Skip to main content
Log in

Evaluation of serum osteocalcin as an index of altered bone metabolism

  • Original Investigations
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Recent evidence suggests that the protein osteocalcin is like the bone alkaline phosphatase produced by osteoblasts and circulates in human blood. With the introduction of a radioimmunoassay for serum osteocalcin it was hoped that this test would provide a useful index of altered bone metabolism. Therefore serum osteocalcin was measured in 88 controls and 112 patients with disorders of calcium and phosphate metabolism, isolated elevation of alkaline serum phosphatase in the absence of disease (isolated hyperphosphatasaemia) and children prone to osteopenia.

In the controls serum osteocalcin was higher in children<15 years (median and range: 11.9, 7.7–15.3 ng/ml) than in adults (3.7, 2.6–5.2 ng/ml) and was highly correlated to alkaline serum phosphatase activity (r=0.87, n=88, P<0.01). Osteocalcin was elevated in primary hypoparathyroidism, low in untreated hypoparathyroidism but normal in hypoparathyroidism (including pseudohypoparathyroidism) during vitamin D treatment. The bone protein was low-normal and increased to high-normal levels during vitamin D therapy in vitamin D deficiency rickets and familial hypophosphataemic rickets, but remained low in patients with end organ resistance to 1,25-dihydroxyvitamin D. Osteocalcin (and urinary hydroxyproline) were not elevated in isolated hyperphosphatasaemia, indicating that mechanisms other than increased bone turnover may account for the markedly elevated serum alkaline phosphatase activity in these subjects. Osteocalcin was decreased in children with diabetes mellitus type I and in patients on glucocorticoid treatment, indicating decreased bone formation. It is concluded that the measurement of serum osteocalcin seems to be a reliable index of bone formation provided that the vitamin D status and renal function are normal. Although serum osteocalcin and alkaline phosphatase were generally correlated there were examples of dissociation between both indices. In some circumstances (e.g. rickets) serum osteocalcin may severe as a useful index of an effective therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

AP:

alkaline phosphatase activity

Gla:

gammacarboxy-glutamic acid

1,25 (OH)2D3 :

1,25-dihydroxyvitamin

D3 :

calcitriol

PTH:

parathyroid hormone

HP:

hypoparathyroidism

PHP:

pseudohypoparathyroidism

IoHPT:

primary hyperparathyroidism

VDR:

vitamin D deficiency rickets

VDDR II:

vitamin D dependency rickets type II

FHL:

familial hypophosphataemic rickets

IH:

isolated hyperphosphatasaemia in the absence of disease

References

  1. Chesney RW, Mazess RB, Hamstra AJ, DeLuca HF, O'Reagan S (1978) Reduction of serum-1,25-dihydroxyvitamin-D3 in children receiving glucocorticoids. Lancet 2:1123–1125

    Google Scholar 

  2. Deftos LJ, Parthemore JG, Price PA (1982) Changes in plasma bone Gla protein during treatment of bone disease. Calcif Tissue Int 34:121–124

    Google Scholar 

  3. Delmas PD, Wahner HW, Mann KG, Riggs BL (1983) Assessment of bone turnover in postmenopausal osteoporosis by measurement of serum bone Gla-protein. J Lab Clin Med 102:470–476

    Google Scholar 

  4. Delmas PD, Wilson DM, Mann KG, Riggs LB (1983) Effect of renal function on plasma levels of bone Gla-protein. J Clin Endocrinol Metab 57:1028–1030

    Google Scholar 

  5. Gundberg CM, Cole DEC, Lian LB, Reade TM, Gallop PM (1983) Serum osteocalcin in the treatment of inherited rickets with 1,25-dihydroxyvitamin D3. J Clin Endocrinol Metab 56:1063–1067

    Google Scholar 

  6. Gundberg CM, Lian JB, Gallop PM, Steinberg JJ (1983) Urinary γ-carboxyglutamic acid and serum osteocalcin as bone markers: studies in osteoporosis and Paget's disease. J Clin Endocrinol Metab 57:1221–1225

    Google Scholar 

  7. Hausamen T-U, Helger R, Rick W, Gross W (1967) Optimal conditions for the determination of serum alkaline phosphatase by a new kinetic method. Clin Chim Acta 15:241–245

    Google Scholar 

  8. Hauschka PV, Lian JB, Gallop PM (1975) Direct indentification of the calcium-binding amino acid, γ-carboxyglutamate, in mineralized tissue. Proc Natl Acad Sci USA 72:3925–3929

    Google Scholar 

  9. Kruse K (1985) Normal bone turnover in isolated hyperphosphatasemia. J Pediatr 106:946–948

    Google Scholar 

  10. Kruse K, Kracht U (1983) Die Hydroxyprolin-Ausscheidung im Morgen-Urin. Ein geeigneter Parameter des Knochen-Umsatzes im Kindesalter. Monatsschr Kinderheilkd 131:797–803

