Bone Health Laboratory Assessments

  • Anna Neyman
  • Linda A. DiMeglio


Ensuring optimal bone accrual and assessing bone health measures when concerns arise are important aspects of adolescent health care. This chapter reviews laboratory assessments which may be considered, including available normative data, which laboratory assessments are most useful in the initial evaluation of common disorders and concerns, and when a referral to an endocrinologist or other bone specialist should be considered.


Calcium Phosphorus Vitamin D 25-hydroxyvitamin D Alkaline phosphatase Rickets 



The authors would like to thank Dr. Erik Imel for his thoughtful review of this chapter.


  1. 1.
    DiMeglio LA, Imel EA. Calcium and phosphate: hormonal regulation and metabolism. In: Burr DB, Allen MR, editors. Basic and applied bone biology. San Diego: Academic Press; 2014. p. 261–82.CrossRefGoogle Scholar
  2. 2.
    Goltzman D. Approach to hypercalcemia. In: De Groot LJ, Chrousos G, Dungan K, et al., editors. Endotext. South Dartmouth; 2000.Google Scholar
  3. 3.
    Sharratt CL, Gilbert CJ, Cornes MC, Ford C, Gama R. EDTA sample contamination is common and often undetected, putting patients at unnecessary risk of harm. Int J Clin Pract. 2009;63(8):1259–62.CrossRefPubMedGoogle Scholar
  4. 4.
    Richmond W, Colgan G, Simon S, Stuart-Hilgenfeld M, Wilson N, Alon US. Random urine calcium/osmolality in the assessment of calciuria in children with decreased muscle mass. Clin Nephrol. 2005;64(4):264–70.CrossRefPubMedGoogle Scholar
  5. 5.
    Ghazali S, Barratt TM. Urinary excretion of calcium and magnesium in children. Arch Dis Child. 1974;49(2):97–101.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Jones AN, Shafer MM, Keuler NS, Crone EM, Hansen KE. Fasting and postprandial spot urine calcium-to-creatinine ratios do not detect hypercalciuria. Osteoporos Int. 2012;23(2):553–62.CrossRefPubMedGoogle Scholar
  7. 7.
    Metz MP. Determining urinary calcium/creatinine cut-offs for the paediatric population using published data. Ann Clin Biochem. 2006;43(Pt 5):398–401.CrossRefPubMedGoogle Scholar
  8. 8.
    Kiessling SG, Goebel J, Somers MJG. Pediatric nephrology in the ICU. Berlin: Springer; 2009.CrossRefGoogle Scholar
  9. 9.
    Penido MG, Alon US. Phosphate homeostasis and its role in bone health. Pediatr Nephrol. 2012;27(11):2039–48.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Shaw N, Hogler W. Biochemical markers of bone metabolism. In: Glorieux FH, Pettifor JM, Juppner H, editors. Pediatric bone. 2nd ed. Amsterdam: Elsevier/Academic Press; 2012. p. 361–81.CrossRefGoogle Scholar
  11. 11.
    Manghat P, Sodi R, Swaminathan R. Phosphate homeostasis and disorders. Ann Clin Biochem. 2014;51(Pt 6):631–56.CrossRefPubMedGoogle Scholar
  12. 12.
    Payne RB. Renal tubular reabsorption of phosphate (TmP/GFR): indications and interpretation. Ann Clin Biochem. 1998;35(Pt 2):201–6.CrossRefPubMedGoogle Scholar
  13. 13.
    de Baaij JH, Hoenderop JG, Bindels RJ. Magnesium in man: implications for health and disease. Physiol Rev. 2015;95(1):1–46.CrossRefPubMedGoogle Scholar
  14. 14.
    Brown EM, Chen CJ. Calcium, magnesium and the control of PTH secretion. Bone Miner. 1989;5(3):249–57.CrossRefPubMedGoogle Scholar
  15. 15.
    Blaine J, Chonchol M, Levi M. Renal control of calcium, phosphate, and magnesium homeostasis. Clin J Am Soc Nephrol. 2015;10(7):1257–72.CrossRefPubMedGoogle Scholar
  16. 16.
    Ayuk J, Gittoes NJ. How should hypomagnesaemia be investigated and treated? Clin Endocrinol. 2011;75(6):743–6.CrossRefGoogle Scholar
  17. 17.
    Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911–30.CrossRefPubMedGoogle Scholar
  18. 18.
    Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266–81.CrossRefPubMedGoogle Scholar
  19. 19.
    Munns CF, Shaw N, Kiely M, et al. Global consensus recommendations on prevention and management of nutritional rickets. J Clin Endocrinol Metab. 2016;101(2):394–415.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Shieh A, Chun RF, Ma C, et al. Effects of high-dose vitamin D2 versus D3 on total and free 25-hydroxyvitamin D and markers of calcium balance. J Clin Endocrinol Metab. 2016;101(8):3070–8.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Binkley N, Krueger DC, Morgan S, Wiebe D. Current status of clinical 25-hydroxyvitamin D measurement: an assessment of between-laboratory agreement. Clin Chim Acta. 2010;411(23–24):1976–82.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Farrell CJ, Martin S, McWhinney B, Straub I, Williams P, Herrmann M. State-of-the-art vitamin D assays: a comparison of automated immunoassays with liquid chromatography-tandem mass spectrometry methods. Clin Chem. 2012;58(3):531–42.CrossRefPubMedGoogle Scholar
  23. 23.
