ESTABLISHMENT OF REFERENCE INTERVAL FOR SOME BONE TURNOVER MARKERS IN HEALTHY, YOUNG, PREMENOPAUSAL EGYPTIAN FEMALES.
- Medical Research Institute, Alexandria University, 165 El-Horreya Avenue, El-Hadara, Alexandria, Egypt.
- Department of Biostatistics, High Institute of Public Health, Alexandria University & FAMCO at UoD.
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Introduction :The appropriateness of Laboratory tests selection and reliability of reference interval is crucial for healthcare delivery and clinical diagnosis. Bone remodeling is a physiological process that occurs continuously in healthy adult bone tissue with coupling of both resorption and formation. Bone turnover markers (BTMs) are classified as either bone formation, or resorption markers. Several BTM reference intervals for healthy premenopausal women have previously been established. This study aims to establish robust reference intervals for some bone turnover markers namely ; alkaline phosphatase , Calcium . Phosphorous , 25(OH) vit D , Carboxy-terminal collagen cross links (CTX-I) in healthy premenopausal Egyptian females between the age of 30-45 yrs. Material and methods : The sample of this study was age-stratified random sample , one hundred fifty one females aged between 30-45years participated and only 131 fulfilled the inclusion criteria and completed all lab tests and the questionnaire. Results : The results showed no statistically significant correlation between age and any of the studied parameters except phosphorus (weak indirect correlation rs=-0.189) and Vit D (intermediate correlation rs=-0.58). Ca and phosphorous and ALK did not statistically differ from the manufacturer .Concerning CTX and Vit D the new averages were lower than that set by the manufacturer , the differences were statistically significant (t=-10.2, p=0.0001 for CTX, and t=-19.7, p=0.0001 for Vit D) . While, the new average for PTH was higher than that of the manufacturer, the difference was statistically significant (t=10.9, p=0.0001).Conclusion : Our trial for establishment of reference interval in Egyptian population may help in harmonization of reporting by Egyptian laboratories. The strength points of this study are the standardization of the preanalytical and analytical conditions with adherence to the CLSI guidelines recommendations together with considering seasonal variation. The small sample size and the absence of the bone mineral density data with relatively low level of 25OHD were the limitations of this study .For a new or improved assay for BTM it is important to include a larger sample size with for a clinical reliable reference range to be used in assessment of the efficancy of the antiresorptive therapy. Key words: Bone turnover markers, reference interval, osteoporosis, premenopause.
- CLSI, defining, establishing and verifying reference intervals in the clinical laboratory; approved guideline ? third edition. C28-A3.Volume 28 No. 30.
- A. Ibrahim,1 M.A. Samy,1 M.K. Matter 1 and A.O.L. Saleh . Bone mineral density in Egyptian adolescents and adults with short stature: results of a national survey EMHJ ? 2011: 17 (8);687-93.
- Cairo University Hospitals.KDIC NEWSLETTER:Vol.3 issue 4 Apr.2012
- Al-Ghazawy O. The growing danger of osteoporosis in the Arab world. nmiddleeast.2011 doi:10.1038/nmiddleeast.2011.158; Published online?29 November 2011
- MohyTaha, MD, (2011) Prevalence of osteoporosis in Middle East systemic literature review, 10th ECOO, April 2011- http://www.scribd.com/ doc/53103901/Osteopoorosis-Cairo-April-2011-v1
- Handa R, Kalla A, Maalouf G. Osteoporosis in developing countries. Best Practice & Research Clinical Rheumatology 2008: 22( 4); 693?708
- EMEA?CHMP (2007) Guidelines on the evaluation of new medicinal products in the treatment of primary osteoporosis.http://www.emea.europa.eu/pdfs/human/ewp/055295en.pdf. Accessed 7 September 2007
8.??? The clinical utility of bone marker measurements in osteoporosis.Gillian?Wheater, Mohsen?Elshahaly, Stephen?P?Tuck, Harish?K?Datta?and Jacob?M?van Laar .Journal of Translational Medicine201311:201 DOI:?10.1186/1479-5876-11-201
- Determinants of Bone Turnover Markers in Healthy Premenopausal Women.SilvanoAdami, Gerolamo Bianchi, Maria Luisa Brandi, SandroGiannini,SergioOrtolani , OmbrettaDiMunno, Bruno Frediani, Maurizio Rossini, On behalf of the BONTURNO study group. Calcif Tissue Int (2008) 82:341?347. DOI 10.1007/s00223-008-9126-5.
