Abstract
Exposure to hypobaric hypoxia at high altitude puts mountaineers at risk of acute mountain sickness. The carbonic anhydrase inhibitor acetazolamide is used to accelerate acclimatization, when it is not feasible to make a controlled and slow ascend. Studies in rodents have suggested that exposure to hypobaric hypoxia deteriorates bone integrity and reduces bone strength. The study investigated the effect of treatment with acetazolamide and the bisphosphonate, zoledronate, on the skeletal effects of exposure to hypobaric hypoxia. Eighty 16-week-old female RjOrl : SWISS mice were divided into five groups: 1. Baseline; 2. Normobaric; 3. Hypobaric hypoxia; 4. Hypobaric hypoxia + acetazolamide, and 5. Hypobaric hypoxia + zoledronate. Acetazolamide was administered in the drinking water (62 mg/kg/day) for four weeks, and zoledronate (100 μg/kg) was administered as a single subcutaneous injection at study start. Exposure to hypobaric hypoxia significantly increased lung wet weight and decreased femoral cortical thickness. Trabecular bone was spared from the detrimental effects of hypobaric hypoxia, although a trend towards reduced bone volume fraction was found at the L4 vertebral body. Treatment with acetazolamide did not have any negative skeletal effects, but could not mitigate the altitude-induced bone loss. Zoledronate was able to prevent the altitude-induced reduction in cortical thickness. In conclusion, simulated high altitude affected primarily cortical bone, whereas trabecular bone was spared. Only treatment with zoledronate prevented the altitude-induced cortical bone loss. The study provides preclinical support for future studies of zoledronate as a potential pharmacological countermeasure for altitude-related bone loss.
Highlights
Prolonged exposure to high altitude environments, i.e. above 2,500 to 3,000 meters, can result in acute mountain sickness (AMS)
Hypobaric hypoxia significantly decreased daily chow consumption (–18%, p < 0.001) resulting in a substantial decrease in body weight (–10%, p = 0.003) after four weeks compared with mice housed at normobaric ambient pressure (Figure 1B and Table 1)
We have recently demonstrated that exposure to simulated high altitude impairs bone integrity
Summary
Prolonged exposure to high altitude environments, i.e. above 2,500 to 3,000 meters, can result in acute mountain sickness (AMS). The initial symptoms of AMS are headache, loss of appetite, fatigue, peripheral edema, sleep apnea, and general malaise [1]. The initial symptoms of AMS are relatively mild, it may progress to lifethreatening high altitude pulmonary edema (HAPE) [2] or high altitude cerebral edema (HACE) [3]. Studies in rodents have suggested that exposure to high-altitude environments may affect the Treatment of High Altitude-Induced Bone Loss musculoskeletal system by reducing bone strength and inducing muscle atrophy [4, 5]. The study reported decreased BMD at the distal radius immediately after the expedition was completed, which was not fully recovered 12 months after returning to a habitual ambient pressure [6]
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