Clinical Use of Bone Markers: a Challenge to Variability

Overview

Journal Adv Lab Med

Publisher De Gruyter

Specialty Biochemistry

Date 2024 Apr 18

PMID 38634081

Authors

Xavier Filella

Nuria Guanabens

Affiliations

Soon will be listed here.

Abstract

Bone markers are a group of substances released into circulation during bone formation and/or resorption. These substances can be measured in blood and urine to obtain information about metabolic bone disorders. This review provides an insight into factors influencing bone marker variability and describes different approaches to minimize variability and interpret results appropriately. Variability in bone marker concentrations results from biological and analytical variability across assays. Other influencing factors include gender, age, physical exercise, circadian rhythm, and diet. The multiplicity of influencing factors hinders the establishment of accurate reference values. Gaining a deep understanding of bone marker variability is the first step to ascertain their clinical usefulness. Bone marker variability can be minimized by controlling as many variables as it is possible and through the standardization of patient preparation and sample collection and handling.

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References

Vasikaran S, Cooper C, Eastell R, Griesmacher A, Morris H, Trenti T . 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(8):1271-1274. DOI: 10.1515/CCLM.2011.602. View

Heijboer A, Cavalier E . The Measurement and Interpretation of Fibroblast Growth Factor 23 (FGF23) Concentrations. Calcif Tissue Int. 2022; 112(2):258-270. PMC: 9859838. DOI: 10.1007/s00223-022-00987-9. View

Garnero P . The Utility of Biomarkers in Osteoporosis Management. Mol Diagn Ther. 2017; 21(4):401-418. DOI: 10.1007/s40291-017-0272-1. View

Bollen A, Martin M, Leroux B, Eyre D . Circadian variation in urinary excretion of bone collagen cross-links. J Bone Miner Res. 1995; 10(12):1885-90. DOI: 10.1002/jbmr.5650101207. View

Szulc P, Naylor K, Hoyle N, Eastell R, Leary E . Use of CTX-I and PINP as bone turnover markers: National Bone Health Alliance recommendations to standardize sample handling and patient preparation to reduce pre-analytical variability. Osteoporos Int. 2017; 28(9):2541-2556. DOI: 10.1007/s00198-017-4082-4. View

Brown J, Albert C, Nassar B, Adachi J, Cole D, Davison K . Bone turnover markers in the management of postmenopausal osteoporosis. Clin Biochem. 2009; 42(10-11):929-42. DOI: 10.1016/j.clinbiochem.2009.04.001. View

Eastell R, Mallinak N, Weiss S, Ettinger M, Pettinger M, Cain D . Biological variability of serum and urinary N-telopeptides of type I collagen in postmenopausal women. J Bone Miner Res. 2000; 15(3):594-8. DOI: 10.1359/jbmr.2000.15.3.594. View

Schafer A, Vittinghoff E, Ramachandran R, Mahmoudi N, Bauer D . Laboratory reproducibility of biochemical markers of bone turnover in clinical practice. Osteoporos Int. 2009; 21(3):439-45. PMC: 2817087. DOI: 10.1007/s00198-009-0974-2. View

Gundberg C, Markowitz M, Mizruchi M, Rosen J . Osteocalcin in human serum: a circadian rhythm. J Clin Endocrinol Metab. 1985; 60(4):736-9. DOI: 10.1210/jcem-60-4-736. View

10.

Smith E, Cai M, McMahon L, Holt S . Biological variability of plasma intact and C-terminal FGF23 measurements. J Clin Endocrinol Metab. 2012; 97(9):3357-65. DOI: 10.1210/jc.2012-1811. View

11.

Lombardi G, Lanteri P, Colombini A, Banfi G . Blood biochemical markers of bone turnover: pre-analytical and technical aspects of sample collection and handling. Clin Chem Lab Med. 2012; 50(5):771-89. DOI: 10.1515/cclm-2011-0614. View

12.

Diez-Perez A, Naylor K, Abrahamsen B, Agnusdei D, Brandi M, Cooper C . International Osteoporosis Foundation and European Calcified Tissue Society Working Group. Recommendations for the screening of adherence to oral bisphosphonates. Osteoporos Int. 2017; 28(3):767-774. PMC: 5302161. DOI: 10.1007/s00198-017-3906-6. View

13.

Carpenter T, Insogna K, Zhang J, Ellis B, Nieman S, Simpson C . Circulating levels of soluble klotho and FGF23 in X-linked hypophosphatemia: circadian variance, effects of treatment, and relationship to parathyroid status. J Clin Endocrinol Metab. 2010; 95(11):E352-7. PMC: 2968736. DOI: 10.1210/jc.2010-0589. View

14.

Vazquez-Sanchez S, Poveda J, Navarro-Garcia J, Gonzalez-Lafuente L, Rodriguez-Sanchez E, Ruilope L . An Overview of FGF-23 as a Novel Candidate Biomarker of Cardiovascular Risk. Front Physiol. 2021; 12:632260. PMC: 7985069. DOI: 10.3389/fphys.2021.632260. View

15.

Morris H, Eastell R, Jorgensen N, Cavalier E, Vasikaran S, Chubb S . Clinical usefulness of bone turnover marker concentrations in osteoporosis. Clin Chim Acta. 2016; 467:34-41. DOI: 10.1016/j.cca.2016.06.036. View

16.

Glover S, Garnero P, Naylor K, Rogers A, Eastell R . Establishing a reference range for bone turnover markers in young, healthy women. Bone. 2008; 42(4):623-30. DOI: 10.1016/j.bone.2007.12.218. View

17.

Brown J, Don-Wauchope A, Douville P, Albert C, Vasikaran S . Current use of bone turnover markers in the management of osteoporosis. Clin Biochem. 2022; 109-110:1-10. DOI: 10.1016/j.clinbiochem.2022.09.002. View

18.

Florez H, Hernandez-Rodriguez J, Carrasco J, Filella X, Prieto-Gonzalez S, Monegal A . Low serum osteocalcin levels are associated with diabetes mellitus in glucocorticoid treated patients. Osteoporos Int. 2021; 33(3):745-750. DOI: 10.1007/s00198-021-06167-z. View

19.

Adami S, Bianchi G, Brandi M, Giannini S, Ortolani S, DiMunno O . Determinants of bone turnover markers in healthy premenopausal women. Calcif Tissue Int. 2008; 82(5):341-7. DOI: 10.1007/s00223-008-9126-5. View

20.

Cavalier E, Lukas P, Bottani M, Aarsand A, Ceriotti F, Coskun A . European Biological Variation Study (EuBIVAS): within- and between-subject biological variation estimates of β-isomerized C-terminal telopeptide of type I collagen (β-CTX), N-terminal propeptide of type I collagen (PINP), osteocalcin, intact.... Osteoporos Int. 2020; 31(8):1461-1470. DOI: 10.1007/s00198-020-05362-8. View