{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T06:41:37Z","timestamp":1777876897670,"version":"3.51.4"},"reference-count":65,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2015,4,6]],"date-time":"2015-04-06T00:00:00Z","timestamp":1428278400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Musculoskeletal"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:p>Denosumab is a human monoclonal antibody which specifically blocks receptor activator of nuclear factor \u03baB ligand and is a very potent antiresorptive drug. Its efficacy in reducing the risk of vertebral, hip and nonskeletal fracture has been proven in a large prospective, randomized multicenter study of 7808 postmenopausal women with osteoporosis [Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) trial]. Denosumab causes somewhat greater increases in bone mineral density (BMD) than the class of bisphosphonate antiresorptives. Denosumab also causes an increase in bone mass and bone strength in the spine, ultradistal and diaphysis of the radius, proximal tibia and the hip. Recently long-term treatment with denosumab has been shown to cause a continued almost linear increase in total hip and femoral neck BMD beyond 3 years up to 8 years. In this respect, denosumab seems to differ from the bisphosphonate group in which the rate of improvement of BMD diminishes and for some drugs becomes negative after 3\u20134 years when the process of secondary mineralization flattens out. This unique property of an antiresorptive drug points towards mechanisms of action which differ from the bisphosphonate group. Both types of antiresorptives decrease cortical porosity but contrary to bisphosphonates the reduction in cortical porosity continues with denosumab which, in addition, also seems to cause a slight continuous modeling-based formation of new bone despite suppression of bone remodeling. The net effect is an increase in cortical thickening and bone mass, and increased strength of cortical bone. This may contribute substantially to the significant further reduction of the nonvertebral fracture risk which was found in the long-term denosumab arm of the FREEDOM extension trial during years 4\u20137.<\/jats:p>","DOI":"10.1177\/1759720x15579189","type":"journal-article","created":{"date-parts":[[2015,4,6]],"date-time":"2015-04-06T21:03:16Z","timestamp":1428354196000},"page":"88-102","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":27,"title":["Effects of denosumab on bone density, mass and strength in women with postmenopausal osteoporosis"],"prefix":"10.1177","volume":"7","author":[{"given":"Ove","family":"T\u00f6rring","sequence":"first","affiliation":[{"name":"Institution for Clinical Science and Education, S\u00f6dersjukhuset, Karolinska Institutet, Sjukhusbacken 10, Stockholm 11883, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2015,4,6]]},"reference":[{"key":"bibr1-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1038\/36593"},{"key":"bibr2-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1472"},{"key":"bibr3-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2010.11.020"},{"key":"bibr4-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-2332"},{"key":"bibr5-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1359\/JBMR.040305"},{"key":"bibr6-1759720X15579189","unstructured":"Bilezikian J., Benhamou C., Lin C., Brown J., Daizadeh N., Ebeling P. (2014) Denosumab restores cortical bone loss at the distal radius associated with aging and reduces wrist fracture risk: analyses from the FREEDOM extension cross-over group. J Bone Miner Res 29(Suppl. 1): abstract #1047. Available at: http:\/\/www.asbmr.org\/education\/2014-abstracts (accessed 22 September 2014)."},{"key":"bibr7-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)07088-2"},{"key":"bibr8-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1001\/jama.296.24.2927"},{"key":"bibr9-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa067312"},{"key":"bibr10-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1494"},{"key":"bibr11-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocd.2012.02.006"},{"key":"bibr12-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-1502"},{"key":"bibr13-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-1597"},{"key":"bibr14-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa030897"},{"key":"bibr15-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-2784"},{"key":"bibr16-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.0809010"},{"key":"bibr17-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1808"},{"key":"bibr18-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1359\/JBMR.040325"},{"key":"bibr19-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0809493"},{"key":"bibr20-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.251"},{"key":"bibr21-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1001\/jama.282.7.637"},{"key":"bibr22-1759720X15579189","unstructured":"Ferrari S., Adachi J., Zapalowski C., Miller P., Reginster J., T\u00f6rring O. (2013) Further reduction in the nonvertebral fracture rate is observed following 3 years of denosumab treatment: results with up to 7 years in the FREEDOM extension. J Bone Miner Res 28(Suppl. 1): abstract #1017. Available at: http:\/\/www.asbmr.org\/education\/2013-abstracts (accessed 23 August 2014)."},{"key":"bibr23-1759720X15579189","unstructured":"Geller M., Wagman R., Ho P., Siddhanti S., Stehman-Breen C., Watts N. (2014) Findings from denosumab (Prolia\n                      (R)\n                      ) post-marketing safety surveillance for atypical femur fracture, osteonecrosis of the jaw, severe symptomatic hypocalcemia, and anaphylaxis. J Bone Miner Res 29(Suppl. 1): abstract FR0388. Available at: http:\/\/www.asbmr.org\/education\/2014-abstracts (accessed 6 October 2014)."