{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:25:08Z","timestamp":1760189108912},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[1989,2,1]],"date-time":"1989-02-01T00:00:00Z","timestamp":602294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"BFB"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1989,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The mechanisms of hypercalcemia were assessed in 15 patients with humoral hypercalcemia of malignancy (HHM) who had tumors at various stages of progression. In patients with early tumors, bone biopsies were generally normal and the hypercalcemia was due to an elevation in renal tubular resorption of calcium. Conversely, osteoclastic resorption was markedly increased in patients with advanced tumors, particularly those in whom the biopsies were obtained postmortem. Osteoclast surface (Oc.S) correlated positively with the stage of tumor progression (r = 0.80, p &amp;lt; 0.002), degree of immobility (r = 0.87, p &amp;lt; 0.002), and level of urinary cyclic AMP excretion (r = 0.60, p &amp;lt; 0.02). When compared with a group of ambulant patients with primary hyperparathyroidism (HPT), osteoblast surface (Ob.S%) in HHM was depressed (median and range): 1.2% (0\u201311.6%) versus 5.3% (1.1\u201332.0%) (p &amp;lt; 0.001). However, a relatively low Ob.S (4%) and raised Oc.S (43.5%) were also seen in an immobilized patient with severe HPT.<\/jats:p>\n               <jats:p>These data suggest that the PTH-related peptides currently invoked in the pathogenesis of HHM may initially cause hypercalcemia by enhancing renal tubular calcium resorption. The increase in osteoclastic activity and depression of osteoblastic activity that subsequently occurs is probably due to the combined effects of immobilization and higher circulating levels of PTHrP on the skeleton. However, the release of other bone-resorbing factors by the tumor, which have a depressant effect on osteoblastic activity, remains possible.<\/jats:p>","DOI":"10.1002\/jbmr.5650040115","type":"journal-article","created":{"date-parts":[[2010,2,3]],"date-time":"2010-02-03T18:10:10Z","timestamp":1265220610000},"page":"103-111","source":"Crossref","is-referenced-by-count":15,"title":["Contrasting mechanisms of hypercalcemia in patients with early and advanced humoral hypercalcemia of malignancy"],"prefix":"10.1093","volume":"4","author":[{"given":"Stuart H.","family":"Dr. Ralston","sequence":"first","affiliation":[{"name":"University Departments of Medicine, Glasgow Royal Infirmary, Glasgow, Scotland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brendan F.","family":"Boyce","sequence":"additional","affiliation":[{"name":"Departments of Pathology, Glasgow Royal Infirmary, Glasgow, Scotland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A.","family":"Cowan","sequence":"additional","affiliation":[{"name":"Departments of Biochemistry, Glasgow Royal Infirmary, Glasgow, Scotland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary D.","family":"Gardner","sequence":"additional","affiliation":[{"name":"Departments of Biochemistry, Glasgow Royal Infirmary, Glasgow, Scotland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William D.","family":"Fraser","sequence":"additional","affiliation":[{"name":"Departments of Biochemistry, Glasgow Royal Infirmary, Glasgow, Scotland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iain T.","family":"Boyle","sequence":"additional","affiliation":[{"name":"University Departments of Medicine, Glasgow Royal Infirmary, Glasgow, Scotland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[1989,2,1]]},"reference":[{"key":"2024012918220045200_bib1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1172\/JCI113555","article-title":"Hypercalcemia of malignancy revisited","volume":"82","author":"Mundy","year":"1988","journal-title":"J Clin Invest"},{"key":"2024012918220045200_bib2","doi-asserted-by":"crossref","first-page":"5408","DOI":"10.1073\/pnas.84.14.5048","article-title":"Parathyroid hormone-related protein purified from a human lung cancer cell line","volume":"84","author":"Moseley","year":"1987","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024012918220045200_bib3","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1126\/science.3616618","article-title":"A parathyroid hormone-related protein implicated in malignant hypercalcaemia: Cloning and expression","volume":"237","author":"Suva","year":"1987","journal-title":"Science"},{"key":"2024012918220045200_bib4","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1172\/JCI113275","article-title":"Parathyroid hormone like protein from renal carcinoma cells: Structural and functional homology with parathyroid hormone","volume":"80","author":"Strewler","year":"1987","journal-title":"J Clin Invest"},{"key":"2024012918220045200_bib5","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/0006-291X(87)90581-X","article-title":"N-terminal amino acid sequence of two novel tumor-derived adenylate cyclase stimulating proteins: Identification of parathyroid hormone-like and parathyroid hormone-unlike domains","volume":"146","author":"Stewart","year":"1987","journal-title":"Biochem Biophys Res Commun"},{"key":"2024012918220045200_bib6","doi-asserted-by":"crossref","first-page":"2010","DOI":"10.1172\/JCI113551","article-title":"Identification of transcripts encoding a parathyroid hormone-like peptide in messenger RNA's from a variety of human and animal tumors associated with humoral hypercalcaemia of malignancy","volume":"81","author":"Ikeda","year":"1988","journal-title":"J Clin Invest"},{"key":"2024012918220045200_bib7","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1126\/science.3685994","article-title":"A