Type 2 Diabetes Mellitus and Fracture Risk: An International Meta-Analysis

Presenter: N. C. Harvey

This International individual participant data meta‑analysis of prospective fracture outcomes in adults with type 2 diabetes mellitus (T2DM), involved pooling data from 951,871 participants (65% women) across 48 cohorts in 31 countries with 10.2 million person‑years of follow‑up; femoral neck bone mineral density (FNBMD) data were available in a large subset.

T2DM was associated with higher risk of major osteoporotic fracture and hip fracture in both sexes. Age‑adjusted hazard ratios were 1.20 in men and 1.11 in women for major osteoporotic fracture, and 1.29 and 1.43, respectively, for hip fracture. Adjustment for FNBMD T‑score modestly increased risk estimates, indicating effects beyond bone density.

T2DM is an independent risk factor for fractures, supporting its incorporation into future FRAX® risk prediction models.

Pathophysiology, Risk Assessment Challenges, and Non-pharmacological Strategies in Diabetic Bone Fragility

Presenter: T. Erdogan

This narrative synthesis focuses on skeletal fragility in older adults with type 1 diabetes (T1D) and type 2 diabetes (T2D), emphasizing mechanisms, limitations of fracture risk assessment, and non‑pharmacological management.

In T1D, insulin deficiency impairs osteoblast function, resulting in reduced bone mineral density (BMD) and predominantly quantitative bone loss. In T2D, fracture risk is increased despite normal or elevated BMD due to poor bone quality, driven by microarchitectural deterioration, advanced glycation end‑product accumulation, low bone turnover, inflammation, and oxidative stress. Standard tools such as dual‑energy X‑ray absorptiometry and FRAX frequently underestimate fracture risk, particularly in T2D. Diabetes‑specific factors, trabecular bone score (TBS), and FRAX adjustments improve risk stratification.

Diabetic bone fragility is multifactorial, requiring enhanced risk assessment and robust non‑pharmacological strategies, including nutrition, exercise, and fall prevention

Skeletal Effects of Anti-diabetic Drugs and Osteoporosis Management in Patients with Diabetes

Presenter: S. Ozkok

This study examines the skeletal effects of commonly used antidiabetic medications and evidence‑based osteoporosis treatment strategies in older adults with diabetes.

Relaxed glycemic targets (glycated hemoglobin [HbA1c] ~8.0–8.5%) in frail older adults may reduce hypoglycemia‑related falls without major skeletal harm. Metformin, dipeptidyl peptidase‑4/DPP4 inhibitors, glucagon‑like peptide‑1/GLP-1 receptor agonists, and sodium–glucose cotransporter‑2/SGLT2 inhibitors show neutral or potentially favorable bone profiles. In contrast, thiazolidinediones are consistently linked to bone loss and increased fracture risk, while insulin use is associated with fractures mainly through hypoglycemia. Antiresorptives (bisphosphonates, denosumab) and anabolic agents are effective in diabetes, with careful consideration of renal and cardiovascular risk.

Individualized, integrated management is essential to reduce fractures in older adults with diabetes.

Incidence of Bone Fracture in Type 2 Diabetes: A Population-based Cohort Study

Presenter: S. Naderpour

This population‑based cohort study used the UK Clinical Practice Research Datalink Aurum linked to Hospital Episode Statistics and included 770,641 adults, of whom 28,149 had type 2 diabetes (T2D), all free of prior fracture at baseline.

Over 245,449 person‑years in T2D and 7,867,206 person‑years in controls, 5,362 and 90,587 first fractures occurred, respectively. Fracture incidence was 21.8 per 1,000 person‑years (95% confidence interval [CI] 21.3–22.4) in T2D versus 11.5 (95% CI 11.4–11.6) without diabetes. The crude incidence rate ratio (IRR) was 1.90 (95% CI 1.85–1.95), attenuated to 1.25 (95% CI 1.21–1.28) after adjustment for age, sex, deprivation, and ethnicity.

T2D is independently associated with a substantially higher risk of first fracture, supporting targeted fracture risk assessment and prevention strategies in this population.

Insulin Resistance and Osteoporosis: Pathogenesis, Clinical Associations, and Therapeutic Strategies

Presenter: T. Griadil

This comprehensive review integrated evidence from recent literature (2020–2025) and clinical data from the National Health and Nutrition Examination Survey and Midlife in the United States II studies to examine mechanisms linking insulin resistance (IR) with skeletal fragility.

