A review of the skeletal effects of exposure to high altitude and potential mechanisms for hypobaric hypoxia-induced bone loss

Abstract

Mountaineering and exposure to high altitude result in physiological adaptations to the reduced inspiratory oxygen availability. Acute mountain sickness (AMS), high altitude pulmonary edema (HAPE), and high altitude cerebral edema (HACE) are well-described harmful effects of exposure to high altitude. Common to AMS, HAPE, and HACE are distinct clinical signs and symptoms of impaired function. However, several studies have suggested that high altitude might result in a substantial bone loss, which usually does not produce any apparent symptoms. This review aims to provide a comprehensive overview of, and map current knowledge of the skeletal effects of hypobaric hypoxia and high altitude. PubMed and Embase were searched from inception to September 6, 2021, to identify studies investigating the skeletal effects of exposure to hypobaric hypoxia and high altitude. Three hundred sixty titles and abstracts were screened, and 20 full-text articles were included (16 in vivo studies and four real-world human studies). In rodents, simulated high altitude up to 2900 m did not result in any adverse skeletal effects. In contrast, studies exposing animals to very high altitude (3500-5500 m) reported substantial reductions in BMD, cortical morphology, and bone strength, as well as deteriorated trabecular microstructure. Detrimental microstructural effects were also reported in rats exposed to simulated extreme altitude (6000 m). Finally, real-world human studies in mountaineers suggested high altitude exposure reduced bone mineral density (BMD) and that the harmful skeletal effects of hypobaric hypoxia were not entirely recovered after 12 months. In conclusion, in vivo and real-world studies demonstrated high altitude exposure results in adverse skeletal effects. The underlying mechanism for hypobaric hypoxia-induced bone loss is not elucidated.

Keywords: Bone loss; High altitude; Hypobaric hypoxia; Mountaineering; Simulated high altitude.