Denosumab for cancer-related bone loss

ABSTRACT

Introduction

Prolonged use of anti-cancer treatments in breast and prostate tumors alters physiological bone turnover leading to adverse skeletal related events, such as osteoporosis, loss of bone mass, and increased risk of fractures. These complications known as cancer treatment-induced bone loss (CTIBL) should be managed with bone targeting agents such as the bisphosphonates and denosumab. The latter is a monoclonal antibody against the receptor activator of nuclear factor-kB ligand (RANKL) that suppresses osteoclasts function and survival increasing bone mass.

Areas covered

This review will focus on the mechanisms associated with bone loss induced by cancer treatments and the most recent evidence about the use of denosumab as preventive and therapeutic strategy to protect bone health. Moreover, we will discuss several key aspects regarding the clinical practical use of denosumab to optimize the management of CTLIB in breast and prostate cancer.

Expert opinion

Denosumab treatment strongly prevents cancer therapies-related skeletal issues in breast and prostate cancer with a good safety profile. Adjuvant six-monthly denosumab delays the time to first fracture onset in early stage breast cancer patients with normal or altered bone mineral density (BMD). Similarly, denosumab treatment is able to prevent fractures and BMD loss in nonmetastatic prostate cancer patients.

KEYWORDS:

• Cancer treatment induced bone loss (CTLIB)
• denosumab
• bone health
• osteoporosis

Article highlights

• Treatment induced bone loss increases fracture risk and requires the use of a bone targeted agent in addition to lifestyle modifications.

• Denosumab treatment in breast and prostate cancer patients reduces the time to first fracture and increases bone mineral density.

• Denosumab is recommended in breast cancer patients treated with hormonal therapy and prostate cancer patients receiving Androgen Deprivation Therapy (ADT) for >6 months with either a BMD T score of <-2 or with ≥2 risk factors for fractures.

• Denosumab is non-inferior to zoledronic acid in preventing first Skeletal Relared Event (SRE) in patients with multiple myeloma with a comparable safety profile.

• Denosumab is well tolerated, even if the duration of treatment remains controversial.

This box summarizes key points contained in the article.

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.

Reviewer disclosures

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