Lifestyle factors and duration of androgen deprivation affect bone mineral density of patients with prostate cancer during first year of therapy.

OBJECTIVES: Androgen deprivation therapy (ADT) is associated with loss of bone mineral density (BMD) and increased fracture risk. We sought to examine the impact of ADT and lifestyle variables on BMD in 120 patients with prostate cancer without bone metastases entering a randomized clinical trial. METHODS: A total of 120 patients with prostate cancer and without bone metastases who had been treated with ADT for less than 12 months were enrolled in a clinical trial of zoledronic acid versus placebo. BMD measurements of the femoral neck, total hip, and lumbar spine were obtained before starting the study treatment by dual energy x-ray absorptiometry. The subjects answered a questionnaire regarding possible osteoporosis risk factors, including dairy product use, caffeinated beverage use, smoking history, alcohol intake, calcium/vitamin D supplementation, thyroid medication, and exercise. RESULTS: The median duration of ADT was 3 months (range 0 to 12). Osteopenia or osteoporosis (T score of less than -1) was detected in two thirds of the subjects at one or more measured sites. The mean baseline BMD Z scores were femoral neck -0.091 +/- 0.959, total hip 0.122 +/- 1.005, and lumbar spine 0.657 +/- 1.789. On multiple linear regression analysis, the duration of ADT was negatively associated with the Z score at all three sites and the body mass index, calcium/vitamin D supplementation, and alcohol use were positively associated with the Z score. CONCLUSIONS: BMD loss is a function of the duration of ADT during the first year of therapy. The body mass index, calcium/vitamin D supplementation, and alcohol use were associated with greater BMD, even after controlling for ADT exposure.

Open-label trial evaluating the safety and efficacy of zoledronic acid in preventing bone loss in patients with hormone-sensitive prostate cancer and bone metastases.

OBJECTIVES: To evaluate the efficacy and safety of zoledronic acid in preventing bone loss in patients with hormone-sensitive prostate cancer and bone metastases who were receiving androgen deprivation therapy. METHODS: Patients received zoledronic acid 4 mg as a 15-minute infusion every 3 weeks for 1 year. Bone mineral density of the lumbar spine (L2 to L4) and total hip was measured by dual-energy x-ray absorptiometry at baseline and 12 months. Biochemical markers of bone turnover (N-telopeptide and bone alkaline phosphatase) and serum creatinine levels were evaluated at baseline and during the study. Skeletal-related events were assessed at each study visit. RESULTS: Of the 221 enrolled patients, 202 and 221 patients were included in the efficacy and safety analyses, respectively. The mean increase in bone mineral density of the lumbar spine and total hip was 7.7% (P <0.001) and 3.6% (P <0.001), respectively. Decreases in N-telopeptide and bone alkaline phosphatase levels were significant and sustained. The median time to the first skeletal-related event was not reached; 11.9% of patients had a skeletal-related event. Arthralgia (20.4%), nausea (14%), fatigue (14%), and back pain (12.2%) were the most common adverse events. Adverse events due to renal function deterioration were infrequent. The mean maximal change in serum creatinine level from baseline was 0.3 mg/dL. CONCLUSIONS: Zoledronic acid administration for 1 year to patients with hormone-sensitive prostate cancer and bone metastases who were receiving androgen deprivation therapy was safe and prevented bone loss, as demonstrated by significant increases in bone mineral density and sustained suppression of biochemical markers of bone turnover.