New and developing pharmacotherapy for osteoporosis in men

ABSTRACT

Introduction: Osteoporosis represents a major health and societal burden in men, as well as in women. However, only a minority of men are screened and treated for osteoporosis and fracture prevention, even after first fracture.

Areas covered: This article provides a comprehensive summary of the currently available drugs for osteoporosis in men as well as insights into new and developing pharmacotherapy.

Expert opinion: To date, therapeutic approaches to osteoporosis in men remain not as well defined as in women, since antifracture efficacy data are lacking for most approved pharmaceuticals. Based on the currently available evidence, bisphosphonates are generally recommended as first line pharmacotherapy in men. Conceptually, osteoanabolic agents, such as teriparatide could be more appropriate for men with primary osteoporosis and low bone turnover. However, osteoanabolic agents display a limited anabolic window during which their stimulatory effects on bone formation prevail over the increase in bone resorption and their use, for theoretical safety reasons, is limited to a cumulative duration of two years. Due to the recent advances in bone biology, future drugs for osteoporosis in men might include more selective antiresorptive compounds which do not markedly inhibit bone formation as well as newer osteoanabolic agents that appear to more selectively stimulate bone formation.

KEYWORDS:

• Male osteoporosis
• bisphosphonate
• denosumab
• teriparatide
• abaloparatide
• cathepsin k inhibitors
• sclerostin inhibitors
• testosterone replacement
• SARMs

Article highlights

• As in women, osteoporosis is a major health and societal burden in men, with an estimated lifetime risk of fracture for males aged 50 years or older between 13% and 30%. Moreover, the consequences of osteoporotic fractures in men are more severe than in women, both in terms of morbidity and mortality.

• Despite recent progress in this field, osteoporosis remains largely underdiagnosed and undertreated in men, even after the first fracture has occurred.

• At present, there is no universally validated strategy for therapeutic decision making in men. Based on cost-effectiveness analyses in the United States, pharmacological treatment is recommended in: a) all men with a non-traumatic hip or vertebral fracture; b) men without fragility fractures but whose BMD (spine and/or hip) is −2.5 SD below the mean of normal young males; c) men who are receiving glucocorticoid treatment and meet therapeutic guidelines(prednisone or equivalent > 7.5 mg/d daily) for more than 3 months and are at moderate or high risk, and d) men with BMD within the osteopenic range (T-score between −1.0 and −2.5 SD) in whom the estimated 10-year fracture probability by the FRAX risk assessment tool is equal or greater than 3% and 20%, respectively, for hip and major osteoporotic fractures.

• Most of the pharmacological agents that are currently available for the treatment of male osteoporosis have been previously tested and approved in women, and then replicated in smaller randomized controlled trials in men, with change in BMD as a primary end-point. Drugs currently approved for the treatment of male osteoporosis include antiresorptive agents such as oral (risedronate and alendronate) or intravenous (zoledronic acid) aminobisphosphonates and denosumab as well as the osteoanabolic agent, teriparatide (a 34 residue amino terminal fragment of full length parathyroid hormone).

• A second osteoanabolic agent, abaloparatide (an 34-residue analogue of the amino terminal fragment of PTHrP), has been recently approved for the treatment of osteoporosis in postmenopausal women. Results in men are expected. Due to recent advances in bone biology, future drugs for osteoporosis in men might include more selective antiresorptive compounds which do not markedly suppress bone formation as well as newer osteoanabolic agents that appear to more selectively stimulate bone formation.

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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.