},{"key":"bibr24-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2010.04.594"},{"key":"bibr25-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2013.07.011"},{"key":"bibr26-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1784"},{"key":"bibr27-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1001\/jama.282.14.1344"},{"key":"bibr28-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.87.4.8415"},{"key":"bibr29-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1001\/jama.292.4.490"},{"key":"bibr30-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.7.3540"},{"key":"bibr31-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2003.18.11.1932"},{"key":"bibr32-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2024"},{"key":"bibr33-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-010-1378-z"},{"key":"bibr34-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2005.06.005"},{"key":"bibr35-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2011.03.769"},{"key":"bibr36-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81569-X"},{"key":"bibr37-1759720X15579189","unstructured":"Lee D., Hoffmann P., Varela A., Kostenuik P., Ominsky M., Keaveny T. (2014) Finite element analysis accurately reflects the improvements in vertebral strength with denosumab in ovariectomized cynomolgus monkeys. J Bone Miner Res 29(Suppl. 1): abstract #SA0388. Available at: http:\/\/www.asbmr.org\/education\/2014-abstracts (accessed 6 October 2014)."},{"key":"bibr38-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.070809"},{"key":"bibr39-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.4.1566"},{"key":"bibr40-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-3795"},{"key":"bibr41-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.536"},{"key":"bibr42-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200102013440503"},{"key":"bibr43-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa044459"},{"key":"bibr44-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-012-2052-4"},{"key":"bibr45-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocd.2012.02.014"},{"key":"bibr46-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-004-0286-7"},{"key":"bibr47-1759720X15579189","doi-asserted-by":"crossref","unstructured":"Ominsky M., Libanati C., Boyce R., Kostenuik P., Baron R., Wagman R. (2013) Continuous modeling-based bone formation: a novel mechanism that could explain the sustained increases in hip bone mineral density (BMD) with denosumab treatment.J Bone Miner Res 28:(Suppl. 1): abstract #LB-MO30. Available at: http:\/\/www.asbmr.org\/education\/2013-abstracts (accessed 23 August 2014).","DOI":"10.1530\/boneabs.3.PP355"},{"key":"bibr48-1759720X15579189","doi-asserted-by":"crossref","unstructured":"Ominsky M., Libanati C., Boyce R., Kostenuik P., Baron R., Wagman R. (2014) Continuous modelling-based bone formation could explain sustained increases in hip bone mineral density with denosumab treatment. Presented at the European Calcified Tissue Society Conference 2014. Abstract #pp355. Available at: http:\/\/www.bone-abstracts.org\/ba\/0003\/ba0003pp355.htm (accessed 5 July 2014).","DOI":"10.1530\/boneabs.3.PP355"},{"key":"bibr49-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2011.04.001"},{"key":"bibr50-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1007\/BF03549782"},{"key":"bibr51-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1479"},{"key":"bibr52-1759720X15579189","author":"Poole K.","year":"2014","journal-title":"J Bone Miner Res"},{"key":"bibr53-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2008.09.019"},{"key":"bibr54-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e318291718c"},{"key":"bibr55-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.149"},{"key":"bibr56-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2013.10.006"},{"key":"bibr57-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2043"},{"key":"bibr58-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.81"},{"key":"bibr59-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1097\/GME.0b013e318267f909"},{"key":"bibr60-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80209-3"},{"key":"bibr61-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.85.1.6267"},{"key":"bibr62-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.7.3597"},{"key":"bibr63-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(97)00173-7"},{"key":"bibr64-1759720X15579189","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2013.11.016"},{"key":"bibr65-1759720X15579189","unstructured":"Zebaze R., Libanati C., McClung M., Zanchetta J., Kendler D., H\u00f6iseth A. (2014b) Denosumab treatment in women with osteoporosis reduces hip cortical porosity. Presented at the European Calcified Tissue Society Conference 2014. Abstract #pp354. Available at: http:\/\/www.bone-abstracts.org\/ba\/0003\/ba0003pp355.htm (accessed 28 August 2014)."}],"container-title":["Therapeutic Advances in Musculoskeletal Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1759720X15579189","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1759720X15579189","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1759720X15579189","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T22:35:39Z","timestamp":1777588539000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/1759720X15579189"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,4,6]]},"references-count":65,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,6]]}},"alternative-id":["10.1177\/1759720X15579189"],"URL":"https:\/\/doi.org\/10.1177\/1759720x15579189","relation":{},"ISSN":["1759-720X","1759-7218"],"issn-type":[{"value":"1759-720X","type":"print"},{"value":"1759-7218","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,4,6]]}}}