Fragility and composition of growing rat bone after one week in spaceflight

Abstract

To gain some insight into the early effects of spaceflight on skeletal metabolism, we quantified the major chemical constituents and a noncollagenous protein, osteocalcin, in the third-lumbar vertebrae and humeri from 8-wk-old rats that were part of the 7-day NASA Spacelab 3 flight experiments. The ratio of calcium to hydroxyproline in the humeral diaphysis increased from 8.5 in preflight to 9.8 in ground simulation control and only to 8.9 in flight bones. There was no demonstrable change in the fraction of nonmineralized collagen. Osteocalcin content was reduced in the humerus and vertebra. Reduced accumulation of mineral and osteocalcin with no associated decrease in collagen in flight animals suggests that both mineralization and collagen metabolism are impaired in growing animals during spaceflight within a few days after launch. Strength tests of the humeri of flight rats showed substantial deficits that appeared to be related, not only to the reduced bone mass, but also to the composition and quality of new bone formed.

Reversal of weightlessness-induced musculoskeletal losses with androgens: quantification by MRI

“…A significant reduction in serum testosterone levels was previously reported in 12-day tail-suspended rats (45,47,48) and in rats flown in the 14-day Cosmos 2014 mission (30). Tail suspension, disuse of limbs, and exposure to microgravity significantly decrease bone formation and can consequently decrease BMD in rats (14,19,29,34,49). Testosterone and anabolic steroids have positive effects on osteoblasts cells in bone formation (21).…”

“…Over the past few years, several countermeasures have been examined to prevent the loss of musculoskeletal mass during exposure to microgravity. These include pharmacological therapies, such as calcitonin and bisphosphonates, and several active and passive exercise regimens, but the outcomes have been limited.The hindlimb-elevation model in rats has been shown to simulate the bone turnover and muscle changes seen in growing rats in spaceflight (18,19,34). This model mimics the effects of microgravity on musculoskeletal systems, metabolic changes affecting bone formation, renal function, electrolyte disturbances, and muscle mass as compared with those recorded from biosatellite animals.…”

“…The hindlimb-elevation model in rats has been shown to simulate the bone turnover and muscle changes seen in growing rats in spaceflight (18,19,34). This model mimics the effects of microgravity on musculoskeletal systems, metabolic changes affecting bone formation, renal function, electrolyte disturbances, and muscle mass as compared with those recorded from biosatellite animals.…”

“…A similar reduction in musculoskeletal mass has been reported due to the immobilization of extremities seen in external bandaging, casting, or neural resectioning (13,25,27,(39)(40)(41)(42)(43). Both mineralization and collagen metabolism seem to be impaired in animals during the first few days of spaceflight (34). Urine analysis in Skylab astronauts has shown a significant loss of minerals, including calcium (10,37).…”

Perspective: skeletal complications of space flight

“…Diminished osteoblast function is a critical factor in the bone loss that develops in weightlessness. Biochemical studies of astronauts in space (diminished serum osteocalcin levels) and studies of animals both before and after space flight or simulated weightless states provide evidence for diminished osteoblast function [3]. Studies have shown that there is a decrease in osteoblast number and activity after space flight [4].…”