BACKGROUND: Age-related physiological changes, chronic diseases and multimorbidity are commonly known as geriatric syndromes, which result in particular health states in older age. Physical activity is widely considered as a powerful tool for both their treatment and prevention. As inactivity is more common in older adults, the benefits of physical exercise in this population are strongest and also have a protective effect. However, very few older adults are meeting the recommended levels of physical activity due to a large number of barriers. In the research of new physical activity therapies, the therapeutic use of hypoxia has been recently suggested for the elderly population or chronic disease patients. Combined with exercise, hypoxic sessions could have lower stress on the locomotive system for a similar physiological strain as compared with normoxia. Currently, interest in hypoxic conditioning has increased and experts around the globe have contributed in promoting its clinical application in disease prevention and treatment. However, the influence of hypoxia on bone remodelling is unclear, and different physiological mechanisms could mediate its effects. On the other hand, fewer studies to date have applied this innovative therapeutic strategy in older adults. AIMS: The general objectives were: (1) to review the current literature of bone metabolism and hypoxic stimulus; (2) to study the effects of passive hypoxic conditioning on the bone mineral density of healthy elderly people; and (3) to study the effects of active hypoxic conditioning on the health parameters of healthy elderly people.METHODS: A systematic review was carried out following Preferred Reporting Item for Systematic Reviews and Meta-Analyses. The PubMed and Web of Science databases were searched for experimental studies written in English that investigated the effects of modification of ambient oxygen on the bone remodelling parameters of healthy organisms. To know the effects of passive hypoxia on the bone mineral density of elderly people, 24 healthy elderly participants were randomly assigned to a hypoxic group (HYP) or control group. During 36 sessions, the HYP group performed an intellectual activity while they were exposed to normobaric hypoxic conditions in a hypoxic chamber (16.1% fraction of inspired oxygen; FiO2). Whole-body and proximal femur bone mineral density (g·cm-2) were measured using dual-energy X-ray absorptiometry. To study the effects of active hypoxic conditioning on the health parameters of healthy elderly people, forty-six healthy elderly individuals were randomly assigned to a hypoxic whole-body vibration group (HWBV), normoxic whole-body vibration group (NWBV) or control group. During 36 sessions, the experimental groups received the same vibration treatment in a hypoxia chamber (HWBV: 16.1% FiO2; NWBV: 21.0% FiO2). A vibration session included 4 bouts of 30 s (12.6 Hz - 4 mm) with a 1 min rest between bouts. Whole-body and proximal femur bone mineral density and body composition were measured using dual-energy X-ray absorptiometry. Isokinetic leg muscle strength was evaluated using a Biodex System-3 isokinetic dynamometer. The Timed Up and Go Test evaluated functional mobility. RESULTS: In the systematic review, thirty-nine studies analysed the effect of sustained or cyclic hypoxia exposure on genetic and protein expression and mineralisation capacity of different cell models; three studies carried out in animal models implemented sustained or cyclic hypoxia, and ten studies examined the effects of sustained, intermittent or cyclic hypoxia on bone health and hormonal responses in humans. After hypoxic exposure, the whole body bone mineral density had a significant increase in the HYP group as compared to the control group, whose values decreased (p=0.008). In the within group analysis, the HYP group significantly increased their whole body bone mineral density (p=0.004), while the control group had a significant decreased in this parameter, with a large effect size (p=0.004; d=1.18). Regarding the effects of active hypoxia, compared to the NWBV and CON (between-group analysis) groups, the HWBV group showed an increase in whole-body bone mineral density (p=0.07), which was significant only in the within-groups analysis (p<0.05). Within the HWBV group, the prevalence of osteopenia/osteoporosis also decreased significantly (p<0.001). There were no significant differences between groups in either muscle mass or strength parameters. Neither statistically significant within group variations nor statistically significant differences between both groups were detected in the Timed Up and Go Test. The NWBV group showed statistically significant improvements in the maximal strength of knee extensors, with a small effect size (p = 0.004; d = 0.54). CONCLUSIONS: Different modes of hypoxic conditioning may have different impacts on bone metabolism both in vivo and in vitro. Additional research is necessary to establish the optimal cyclical dose of oxygen concentration and exposure time. On the other hand, passive hypoxia exposure at 16.1% FiO2 during 36 sessions is apparently enough to significantly increase whole-body bone mineral density in older adults, but not in a specific region such as the proximal femur. Combined with WBV training, hypoxic stimuli seemed to generate positive effects on the whole body and proximal femur bone mineral density of an elderly population. Although changes did not differ significantly between groups, the benefits observed only within the vibration exercise plus hypoxia may be considered promising, but they should be confirmed in future large-scale studies. However, active hypoxia does not cause any effect on the muscle mass or strength of older adults. Functional mobility also did not change following an active hypoxia protocol. Our finding suggests that the work/rest ratio and the accumulated volume could be important factors when untrained elderly people are subjected to vibration training in hypoxic conditions. High stress during the session could limit their capacity for improvement.