Diabetes increases the risk of bone fracture - many studies

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Adolescents with long-duration type 1 diabetes have low bone mass and reduced levels of bone indices reflecting altered bone resorption - June 2025

Bone. 2025 Jun 4:117560. doi: 10.1016/j.bone.2025.117560
Diana Swolin-Eide 1, Auste Pundziute Lyckå 2, Daniel Novak 3, Björn Andersson 4, Gun Forsander 5, Per Magnusson 6

The prevalence of type 1 diabetes (T1D) is increasing globally and is associated with severe complications, including an increased risk of fractures. This case-control study investigated whether young individuals with well-controlled, long-duration T1D have differences in bone mass and bone biomarkers in comparison with healthy matched controls. Fifty individuals, aged 15.0-17.9 years, with a T1D duration of at least 8 years and (mean ± SD) 10.6 ± 2.1 years were included, hence the participants had diabetes throughout most part of their puberty and growth spurt. The mean HbA1c since diabetes diagnosis was 56 ± 6 mmol/mol (7.3 ± 0.6 %). Bone mass was assessed by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography (pQCT). Clinical follow-up data were retrieved from the Swedish National Diabetes Registry. The control group comprised 50 healthy matched adolescents, aged 15.1-17.9 years. The groups were well-matched with no significant differences in age, sex, weight, height, body mass index and the self-reported physical activity. Total body less head aBMD and Z-scores were significantly lower in T1D individuals, p < 0.05. Total tibia density and trabecular density, by pQCT, were also lower in the T1D group, p < 0.05. There were no differences between the groups for parathyroid hormone, 25-hydroxyvitamin D, bone-specific alkaline phosphatase (BALP), intact procollagen type I N-propeptide (PINP), sclerostin, bioactive sclerostin and osteoprotegerin. However, individuals with T1D had reduced levels of C-terminal telopeptide of type I collagen (CTX) (p < 0.001) and nuclear factor κB ligand (a.k.a. RANKL) (p = 0.01), indicating altered regulation of osteoclasts. In conclusion, young individuals with well-controlled, long-duration T1D have subnormal bone mass accrual, impaired microstructure at several sites and suppressed RANKL-mediated osteoclastogenesis resulting in reduced bone resorption. Based on these findings, we suggest that bone health should be monitored in pediatric diabetes care to potentially intervene early in life in susceptible individuals to achieve optimal peak bone mass.
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Bone metabolism and fracture risk in type 2 diabetes mellitus [Review] 2011

Endocr J. 2011;58(8):613-24. Epub 2011 Jul 20.
Yamaguchi T, Sugimoto T.
Internal Medicine 1, Shimane University Faculty of Medicine, Japan. yamaguch at med.shimane-u.ac.jp

Osteoporosis and type 2 diabetes mellitus (T2DM) are now prevalent in aging and westernized societies, and adversely affect the health of the elderly people by causing fractures and vascular complications, respectively. Recent experimental and clinical studies show that both disorders are etiologically related to each other through the actions of osteocalcin and adiponectin. Meta-analyses of multiple clinical studies show that hip fracture risk of T2DM patients is increased to 1.4 to 1.7-folds, although BMD of the patients is not diminished. Vertebral fracture risk of T2DM patients is also increased, and BMD is not useful for assessing its risk. These findings suggest that bone fragility in T2DM depends on bone quality deterioration rather than bone mass reduction. Thus, surrogate markers are needed to replace the insensitivity of BMD in assessing fracture risks of T2DM patients. Markers related to advanced glycation end products as well as insulin-like growth factor-I may be such candidates, because these substances were experimentally shown to modulate bone quality in DM. In practice, it is important for physicians to assess fracture risk in T2DM patients by evaluating prior VFs and fracture histories using spine X-ray and interview, respectively, until the usefulness of surrogate markers is established.

Graph summarizing many studies shows a consistent aBMD difference with diabetes

PMID: 21778617
PDF is attached at bottom of this page

Bone health and type 2 diabetes mellitus: a systematic review Jan 2011

Physiother Can. 2011 Winter;63(1):8-20. Epub 2011 Jan 20.
Gorman E, Chudyk AM, Madden KM, Ashe MC.
Erin Gorman, BHK: Centre for Hip Health and Mobility and Department of Family Practice, University of British Columbia, Vancouver, British Columbia.

