Can Hypoxic Conditioning Improve Bone Metabolism? A Systematic Review

Abstract

Among other functions, hypoxia-inducible factor plays a critical role in bone–vascular coupling and bone formation. Studies have suggested that hypoxic conditioning could be a potential nonpharmacological strategy for treating skeletal diseases. However, there is no clear consensus regarding the bone metabolism response to hypoxia. Therefore, this review aims to examine the impact of different modes of hypoxia conditioning on bone metabolism. 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 bone remodelling parameters of healthy organisms. 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; ten studies examined the effect of sustained, intermittent or cyclic hypoxia on bone health and hormonal responses in humans. 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.

Intermittent hypoxia inhibits mandibular cartilage growth with reduced TGF-β and SOX9 expressions in neonatal rats

“…The IH treatment significantly upregulated BMD and BMC/TV in the cancellous bone region of the mandibular condyle. The bony microstructural changes occurring in adult patients with obstructive sleep apnea (OSA) are controversial 30 . Positive BMD responses were reported for the alveolar bone of adolescent rats 10 and the lumbar vertebrae of adult rats 31 exposed to IH.…”

“Take My Bone Away?” Hypoxia and bone: A narrative review

“…Hitherto, this review has mostly examined the molecular response of bone cells to hypoxia. However, it is also pertinent to inspect the responses from the available in vivo studies (for a more comprehensive overview, please see the work of Camacho‐Cardenosa, Camacho‐Cardenosa, Timón, et al (2019). Like the other experimental approaches considered in this review, it has been suggested that different types of in vivo hypoxic exposure may elicit different responses.…”

Effects of normobaric cyclic hypoxia exposure on mesenchymal stem-cell differentiation–pilot study on bone parameters in elderly

“…That was positively correlated to increasing exposure time to hypoxia, during the differentiation into osteoblasts or adipocytes, respectively, in vitro . It has been reported that bone formation decreased in sustained hypoxia[ 33 ]. Our data indicate that this may be due, in part, to the effect on MSC differentiation.…”