# Microgravity, Bone Homeostasis, and Insulin-Like Growth Factor-1
## 10 Discussion
### Igf-1  
The potential role of rIGF-1 in maintaining skeletal mass in space was recognized by [PERSON] and associates who found that the complex IGF-1 and its specific binding protein, IGFBP-3 stimulated bone turnover in an animal model flown in space [55]. [PERSON] and associates found that administration of IGF-1 to rodents flown for 10 days aboard the Space Shuttle increased their humerus periosteal bone formation by 37.6% [56].  
In light of the central role that IGF-1 plays in all phases of bone formation and preservation, it is perhaps surprising that there are no published proof of principle trials assessing the efficacy of rIGF-1 in preventing bone loss in astronauts, particularly in light of the fact that rIGF-1 is available in an easy to use nasal spray and when used judiciously is generally well tolerated [70]. IGF-1 administration would have the added advantage of bolstering muscle growth and exerting a positive effect on immunoregulation. rIGF-1 has been used to treat patients with IGF-1 deficiency, adolescents with anorexia nervosa and low bone mass, and patients with diabetes mellitus, a disorder characterized by low circulating levels of IGF-1. The side effects of rIGF-1 are dose-related and may include extremity edema, jaw pain, arthalgias, mylgias, and hypoglycemia [71; 72].  
It is recognized that IGF1/IGF1 Rt studies done under simulated conditions of microgravity do not necessarily equate with those done in the zero gravity of space. Simulated microgravity studies achieve at best a thousand-fold reduction in gravitational forces (\(\geq\)1 \(\times\) 10\({}^{-3}\) g) whereas in space the force of gravity is a million-fold less than that experienced on Earth (1 \(\times\) 10\({}^{-6}\) g). As noted in this review, osteoblasts grown in space have extended cell shapes, fragmented and condensed nuclei, shortened microtubules, defective actin microfilaments, smaller and fewer focal adhesions, and even a complete implosion of the cytoskeleton. In contrast, osteoblasts grown in simulated microgravity are characterized more by disruption in functional than in structural aberrations. Thus, although rIGF-1 proved useful in reversing the recalcitrance of blastocysts to mechanostressors in simulated microgravity, the same may not be true in space.  
Unfortunately, the adverse effects of microgravity on the skeletal system may persist for years postflight. In addition, astronauts experience a variety of other stressors, including social isolation, sleep deprivation, confinement, solar radiation, and alterations in circadian rhythms; on landing they experience the stress of the sudden readjustment to Earth's gravity field [73].  
In their approach to future space missions, scientists are faced with the need to carefully balance factors that enhance bone loss with those that have the potential to prevent or remit bone loss (see Figure 5).  
The United States, Russia, and China are planning to establish colonies on our moon sometime in the 2030s. The force of gravity on the Moon is 1.6 m/s\({}^{2}\) which is 16.7% of Earth's gravity or \(\sim\)1 \(\times\) 10\({}^{-2}\) g, well within the range of simulated microgravity studies already performed. It would seem that rIFG-1 may hold greater promise as a therapy to abrogate hypogravity-related changes in bone homeostasis in astronauts destined to colonize the moon than those aboard a spaceship.