Bone Health and Metabolic Response in Microgravity

Exposure to microgravity during spaceflight precipitates a rapid and site‐specific loss of bone mass, driven by an imbalance between bone resorption and formation. Reduced mechanical loading disrupts osteocyte function and induces osteoclast activation, while impairing osteoblast differentiation and mineral deposition. These cellular changes manifest as thinning of cortical bone, loss of trabecular connectivity and compromised material properties, increasing fracture risk. Concurrently, skeletal interoceptive signals influence systemic energy metabolism, with neuroendocrine pathways modulating both bone turnover and adipose storage. The interplay between altered mechanotransduction, bioenergetic shifts in bone cells and central regulatory networks underpins the dual challenge of maintaining skeletal integrity and metabolic homeostasis in weightless environments. Development of pharmacological and mechanical countermeasures is critical to safeguarding astronaut health on long‐duration missions and may offer insights into terrestrial conditions of disuse osteoporosis.

Research from Nature Portfolio

Studies of mature mice after a 30-day spaceflight revealed pronounced trabecular and cortical bone loss accompanied by osteocyte death and marrow adiposity, with impaired recovery persisting after return to Earth gravity. Tissue-level analyses showed reduced hardness and increased empty lacunae, highlighting the role of osteocyte viability in remodelling under microgravity.

Cell‐based experiments under simulated microgravity demonstrated that primary cilia on osteoblasts progressively disappear, leading to inhibited differentiation, maturation and mineralisation. Restoration of ciliary structure partially rescues osteogenic activity, suggesting targeted modulation of cytoskeletal elements as a countermeasure.

Comparative studies of mice exposed to hypergravity and microgravity conditions have shown that elevated gravitational forces enhance expression of bone formation markers and increase muscle mass, whereas true microgravity induces rapid bone loss. Gene expression analyses indicated gravity-dependent regulation of osteogenic and myogenic pathways, underscoring the sensitivity of skeletal cells to mechanical load.

Bone Health and Metabolic Response in Microgravity publication trend

The graph below shows the total number of articles in bone health and metabolic response in microgravity across all publications each year (not limited to Nature Index journals).

Technical terms

Osteoclast: Multinucleated cell responsible for bone resorption by secreting acids and proteolytic enzymes.

Osteoblast: Bone‐forming cell that synthesises osteoid matrix and regulates mineralisation.

Osteocyte: Mechanosensitive cell embedded in bone matrix, orchestrating remodelling via regulatory signalling.

Mechanosensitivity: Ability of bone cells to perceive and transduce mechanical stimuli into biochemical responses.

Skeletal interoception: Communication pathway by which bone cells signal central nervous centres to regulate systemic physiology.

References

1. One-month spaceflight compromises the bone microstructure, tissue-level mechanical properties, osteocyte survival and lacunae volume in mature mice skeletons. Scientific Reports (2017).
2. Microgravity induces inhibition of osteoblastic differentiation and mineralization through abrogating primary cilia. Scientific Reports (2017).
3. Hypergravity and microgravity exhibited reversal effects on the bone and muscle mass in mice. Scientific Reports (2019).
4. Unloading‐Induced Skeletal Interoception Alters Hypothalamic Signaling to Promote Bone Loss and Fat Metabolism. Advanced Science (2023).
5. Glucose- and glutamine-dependent bioenergetics sensitize bone mechanoresponse after unloading by modulating osteocyte calcium dynamics. Journal of Clinical Investigation (2023).
6. D-Mannose prevents bone loss under weightlessness. Journal of Translational Medicine (2023).