.

Frozen shoulder Diabetes is a risk factor for this condition, where shoulders usually just one become sore, stiff, and lose functionality.

Request An Appointment. Do Not Fill This Out. Shoulder Injuries — Rotator and Labral Tears. Understanding Arthritis: Three Top Types. Please see our very detailed article on to learn more about Prolotherapy and Knee Osteoarthritis. In a study that we cite, in other articles on our website, published in the prestigious international journal Therapeutic advances in musculoskeletal disease , doctors wrote of excellent patient outcomes in a study of Prolotherapy injections for with knee osteoarthritis 8.

Poor blood glucose control and an elevated HbA1c increase the risk for poor healing, as well as the development of adult-onset diabetes and its associated health risks, which can lead to heart disease. Every day we treat patients with joint pain, arthritis, and sports injuries whose goal is to heal and return to their normal lives.

High glucose levels compromise that goal and put them at risk for further diseases in the future. Fortunately, we have worked with many patients over the years with type 2 diabetes and have helped them on their path to healing and a better dietary lifestyle. We have been doing Prolotherapy for many years now, having started in January Likewise, we have treated people who are a little overweight to those who were very overweight.

So what happens when these people get Prolotherapy? For many, their pain goes away. Obesity, diabetes, and other medical conditions can slow the effects of Prolotherapy. If this occurs instead of the person needing three to six visits of Prolotherapy they may need six to ten visits.

Over the course of the last almost 30 years and having performed thousands of Prolotherapy sessions on diabetics we have found it very well tolerated. Most of the diabetics tell us that it raises their blood sugar only a mild amount like points. This is also for a short time perhaps a few hours.

In regards to those who are very overweight, they do not need to loose weight for the Prolotherapy to help them. We would encourage them to lose weight because it would mean less stress on their joints. When there is less stress on the joints, they need less Prolotherapy.

So if they want to need less Prolotherapy, then loose some weight. For the person with the complicated medical condition, all we can say is that it would be best to get a comprehensive medical evaluation and treatment. The healthier you are the better you will heal from the Prolotherapy.

You can still get Prolotherapy alone, but your healing may be slower. Type 2 diabetes mellitus and osteoarthritis. In Seminars in arthritis and rheumatism Jan WB Saunders. Osteoarthritis and type 2 diabetes mellitus: What are the links?. diabetes research and clinical practice.

Abnormal subchondral bone remodeling and its association with articular cartilage degradation in knees of type 2 diabetes patients. Bone research. Factors associated with falls in patients with knee osteoarthritis: A cross-sectional study.

Association of diabetes mellitus and biochemical knee cartilage composition assessed by T2 relaxation time measurements: Data from the osteoarthritis initiative. Journal of Magnetic Resonance Imaging. Diabetes is a risk factor for restricted range of motion and poor clinical outcome after total knee arthroplasty.

The Journal of arthroplasty. Clinical Outcome Evaluation of Primary Total Knee Arthroplasty in Patients with Diabetes Mellitus. Medical science monitor: international medical journal of experimental and clinical research.

Clinical Characteristics of Patients with Type 2 Diabetes Mellitus Receiving a Primary Total Knee or Hip Arthroplasty. Journal of Diabetes Research. Therapeutic effects of prolotherapy with intra-articular dextrose injection in patients with moderate knee osteoarthritis: a single-arm study with 6 months follow up.

Ther Adv Musculoskelet Dis. Hypertonic dextrose injections prolotherapy for knee osteoarthritis: results of a single-arm uncontrolled study with 1-year follow-up. Both exendin-4 and liraglutide are GLP-1 receptor agonists that can not only promote bone formation directly but also inhibit osteoclast differentiation and bone resorption.

On the other hand, studies have found that Exendin-4 can inhibit RANKL-induced osteoclast differentiation and bone resorption by activating GLP-1 receptors, thereby preventing bone trabecular microstructure deterioration and enhancing bone strength It can also inhibit macrophages to produce tumor necrosis factor-α TNF-α in lipopolysaccharide LPS environments, thereby reducing LPS-induced osteoclast differentiation and bone resorption DPP-4 inhibitors, including sitagliptin, saxagliptin and linagliptin, achieve blood glucose control in patients with diabetes by extending the circulating half-life period of endogenous insulin.

