Top

Published in:

01-02-2013 | Original Article

Significant inverse relationship between serum undercarboxylated osteocalcin and glycemic control in maintenance hemodialysis patients

Authors: S. Okuno, E. Ishimura, N. Tsuboniwa, K. Norimine, K. Yamakawa, T. Yamakawa, S. Shoji, K. Mori, Y. Nishizawa, M. Inaba

Published in: Osteoporosis International | Issue 2/2013

Abstract

Summary

Increased levels of serum undercarboxylated osteocalcin, which were associated with bone metabolism markers, correlated inversely with indices of glucose metabolism (plasma glucose, hemoglobin A1C, and glycated albumin) in hemodialysis patients with abnormalities of bone metabolism.

Introduction

Undercarboxylated osteocalcin (ucOC), a possible marker of bone metabolism and one of the osteoblast-specific secreted proteins, has recently been reported to be associated with glucose metabolism. We tested the hypothesis that ucOC levels are associated with indices of glucose metabolism in chronic hemodialysis patients with abnormalities of bone metabolism.

Methods

Serum ucOC, bone alkaline phosphatase (BAP, a bone formation marker), and tartrate-resistant acid phosphatase-5b (TRACP-5b, a bone resorption marker) were measured in 189 maintenance hemodialysis patients (96 diabetics and 93 non-diabetics), and their relationships with glucose metabolism were examined.

Results

ucOC correlated positively with BAP (ρ = 0.489, p < 0.0001), TRACP-5b (ρ = 0.585, p < 0.0001) and intact parathyroid hormone (iPTH; ρ = 0.621, p < 0.0001). Serum ucOC levels in the diabetic patients were lower than those of non-diabetic patients (p < 0.001), although there were no significant differences in serum BAP or TRACP-5b between diabetic and non-diabetic patients. Serum ucOC correlated negatively with plasma glucose (ρ = −0.303, p < 0.0001), hemoglobin A1C (ρ = −0.214, p < 0.01), and glycated albumin (ρ = −0.271, p < 0.001), although serum BAP or TRACP-5b did not. In multiple linear regression analysis, log [plasma glucose], log [hemoglobin A1C], and log [glycated albumin] were associated significantly with log [ucOC] after adjustment for age, gender, hemodialysis duration, and body mass index but were not associated with log [BAP], log [TRACP-5b], or log [intact PTH].

Conclusion

Increased levels of serum ucOC, which were associated with bone metabolism markers, were inversely associated with indices of glucose metabolism in hemodialysis patients.

Urena P, De Vernejoul MC (1999) Circulating biochemical markers of bone remodeling in uremic patients. Kidney Int 55:2141–2156PubMedCrossRef

Yu XP, Chandrasekhar S (1997) Parathyroid hormone (PTH 1–34) regulation of rat osteocalcin gene transcription. Endocrinology 138:3085–3092PubMedCrossRef

Szulc P, Chapuy MC, Meunier PJ, Delmas PD (1993) Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture in elderly women. J Clin Invest 91:1769–1774PubMedCrossRef

Szulc P, Arlot M, Chapuy MC, Duboeuf F, Meunier PJ, Delmas PD (1994) Serum undercarboxylated osteocalcin correlates with hip bone mineral density in elderly women. J Bone Miner Res 9:1591–1595PubMedCrossRef

Delmas PD, Eastell R, Garnero P, Seibel MJ, Stepan J (2000) The use of biochemical markers of bone turnover in osteoporosis. Committee of Scientific Advisors of the International Osteoporosis Foundation. Osteoporos Int 11(Suppl 6):S2–S17PubMedCrossRef

Ducy P, Desbois C, Boyce B, Pinero G, Story B, Dunstan C, Smith E, Bonadio J, Goldstein S, Gundberg C, Bradley A, Karsenty G (1996) Increased bone formation in osteocalcin-deficient mice. Nature 382:448–452PubMedCrossRef

Nickolas TL, Cremers S, Zhang A, Thomas V, Stein E, Cohen A, Chauncey R, Nikkel L, Yin MT, Liu XS, Boutroy S, Staron RB, Leonard MB, McMahon DJ, Dworakowski E, Shane E (2011) Discriminants of prevalent fractures in chronic kidney disease. J Am Soc Nephrol 22:1560–1572

Motyl KJ, McCabe LR, Schwartz AV (2010) Bone and glucose metabolism: a two-way street. Arch Biochem Biophys 503:2–10PubMedCrossRef

Ng KW (2011) Regulation of glucose metabolism and the skeleton. Clin Endocrinol (Oxf) 75:147–155

10.

Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, Dacquin R, Mee PJ, McKee MD, Jung DY, Zhang Z, Kim JK, Mauvais-Jarvis F, Ducy P, Karsenty G (2007) Endocrine regulation of energy metabolism by the skeleton. Cell 130:456–469PubMedCrossRef

11.

Ferron M, Hinoi E, Karsenty G, Ducy P (2008) Osteocalcin differentially regulates beta cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc Natl Acad Sci U S A 105:5266–5270PubMedCrossRef

12.

Confavreux CB (2011) Bone: from a reservoir of minerals to a regulator of energy metabolism. Kidney Int Suppl 121:S14–S19PubMedCrossRef

13.

Clemens TL, Karsenty G (2011) The osteoblast: an insulin target cell controlling glucose homeostasis. J Bone Miner Res 26:677–680PubMedCrossRef

14.

Dobnig H, Piswanger-Solkner JC, Roth M, Obermayer-Pietsch B, Tiran A, Strele A, Maier E, Maritschnegg P, Sieberer C, Fahrleitner-Pammer A (2006) Type 2 diabetes mellitus in nursing home patients: effects on bone turnover, bone mass, and fracture risk. J Clin Endocrinol Metab 91:3355–3363PubMedCrossRef

15.

Im JA, Yu BP, Jeon JY, Kim SH (2008) Relationship between osteocalcin and glucose metabolism in postmenopausal women. Clin Chim Acta 396:66–69PubMedCrossRef

16.

Zhou M, Ma X, Li H, Pan X, Tang J, Gao Y, Hou X, Lu H, Bao Y, Jia W (2009) Serum osteocalcin concentrations in relation to glucose and lipid metabolism in Chinese individuals. Eur J Endocrinol 161:723–729PubMedCrossRef

17.

Kanazawa I, Yamaguchi T, Yamauchi M, Yamamoto M, Kurioka S, Yano S, Sugimoto T (2011) Serum undercarboxylated osteocalcin was inversely associated with plasma glucose level and fat mass in type 2 diabetes mellitus. Osteoporos Int 22:187–194PubMedCrossRef

18.

Pittas AG, Harris SS, Eliades M, Stark P, Dawson-Hughes B (2009) Association between serum osteocalcin and markers of metabolic phenotype. J Clin Endocrinol Metab 94:827–832PubMedCrossRef

19.

Kindblom JM, Ohlsson C, Ljunggren O, Karlsson MK, Tivesten A, Smith U, Mellstrom D (2009) Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men. J Bone Miner Res 24:785–791PubMedCrossRef

20.

Yeap BB, Chubb SA, Flicker L, McCaul KA, Ebeling PR, Beilby JP, Norman PE (2010) Reduced serum total osteocalcin is associated with metabolic syndrome in older men via waist circumference, hyperglycemia, and triglyceride levels. Eur J Endocrinol 163:265–272PubMedCrossRef

21.

(2009) KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl 113:S1–S130

22.

Okuno S, Inaba M, Kitatani K, Ishimura E, Yamakawa T, Nishizawa Y (2005) Serum levels of C-terminal telopeptide of type I collagen: a useful new marker of cortical bone loss in hemodialysis patients. Osteoporos Int 16:501–509PubMedCrossRef

23.

Gomez B Jr, Ardakani S, Ju J, Jenkins D, Cerelli MJ, Daniloff GY, Kung VT (1995) Monoclonal antibody assay for measuring bone-specific alkaline phosphatase activity in serum. Clin Chem 41:1560–1566PubMed

24.

Kumeda Y, Inaba M, Tahara H, Kurioka Y, Ishikawa T, Morii H, Nishizawa Y (2000) Persistent increase in bone turnover in Graves' patients with subclinical hyperthyroidism. J Clin Endocrinol Metab 85:4157–4161PubMedCrossRef

25.

Nishizawa Y, Inaba M, Ishii M, Yamashita H, Miki T, Goto H, Yamada S, Chaki O, Kurasawa K, Mochizuki Y (2008) Reference intervals of serum tartrate-resistant acid phosphatase type 5b activity measured with a novel assay in Japanese subjects. J Bone Miner Metab 26:265–270PubMedCrossRef

26.

Ohashi T, Igarashi Y, Mochizuki Y, Miura T, Inaba N, Katayama K, Tomonaga T, Nomura F (2007) Development of a novel fragments absorbed immunocapture enzyme assay system for tartrate-resistant acid phosphatase 5b. Clin Chim Acta 376:205–212PubMedCrossRef

27.