Purpose: To systematically review the literature related to bone health in older adults with type 2 diabetes mellitus (T2DM).

Methods: We conducted a systematic review of the literature from January 2005 until February 2010, using keywords related to T2DM and bone-health imaging technology in older adults (aged ?60 years) to search PubMed, OVID MEDLINE, Ageline, CINAHL, Embase, and PsycINFO.

Results: We found a total of 13 studies that met the inclusion criteria for this review. The majority of the studies used dual X-ray absorptiometry (DXA) and showed either higher or similar areal bone mineral density (aBMD) for older adults with T2DM relative to healthy controls. Studies using more advanced imaging suggested that there may be differences in bone geometry between older adults with and without T2DM.

Conclusions: Older adults with T2DM have similar or higher aBMD at the hip relative to older adults without T2DM, despite previous literature reporting an increased risk of low-trauma fractures. Recent studies with advanced imaging have suggested that there may be differences in bone geometry between older adults with T2DM and those without. Health professionals, especially physiotherapists, should be aware of the increased risk and include assessment of fall risk factors and exercise prescription for fall prevention for older adults with T2DM.

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Osteoporosis and risk of fracture in patients with diabetes: an update - 2011

Aging Clin Exp Res. 2011 Apr;23(2):84-90.
Montagnani A, Gonnelli S, Alessandri M, Nuti R.
Metabolic Bone Diseases and Osteoporosis Unit, Department of Internal Medicine, Misericordia Hospital, Via Senese, Grosseto, Italy. montagnaniand at gmail.com

Diabetes mellitus (DM) and osteoporotic fractures are two of the most important causes of mortality and morbidity in older subjects. Recent data report a close association between fragility fracture risk and DM of both type 1 (DM1) and type 2 (DM2). However, DM1 is associated with reduced bone mineral density (BMD), whereas patients with DM2 generally have normal or increased BMD. This apparent paradox may be explained by the fact that, at a given level of BMD, diabetic patients present lower bone quality with respect to non-diabetics, as shown by several studies reporting that diabetes may affect bone tissue by means of various mechanisms, including hyperinsulinemia, deposition of advanced glycosylation endproducts (AGEs) in collagen, reduced serum levels of IGF-1, hypercalciuria, renal failure, microangiopathy and inflammation. In addition, the propensity to fall and several comorbidities may further explain the higher fracture incidence in DM patients with respect to the general population. It is reasonable to expect that close metabolic control of diabetes may improve bone status, although its effect on reduction of fracture risk has not yet been demonstrated. However, metformin has a direct effect on bone tissue by reducing AGE accumulation, whereas insulin acts directly on osteoclast activity, and thiazolidinediones (TZD) may have a negative effect by switching mesenchymal progenitor cells to adipose rather than bone tissue. New prospects include the incretins, a class of antidiabetic drugs which may play a role linking nutrition and bone metabolism. Better knowledge on how diabetes and its treatments influence bone tissue may lie at the basis of effective prevention of bone fracture in diabetic patients. Thus, close glycemic control, adequate intake of calcium and vitamin D, screening for low BMD, and prevention and treatment of diabetic complications are key elements in the management of osteoporosis in both DM1 and DM2. Attention should be paid to treating diabetes with TZD in women with DM2, particularly if elderly. Lastly, patients with osteoporosis and diabetes should be offered the same pharmacological treatments as non-diabetics, although specific trials on the effects of anti-osteoporotic drugs in the diabetic population are lacking.

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Diabetes, Diabetic Complications, and Fracture Risk (T1D) Feb 2015

Bone and Diabetes (AV Schwartz and P Vestergaard, Section Editors)
Published: 04 February 2015 Volume 13, pages 106–115
Ling Oei, Fernando Rivadeneira, M. Carola Zillikens & Edwin H. G. Oei