Animal experiments have shown that the DPP-4 inhibitor linagliptin can inhibit the increase in TNF-α and RANKL mRNA expression levels in mice treated with LPS, prevent LPS-induced osteoclast differentiation and bone resorption, induce macrophages to differentiate to the M2 phenotype, and inhibit TNF-α-induced osteoclast differentiation and dental root resorption, thereby improving inflammation-induced bone resorption There are relatively few human studies on the effects of DPP-4 inhibitors on bones.

However, meta-analysis and cohort studies have shown that DPP-4 inhibitors can reduce the risk of fractures compared with placebo and other anti-diabetic drugs 34 — Studies on the effects of sulfonylureas on bone metabolism are still lacking, and there are conflicting results in existing data.

Some studies have shown that it has a potential stimulating impact on the proliferation and differentiation of osteoblasts and has a protective effect on osteoblasts in hyperglycemic environments 5 , 37 , but some studies have found that it increases the risk of falls and fractures 38 , Therefore, further research is needed on the effect of sulfonylureas on bone metabolism.

The effect of anti-diabetes drugs on bone healing under diabetic conditions should be fully considered in clinical application.

In the absence of other contraindications or adverse reactions, doctors should minimize the use of drugs such as thiazolidinediones that may lead to diabetes bone-related complications 40 and try to use metformin, DPP-4I, GLP-1 receptor agonists and other drugs that can effectively promote bone healing to improve the overall bone condition of patients with diabetes.

In recent years, natural medicine extracts have received increasing attention. Studies have found that several natural medicine extracts play an active role in bone regeneration. The following is a brief introduction to natural medicine extracts that can improve bone healing. Berberine, curcumin and resveratrol all play a dual role in antidiabetes and promoting bone healing and have broad clinical application prospects.

Studies have found that berberine can activate osteoblast and osteoblast biomarker genes and promote bone regeneration. It can also inhibit bone loss caused by the T2DM drug pioglitazone through the AMPK pathway The latest study by Jingjing Shao et al. In addition, in vivo studies have shown that the combined application of berberine and insulin can promote implant osseointegration in diabetic rats Curcumin is a polyphenolic phytochemical that is mainly extracted from turmeric.

It has a positive effect on preventing and treating osteoporosis and bone deterioration in rheumatoid arthritis and other inflammatory diseases In improving diabetic bone healing, curcumin has been shown to inhibit bone resorption and reduce the number of osteoclasts stimulated by diabetes Resveratrol is a polyphenol plant antitoxin that is mainly extracted from plants and fruits such as grapevines.

Research by Yunwei Hua et al. The results showed that resveratrol is effective in preventing bone density loss in patients with T2DM In addition, there are natural medicine extracts such as baicalein, ophiopogonin D OP-D , and tubeimoside I TBMS1.

Although they do not have anti-diabetic effects, they have also been proven in preclinical studies to improve bone healing in diabetic animal models. These drugs still lack more experiments to verify their effectiveness in clinical applications.

In vivo experiments of baicalein have been proven to have no effect on the insulin sensitivity index in chronic periodontitis with DM animal models, but baicalein can reduce alveolar bone loss in diabetic rats by increasing the expression of phospho-nuclear factor erythroid 2-related factor 2 pNrf2 OP-D can act as an antioxidant to protect cells from oxidative stress-induced damage TBMS1 is a pentacyclic triterpene saponin compound isolated from the plant Fritillaria Vulgaris.

In vivo and in vitro experiments targeting osteoclasts and RANKL-induced signaling pathways have found that TBMS1 has a protective effect on bone loss in T2DM rats by inhibiting osteoclast formation, bone resorption, and the RANKL-induced NF-κB signaling pathway Morroniside is mainly extracted from Cornus officinalis.

