Published peer-reviewed spaceflight studies of laboratory animals are compiled in Table 2. Animal studies have several theoretical advantages over human studies for investigating the effects of spaceflight on bone and mineral metabolism: the experimental conditions can be more carefully controlled, the subject population is more uniform, and more invasive techniques can be used. However, the enormous potential for meaningful animal investigation has not been exploited. Only small numbers of immature animals have been flown at one time, and no longitudinal studies have been performed. Crew interaction with the animals during spaceflight has been uncommon. Thus most studies have been observational. Animal experiments have been of relatively short duration (4-18 days) compared with human flights aboard Skylab (up to 84 days) and Mir (>1 yr).
With the exception of one spaceflight study in monkeys (62) and another investigating embryogenesis in chickens (42), the rat has been the animal model of choice for bone research. The rat is an established model for many aspects of human bone metabolism, but it has some limitations. The lack of a well-developed Haversion system renders most small mammals, including the rat, unsuitable for investigating the effects of spaceflight on cortical bone remodeling. All spaceflight studies have been performed in growing rats because either the investigator 1) was primarily interested in the effects of spaceflight on bone growth, or 2) was forced to use young rats because weight restrictions would result in inadequate statistical power if a smaller number of heavier, older rats were flown. The growing rat is an established model for studying the skeleton of growing humans but is a problematic model for the adult human. The principal processes that determine cortical and cancellous bone mass and architecture during growth (periosteal bone formation and endochondral ossification) differ from processes in adults (endocortical and cancellous remodeling).
The periosteal bone formation rate in bones in growing rats is often reduced during spaceflight, thereby resulting in a "relative" osteopenia (2, 9, 16, 34, 50, 58). The decrease has been reported in ovariectomized (OVX) and male rats. The term "relative" indicates that the deficit in bone mass was due to a failure to add as much bone and distinguishes the changes from those observed in adult humans in whom the osteopenia results from a net bone loss. Bone formation may be inhibited after as few as 4 days of spaceflight and is associated with decreased mRNA levels for bone matrix proteins (2, 5, 18, 53). The molecular mechanism is unknown, but there is evidence for changes in selected cytokines (e.g., transforming growth factor-
and insulin-like growth factor I) that have been implicated in the regulation of bone formation (5, 53, 64). Structural changes in the growth plate are consistent with disturbed longitudinal bone growth (33), but no changes in the rate of endochondral bone growth rate during spaceflight have been measured (44).
Impaired cortical bone mechanical properties have been observed after spaceflight (35, 41, 48). In part, the deficit appears to be due to altered bone geometry associated with an observed reduction in the periosteal bone formation rate (41, 48). However, evidence for altered bone matrix ultrastructure and mineralization has been reported, suggesting that spaceflight may result in a degradation of bone material properties as well (31, 32, 35, 37, 45). The altered geometry and abnormal material properties are associated with site- and gene-specific changes in expression of bone matrix proteins (5, 18).
The effects of spaceflight on material and mechanical properties of cancellous bone have not been investigated. However, spaceflight has been reported to inhibit bone formation and induce bone loss at cancellous sites in monkeys (62) and rats (16, 26, 27, 46, 51, 52, 59). One study suggests that spaceflight may inhibit normal bone repair following fracture (15).
There is minimal evidence that spaceflight increases bone resorption at either cortical or cancellous bone sites in growing male rats (7). In contrast to males, the osteoclast number increased in pregnant growing rats (51). Spaceflight accelerated OVX-induced cancellous bone loss in the proximal tibial metaphysis and induced bone loss in the epiphysis (9, 54). The bone loss in the metaphysis of OVX rats was due to excess bone resorption; there was no reduction in bone formation (9). These results suggest that there may be sex differences related to gonadal hormone levels that influence the skeletal response to spaceflight.
It is important to emphasize that skeletal abnormalities have not been observed in all spaceflight studies. There is evidence that nonweight-bearing bones are less affected by spaceflight than weight-bearing bones (28, 31, 37, 38) and that the skeletal effects of spaceflight are progressive (2, 46). However, changes are not always detected in weight-bearing bones after spaceflight (3, 14, 17, 27, 36, 44, 47, 48, 53, 57, 59, 61). These negative studies suggest that the effects of spaceflight may be influenced by caging conditions, age, or other unknown factors.
Answers to all your Biology Questions