Diabetes and osteoporosis are both common diseases with increasing prevalences in the aging population. There is increasing evidence corroborating an association between diabetes mellitus and bone. This review will discuss the disease complications of diabetes on the skeleton, highlighting findings from epidemiological, molecular, and imaging studies in animal models and humans. Compared to control subjects, decreased bone mineral density (BMD) has been observed in type 1 diabetes mellitus, while on average, higher BMD has been found in type 2 diabetes; nonetheless, patients with both types of diabetes are seemingly at increased risk of fractures. Conventional diagnostics such as DXA measurements and the current fracture risk assessment tool (FRAX) risk prediction algorithm for estimating risk of osteoporotic fractures are not sufficient in the case of diabetes. A deterioration in bone microarchitecture and an inefficient distribution of bone mass with insufficiency of repair and adaptation mechanisms appear to be factors of relevance. A highly complex and heterogeneous molecular pathophysiology underlies diabetes-related bone disease, involving hormonal, immune, and perhaps genetic pathways. The detrimental effects of chronically elevated glucose levels on bone should be added to the more well-known complications of diabetes.
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Diabetes and bone - 2022

Review • Arch. Endocrinol. Metab. 66 (5) • 2022 • https://doi.org/10.20945/2359-3997000000552

Globally, one in 11 adults has diabetes mellitus of which 90% have type 2 diabetes. The numbers for osteoporosis are no less staggering: 1 in 3 women has a fracture after menopause, and the same is true for 1 in 5 men after the age of 50 years. Aging is associated with several physiological changes that cause insulin resistance and impaired insulin secretion, which in turn lead to hyperglycemia. The negative balance between bone resorption and formation is a natural process that appears after the fourth decade of life and lasts for the following decades, eroding the bone structure and increasing the risk of fractures.
Not incidentally, it has been acknowledged that diabetes mellitus, regardless of whether type 1 or 2, is associated with an increased risk of fracture. The nuances that differentiate bone damage in the two main forms of diabetes are part of the intrinsic heterogeneity of diabetes, which is enhanced when associated with a condition as complex as osteoporosis. This narrative review addresses the main parameters related to the increased risk of fractures in individuals with diabetes, and the mutual factors affecting the treatment of diabetes mellitus and osteoporosis.
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See also Hypothesis: Vitamin D is the link between Osteoporosis, Obesity, and Diabetes – April 2014

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See also Overview Fractures and vitamin D

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See also Possible link between osteoporosis and diabetes – July 2010

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See also Hip fractures are predicted by 10 factors – low Vitamin D was the biggest risk – Aug 2023

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Diabetes Mellitus and Bone Fracture Risk: Perplexity AI June 2025

Recent research has revealed that diabetes mellitus, both type 1 (T1D) and type 2 (T2D), represents a significant risk factor for bone fractures beyond the traditionally recognized complications of this metabolic disorder. The relationship between diabetes and fracture risk is paradoxical and multifaceted, particularly in T2D where patients often maintain normal or even elevated bone mineral density yet experience increased fracture rates. Meta-analyses demonstrate that patients with diabetes have substantially elevated risks of total, hip, upper arm, and ankle fractures, with T1D patients showing more pronounced effects than those with T2D 1. This association appears to be independent of bone mineral density measurements and involves complex pathophysiological mechanisms including altered bone quality, advanced glycation end product accumulation, and increased fall risk related to diabetic complications.

Epidemiological Evidence of Increased Fracture Risk (T1 and T2)