A study by Yi Sun et al. In vivo experiments in a T1DM rat model also showed that morroniside can reduce bone loss and improve bone microstructure. Glycyrrhizin is a high mobility group box-1 HMGB1 inhibitor. Experiments have shown that glycyrrhizin can significantly attenuate the upregulation and interaction of HG-induced ligand receptors for RAGE by inhibiting HMGB1, reducing oxidative stress, reversing the downregulation of osteogenic markers, and promoting osteogenic differentiation Traditional Chinese natural medicine and extracts of natural medicine are often used under diabetic conditions as a supplement rather than professional medical advice.

While natural medicine extracts are popular, there are still regulation, safety and efficacy concerns. Except for resveratrol, none of the other natural medicinal extracts listed above has been tested in clinical trials for bone healing in diabetic patients.

The preclinical trials of natural medicinal extracts in diabetic bone healing have not been examined thoroughly, and the mechanism of natural medicinal extracts in improving diabetic bone healing is not completely clear.

At the same time, there is still a lack of clinical trials. Although we believe that natural medicine extracts have great application prospects and are highly likely to become an important complementary therapy for diabetic bone healing, a large number of reproducible experiments are still needed to confirm the efficacy and safety of natural medicinal extracts in promoting diabetic bone healing.

Effective anti-osteoporosis drugs, such as vitamin D, bisphosphonates e. Vitamin D is an essential steroid hormone for the human body, and 1α,dihydroxy vitamin D3 1,25VD3 , as the main active form of vitamin D3, binds to the vitamin D binding protein in the plasma to reach target tissues and exert endocrine effects, regulating the metabolism of calcium and phosphorus.

Experiments have shown that 1,25VD3 can reverse the reduction in osseointegration and mechanical strength, reduce the damage caused by AGEs-induced osteogenic differentiation, and downregulate the expression of RAGE, thereby promoting the osseointegration of T2DM titanium implants A recent longitudinal study in 35 postmenopausal women found that bone fragility due to T2DM and aging was significantly improved after IU daily vitamin D supplementation for 12 months In an in vivo study, risedronate reduced the number and function of osteoclasts in diabetic mice, and increased bone mineral density and vertebral mechanical strength in the femoral shaft and vertebral body In another experiment, both alendronate and raloxifene were found to have an anti-bone resorption effect in diabetic animal models, reducing bone turnover rate and increasing bone mechanical strength Zoledronate and sclerotin antibodies also prevented bone defects by reversing the adverse effects of diabetes on bone mass and strength in rats 60 , At the same time, there are clinical trials demonstrating the effectiveness of these drugs in the treatment of diabetic osteoporosis patients.

A retrospective analysis of the 3-year placebo-controlled freedom study and the 7-year extension study found that denosumab significantly increased bone mineral density and reduced the risk of vertebral fracture in patients with osteoporosis and diabetes Another retrospective national cohort study in Denmark found that patients treated with alendronate and denosumab had a similar risk of osteoporotic fractures in patients with diabetes, suggesting that the two agents have similar efficacy in preventing osteoporotic fractures in patients with diabetes In exploratory trials of postmenopausal women with T2DM, treatment with either bazedoxifene or raloxifene improved bone resorption markers without affecting glucose metabolism 64 , Therefore, we believe that these anti-osteoporosis drugs have a potential role in promoting bone healing in diabetic patients, which may provide new ideas for the treatment of diabetic osteoporosis or poor bone healing.

Finding drugs that can effectively control blood glucose while maintaining bone health may become a direction for future research in the treatment of diabetic osteoporosis. In addition to the abovementioned anti-diabetes drugs, natural medicine extracts and osteoporosis drugs, some drugs also have a significant effect on promoting bone healing in patients with diabetes.

Doxycycline is a tetracyclic antibiotic that is often used clinically to treat various infectious diseases caused by sensitive gram-positive bacteria and gram-negative bacilli.

