{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T06:36:37Z","timestamp":1781073397333,"version":"3.54.1"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2010,9,13]],"date-time":"2010-09-13T00:00:00Z","timestamp":1284336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Osteoporotic patients treated with antiresorptive or anabolic agents experience an increase in bone mass and a reduction in incident fractures. However, the effects of these medications on bone quality and strength after a prolonged discontinuation of treatment are not known. We evaluated these effects in an osteoporotic rat model. Six-month-old ovariectomized (OVX) rats were treated with placebo, alendronate (ALN, 2\u2009\u00b5g\/kg), parathyroid hormone [PTH(1\u201334); 20\u2009\u00b5g\/kg], or raloxifene (RAL, 2\u2009mg\/kg) three times a week for 4 months and withdrawn from the treatments for 8 months. Treatment with ALN, PTH, and RAL increased the vertebral trabecular bone volume (BV\/TV) by 47%, 53%, and 31%, with corresponding increases in vertebral compression load by 27%, 51%, and 31%, respectively (p\u2009&amp;lt;\u2009.001). The resulting bone strength was similar to that of the sham-OVX control group with ALN and RAL and higher (p\u2009&amp;lt;\u2009.001) with PTH treatment. After 4 months of withdrawal, bone turnover (BFR\/BS) remained suppressed in the ALN group versus the OVX controls (p\u2009&amp;lt;\u2009.001). The vertebral strength was higher than in the OVX group only in ALN-treated group (p\u2009&amp;lt;\u2009.05), whereas only the PTH-treated animals showed a higher maximum load in tibial bending versus the OVX controls (p\u2009&amp;lt;\u2009.05). The vertebral BV\/TV returned to the OVX group level in both the PTH and RAL groups 4 months after withdrawal but remained 25% higher than the OVX controls up to 8 months after withdrawal of ALN (p\u2009&amp;lt;\u2009.05). Interestingly, cortical bone mineral density increased only with PTH treatment (p\u2009&amp;lt;\u2009.05) but was not different among the experimental groups after withdrawal. At 8 months after treatment withdrawal, none of the treatment groups was different from the OVX control group for cortical or cancellous bone strength. In summary, both ALN and PTH maintained bone strength (maximum load) 4 months after discontinuation of treatment despite changes in bone mass and bone turnover; however, PTH maintained cortical bone strength, whereas ALN maintained cancellous bone strength. Additional studies on the long-term effects on bone strength after discontinuation and with combination of osteoporosis medications are needed to improve our treatment of osteoporosis. \u00a9 2011 American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbmr.249","type":"journal-article","created":{"date-parts":[[2010,9,13]],"date-time":"2010-09-13T19:20:31Z","timestamp":1284405631000},"page":"569-581","source":"Crossref","is-referenced-by-count":16,"title":["Differential maintenance of cortical and cancellous bone strength following discontinuation of bone-active agents"],"prefix":"10.1093","volume":"26","author":[{"given":"Mohammad","family":"Shahnazari","sequence":"first","affiliation":[{"name":"Department of Medicine, University of California Davis Medical Center, Sacramento, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California Davis Medical Center, Sacramento, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bob","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California Davis Medical Center, Sacramento, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Panganiban","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering, University of California Berkeley, Berkeley, CA, USA"},{"name":"Materials Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert O","family":"Ritchie","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering, University of California Berkeley, Berkeley, CA, USA"},{"name":"Materials Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda","family":"Hagar","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, University of California Davis, Davis, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy E","family":"Lane","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California Davis Medical Center, Sacramento, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,9,13]]},"reference":[{"key":"2024020318055622700_bib1","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1210\/er.2001-2002","article-title":"Meta-analysis of alendronate for the treatment of postmenopausal women","volume":"23","author":"Cranney","year":"2002","journal-title":"Endocr Rev."},{"key":"2024020318055622700_bib2","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1210\/er.2001-4002","article-title":"Meta-analysis of raloxifene for the prevention and treatment of postmenopausal osteoporosis","volume":"23","author":"Cranney","year":"2002","journal-title":"Endocr Rev."},{"key":"2024020318055622700_bib3","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1056\/NEJM200105103441904","article-title":"Effect of parathyroid hormone(1\u201334) on fractures and bone mineral density in postmenopausal women with osteoporosis","volume":"344","author":"Neer","year":"2001","journal-title":"N Engl J Med."},{"key":"2024020318055622700_bib4","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":"2024020318055622700_bib5","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":"2024020318055622700_bib6","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1359\/jbmr.2001.16.5.925","article-title":"Parathyroid hormone added to established hormone therapy: effects on vertebral fracture and maintenance of bone mass after parathyroid hormone withdrawal","volume":"16","author":"Cosman","year":"2001","journal-title":"J Bone Miner Res."},{"key":"2024020318055622700_bib7","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1001\/archinte.164.18.2024","article-title":"Sustained vertebral fracture risk reduction after withdrawal of teriparatide in postmenopausal women with osteoporosis","volume":"164","author":"Lindsay","year":"2004","journal-title":"Arch Intern Med."