Introduction

The principle that bone adapts to mechanical loads is well-established, but most research focuses on the extremes: normal Earth gravity (1g) and complete unloading (microgravity). This leaves a critical gap in understanding how the musculoskeletal system responds to partial gravity, such as that on the Moon (~16% of Earth’s gravity) or Mars (~38%). This study aimed to define the relationship between varying levels of reduced mechanical loading and the corresponding changes in bone and muscle, providing a crucial dataset for predicting astronaut health on future long-duration missions beyond low-Earth orbit.

Research Objective

The primary goal was to characterize musculoskeletal adaptation across a continuum of loading between normal weight-bearing and complete disuse. The specific objectives were to:

  • Employ a Partial Weight Suspension (PWS) system to expose mice to a range of controlled, reduced loading levels for 21 days.
  • Test the hypothesis that there is a linear, proportional relationship between the percentage of weight-bearing and the degree of bone and muscle loss.
  • Compare the effects of partial unloading to traditional hindlimb unloading (HLU) and fully weight-bearing control groups to better understand different disuse models.

Key Findings

  • Musculoskeletal loss was directly proportional to the degree of unloading. A strong linear relationship was found between the level of weight-bearing and key outcomes, including calf muscle mass, total body and hindlimb Bone Mineral Density (BMD), trabecular bone volume, and cortical bone area.
  • Even minor load reduction caused significant deterioration. Mice bearing 70% of their normal body weight still experienced significant bone loss and muscle atrophy compared to fully loaded controls.
  • Hindlimb BMD decreased by approximately 1.2% for every 10% decrease in weight-bearing across the PWS groups, quantifying the dose-response relationship.
  • An unexpected discrepancy was observed between unloading models. Mice bearing 20% of their body weight (PWB20) did not have better bone outcomes than completely hindlimb unloaded (HLU) mice, despite the PWB20 group showing significantly less muscle atrophy. This suggests HLU is not equivalent to 0% weight-bearing and that other systemic factors, like fluid shifts, may play a protective role for bone in that specific model.
  • The PWS system was found to be less stressful for the animals than the traditional HLU tail-suspension model, as measured by fecal corticosterone metabolites.

Methodology

  • Organisms: Skeletally mature female C57Bl/6 mice.
  • Experimental Conditions: For 21 days, mice were placed in a Partial Weight Suspension (PWS) harness system that offloaded a specific amount of body weight while allowing normal quadrupedal movement. Groups were subjected to loading at 20%, 40%, 70%, or 100% of their body weight. These were compared against a traditional hindlimb unloading (HLU) group and a normally housed control group.
  • Key Techniques: Musculoskeletal changes were evaluated using Dual-energy X-ray absorptiometry (DXA) for bone density, micro-computed tomography (μCT) for detailed 3D bone architecture, dissection for muscle mass, and three-point bending tests for femoral bone strength.

Importance for Space Missions

This research provides the first granular data on how the musculoskeletal system adapts to the partial gravity environments of the Moon and Mars. The key takeaway is that partial gravity alone is not sufficient to prevent significant bone and muscle deconditioning. The proportional nature of this loss means that astronauts on future lunar or Martian outposts will face predictable, mission-relevant declines in musculoskeletal health. These findings are critical for designing and validating targeted countermeasures, such as specific exercise regimens, that are tailored to the unique loading conditions of these extraterrestrial environments.

Knowledge Gaps & Future Research

While this study establishes a foundational dose-response curve, several questions remain:

  • Why did HLU mice maintain bone mass better than PWB20 mice, despite greater muscle loss? Future work must disentangle the effects of local mechanical strain, systemic factors like cephalad fluid shifts, and stress hormones.
  • What is the precise mechanical strain threshold that triggers bone resorption? This study suggests the “lazy zone” where bone mass is stable is much narrower than previously theorized.
  • What are the long-term effects of partial unloading beyond the 21-day period studied here?
  • Future studies should directly measure bone strain in these models to better correlate mechanical signals with biological responses.

Results

This study successfully demonstrates that musculoskeletal deterioration is directly proportional to the level of reduced mechanical loading. By establishing a tunable ground-based model that mimics partial gravity, these findings provide an essential framework for predicting astronaut health risks on missions to the Moon and Mars. The results underscore the critical need for developing specific and robust countermeasures to ensure crew health and mission success in environments with less than 1g.

Data Visualization