In addition, zinc is considered to be a potential drug to prevent bone loss caused by diabetes. Studies have found that both zinc carbonate and zinc sulfate have a positive effect on maintaining bone structure and biomechanical parameters At present, relevant clinical studies have reported that zinc supplements have achieved obvious efficacy in the treatment of postmenopausal women with osteoporosis, but unfortunately, there is currently a lack of clinical trials and reports on the application of doxycycline and zinc supplements in the treatment of compromised bone healing under diabetic conditions.

We believe that both doxycycline and zinc supplements can be used as complementary treatments for compromised diabetic bone healing. Moreover, previous studies have shown that diabetic complications also play an important role in causing bone fragility and damaging bone health in patients with diabetes.

A study concerning aging individuals with T1DM for more than 50 years indicated that lipid profile is associated with bone mineral density BMD values, suggesting that drugs controlling cardiovascular disease may be useful in promoting bone health in T1DM Additionally, diabetic microvascular complications including neuropathy, retinopathy, and nephropathy are relevant to increased fracture risks 70 , Therefore, drugs that can prevent or improve diabetic microvascular complications such as aspirin, angiotensin-converting enzyme inhibitors, statins may be of potential benefits to bone health under diabetic conditions Previous studies have revealed that various hormones can promote bone healing under diabetic conditions.

Uncarboxylated osteocalcin is a multifunctional hormone secreted by mature osteoblasts 73 that plays an essential role in promoting the osteogenic differentiation of BMSCs Adrenomedullin 2 ADM2 is an endogenous peptide belonging to the calcitonin family 76 that decreases significantly under diabetic conditions, and the reduction in ADM2 levels is associated with DM-related metabolic disorders Studies have shown that ADM2 therapy can promote M1 macrophage polarization toward the M2 phenotype by activating the PPARγ-mediated NF-κB signaling pathway and improve bone regeneration in diabetic rats Norepinephrine NE is the primary medium of the sympathetic nervous system, and its ability to affect MSC migration has been shown in previous experiments both in vitro and in vivo PTH enhances the MSC survival rate by inhibiting their aging and apoptosis 81 and promotes MSC differentiation toward osteogenesis rather than adipogenesis In the fight against glucolipotoxicity, PTH can promote osteogenic differentiation of BMSCs by activating the p38 MAPK signaling pathway Moreover, in vivo studies have shown that human parathyroid hormone 1 — 34 has a positive effect on bone fracture healing in T2DM Recombinant human parathyroid hormone has been used as a drug to cure osteoporosis clinically However, clinical trials are needed to further assess the effectiveness of recombinant hPTH in bone healing under diabetic conditions.

Adiponectin APN plays a vital role in regulating energy metabolism at the cellular and systemic levels in diabetic environments In patients with T2DM, APN concentration in plasma was significantly reduced, which is associated with damage in bone healing in diabetic states In addition, APN activates the AMPK signaling pathway, plays an antioxidant role and protects mitochondria, reverses osteoblast damage, and improves bone integration in titanium implants Therefore, integrating APN in scaffold-based systems may serve as a potential strategy to promote bone healing, but it still needs further investigation.

Many studies have demonstrated that activating or inhibiting signaling pathways associated with BMSC osteogenesis by designing specific signaling pathway regulators can promote bone healing in diabetic environments.

GSK-3β, a kinase involved in blood glucose regulation 89 , is a negative regulator of the Wnt signaling pathway and plays an important role in the regulation of bone metabolism In hyperglycemic environments, GSK-3β is activated, and the Wnt signaling pathway is inhibited, damaging the proliferation of BMSCs CHIR is a GSK-3β inhibitor that inhibits the expression of β-catenin and CyclinD1 in hyperglycemic environments, promoting osteogenesis of BMSCs In addition, previous studies have found that LiCl at 15 mM, as an inhibitor of GSK-3β, can also effectively reverse the inhibitory effect of hyperglycemia on BMSC osteogenesis Brain and muscle ARNT-like protein 1 BMAL1 is a core biological clock protein secreted by the suprachiasmatic nucleus, peripheral tissue, and stem cells The study found that the overexpression of BMAL1 restores the bone-forming ability of BMSCs from diabetic rats by inhibiting the expression of the NF-κB signaling pathway Therefore, bone metabolic balance in T2DM can be reconstructed by overexpression of BMAL1.

