{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:46:45Z","timestamp":1787021205784,"version":"build-2736575974"},"reference-count":45,"publisher":"The Endocrine Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Considerable progress has been made in the development and testing of agents to treat osteoporosis. Most impressive are reports on new antiresorptive agents\u2014both bisphosphonates (ibandronate and zoledronic acid) and monoclonal antibodies (MAbs) (denosumab) directed against receptor activator of nuclear factor \u03baB-ligand, a key molecule in the control of commitment and activation of osteoclasts. Bisphosphonates promise convenience and potency at slowing bone loss, whereas denosumab offers powerful suppression of resorption and rapid offset of action. Attention is also shifting from the osteoclast as a target for new therapies to the osteoblast and the osteocyte, with its complex network within the depths of bone. Wnt signaling through the frizzled receptor and its coreceptor, the low-density lipoprotein receptor related protein-5, appears from both molecular and in vivo evidence to be a pivotal pathway for modulating osteoblastic activity, bone formation, and bone strength. The recently identified product of the SOST gene or sclerostin has also been shown to block Wnt signaling. Sclerostin is produced by the osteocytes buried in the bone and is a new target to treat bone loss. Clinical trial reports indicate that the calcimimetic cinacalcet can effectively treat PTH hypersecretion due to primary and secondary hyperparathyroidism and parathyroid carcinoma. Lastly, it is now recognized that the matrix protein dentin matrix protein-1 enhances the release of the phosphate-regulating factor fibroblast growth factor 23 and that mutations in dentin matrix protein-1 play a causative role in a form of hypophosphatemic rickets.<\/jats:p>","DOI":"10.1210\/jc.2007-0042","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T15:26:32Z","timestamp":1173194792000},"page":"747-753","source":"Crossref","is-referenced-by-count":68,"title":["Update in Osteoporosis and Metabolic Bone Disorders"],"prefix":"10.1210","volume":"92","author":[{"given":"Dolores","family":"Shoback","sequence":"first","affiliation":[{"name":"Endocrine Research Unit, San Francisco Department of Veterans Affairs Medical Center, and Department of Medicine, University of California, San Francisco 94121"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613501611800_R1","doi-asserted-by":"crossref","first-page":"3318","DOI":"10.1172\/JCI27071","article-title":"Pathogenesis of osteoporosis. Concepts, conflicts, and prospects.","volume":"115","author":"Raisz","year":"2005","journal-title":"J Clin Invest"},{"key":"2020071613501611800_R2","doi-asserted-by":"crossref","first-page":"2010","DOI":"10.1016\/S0140-6736(06)68891-0","article-title":"Osteoporosis.","volume":"367","author":"Sambrook","year":"2006","journal-title":"Lancet"},{"key":"2020071613501611800_R3","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1359\/JBMR.050313","article-title":"Monthly oral ibandronate therapy in postmenopausal osteoporosis: 1-year results from the MOBILE Study.","volume":"20","author":"Miller","year":"2005","journal-title":"J Bone Miner Res"},{"key":"2020071613501611800_R4","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1136\/ard.2005.044958","article-title":"Efficacy and tolerability of once-monthly oral ibandronate in postmenopausal osteoporosis: 2 year results from the MOBILE study.","volume":"65","author":"Reginster","year":"2006","journal-title":"Ann Rheum Dis"},{"key":"2020071613501611800_R5","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1002\/art.21918","article-title":"Intravenous ibandronate injections in postmenopausal women with osteoporosis: one year results from the Dosing Intravenous Administration Study.","volume":"54","author":"Delmas","year":"2006","journal-title":"Arthritis Rheum"},{"issue":"Suppl 1","key":"2020071613501611800_R6","first-page":"S16","article-title":"Effect of once-yearly infusion of zoledronic acid 5 mg on spine and hip fracture reduction in postmenopausal women with osteoporosis: the HORIZON pivotal fracture trial","volume":"21","author":"Black","year":"2006","journal-title":"J Bone Min Res"},{"key":"2020071613501611800_R7","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1056\/NEJMoa044459","article-title":"Denosumab in postmenopausal women with low bone mineral density.","volume":"354","author":"McClung","year":"2006","journal-title":"N Engl J Med"},{"key":"2020071613501611800_R8","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1111\/j.1523-1755.2005.00596.x","article-title":"Effects of the calcimimetic cinacalcet HCL on cardiovascular disease, fracture, and health-related quality of life in secondary hyperparathyroidism.","volume":"68","author":"Cunningham","year":"2005","journal-title":"Kidney Int"},{"key":"2020071613501611800_R9","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1111\/j.1523-1755.2005.67139.x","article-title":"Achieving NKF-K\/DOQI bone metabolism and disease treatment goals with cinacalcet HCL.","volume":"67","author":"Moe","year":"2005","journal-title":"Kidney Int"},{"issue":"Suppl 