Objectives:The early changes in bone metabolism that precede the documented decrease in bone formation witnessed in previous Cosmos flights are not understood. A primary defect in osteoblast rather than osteoclast function is suggested by bone histomorphometry measurements and kinetic studies with stable calcium isotopes in young animals. Osteocalcin, a noncollagenous bone protein synthesized by the osteoblast, has been suggested as a good biochemical marker for bone turnover or bone formation. This study was to determine if microgravity affects either the bone content or circulating levels of osteocalcin.
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Approach:
Blood was obtained from all animals at sacrifice and analyzed for Ca, P, total protein, and alkaline phosphatase. The humeri from flight and control rats were tested for breaking strength in three-point bending using an Instron materials testing machine. The load was applied to the medial surface at midshaft halfway between the outer supports, which were 17 mm apart beneath the posterior aspect of the bone. The deformation rate was 1 mm per minute; load deformation curves were analyzed for ultimate load and deformation, work to ultimate load, and initial stiffness. Third lumbar vertebrae were ground to a fine powder in a liquid nitrogen mill, and osteocalcin was extracted from 1 mg portions of bone powder. Because bone and serum osteocalcin in rats are age dependent, flight values were compared to both actual and estimated control values in order to compensate for the age difference between the two groups of rats.
Results:
Vertebral osteocalcin content was decreased in flight animals relative to controls, as were humeral breaking strength and serum osteocalcin levels, even after adjustment for age-related changes. The bone osteocalcin decrement was greater than the decrement in bone mass, indicating that osteocalcin per unit bone mass was reduced. The normal inverse relationship between serum and bone osteocalcin was disrupted in the flight rats, whose serum content was much lower. If the source of serum osteocalcin is new synthesis by the bone cells, then these decreased levels are likely to represent decreased osteoblast activity associated with reduced skeletal growth during space flight. Although a dose-dependent, steroid-induced decrease in serum osteocalcin has been reported, this does not appear to be a factor here since serum corticosterone was the same in all groups and unrelated to serum osteocalcin. While the function of osteocalcin may not yet be known, it appears to be a most sensitive indicator of the early effects of space flight on metabolism.
Arnaud SB, et al. Early Effects of Weightlessness on Growing Bone. Space Life Sciences Symposium: Three Decades of Life Science Research in Space; 1987, NASA TM-108002: 226-7.
Buckendahl PE, Cann CE, Grindeland RE, Martin RB, Mechanic G, Arnuad SB. Osteocalcin as an Indicator of Bone Metabolism During Spaceflight. Abstract 83.26. 36th Annual Fall Meeting of the American Physiological Society; 1985 Oct 13-18; Buffalo (NY) Physiologist 1985; 28(4):379.
Patterson -Buckendahl PE, et al. Effects of Simulated Weightlessness on Rat Osteocalcin and Bone Calcium. American Journel of Physiology 1989; 257:R1103-9.
Patterson -Buckendahl PE, et al. Osteocalcin as an Indicator of Bone Metabolism During Spaceflight. Abstract S-227. Proceedings of the Seventh Annual Meeting on the IUPS Commission on Gravitational Physiology; 1985 Oct 13-18; Niagara Falls(NY).
Patterson -Buckendahl PE, et al.Fragility and Composition of Growing Rat Bone After One Week in Spaceflight. American Journal of Physiology 1987; 252:R240-6.
Patterson -Buckendahl PE, Grindeland RE, Martin RB, Cann CE, Arnaud SB. Osteocalcin as an Indicator of Bone Metabolism During Spaceflight. Physiologist 1985; 28(6 Suppl):S227-S228.
Activity, enzymic, Alkaline phosphatase (AP), serum, rat, Analyzer
Content, 1,25 Dihydroxyvitamin D (1,25(OH)2D), serum, rat
Content, Calcium, serum, rat, Automated analysis
Content, Calcium, vertebra, bone, rat
Content, Collagen, vertebra, bone, rat
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Content, Osteocalcin (OC), serum, bone, rat,, Immunochemistry
Content, Osteocalcin (OC), vertebra, bone, rat,, Immunochemistry
Content, Phosphorous, vertebra, bone, rat
Content, Phosphorus (Pi), serum, bone, rat,, Biochemistry,