},{"key":"2024020318055622700_bib8","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1359\/jbmr.2000.15.5.944","article-title":"Bone mass continues to increase at the hip after parathyroid hormone treatment is discontinued in glucocorticoid-induced osteoporosis: results of a randomized controlled clinical trial","volume":"15","author":"Lane","year":"2000","journal-title":"J Bone Miner Res."},{"key":"2024020318055622700_bib9","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1359\/jbmr.080501","article-title":"Recovery of trabecular and cortical bone turnover after discontinuation of risedronate and alendronate therapy in ovariectomized rats","volume":"23","author":"Fuchs","year":"2008","journal-title":"J Bone Miner Res."},{"key":"2024020318055622700_bib10","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/S8756-3282(01)00582-8","article-title":"Maintenance of cancellous bone in ovariectomized, human parathyroid hormone [hPTH(1\u201384)]-treated rats by estrogen, risedronate, or reduced hPTH","volume":"29","author":"Iwaniec","year":"2001","journal-title":"Bone."},{"key":"2024020318055622700_bib11","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1016\/j.jbiomech.2008.02.032","article-title":"Indirect determination of trabecular bone effective tissue failure properties using micro-finite element simulations","volume":"41","author":"Verhulp","year":"2008","journal-title":"J Biomech."},{"key":"2024020318055622700_bib12","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1016\/j.bone.2009.11.019","article-title":"Higher doses of bisphosphonates further improve bone mass, architecture, and strength but not the tissue material properties in aged rats","volume":"46","author":"Shahnazari","year":"2010","journal-title":"Bone."},{"key":"2024020318055622700_bib13","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1002\/jbmr.5650020617","article-title":"Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee","volume":"2","author":"Parfitt","year":"1987","journal-title":"J Bone Miner Res."},{"key":"2024020318055622700_bib14","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S8756-3282(01)00486-0","article-title":"Bone biomechanical properties in prostaglandin EP1 and EP2 knockout mice","volume":"29","author":"Akhter","year":"2001","journal-title":"Bone."},{"key":"2024020318055622700_bib15","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1002\/jor.1100160516","article-title":"Finite-element modeling of trabecular bone: comparison with mechanical testing and determination of tissue modulus","volume":"16","author":"Ladd","year":"1998","journal-title":"J Orthop Res."},{"key":"2024020318055622700_bib16","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/0021-9290(95)80008-5","article-title":"A new method to determine trabecular bone elastic properties and loading using micromechanical finite-element models","volume":"28","author":"van Rietbergen","year":"1995","journal-title":"J Biomech."},{"key":"2024020318055622700_bib17","doi-asserted-by":"crossref","first-page":"421","DOI":"10.3233\/THC-1998-65-614","article-title":"Mechanical analysis of bone and its microarchitecture based on in vivo voxel images","volume":"6","author":"Ulrich","year":"1998","journal-title":"Technol Health Care."},{"key":"2024020318055622700_bib18","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1359\/jbmr.2006.21.2.307","article-title":"Cortical and trabecular load sharing in the human vertebral body","volume":"21","author":"Eswaran","year":"2006","journal-title":"J Bone Miner Res."},{"key":"2024020318055622700_bib19","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/8756-3282(89)90077-X","article-title":"Loss of the anabolic effect of parathyroid hormone on bone after discontinuation of hormone in rats","volume":"10","author":"Gunness-Hey","year":"1989","journal-title":"Bone."},{"key":"2024020318055622700_bib20","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1002\/jbmr.5650110205","article-title":"Maintaining bone mass by bisphosphonate incadronate disodium (YM175) sequential treatment after discontinuation of intermittent human parathyroid hormone (1\u201334) administration in ovariectomized rats","volume":"11","author":"Takano","year":"1996","journal-title":"J Bone Miner Res."},{"key":"2024020318055622700_bib21","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1097\/01.blo.0000132263.14046.0c","article-title":"Biomechanical considerations of fracture treatment and bone quality maintenance in elderly patients and patients with osteoporosis","volume":"425","author":"Chao","year":"2004","journal-title":"Clin Orthop Relat Res."},{"key":"2024020318055622700_bib22","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S8756-3282(99)00098-8","article-title":"The ability of three-dimensional structural indices to reflect mechanical aspects of trabecular bone","volume":"25","author":"Ulrich","year":"1999","journal-title":"Bone."},{"key":"2024020318055622700_bib23","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/0021-9290(94)90014-0","article-title":"The relationship between the structural and orthogonal compressive properties of trabecular bone","volume":"27","author":"Goulet","year":"1994","journal-title":"J Biomech."},{"key":"2024020318055622700_bib24","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/S8756-3282(97)00198-1","article-title":"Effects of intermittent administration of low dose human PTH(1\u201334) on cancellous and cortical bone of lumbar vertebral bodies in adult beagles","volume":"21","author":"Zhang","year":"1997","journal-title":"Bone."},{"key":"2024020318055622700_bib25","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1359\/jbmr.080805","article-title":"Femoral bone strength and its relation to cortical and trabecular changes after treatment with PTH, alendronate, and their combination as assessed by finite element analysis of quantitative CT scans","volume":"23","author":"Keaveny","year":"2008","journal-title":"J Bone Miner Res."