1","key":"2020071613501611800_R10","first-page":"S440","article-title":"Cinacalcet reduces hypercalcemia in patients with parathyroid carcinoma","volume":"21","author":"Silverberg","year":"2006","journal-title":"J Bone Miner Res"},{"key":"2020071613501611800_R11","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1210\/jc.2004-0842","article-title":"Cinacalcet hydrochloride maintains long-term normocalcemia in patients with primary hyperparathyroidism.","volume":"90","author":"Peacock","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"issue":"Suppl 1","key":"2020071613501611800_R12","first-page":"S38","article-title":"Long-term control of primary hyperparathyroidism with cinacalcet","volume":"21","author":"Peacock","year":"2006","journal-title":"J Bone Miner Res"},{"key":"2020071613501611800_R13","doi-asserted-by":"crossref","first-page":"6120","DOI":"10.1074\/jbc.C500457200","article-title":"Regulation of fibroblast growth factor-23 signaling by Klotho.","volume":"281","author":"Kurosu","year":"2006","journal-title":"J Biol Chem"},{"key":"2020071613501611800_R14","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1038\/nature05315","article-title":"Klotho converts canonical FGF receptor into a specific receptor for FGF23.","volume":"444","author":"Urakawa","year":"2006","journal-title":"Nature"},{"key":"2020071613501611800_R15","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1038\/ng1358","article-title":"Mutations in GALNT3, encoding a protein involved in O-linked glycosylation, cause familial tumoral calcinosis.","volume":"36","author":"Topaz","year":"2004","journal-title":"Nat Genet"},{"key":"2020071613501611800_R16","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.1210\/jc.2004-2238","article-title":"A novel recessive mutation in fibroblast growth factor-23 causes familial tumoral calcinosis.","volume":"90","author":"Larsson","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613501611800_R17","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1038\/ng1905","article-title":"Loss of DMP-1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism.","volume":"38","author":"Feng","year":"2006","journal-title":"Nat Genet"},{"key":"2020071613501611800_R18","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1038\/ng1868","article-title":"DMP-1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis.","volume":"38","author":"Lorenz-Depiereux, Bastepe","year":"2006","journal-title":"Nat Genet"},{"key":"2020071613501611800_R19","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1172\/JCI28551","article-title":"Regulation of bone mass by Wnt signaling.","volume":"116","author":"Krishnan","year":"2006","journal-title":"J Clin Invest"},{"key":"2020071613501611800_R20","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1096\/fj.05-4221fje","article-title":"Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation.","volume":"19","author":"Poole","year":"2005","journal-title":"FASEB J"},{"key":"2020071613501611800_R21","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1359\/JBMR.040325","volume":"19","author":"Chesnut","journal-title":"J Bone Miner Res"},{"key":"2020071613501611800_R22","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1016\/S0140-6736(96)07088-2","article-title":"Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures.","volume":"348","author":"Black","year":"1996","journal-title":"Lancet"},{"key":"2020071613501611800_R23","doi-asserted-by":"crossref","first-page":"4118","DOI":"10.1210\/jcem.85.11.6953","article-title":"Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial. FIT Research Group.","volume":"85","author":"Black","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613501611800_R24","doi-asserted-by":"crossref","first-page":"2927","DOI":"10.1001\/jama.296.24.2927","article-title":"Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial.","volume":"296","author":"Black","year":"2006","journal-title":"JAMA"},{"key":"2020071613501611800_R25","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s00296-005-0004-4","article-title":"Effect of risedronate in men with primary and secondary osteoporosis: results of a 1-year study.","volume":"26","author":"Ringe","year":"2006","journal-title":"Rheumatol Int"},{"key":"2020071613501611800_R26","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1210\/jc.2004-0952","article-title":"Severely suppressed bone turnover: a potential complication of alendronate therapy.","volume":"90","author":"Odvina","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613501611800_R27","doi-asserted-by":"crossref","first-page":"753","DOI":"10.7326\/0003-4819-144-10-200605160-00009","article-title":"Systematic review: bisphosphonates and osteonecrosis of the jaws.","volume":"144","author":"Woo","year":"2006","journal-title":"Ann Intern Med"},{"key":"2020071613501611800_R28","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.tripleo.2006.06.004","article-title":"Bisphosphonate-related osteonecrosis of the jaw: background and guidelines for diagnosis, staging and management.","volume":"102","author":"Ruggiero","year":"2006","journal-title":"Oral Surg Oral Med Oral Pathol Oral Radiol Endod"},{"key":"2020071613501611800_R29","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1200\/jop.2006.2.1.7","article-title":"Practical