Increased fracture risk represents an emerging and severe complication of diabetes. The resulting prolonged immobility and hospitalisations can lead to substantial morbidity and mortality. In type 1 diabetes, bone mass and bone strength are reduced, resulting in up to a five-times greater risk of fractures throughout life. In type 2 diabetes, fracture risk is increased despite a normal bone mass. Conventional dual-energy x-ray absorptiometry might underestimate fracture risk, but can be improved by applying specific adjustments. Bone fragility in diabetes can result from cellular abnormalities, matrix interactions, immune and vascular changes, and musculoskeletal maladaptation to chronic hyperglycaemia. This Review summarises how the bone microenvironment responds to type 1 and type 2 diabetes, and the mechanisms underlying fragility fractures. We describe the value of novel imaging technologies and the clinical utility of biomarkers, and discuss current and future therapeutic approaches that protect bone health in people with diabetes.
Bibliografisk noteFunding Information:
All authors are beneficiaries of the FIDELIO consortium, an EU-funded Innovative Training Network under the Marie Skłodowska-Curie grant agreement number 860898 (grant received by authors' institutions). BB, MF, RM, NN, MR, and FR are members of the COST Action CA18139 GEMSTONE (Genomics of MusculoSkeletal traits Translational Network) supported by COST (European Cooperation in Science and Technology; grant received by authors' institutions). MR also reports honoraria for lectures from Amgen and DiaSorin; participation on an advisory board by Amgen; and provision of material by Acceleron Pharma and Novartis. MF also reports research grants from Novo Nordisk Foundation; chairmanship of the Expert Committee on treatment of rare bone diseases of the Danish Medicines Council; and receipt of drug and placebo free of charge from Novo Nordisk AS for an investigator-initiated trial. NN also reports research grants from Abiogen (received by his institution); consulting fees from UCB, Lilly, and Abiogen; and honoraria by Lilly. LCH reports a research grant of the Deutsche Forschungsgemeinschaft (received by his institution); consulting fees from Alexion, Amgen, Kyowa Kirin International, Takeda, and UCB (personal fees); support for attending meetings and/or travel from the above companies (personal fees); and participation on data safety monitoring boards or advisory boards of the above companies (personal fees). RE reports research grants from the EU, US Food and Drug Administration, American Society for Bone and Mineral Research, Alexion, Pharmacosmos, and Roche (received by his institution); consulting fees from Immunodiagnostic Systems (IDS), Sandoz, Samsung, Haoma Medica, CL Bio, Biocon, Amgen, Pharmacosmos, and Takeda (received by his institution); and participation on a Data Safety Monitoring Board or Advisory Board of the STOPFOP trial (no funding). SF reports research grants by Amgen, Alexion, and Agnovos (received by his institution); royalties or licenses by ProAxsis (received by his institution); consulting fees from Amgen, UCB, and Agnovos (received by Strongbones); payment/honoraria by Amgen, UCB, and Agnovos (received by Strongbones); participation on a Data Safety Monitoring Board for Radius (receipt by Strongbones); and serving as co-chair of Capture the Fracture steering committee and vice chair of the International Osteoporosis Foundation council of scientific advisors.