Adjuvant pharmacological strategies for the musculoskeletal system during long-term space missions

Despite 2 h of daily exercise training, muscle wasting and bone loss are still present after 6-month missions to the international space station. Some crew members lose bone much faster than others. In preparation for missions to the Moon and Mars, space agencies are therefore reviewing their countermeasure portfolios. Here, we discuss the potential of current pharmacological strategies. Bone loss in space is fuelled by bone resorption. Alendronate, an oral bisphosphonate, reduced bone losses in experimental bed rest and space. However, gastrointestinal side effects precluded its further utilization in space. Zoledronate (a potent bisphosphonate), denosumab (RANKL antagonist) and romosozumab (sclerostin antagonist) are all administered via injection. They effectively suppress bone resorption and are routinely prescribed against osteoporosis. Their serious adverse effects, namely, osteonecrosis of the jaw and atypical femur fractures occur very rarely when the usage is limited to 1 or 2 years. Hence, utilization of one of these compounds may outweigh the bone risks of space travelling, in particular in those with high bone resorption rates. Muscle wasting in space is likely due to hampered muscle protein synthesis. Even though this might theoretically be countered by the synthesis-boosting effects of anabolic steroids, the practical grounds for such recommendation are currently weak. Moreover, they reveal their full potential only when combined with an anabolic exercise stimulus, for example, via strength training. It therefore seems that a combination of exercise and pharmacological countermeasures should be considered for musculoskeletal health on the way to the Moon and Mars and back.