First-line treatment of osteoporosis with osteoanabolic therapy: a new opportunity

Abstract

Osteoporosis is a national health priority, and over six million Australians over the age of 50 years have poor bone health. Fragility fractures due to osteoporosis are associated with an increased morbidity and mortality risk and a high economic cost to the community. It is a chronic condition requiring long-term management. Despite notable advances in pharmacotherapy, large treatment gaps remain. Antiresorptive drugs have been the foundation of treatment; however, their efficacy wanes and rare adverse effects accumulate with prolonged use. Osteoanabolic drugs form new bone and can also restore deteriorated bone microarchitecture, in addition to increasing bone mineral density. Currently, antiresorptive drugs are used as first-line drugs for osteoporosis. However, recent studies have highlighted the superiority of anabolic drugs for fracture reduction over antiresorptives. Furthermore, for patients at very high risk or imminent risk of fracture, the use of sequential therapy with an osteoanabolic medication followed by an antiresorptive is superior to achieving optimal long-term bone health outcomes. This article will discuss the evidence supporting the anti-fracture benefits of osteoanabolic drugs, emphasising their benefits as first-line agents for osteoporosis. Challenges surrounding transitions between osteoanabolic and antiresorptive medications are also discussed, highlighting considerations for the optimal treatment sequence with a focus on recent updates to Australian prescribing recommendations and PBS requirements.

Keywords: anabolic treatment; fracture; osteoporosis.

Figure 1

Cellular and molecular mechanisms involved in bone remodelling, highlighting the role of antiresorptive and anabolic agents in regulating osteoclast and osteoblast activity. Denosumab: a monoclonal antibody that blocks receptor activator of nuclear factor kappa‐B ligand (RANKL), thereby preventing osteoclast formation and reducing bone resorption. Bisphosphonate, oestrogen and selective oestrogen receptor modulators (SERMs): these agents inhibit osteoclast activity, thereby reducing bone breakdown. Teriparatide and abaloparatide: analogues of parathyroid hormone (PTH) that increase bone formation. Romosozumab: a monoclonal antibody that inhibits sclerostin, a protein produced by osteocytes that suppresses osteoblast activity, thereby promoting bone formation.

Figure 2

Incidence of new vertebral fractures in patients treated with teriparatide or risedronate.

Figure 3

Updated osteoporosis guidelines endorsed by RACGP and Healthy Bones Australia.