Monoclonal antibodies for treating osteoporosis

ABSTRACT

Introduction: Osteoporosis is the most widespread skeletal disease requiring innovative therapeutic strategies for its management. The understanding of receptor activator of nuclear factor kappa-B ligand (RANKL) and sclerostin’s role in bone cell biology is completely changing the therapeutic landscape. RANKL supports osteoclast formation and activity and is mainly produced by cells of osteoblastic lineage. Sclerostin, an antagonist of the Wnt pathway, has a key role in bone formation and is mainly secreted by osteocytes. High levels of RANKL and sclerostin have been detected in osteoporosis, leading to the production of antibodies able to neutralize their activity.

Areas covered: In this review, the authors give an overview and discuss the literature and data on denosumab and romosozumab to treat osteoporosis. Clinical studies indicate that long-term treatment with denosumab causes a continuous increase in bone mineral density with low incidence of adverse effects. Romosozumab treatment gives increases bone formation and improves bone mineral density (BMD) though further studies are needed to better evaluate the adverse effects.

Expert opinion: Denosumab and romosozumab show promise in the treatment of osteoporosis. Furthermore, their different mechanisms of action compared to existing anti-osteoporotic drugs may permit alternative strategies for osteoporosis treatment down the line.

KEYWORDS:

• Osteoporosis
• RANKL
• denosumab
• sclerostin
• romosozumab

Article highlights

• The discovery of RANKL’s and sclerostin’s role in osteoporosis has led to the development of two important monoclonal antibodies: denosumab and romosozmab.

• Denosumab is the only monoclonal antibody approved by the FDA as a therapy for osteoporosis. Clinical studies indicate that the treatment of osteoporotic patients with denosumab for a 10-year period leads to a continuous increase in bone mineral density (BMD) with a low incidence of adverse effects.

• Romosozumab treatment increases bone formation development and improves BMD. However, recent studies have highlighted a risk of developing cardiovascular adverse events; thus, further investigation is needed to obtain their approval in clinical practice.

• The therapeutic efficacy of denosumab is quickly inverted after treatment discontinuation, thus leading to a fast loss of its curative effects. Consequently, spontaneous single or multiple vertebral fractures have been observed during the discontinuation period.

• Denosumab and romosozumab have better patient compliance compared to the classical therapeutic approaches for osteoporosis as both antibodies require comfortable administration.

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Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has not been funded.