Type 1 Diabetes and Fracture Incidence
Type 1 diabetes demonstrates the most dramatic association with fracture risk among diabetic populations. Recent meta-analyses reveal that individuals with T1D face substantially elevated fracture risks compared to non-diabetic populations. A comprehensive meta-analysis of 78,130 individuals across 19 countries found that T1D was associated with increased risk for incident osteoporotic fracture among both men (hazard ratio 2.90; 95% CI, 1.30-6.48) and women (hazard ratio 1.65; 95% CI, 1.23-2.21) 2. The magnitude of this risk is particularly striking for hip fractures, where T1D patients demonstrate a five-fold increase in risk compared to individuals without diabetes 4. Multiple systematic reviews have consistently documented that the risk of any fracture is approximately three-fold increased in patients with T1D, with some variation by sex, showing 1.8-fold increased risk in men and 4.1-fold increased risk in women 15.
The fracture risk in T1D appears to manifest across the lifespan, affecting both young and older adults. Studies utilizing large databases such as The Health Improvement Network (THIN) have demonstrated that women with T1D experience increased fracture risks at all ages, while men show elevated risks from age 30 and older 15. This age-related pattern suggests that the bone health complications of T1D develop relatively early in the disease course and persist throughout life. The early onset of fracture risk in T1D may be attributed to the impact of insulinopenia on peak bone mass acquisition during critical developmental periods, as insulin and insulin-like growth factor 1 deficiency suppress mesenchymal stem cell differentiation into osteoblasts and reduce osteoblastic activity 5.
Type 2 Diabetes and Fracture Risk Patterns
Type 2 diabetes presents a more complex epidemiological picture regarding fracture risk. While the relative risk increase is generally lower than that observed in T1D, the absolute impact may be greater due to the substantially larger population affected by T2D. Meta-analyses indicate that T2D is associated with approximately 30% higher risk of hip fractures compared to non-diabetic individuals 4. Large-scale studies have demonstrated that T2D patients experience increased risks of total fractures (relative risk 1.32; 95% CI 1.17-1.48), hip fractures (relative risk 1.77; 95% CI 1.56-2.02), upper arm fractures (relative risk 1.47; 95% CI 1.02-2.10), and ankle fractures (relative risk 1.24; 95% CI 1.10-1.40) 1.
The Rotterdam Study, encompassing 6,655 men and women aged 55 and older, found that nonvertebral fracture risk was increased for patients with T2D (hazard ratio 1.33) compared with weight and age-matched controls 3. Similarly, the Study of Osteoporotic Fractures demonstrated that women 65 years or older with T2D were at increased risk of hip fracture (relative risk 1.82), as well as proximal humerus and foot fractures 3. The Health Aging and Body Composition study revealed that T2D was associated with accelerated bone loss at the hip and an increased risk of overall fracture (relative risk 1.64) even after adjustment for hip bone mineral density 3.

Comparative Risk Between Diabetes Types

Direct comparisons between T1D and T2D reveal important differences in fracture risk magnitude and patterns. Meta-analyses indicate that compared with patients with T2D,
patients with T1D have greater risk of

• total fractures (relative risk 1.24; 95% CI 1.08-1.41),
• hip fractures (relative risk 3.43; 95% CI 2.27-5.17), and
• ankle fractures (relative risk 1.71; 95% CI 1.06-2.78) 1.

The particularly pronounced difference in hip fracture risk between the two diabetes types suggests that the pathophysiological mechanisms underlying bone fragility may differ substantially between T1D and T2D.

High-Risk Fracture Sites (hip)

The association between diabetes and fracture risk varies significantly by anatomical location, suggesting that certain skeletal sites may be more vulnerable to diabetes-related bone changes. Hip fractures represent the most consistently elevated risk across both diabetes types, with meta-analyses showing strong associations for both T1D and T2D 1 4. The elevated hip fracture risk is particularly concerning given the significant morbidity and mortality associated with these injuries in older adults.
Ankle fractures demonstrate notable increases in risk among diabetic patients, with meta-analyses revealing a 24% increase in risk overall and a 71% higher risk in T1D compared to T2D 1. This pattern may reflect the contribution of diabetic peripheral neuropathy to fall risk and altered gait mechanics. Foot fractures also show elevated risk in diabetic populations, with some studies suggesting this represents the greatest elevation of fracture risk in T2D, where relative risk was 37% higher than comparator populations without diabetes 6.
Sites with Variable or No Increased Risk
Interestingly, certain fracture sites do not demonstrate consistent increases in risk among diabetic patients. Distal forearm fractures show no significant impact from diabetes mellitus (relative risk 1.02; 95% CI 0.88-1.19) 1. Vertebral fractures present mixed results, with some meta-analyses showing non-significant associations (relative risk 1.56; 95% CI 0.78-3.12) 1, while other studies suggest increased risks. The variable findings for vertebral fractures may reflect methodological differences in fracture detection and classification across studies.
The differential risk patterns across anatomical sites suggest that diabetes-related bone changes may not affect all skeletal regions uniformly. Sites that bear greater mechanical loads or are more susceptible to fall-related trauma may demonstrate higher fracture rates, while the intrinsic bone changes associated with diabetes may have varying effects on different bone types and anatomical locations.

