Bone effects of cancer therapies

Abstract

Agents used for systemic chemotherapy can alter normal bone homeostasis through mechanisms that affect both osteoblast and osteoclast function. The identification of those agents that influence maintenance of the bone-remodeling compartment is an important component of the drug development and testing process. This brief review focuses on preclinical and clinical data illustrating the effect of several classes of chemotherapeutic agents on skeletal development and bone remodeling. New preclinical data demonstrate that several classes of chemotherapeutic agents, including histone deacetylase inhibitors and proteasome inhibitors, alter osteoblast and osteoclast function. Preclinical data on retinoic acid analogues demonstrate that these agents inhibit osteoclastogenesis. In addition, a dose-dependent effect of methotrexate treatment on growth plate thickness and primary spongiosa height in rats has been demonstrated. Two recently published analyses of clinical data from trials of bortezomib in myeloma patients found increased biochemical markers of bone formation and evidence of increased bone deposition after bortezomib treatment. Several classes of chemotherapeutic agents alter bone metabolism and negatively impact bone homeostasis. Bone mineral density (BMD) monitoring guidelines for patients receiving systemic chemotherapy are not established. Limited guidelines exist for BMD monitoring in patients receiving long-term hormonal modulation; however, the negative effect of other chemotherapeutic agents on the skeleton is underappreciated.