Managing Bone Fragility in Older Adults with Diabetes: Pathophysiology, Assessment, and Therapeutic Considerations

Older adults with diabetes mellitus, encompassing both type 1 diabetes (T1D) and type 2 diabetes (T2D), face a substantially elevated risk of fragility fractures, contributing significantly to morbidity and mortality in this vulnerable population. The underlying pathophysiology differs between the two types: T1D is typically characterized by reduced bone mineral density (BMD) stemming from insulinopenia, whereas T2D often presents with normal or even high BMD but compromised bone quality due to factors, including altered microarchitecture, accumulation of advanced glycation end products (AGEs), and low bone turnover. These distinct mechanisms create challenges for accurate fracture risk assessment, as standard tools such as dual-energy X-ray absorptiometry (DXA)-measured BMD and the Fracture Risk Assessment Tool (FRAX) often underestimate the true risk, particularly in T2D. Effective management necessitates a comprehensive, individualized approach. This includes optimizing glycemic control while minimizing hypoglycemia, implementing lifestyle modifications such as adequate nutrition (calcium, vitamin D, protein) and appropriate exercise, and crucially, proactive fall prevention strategies. Careful consideration must be given to the selection of antidiabetic medications, avoiding agents known to harm bone (e.g., thiazolidinediones) and preferring those with neutral or potentially beneficial skeletal effects (e.g., metformin, dipeptidyl peptidase-4 inhibitors [DPP-4i], glucagon-like peptide-1 receptor agonists [GLP-1 RAs]). Osteoporosis pharmacotherapies, including antiresorptive (bisphosphonates, denosumab) and anabolic agents (teriparatide, abaloparatide, romosozumab), appear effective in patients with diabetes largely on the basis of post hoc analyses and observational data, although evidence specific to this population remains limited. Integrating geriatric principles, such as assessing frailty and polypharmacy, is essential for optimizing care and improving outcomes for older adults with diabetes and bone fragility.