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. 1987 Apr;79(4):1249–1253. doi: 10.1172/JCI112944

1,25-Dihydroxyvitamin D stimulation test for osteoblast function in normal and osteoporotic postmenopausal women.

R J Duda Jr, R Kumar, K I Nelson, A R Zinsmeister, K G Mann, B L Riggs
PMCID: PMC424323  PMID: 3494046

Abstract

The cause of bone loss in postmenopausal osteoporosis--decreased bone formation or increased bone resorption--is controversial. Synthesis of bone--Gla protein (BGP), a specific osteoblast product, is stimulated by 1,25-dihydroxyvitamin D3 [1,25(OH)2D] in vitro. Thus, increases in serum BGP levels during 1,25(OH)2D administration might provide a useful dynamic index of osteoblast function. We compared 14 postmenopausal osteoporotic women with 12 age-matched postmenopausal normal women before and during 6 d of 1,25(OH)2D administration (2.0 micrograms/d). Serum BGP levels were similar at baseline and increased during treatment in both groups (P less than 0.001). However, trend analysis showed a greater (P less than 0.01) increase in the osteoporotic women. These data do not support the hypothesis that defective osteoblast function is the major cause of bone loss in postmenopausal osteoporosis.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beresford J. N., Gallagher J. A., Poser J. W., Russell R. G. 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 Relat Res. 1984;5(5):229–234. doi: 10.1016/0221-8747(84)90064-x. [DOI] [PubMed] [Google Scholar]
  2. Brown J. P., Delmas P. D., Malaval L., Edouard C., Chapuy M. C., Meunier P. J. Serum bone Gla-protein: a specific marker for bone formation in postmenopausal osteoporosis. Lancet. 1984 May 19;1(8386):1091–1093. doi: 10.1016/s0140-6736(84)92506-6. [DOI] [PubMed] [Google Scholar]
  3. Charles P., Poser J. W., Mosekilde L., Jensen F. T. Estimation of bone turnover evaluated by 47Ca-kinetics. Efficiency of serum bone gamma-carboxyglutamic acid-containing protein, serum alkaline phosphatase, and urinary hydroxyproline excretion. J Clin Invest. 1985 Dec;76(6):2254–2258. doi: 10.1172/JCI112234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chen T. L., Cone C. M., Morey-Holton E., Feldman D. 1 alpha,25-dihydroxyvitamin D3 receptors in cultured rat osteoblast-like cells. Glucocorticoid treatment increases receptor content. J Biol Chem. 1983 Apr 10;258(7):4350–4355. [PubMed] [Google Scholar]
  5. Darby A. J., Meunier P. J. Mean wall thickness and formation periods of trabecular bone packets in idiopathic osteoporosis. Calcif Tissue Int. 1981;33(3):199–204. doi: 10.1007/BF02409438. [DOI] [PubMed] [Google Scholar]
  6. Delmas P. D., Malaval L., Arlot M. E., Meunier P. J. Serum bone Gla-protein compared to bone histomorphometry in endocrine diseases. Bone. 1985;6(5):339–341. doi: 10.1016/8756-3282(85)90326-6. [DOI] [PubMed] [Google Scholar]
  7. Delmas P. D., Stenner D., Wahner H. W., Mann K. G., Riggs B. L. Increase in serum bone gamma-carboxyglutamic acid protein with aging in women. Implications for the mechanism of age-related bone loss. J Clin Invest. 1983 May;71(5):1316–1321. doi: 10.1172/JCI110882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Delmas P. D., Wahner H. W., Mann K. G., Riggs B. L. Assessment of bone turnover in postmenopausal osteoporosis by measurement of serum bone Gla-protein. J Lab Clin Med. 1983 Oct;102(4):470–476. [PubMed] [Google Scholar]
  9. Eisman J. A., Hamstra A. J., Kream B. E., DeLuca H. F. A sensitive, precise, and convenient method for determination of 1,25-dihydroxyvitamin D in human plasma. Arch Biochem Biophys. 1976 Sep;176(1):235–243. doi: 10.1016/0003-9861(76)90161-2. [DOI] [PubMed] [Google Scholar]
  10. Eisman J. A., Shepard R. M., DeLuca H. F. Determination of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 in human plasma using high-pressure liquid chromatography. Anal Biochem. 1977 May 15;80(1):298–305. doi: 10.1016/0003-2697(77)90648-0. [DOI] [PubMed] [Google Scholar]
  11. Gundberg C. M., Cole D. E., Lian J. B., Reade T. M., Gallop P. M. Serum osteocalcin in the treatment of inherited rickets with 1,25-dihydroxyvitamin D3. J Clin Endocrinol Metab. 1983 May;56(5):1063–1067. doi: 10.1210/jcem-56-5-1063. [DOI] [PubMed] [Google Scholar]
  12. Gundberg C. M., Lian J. B., Gallop P. M., Steinberg J. J. Urinary gamma-carboxyglutamic acid and serum osteocalcin as bone markers: studies in osteoporosis and Paget's disease. J Clin Endocrinol Metab. 1983 Dec;57(6):1221–1225. doi: 10.1210/jcem-57-6-1221. [DOI] [PubMed] [Google Scholar]