Shidara K, Inaba M, Okuno S, Yamada S, Kumeda Y, Imanishi Y, Yamakawa T, Ishimura E, Nishizawa Y (2008) Serum levels of TRAP5b, a new bone resorption marker unaffected by renal dysfunction, as a useful marker of cortical bone loss in hemodialysis patients. Calcif Tissue Int 82:278–287PubMedCrossRef

28.

Kanazawa I, Yamaguchi T, Yamauchi M, Yamamoto M, Kurioka S, Yano S, Sugimoto T (2009) Adiponectin is associated with changes in bone markers during glycemic control in type 2 diabetes mellitus. J Clin Endocrinol Metab 94:3031–3037PubMedCrossRef

29.

Nishimura J, Arai N, Tohmatsu J (2007) Measurement of serum undercarboxylated osteocalcin by ECLIA with the “Picolumi ucOC” kit. Clin Calcium 17:1702–1708 (in Japanese)PubMed

30.

Yamada S, Inaba M, Kurajoh M, Shidara K, Imanishi Y, Ishimura E, Nishizawa Y (2008) Utility of serum tartrate-resistant acid phosphatase (TRACP5b) as a bone resorption marker in patients with chronic kidney disease: independence from renal dysfunction. Clin Endocrinol (Oxf) 69:189–196CrossRef

31.

Inaba M, Nishizawa Y, Mita K, Kumeda Y, Emoto M, Kawagishi T, Ishimura E, Nakatsuka K, Shioi A, Morii H (1999) Poor glycemic control impairs the response of biochemical parameters of bone formation and resorption to exogenous 1,25-dihydroxyvitamin D3 in patients with type 2 diabetes. Osteoporos Int 9:525–531PubMedCrossRef

32.

Gerdhem P, Isaksson A, Akesson K, Obrant KJ (2005) Increased bone density and decreased bone turnover, but no evident alteration of fracture susceptibility in elderly women with diabetes mellitus. Osteoporos Int 16:1506–1512PubMedCrossRef

33.

Martin KJ, Gonzalez EA (2007) Metabolic bone disease in chronic kidney disease. J Am Soc Nephrol 18:875–885PubMedCrossRef

34.

Malluche HH, Monier-Faugere MC (1992) Risk of adynamic bone disease in dialyzed patients. Kidney Int Suppl 38:S62–S67PubMed

35.

Kanazawa I, Yamaguchi T, Yamamoto M, Yamauchi M, Kurioka S, Yano S, Sugimoto T (2009) Serum osteocalcin level is associated with glucose metabolism and atherosclerosis parameters in type 2 diabetes mellitus. J Clin Endocrinol Metab 94:45–49PubMedCrossRef

36.

Iki M, Tamaki J, Fujita Y, Kouda K, Yura A, Kadowaki E, Sato Y, Moon JS, Tomioka K, Okamoto N, Kurumatani N (2011) Serum undercarboxylated osteocalcin levels are inversely associated with glycemic status and insulin resistance in an elderly Japanese male population: Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Study. Osteoporos Int 23:761–770

37.

Hwang YC, Jeong IK, Ahn KJ, Chung HY (2009) The uncarboxylated form of osteocalcin is associated with improved glucose tolerance and enhanced beta-cell function in middle-aged male subjects. Diabetes Metab Res Rev 25:768–772PubMedCrossRef

Title: Significant inverse relationship between serum undercarboxylated osteocalcin and glycemic control in maintenance hemodialysis patients
Authors: S. Okuno
E. Ishimura
N. Tsuboniwa
K. Norimine
K. Yamakawa
T. Yamakawa
S. Shoji
K. Mori
Y. Nishizawa
M. Inaba
Publication date: 01-02-2013
Publisher: Springer-Verlag
Published in: Osteoporosis International / Issue 2/2013
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-012-2003-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Significant inverse relationship between serum undercarboxylated osteocalcin and glycemic control in maintenance hemodialysis patients

Abstract

Summary

Introduction

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 2/2013

Life expectancy following diagnosis of a vertebral compression fracture

Educational level and use of osteoporosis drugs in elderly men and women: a Swedish nationwide register-based study

Health risks and benefits from calcium and vitamin D supplementation: Women's Health Initiative clinical trial and cohort study

Does frequency of resistance training affect tibial cortical bone density in older women? A randomized controlled trial

Models of care for the secondary prevention of osteoporotic fractures: a systematic review and meta-analysis

Discrimination of fractures by low-frequency axial transmission ultrasound in postmenopausal females