Hyperglycaemia induced osteoporosis: Is there a hope with dipeptidyl peptidase-4 inhibitors?

Diabetes mellitus and osteoporosis are chronic illnesses associated with adverse health outcomes. Studies have reported common linkages between energy and bone metabolism. Specifically, significant effect of glucose metabolism on bone homoeostasis has improved the understanding of hyperglycaemia-induced bone degeneration. The study of skeletal endocrinology has also enabled the elucidation of pathways involved in glucose associated abnormality in bone homoeostasis. Insulin is central molecule in glucose and bone homoeostasis. Bone markers like osteocalcin, bone morphogenic protein and sclerostin control both bone and glucose metabolism. The interaction between gut-bone axis is mainly mediated by incretins. These hormones exert anabolic effect and alter bone remodelling process by enhancing bone alkaline phosphatase activity and type-1 collagen levels. Additionally, incretins also exhibit anti-inflammatory and anti-oxidative properties. Incretin degradation is mediated by Dipeptidyl Peptidase-4 (DPP-4), which is reported to be elevated in patients with osteoporosis. This association of incretins and bone homoeostasis possesses untapped therapeutic potential which needs to be further explored. In view of the concomitant occurrence, the present review summarises the correlation between diabetes mellitus, osteoporosis, incretins and DPP-4 and discusses the current evidence on DPP-4 inhibitors as new therapeutic alternative for osteoporosis.