  13. Gundberg C. M., Weinstein R. S. Multiple immunoreactive forms of osteocalcin in uremic serum. J Clin Invest. 1986 Jun;77(6):1762–1767. doi: 10.1172/JCI112499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Harris W. H., Heaney R. P. Skeletal renewal and metabolic bone disease. N Engl J Med. 1969 Jan 23;280(4):193–contd. doi: 10.1056/NEJM196901232800405. [DOI] [PubMed] [Google Scholar]
  15. Hauschka P. V., Lian J. B., Gallop P. M. Direct identification of the calcium-binding amino acid, gamma-carboxyglutamate, in mineralized tissue. Proc Natl Acad Sci U S A. 1975 Oct;72(10):3925–3929. doi: 10.1073/pnas.72.10.3925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Heaney R. P., Recker R. R., Saville P. D. Menopausal changes in bone remodeling. J Lab Clin Med. 1978 Dec;92(6):964–970. [PubMed] [Google Scholar]
  17. Kivirikko K. I., Laitinen O., Prockop D. J. Modifications of a specific assay for hydroxyproline in urine. Anal Biochem. 1967 May;19(2):249–255. doi: 10.1016/0003-2697(67)90160-1. [DOI] [PubMed] [Google Scholar]
  18. Kruse H. P., Kuhlencordt F. Pathogenesis and natural course of primary osteoporosis. Lancet. 1980 Feb 9;1(8163):280–282. doi: 10.1016/s0140-6736(80)90779-5. [DOI] [PubMed] [Google Scholar]
  19. Kumar R., Cohen W. R., Silva P., Epstein F. H. Elevated 1,25-dihydroxyvitamin D plasma levels in normal human pregnancy and lactation. J Clin Invest. 1979 Feb;63(2):342–344. doi: 10.1172/JCI109308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nordin B. E., Aaron J., Speed R., Crilly R. G. Bone formation and resorption as the determinants of trabecular bone volume in postmenopausal osteoporosis. Lancet. 1981 Aug 8;2(8241):277–279. doi: 10.1016/s0140-6736(81)90526-2. [DOI] [PubMed] [Google Scholar]
  21. Parfitt A. M., Mathews C. H., Villanueva A. R., Kleerekoper M., Frame B., Rao D. S. Relationships between surface, volume, and thickness of iliac trabecular bone in aging and in osteoporosis. Implications for the microanatomic and cellular mechanisms of bone loss. J Clin Invest. 1983 Oct;72(4):1396–1409. doi: 10.1172/JCI111096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Price P. A., Baukol S. A. 1,25-Dihydroxyvitamin D3 increases synthesis of the vitamin K-dependent bone protein by osteosarcoma cells. J Biol Chem. 1980 Dec 25;255(24):11660–11663. [PubMed] [Google Scholar]
  23. Price P. A., Otsuka A. A., Poser J. W., Kristaponis J., Raman N. Characterization of a gamma-carboxyglutamic acid-containing protein from bone. Proc Natl Acad Sci U S A. 1976 May;73(5):1447–1451. doi: 10.1073/pnas.73.5.1447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Price P. A., Parthemore J. G., Deftos L. J. New biochemical marker for bone metabolism. Measurement by radioimmunoassay of bone GLA protein in the plasma of normal subjects and patients with bone disease. J Clin Invest. 1980 Nov;66(5):878–883. doi: 10.1172/JCI109954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Reeve J., Green J. R., Hesp R., Hulme P. Rates of new bone formation in patients with crush fracture osteoporosis. Clin Sci (Lond) 1982 Aug;63(2):153–160. doi: 10.1042/cs0630153. [DOI] [PubMed] [Google Scholar]
  26. Riggs B. L., Tsai K. S., Mann K. G. Effect of acute increases in bone matrix degradation on circulating levels of bone-Gla protein. J Bone Miner Res. 1986 Dec;1(6):539–542. doi: 10.1002/jbmr.5650010608. [DOI] [PubMed] [Google Scholar]
  27. Riggs B. L., Wahner H. W., Dunn W. L., Mazess R. B., Offord K. P., Melton L. J., 3rd Differential changes in bone mineral density of the appendicular and axial skeleton with aging: relationship to spinal osteoporosis. J Clin Invest. 1981 Feb;67(2):328–335. doi: 10.1172/JCI110039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Whyte M. P., Bergfeld M. A., Murphy W. A., Avioli L. V., Teitelbaum S. L. Postmenopausal osteoporosis. A heterogeneous disorder as assessed by histomorphometric analysis of Iliac crest bone from untreated patients. Am J Med. 1982 Feb;72(2):193–202. doi: 10.1016/0002-9343(82)90810-5. [DOI] [PubMed] [Google Scholar]
  29. Wu K., Jett S., Frost H. M. Bone resorption rates in rib in physiological, senile, and postmenopausal osteoporoses. J Lab Clin Med. 1967 May;69(5):810–818. [PubMed] [Google Scholar]
  30. Zerwekh J. E., Sakhaee K., Pak C. Y. Short-term 1,25-dihydroxyvitamin D3 administration raises serum osteocalcin in patients with postmenopausal osteoporosis. J Clin Endocrinol Metab. 1985 Mar;60(3):615–617. doi: 10.1210/jcem-60-3-615. [DOI] [PubMed] [Google Scholar]

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