Diabetes-Induced Osteoporosis and Bone Health

Diabetes mellitus is increasingly recognised as a driver of skeletal fragility, a condition sometimes termed “diaporosis.” Both type 1 and type 2 diabetes are associated with compromised bone quality and elevated fracture risk, yet the underlying mechanisms differ. Chronic hyperglycaemia fosters formation of advanced glycation end products in collagenous bone matrix, leading to impaired material properties and microarchitectural deterioration. Insulin deficiency and resistance disrupt osteoblast and osteoclast activity, favouring bone resorption over formation. Diabetes-related microvascular disease, neuropathy and reductions in muscle mass further increase the propensity for falls. Perturbations in calcium, vitamin D and parathyroid hormone homeostasis are common, while some antihyperglycaemic therapies exert off-target effects on bone cells. Clinically, bone mineral density may be normal or only modestly reduced, yet fracture rates are disproportionately high, underscoring the need for tailored screening and management strategies. Recent advances have illuminated endocrine cross-talk between bone and glucose metabolism, highlighting osteocalcin and other osteokines as modulators of insulin sensitivity. A deeper understanding of these pathways is guiding development of interventions that preserve skeletal integrity without compromising glycaemic control, with important implications for an ageing global population burdened by diabetes.

Research from Nature Portfolio

Meta-analysis of randomised controlled trials has clarified the skeletal safety profile of dipeptidyl peptidase-4 inhibitors. Pooling data from over sixty trials with more than 60 000 participants revealed no significant difference in fracture incidence between patients receiving DPP-4 inhibitors and those on placebo or alternative antihyperglycaemic agents. The neutral effect persisted across subgroups defined by type of DPP-4 inhibitor, duration of follow-up and comparator regimens. This finding supports the continued use of DPP-4 inhibitors in individuals at risk of osteoporosis without adding fracture liability.

Diabetes-Induced Osteoporosis and Bone Health publication trend

The graph below shows the total number of articles in diabetes-induced osteoporosis and bone health across all publications each year (not limited to Nature Index journals).

Technical terms

Osteoporosis: A systemic skeletal disorder characterised by diminished bone strength and increased fracture susceptibility.

Bone mineral density (BMD): A quantitative measure of bone mass per unit area, used to assess fracture risk.

Advanced glycation end products (AGEs): Irreversible modifications of proteins or lipids by sugars, impairing collagen integrity in bone.

Dipeptidyl peptidase-4 (DPP-4): An enzyme that degrades incretins and influences bone remodelling through effects on osteoblasts and osteoclasts.

Glucagon-like peptide-1 receptor agonists (GLP-1 RA): Drugs that mimic endogenous GLP-1 to enhance insulin secretion, with emerging bone-modulatory actions.

Sodium-glucose cotransporter-2 inhibitors (SGLT-2i): Agents that promote urinary glucose excretion and may affect bone turnover and fracture risk.

References

1. Bone Loss in Diabetes Mellitus: Diaporosis. International Journal of Molecular Sciences (2024).
2. The Interplay Between Bone and Glucose Metabolism. Frontiers in Endocrinology (2020).
3. Dipeptidyl peptidase-4 inhibitors and fracture risk: an updated meta-analysis of randomized clinical trials. Scientific Reports (2016).
4. Risk of bone fracture by using dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, or sodium-glucose cotransporter-2 inhibitors in patients with type 2 diabetes mellitus: a network meta-analysis of population-based cohort studies. Frontiers in Endocrinology (2024).
5. Clinical implications of fracture severity risk with pioglitazone: a systematic review and meta-analysis of clinical randomized trials. Frontiers in Pharmacology (2025).