Bone anabolics in osteoporosis: Actuality and perspectives

Abstract

Vertebral and nonvertebral fractures prevention is the main goal for osteoporosis therapy by inhibiting bone resorption and/or stimulating bone formation. Antiresorptive drugs decrease the activation frequency, thereby determining a secondary decrease in bone formation rate and a low bone turnover. Bisphosphonates are today’s mainstay among antiresorptive treatment of osteoporosis. Also, oral selective estrogen receptor modulators and recently denosumab have a negative effect on bone turnover. Agents active on bone formation are considered a better perspective in the treatment of severe osteoporosis. Recombinant-human parathyroid hormone (PTH) has showed to increase bone formation and significantly decrease vertebral fractures in severe patients, but with a modest effect on nonvertebral fractures. The study of Wnt signaling pathway, that induces prevalently an osteoblastic activity, opens large possibilities to antagonists of Wnt-inhibitors, such as sclerostin antibodies and dickkopf-1 antagonists, with potential effects not only on trabecular bone but also on cortical bone.

Keywords: Anabolic therapy; Bone mass; Bone fracture; Osteoporosis

Core tip: The study of agents active on bone formation is the main objective in the treatment of severe osteoporosis. rhparathyroid hormone (rhPTH) decreases vertebral, but not nonvertebral, fractures. On the contrary, antagonists of Wnt-inhibitors, that exert their effects mostly through a bone remodeling-independent mechanism, open new perspectives to improve not only trabecular bone but also cortical bone, with potential positive effect also on nonvertebral fractures incidence. The perspective in osteoporosis treatment should be more effective and better tolerated therapies aimed at minimizing individually fractures risk.