Romosozumab for the treatment of postmenopausal women at high risk of fracture

ABSTRACT

Introduction

Romosozumab is a monoclonal antibody that binds to sclerostin (an inhibitor of the Wingless-related integration site (Wnt) signaling pathway). It is a new osteoanabolic drug that simultaneously increases bone formation and decreases bone resorption. It has recently been approved by the US and EU authorities in postmenopausal women with at high risk of fractures.

Areas covered

The literature on romosozumab in preclinical and in phase II and III clinical studies has been reviewed about the effect on bone, bone markers, and fracture reduction and its safety.

Expert opinion

Compared to antiresorptive agents, its unique mechanism of action results in a quicker and greater increase in bone mineral density, it repairs and restores trabecular and cortical bone microarchitecture, and reduces fracture risk more rapidly and more effectively than alendronate, with persisting effects for at least two years after transition to antiresorptive agents. This finding has introduced the concept that, in patients at very high risk of fractures, the optimal sequence of treatment is to start with an osteoanabolic agent, followed by a potent AR drug. Recent national and international guidelines recommend the use of romosozumab as an initial treatment in patients at very high fracture risk without a history of stroke or myocardial infarction.

KEYWORDS:

• Romosozumab
• osteoporosis
• very high fracture risk
• osteoanabolic agents
• sequential treatment
• fracture prevention

Article highlights

• Romosozumab, an inhibitor of sclerostin, is a new osteoanabolic drug that simultaneously increases bone formation and decreases bone resorption, in preclinical and clinical studies

• One year treatment with romosozumab reduces fracture risk more rapidly and more effectively than placebo or alendronate, with persisting effects for at least two years after transition to antiresorptive treatment.

• The overall incidence of adverse events and serious adverse events was similar compared to placebo or alendronate, except, during the first year, for mild injection site reaction. In comparison with alendronate, there was a numerical non-significant imbalance of all adjudicated serious cardiovascular adverse events. Patients with a history of myocardial infarction or stroke should not be considered for treatment with romosozumab.

• Recent national and international guidelines recommend the use of romosozumab as initial treatment in patients at very high fracture risk without a history of stroke or myocardial infarction.

Declaration of interest

P Geusens has worked on clinical studies/ advisory boards/ has received speaker fees from Abbvie, Amgen, Bristol Myers Squibb, Celgene, Janssen, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, UCB, Fresenius, Mylan, Viatris, Sandoz, and Merck. NM Appelman-Dijkstra has worked on clinical studies/ received speaker fees from Amgen, UCB, Kyow a Kirin and Takeda as well as having worked on clinical studies/ advisory boards/ has received speaker fees from Amgen and UCB. W Lems declares advisory board and speaker fees from Amgen, UCB, Pfizer and Galapagos. J van den Bergh declares advisory board/ speaker fees from Amgen and UCB. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has received consulting fees and honorarium from Amgen and UCB, companies that market romosozumab. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Company review

UCB provided a scientific accuracy review of the sections of the paper relating to clinical data and safety and tolerability at the request of the journal editor.

Additional information

Funding

This paper was not funded.