No abstract

We proposed that there are significant correlations between muscle strength and bone mineral density in premenopausal women and that these correlations are site-specific. To test this hypothesis, we examined the relationships among site-specific bone mineral density, physical activity, and muscle strength in a group of 96 healthy premenopausal Caucasian women. Bone mineral density was measured at the lumbar spine and at three sites in the proximal femur (trochanter, femoral neck, and Ward's triangle) with dual-energy x-ray absorptiometry and at the mid-radius with single-photon absorptiometry. The muscle strength of hip and spinal muscle groups was determined with a strain gauge isodynamometer, and grip strength was measured with the JAMAR dynamometer. The strength of shoulder girdle muscle groups was evaluated with the use of free weights. Physical activity was determined by surveying the subjects and by using a standardized scale. Data analysis revealed significant linear correlations of muscle strength with bone mineral density at the mid-radius (r = 0.31; P = 0.002) and at the hip (r = 0.26; P = 0.01). Grip strength was significantly correlated with bone mineral density of both the spine and the femur (r = 0.24, r = 0.34; P < 0.05 for both). Back extensor strength correlated with bone mineral density of the hip (Ward's triangle; r = 0.23; P = 0.023). However, there was no significant positive correlation between the strength of the spinal flexor or extensor muscles and the site-related bone mass (lumbar spine). Only one of the three components of the physical activity score (job) positively correlated with vertebral bone mineral density (r = 0.21; P = 0.04). Physical activity negatively correlated with age (r = 0.24; P = 0.02). We conclude that in premenopausal women, the effect of muscle strength on bone mass is more systemic than site-specific. A positive correlation between vertebral bone mass and components of physical activity demonstrates that even job-related physical activity is an important factor in maintaining adequate bone mass.

BACKGROUND.The most common site of metastases in prostate cancer is the skeleton and occurs in 70-80% of patients with prostate carcinoma. Calciotrophic peptides are important in the growth and development of normal bone matrix. METHODS. Three human prostate carcinoma cells lines, DU-145, PC-3, and LNCaP, were exposed to varying concentrations of parathyroid hormone (PTH) or calcitonin (CT). Cell proliferation and chemotaxis were assessed. RESULTS. Proliferation increased in LNCaP cells in a dose-dependent manner following treatment with PTH. Proliferation was not altered in PC-3 cells in response to PTH. Proliferation was decreased in DU-145 and PC-3 cells and increased in LNCaP cells after treatment with CT. Cell chemotaxis was increased in the presence of PTH in DU-145 and PC-3 cells compared to vehicle-treated controls. CONCLUSIONS. The combined proliferation and chemotaxis data suggest that PTH has a dual role in prostate carcinoma resulting in an increase in the number and migration of selected prostate cancer cells. With CT, chemotaxis was unchanged in the DU-145 and PC-3 cells and significantly elevated in the LNCaP cell line. The calciotrophic hormones, PTH and CT, may play an integral role in the regulation of prostate cell growth and metastases.

Osteoclasts attach to mineralized surfaces and resorb bone matrix, releasing calcium into the area surrounding the osteoclast. The production of high levels of extracellular calcium increases intracellular calcium concentrations ([Ca2+]i), and bone resorption is decreased. To study this mechanism, the dihydropyridine-sensitive L-type calcium channel antagonists PN 200-110, (-)202-791, and nifedipine were studied for their effects on bone resorption using the disaggregated osteoclast pit assay. Changes in [Ca2+]i after treatment with these compounds were determined with the fluoroprobe fura2. In osteoclast-enriched cultures, significant decreases in bone resorption were noted in the presence of PN 200-110 and (-)202-791. The decrease in bone resorption correlated with an increase in [Ca2+]i. To determine whether the effects of these compounds on osteoclasts were mediated via osteoblasts, proliferation and differentiation of rat osteoblast-like cells (ROS 17/2.8) were examined after the addition of these agents. There were no changes in osteoblast proliferation or differentiation, as determined by [3H]thymidine incorporation and specific activity of alkaline phosphatase, after treatment with these compounds at concentrations that inhibited bone resorption in the disaggregated pit assay. This lack of effect of calcium channel antagonists on osteoblast growth and differentiation at concentrations used to inhibit osteoclast function suggests that the effects of PN 200-110 and (-)202-791 on the osteoclast are not mediated via the osteoblast. In addition, conditioned medium recovered from ROS 17/2.8 cultures treated with PN 200-110 or (-)202-791 had no effect on pit formation compared to the conditioned medium from cell-free cultures. This lack of effect of calcium channel conditioned medium on bone resorption provides additional evidence that PN 200-110 and (-)202-791 are decreasing bone resorption directly by altering osteoclast function, not through osteoblast-osteoclast interactions. The addition of (-)202-791 or PN 200-110 to osteoclasts resulted in a dose-dependent rise in [Ca2+]i. These data suggest that calcium channel antagonists may bind to the calcium channel of the osteoclast and lock it in an open state, leading to increased [Ca2+]i and decreased bone resorption.

The purpose of this study was to elucidate the mechanisms by which cobalt chromium particulate wear debris contribute to the aseptic loosening of total joint prostheses. Incubation of macrophages with cobalt chromium led to release of tumor necrosis factor-alpha (TNF-alpha) and prostaglandin E2 (PGE2), but did not lead to release of interleukin-1 beta (IL-1 beta) or interleukin 6 (IL-6). Exposure of macrophages cocultured with osteoblasts to cobalt chromium also led to significant release of TNF-alpha and PGE2, but did not lead to significant IL-6 or IL-1 beta production. The release of PGE2 in the coculture system was greater than that detected when macrophages were exposed to cobalt chromium without the osteoblast contribution. Exposure of radiolabeled calvaria to media from macrophages incubated with cobalt chromium in coculture with osteoblasts led to release of 45Ca. In contrast, exposure of radiolabeled calvaria to media from isolated macrophages incubated with these particles did not result in release of 45Ca. Exposure of macrophages to cobalt chromium was toxic, as reflected by release of the intracellular enzyme lactate dehydrogenase. Macrophages play a role in the initiation of bone resorption at the interface through the phagocytosis of cobalt chromium particles and subsequent release of TNF-alpha and PGE2. The presence of osteoblasts at the interface may be required for amplification of the inflammatory response and ultimately for bone resorption.