Androgen-Deprivation Therapy Has Impact on Bone Density and Physical Functioning at Three Years

FigureResearchers have previously shown that androgen-deprivation therapy (ADT) for prostate cancer is associated with worse physical functioning and aggregate physical quality of life 12 months after initiating treatment. Now, as reported at the Genitourinary Cancers Symposium (Abstracts193 and 16), the researchers, led by Shabbir M.H. Alibhai, MD, MSc, from Princess Margaret Hospital and the University of Toronto, found that those declines continue through three years. By contrast, the loss of bone mineral density associated with the first year of ADT was found to slow substantially in the second and third years of therapy. To assess physical functioning, the researchers enrolled 87 prostate cancer patients taking ADT, 86 not taking ADT, and 86 healthy controls. At baseline, all three groups were similar in age and physical function, as assessed with the six-minute walk test (6MWT), grip strength, and the Timed Up and Go (TUG) test; aggregate physical and mental functioning were measured using the Medical Outcomes Study SF-36. The 6MWT distance improved between baseline and three months in the two groups of men not on ADT but remained stable in men taking ADT. Between three and 36 months the 6MWT remained relatively constant for all three groups. Grip strength remained relatively constant throughout the three-year period for the two control groups. By contrast, grip strength declined rapidly in the first three months of therapy for patients on ADT, and then continued to decline more slowly during the rest of the study period. The TUG test scores worsened slowly over the three-year period for patients on ADT, but were relatively stable or improved slightly for individuals in the control groups. The physical functioning SF-36 scores declined during the first 12 months for patients on ADT compared with controls, but then appeared to stabilize. The mental-functioning SF-36 score remained relatively constant for all groups throughout the study period, although the vitality score declined significantly for patients on ADT compared with controls, particularly in the first year of treatment. Alibhai explained that one can look at the two- and three-year data in one of two ways: "The good-news story is that they don't get any worse. The declines are upfront in the first six to 12 months, and then they are generally stable for the next two or two and a half years. "The bad-news story is that they are not getting better. They have the decline and then they do not seem to be able to recover based on objective measures or on self-report. Three years later they are still at a lower level than when they began therapy." He added that although some studies do suggest that early interventions with exercise routines, including resistance exercise, may help minimize the impact of ADT, the problem is how to get that information out to patients and get them to stay on an exercise regimen. In the prospective bone density study, 80 men with prostate cancer treated with ADT and 80 men with prostate cancer who did not receive ADT were followed. The mean age was 69.4 years, and about 50% of participants had osteopenia at baseline and about 5% had osteoporosis. During the first year of ADT, bone density loss was significantly greater in the lumbar spine of patients on ADT than those not on ADT. There were non-significant trends of increased loss in femoral neck and hip sites in patients on ADT compared with those not on ADT. During the subsequent 24 months (years 2 and 3), patients on ADT showed very little loss of bone density in their lumbar spine. Moreover, there were no significant differences in bone density changes at any of the three sites between the two patients groups during the later study years. In a multivariate analysis, the team found that men who were taking vitamin D in the first year had significantly better bone density in the lumbar spine than other men."That is good news, because it suggests that you can reduce the losses with a simple intervention that is cheap and minimally toxic," he said. Losses in bone mineral density with ADT use were greatest at the lumbar spine and in the first year compared with years 2 and 3 and independent of age. Vitamin D appeared to be protective particularly in the first year of ADT use—"good news, because it suggests that you can reduce the losses with a simple intervention that is cheap and minimally toxic."

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