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Erschienen in: Osteoporosis International 8/2008

01.08.2008 | Original Article

Link between obstructive sleep apnea and increased bone resorption in men

verfasst von: H. Tomiyama, R. Okazaki, D. Inoue, H. Ochiai, K. Shiina, Y. Takata, H. Hashimoto, A. Yamashina

Erschienen in: Osteoporosis International | Ausgabe 8/2008

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Abstract

Summary

The bone metabolic abnormalities in patients with obstructive sleep apnea (OSA) were examined. Severity-dependent increases in the serum/urinary levels of bone resorption markers and their attenuation following continuous positive airway pressure therapy in subjects with OSA provide the first evidence of a link between OSA and abnormal bone metabolism.

Introduction

Hypoxia, microinflammation and oxidative stress, well-known pathophysiological features of obstructive sleep apnea (OSA), are also known to affect bone metabolism. We examined the bone metabolic abnormalities in patients with OSA and also the effects of continuous positive airway pressure (CPAP) therapy on these abnormalities.

Methods

A cross-sectional and prospective study was conducted in 50 consecutive male subjects visiting a sleep clinic and 15 age-matched control subjects without OSA. Plasma concentrations of IL-1β, IL-6, TNF-alfa, 3-nitrotyrosine, osteocalcin, bone-specific alkaline phosphatase (BAP), and urinary concentrations of cross-linked C-terminal telopeptide of type I collagen (CTX) were examined before and after 3 months’ CPAP in subjects with OSA.

Results

The plasma levels of the cytokines as well as the urinary CTX levels were higher in subjects with severe OSA than in those with mild OSA or control subjects. Significant decrease of the urinary excretion of CTX (before: 211 ± 107 vs. after: 128 ± 59 μg/mmol/creatinine; p < 0.01) as well as of the plasma levels of the cytokines was observed following 3 months’ CPAP.