As a glycoprotein secreted on the surface of cells, Semaphorin3B is closely related to the bone metabolism process, and it can improve defects in BMSC proliferation and osteogenesis in hyperglycemic environments by activating the Akt signaling pathway Growth differentiation factor 11 GDF11 is a bone morphological protein BMP whose expression is positively correlated with the incidence of osteoporosis in diabetic patients A study was conducted to regularly inject GDF11 inhibitors into the tooth extraction socket in T2DM pigs, and it found that GDF11 can improve bone healing in the tooth extraction socket and promote osteogenesis of MSCs under T2DM conditions Although these signaling pathway regulators mentioned above are only currently used in laboratories, they help us understand the underlying mechanisms in compromised bone healing under diabetic conditions, and they can be used as potential therapeutic targets to recover abnormal bone homeostasis caused by DM.

BMP is one of the most potent inducers of bone differentiation in MSCs In the BMP family, BMP2, BMP4, BMP6, BMP7 and BMP9 all have bone-forming properties Studies in streptozocin-induced diabetic mice have shown that BMP6 treatment can reduce bone loss in diabetic mice and that BMP6 plays an important role in T1DM-related bone loss Vascular endothelial growth factors VEGF induce bone formation through direct and indirect pathways.

VEGF can directly attract MSCs and promote osteogenesis while also promoting local angiogenesis, enhancing vascular permeability, accumulating MSCs, and indirectly promoting bone regeneration Basic fibroblast growth factor bFGF is a mitogen that regulates bone cell proliferation, differentiation and mineralization Several studies have shown a synergistic effect on promoting bone differentiation of MSCs between BMP and VEGF and between BMP, VEGF and bFGF This joint application is a new and promising improvement strategy in bone tissue engineering.

In future studies, researchers can further explore the factors affecting its synergy and effectively promote bone regeneration in diabetic environments. Insulin-like growth factors IGF1 , when combined with IGF1 receptors, play an essential role in bone development, growth and physiological strength maintenance but require daily injections or surgical implants.

A current study has shown that expressing codon-optimized Pro-IGF-1 with e-peptide in the chloroplast can be administered orally, significantly promoting bone regeneration in diabetic mice This new type of administration can not only facilitate affordability but also enhance patient compliance; therefore, it may be a potential treatment for bone healing in diabetic patients.

Progranulin PGRN is a multifunctional cytokine that has been shown to promote cartilage formation and participate in physiological fracture healing mainly through TNF receptor 2 TNFR2 signaling pathways The latest experiments have found that local application of recombinant PGRN in diabetic rats can effectively promote the healing of diabetic fractures.

The combination of bone-induced growth factors with bone-conductive biomaterials is also an important and promising way to promote bone regeneration BMP-4 can regulate macrophage cell differentiation to M2 macrophage polarization to improve the inflammatory microenvironment Jian Li et al.

In addition, some studies have achieved the delivery of growth factors through nonviral gene therapy, which can avoid the side effects of overdosing on recombinant human proteins Behnoush Khorsand et al. In complicated diabetic environments, an autonomous tissue engineering system that can release growth factors accurately according to the dynamic environment is required in future research.

Moreover, clinical experiments are also expected to be evaluated. Exosomes, with a diameter of nm, are extracellular organelles secreted by cells and are capable of carrying bioactive substances such as noncoding RNA, mRNA, DNA, proteins, and other molecules Exosomes can transport specific miRNAs and mediate cell and tissue-to-tissue communication Studies have shown that both exosomes secreted by bone marrow stem cells in rats with T1DM dBMSC-exos and exosomes secreted by normal rat bone marrow stem cells nBMSC-exos can promote bone regeneration and angiogenesis, but the effect of dBMSC-exos is weaker than that of nBMSC-exos Studies have also shown that exosomes derived from adipose-derived mesenchymal stem cells AMSCs inhibit the secretion of IL-1β and IL by osteoclasts in hyperglycemic environments, reducing bone absorption and restoring bone loss However, at present, MSC exosome-related research is still in the preclinical stage, and the traditional methods of exosome separation and characterization identification are not effective for clinical application.

