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Licensed Unlicensed Requires Authentication Published by De Gruyter June 18, 2015

Reference intervals for bone turnover markers in Spanish premenopausal women

  • Núria Guañabens EMAIL logo , Xavier Filella , Ana Monegal , Carmen Gómez-Vaquero , María Bonet , Dolors Buquet , Enrique Casado , Dacia Cerdá , Alba Erra , Silvia Martinez , Núria Montalá , Concepción Pitarch , Eduardo Kanterewicz , Miquel Sala , Xavier Surís , Ferran Torres and on behalf of the LabOscat Study Group

Abstract

Background: The aims of this study were to establish robust reference intervals and to investigate the factors influencing bone turnover markers (BTMs) in healthy premenopausal Spanish women.

Methods: A total of 184 women (35–45 years) from 13 centers in Catalonia were analyzed. Blood and second void urine samples were collected between 8 a.m. and 10 a.m. after an overnight fast. Serum procollagen type I amino-terminal propeptide (PINP) and serum cross-linked C-terminal telopeptide of type I collagen (CTX-I) were measured by two automated assays (Roche and IDS), bone alkaline phosphatase (bone ALP) by ELISA, osteocalcin (OC) by IRMA and urinary NTX-I by ELISA. PTH and 25-hydroxyvitamin D (25OHD) levels were measured. All participants completed a questionnaire on lifestyle factors.

Results: Reference intervals were: PINP: 22.7–63.1 and 21.8–65.5 μg/L, bone ALP: 6.0–13.6 μg/L, OC: 8.0–23.0 μg/L, CTX-I: 137–484 and 109–544 ng/L and NTX-I: 19.6–68.9 nM/mM. Oral contraceptive pills (OCPs) influenced PINP (p=0.007), and low body mass index (BMI) was associated with higher BTMs except for bone ALP. Women under 40 had higher median values of most BTMs. CTX-I was influenced by calcium intake (p=0.010) and PTH (p=0.007). 25OHD levels did not influence BTMs. Concordance between the two automated assays for PINP and particularly CTX-I was poor.

Conclusions: Robust reference intervals for BTMs in a Southern European country are provided. The effects of OCPs and BMI on their levels are significant, whilst serum 25OHD levels did not influence BTMs. Age, calcium intake, BMI and PTH influenced CTX-I. The two automated assays for measuring PINP and CTX-I are not interchangeable.


Corresponding author: Núria Guañabens, Service of Rheumatology, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, C/Villarroel 170, 08036 Barcelona, Spain, Phone: +34 93 2275400 ext 2236, E-mail:

Acknowledgments

This study was funded by a research grant from the Catalan Society of Rheumatology. The kits were generously provided by Roche Diagnostics and by Immunodiagnostic Systems, Spain.

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

LabOscat Study group

Marta Larrosa, Rheumatology Department, University Institute Parc Taulí, Sabadell; Joan Miquel Nolla, Rheumatology Department, IDIBELL, Hospital Universitari de Bellvitge, L’Hospitalet, Barcelona; Pilar Peris, Rheumatology Department, Hospital Clinic, IDIBAPS, CIBERehd, Barcelona; Daniel Roig-Vilaseca, Rheumatology Department, Hospital Moisés Broggi, Barcelona.

References

1. Naylor K, Eastell R. Bone turnover markers: use in osteoporosis. Nat Rev Rheumatol 2012;8:379–89.10.1038/nrrheum.2012.86Search in Google Scholar

2. Biver E, Chopin F, Coiffier G, Brentano TF, Bouvard B, Garnero P, et al. Bone turnover markers for osteoporotic status assessment? A systematic review of their diagnosis value at baseline in osteoporosis. J Bone Spine 2012;79:20–5.10.1016/j.jbspin.2011.05.003Search in Google Scholar

3. Garnero P. Bone markers in osteoporosis. Curr Osteoporos Rep 2009;7:84–90.10.1007/s11914-009-0014-3Search in Google Scholar

4. Cerdá Gabaroi D, Peris P, Monegal A, Albaladejo C, Martínez MA, Muxí A, et al. Search for hidden secondary causes in postmenopausal women with osteoporosis. Menopause 2010;17:135–9.10.1097/gme.0b013e3181ade8e5Search in Google Scholar

5. Fitzpatrick L. Secondary causes of osteoporosis. Mayo Clin Proc 2002;77:453–68.10.1016/S0025-6196(11)62214-3Search in Google Scholar

6. Grey A, Bolland M, Wattie D, Horne A, Gamble G, Reid IR. Prolonged antiresorptive activity of zoledronate: a randomized, controlled trial. J Bone Miner Res 2010;25:2251–5.10.1002/jbmr.103Search in Google Scholar

7. Eastell R, Christiansen C, Grauer A, Kutilek S, Libanati C, McClung MR, et al. Effects of denosumab on bone turnover markers in postmenopausal osteoporosis. J Bone Miner Res 2011;26:530–7.10.1002/jbmr.251Search in Google Scholar

8. Reid IR, Black DM, Eastell R, Bucci-Rechtweg C, Su G, Hue TF, et al. HORIZON Pivotal Fracture Trial and HORIZON Recurrent Fracture Trial Steering Committees. Reduction in the risk of clinical fractures after a single dose of zoledronic acid 5 milligrams. J Clin Endocrinol Metab 2013;98:557–63.10.1210/jc.2012-2868Search in Google Scholar

