Drugs Causing Bone Loss

Handb Exp Pharmacol. 2020:262:475-497. doi: 10.1007/164_2019_340.

Abstract

Drugs may cause bone loss by lowering sex steroid levels (e.g., aromatase inhibitors in breast cancer, GnRH agonists in prostate cancer, or depot medroxyprogestone acetate - DMPA), interfere with vitamin D levels (liver inducing anti-epileptic drugs), or directly by toxic effects on bone cells (chemotherapy, phenytoin, or thiazolidinedions, which diverts mesenchymal stem cells from forming osteoblasts to forming adipocytes). However, besides effects on the mineralized matrix, interactions with collagen and other parts of the unmineralized matrix may decrease bone biomechanical competence in a manner that may not correlate with bone mineral density (BMD) measured by dual energy absorptiometry (DXA).Some drugs and drug classes may decrease BMD like the thiazolidinediones and consequently increase fracture risk. Other drugs such as glucocorticoids may decrease BMD, and thus increase fracture risk. However, glucocorticoids may also interfere with the unmineralized matrix leading to an increase in fracture risk, not mirrored in BMD changes. Some drugs such as selective serotonin reuptake inhibitors (SSRI), paracetamol, and non-steroidal anti-inflammatory drugs (NSAIDs) may not per se be associated with bone loss, but fracture risk may be increased, possibly stemming from an increased risk of falls stemming from effects on postural balance mediated by effects on the central nervous system or cardiovascular system.This paper performs a systematic review of drugs inducing bone loss or associated with fracture risk. The chapter is organized by the Anatomical Therapeutic Chemical (ATC) classification.

Keywords: Acetaminophen; Androgen deprivation therapy; Antiepileptic drugs; Antiviral therapy; Aromatase inhibitors; Azathioprine; Bone mineral density; Budesonide; Chemotherapy; Cyclosporine; Depot medroxyprogesterone acetate; Fracture; Glucocorticoid; GnRH agonist; Heparin; Levothyroxine; Loop diuretic; Methotrexate; Neuroleptic; Non-steroid anti-inflammatory; Opioid; Oral contraceptives; Paracetamol; Protein pump inhibitor; Sedatives; Selective serotonin reuptake inhibitors; Statin; Tamoxifen; Thiazide; Thiazolidinedones; Thyroid hormones; Vitamin A; Vitamin K antagonists.

Publication types

  • Systematic Review

MeSH terms

  • Bone Density / physiology
  • Bone and Bones
  • Fractures, Bone*
  • Humans
  • Medroxyprogesterone Acetate
  • Pharmaceutical Preparations*

Substances

  • Pharmaceutical Preparations
  • Medroxyprogesterone Acetate