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Serum intact molecule of bone Gla-protein in patients with abnormal bone and calcium metabolism

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Abstract

A circulating level of bone Gla-protein (BGP) has been estimated one of the most promising markers for bone turnover in patients with metabolic bone diseases. Although previous bone histomorphometric studies have revealed that serum BGP levels are mainly related to osteoblastic bone formation, multiple immunoreactive forms of BGP present in uremic sera are attributed to both osteoclastic bone resorption and decreased renal metabolism itself. Chromatography and cross-reactivity tests showed that an immunoradiometric assay (IRMA) for BGP specifically recognizes intact molecules of BGP and excludes BGP fragments found in uremic sera. Serum levels of BGP determined by IRMA were found significantly higher than those determined by radioimmnoassay. Elevated serum BGP levels determined by IRMA in primary hyperparathyroidism decreased and returned within the reference range more than 1 year following successful parathyroidectomy. Intermittent oral administration of high dose of 1,25 (OH)2D3 enhanced elevated serum BGP levels determined by IRMA which significantly increased from the initial levels at week 4 and at week 8, afterwards gradually returning to the basal levels at week 16. In addition, similar treatment effects were observed in serum prcollagen type I c-terminal peptide (P1CP), a marker for bone matrix formation.

In conclusion, the measurement of serum BGP concentration utilizing IRMA, which specifically recognizes intact whole molecules of BGP, is useful to assess bone turnover and treatment effects in metabolic bone diseases, particularly in hyperparathyroidism.

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References

  1. Nakatsuka K, Nishizawa Y, Morii H: Osteoporosis: Its clinical spectrum and pathophysiology. (in Japanese) Metab Dis 28:3–25,1991

    Google Scholar 

  2. Johansen JS, Riis BJ, Delmas PD, Christiansen C: Plasma BGP: An indicator of spontaneous bone loss and of the effect of oestrogen treatment in postmenopausal women. Eur J Clin Invest 18:191–195,1988

    CAS  PubMed  Google Scholar 

  3. Piedra C De la, Torres R, Rapado A, Diaz-Curiel M: Serum procollagen I carboxyterminal extension peptide/serum tartrate resistant acid phosphatase ratio as an index of bone remodeling. Osteoporosis 1990 (eds by Christiansen C, Overgaad K) pp. 892–894,1990

  4. Ljunghall S, Lindh E: Assessment of bone turnover with biochemical markers. J Int Med 225:219–220,1989

    CAS  Google Scholar 

  5. Hauschka PV, Lian JB, Gallop PM: Direct identification of the calcium-binding amini acid, carboxyglutamate, in mineralized tissue. Proc Natl Acad Sci USA 72:3925–3929,1975

    CAS  PubMed  Google Scholar 

  6. Price PA, Otsuka AS, Poser JW, Kristaponis I, Raman N: Characterization of a carboxyglutamic acid-containig protein from bone. Proc Natl Acad Sci USA 73:1447–1451,1976

    CAS  PubMed  Google Scholar 

  7. Parfitt AM, Simon LS, Villanueva AR, Krane SM: Procollagen type I carboxyterminal extension peptide in serum as a marker of a collagen biosynthesis in bone. Correlation with iliac bone formation rates and comparison with total alkaline phosphatase. J Bone Min Res 2:427–436,1987

    CAS  Google Scholar 

  8. Nakatsuka K, Miki T, Nishizawa Y, Tabata T, Inoue T, Morii H, Ogata E: Circulating bone Gla-protein in end-stage renal disease determined by newly developed two-site immunoradiometric assay. (eds by Morii H) Contrib Nephrol Karger: Basel, pp. 147–154, 1991

    Google Scholar 

  9. Price PA, Nishimoto SK: Radioimmunoassay for the vitamin K-dependent protein of bone and its discovery in plasma. Proc Natl Acad Sci USA 77:2234–2238,1980

    CAS  PubMed  Google Scholar 

  10. Gundberg CM, Weinstein RS: Multiple immunoreactive forms of osteocalcin in uremic serum. J Clin Endocrinol Metab 57:1028–1030,1983

    Google Scholar 

  11. Yoshida H, Miki T, Nakatsuka K, Sekiya K, Sasao K, Nishizawa Y, Morii H: Two-site enzymeimmunoassay for serum procollagen type I carboxyterminal peptide in metabolic bone disease. J Bone Min Res 6: 243 (S),1991

    Google Scholar 

  12. Nakatsuka K, Miki T, Nishizawa Y, Morii H, Omae H, Terasawa T, Tabata T, Inoue T: Clinical significance of serum tartrate resistant acid phosphatase activities in patients with end-stage renal disease receiving dialysis. (in Japanese) Kidney Metab Bone Dis 4:301–310,1991

    Google Scholar 

  13. Fukase M, Fujita T, Matsumoto T, Ogata E, Ijima T, Takezawa J, Saito K, Ishige H, Fujimoto M: Clinical studies using a highly sensitive radioimmunoassay for mid-region and carboxy terminal of parathyroid hormone in normal, hypo- and hypercalcemic states. (in Japanese) Folia Endocrinol 65: 807–827,1989

    CAS  Google Scholar 

  14. Lian JB, Friedman PA: The vitamin K-dependent synthesis of gamma carboxyglutamic acid by bone microsome. J Biol Chem 253:6623–6626,1978

    CAS  PubMed  Google Scholar 

  15. Price PA, Williamson MK, Lothringer JW: Origin of the vitamin K dependent bone protein found in plasma and its clearance by kidney and bone. J Biol Chem 256:12760–12766,1981

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  17. Slovic DM, Gundberg CM, Neer RM, Lian JB: Clinical evaluation of bone turnover by serum osteocalcin measurements in a hospital setting. J Clin Endocrinol Metab 59:228–230,1984

