Simulated Galactic Cosmic Radiation Exposure Impairs Mouse Vertebral Bone Adaptations to Exercise During Recovery From Partial Weightbearing

Partial weightbearing that simulates Lunar gravity (1/6th of Earth’s gravitational force) results in a loss of bone volume. High energy radiation like that found in galactic cosmic radiation exposure also negatively affects the skeleton. Because resistance training is the most effective exercise mode to counteract disuse-induced bone loss, this experiment combined low-dose, high-energy simulated galactic cosmic radiation (GCR) exposure, followed by a period of partial weightbearing (PWB), and then a period of resistance exercise or normal cage activity during recovery. Young adult female BALB/c mice were randomly assigned to age-matched cage controls (CC) or PWB (G/6) groups. From there, animals were further divided into 0.5 Gy 36Fe radiation exposure (RAD) or sham exposure (SHAM) groups. Radiation exposure was performed at NASA’s Space Radiation Laboratory at Brookhaven National Laboratory before shipping to Texas A&M. GCR was followed by a 21-day period of PWB, equivalent to being placed in a simulated lunar gravity environment. A 21-day recovery period began on Day 22, during which PWB animals were assigned to one of two groups: recovery with normal cage activity (G/6 + Rec) or resistance training during recovery (G/6 + RecEX). The latter group was trained three times every four days with a tower climbing training regimen, climbing a 1-meter wire mesh tower at an 85° angle. This training was repeated for a total of 15 climb sessions. As the exercise period progressed, weights were taped on to the mice tails. Ex vivo micro-computed tomography (μCT) scans were performed by Matthew Allen, PhD at the Indiana University School of Medicine to quantify cancellous bone microarchitecture in the 4th lumbar vertebral body. Means for cancellous bone volume (%BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N) from Day 42 of the experiment were compared to Day 21 means by 2-way ANOVA to determine the changes occurring through the recovery period. RecEX had no significant affect on ∆BV/TV or ∆Tb.Th, but ∆BV/TV and ∆Tb.Th were significantly lower in RAD groups than in SHAM groups (p\u3c0.001). ∆Tb.N was significantly higher in exercised groups than non-exercised groups (p\u3c0.05), but no significant differences in ∆Tb.N were shown between RAD and SHAM groups. These data suggest that GCR exposure diminishes the ability of bone to respond to exercise during recovery form a period of reduced weightbearing

Positive impact of low-dose, high-energy radiation on bone in partial- and/or full-weightbearing mice

Astronauts traveling beyond low Earth orbit will be exposed to galactic cosmic radiation (GCR); understanding how high energy ionizing radiation modifies the bone response to mechanical unloading is important to assuring crew health. To investigate this, we exposed 4-mo-old female Balb/cBYJ mice to an acute space-relevant dose of 0.5 Gy 56Fe or sham (n = ~8/group); 4 days later, half of the mice were also subjected to a ground-based analog for 1/6 g (partial weightbearing) (G/6) for 21 days. Microcomputed tomography (µ-CT) of the distal femur reveals that 56Fe exposure resulted in 65-78% greater volume and improved microarchitecture of cancellous bone after 21 d compared to sham controls. Radiation also leads to significant increases in three measures of energy absorption at the mid-shaft femur and an increase in stiffness of the L4 vertebra. No significant effects of radiation on bone formation indices are detected; however, G/6 leads to reduced % mineralizing surface on the inner mid-tibial bone surface. In separate groups allowed 21 days of weightbearing recovery from G/6 and/or 56Fe exposure, radiation-exposed mice still exhibit greater bone mass and improved microarchitecture vs. sham control. However, femoral bone energy absorption values are no longer higher in the 56Fe-exposed WB mice vs. sham controls. We provide evidence for persistent positive impacts of high-LET radiation exposure preceding a period of full or partial weightbearing on bone mass and microarchitecture in the distal femur and, for full weightbearing mice only and more transiently, cortical bone energy absorption values

Twenty-One Days of Lunar Environment Alters Muscle Fiber Areas in Mouse Gastrocnemius

Download PD

Sequential High-Impact Loading and Zoledronic Acid Before Hindlimb Unloading Protects Against Decrements in Bone Microarchitecture and Strength

The purpose of our investigation was to evaluate the efficacy of prophylactic interventions consisting of impact loading (free-fall landing) and/or a bisphosphonate (zoledronic acid), to counter disuse-induced bone loss of adult male rats (6 months old) subjected to 28 days of hindlimb unloading. Furthermore, we aimed to define the effects of these treatments on mechanical strength properties and bone turnover. We hypothesized that monotherapy would mitigate adverse alterations in bone mass, microarchitecture, and strength, while the combined sequential treatment would completely prevent them. Animals were assigned to one of six groups (n=12 each): baseline control (BC, euthanized on study day 0), cage control (CC), hindlimb unloading (HU), zoledronic acid treatment plus hindlimb unloading (ZA+HU), impact loading treatment plus hindlimb unloading (IL+HU), and impact loading and zoledronic acid treatments plus hindlimb unloading (IL+ZA+HU). IL animals were dropped 25 times (five drops from 30 cm followed by 20 drops from 60 cm) three times per week for the first five weeks of the study. ZA (60 μg/kg body weight) was administered on day 36, immediately following IL and just prior to HU. HU began on day 37 and persisted for four weeks. At the distal femur metaphysis (DFM) and femoral neck (FN), HU caused declines in cancellous bone volume fraction (BV/TV, -25%) and total volumetric bone mineral density (vBMD, -14%), respectively, compared to CC. Mechanical strength and bone turnover were also impaired due to unloading. Individually, IL and ZA attenuated HU-induced changes in mass, microarchitecture, and strength, but when given sequentially, IL+ZA fully rescued them. While HU caused an uncoupling of bone remodeling, ZA treatment successfully reduced bone degradation without affecting bone formation. Treatment with IL followed by ZA resulted in enhanced DFM BV/TV (+20%) and trabecular thickness (Tb.Th, +5%). Also, FN ultimate force was highest with combination treatment. While IL and ZA alone attenuated the deleterious effects of disuse on bone quality, when the two were administered in sequence adult male rats were fully protected against HU-induced alterations in bone mass, microarchitecture, strength, and turnover