Methodological issues in systems biology and systems physiology

Microgravity-induced bone loss: lessons learned from systematic reviews and meta-analysis

Background

Space exploration remains technologically and medically challenging. While large-scale medical studies are impossible in space travelers, meta-analysis allows combining data from small crews that participated in space missions over several decades.

Aims

To quantify the spatial and temporal aspects of microgravity-induced bone loss, we performed a meta-analysis of systematically identified studies.

Methods

We searched Medline, Embase, Web of Science, BIOSIS, NASA Technical reports, and HathiTrust, with the last update in November 2019. From 25 articles selected to minimize the overlap between reported populations, we extracted post-flight bone density values for 148 individuals, and in-flight and post-flight biochemical bone marker values for 124 individuals who participated in spaceflights ranging from 4 to 252 days in duration.

Results

The reported sample size varied from 1 to 58 people, however limited availability of individual parameters did not allow stratification even by age, sex, and mission duration. Overall, a percentage difference in bone density relative to pre-flight was positive in the skull, +2.2% [95% confidence interval: +1.1, +3.3]; neutral in the thorax/upper limbs, -0.7% [-1.3, -0.2]; and negative in the lumbar spine/pelvis, -6.2 [-6.7, -5.6], and lower limbs, -5.4% [-6.0, -4.9]. In the lower limb region, the rate of bone loss was -0.8% [-1.1, -0.5] per month. Bone resorption increased hyperbolically with a time to half-max of 11 days [9, 13] and plateaued at 113% [108, 117] above pre-flight. Bone formation remained unchanged during the first 30 days and increased thereafter at 7% [5, 10] per month. Upon landing, resorption markers decreased to pre-flight levels at an exponential rate that was faster after longer flights, while formation markers increased linearly at 84% [39, 129] per month for 3-5 months post-flight.

Conclusions

These estimates allowed us to calculate sample sizes required to detect spaceflight-related changes in bone parameters, thus informing the design of future spaceflight studies. Understanding the dynamics of changes in bone density and turnover in space travelers is imperative for a design of successful countermeasures