Bone accrual in children and adolescents with type 1 diabetes: current knowledge and future directions

Abstract

Purpose of review Skeletal fragility is now recognized as a significant complication of type 1 diabetes (T1D). Many patients with T1D develop the disease in childhood and prior to the attainment of peak bone mass and strength. This manuscript will review recent studies investigating the effects of T1D on skeletal development. Recent findings Mild-to-moderate deficits in bone density, structure, and mineral accrual were reported early in the course of T1D in some but not all studies. Childhood-onset disease was associated with a more severe skeletal phenotype in some adult studies. Lower than expected bone mass for muscle size was been described. Hemoglobin A1c was negatively associated with bone density and structure in several studies, though the mechanism was not clear. Summary The use of advanced imaging techniques has shown that the adverse effects of T1D on the developing skeleton extend beyond bone density to include abnormalities in bone size, shape, microarchitecture, and strength. Despite these gains, a uniform understanding of the pathophysiology underlying skeletal fragility in this disorder remains elusive. Longitudinal studies, especially in association with interventions to reduce hyperglycemia or improve muscle strength, are needed to inform bone healthcare in T1D.

Effects of diabetes on osteocytes

“…Fracture risk in T1D is exacerbated by poor glycemic control, longer disease duration, and diabetic neuropathy [6,7,25]. Furthermore, T1D is associated with reduced BMD, bone size, and strength that make the skeleton vulnerable to fractures [6,7].…”

“…Fracture risk in T1D is exacerbated by poor glycemic control, longer disease duration, and diabetic neuropathy [6,7,25]. Furthermore, T1D is associated with reduced BMD, bone size, and strength that make the skeleton vulnerable to fractures [6,7]. There is also compelling evidence that prolonged hyperglycemia and a pro-inflammatory bone microenvironment in the setting of T1D may cause osteocytes to relay signals that enhance osteoclast activity [26], thereby contributing to a negative bone balance between bone formation and resorption.…”

“…With the juvenile onset of T1D, bone mineral density (BMD), skeletal size, and strength are diminished throughout growth and development, leading to suboptimal peak bone strength. This contributes to a 6-fold increased lifetime risk of fractures in the T1D population [6,7]. Noteworthy, however, is while perceived to be juvenile, nearly 50% of individuals with T1D are diagnosed as adults [8].…”

Skeletal health in diabetes

“…In the 2021 issue of the Journal, we published seven articles. To prevent fractures in later life, Dr Weber [4] elegantly reviewed factors affecting bone accrual in children and adolescents with type 1 diabetes (T1D). Identifying modifiable factors such as optimal glycemic control from the early stage of diabetes may help to optimize bone accrual and may prevent fracture in later life.…”