Conclusions

Severity-dependent increases in the serum/urinary levels of bone resorption markers and their reversal following CPAP in subjects with OSA provide the first evidence of a link between OSA and abnormal bone metabolism.
Literatur
1.
2.
Zurück zum Zitat Caples SM, Gami AS, Somers VK (2005) Obstructive sleep apnea. Ann Intern Med 142:187–97PubMed Caples SM, Gami AS, Somers VK (2005) Obstructive sleep apnea. Ann Intern Med 142:187–97PubMed
3.
Zurück zum Zitat Shamsuzzaman AS, Gersh BJ, Somers VK (2003) Obstructive sleep apnea: implications for cardiac and vascular disease. JAMA 290:1906–1914PubMedCrossRef Shamsuzzaman AS, Gersh BJ, Somers VK (2003) Obstructive sleep apnea: implications for cardiac and vascular disease. JAMA 290:1906–1914PubMedCrossRef
4.
Zurück zum Zitat Hatipoglu U, Rubinstein I (2003) Inflammation and obstructive sleep apnea syndrome pathogenesis: a working hypothesis. Respiration 70:665–671PubMedCrossRef Hatipoglu U, Rubinstein I (2003) Inflammation and obstructive sleep apnea syndrome pathogenesis: a working hypothesis. Respiration 70:665–671PubMedCrossRef
5.
Zurück zum Zitat Schulz R, Mahmoudi S, Hattar K et al (2000) Enhanced release of superoxide from polymorphonuclear neutrophils in obstructive sleep apnea. Impact of continuous positive airway pressure therapy. Am J Respir Crit Care Med 162:566–570PubMed Schulz R, Mahmoudi S, Hattar K et al (2000) Enhanced release of superoxide from polymorphonuclear neutrophils in obstructive sleep apnea. Impact of continuous positive airway pressure therapy. Am J Respir Crit Care Med 162:566–570PubMed
6.
Zurück zum Zitat Becker HF, Jerrentrup A, Ploch T et al (2003) Effect of nasal continuous positive airway pressure treatment on blood pressure in patients with obstructive sleep apnea. Circulation 107:68–73PubMedCrossRef Becker HF, Jerrentrup A, Ploch T et al (2003) Effect of nasal continuous positive airway pressure treatment on blood pressure in patients with obstructive sleep apnea. Circulation 107:68–73PubMedCrossRef
7.
Zurück zum Zitat Pepperell JC, Ramdassingh-Dow S, Crosthwaite N et al (2002) Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnea: a randomised parallel trial. Lancet 359:204–210PubMedCrossRef Pepperell JC, Ramdassingh-Dow S, Crosthwaite N et al (2002) Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnea: a randomised parallel trial. Lancet 359:204–210PubMedCrossRef
8.
Zurück zum Zitat Marin JM, Carrizo SJ, Vicente E et al (2005) Long-term cardiovascular outcomes in men with obstructive sleep apnea-hypopnea with or without treatment with continuous positive airway pressure: an observational study. Lancet 365:1046–1053PubMed Marin JM, Carrizo SJ, Vicente E et al (2005) Long-term cardiovascular outcomes in men with obstructive sleep apnea-hypopnea with or without treatment with continuous positive airway pressure: an observational study. Lancet 365:1046–1053PubMed
9.
Zurück zum Zitat Doherty LS, Kiely JL, Swan V et al (2005) Long-term effects of nasal continuous positive airway pressure therapy on cardiovascular outcomes in sleep apnea syndrome. Chest 127:2076–2084PubMedCrossRef Doherty LS, Kiely JL, Swan V et al (2005) Long-term effects of nasal continuous positive airway pressure therapy on cardiovascular outcomes in sleep apnea syndrome. Chest 127:2076–2084PubMedCrossRef
10.
Zurück zum Zitat Young T, Palta M, Dempsey J et al (1993) The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 328:1230–1235PubMedCrossRef Young T, Palta M, Dempsey J et al (1993) The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 328:1230–1235PubMedCrossRef
11.
Zurück zum Zitat Papaioannou A, Parkinson W, Ferko N et al (2003) Prevalence of vertebral fractures among patients with chronic obstructive pulmonary disease in Canada. Osteoporos Int 14:913–917PubMedCrossRef Papaioannou A, Parkinson W, Ferko N et al (2003) Prevalence of vertebral fractures among patients with chronic obstructive pulmonary disease in Canada. Osteoporos Int 14:913–917PubMedCrossRef
12.
Zurück zum Zitat Arnett TR, Gibbons DC, Utting JC et al (2003) Hypoxia is a major stimulator of osteoclast formation and bone resorption. J Cell Physiol 196:2–8PubMedCrossRef Arnett TR, Gibbons DC, Utting JC et al (2003) Hypoxia is a major stimulator of osteoclast formation and bone resorption. J Cell Physiol 196:2–8PubMedCrossRef
13.
Zurück zum Zitat Basu S, Michaelsson K, Olofsson H et al (2001) Association between oxidative stress and bone mineral density. Biochem Biophys Res Commun 288:275–279PubMedCrossRef Basu S, Michaelsson K, Olofsson H et al (2001) Association between oxidative stress and bone mineral density. Biochem Biophys Res Commun 288:275–279PubMedCrossRef
14.