9. Peris P, Alvarez L, Monegal A, Guañabens N, Durán M, Pons F, et al. Biochemical markers of bone turnover after surgical menopause and hormone replacement therapy. Bone 1999;25:349–53.10.1016/S8756-3282(99)00175-1Search in Google Scholar

10. Eastell R, Garnero P, Audebert C, Cahall DL. Reference intervals of bone turnover markers in healthy premenopausal women: results from a cross-sectional European study. Bone 2012;50:1141–7.10.1016/j.bone.2012.02.003Search in Google Scholar PubMed

11. Glover SJ, Gall M, Schoenborn-Kellenberger O, Wagener M, Garnero P, Boonen S, et al. Establishing a reference interval for bone turnover markers in 637 healthy, young, premenopausal women from the United Kingdom, France, Belgium and the United States. J Bone Miner Res 2009;24:389–97.10.1359/jbmr.080703Search in Google Scholar

12. de Papp AE, Bone HG, Caulfield MP, Kagan R, Buinewicz A, Chen E, et al. A cross-sectional study of bone turnover markers in healthy premenopausal women. Bone 2007;40:1222–30.10.1016/j.bone.2007.01.008Search in Google Scholar

13. Michelsen J, Wallaschofski H, Friedrich N, Spielhagen C, Rettig R, Ittermann T, et al. Reference intervals for serum concentrations of three bone turnover markers for men and women. Bone 2013;57:399–404.10.1016/j.bone.2013.09.010Search in Google Scholar

14. Martínez J, Olmos JM, Hernández JL, Pinedo G, Llorca J, Obregón E, et al. Bone turnover markers in Spanish postmenopausal women: the Camargo cohort study. Clin Chim Acta 2009;409:70–4.10.1016/j.cca.2009.08.020Search in Google Scholar

15. Kanterewicz E, Peris P, Puigoriol E, Yáñez A, Rosique P, Del Rio L; FRODOS Research Group. Distribution of serum βCTX in a population-based study of postmenopausal women taking into account different anti-osteoporotic therapies (the FRODOS Cohort).J Bone Miner Metab 2013;31:231–9.10.1007/s00774-012-0410-0Search in Google Scholar

16. Dominguez Cabrera C, Sosa Henríquez M, Traba ML, Alvarez Villafañe E, de la Piedra C. Biochemical markers of bone formation in the study of postmenopausal osteoporosis. Osteoporos Int 1998;8:147–51.10.1007/BF02672511Search in Google Scholar

17. Rubert M, Martinez MJ, de la Piedra C. Normal values of the aminoterminal propeptide of type I collagen (PINP) and the isomer beta I collagen carboxyterminal telopeptide (βCTX) in serum of healthy premenopausal women of the Community of Madrid. Rev Osteoporos Metab Miner 2014;6:20–2.10.4321/S1889-836X2014000100005Search in Google Scholar

18. Glover SJ, Garnero P, Naylor K, Rogers A, Eastell R. Establishing a reference range for bone turnover markers in young, healthy women. Bone 2008;42:623–30.10.1016/j.bone.2007.12.218Search in Google Scholar

19. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1:307–10.Search in Google Scholar

20. Bland, JM, Altman, DG. Comparing methods of measurement: why plotting difference against standard methods is misleading. Lancet 1995;346:1085–7.10.1016/S0140-6736(95)91748-9Search in Google Scholar

21. Lin LI. A concordance correlation coefficient to evaluate reproducibility. Biometrics 1989;45:255–68.10.2307/2532051Search in Google Scholar

22. Lin LI. A note on the concordance correlation coefficient. Biometrics 2000;56:324–5.Search in Google Scholar

23. Available from: http://www.niwa.co.nz/node/104318/concordance. Accessed 15 May, 2014.Search in Google Scholar

24. Adami S, Bianchi G, Brandi ML, Giannini S, Ortolani S, DiMunno O, et al.; BONTURNO study group. Determinants of bone turnover markers in healthy premenopausal women. Calcif Tissue Int 2008;82:341–7.10.1007/s00223-008-9126-5Search in Google Scholar PubMed

25. Vasikaran S, Chubb P, Ebeling P, Jenkins N, Jones G, Kotowicz M, et al. Harmonized Australian reference intervals for serum PINP and CTX in adults. Clin Biochem Rev 2014;35:237–42.Search in Google Scholar

26. Vasikaran S, Cooper C, Eastell R, Griesmacher A, Morris HA, Trenti T, et al. International Osteoporosis Foundation and International Federation of Clinical Chemistry and Laboratory Medicine position on bone marker standards in osteoporosis. Clin Chem Lab Med 2011;49:1271–4.10.1515/CCLM.2011.602Search in Google Scholar PubMed

27. Vasikaran S, Eastell R, Bruyère O, Foldes AJ, Garnero P, Griesmacher A, et al. IOF-IFCC Bone Marker Standards Working Group. Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int 2011;22:391–420.10.1007/s00198-010-1501-1Search in Google Scholar PubMed

28. Krege JH, Lane NE, Harris JM, Miller PD. PINP as a biological response marker during teriparatide treatment for osteoporosis. Osteoporos Int 2014;25:2159–71.10.1007/s00198-014-2646-0Search in Google Scholar PubMed PubMed Central

Received: 2015-2-16
Accepted: 2015-5-18
Published Online: 2015-6-18
Published in Print: 2016-2-1

©2016 by De Gruyter

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