Bone metabolism parameters and inactive matrix Gla protein in patients with obstructive sleep apnea†

Vilović, Marino; Đogaš, Zoran; Kurir, Tina Tičinović; Borovac, Josip Anđelo; Šupe‐Domić, Daniela; Vilovic, Tina; Ivkovic, Natalija; Rušić, Doris; Novak, Anita; Božić, Joško

doi:10.1093/sleep/zsz243

Cited by 12 publications

(14 citation statements)

References 45 publications

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“…31,32 Chronic intermittent hypoxia was first reported as a model for OSA in 1992. 33,34 Animals exposed to cycles of intermittent hypoxia for several days were found to develop a long-term hypertensive response, similar to OSA patients.…”

Section: Discussionmentioning

confidence: 97%

Orexin-A Reverse Bone Mass Loss Induced by Chronic Intermittent Hypoxia Through OX1R-Nrf2/HIF-1α Pathway

Gu¹,

Ru²,

Wang³

et al. 2022

DDDT

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Background: Recent studies suggest that there is a potential connection between obstructive sleep apnea (OSA) and osteoporosis through dysregulation of bone metabolism. Orexin-A, a neuroprotective peptide secreted by the hypothalamus, is at a lower level in the plasma of OSA patients, which regulates appetite, energy expenditure and sleep-wake states. However, the protective effect of orexin-A on bone metabolism in OSA is unclear. Purpose: To investigate whether the activation of OX1R by orexin-A can reverse bone mass loss induced by chronic intermittent hypoxia (CIH). Methods: Mice were randomly divided into the normoxia group and CIH group. Within the CIH or normoxia groups, treatment groups were given a subcutaneous injection of either orexin-A or saline vehicle once every day for 4 weeks and then femurs were removed for micro-CT scans. Histology and immunohistochemical staining were performed to observe and calculate the changes in femurs as a result of hypoxia. Cell immunofluorescence and immunohistochemical staining were used to detect the expression of orexin receptors in MC3T3-E1 cells or in bones. CCK-8 assay, ALP assay kit and alizarin red staining were used to detect the viability, alkaline phosphatase (ALP) activity, and capacity of mineralization, respectively. The effect of orexin-A on osteogenic differentiation of MC3T3-E1 cells was evaluated using qRT-PCR, Western blot and cell staining. Results: CIH led to a decrease in the amount and density of trabecular bone, downregulated OCN expression while increasing osteoclast numbers in femurs and inhibited the expression of RUNX2, OSX, OPN and Nrf2 in MC3T3-E1 cells. Orexin-A treatment alleviated these CIH-induced effects by combining to OX1R. The level of HIF-1α was elevated both in CIH and orexin-A treatment groups. Conclusion: CIH environment inhibits osteogenesis and orexin-A can reverse bone mass loss induced by CIH through OX1R-Nrf2 /HIF-1α pathway.

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Section: Discussionmentioning

confidence: 97%

Orexin-A Reverse Bone Mass Loss Induced by Chronic Intermittent Hypoxia Through OX1R-Nrf2/HIF-1α Pathway

Gu¹,

Ru²,

Wang³

et al. 2022

DDDT

View full text Add to dashboard Cite

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“…Measurement of BMD by dual-energy x-ray absorptiometry revealed an association between OSA and alterations in bone metabolism/architecture 21 , 33 – 39 . However, such absorptiometry is limited in measuring alterations in a large body mass index 40 – 42 .…”

Section: Discussionmentioning

confidence: 97%

Bone mineral density alteration in obstructive sleep apnea by derived computed tomography screening

Daniel

Cohen-Freud

Shelef

et al. 2022

Sci Rep

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The association between obstructive sleep apnea (OSA) and bone mineral density (BMD) is poorly elucidated and has contradictory findings. Abdominal computed tomography (CT) for other indications can provide a valuable opportunity for osteoporosis screening. Thus, we retrospectively explored the association between OSA and BMD by examining abdominal CT vertebrae images for a multitude of conditions and indications. We included 315 subjects (174 with OSA and 141 without OSA) who performed at least two CT scans (under similar settings). Both groups had a similar duration between the first and second CT scans of 3.6 years. BMD decreased in those with OSA and increased age. A multivariate linear regression indicated that OSA is associated with BMD alterations after controlling for age, gender, and cardiovascular diseases. Here, we report that OSA is associated with BMD alterations. Further studies are required to untangle the complex affect of OSA on BMD and the possible clinical implications of vertebra-depressed or femoral neck fractures.

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“…Inflammatory mediators potently inhibit vitamin K-dependent protein such as growth arrest-specific 6 (Gas6), resulting in augmentation of the inflammatory response [53]. Conditions associated with hypoxia, such as obstructive sleep apnea, exhibit excessive increases in plasma dp-ucMGP levels and bone turnover markers [54]. Inflammatory conditions, such as irritable bowel syndrome, are associated with elevated dp-ucMGP.…”

Section: Gut Microbiome Disintegration Depletes Gut-derived Mk In Covid-19 Vulnerable Groupsmentioning

confidence: 99%

Vitamin K in COVID-19—Potential Anti-COVID-19 Properties of Fermented Milk Fortified with Bee Honey as a Natural Source of Vitamin K and Probiotics

et al. 2021

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Vitamin K deficiency is evident in severe and fatal COVID-19 patients. It is associated with the cytokine storm, thrombotic complications, multiple organ damage, and high mortality, suggesting a key role of vitamin K in the pathology of COVID-19. To support this view, we summarized findings reported from machine learning studies, molecular simulation, and human studies on the association between vitamin K and SARS-CoV-2. We also investigated the literature for the association between vitamin K antagonists (VKA) and the prognosis of COVID-19. In addition, we speculated that fermented milk fortified with bee honey as a natural source of vitamin K and probiotics may protect against COVID-19 and its severity. The results reported by several studies emphasize vitamin K deficiency in COVID-19 and related complications. However, the literature on the role of VKA and other oral anticoagulants in COVID-19 is controversial: some studies report reductions in (intensive care unit admission, mechanical ventilation, and mortality), others report no effect on mortality, while some studies report higher mortality among patients on chronic oral anticoagulants, including VKA. Supplementing fermented milk with honey increases milk peptides, bacterial vitamin K production, and compounds that act as potent antioxidants: phenols, sulforaphane, and metabolites of lactobacilli. Lactobacilli are probiotic bacteria that are suggested to interfere with various aspects of COVID-19 infection ranging from receptor binding to metabolic pathways involved in disease prognosis. Thus, fermented milk that contains natural honey may be a dietary manipulation capable of correcting nutritional and immune deficiencies that predispose to and aggravate COVID-19. Empirical studies are warranted to investigate the benefits of these compounds.

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Bone metabolism parameters and inactive matrix Gla protein in patients with obstructive sleep apnea†

Cited by 12 publications

References 45 publications

Orexin-A Reverse Bone Mass Loss Induced by Chronic Intermittent Hypoxia Through OX1R-Nrf2/HIF-1α Pathway

Orexin-A Reverse Bone Mass Loss Induced by Chronic Intermittent Hypoxia Through OX1R-Nrf2/HIF-1α Pathway

Bone mineral density alteration in obstructive sleep apnea by derived computed tomography screening

Vitamin K in COVID-19—Potential Anti-COVID-19 Properties of Fermented Milk Fortified with Bee Honey as a Natural Source of Vitamin K and Probiotics

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