Zurück zum Zitat Clowes JA, Riggs BL, Khosla S (2005) The role of the immune system in the pathophysiology of osteoporosis. Immunol Rev 208:207–227PubMedCrossRef Clowes JA, Riggs BL, Khosla S (2005) The role of the immune system in the pathophysiology of osteoporosis. Immunol Rev 208:207–227PubMedCrossRef
15.
Zurück zum Zitat Raisz LG (2005) Pathogenesis of osteoporosis: concepts, conflicts, and prospects. J Clin Invest 115:3318–3325PubMedCrossRef Raisz LG (2005) Pathogenesis of osteoporosis: concepts, conflicts, and prospects. J Clin Invest 115:3318–3325PubMedCrossRef
16.
Zurück zum Zitat Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep 22:667–689 Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep 22:667–689
17.
Zurück zum Zitat Shiina K, Tomiyama H, Takata Y et al (2006) Concurrent presence of metabolic syndrome in obstructive sleep apnea syndrome exacerbates the cardiovascular risk: a sleep clinic cohort study. Hypertens Res 29:433–441PubMedCrossRef Shiina K, Tomiyama H, Takata Y et al (2006) Concurrent presence of metabolic syndrome in obstructive sleep apnea syndrome exacerbates the cardiovascular risk: a sleep clinic cohort study. Hypertens Res 29:433–441PubMedCrossRef
18.
Zurück zum Zitat Rechtshaffen AK, A (ed) 1968 A Manual of Standardized Terminology: Techniques and Scoring System for Sleep Stages of Human Subjects. UCLA Brain Information Service/Brain Research Institute, Los Angeles Rechtshaffen AK, A (ed) 1968 A Manual of Standardized Terminology: Techniques and Scoring System for Sleep Stages of Human Subjects. UCLA Brain Information Service/Brain Research Institute, Los Angeles
19.
Zurück zum Zitat Chaudhary B, Dasti S, Park Y et al (1998) Hour-to-hour variability of oxygen saturation in sleep apnea. Chest 113:719–722PubMedCrossRef Chaudhary B, Dasti S, Park Y et al (1998) Hour-to-hour variability of oxygen saturation in sleep apnea. Chest 113:719–722PubMedCrossRef
20.
Zurück zum Zitat Sun YC, Chang PY, Tsao KC et al (2007) Establishment of a sandwich ELISA using commercial antibody for plasma or serum 3-nitrotyrosine (3NT). Elevation in inflammatory diseases and complementary between 3NT and myeloperoxidase. Clin Chim Acta 378:175–180PubMedCrossRef Sun YC, Chang PY, Tsao KC et al (2007) Establishment of a sandwich ELISA using commercial antibody for plasma or serum 3-nitrotyrosine (3NT). Elevation in inflammatory diseases and complementary between 3NT and myeloperoxidase. Clin Chim Acta 378:175–180PubMedCrossRef
21.
Zurück zum Zitat Utting JC, Robins SP, Brandao-Burch A et al (2006) Hypoxia inhibits the growth, differentiation and bone-forming capacity of rat osteoblasts. Exp Cell Res 312:1693–1702PubMedCrossRef Utting JC, Robins SP, Brandao-Burch A et al (2006) Hypoxia inhibits the growth, differentiation and bone-forming capacity of rat osteoblasts. Exp Cell Res 312:1693–1702PubMedCrossRef
22.
Zurück zum Zitat Miller RG, Segal JB, Ashar BH et al (2006) High prevalence and correlates of low bone mineral density in young adults with sickle cell disease. Am J Hematol 81:236–241PubMedCrossRef Miller RG, Segal JB, Ashar BH et al (2006) High prevalence and correlates of low bone mineral density in young adults with sickle cell disease. Am J Hematol 81:236–241PubMedCrossRef
23.
Zurück zum Zitat Ionescu AA, Schoon E (2003) Osteoporosis in chronic obstructive pulmonary disease. Eur Respir J Suppl 46:64s–75sPubMedCrossRef Ionescu AA, Schoon E (2003) Osteoporosis in chronic obstructive pulmonary disease. Eur Respir J Suppl 46:64s–75sPubMedCrossRef
24.
Zurück zum Zitat Mineo TC, Ambrogi V, Mineo D et al (2005) Bone mineral density improvement after lung volume reduction surgery for severe emphysema. Chest 127:1960–1966PubMedCrossRef Mineo TC, Ambrogi V, Mineo D et al (2005) Bone mineral density improvement after lung volume reduction surgery for severe emphysema. Chest 127:1960–1966PubMedCrossRef
25.
Zurück zum Zitat Bonnick SL, Shulman L (2006) Monitoring osteoporosis therapy: bone mineral density, bone turnover markers, or both. Am J Med 119:S25–31PubMedCrossRef Bonnick SL, Shulman L (2006) Monitoring osteoporosis therapy: bone mineral density, bone turnover markers, or both. Am J Med 119:S25–31PubMedCrossRef
26.
Zurück zum Zitat Szulc P, Seeman E, Delmas PD (2000) Biochemical measurements of bone turnover in children and adolescents. Osteoporos Int 11:281–294PubMedCrossRef Szulc P, Seeman E, Delmas PD (2000) Biochemical measurements of bone turnover in children and adolescents. Osteoporos Int 11:281–294PubMedCrossRef
27.
Zurück zum Zitat Ueda M, Inaba M, Okuno S et al (2005) Serum BAP as the clinically useful marker for predicting BMD reduction in diabetic hemodialysis patients with low PTH. Life Sci 77:1130–1139PubMedCrossRef Ueda M, Inaba M, Okuno S et al (2005) Serum BAP as the clinically useful marker for predicting BMD reduction in diabetic hemodialysis patients with low PTH. Life Sci 77:1130–1139PubMedCrossRef
28.
