Therapy Insight: osteoporosis during hormone therapy for prostate cancer.
The intended therapeutic effect of gonadotropin-releasing-hormone (GnRH) agonists is hypogonadism, which is a leading cause of osteoporosis in men. Observations are consistent with this effect: GnRH agonists decrease bone mineral density and increase fracture risk in men with prostate cancer. Estrogens play a central role in homeostasis of the normal male skeleton and evidence suggests that estrogen deficiency is primarily responsible for the adverse skeletal effects of GnRH agonists. The mechanism of treatment-related bone loss involves acceleration of physiologic bone turnover. In small, randomized, controlled trials, bisphosphonates (pamidronate, zoledronic acid) and selective estrogen-receptor modulators (raloxifene, toremifene) increased bone mineral density in GnRH-agonist-treated men. Two ongoing large, randomized, placebo-controlled studies will prospectively define fracture outcomes in men with prostate cancer and assess the efficacy of novel pharmacologic interventions (AMG 162, toremifene) in GnRH-agonist-treated men.
Smith
Matthew R
MR
Harvard Medical School, Boston, MA, USA. smith.matthew@mgh.harvard.edu
D015519:Bone Density / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D008297:Male; D010024:Osteoporosis / Q000139:chemically induced* / Q000628:therapy; D011471:Prostatic Neoplasms / Q000188:drug therapy*
D007987:Gonadotropin-Releasing Hormone