Background to and management of treatment-related bone loss in prostate cancer

Prostate cancer is a common disease among older men. Androgen suppression by either orchiectomy or administration of luteinising hormone-releasing hormone (LHRH) analogues is the mainstay of treatment. Since the use of prostate-specific antigen (PSA) serum testing has become widespread, however, the timing of endocrine therapy has expanded considerably to include patients with limited involvement of extraprostatic sites and patients presenting an isolated elevation of PSA after radical treatments. These patients are expected to be treated for a long time, since they have a rather low risk of disease progression and there is no recommended time limit for LHRH analogue therapy. The long-term adverse effects of androgen deprivation therapy, therefore, deserve more attention than they have received in the past. Osteoporosis represents a special concern for men with prostate cancer receiving androgen deprivation therapy. The rate of bone loss in these men seems to, markedly exceed that associated with menopause in women, and fractures occur more frequently than in the healthy elderly male population. Serial bone mineral density (BMD) evaluation could allow the detection of patients with prostate cancer who are at greater risk of osteoporosis and adverse skeletal events after androgen deprivation therapy, such as patients already osteopenic or osteoporotic at baseline and men with rapid bone loss during treatment. BMD evaluated during treatment could also be a potential surrogate parameter of antiosteoporotic therapeutic efficacy. Treatment of bone loss induced by androgen deprivation comprises general prevention measures, antiosteoporotic drugs and the use of alternative endocrine therapies. Optimising lifestyle and diet is important, although it cannot completely prevent bone loss. Patients with nonsevere bone disease may benefit from calcium and vitamin D supplements. Men who are osteoporotic before androgen deprivation or men becoming osteoporotic during treatment and/or experiencing adverse skeletal events may also require bisphosphonates. The effectiveness of these drugs in preventing fractures has been shown in a single randomised study involving patients with osteoporosis, but it has not yet been established in a prostatic cancer population without bone metastases given androgen deprivation therapy. Different forms of endocrine therapy such as low-dose estrogens, anti-androgens and intermittent androgen ablation are under investigation. They could offer the advantage of avoiding (or limiting) treatment-related bone loss. In our opinion, however, the data available so far are not robust enough to recommend these alternative endocrine therapies instead of standard androgen deprivation in routine clinical practice.