Bone resorption and bone metastasis risk.

Breast cancer tumors have a tendency to metastasize to the bone. After development of a bone metastasis, the median survival time is 40 months. Currently, little is known about the modifiable risk factors for developing bone metastases in women diagnosed with breast cancer. One possible modifiable risk factor is increased bone resorption. Increased bone resorption is caused by an imbalance between osteoblasts and osteoclasts favoring osteoclast-driven bone resorption. Osteoclast activity results in the release of growth factors from the bony matrix that are requirement for successful breast cancer tumor cell proliferation within the bone. Mice studies have shown that mice that have been genetically engineered to have higher bone mineral density, and thus lower bone resorption, have a decreased incidence of bone metastases. Alternatively, mice genetically engineered to have lower bone mineral density or increased bone resorption have a higher incidence of bone metastases. In human studies, antiosteoporotic drugs have been shown to decrease osteoclast activity and prevent bone metastases. These studies suggest that increased osteoclast activity, which results in low bone mineral density, may be a modifiable risk factor for developing bone metastases in women with breast cancer. Women undergoing chemotherapy for breast cancer develop low bone mineral density in response to the direct effects of chemotherapeutic drugs on bone cells-including osteoclasts, osteoblasts, and osteocytes-and through the decrease in circulating estrogen as a result of chemotherapy-induced ovarian dysfunction. Therefore, it is important for future studies to determine the risk of developing bone metastases associated with increasing bone resorption as measured by low or decreasing bone mineral density in women diagnosed with breast cancer, as well as to determine the best intervention(s) to promote a balance between osteoclasts and osteoblasts to favor osteoblast activity during chemotherapy treatment.

Effect of resistance exercise on bone mineral density in premenopausal women.

OBJECTIVE: To assess the effect of 9 months of strength training on total body and regional bone mineral density (BMD, g/cm(2)) in 58 premenopausal women aged 30-50 years. METHODS: Participants were randomized to either twice weekly supervised strength training for 15 weeks followed by 24 weeks of unsupervised training (treatment group) or control group. Height, weight, maximal muscular strength, nutrient intake and physical activity were assessed. Total body dual energy X-ray absorptiometry (DXA, Lunar Prodigy) scans were taken and analyzed for body composition (lean and fat mass), and BMD for total body and its sub-regions (spine, hip, arms and legs). All measurements were performed at baseline, 15 and 39 weeks. Analysis of covariance was used to assess group differences in BMD change adjusted for baseline BMD, weight, energy and calcium intake. RESULTS: At baseline, the two groups had similar BMD and body size characteristics ( P<0.05 for all), except that the treatment group had lower body weight (-7.1 kg), and higher energy (+259 kJ/d) and calcium (+232 mg/d) intake at baseline. Adjusted % change in BMD over 15 weeks (0.5% vs. 0.4%) or 39 weeks (0.9% vs. 1.2%) did not differ significantly between the exercise and control groups, respectively. The exercise group increased BMD at the spine and legs (1-2.2%), while there was no change in the controls, but differences between groups were not significant. CONCLUSION: Strength training over 9 months did not lead to significantly greater change in total body or regional BMD in premenopausal women.