{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T15:28:17Z","timestamp":1759937297282},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[1994,3,1]],"date-time":"1994-03-01T00:00:00Z","timestamp":762480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Savon Korkean Teknologian"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1994,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We developed a sensitive two-site sandwich ELISA for quantitative analysis of human osteocalcin in serum or plasma. Our method is based on two different highly specific antibodies recognizing epitopes at different ends of the protein so that only intact osteocalcin is detected. The method is fast (total analysis time less than 6 h\/96 wells), precise (intraassay variation less than 2.3% at four different levels; n = 10, and interassay variation less than 2.5%, n = 5, respectively), and accurate, with a mean recovery of 105%. The detection limit in serum is approximately 0.1 \u03bcg\/liter. The mean concentration of osteocalcin in normal serum with this assay is 3.3 \u03bcg\/liter (SD 3.7 \u03bcg\/liter; range 0.1\u201313.1 \u03bcg\/liter; n = 41), and the reference range is 0.28\u201310.1 \u03bcg\/liter (10 and 90% confidence limits). The method shows a reasonable positive linear correlation with other osteocalcin assays (Incstar, r = 0.55, p &amp;lt; 0.05, n = 13; Henning Oscatest, r = 0.52, p &amp;lt; 0.005, n = 34). A good correlation (r = 0.70, p &amp;lt; 0.001) between individual osteocalcin and bone-specific alkaline phosphatase serum concentrations was observed in normal subjects. We found a low or undetectable concentration of intact osteocalcin in serum of all four of our patients with acute primary hyperparathyroidism, and in all five patients with hypocalcemic secondary hyperparathyroidism, which suggests that PTH effectively inhibited the synthesis of osteocalcin in osteoblasts. The serum concentration of intact osteocalcin was elevated in two of three patients with chronic primary hyperparathyroidism. In five patients with normocalcemic secondary hyperparathyroidism, the serum concentration of intact osteocalcin was low: three had a normal and two had an elevated value. An age-related decrease in intact osteocalcin in serum of females younger than 50 years and an increase in older women were observed.<\/jats:p>","DOI":"10.1002\/jbmr.5650090309","type":"journal-article","created":{"date-parts":[[2010,2,3]],"date-time":"2010-02-03T16:30:05Z","timestamp":1265214605000},"page":"347-354","source":"Crossref","is-referenced-by-count":30,"title":["Two-site enzyme immunoassay for measuring intact human osteocalcin in serum"],"prefix":"10.1093","volume":"9","author":[{"given":"Markku","family":"Parviainen","sequence":"first","affiliation":[{"name":"Department of Clinical Chemistry, University of Kuopio, and the Center for Diagnostic Biotechnology, A.I. Virtanen Institute, Kuopio, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilpo","family":"Kuronen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biotechnology, University of Kuopio, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harri","family":"Kokko","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biotechnology, University of Kuopio, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mari","family":"Lakaniemi","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, University of Kuopio, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kari","family":"Savolainen","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, University of Kuopio, and the Center for Diagnostic Biotechnology, A.I. Virtanen Institute, Kuopio, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilkka","family":"Mononen","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, University of Kuopio, and the Center for Diagnostic Biotechnology, A.I. Virtanen Institute, Kuopio, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[1994,3,1]]},"reference":[{"key":"2024013113130288400_bib1","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1172\/JCI109954","article-title":"New biochemical marker for bone metabolism: Measurement by radioimmunoassay of bone gla protein in the plasma of normal subjects and patients with bone disease","volume":"66","author":"Price","year":"1980","journal-title":"J Clin Invest"},{"key":"2024013113130288400_bib2","first-page":"418","article-title":"Morphology and biochemistry of bone remodeling: possible control by vitamin D, parathyroid hormone, and other substances","volume":"59","author":"Huffer","year":"1988","journal-title":"Lab Invest"},{"key":"2024013113130288400_bib3","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/0167-4781(90)90018-W","article-title":"Effect of 1,25(OH)2D3 on its receptor mRNA levels and osteocalcin synthesis in human osteosarcoma cells","volume":"1048","author":"Mahonen","year":"1990","journal-title":"Biochim Biophys Acta"},{"key":"2024013113130288400_bib4","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1093\/clinchem\/36.9.1620","article-title":"Measurement of serum bone gla-protein (BGP) in humans with an ovine BGP-based radioimmunoassay","volume":"36","author":"Pastoureau","year":"1990","journal-title":"Clin Chem"},{"key":"2024013113130288400_bib5","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1093\/clinchem\/35.10.2087","article-title":"Solid-phase enzymoimmunoassay for osteocalcin in human serum or plasma, with use of a monoclonal antibody","volume":"35","author":"Power","year":"1989","journal-title":"Clin Chem"},{"key":"2024013113130288400_bib6","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1007\/BF02555196","article-title":"Radioimmunoassay for human osteocalcin using an antibody raised against the synthetic human (h37\u201349) sequence","volume":"39","author":"J\u00fcppner","year":"1986","journal-title":"Calcif Tissue Int"},{"key":"2024013113130288400_bib7","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/0026-0495(88)90122-9","article-title":"Development of a new radioimmunoassay for human osteocalcin: Evidence for a mid-molecule epitope","volume":"37","author":"Taylor","year":"1988","journal-title":"Metabolism"},{"key":"2024013113130288400_bib8","first-page":"152","article-title":"Specific radioimmunoassay for ovine bone gla-protein (osteocalcin)","volume":"119","author":"Pastoureau","year":"1988","journal-title":"Acta Endocrinol (Copenh)"},{"issue":"Suppl.","key":"2024013113130288400_bib9","doi-asserted-by":"crossref","first-page":"S26","DOI":"10.1007\/BF02555084","article-title":"Use of non-collagen markers in osteoporosis studies","volume":"49","author":"Parviainen","year":"1991","journal-title":"Calcif Tissue Int"},{"key":"2024013113130288400_bib10","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1210\/jcem-62-2-379","article-title":"Low serum osteocalcin levels in glucocorticoid-treated asthmatics","volume":"62","author":"Reid","year":"1986","journal-title":"J Clin Endocrinol Metab"},{"key":"2024013113130288400_bib11","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1210\/jcem-66-5-951","article-title":"Concurrent assays of circulating bone gla-protein and bone alkaline phosphatase: Effects of sex, age, and metabolic bone disease","volume":"66","author":"Duda","year":"1988","journal-title":"J Clin Endocrinol Metab"},{"key":"2024013113130288400_bib12","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1210\/edrv-9-4-437","article-title":"Serum and urinary markers of bone remodeling: Assessment of bone turnover (review)","volume":"9","author":"Epstein","year":"1988","journal-title":"Endocr Rev"},{"key":"2024013113130288400_bib13","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1002\/jbmr.5650050506","article-title":"Comparison of monoclonal and polyclonal antibody-based immunoassays for osteocalcin: A study of sources of variation in assay results","volume":"5","author":"Tracy","year":"1990","journal-title":"J Bone Miner Res"},{"key":"2024013113130288400_bib14"},{"key":"2024013113130288400_bib15"},{"key":"2024013113130288400_bib16","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/0022-1759(93)90127-S","article-title":"Production of monoclonal and polyclonal antibodies against human osteocalcin sequences and development of a two-site ELISA for intact human osteocalcin","volume":"163","author":"Kuronen","year":"1993","journal-title":"J Immunol Methods"},{"key":"2024013113130288400_bib17","volume-title":"Interpretation of Paragon system Isopal alkaline phosphatase isoenzyme kit","author":"Chevigne"},{"key":"2024013113130288400_bib18","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/0009-8981(81)90396-X","article-title":"An improved method for routine determination of vitamin D and its hydroxylated metabolites in serum from children and adults","volume":"114","author":"Parviainen","year":"1981","journal-title":"Clin Chim Acta"},{"key":"2024013113130288400_bib19","first-page":"622","volume-title":"Vitamin D. Molecular, Cellular and Clinical Endocrinology","author":"Pirskanen","year":"1988"},{"key":"2024013113130288400_bib20","first-page":"903","volume-title":"Clinical Endocrinology","author":"Fischer","year":"1986"},{"key":"2024013113130288400_bib21","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1093\/clinchem\/31.10.1720","article-title":"Determination of osteocalcin in human serum: Results with two kits compared with those by a well-characterized assay","volume":"31","author":"Gundberg","year":"1985","journal-title":"Clin Chem"},{"key":"2024013113130288400_bib22","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1093\/clinchem\/35.7.1408","article-title":"Radioimmunoassay of osteocalcin with polyclonal and monoclonal antibodies","volume":"35","author":"Power","year":"1989","journal-title":"Clin Chem"},{"key":"2024013113130288400_bib23","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1093\/clinchem\/37.2.281","article-title":"Osteocalcin concentrations in plasma prepared with different anticoagulants","volume":"37","author":"Power","year":"1991","journal-title":"Clin Chem"},{"key":"2024013113130288400_bib24","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1210\/jcem-59-2-228","article-title":"Clinical evaluation of bone turnover by serum osteocalcin measurements in a hospital setting","volume":"59","author":"Slovik","year":"1984","journal-title":"J Clin Endocrinol Metab"},{"key":"2024013113130288400_bib25","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1111\/j.1365-2362.1986.tb01342.x","article-title":"Primary hyperparathyroidism: evaluated by 47calcium kinetics, calcium balance and serum bone-gla-protein","volume":"16","author":"Charles","year":"1986","journal-title":"Eur J Clin Invest"},{"key":"2024013113130288400_bib26","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1007\/BF02555209","article-title":"Serum bone gla protein (BGP) and other markers of bone mineral metabolism in postmenopausal osteoporosis","volume":"39","author":"Ismail","year":"1986","journal-title":"Calcif Tissue Int"},{"key":"2024013113130288400_bib27","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1172\/JCI110882","article-title":"Increase in serum bone gammacarboxyglutamic acid protein with aging in women","volume":"71","author":"Delmas","year":"1983","journal-title":"J Clin Invest"},{"key":"2024013113130288400_bib28","doi-asserted-by":"crossref","first-page":"2406","DOI":"10.1093\/clinchem\/34.12.2406","article-title":"Alkaline phosphatase isoenzymes in serum determined by high-performance anion-exchange liquid chromatography with detection by enzyme reaction","volume":"34","author":"Parviainen","year":"1988","journal-title":"Clin Chem"},{"key":"2024013113130288400_bib29","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/0009-8981(88)90014-9","article-title":"Reference limits of bone and liver alkaline phosphatase isoenzymes in the serum of healthy subjects according to age and sex as determined by wheat germ lectin affinity electrophoresis","volume":"173","author":"Kuwana","year":"1988","journal-title":"Clin Chim Acta"}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjbmr.5650090309","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/9\/3\/347\/56496578\/5650090309.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/9\/3\/347\/56496578\/5650090309.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T14:57:57Z","timestamp":1710341877000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/9\/3\/347-354\/7500828"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,3,1]]},"references-count":29,"journal-issue":{"issue":"3","published-online":{"date-parts":[[1994,3,1]]},"published-print":{"date-parts":[[1994,3,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jbmr.5650090309","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[1994,3,1]]},"published":{"date-parts":[[1994,3,1]]}}}