Bone Quality Versus Bone Mineral Density Paradox

One of the most intriguing aspects of diabetes-related fracture risk is the apparent paradox between bone mineral density measurements and actual fracture incidence. This phenomenon is particularly pronounced in T2D, where patients often maintain normal or even elevated bone mineral density yet experience increased fracture rates 3 4. Studies demonstrate that individuals with T2D have higher bone mineral density (hip Z-scores of 0.27 ± 0.16) compared to controls, yet still experience increased fracture risk 5. This contradiction suggests that traditional bone density measurements fail to capture important aspects of bone strength that are compromised in diabetes.
Type 1 diabetes presents a different pattern, with modest reductions in bone mineral density (hip Z-scores of -0.37 ± 0.16) accompanied by disproportionately increased fracture risk 5. Even in T1D, the magnitude of fracture risk increase cannot be fully explained by the observed reductions in bone density. High-resolution peripheral quantitative computed tomography studies have revealed that T1D is associated with lower total bone mineral density, larger bone area, and poorer trabecular microarchitecture compared to controls 10. These findings suggest that both diabetes types affect bone quality through mechanisms that extend beyond simple mineral density changes.

Advanced Glycation End Products and Bone Matrix Alterations

The accumulation of advanced glycation end products (AGEs) represents a key mechanism linking chronic hyperglycemia to compromised bone quality. Hyperglycemia leads to increased production of AGEs through nonenzymatic glycation of macromolecules, including bone matrix proteins 9. AGEs can accumulate in human diabetic bone, with studies showing that pentosidine, a biomarker for AGEs, correlates with reduced bone material strength in postmenopausal women with T2D 9.
AGEs affect bone cells through multiple pathways, including interaction with the receptor for AGEs (RAGE) and direct effects on cellular function. In osteoblasts, AGEs suppress cell growth, promote apoptosis, and downregulate differentiation, thereby impairing mineralization 9. They increase mRNA expression of RANKL, promoting osteoclast activity, while decreasing alkaline phosphatase and osteocalcin expression in osteoblasts 9. The effects of AGEs appear to be biphasic, with low concentrations initially having protective effects but becoming detrimental with prolonged exposure or higher concentrations 9.
AGEs also directly alter bone matrix properties by affecting collagen cross-linking. While normal collagen cross-linking contributes to bone strength through enzymatic immature divalent cross-links and mature trivalent cross-links, diabetes promotes the formation of non-enzymatic cross-links that compromise bone mechanical properties 16. These pathological cross-links reduce bone toughness and increase brittleness, contributing to the increased fracture risk despite normal bone density measurements.

Cellular and Microarchitectural Changes

Diabetes significantly impacts bone cells and bone microarchitecture through multiple mechanisms. Chronic hyperglycemia reduces the mesenchymal stem cell population and viability, which is critical for bone formation and repair 5. Studies demonstrate that diabetes causes premature accumulation of AGEs and senescent cells that negatively affect osteocyte viability and functions through increased RAGE signaling and production of pro-inflammatory senescence-associated secretory phenotype factors 11.
High-resolution imaging studies reveal specific microarchitectural deficits in diabetic bone. Patients with T1D show poorer trabecular and cortical microarchitecture at the radius compared to controls 10. Among individuals with T1D, higher HbA1c levels, AGE accumulation, and microvascular complications are associated with deficits in trabecular microarchitecture and lower bone mineral density 10. T2D patients demonstrate increased cortical porosity in postmenopausal women, which may contribute to reduced bone strength despite normal density measurements 20.
The diabetic environment also affects bone turnover patterns. Type 2 diabetes is characterized by decreased circulating biochemical markers of bone turnover, suggesting a state of low bone turnover that may impair the normal bone remodeling process necessary for maintaining bone quality 20. Increased bone marrow adiposity in T2D may further compromise bone health by releasing cytokines and free fatty acids that promote chronic inflammation and inhibit osteoblastic activity 5.

Glycemic Control and Fracture Risk

The relationship between glycemic control and fracture risk in diabetes presents a complex, non-linear pattern that challenges simple assumptions about optimal glucose management for bone health. Recent large-scale studies reveal that fracture risk demonstrates a cubic relationship with HbA1c levels, with both very tight and poor glycemic control associated with increased fracture risk 12. A study of 10,572 elderly patients with diabetes found that HbA1c between 6.5-6.9% was associated with the lowest fracture risk, while both lower and higher values increased risk 12.
Poor glycemic control clearly contributes to fracture risk through multiple pathways. A comprehensive analysis of 157,439 individuals with T2D demonstrated that each 1% increase in longitudinal HbA1c over two years resulted in an 8% increase in fracture risk 13. Patients with poor glycemic control (HbA1c ≥9%) showed a 29% increase in fracture risk compared to those with adequate control (6-9%) 13. This relationship persisted even after adjustment for multiple diabetic comorbidities, suggesting a direct effect of hyperglycemia on bone health beyond its role in promoting complications.
Paradoxically, very tight glycemic control may also increase fracture risk, particularly in elderly patients. Studies suggest this may be related to increased hypoglycemic episodes, which can lead to falls and subsequent fractures 12. The Health, Aging and Body Composition study found that an HbA1c <6% compared to an HbA1c >8% was associated with increased fall risk in elderly patients with diabetes, but only among insulin users 12. This pattern suggests that hypoglycemia-induced falls may mediate the relationship between very tight glycemic control and fracture risk.

