Skeletal Fragility in Adult People Living With Type 1 Diabetes

Advances in monitoring and treatment of people living with Type 1 Diabetes (T1D) have led to longer life expectancy, but with it an ageing population of T1D patients with age-associated conditions. While diabetic macrovascular, brain, eye, nerve and kidney complications are widely recognized, bone fragility with concomitant fracture has received considerably less attention, even though bone fractures lead to very high morbidity and mortality. Hip fracture risk is up to 6-fold higher in T1D compared to age- and sex-matched non-diabetic controls and is significantly higher than in type 2 diabetes. Hip fractures occur at a younger age and their consequences are worse compared to non-diabetics. The risk of nonvertebral fractures is also significantly increased. The mechanisms of bone fragility in T1D are complex. Hip bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DXA) underestimates hip fracture risk in T1D. However, it is the preferred modality to assess bone status in T1D in clinical practice and is recommended in all T1D patients with poor glycemic control and/or microvascular complications. Trabecular bone score (TBS) is only mildly reduced and its ability to predict fractures in T1D is yet unknown. Bone turnover markers, particularly the formation marker P1NP, are suppressed and do not predict fracture risk in T1D. Altered bone quality in part due to the formation of advanced glycation end products (AGEs) in collagen type 1 in bone is thought to be a major contributor. T1D-related risk factors for fractures include disease onset before peak bone mass attainment (age < 20 years), longer disease duration, poor glycemic control (HbA1c≥ 8%), episodes of hypoglycemia, falls, and microvascular complications. There is scant evidence for therapeutic interventions to prevent or treat skeletal fragility in T1D. Until more data is available, treatment with currently available anti-osteoporosis therapies is recommended in T1D patient with previous hip or vertebral fragility fracture, more than 1 other fragility fracture, BMD T-score lower than -2.5 at the femoral neck or spine, and elevated FRAX score. Fracture risk assessment needs to be part of the routine clinical management of people living with T1D.