- E. de Papp et al. / Bone 40 (2007) 1222?1230.
- Seibel MJ. Biochemical markers of bone turnover: part I: biochemistry and variability. ClinBiochem Rev2005;26:97-122.
- Samuel D Vasikaran, SA Paul Chubb,Peter R Ebeling, Nicole Jenkins, Graham RD Jones, Mark A Kotowicz, Howard A Morris, Hans-Gerhard Schneider, Markus J Seibel, Greg Ward. Mini-Review,Harmonised Australian Reference Intervals for Serum PINP and CTX in Adults. ClinBiochem Rev 2014; 35: 237-42.
- Vasikaran S, Eastell R, Bruy?re O, Foldes AJ, Garnero P, Griesmacher A, et al; IOF-IFCC Bone Marker StandardsWorking Group. Markers of bone turnover for theprediction of fracture risk and monitoring of osteoporosistreatment: a need for international reference standards.OsteoporosInt 2011;22:391-420.
- Naylor K, Eastell R. Bone turnover markers: use in osteoporosis. Nat Rev Rheumatol 2012;8:379?89.
- 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 baselinein osteoporosis. J Bone Spine 2012;79:20?5.
- Garnero P. Bone markers in osteoporosis.CurrOsteoporos Rep2009;7:84?90.
- 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, premenopausalwomen from the United Kingdom, France, Belgium, and the United States. J Bone Miner Res 2009;24:389 397.
- Cerda Gabaroi D, Peris P, Monegal A, Albaladejo C, Martinez MA, Muxi A, et al. Search for hidden secondary causes in postmenopausalwomen with osteoporosis. Menopause 2010;17:135?9.
- Fitzpatrick L. Secondary causes of osteoporosis. Mayo ClinProc2002;77:453?68.
- F Gossiel, J Finigan, R Jacques, D Reid, D Felsenberg, C Roux, C Glueer, R Eastell. Establishingreference intervals for bone turnover markers in healthy postmenopausal women in a nonfasting state.BoneKEy Reports 2014; 3:573. doi:10.1038/bonekey.2014.68.
- 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.
- Eastell R, Christiansen C, Grauer A, Kutilek S, Libanati C, McClung MR, et al. Effects of denosumab on bone turnovermarkers in postmenopausal osteoporosis. J Bone Miner Res2011;26:530?7.
- P. Wu, E. Y. Liao, G. Huang, R. C. Dai, and H. Zhang, ?A comparison study of the reference curves of bone mineral density at different skeletal sites in nativeChinese, Japanese, and American Caucasian women,? Calcified Tissue International, vol. 73, no. 2, pp. 122?132, 2003
- Hannon R, Eastell R (2000) Preanalytical variability of biochemical markers of bone turnover. OsteoporosInt 11(Suppl 6):S30?S44.
- Glover SJ, Garnero P, Naylor K, Rogers A, Eastell R. Establishing a reference range for bone turnover markers in young, healthy women. Bone 2008;42:623 630.
- Adami S, Bianchi G, Brandi ML, Giannini S, Ortolani S, DiMunno O et al. Determinants of bone turnover markers in healthy premenopausal women. Calcif Tissue Int 2008;82:341 347.
- Eastell R, Garnero P, Audebert C, Cahall DL. Reference intervals of bone turnover markers inhealthy premenopausal women: results from a cross-sectional European study. Bone 2012;50:1141 1147.
- de Papp AE, Bone HG, Caulfield MP, Kagan R, Buinewicz A, Chen E, et al. A cross-sectional study of bone turnover markersin healthy premenopausal women. Bone 2007;40:1222?30.
- 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.
- Martinez J, Olmos JM, Hernandez JL, Pinedo G, Llorca J, Obregon E, et al. Bone turnover markers in Spanish postmenopausal women: the Camargo cohort study. ClinChimActa 2009;409:70?4.