Zurück zum Zitat Ryan S, Taylor CT, McNicholas WT (2005) Selective activation of inflammatory pathways by intermittent hypoxia in obstructive sleep apnea syndrome. Circulation 112:2660–2667PubMedCrossRef Ryan S, Taylor CT, McNicholas WT (2005) Selective activation of inflammatory pathways by intermittent hypoxia in obstructive sleep apnea syndrome. Circulation 112:2660–2667PubMedCrossRef
29.
Zurück zum Zitat Alam I, Lewis K, Stephens JW, Baxter JN (2007) Obesity, metabolic syndrome and sleep apnea: all pro-inflammatory states. Obes Rev 8:119–127PubMedCrossRef Alam I, Lewis K, Stephens JW, Baxter JN (2007) Obesity, metabolic syndrome and sleep apnea: all pro-inflammatory states. Obes Rev 8:119–127PubMedCrossRef
30.
Zurück zum Zitat Vgontzas AN, Pejovic S, Zoumakis E et al (2007) Hypothalamic-pituitary-adrenal axis activity in obese men with and without sleep apnea: effects of continuous positive airway pressure therapy. J Clin Endocrinol Metab 92:4199–4207PubMedCrossRef Vgontzas AN, Pejovic S, Zoumakis E et al (2007) Hypothalamic-pituitary-adrenal axis activity in obese men with and without sleep apnea: effects of continuous positive airway pressure therapy. J Clin Endocrinol Metab 92:4199–4207PubMedCrossRef
31.
Zurück zum Zitat Manelli F, Giustina A (2000) Glucocorticoid-induced osteoporosis. Trends Endocrinol Metab. 11:79–85PubMedCrossRef Manelli F, Giustina A (2000) Glucocorticoid-induced osteoporosis. Trends Endocrinol Metab. 11:79–85PubMedCrossRef
32.
Zurück zum Zitat Tanaka S, Nakamura K, Takahasi N et al (2005) Role of RANKL in physiological and pathological bone resorption and therapeutics targeting the RANKL-RANK signaling system. Immunol Rev 208:30–49PubMedCrossRef Tanaka S, Nakamura K, Takahasi N et al (2005) Role of RANKL in physiological and pathological bone resorption and therapeutics targeting the RANKL-RANK signaling system. Immunol Rev 208:30–49PubMedCrossRef
34.
Zurück zum Zitat Boyle WJ, Simonet WS, Lacey DL (2003) Osteoclast differentiation and activation. Nature 423:337–342PubMedCrossRef Boyle WJ, Simonet WS, Lacey DL (2003) Osteoclast differentiation and activation. Nature 423:337–342PubMedCrossRef
35.
Zurück zum Zitat Rogers A, Eastell R (2005) Circulating osteoprotegerin and receptor activator for nuclear factor kappaB ligand: clinical utility in metabolic bone disease assessment. J Clin Endocrinol Metab 90:6323–6331PubMedCrossRef Rogers A, Eastell R (2005) Circulating osteoprotegerin and receptor activator for nuclear factor kappaB ligand: clinical utility in metabolic bone disease assessment. J Clin Endocrinol Metab 90:6323–6331PubMedCrossRef
36.
Zurück zum Zitat Bravo Mde L, Serpero LD, Barcelo A, Barbe F, Agusti A, Gozal D (2007) Inflammatory proteins in patients with obstructive sleep apnea with and without daytime sleepiness. Sleep Breath 11:177–185PubMedCrossRef Bravo Mde L, Serpero LD, Barcelo A, Barbe F, Agusti A, Gozal D (2007) Inflammatory proteins in patients with obstructive sleep apnea with and without daytime sleepiness. Sleep Breath 11:177–185PubMedCrossRef
37.
Zurück zum Zitat Yokoe T, Minoguchi K, Matsuo H et al (2003) Elevated levels of C-reactive protein and interleukin-6 in patients with obstructive sleep apnea syndrome are decreased by nasal continuous positive airway pressure. Circulation 107:1129–1134PubMedCrossRef Yokoe T, Minoguchi K, Matsuo H et al (2003) Elevated levels of C-reactive protein and interleukin-6 in patients with obstructive sleep apnea syndrome are decreased by nasal continuous positive airway pressure. Circulation 107:1129–1134PubMedCrossRef
38.
Zurück zum Zitat Tomlinson JW, Bujalska I, Stewart PM, Cooper MS (2000) The role of 11 beta-hydroxysteroid dehydrogenase in central obesity and osteoporosis. Endocr Res 26:711–722PubMedCrossRef Tomlinson JW, Bujalska I, Stewart PM, Cooper MS (2000) The role of 11 beta-hydroxysteroid dehydrogenase in central obesity and osteoporosis. Endocr Res 26:711–722PubMedCrossRef
39.
Zurück zum Zitat Fulkerson JA, Himes JH, French SA et al (2004) Bone outcomes and technical measurement issues of bone health among children and adolescents: considerations for nutrition and physical activity intervention trials. Osteoporos Int 15:929–941PubMedCrossRef Fulkerson JA, Himes JH, French SA et al (2004) Bone outcomes and technical measurement issues of bone health among children and adolescents: considerations for nutrition and physical activity intervention trials. Osteoporos Int 15:929–941PubMedCrossRef
Metadaten
Titel
Link between obstructive sleep apnea and increased bone resorption in men
verfasst von
H. Tomiyama
R. Okazaki
D. Inoue
H. Ochiai
K. Shiina
Y. Takata
H. Hashimoto
A. Yamashina
Publikationsdatum
01.08.2008
Verlag
Springer-Verlag
Erschienen in
Osteoporosis International / Ausgabe 8/2008
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-007-0556-0

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