guidelines for the prevention, diagnosis, and treatment of osteonecrosis of the jaw in patients with cancer.","volume":"2","author":"Ruggiero","year":"2006","journal-title":"J Oncol Pract"},{"key":"2020071613501611800_R30","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1056\/NEJMp068157","article-title":"Osteonecrosis of the jaw\u2013do bisphosphonates pose a risk?","volume":"355","author":"Bilezikian","year":"2006","journal-title":"N Engl J Med"},{"key":"2020071613501611800_R31","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1093\/jnci\/djh319","article-title":"Invasive breast cancer risk reduction in postmenopausal women with osteoporosis treated with raloxifen for 8 years: results form the Continuing Outcomes Relevant to Evista Trial.","volume":"96","author":"Martino","year":"2004","journal-title":"J Natl Cancer Inst"},{"key":"2020071613501611800_R32","doi-asserted-by":"crossref","first-page":"2727","DOI":"10.1001\/jama.295.23.joc60074","article-title":"Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 Trial.","volume":"295","author":"Vogel","year":"2006","journal-title":"JAMA"},{"key":"2020071613501611800_R33","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1056\/NEJMoa062462","article-title":"Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women.","volume":"355","author":"Barrett-Connor","year":"2006","journal-title":"N Engl J Med"},{"key":"2020071613501611800_R34","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1056\/NEJMoa031975","article-title":"The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis.","volume":"349","author":"Black","year":"2003","journal-title":"N Engl J Med"},{"key":"2020071613501611800_R35","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1056\/NEJMoa035725","article-title":"The effects of parathyroid hormone, alendronate, or both in men with osteoporosis.","volume":"349","author":"Finkelstein","year":"2003","journal-title":"N Engl J Med"},{"key":"2020071613501611800_R36","doi-asserted-by":"crossref","first-page":"2882","DOI":"10.1210\/jc.2006-0190","article-title":"Effects of teriparatide, alendronate, or both on bone turnover osteoporotic men.","volume":"91","author":"Finkelstein","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613501611800_R37","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1056\/NEJMoa050336","article-title":"One year of alendronate after one year of parathyroid hormone (1\u201384) for osteoporosis.","volume":"353","author":"Black","year":"2005","journal-title":"N Engl J Med"},{"key":"2020071613501611800_R38","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1056\/NEJMoa022436","article-title":"The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis.","volume":"350","author":"Meunier","year":"2004","journal-title":"N Engl J Med"},{"key":"2020071613501611800_R39","doi-asserted-by":"crossref","first-page":"2816","DOI":"10.1210\/jc.2004-1774","article-title":"Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: treatment of peripheral osteoporosis (TROPOS) study.","volume":"90","author":"Reginster","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613501611800_R40","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1007\/s00198-005-1867-7","article-title":"Estimates of optimal vitamin D status.","volume":"16","author":"Dawson-Hughes","year":"2005","journal-title":"Osteo Int"},{"key":"2020071613501611800_R41","doi-asserted-by":"crossref","first-page":"3215","DOI":"10.1210\/jc.2004-2364","article-title":"Prevalence of vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy.","volume":"90","author":"Holick","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613501611800_R42","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1001\/jama.293.18.2257","article-title":"Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials.","volume":"293","author":"Bischoff-Ferrari","year":"2005","journal-title":"JAMA"},{"key":"2020071613501611800_R43","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1056\/NEJMoa055218","article-title":"Calcium plus vitamin D supplementation and the risk of fractures.","volume":"354","author":"Jackson","year":"2006","journal-title":"N Engl J Med"},{"key":"2020071613501611800_R44","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1001\/jama.294.10.1260","article-title":"Tumor-induced osteomalacia.","volume":"294","author":"Jan de Beur","year":"2005","journal-title":"JAMA"},{"key":"2020071613501611800_R45","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1038\/ng1106-1230","article-title":"Bone talk.","volume":"38","author":"Schiavi","year":"2006","journal-title":"Nat Genet"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/92\/3\/747\/9051147\/jcem0747.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/92\/3\/747\/9051147\/jcem0747.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T20:46:37Z","timestamp":1594932397000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/92\/3\/747\/2596639"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,3,1]]},"references-count":45,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2007,3,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2007-0042","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,3,1]]}}}