    Google Scholar 

  11. Kruse K, Kracht U (1985) Isolierte Erhöhung der alkalischen Serum-Phosphatase. Dtsch Med Wochenschr 110:669–674

    Google Scholar 

  12. Lauffenburger T, Olah AJ, Dambacher MA, Guncaga J, Lentner C, Haas HG (1977) Bone remodeling and calcium metabolism: a correlated histomorphometric, calcium kinetic, and biochemical study in patients with osteoporosis and Paget's disease. Metabolism 26:589–605

    Google Scholar 

  13. Levin ME, Boisseau VC, Avioli LV (1976) Effects of diabetes mellitus on bone mass in juvenile and adult-onset diabetes. N Engl J Med 294:241–245

    Google Scholar 

  14. Lobaugh B, Burch WM, Drezner MK (1984) Abnormalities of vitamin D metabolism and action in the vitamin D resistant rachitic and osteomalacic diseases. In: Kumar R (ed) Vitamin D metabolism: basic and clinical aspects. Nijhof, The Hague, 665–720

    Google Scholar 

  15. Markestad T, Halvorsen S, Seeger Halvorsen K, Aksnes L, Aarskog D (1984) Plasma concentrations of vitamin D metabolites before and during treatment of vitamin D deficiency rickets in children. Acta Paediatr Scand 73:225–231

    Google Scholar 

  16. Marx SJ, Liberman UA, Eil C, Gamblin GT, DeGrange DA, Balsan S (1984) Hereditary resistance to 1,25-dihydroxyvitamin D. Recent Prog Horm Res 40:589–620

    Google Scholar 

  17. Moss DW (1982) Alkaline phosphatase isoenzymes. Clin Chem 28:2007–2016

    Google Scholar 

  18. Pødenphant J, Christiansen C, Catherwood BD, Deftos L (1984) Serum bone Gla protein variations during estrogen and calcium prophylaxis of postmenopausal women. Calcif Tissue Int 36:536–540

    Google Scholar 

  19. Posen S, Lee C, Vines R, Kilham H, Latham S, Keefe JF (1977) Transient hyperphosphatasemia of infancy — an insufficiently recognized syndrome. Clin Chem 23:292–296

    Google Scholar 

  20. Poser JW, Esch FS, Ling HC, Price PA (1980) Isolation and sequence of the vitamin K-dependent protein from human bone. Undercarboxylation of the first glutamic acid residue. J Biol Chem 255:8685–8691

    Google Scholar 

  21. Price PA (1984) The effect of 1,25-dihydroxyvitamin D3 on the vitamin K-dependent protein of bone. In: Kumar R (ed) Vitamin D metabolism: basic and clinical aspects. Nijhof, The Hague, 397–410

    Google Scholar 

  22. Price PA, Baukol SA (1981) 1,25-dihydroxyvitamin D3 increases serum levels of the vitamin K-dependent bone protein. Biochem Biophys Res Commun 99:928–935

    Google Scholar 

  23. Price PA, Otsuka AS, Poser JW, Kristaponis J, Raman N (1976) Characterization of a γ-carboxyglutamic acid-containing protein from bone. Proc Natl Acad Sci USA 73:1447–1451

    Google Scholar 

  24. Price PA, Parthemore JG, Deftos LJ (1980) New biochemical marker of bone metabolism. Measurement by radioimmunoassay of bone Gla protein in the plasma of normal subjects and patients with bone disease. J Clin Invest 66:878–883

    Google Scholar 

  25. 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 256:12760–12766

    Google Scholar 

  26. Rosenbloom AL, Lezotte DC, Weber FT, Gudat J, Heller DR, Weber ML, Klein S, Kennedy BB (1977) Diminution of bone mass in childhood diabetes. Diabetes 26:1052–1055

    Google Scholar 

  27. Uhlig R (1981) Familiäre Pseudovitamin-D-Mangelrachitis mit Alopezie als Folge von hochgradiger Endorganresistenz gegen 1,25-(OH)2-Cholecalciferol. Therapierbarkeit einer weiteren Vitamin-D3-Stoffwechselstörung. Monatschr Kinderheilkd 129: 420–422

    Google Scholar 

  28. Wiske PS, Wentworth SM, Norton JA Jr, Epstein S, Johnston CC Jr (1982) Evaluation of bone mass and growth in young diabetics. Metabolism 31:848–854

    Google Scholar 

  29. Zerwekh JE, Sakhaee K, Pak CYC (1985) Short-term 1,25-dihydroxyvitamin D3 administration raises serum osteocalcin in patients with postmenopausal osteoporosis. J Clin Endocrinol Metab 60:615–617

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kruse, K., Kracht, U. Evaluation of serum osteocalcin as an index of altered bone metabolism. Eur J Pediatr 145, 27–33 (1986). https://doi.org/10.1007/BF00441848

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00441848

Key words

Navigation