The impact of diabetes mellitus on skeletal health: an established phenomenon with inestablished causes?

Abstract Diabetes mellitus and osteoporosis affect a large proportion of older adults. In this context, diabetes may influence the bone in multiple pathways, some with contradictory effects. These mechanisms include changes in insulin and insulin-like growth factors levels, hypercalciuria associated with glycosuria, reduced renal function, obesity, higher concentrations of advanced glycation end products in collagen, angiopathies, neuropathies and inflammation. Although it is assumed that the decreased bone strength in diabetes may contribute to fracture risk, a very high number of available clinical and/or epidemiological studies as well as animal model studies brought about heterogeneous or even contradictory results on the skeletal involvement in patients with diabetes mellitus. In addition, bone mineral density (BMD) is a convenient predictor for fracture and the type 1 diabetes is associated with modest reductions in BMD. However, type 2 diabetes can be related to the elevated BMD. The immediate improvement in these discrepancies is to consider the complex pathophysiology of diabetes as well as influences of gender, age, treatment and duration of the disease. It is important also to improve further the choice of investigated biochemical markers and the standardization of the bone mass measurements. Along these lines, several recent cohort studies undeniably indicated that diabetes itself is associated with increased risk of osteoporosis.