Although insulin signaling via the PI3K/Akt/mTOR pathway has anabolic effects on bone, systemic IR was consistently associated with the “diabetic bone paradox,” characterized by preserved or increased bone mineral density alongside elevated fracture risk. This fragility was driven by chronic inflammation, oxidative stress, and accumulation of advanced glycation endproducts, leading to impaired collagen quality, suppressed osteoblast function, and low bone turnover. Standard dual‑energy X‑ray absorptiometry underestimated risk by failing to capture cortical porosity. Metformin showed osteoprotective effects, whereas thiazolidinediones were associated with bone loss.

IR acts as a silent pathogen for skeletal health, degrading bone quality independently of bone mass and necessitating metabolically informed osteoporosis management.

GLP-1 Receptor Agonists and Musculoskeletal Outcomes

Presenter: C. Beaudart

This PRISMA‑adherent systematic review and random‑effects meta‑analysis synthesized evidence from randomized controlled trials and real‑world evidence studies evaluating musculoskeletal effects of glucagon‑like peptide‑1 receptor agonists (GLP‑1 RAs).

From 1,148 records, 61 studies (47 randomized controlled trials, 13 real‑world evidence studies, one pharmacovigilance study; 1,250,778 individuals) were included, covering semaglutide, liraglutide, exenatide, dulaglutide, and tirzepatide. No significant effects were observed on bone mineral density or fracture risk at any site. Muscle outcomes showed a consistent reduction in lean body mass/fat‑free mass (standardized mean difference −0.52, 95% confidence interval −0.80 to −0.23; I² = 88%), driven mainly by liraglutide and semaglutide. No significant changes were seen in WOMAC pain, stiffness, or physical function.

GLP‑1 RAs appear neutral for bone and joint outcomes but are associated with loss of muscle mass/lean mass, warranting further investigation of clinical relevance.

High Prevalence of Osteoporosis in Autoimmune and Inflammatory Diseases

Presenter : E. Bischoff

This narrative review examined osteoporosis as a comorbidity in autoimmune and inflammatory diseases, integrating epidemiological evidence, pathophysiological mechanisms, and current guideline recommendations.

Studies consistently report increased prevalence of low bone mass and fragility fractures in autoimmune and inflammatory conditions. Chronic systemic inflammation promotes bone loss through cytokine‑mediated mechanisms, particularly tumor necrosis factor‑α (TNF α) and interleukin‑6 (IL6), which enhance osteoclast activity and suppress osteoblast function, leading to microarchitectural deterioration. Long‑term glucocorticoid exposure further increases fracture risk, even when bone mineral density is not markedly reduced. In ankylosing spondylitis, spinal dual‑energy X‑ray absorptiometry (DXA) may overestimate bone mineral density due to ossification. Radiofrequency Echographic Multi‑Spectrometry (REMS) shows high precision, detects smaller bone mineral density (BMD) changes over shorter intervals, and REMS‑derived Fragility Score may better predict incident fractures than T‑scores.

Osteoporosis is common yet under‑recognized in autoimmune and inflammatory diseases, and REMS may improve early detection and fracture prevention, though prospective validation is needed.

Incidence of New Osteoporotic Fractures Up to Three Years of Followup in Subjects with Type 2 Diabetes Mellitus who initiate Any Osteoporosis Medication Compared to Nondiabetics: A Population-Based Cohort Study

Presenter: L. Gomez Rodriguez

This population‑based cohort study used real‑world primary care data from the SIDIAP database to compare osteoporotic fracture (OF) incidence in patients with type 2 diabetes mellitus (T2DM) and non‑diabetic individuals initiating osteoporosis medication (OM).

Among 42,946 initiators (5,828 T2DM; 37,118 non‑diabetic), patients with T2DM were older (mean 74.1 vs 68.1 years) and predominantly female. OF incidence rates (per 1,000 person‑years) were higher in T2DM than non‑diabetics for overall OF (53.7 vs 31.5), hip fracture (18.7 vs 8.1), and vertebral fracture (32.8 vs 22.5). For all OM, incidence rate ratios decreased over follow‑up periods (4–36 months) compared with 0–3 months in both groups.

In real‑life conditions, osteoporosis medications show comparable effectiveness in reducing fracture incidence in patients with T2DM and non‑diabetic individuals, despite higher baseline fracture risk in T2DM.

 WCO-IOF-ESCEO Congress, April 16-19, 2026, Prague, Czech Republic