Duration of Diabetes and Progressive Risk

The duration of diabetes represents a significant modifier of fracture risk, with longer disease exposure associated with progressively higher fracture rates. This relationship likely reflects the cumulative effects of chronic hyperglycemia on bone metabolism and the development of diabetes-related complications that contribute to fracture risk. Studies consistently demonstrate that fracture risk increases with diabetes duration, suggesting that early intervention and optimal management throughout the disease course may be critical for bone health preservation.
The progressive nature of diabetes-related bone changes is supported by evidence that AGE accumulation and bone quality deterioration occur over time with sustained exposure to hyperglycemia. The concept of "hyperglycemic memory" suggests that bone cells previously exposed to high glucose levels may retain functional impairments even after glucose control improves 5. This finding has important implications for the timing of interventions and suggests that early, aggressive management may be necessary to prevent irreversible bone changes.

Diabetic Complications and Fracture Risk

Diabetic complications significantly contribute to fracture risk through both direct effects on bone metabolism and indirect effects on fall risk. Peripheral neuropathy represents a particularly important risk factor, as it impairs proprioception, balance, and gait stability, thereby increasing fall risk 6. Studies have demonstrated significant associations between neuropathy and fracture risk in people with T2D over age 50 6. The elevated risk of foot fractures in diabetic patients may be particularly related to neuropathy-induced changes in gait mechanics and reduced protective sensations.
Diabetic retinopathy contributes to fracture risk by impairing vision and increasing fall risk. Studies show that higher HbA1c levels and retinopathy are associated with deficits in trabecular microarchitecture 10. Diabetic nephropathy may affect bone health through multiple mechanisms, including altered mineral metabolism, secondary hyperparathyroidism, and potential development of renal osteodystrophy 3. Macroalbuminuria has been associated with larger total bone area, lower cortical thickness, and lower bone mineral density 10.
Cardiovascular disease, another common diabetic complication, may contribute to fracture risk through effects on mobility, physical function, and medication use. The complex interplay between these complications and bone health underscores the importance of comprehensive diabetes management that addresses all aspects of the disease to optimize bone health outcomes.

Limitations of Current Fracture Risk Assessment Tools

Traditional fracture risk assessment tools, including the FRAX calculator, demonstrate significant limitations when applied to diabetic patients. Studies consistently show that FRAX underestimates fracture risk in individuals with diabetes, particularly for hip fractures where the observed/predicted ratio reaches 1.85 (95% CI 1.51-2.20) among diabetic patients 7. This underestimation occurs because current risk assessment tools do not adequately account for the diabetes-specific mechanisms that compromise bone quality beyond bone mineral density measurements.
Several approaches have been proposed to improve FRAX performance in diabetic patients, including using the rheumatoid arthritis input as a proxy, applying trabecular bone score adjustments, reducing femoral neck T-score input by 0.5 standard deviations, or increasing age input by 10 years 7. While each approach shows some improvement in risk prediction, no single method proves optimal for all fracture outcomes and diabetes durations. The trabecular bone score adjustment appears particularly promising as it can be applied to the general population and partially addresses the bone quality deficits not captured by standard bone density measurements.
Novel Assessment Approaches
Advanced imaging techniques provide superior insights into diabetes-related bone changes compared to standard dual-energy X-ray absorptiometry. High-resolution peripheral quantitative computed tomography reveals specific microarchitectural deficits in diabetic patients, including increased cortical porosity and compromised trabecular architecture 10 20. The trabecular bone score, which assesses bone texture from lumbar spine DXA images, consistently shows lower values in diabetic patients compared to non-diabetic individuals and may provide better fracture risk prediction 7 20.
Biochemical markers offer additional assessment opportunities, with serum sclerostin levels found to be increased in T2D and predictive of fracture risk independent of bone mineral density 20. Advanced glycation end product measurements, including skin autofluorescence, may provide novel biomarkers for assessing diabetes-related bone quality deterioration 9 10. These approaches represent promising directions for developing diabetes-specific bone health assessment tools.