    Binkley N, Dawson-Hughes B, Durazo-Arvizu, Thamm M, Tian L, Merkel JM, Jones JC, Carter GD, Sempos CT. Vitamin D measurement standardization: the way out of the chaos. J Steroid Biochem Mol Biol. 2017;173:117–21.Google Scholar
  24. 24.
    Zittermann A, Ernst JB, Becker T, et al. Measurement of circulating 1,25-dihydroxyvitamin D: comparison of an automated method with a liquid chromatography tandem mass spectrometry method. Int J Anal Chem. 2016;2016:8501435.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Endocrine Society. Choosing wisely: don’t routinely measure 1,25-dihydroxyvitamin D unless the patient has hypercalcemia or decreased kidney function. 2013. Available at: Accessed Oct 2017.
  26. 26.
    Martin KJ, Akhtar I, Gonzalez EA. Parathyroid hormone: new assays, new receptors. Semin Nephrol. 2004;24(1):3–9.CrossRefPubMedGoogle Scholar
  27. 27.
    D’Amour P. Circulating PTH molecular forms: what we know and what we don’t. Kidney Int Suppl. 2006;102:S29–33.CrossRefGoogle Scholar
  28. 28.
    Martin TJ. Parathyroid hormone-related protein, its regulation of cartilage and bone development, and role in treating bone diseases. Physiol Rev. 2016;96(3):831–71.CrossRefPubMedGoogle Scholar
  29. 29.
    Chew CK, Clarke BL. Biochemical testing relevant to bone. Endocrinol Metab Clin N Am. 2017;46(3):649–67.CrossRefGoogle Scholar
  30. 30.
    Saraff V, Narayanan VK, Lawson AJ, Shaw NJ, Preece MA, Hogler W. A diagnostic algorithm for children with low alkaline phosphatase activities: lessons learned from laboratory screening for hypophosphatasia. J Pediatr. 2016;172:181–186 e181.CrossRefPubMedGoogle Scholar
  31. 31.
    Wheater G, Elshahaly M, Tuck SP, Datta HK, van Laar JM. The clinical utility of bone marker measurements in osteoporosis. J Transl Med. 2013;11:201.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Quarles LD. Role of FGF23 in vitamin D and phosphate metabolism: implications in chronic kidney disease. Exp Cell Res. 2012;318(9):1040–8.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Schiavi SC, Kumar R. The phosphatonin pathway: new insights in phosphate homeostasis. Kidney Int. 2004;65(1):1–14.CrossRefPubMedGoogle Scholar
  34. 34.
    El-Maouche D, Dumitrescu CE, Andreopoulou P, et al. Stability and degradation of fibroblast growth factor 23 (FGF23): the effect of time and temperature and assay type. Osteoporos Int. 2016;27(7):2345–53.CrossRefPubMedGoogle Scholar
  35. 35.
    Folsom LJ, Imel EA. Hyperphosphatemic familial tumoral calcinosis: genetic models of deficient FGF23 action. Curr Osteoporos Rep. 2015;13(2):78–87.CrossRefPubMedGoogle Scholar
  36. 36.
    Gelfand IM, Eugster EA, DiMeglio LA. Presentation and clinical progression of pseudohypoparathyroidism with multi-hormone resistance and Albright hereditary osteodystrophy: a case series. J Pediatr. 2006;149(6):877–80.CrossRefPubMedGoogle Scholar
  37. 37.
    Lietman SA, Germain-Lee EL, Levine MA. Hypercalcemia in children and adolescents. Curr Opin Pediatr. 2010;22(4):508–15.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Attie MF, Gill JR Jr, Stock JL, et al. Urinary calcium excretion in familial hypocalciuric hypercalcemia. Persistence of relative hypocalciuria after induction of hypoparathyroidism. J Clin Invest. 1983;72(2):667–76.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Hendy GN, Guarnieri V, Canaff L. Calcium-sensing receptor and associated diseases. Prog Mol Biol Transl Sci. 2009;89:31–95.CrossRefPubMedGoogle Scholar
  40. 40.
    Kelly A, Levine M. Disorders of calcium, phosphate, parathyroid hormone and vitamin D. In: Kappy M, Allen D, Geffner M, editors. Pediatric practice: endocrinology. Springfield: Thomas Publisher; 2009. p. 191–256.Google Scholar
  41. 41.
    Root AW, Diamond FB. Chapter 18 – Disorders of mineral homeostasis in children and adolescents. In: Sperling MA, editor. Pediatric endocrinology. Philadelphia: Saunders; 2014. p. 734–845.e731.Google Scholar
  42. 42.
    Carpenter TO, Imel EA, Holm IA, Jan de Beur SM, Insogna KLA. Clinician’s guide to X-linked hypophosphatemia. J Bone Miner Res. 2011;26(7):1381–8.Google Scholar
  43. 43.
    Bohm NM, Hoover KC, Wahlquist AE, Zhu Y, Velez JC. Case-control study and case series of pseudohyperphosphatemia during exposure to liposomal amphotericin B. Antimicrob Agents Chemother. 2015;59(11):6816–23.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Tripkovic L, Lambert H, Hart K, et al. Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis. Am J Clin Nutr. 2012;95(6):1357–64.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Ferrari S, Bianchi ML, Eisman JA, et al. Osteoporosis in young adults: pathophysiology, diagnosis, and management. Osteoporos Int. 2012;23(12):2735–48.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Pediatrics, Division of Pediatric Endocrinology/DiabetologyRiley Hospital for Children at Indiana University Health, Indiana University School of MedicineIndianapolisUSA

Personalised recommendations