Targeting fundamental aging mechanisms to treat osteoporosis

ABSTRACT

Introduction: Osteoporotic fractures represent a growing burden of mortality, morbidity and socioeconomic cost to health-care systems worldwide. Osteoporosis is a disease uniquely associated with aging, therefore, an understanding of the physiological mechanisms underpinning its development as we age may open new avenues for therapeutic exploitation. Novel treatments, as well as refinement of the current approaches, are vital in the effort to sustain healthy, independent patients across the lifespan.

Areas covered: This review covers the anabolic and catabolic pathways seen in bone maintenance, highlighting how they are changed with age, leading to osteoporosis. It will also discuss how these changes may be targeted therapeutically, in the development of new therapies, and the refinement of those already in use.

Expert opinion: New effective and safe treatments for osteoporosis are still needed. Bone anabolics seem to be the most appropriate therapeutic approach to osteoporosis in older persons. Considering that bone and muscle mass synchronically decline with aging thus predisposing older persons to falls and fractures, combined therapeutic approaches to osteosarcopenia with a dual anabolic effect on muscle and bone will be a major advance in the treatment of these devastating conditions in the future.

KEYWORDS:

• Osteoporosis
• Anabolics
• aging
• kynurenines
• Wnts
• RANKL
• Sclerostin
• Osteosarcopenia
• Antiresorptives

Article highlights

• Despite recent advances, osteoporosis still requires new safe and effective treatments with strong anti-fracture effects

• Aging presents a range of physiological challenges that together drive the pathogenesis of primary osteoporosis

• Many of these physiological changes are currently targeted in osteoporosis therapies, but there are a range of unexplored areas for therapeutic exploitation

• Age related changes such as cellular senescence, stem cell aging, changes in anabolic signaling pathways and muscle and fat cross talk are all being investigated as possible therapeutic targets

• Dual therapies with strong anabolic effect on muscle and bone will have a strong impact on the adverse outcomes associated with these conditions into the future

This box summarizes key points contained in the article.

Declaration of interest

J Feehan is supported by an Australian Government Research Training Program Scholarship. G Duque is a consultant to Lilly and Amgen Australia and is a member of the board of speakers for Amgen, Lilly, Sanofi and Novartis Australia. 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

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper is funded by the Australian Institute for Musculoskeletal Science (AIMSS).