Clinical and translational pharmacology of drugs for the prevention and treatment of bone metastases and cancer-induced bone loss

Br J Clin Pharmacol. 2019 Jun;85(6):1114-1124. doi: 10.1111/bcp.13852. Epub 2019 Feb 16.

Abstract

Bone disease is a frequent event in cancer patients, both due to cancer spread to bone and to cancer therapies. Bone is the organ most frequently affected by metastatic disease when considering the two most frequent cancers in the Western world (breast and prostate cancers). Bone metastases can have a substantial detrimental effect on patients' quality of life, as well as significant morbidity due to complications collectively known as skeletal-related events (SREs), which include hypercalcaemia, pathological fractures, spinal cord compression, and need of radiotherapy or surgery to the bone. These have been successfully mitigated with the development of bone-targeted agents (BTAs; bisphosphonates and denosumab), focused on inhibiting osteoclast activity. The potential direct antitumour effect of bisphosphonates, as well as the impact of osteoclast inhibition with subsequent decrease in bone metabolism, have also propelled investigation on the role of BTAs in preventing cancer relapse in bone. In this review, the authors aimed to discuss the role of BTAs in the treatment and prevention of bone metastases, as well as their potential value in preventing cancer treatment-induced bone loss (CTIBL). The review will focus on breast and prostate cancers, with the aim of providing the most relevant clinical data emerging from bench to bedside translational research in the field of cancer-induced bone disease.

Keywords: Ra-223; bisphosphonates; bone metastases; bone-targeted agents; denosumab.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects*
  • Bone Density Conservation Agents / adverse effects
  • Bone Density Conservation Agents / therapeutic use*
  • Bone Diseases, Metabolic / chemically induced
  • Bone Diseases, Metabolic / drug therapy*
  • Bone Diseases, Metabolic / pathology
  • Bone Diseases, Metabolic / physiopathology
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / physiopathology
  • Bone Neoplasms / secondary
  • Bone Remodeling / drug effects*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Chemotherapy, Adjuvant
  • Female
  • Humans
  • Male
  • Palliative Care
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Risk Factors
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Bone Density Conservation Agents