In the future, we need to further explore the exact mechanism of MSC exosomes in bone formation, bone cell differentiation, angiogenesis, inflammatory response, etc.

Developing large-scale methods for the production, separation and purification of exosomes is also of vital importance. Several miRNAs regulate BMSC proliferation, migration, differentiation and apoptosis and are important regulatory factors in bone healing The miRNA from the exosome source can be steadily transferred from the bone microenvironment to BMSCs, regulating bone differentiation and bone healing, but the hyperglycemic environment can affect its expression.

The study found that in hyperglycemic environments, the expression of miRp in osteocyte-derived exosomes may inhibit the expression of Gal-3 in osteoblasts, which in turn can lead to a decrease in bone capacity MiRp levels also rise in exosomes secreted by diabetic bone marrow-derived macrophages, which can be transferred to BMSCs to inhibit bone regeneration by targeting Smad1 Designing specific inhibitors of the miRNA as mentioned above may be a potential strategy to reverse the adverse effects of hyperglycemia on bone healing in diabetic patients.

Hyperbaric oxygen therapy can improve the biometric properties of the femur in diabetic animal models and increase the content of collagen and crystalline hydroxyapatite In addition, some studies have evaluated the effectiveness of hyperbaric oxygen therapy for implant bone integration in diabetic states through diabetic animal models, and the results showed that HBO therapy can enhance implant bone integration by calculating BIC through tissue morphology However, some studies suggest that HBO only improves early bone integration in diabetic rabbits, which is not enough to improve the mechanical stability of implants Therefore, it can be determined that HBO has positive effects on bone integration in diabetic environments at the histological and biomechanical levels, but there is a lack of studies of its specific mechanisms, and further clinical research is needed to evaluate the effectiveness of HBO as an auxiliary treatment for diabetic patients.

Ultrasound is an oscillating longitudinal pressure wave with a frequency over 20 kHz that cannot be detected by the human auditory system. Ultrasound has applications in many medical fields, including low-intensity pulsed ultrasound LIPUS for diagnostic imaging, medium-intensity ultrasound for physical therapy, and high-intensity focused ultrasound for surgical resection.

LIPUS has been used clinically for more than 20 years. A large number of in vivo and in vitro experiments and clinical trials have verified the safety and effectiveness of LIPUS in promoting bone healing , However, there are relatively few studies on LIPUS in bone healing in patients with diabetes.

Past experiments have shown that in diabetic rat fracture models, LIPUS can increase the expression of growth factors in the diabetic group and promote cartilage formation and angiogenesis An experiment aimed at the effect of LIPUS on the alveolar structure in the process of orthodontic force in diabetic patients found that the application of LIPUS treatment, 10 minutes a day for one week, can promote normal and diabetic mandibular slice organ culture MSOCs bone remodeling and restoration of cementum and dentin Although we believe that ultrasound has clinical potential in promoting bone healing in patients with diabetes and can even be used in the dental field, more experiments are still needed to prove and explore the underlying mechanism.

Photobiomodulation PBM is a nonthermal light treatment that involves endogenous chromophores. Previous experiments have shown that PBM can promote bone healing in diabetic rat models by improving the viability of osteoblasts and mesenchymal cells , Experiments on diabetic rats proved that PBM treatment can improve the viability of osteoblasts, significantly increase the mRNA expression of RUNX2 and osteocalcin, and increase the activity of alkaline phosphatase and the production of the mineralized matrix, thereby regulating the bone healing process , In addition, PBM has also been shown to improve the survival, proliferation and apoptosis of BMSCs in diabetic rats Low-level laser therapy LLLT refers to radiation with a wavelength range of nm and a power of 1 mW mW.

