Prevention and treatment of side-effects of systemic treatment: bone loss.

Cancer treatment-induced bone loss (CTIBL) is generally more rapid and severe than bone loss associated with menopause in women or ageing in men and women. In premenopausal women with breast cancer, CTIBL is mainly caused by chemotherapy with resultant ovarian failure, by GnRH agonists or by tamoxifen. In postmenopausal women, steroidal and non-steroidal aromatase inhibitors (AIs) increase bone turnover, decrease bone mass and increase fracture rate (hazard ratio increased to 1.38-1.55 compared with tamoxifen). Zoledronic acid can prevent bone loss in premenopausal women receiving adjuvant therapy with goserelin in combination with either anastrozole or tamoxifen and in postmenopausal women receiving AIs. Denosumab has been shown in a placebo-controlled study to significantly increase bone mineral density in postmenopausal women under AIs. More limited studies indicate that oral bisphosphonates used at licensed doses for the treatment of postmenopausal osteoporosis can also prevent AI-induced bone loss. In prostate cancer, bone loss that occurs with androgen deprivation therapy (ADT) also leads to an increased fracture rate. The bisphosphonates pamidronate and alendronate can prevent bone loss whereas zoledronic acid can increase bone mass under ADT. As for breast cancer, delay in bisphosphonate therapy is detrimental to bone health. The protective effects of denosumab on bone loss and incidental vertebral fractures have been demonstrated in a 3-year placebo-controlled trial.