},{"key":"2024020318055622700_bib26","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/BF02058659","article-title":"The relative contribution of trabecular and cortical bone to the strength of human lumbar vertebrae","volume":"3","author":"Rockoff","year":"1969","journal-title":"Calcif Tissue Res."},{"key":"2024020318055622700_bib27","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/8756-3282(93)90081-K","article-title":"Basic biomechanical measurements of bone: a tutorial","volume":"14","author":"Turner","year":"1993","journal-title":"Bone."},{"key":"2024020318055622700_bib28","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1002\/jbm.a.31974","article-title":"Mechanical behavior of human cortical bone in cycles of advancing tensile strain for two age groups","volume":"89","author":"Nyman","year":"2009","journal-title":"J Biomed Mater Res A."},{"key":"2024020318055622700_bib29","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/0021-9290(95)00048-8","article-title":"The effects of ageing and changes in mineral content in degrading the toughness of human femora","volume":"29","author":"Currey","year":"1996","journal-title":"J Biomech."},{"key":"2024020318055622700_bib30","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1210\/jc.2002-021988","article-title":"Effects of intermittent parathyroid hormone administration on bone mineralization density in iliac crest biopsies from patients with osteoporosis: a paired study before and after treatment","volume":"88","author":"Misof","year":"2003","journal-title":"J Clin Endocrinol Metab."},{"key":"2024020318055622700_bib31","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1007\/s00223-008-9108-7","article-title":"Effects of treatment with parathyroid hormone 1\u201384 on quantity and biomechanical properties of thoracic vertebral trabecular bone in ovariectomized rhesus monkeys","volume":"82","author":"Fox","year":"2008","journal-title":"Calcif Tissue Int."},{"key":"2024020318055622700_bib32","first-page":"1","article-title":"Prolonged Treatments with Anti-Resorptive Agents and PTH Have Different Effects on Bone Strength and the Degree of Mineralization in Old Estrogen Deficient Osteoporotic Rats","author":"Cheng","year":"2009","journal-title":"J Bone Miner Res."},{"key":"2024020318055622700_bib33","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/s00198-007-0475-0","article-title":"Effect of prior and ongoing raloxifene therapy on response to PTH and maintenance of BMD after PTH therapy","volume":"19","author":"Cosman","year":"2008","journal-title":"Osteoporos Int."},{"key":"2024020318055622700_bib34","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":"2024020318055622700_bib35","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s11914-004-0008-0","article-title":"Therapeutic potential of parathyroid hormone","volume":"2","author":"Cosman","year":"2004","journal-title":"Curr Osteoporos Rep."},{"key":"2024020318055622700_bib36","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.bone.2008.09.019","article-title":"Cancellous and cortical bone architecture and turnover at the iliac crest of postmenopausal osteoporotic women treated with parathyroid hormone 1\u201384","volume":"44","author":"Recker","year":"2009","journal-title":"Bone."},{"key":"2024020318055622700_bib37","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.bone.2007.04.197","article-title":"Effects of daily treatment with parathyroid hormone 1\u201384 for 16 months on density, architecture and biomechanical properties of cortical bone in adult ovariectomized rhesus monkeys","volume":"41","author":"Fox","year":"2007","journal-title":"Bone."},{"key":"2024020318055622700_bib38","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s00223-007-9036-y","article-title":"Effects of treatment of ovariectomized adult rhesus monkeys with parathyroid hormone 1\u201384 for 16 months on trabecular and cortical bone structure and biomechanical properties of the proximal femur","volume":"81","author":"Fox","year":"2007","journal-title":"Calcif Tissue Int."},{"key":"2024020318055622700_bib39","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1016\/j.bone.2006.09.008","article-title":"Skeletal actions of intermittent parathyroid hormone: effects on bone remodelling and structure","volume":"40","author":"Compston","year":"2007","journal-title":"Bone."},{"key":"2024020318055622700_bib40","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1359\/jbmr.2001.16.1.157","article-title":"Intermittently administered human parathyroid hormone(1\u201334) treatment increases intracortical bone turnover and porosity without reducing bone strength in the humerus of ovariectomized cynomolgus monkeys","volume":"16","author":"Burr","year":"2001","journal-title":"J Bone Miner Res."},{"key":"2024020318055622700_bib41","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1359\/jbmr.81005","article-title":"Prolonged treatments with antiresorptive agents and PTH have different effects on bone strength and the degree of mineralization in old estrogen-deficient osteoporotic rats","volume":"24","author":"Cheng","year":"2009","journal-title":"J Bone Miner Res."}],"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.249","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/26\/3\/569\/56559067\/249_ftp.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/26\/3\/569\/56559067\/249_ftp.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T14:53:58Z","timestamp":1710341638000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/26\/3\/569-581\/7598116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,9,13]]},"references-count":41,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2010,9,13]]},"published-print":{"date-parts":[[2011,3,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jbmr.249","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2011,3,1]]},"published":{"date-parts":[[2010,9,13]]}}}