- Kanterewicz E, Peris P, Puigoriol E, Yanez A, Rosique P, DelRio L; FRODOS Research Group. Distribution of serum βCTX ina population-based study of postmenopausal women takinginto account different anti-osteoporotic therapies (the FRODOSCohort).J Bone Miner Metab 2013;31:231?9.
- Dominguez Cabrera C, Sosa Henriquez M, Traba ML, Alvarez VillafaneE, de la Piedra C. Biochemical markers of bone formationin the study of postmenopausal osteoporosis. OsteoporosInt1998;8:147?51.
- Rubert M, Martinez MJ, de la Piedra C. Normal values of the aminoterminalpropeptide of type I collagen (PINP) and the isomerbeta I collagen carboxyterminaltelopeptide (βCTX) in serum ofhealthy premenopausal women of the Community of Madrid. Rev OsteoporosMetab Miner 2014;6:20?2.
- Wei-Wei Hu, Zeng Zhang, Jin-Wei He, Wen-Zhen Fu, ChunWang, Hao Zhang, HuaYue,Jie-Mei Gu, and Zhen-Lin Zhang. Research Article.Establishing Reference Intervals for Bone Turnover Markers inthe Healthy Shanghai Population and the Relationship withBone Mineral Density in Postmenopausal Women.International Journal of Endocrinology. 2013, Article ID 513925, 7 pages
- Melton LJ III, Atkinson EJ, O?Fallon WM, Wahner HW, RiggsBL (1993) Long-term fracture prediction by bone mineralassessed at different skeletal sites. J Bone Miner Res 8:1227?1233.
- Hu W, et al. Establishing Reference Intervals for Bone Turnover Markers in the Healthy Shanghai Population and the Relationship with Bone Mineral Density in Postmenopausal Women. International Journal of Endocrinology 2013
- Stokes FJ, Ivanov P, Bailey LM, Fraser WD.The effectsof sampling procedures and storage conditions on shorttermstability of blood-based biochemical markers ofbone metabolism.ClinChem 2011;57:138-40
- Khosrow Adeli,1* Victoria Higgins,1 Michelle Nieuwesteeg,1 Joshua E. Raizman,1 Yunqi Chen,1 Suzy L. Wong,2 and David Blais. Biochemical Marker Reference Values across Pediatric, Adult, and Geriatric Ages: Establishment of Robust Pediatric and Adult Reference Intervals on the Basis of the Canadian Health Measures Survey. Clinical Chemistry 61:8 1049?1062 (2015)
- Jenkins, M. Black, E. Paul, J.A. Pasco, M.A. Kotowicz, H.-G. Schneider. Original Full Length ArticleAge-related reference intervals for bone turnover markers from anAustralian reference population. Bone 55 (2013) 271?276
- Lenora J, Ivaska KK, Obrant KJ, Gerhem P. Prediction of bone loss using biochemicalmarkers of bone turnover. OsteoporosInt 2007;18(9):1297?305.
- Qvist P, Christgau P, Pedersen BJ, Schlemmer A, Christiansen C. Circadian variation in the serum concentration of C-terminal telopeptides of type I collagen (serum CTX): effects of gender, age, menopausal status, posture, daylight, serum cortisol and fasting. Bone 2002;31:57?61.
- Chiu KM, Ju J Mayes D, Bacchetti P, Weitz S, Arnaud CD, Changes in bone resorption during menstrual cycle. J Bone Miner Res 1999;14: 609?15.
[Rania Mohamed El Sharkawy, Noha S. Kandil and MoatazaM. Abdel Wahab (2017); ESTABLISHMENT OF REFERENCE INTERVAL FOR SOME BONE TURNOVER MARKERS IN HEALTHY, YOUNG, PREMENOPAUSAL EGYPTIAN FEMALES. Int. J. of Adv. Res. 5 (Mar). 1522-1531] (ISSN 2320-5407). www.journalijar.com
1Medical Research Institute, Alexandria University, 165 El-Horreya Avenue, El-Hadara, Alexandria, Egypt