A noninvasive analysis of urinary musculoskeletal collagen metabolism markers from rhesus monkeys subject to chronic hypergravity.

A decrease in load-bearing activity, as experienced during spaceflight or immobilization, affects the musculoskeletal system in animals and humans, resulting in the loss of bone and connective tissue. It has been suggested that hypergravity (HG) can counteract the deleterious effects of microgravity-induced musculoskeletal resorption. However, little consensus information has been collected on the noninvasive measurement of collagen degradation products associated with enhanced load-bearing stress on the skeleton. The purpose of this study is to assess the urinary collagen metabolic profiles of rhesus monkeys (Macaca mulatta) during 1) 2 wk of basal 1 G (pre-HG), 2) 2 wk of HG (2 G), and 3) two periods of post-HG recovery (1 G). Urine was collected over a 24-h period from six individual rhesus monkeys. Hydroxyproline (Hyp) and collagen cross-links (hydroxylysylpyridinoline and lysylpyridinoline) were measured by reverse-phase HPLC. Urinary calcium, measured by atomic absorption, and creatinine were also assayed. The results indicate no changes in nonreducible cross-links and Hyp during HG. Collagen cross-link biomarker levels were significantly elevated during the 2nd wk of HG. Urinary calcium content was significantly lower during HG than during the 1-G control period, suggesting calcium retention by the body. We conclude that there is an adaptation of the nonhuman primate musculoskeletal system during hyperloading and that noninvasive measurements of musculoskeletal biomarkers can be used as indicators of collagen and mineral metabolism during HG and recovery in nonhuman primates.

Circulating osteocalcin in rats is inversely responsive to changes in corticosterone.

Decreased bone formation in rats during spaceflight may be attributable to corticosteroid excess induced by environmental factors other than weightlessness that are associated with spaceflight experiments. To determine whether decreased osteocalcin, which may reflect altered bone formation rate, could be associated with corticosteroid excess, we measured serum osteocalcin in rats after injection of corticosterone or in response to various environmental stimuli. Exogenous steroid elicited a time- and dose-related decrease in serum osteocalcin, which was significant within 1 h of administration and maximally 25% below controls 1.5 h after injection of 3.3 mg corticosterone/kg body wt, the highest dose we tested. Adrenalectomy resulted in a 38% increase in osteocalcin. Exposure to environmental stressors lasting from 1.5 h to 3 wk also resulted in decreased osteocalcin levels, which showed a strong negative correlation (P less than 0.001) with serum corticosterone levels and adrenal mass after 1-3 wk of chronic cold exposure. Changes in serum osteocalcin were maximally about +/- 40% after 3 wk of chronic exposure to steroid excess or depletion. The response of osteocalcin to the well-defined adrenal hormone system implies an important role for corticosteroids in the control of serum osteocalcin.