Approximately one third of patients with prostate cancer receive androgen deprivation therapy (ADT). This treatment is associated with higher incidence of fractures and increased mortality of fractures. However, only a minority of patients receiving ADT has their bone mineral density (BMD) documented before or after initiation of ADT. Therefore, the aim of this study was to determine whether the implementation of a screening and treatment protocol reduced the rate of osteoporotic fractures in men with prostate cancer receiving ADT.
This study included 1482 patients with prostate cancer receiving leuprolide identified in the electronic medical system of Kaiser Permanente Southern California. Of them, 1071 were included in the Healthy Bone Program (HBP) comprising BMD measurement by dual energy X-ray absorptiometry and treatment. The indications of anti-osteoporotic treatment were established using T-score corresponding to the number of standard deviations below the mean in young healthy adult men. Men with T-score ≥-2.5 were advised on smoking cessation, regular exercise, adequate calcium intake (1200 mg/d) and adequate vitamin D intake (400-800 IU/d). Men with T-score <-2.5 were also treated with pharmacological intervention (mainly bisphosphonates). The remaining 411 men received standard care. Strict exclusion criteria were used to reduce the selection bias.
The men who were included in the HBP had much lower incidence of hip fracture (5 vs 18 fractures per 1000 person-years). After adjustment for confounders, patients who were not enrolled in the HBP had a fourfold higher risk of hip fracture compared with the HBP patients (hazard risk = 4.19, 95% confidence interval 1.92 – 9.13, p<0.001).
In this study men with prostate cancer receiving ADT and enrolled in an active screening and treatment protocol experienced 72% lower rate of hip fracture compared with the nonscreened group. This difference may seem astonishingly high; however, two facts need to be remembered. Some older men have low BMD and high risk of fracture. ADT accelerates bone turnover leading to a rapid bone loss associated with a deterioration of bone microarchitecture and higher bone fragility. This rapid bone loss may be particularly dangerous in men with low BMD at baseline. ADT-induced hypogonadism may also result in rapid loss of muscle mass and strength leading to a higher risk of falling. Thus, the detection and treatment of men with low BMD may decrease markedly the risk of fracture. Moreover, the implementation if lifestyle changes may have a beneficial effect on bone and muscle.
Some limitations of the study have to be recognized: retrospective identification of patients, observational design, potential imbalance in risk factors and medical care between two groups of men. However, despite these limitations, the paper and accompanying comment are important because they raise two major points. Firstly, ADT increases bone fragility. Thus, critical judgment of indications for ADT is necessary before its initiation in order to avoid the severe adverse effects. Secondly, the implementation of an osteoporosis management program in patients with prostate cancer receiving ADT may have a beneficial effect.
Reference: Zhumkhawala AA, Gleason JM, Cheetham TC, Niu F, Loo RK, Dell RM, Jacobsen SJ, Chien GW. Osteoporosis management program decreases incidence of hip fracture in patients with prostate cancer receiving androgen deprivation therapy Urology. 2013 May; 81(5):1010-7.