Bone is living tissue that strengthens with exercise and deteriorates with long-term inactivity and aging. Excessive bone loss and thinning, a condition known as osteoporosis, increases the risk of bone breakage and is associated with poor health outcomes, especially in the elderly. Development of new therapies targeting pathways that promote bone formation and block bone resorption are therefore critical.

Establishing models of bone disease lays the foundation for studying bone dynamics and serves as a conduit for testing of candidate bone-modifying drugs. On Earth, there are many challenges in generating appropriate and reproducible rodent models of bone disease. In normal, aging mice, signs of osteoporosis do not begin until after 12-15 months of age, which introduces experimental challenges such as variability and costs in maintenance of aged mouse colonies. Furthermore, weight-bearing exercise and activity contribute to healthy bone mass, which can confound results of pharmacological interventions aimed at promoting bone growth. Other models of osteoporosis include postmenopausal and immobilization osteoporosis. However, these models have their own set of challenges. For example, it takes between 3-4 months after removal of the ovaries to observe the earliest changes in cortical bone width and marrow cavity area of the femoral and tibial shaft and almost nine months for observable changes in biomechanical strength. Immobilization through surgical (e.g. spinal cord resection) or conservative (e.g. hindlimb suspension) methods take 14-30 days following immobilization to display any significant bone loss, and in addition, introduce other caveats such as loss of neural input to lower limb tissues and chronic stress.

Spaceflight offers a clear advantage in generating a bone disease model. Exposure to the microgravity environment eliminates the confounding effects of weight on bone homeostasis and promotion of growth. Moreover, microgravity creates an accelerated model of osteoporosis owing to a 10- to 20-fold increase in the rate of bone loss that begins within the first few days of arrival on the space station. Astronauts lose about 11% of their hip bone mass following a four- to six-month mission despite rigorous daily exercise. In mice, exposure to 12 days of microgravity is sufficient for observable changes in bone parameters including a 7% decrease in bone volume, an 11% decrease in cortical thickness and an 11% decrease in maximal force of the femur. Other models for studying bone biology in space include genetically modified fluorescent medaka (Japanese rice fish) and cell-culture.

For over a decade, pharmaceutical companies have tested bone modifying drugs in space-flown mouse models. Amgen developed two bone modifying drugs: 1) Prolia (denosumab), a ligand inhibitor of osteoprotegerin that blocks bone resorption and 2) Evenity (romosozumab), a humanized monoclonal antibody targeting the glycoprotein sclerotin (SOST) which promotes bone formation and reduces bone resorption. Treatment of mice in microgravity with either drug led to increased bone mineral density, bone strength, and improved structure compared to untreated controls. The FDA recently approved Evenity for the treatment of osteoporosis in postmenopausal women at high risk for osteoporotic fracture. These pharmacological studies demonstrate the added benefits of using the space environment for preclinical testing of osteoporotic drugs. Additional drugs are in the pipeline (NELL-1, bisphosphonates, and testosterone) with varied mechanistic targets, which will contribute to expanding pharmacological interventions for osteoporosis and bone disease.

The space station is equipped to address a broad range of bone-related research questions. Axiom Space is developing a state-of-the art rodent habitat to be used as a space vivarium; it will support up to 300 mice for modeling bone diseases in space. Additionally, facilities are available for examining bone density in rodents using Dual-Energy X-ray Absorptiometry (DEXA), which is the gold standard for assessing bone loss in human patients terrestrially.