nach oben

Osteoporosis International

Erschienen in:

01.03.2015 | Original Article

Increased undercarboxylated osteocalcin/intact osteocalcin ratio in patients undergoing hemodialysis

verfasst von: Y. Nagata, M. Inaba, Y. Imanishi, H. Okazaki, S. Yamada, K. Mori, S. Shoji, H. Koyama, S. Okuno

Erschienen in: Osteoporosis International | Ausgabe 3/2015

Einloggen, um Zugang zu erhalten

Abstract

Summary

Serum undercarboxylated osteocalcin (ucOC)/intact osteocalcin (iOC) ratio increased >1.0 in the patients undergoing hemodialysis, particularly in those with high bone turnover state. Consequently, serum ucOC/iOC ratio might lose its significance as a bone metabolic marker to indicate vitamin K deficiency in hemodialysis patients.

Introduction

Serum intact osteocalcin (iOC), undercarboxylated OC (ucOC), and the ucOC/iOC ratio are considered clinically relevant indices in pre-dialysis chronic kidney disease (CKD) and hemodialysis (HD) patients, despite their accumulation in uremic serum.

Methods

Serum iOC and ucOC were measured along with serum intact parathyroid hormone (iPTH), bone alkaline phosphatase (BAP), and tartrate-resistant acid phosphatase (TRACP)-5b in 89 pre-dialysis CKD and 189 HD patients.

Results

Serum iOC and ucOC showed significantly negative correlations with estimated glomerular filtration rate in pre-dialysis CKD patients, although serum ucOC/iOC ratio did not correlate. Serum ucOC was significantly greater in HD patients than in pre-dialysis CKD patients, while serum iOC did not differ significantly, resulting in serum ucOC/iOC ratio >1.0 in 135 (71.4 %) out of 189 HD patients. HD patients with high serum ucOC/iOC ratio (>1.0) had a significantly younger age and significantly higher values of body mass index, serum creatinine, albumin, phosphate, iPTH, and TRACP-5b than those with low ucOC/iOC ratio (≤1.0). The baseline iPTH and P1NP correlated with the changes of the ucOC/iOC ratio during the 2 days of the inter-dialytic period. Multivariate analysis showed that log [ucOC/iOC] in HD patients was significantly associated with log [iPTH], log [BAP], or log [TRACP-5b].

Conclusions

Serum ucOC/iOC ratio >1.0 was observed in as high as 71.4 % of HD patients, preferentially with high bone turnover state, in comparison with pre-dialysis CKD patients. These data suggested that serum ucOC/iOC ratio might lose its significance as a bone metabolic marker to indicate vitamin K deficiency in HD patients.

Delmas PD (1990) Biochemical markers of bone turnover for the clinical assessment of metabolic bone disease. Endocrinol Metab Clin North Am 19:1–18PubMed

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–S17CrossRefPubMed

Price PA, Williamson MK, Lothringer JW (1981) Origin of the vitamin K-dependent bone protein found in plasma and its clearance by kidney and bone. J Biol Chem 256:12760–12766PubMed

Price PA, Williamson MK (1981) Effects of warfarin on bone. Studies on the vitamin K-dependent protein of rat bone. J Biol Chem 256:12754–12759PubMed

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 16:501–509CrossRefPubMed

Maeno Y, Inaba M, Okuno S, Yamakawa T, Ishimura E, Nishizawa Y (2005) Serum concentrations of cross-linked N-telopeptides of type I collagen: new marker of bone resorption in hemodialysis patients. Clin Chem 51:2312–2317CrossRefPubMed

Nagasue K, Inaba M, Okuno S, Kitatani K, Imanishi Y, Ishimura E, Miki T, Kim M, Nishizawa Y (2003) Serum N-terminal midfragment vs. intact osteocalcin immunoradiometric assay as markers for bone turnover and bone loss in hemodialysis patients. Biomed Pharmacother 57:98–104CrossRefPubMed

Nimptsch K, Hailer S, Rohrmann S, Gedrich K, Wolfram G, Linseisen J (2007) Determinants and correlates of serum undercarboxylated osteocalcin. Ann Nutr Metab 51:563–570CrossRefPubMed

Kasukawa Y, Miyakoshi N, Ebina T, Aizawa T, Hongo M, Nozaka K, Ishikawa Y, Saito H, Chida S, Shimada Y (2013) Effects of risedronate alone or combined with vitamin K on serum undercarboxylated osteocalcin and osteocalcin levels in postmenopausal osteoporosis. J Bone Miner Metab 32:290–297CrossRefPubMed

10.

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 9:1591–1595CrossRefPubMed

11.

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 91:1769–1774CrossRefPubMedCentralPubMed

12.

Imai E, Horio M, Watanabe T et al (2009) Prevalence of chronic kidney disease in the Japanese general population. Clin Exp Nephrol 13:621–630CrossRefPubMed

13.

Maeno Y, Inaba M, Okuno S, Kohno K, Maekawa K, Yamakawa T, Ishimura E, Nishizawa Y (2009) Significant association of fracture of the lumbar spine with mortality in female hemodialysis patients: a prospective observational study. Calcif Tissue Int 85:310–316CrossRefPubMed

14.

Gal-Moscovici A, Sprague SM (2007) Osteoporosis and chronic kidney disease. Semin Dial 20:423–430CrossRefPubMed

15.

Klawansky S, Komaroff E, Cavanaugh PF Jr, Mitchell DY, Gordon MJ, Connelly JE, Ross SD (2003) Relationship between age, renal function and bone mineral density in the US population. Osteoporos Int 14:570–576CrossRefPubMed

16.

Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group (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: S1-130

17.

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 9:525–531CrossRefPubMed

18.

Takahashi M, Kushida K, Nagano A, Inoue T (2000) Comparison of the analytical and clinical performance characteristics of an N-MID versus an intact osteocalcin immunoradiometric assay. Clin Chim Acta 294:67–76CrossRefPubMed

19.

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 85:4157–4161PubMed

20.

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 22:187–194CrossRefPubMed

21.

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 94:45–49CrossRefPubMed

22.

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

23.

Miyauchi A, Matsumoto T, Sugimoto T, Tsujimoto M, Warner MR, Nakamura T (2010) Effects of teriparatide on bone mineral density and bone turnover markers in Japanese subjects with osteoporosis at high risk of fracture in a 24-month clinical study: 12-month, randomized, placebo-controlled, double-blind and 12-month open-label phases. Bone 47:493–502CrossRefPubMed

24.

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 26:265–270CrossRefPubMed

25.

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 376:205–212CrossRefPubMed

26.

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 82:278–287CrossRefPubMed

27.

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

28.

Miki T, Nakatsuka K, Naka H, Kitatani K, Saito S, Masaki H, Tomiyoshi Y, Morii H, Nishizawa Y (2003) Vitamin K (2) (menaquinone 4) reduces serum undercarboxylated osteocalcin level as early as 2 weeks in elderly women with established osteoporosis. J Bone Miner Metab 21:161–165CrossRefPubMed

29.

Shiraki M, Aoki C, Yamazaki N, Ito Y, Tsugawa N, Suhara Y, Okano T (2007) Clinical assessment of undercarboxylated osteocalcin measurement in serum using an electrochemiluminescence immunoassay: establishments of cut-off values to determine vitamin K insufficiency in bone and to predict fracture leading to clinical use of vitamin K2. Iyaku Yakugaku 57:537–546 (in Japanese)

30.

Shiraki M, Yamazaki Y, Shiraki Y, Hosoi T, Tsugawa N, Okano T (2010) High level of serum undercarboxylated osteocalcin in patients with incident fractures during bisphosphonate treatment. J Bone Miner Metab 28:578–584CrossRefPubMed

31.

Prats-Puig A, Mas-Parareda M, Riera-Perez E et al (2010) Carboxylation of osteocalcin affects its association with metabolic parameters in healthy children. Diabetes Care 33:661–663CrossRefPubMedCentralPubMed

32.

Westenfeld R, Krueger T, Schlieper G, Cranenburg EC, Magdeleyns EJ, Heidenreich S, Holzmann S, Vermeer C, Jahnen-Dechent W, Ketteler M, Floege J, Schurgers LJ (2012) Effect of vitamin K2 supplementation on functional vitamin K deficiency in hemodialysis patients: a randomized trial. Am J Kidney Dis 59:186–195CrossRefPubMed

33.

Holden RM, Morton AR, Garland JS, Pavlov A, Day AG, Booth SL (2010) Vitamins K and D status in stages 3-5 chronic kidney disease. Clin J Am Soc Nephrol 5:590–597CrossRefPubMedCentralPubMed

34.

Pilkey RM, Morton AR, Boffa MB, Noordhof C, Day AG, Su Y, Miller LM, Koschinsky ML, Booth SL (2007) Subclinical vitamin K deficiency in hemodialysis patients. Am J Kidney Dis 49:432–439CrossRefPubMed

35.

Garnero P, Grimaux M, Seguin P, Delmas PD (1994) Characterization of immunoreactive forms of human osteocalcin generated in vivo and in vitro. J Bone Miner Res 9:255–264CrossRefPubMed

36.

Rosenquist C, Bonde M, Qvist P (1994) A competitive immunoassay (ELISA) for the detection of N-terminal-related osteocalcin; improved stability of osteocalcin in serum. J Bone Miner Res 9:S37

Titel: Increased undercarboxylated osteocalcin/intact osteocalcin ratio in patients undergoing hemodialysis
verfasst von: Y. Nagata
M. Inaba
Y. Imanishi
H. Okazaki
S. Yamada
K. Mori
S. Shoji
H. Koyama
S. Okuno
Publikationsdatum: 01.03.2015
Verlag: Springer London
Erschienen in: Osteoporosis International / Ausgabe 3/2015
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-014-2954-4

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen.
» Jetzt entdecken

Neu im Fachgebiet Orthopädie und Unfallchirurgie

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Arthroskopie kann Knieprothese nicht hinauszögern

25.04.2024 Gonarthrose Nachrichten

Ein arthroskopischer Eingriff bei Kniearthrose macht im Hinblick darauf, ob und wann ein Gelenkersatz fällig wird, offenbar keinen Unterschied.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Ärztliche Empathie hilft gegen Rückenschmerzen

23.04.2024 Leitsymptom Rückenschmerzen Nachrichten

Personen mit chronischen Rückenschmerzen, die von einfühlsamen Ärzten und Ärztinnen betreut werden, berichten über weniger Beschwerden und eine bessere Lebensqualität.

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Summary

Introduction

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2015

Is thoracolumbar fascia injury the cause of residual back pain after percutaneous vertebroplasty? A prospective cohort study

Association between dietary fat intake and bone mineral density in Korean adults: data from Korea National Health and Nutrition Examination Survey IV (2008∼2009)

Exercise characteristics influence femoral cross-sectional geometry: a magnetic resonance imaging study in elite female athletes

Calcium gluconate supplementation is effective to balance calcium homeostasis in patients with gastrectomy

Hyponatremia and osteoporosis: insights from the Danish National Patient Registry