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.
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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
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
Deftos LJ, Parthemore JG, Price PA (1982) Changes in plasma bone Gla protein during treatment of bone disease. Calcif Tissue Int 34:121–124
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
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
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
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
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
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
Kruse K (1985) Normal bone turnover in isolated hyperphosphatasemia. J Pediatr 106:946–948
Kruse K, Kracht U (1983) Die Hydroxyprolin-Ausscheidung im Morgen-Urin. Ein geeigneter Parameter des Knochen-Umsatzes im Kindesalter. Monatsschr Kinderheilkd 131:797–803
Kruse K, Kracht U (1985) Isolierte Erhöhung der alkalischen Serum-Phosphatase. Dtsch Med Wochenschr 110:669–674
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
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
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
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
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
Moss DW (1982) Alkaline phosphatase isoenzymes. Clin Chem 28:2007–2016
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
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
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
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
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
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
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
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
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
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
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
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
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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
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DOI: https://doi.org/10.1007/BF00441848