The Effect of Chronic Long-Term Intermittent Hypobaric Hypoxia on Bone Mineral Density in Rats: Role of Nitric Oxide

Abstract

Intermittent hypoxia is the most common pattern of hypoxic exposure in humans. The effect of chronic long-term intermittent hypobaric hypoxia (CLTIHH) on bone metabolism is not investigated. We examined the effect of CLTIHH on bone metabolism and the role of nitric oxide (NO) in this process. The rats were divided into three groups in this study. The animals in groups I and II have been exposed to CLTIHH. The animals in group II were also treated with nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester. To obtain CLTIHH, rats were placed in a hypobaric chamber (430 mm Hg; 5 h/day, 5 days/week, 5 weeks). The group III (control) rats breathed room air in the same environment. At the begining of the experiments, bone mineral density (BMD) of the animals were measured, and blood samples were collected from the tail vein. After the 5-week CLTIHH period, the same measurements were repeated. Parathyroid hormone, calcium, phosphate, bone alkaline phosphatase (b-ALP), NO, interleukin 1 beta, interleukin 6, and tumor necrosis factor alpha levels were determined. The cytokines, NO levels, and BMD in CLTIHH-induced rats were higher compared with baseline and control values. The cytokines, b-ALP, and BMD increased while NO levels decreased in the group II compared with baseline values. BMD values of group II were lower than group I but higher than control group. Our results suggested that CLTIHH has positive effects on bone density. Intermittent hypoxia protocols may be developed for treatment and prevention of osteopenia and osteoporosis.

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

“…Cyclic exposure appears to produce varying responses. One study has reported improvements in structural measures of bone following 5 weeks of exposure of 4,500 m, lasting 5 hr a day for 5 days a week (Guner et al, 2013). Yet, others have noted that less severe exposures are unable to yield similar responses (Camacho‐Cardenosa, Camacho‐Cardenosa, Burtscher, et al, 2019; Martínez‐Guardado et al, 2019; Ramos‐Campo, Rubio Arias, & Jimenez Diaz, 2015).…”

Obstructive Sleep Apnea and Metabolic Bone Disease: Insights Into the Relationship Between Bone and Sleep

“…Much of this data comes from simulated hypoxia in rats; the effect of hypoxia on bone cells in humans may ultimately depend on the duration, severity, frequency, and chronicity of the hypoxia …”

“…(81) Much of this data comes from simulated hypoxia in rats; the effect of hypoxia on bone cells in humans may ultimately depend on the duration, severity, frequency, and chronicity of the hypoxia. (83) Sleep fragmentation, sleep deficiency, and bone Recurrent awakenings occur throughout the night in those affected by OSA, resulting in the buildup of sleep loss or sleep "debt." Although the amount of sleep required by an individual varies, evidence suggests physiologic and neurobehavioral deficits are more likely with less than 7 hours of sleep per night.…”

Can sleep apnea be a secondary cause of osteoporosis in young people?

“…19 IH protocol was found to increase BMD values in rats in a study for 5 days/week for 5 weeks. 20 Torres et al reported that IH (6 h/day for 32 days) model in a mouse model did not significantly modify BMD and concluded that IH preserved BMD in their mouse model. 21 Adding to that, the presence of underlying conditions such as hypertension or obesity, as well as age, sex, or genotypic variance may be important factors tilting the balance between an appropriate homeostatic response and decompensation.…”

“…The adaptive or mal‐adaptive responses can be generally predicted by the frequency, severity and duration of IH . IH protocol was found to increase BMD values in rats in a study for 5 days/week for 5 weeks . Torres et al .…”