similarity of synthetic peptide from human tumor to parathyroid hormone in vivo and in vitro","volume":"238","author":"Horiuchi","year":"1987","journal-title":"Science"},{"key":"2024012918220045200_bib8","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1126\/science.3685995","article-title":"Parathyroid hormone-related protein of malignancy: Active synthetic fragments","volume":"238","author":"Kemp","year":"1987","journal-title":"Science"},{"key":"2024012918220045200_bib9","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1172\/JCI113406","article-title":"Effects of a synthetic peptide of a parathyroid hormone-related protein on calcium homeostasis, renal tubular calcium reabsorption and bone metabolism in vivo and in vitro in rodents","volume":"81","author":"Yates","year":"1988","journal-title":"J Clin Invest"},{"key":"2024012918220045200_bib10","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1210\/jcem-55-2-219","article-title":"Quantitative bone histomorphometry in humoral hypercalcemia of malignancy: Uncoupling of bone cell activity","volume":"55","author":"Stewart","year":"1982","journal-title":"J Clin Endocrinol Metab"},{"key":"2024012918220045200_bib11","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1210\/jcem-55-6-1066","article-title":"Quantitative bone histology in the hypercalcaemia of malignant disease","volume":"55","author":"McDonnell","year":"1982","journal-title":"J Clin Endocrinol Metab"},{"key":"2024012918220045200_bib12","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1172\/JCI111478","article-title":"Failure of parathyroid hormone antagonists to inhibit in vitro bone resorbing activity produced by two animal models of the humoral hypercalcemia of malignancy","volume":"74","author":"D'Souza","year":"1984","journal-title":"J Clin Invest"},{"key":"2024012918220045200_bib13","first-page":"325","article-title":"Humoral hypercalcaemia of malignancy: Metabolic and histomorphometric studies during surgical removal of the primary tumour","volume":"277","author":"Ralston","year":"1986","journal-title":"Q J Med"},{"key":"2024012918220045200_bib14","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1056\/NEJM198012113032401","article-title":"Biochemical evaluation of patients with cancer-associated hypercalcemia: Evidence for humoral and non-humoral groups","volume":"303","author":"Stewart","year":"1980","journal-title":"N Engl J Med"},{"key":"2024012918220045200_bib15","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1042\/cs0660187","article-title":"Hypercalcaemia of malignancy: Evidence for a non-parathyroid humoral agent with an effect on renal tubular calcium handling","volume":"66","author":"Ralston","year":"1984","journal-title":"Clin Sci"},{"key":"2024012918220045200_bib16","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1136\/bmj.288.6428.1405","article-title":"Relative contribution of humoral and metastatic factors to the pathogenesis of hypercalcaemia in malignancy","volume":"288","author":"Ralston","year":"1984","journal-title":"Br Med J"},{"key":"2024012918220045200_bib17","first-page":"473","volume-title":"Calcium Phosphate and Magnesium Metabolism","author":"Nordin","year":"1976"},{"key":"2024012918220045200_bib18","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/B978-0-12-068701-5.50008-7","volume-title":"Metabolic Bone Disease","author":"Bijvoet","year":"1977"},{"key":"2024012918220045200_bib19","first-page":"204","article-title":"Arginine blocks the action of parathyroid hormone but not vasopressin on the renal tubule in man","volume":"111","author":"O'Reilly","year":"1987","journal-title":"Endocrinology"},{"key":"2024012918220045200_bib20","first-page":"821","article-title":"Focal osteomalacia complicating low dose diphosphonate therapy in Paget's disease","volume":"1","author":"Boyce","year":"1982","journal-title":"Lancet"},{"key":"2024012918220045200_bib21","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1002\/1097-0142(19820401)49:7<1449::AID-CNCR2820490723>3.0.CO;2-V","article-title":"Abnormal bone and parathyroid histology in carcinoma patients with pseudohy-perparathyroidism","volume":"49","author":"Sharp","year":"1982","journal-title":"Cancer"},{"key":"2024012918220045200_bib22","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/S0140-6736(69)91353-1","article-title":"Relation between serum and urinary calcium with particular reference to parathyroid activity","volume":"1","author":"Peacock","year":"1969","journal-title":"Lancet"},{"key":"2024012918220045200_bib23","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1210\/endo-119-3-1004","article-title":"Parathyroid hormone-like changes in renal calcium and phosphate reabsorption induced by Leydig cell tumor in thyroparathyroidectomised rats","volume":"119","author":"Rizzoli","year":"1986","journal-title":"Endocrinology"}],"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.5650040115","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/4\/1\/103\/56449711\/5650040115.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/4\/1\/103\/56449711\/5650040115.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T14:49:51Z","timestamp":1710341391000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/4\/1\/103-111\/7501957"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1989,2,1]]},"references-count":23,"journal-issue":{"issue":"1","published-online":{"date-parts":[[1989,2,1]]},"published-print":{"date-parts":[[1989,2,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jbmr.5650040115","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[1989,2,1]]},"published":{"date-parts":[[1989,2,1]]}}}