Treatment Approaches and Medication Effects

The management of bone health in diabetic patients requires consideration of both diabetes-specific factors and traditional osteoporosis risk factors. Studies suggest that some diabetes medications may influence fracture risk, though the evidence remains mixed. Recent analyses have found associations between certain diabetes treatments and fracture risk, with sodium-glucose cotransporter 2 inhibitors and lifestyle therapy associated with higher fracture risk compared to other diabetes treatments 18. However, these associations may reflect confounding factors related to disease severity rather than direct medication effects.
Insulin therapy presents a complex relationship with bone health. While insulin is anabolic to bone and promotes bone formation, studies show that insulin use is associated with increased fracture risk 4. This apparent paradox likely reflects the fact that insulin use serves as a marker of more severe diabetes rather than indicating direct negative effects of insulin on bone. Patients requiring insulin typically have longer diabetes duration, poorer glycemic control, and more complications, all of which contribute to fracture risk.
The timing and intensity of diabetes treatment may have important implications for bone health. Early aggressive management to achieve optimal glycemic control while avoiding hypoglycemia may help preserve bone quality and prevent the accumulation of irreversible changes such as AGE formation. However, the relationship between glycemic targets and bone health requires careful individualization, particularly in elderly patients where very tight control may increase hypoglycemia and fall risk.

Fall Prevention and Comprehensive Care

Given the significant contribution of falls to fracture risk in diabetic patients, comprehensive fracture prevention strategies must address both bone health and fall risk. Diabetic patients experience increased fall risk due to multiple factors including peripheral neuropathy, retinopathy, hypoglycemic episodes, cardiovascular disease, and medication effects 8. Studies demonstrate that patients with diabetes are fearful of falls, and this fear may contribute to reduced physical activity and further increase fracture risk 15.
Fall prevention interventions should include regular assessment of diabetic complications that affect balance and mobility, optimization of glucose control to minimize hypoglycemic episodes, review of medications that may increase fall risk, and implementation of structured exercise programs to improve strength and balance. Environmental modifications and assistive devices may be particularly important for patients with significant neuropathy or visual impairment.
The multifactorial nature of fracture risk in diabetes necessitates collaborative care involving endocrinologists, orthopedic specialists, and other healthcare providers. Regular bone health assessment should be integrated into routine diabetes care, with consideration of earlier intervention with antiosteoporotic medications in high-risk patients. The development of diabetes-specific fracture risk assessment tools and treatment guidelines represents an important area for future clinical development.

Conclusion (T1 and T2)

The association between diabetes mellitus and bone fracture risk represents a significant and underappreciated complication of this common metabolic disorder. Both type 1 and type 2 diabetes substantially increase fracture risk through complex mechanisms that extend well beyond traditional bone density measurements. The paradoxical combination of normal or elevated bone mineral density with increased fracture risk in diabetes highlights fundamental limitations in current approaches to bone health assessment and management.
The pathophysiology underlying diabetes-related bone fragility involves multiple interconnected mechanisms, including advanced glycation end product accumulation, altered bone microarchitecture, compromised cellular function, and increased fall risk from diabetic complications. These changes appear to develop progressively over time and may be partially irreversible, emphasizing the importance of early intervention and optimal diabetes management throughout the disease course.
Current evidence suggests that fracture risk assessment in diabetic patients requires modification of existing tools and consideration of diabetes-specific factors. The optimal approach to glycemic control for bone health appears to involve avoiding both very tight control that increases hypoglycemia risk and poor control that promotes AGE accumulation and complications. Comprehensive fracture prevention strategies must address both bone health and fall risk through multidisciplinary care approaches.
Future research priorities should focus on developing improved fracture risk assessment tools specifically for diabetic populations, understanding the optimal timing and targets for interventions to preserve bone health, and evaluating the effectiveness of various therapeutic approaches in reducing fracture risk. The recognition of bone fragility as a significant diabetic complication represents an important step toward improving comprehensive care for the millions of individuals affected by this condition.
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