{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T21:51:39Z","timestamp":1791150699416,"version":"4.1.0"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[1994,12,1]],"date-time":"1994-12-01T00:00:00Z","timestamp":786240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Dutch Organization for Scientific Research.","award":["NWO 900-541-191"],"award-info":[{"award-number":["NWO 900-541-191"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1994,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We investigated the structural requirements for the binding of bisphosphonates to bone mineral and the relation between their affinity for bone and their effects on bone resorption in vitro. For this we used fetal mouse long bones in culture and bisphosphonates with variable R1 and R2 structures. In addition, we studied the effect of structural differences in the incorporation of calcium into bone. We found that bisphosphonates containing a hydroxyl group in the R1 position have the highest affinity for bone mineral. This was related to their capacity to inhibit the incorporation of calcium into long bones but not to their antiresorptive potency. The latter was primarily determined by R2. Furthermore, the effect of bisphosphonates on calcification, but not on resorption of bone explants, was mainly determined by the mode of addition. The continuous presence of bisphosphonate during culture inhibited calcification even at very low concentrations, but short incubation of the bones with relatively high concentrations had no effect. This is probably a result of differences in the availability of the compound to the process of calcification. Because, in vivo, the more potent bisphosphonates inhibit resorption without adversely affecting mineralization of the skeleton and they disappear rapidly from the circulation after administration, we suggest that cultures of bone explants incubated with bisphosphonates for short times rather than cultures in which the drugs are continuously present provide more accurate information about the in vivo effect of these compounds on both resorption and calcification.<\/jats:p>","DOI":"10.1002\/jbmr.5650091206","type":"journal-article","created":{"date-parts":[[2010,2,3]],"date-time":"2010-02-03T16:16:16Z","timestamp":1265213776000},"page":"1875-1882","source":"Crossref","is-referenced-by-count":113,"title":["Structural requirements for bisphosphonate actions in vitro"],"prefix":"10.1093","volume":"9","author":[{"given":"Ermond","family":"van Beek","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolic Diseases, University Hospital, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique","family":"Hoekstra","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolic Diseases, University Hospital, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjan","family":"van De Ruit","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolic Diseases, University Hospital, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens","family":"L\u00f6wik","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolic Diseases, University Hospital, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Socrates","family":"Papapoulos","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolic Diseases, University Hospital, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[1994,12,1]]},"reference":[{"key":"2024013113132653700_bib1","first-page":"265","volume-title":"Bone and Mineral Research","author":"Geddes","year":"1994"},{"key":"2024013113132653700_bib2","doi-asserted-by":"crossref","first-page":"919","DOI":"10.2165\/00003495-199142060-00003","article-title":"Bisphosphonates: Pharmacology and use in the treatment of tumor-induced hypercalcemic and metastatic bone disease","volume":"42","author":"Fleisch","year":"1991","journal-title":"Drugs"},{"key":"2024013113132653700_bib3","first-page":"525","volume-title":"Clinical Disorders of Bone and Mineral Metabolism","author":"Bijvoet","year":"1989"},{"key":"2024013113132653700_bib4","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/1043-2760(93)90059-N","article-title":"Role of bisphosphonates in metabolic bone diseases","volume":"4","author":"Hamdy","year":"1993","journal-title":"Trends Endocrinol Metab"},{"key":"2024013113132653700_bib5","doi-asserted-by":"crossref","first-page":"S41","DOI":"10.1016\/S8756-3282(09)80009-4","article-title":"The use of bisphosphonates in the treatment of osteoporosis","volume":"13","author":"Papapoulos","year":"1992","journal-title":"Bone"},{"key":"2024013113132653700_bib6","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/BF02405012","article-title":"Structure-activity relationships of various bisphosphonates","volume":"35","author":"Shinoda","year":"1983","journal-title":"Calcif Tissue Int"},{"key":"2024013113132653700_bib7","first-page":"389","article-title":"Antire-sorptive dose-response relationships across three generations of bisphosphonates","volume":"15","author":"Sietsema","year":"1989","journal-title":"Drugs Exp Clin Res"},{"key":"2024013113132653700_bib8","first-page":"1","article-title":"Symposium CEMO IV","volume-title":"Diphosphonates and Bone","author":"Benedict","year":"1982"},{"key":"2024013113132653700_bib9","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1080\/10426509308032381","article-title":"Bisphosphonates: Molecular modelling, structure-activity relationship and the rational design of new analogs","volume":"76","author":"Ebetino","year":"1993","journal-title":"Phosphorus Sulfur Silicon"},{"key":"2024013113132653700_bib10","first-page":"27","article-title":"Two modes of action of bisphosphonates on osteoclastic resorption of mineralized matrix","volume":"1","author":"Boonekamp","year":"1986","journal-title":"Bone Miner"},{"key":"2024013113132653700_bib11","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1002\/jbmr.5650030210","article-title":"Migration and phenotypic transformation of osteoclast precursors into mature osteoclasts: The effect of a bisphosphonate","volume":"3","author":"L\u00f6wik","year":"1988","journal-title":"J Bone Miner Res"},{"key":"2024013113132653700_bib12","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1172\/JCI115539","article-title":"Bisphosphonate action; 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