    Google Scholar 

  18. Brown JP, Delmas PD, Malaval L, Edouard C, Chapuy MC, Meunier PJ: Serum bpne Gla-protein: A specific marker for bone formation in postmenopausal osteoporosis. Lancet i: 1091–1093,1984

    Google Scholar 

  19. Malluche HH, Faugere MC, Fanti P, Price PA: Plasma levels of bone Gla-protein reflect bone formation in patients on chronic maintenance dialysis. Kidney Int 36:869–874,1984

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  21. Wilkinson MR, Wafstafje C, Delfbrige L, Wiseman J, Posen S: Serum osteocalcin concentrations in Paget's disease of bone. Arch Int Med 146:268–271,1986

    CAS  Google Scholar 

  22. Delmas PD, Demiaux B, Malaval L, Chapuy MC, Edouard C, Meunier PJ: Serum bone gamma carboxyglutamic acid-containing protein in primary hyperparathyroidism and in malignant hypercalcemia. J Clin Invest 77:985–991,1986

    CAS  PubMed  Google Scholar 

  23. Pietschmann P. Niederle B, Anvari A, Woloszczuk W: Serum osteocalcin levels in primary hyperparathyroidism. Klin Wochenschr 69:351–353,1991

    Article  CAS  PubMed  Google Scholar 

  24. Papaoulos SE, Frohlich M, Mudde AH, Marinck LD, Berg HVD, Bijvoet OLM: Serum osteocalcin in Paget's disease of bone: Basal concentrations and response to bisphosphonate treatment. J Clin Endocrinol Metab 65:89–94,1987

    Google Scholar 

  25. Stepan JJ, Lachmanova J, Strakova M, Pacovsky V: Serum osteocalcin, bone alkaline phosphatase and plasma tartrate resistant acid phosphatase in patients on chronic maintenance hemodialysis. Bone Min 3:177–183,1987

    CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  27. Nakatsuka K, Miki T, Nishizawa Y, Iba K, Morii H: Characteristics of biochemical markers for bone formation in the elderly. J Bone Min Metab 10 (in press),1992

  28. Price PA, Baukol SA: 1,25-dihydroxyvitamin D3 increases synthesis of the vitamin K-dependent bone protein by osteosarcoma cells. J Biol Chem 255:11660–11663,1980

    CAS  PubMed  Google Scholar 

  29. Mizunashi K, Furukawa Y, Miura R, Yunita S, Sohn E, Yoshinaga K: Effect of active vitamin D3 and parathyroid hormone on the serum osteocalcin in idiopathic hypoparathyroidism and pseudohypoparathyroidism. J Clin Invest 82:861–865,1988

    CAS  PubMed  Google Scholar 

  30. Coen G, Donato G, Bondatti F, Landi A, Massimetti C, Smacchi A, Cinotti GA: Short and long term effect of 1,25 (OH)2D3 on serum concentrations of bone GLA protein in predislysis chronic renal failure. Proc EDTA-ERA 22:1223–1228, 1985

    Google Scholar 

  31. Duda RJ, Kumar R, Nelson KI, Zinsmeister AR, Mann KG, Riggs BL: 1,25-dihydroxyvitamin D stimulation test for osteoblast function in normal and osteopenic postmenopausal women. J Clin Invest 79:1249–1253,1987

    PubMed  Google Scholar 

  32. Slatopolsky E, Weerts C, Thielan J, Horst R, Harter H, Martin KJ: Marked suppression of secondary hyperparathyroidism by intravenous administration of 1,25-dihydroxycholecalciferol in uremic patients. J Clin Invest 74:2136–2143,1984

    CAS  PubMed  Google Scholar 

  33. Tsukamoto Y, Nomura Y, Marumo F: Pharmacological parathyroidectomy by oral 1,25 (OH)2D3 pulse therapy. Nephron 51:130–131,1989

    CAS  PubMed  Google Scholar 

  34. Chamber TJ, Athanasou NA, Fuller K: Effect of parathyroid hormone and calcitonin on the cytoplasmic apreading of isolated osteoclast. J Endocrinol 102:281–284,1984

    Google Scholar 

  35. Boresford JN, Gallagher JA, Poser JW, Russell RGG: Production of osteocalcin by human bone cells in vitro. Effects of 1,25 (OH)2D3, 24, 25 (OH)2D3, parathyroid hormone and glucocorticoids. Metab Bone Dis Rel Res 5:229–234,1984

    Google Scholar 

  36. Lian JB, Coutts M, Canalis E: Studies of hormonal regulation of osteocalcin synthesis in cultured fetal rat calvaria. J Biol Chem 360:8706–8710,1985

    Google Scholar 

  37. Riggs BL, Tsai KS, Mann KG: Evidence that serum bone Glaprotein is a measure of bone fornation but not bone resorption. Calcif Tissue Int 36: 497 (S),1984

    Google Scholar 

  38. Cole DEC, Gundberg CM: Changes in serum osteocalcin associated with parathyroid hormone infusion in X-linked hypophosphatemic rickets. Clin Chim Acta 151:1–7,1985

    Article  CAS  PubMed  Google Scholar 

  39. Miki T, Nakatsuka K, Tabata T, Nishizawa Y, Morii H: Serum BGP levels in patients with chronic hemodialysis. J Bone Min Metab 9:58–59,1991

    Google Scholar 

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Nakatsuka, K., Miki, T., Shoji, S. et al. Serum intact molecule of bone Gla-protein in patients with abnormal bone and calcium metabolism. J Bone Miner Metab 10, 18–27 (1992). https://doi.org/10.1007/BF02378979

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