It has the characteristics of relatively low energy density and has been used clinically to treat various diseases The effect of LLLT in promoting bone healing has been verified by a large number of experiments, mainly by promoting the proliferation of osteoblasts, increasing the growth factor secreted by osteoblasts , the transportation of calcium and increasing angiogenesis to promote bone healing However, there are relatively few studies on diabetic bone healing.

A previous study on the effect of LLLT and dual-type allograft materials on the healing of diabetic bone found that LLLT can effectively stimulate osteoblast production but cannot promote bone formation However, other studies have shown that LLLT can stimulate bone metabolism, reduce bone resorption area, increase RUNX-2 expression, increase serum alkaline phosphatase levels, increase cortical area, fracture strength, BMD and bone mineral content BMC , and promote bone healing , Different experiments have shown almost the opposite results, which suggests that whether LLLT can promote the healing of diabetic bone, as well as the specific mechanism of promoting diabetic bone healing, still need many experiments to be studied.

In the past few decades, low-intensity pulsed electromagnetic fields LIPEMFs have played a positive role in the skeletal system. The application of PEMF treatment for patients with osteoporosis can significantly increase bone density and prevent bone loss , The positive effect of LIPEMF in promoting bone healing has been confirmed in a large number of experiments.

Many preclinical experiments have proven that LIPEMF can effectively promote bone healing in diabetic animal models. However, there is still a lack of clinical trials for bone healing in diabetic patients. Although we believe that LIPEMF has clinical potential in promoting diabetic bone healing and may become a potential method to inhibit diabetic osteoporosis, its effectiveness lacks clinical experimental support.

To date, with the continuous progress of preclinical studies, the mechanism of HBO therapy, LIPUS, PBM, LLLT and LIPEMF in promoting diabetic bone healing has been gradually clarified. We believe that the physical therapies mentioned above have clinical potential in promoting diabetic bone healing.

However, there have been no clinical studies to confirm these findings. With the gradual increase in the number of patients with diabetes and the occurrence of a large number of related bone healing complications, we believe that it is necessary to further study the potential role and safety of physical replacement therapy in bone healing in patients with diabetes, and these therapies may become an important part of the treatment of bone healing complications of diabetes.

With the improvement of living standards and the rising prevalence of diabetes, it is urgent to explore how to improve bone healing repair in diabetes. This paper reviews the effects and possible mechanisms of diabetes on bone healing and summarizes several current methods to improve bone healing under diabetic conditions, although some studies are still in their early stages, including the use of drugs, hormones, signaling pathway regulators, growth factors, exosomes, etc.

In addition, some physical therapies, such as hyperbaric oxygen, ultrasound, laser, and pulsed electromagnetic fields, also have a certain clinical potential in promoting bone healing under diabetic conditions Figure 2. Some clinical trials have proven that drugs related to glycemic control are beneficial to bone health in patients with diabetes.

For example, metformin can increase the level of bone formation marker in T2DM patients , liraglutide has an anti-resorptive effect on bone turnover in patients with T2DM , GLP-1 receptor agonists can increase BMD at multiple sites of the body in T2DM patients , denosumab can significantly increase BMD and decrease vertebral fracture risk in postmenopausal women with osteoporosis and diabetes 62 , etc.

LLLT can improve implant stability in patients with diabetes in 6 months trial However, there is no clinical research evidence specifically designed to improve fracture healing in patients with diabetes And at present, there is no direct proof in existing clinical trials that the abovementioned methods have beneficial effects in improving bone healing under diabetic conditions.

Therefore, clinical research on the methods mentioned above still lacks research, and their effectiveness and potential for clinical application still need to be further explored.

Whether they can be adopted by clinical applications also needs further discussion. YC and YZ conceived and wrote the manuscript. JL and SZ reviewed and edited the manuscript. All authors contributed to the article and approved the submitted version. This work was supported by grants from the Crosswise Tasks of Sichuan University Document No.

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. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

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