The effects of microgravity on bone structure and function

Abstract

Humans are spending an increasing amount of time in space, where exposure to conditions of microgravity causes 1–2% bone loss per month in astronauts. Through data collected from astronauts, as well as animal and cellular experiments conducted in space, it is evident that microgravity induces skeletal deconditioning in weight-bearing bones. This review identifies contentions in current literature describing the effect of microgravity on non-weight-bearing bones, different bone compartments, as well as the skeletal recovery process in human and animal spaceflight data. Experiments in space are not readily available, and experimental designs are often limited due to logistical and technical reasons. This review introduces a plethora of on-ground research that elucidate the intricate process of bone loss, utilising technology that simulates microgravity. Observations from these studies are largely congruent to data obtained from spaceflight experiments, while offering more insights behind the molecular mechanisms leading to microgravity-induced bone loss. These insights are discussed herein, as well as how that knowledge has contributed to studies of current therapeutic agents. This review also points out discrepancies in existing data, highlighting knowledge gaps in our current understanding. Further dissection of the exact mechanisms of microgravity-induced bone loss will enable the development of more effective preventative and therapeutic measures to protect against bone loss, both in space and possibly on ground.

Activation of RANKL-producing cells under simulated microgravity with a three-dimensional clinostat in regenerating goldfish scales

“…In addition, the mRNA expression levels of the osteoblastic markers, Col1a1 and Ocn, in the simulated microgravity treatments were significantly lower than that in the 1G control (Figure 5). These changes were closely related to the loss of bone mass in astronauts during spaceflight (Whedon et al, 1976;Rambaut and Johnston, 1979;Tilton et al, 1980;Caillot-Augusseau et al, 1998;Man et al, 2022). This indicates that the regenerating scales sensitively respond to the three-dimensional clinostat simulating microgravity conditions similar to those that astronauts are subjected to during space flights.…”

“…We found that Rankl mRNA expression levels in the regenerating scales after microgravity treatments were significantly higher than that of the mRNA expression levels in the control (1G) scales (Figure 3). OPG is a circulating decoy receptor for RANKL and downregulates osteoclastogenesis, resulting from the inhibition of the interaction between RANKL and RANK (Man et al, 2022). Thus, the RANK/RANKL/OPG system has an essential function in osteoclastogenesis regulation.…”

“…Furthermore, the urinary concentration of bone formation markers, bone alkaline phosphatase, intact osteocalcin, and procollagen type I N-terminal propeptide decreased by 27%, 38%, and 28%, respectively (Caillot-Augusseau et al, 1998). Therefore, a significant loss of bone mass is one of the most frequently observed manifestations among astronauts during spaceflight (Man et al, 2022).…”

“…Bone is an active tissue with osteoclasts (boneresorptive cells) and osteoblasts (bone-formative cells) present in the calcified bone matrix. Osteoblasts secrete bone matrix and are then transformed into osteocytes (Igarashi-Migitaka et al, 2020;Man et al, 2022). The receptor activator of nuclear factor-κB (RANK) is expressed in the osteoclasts, and the osteoblasts produce its ligand (RANKL); both play critical roles in bone metabolism (Nagy and Penninger, 2015;Ono and Nakashima, 2018).…”

Space Medicine: Inspiring a new generation of physicians

“…This decreases their capacity to maintain healthy bone and skeletal muscle tissue, and the ability to respond and adapt to the mechanical environment. Additionally, commitment of BMSCs down the adipogenic lineage reduces the ability of bone and skeletal muscle tissue to regenerate and recover following injury 23 24. These effects are similar to what is seen with ageing, and thus, microgravity research could prove useful for understanding the process of ageing 15 22 25…”