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Seventy\u2010six 12\u2010week\u2010old female Sprague\u2013Dawley rats were either sham operated or bilaterally ovariectomized (OVX). Following confirmation of osteoporosis 3 months after OVX, the remaining 64 animals received alendronate therapy. After 3 months of alendronate treatment, all rats underwent unilateral transverse tibial osteotomy. Animals were immediately randomly assigned to one of four groups: (1) alendronate followed by vehicle (ALN\u2010VEH), (2) continuation of alendronate (ALN\u2010ALN), (3) alendronate followed by once\u2010weekly PTH alone (ALN\u2010PTH), (4) continuation of alendronate combined with once\u2010weekly PTH (ALN\u2010ALN\u2009+\u2009PTH) until collection at 4 or 8 weeks after osteotomy. The fractured tibia was assessed using x\u2010ray, dual\u2010energy x\u2010ray absorptiometry, microcomputed tomography, biomechanical testing, histology, and sequential fluorescence labeling. The ALN\u2010ALN\u2009+\u2009PTH treatment significantly increased total callus volume, mineralized callus volume, mineralized callus volume\/total callus volume, and biomechanical strength of the callus relative to ALN\u2010VEH and ALN\u2010PTH treatments at both 4 and 8 weeks and produced more mature trabecular bone compared with ALN\u2010ALN treatment at 8 weeks. RANKL\/osteoprotegerin (OPG) are osteoclastogenesis markers, while cluster of differentiation 31 (CD31) is an important marker of angiogenesis. Qualitative immunohistochemical analysis revealed that CD31 and OPG expression was was strong after ALN\u2010ALN\u2009+\u2009PTH compared with ALN\u2010ALN treatment, whereas RANKL expression was weak after ALN\u2010ALN\u2009+\u2009PTH versus ALN\u2010PTH treatment. Our study showed that once\u2010weekly PTH combined with alendronate was beneficial in promoting the healing of fractures acquired after long\u2010term alendronate therapy in OVX\u2010induced osteoporotic rats.<\/jats:p>","DOI":"10.1002\/jor.24953","type":"journal-article","created":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T11:54:19Z","timestamp":1608119659000},"page":"2103-2115","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Once\u2010weekly parathyroid hormone combined with ongoing long\u2010term alendronate treatment promotes osteoporotic fracture healing in ovariectomized rats"],"prefix":"10.1002","volume":"39","author":[{"given":"Chenggui","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Orthopedics Peking University Third Hospital  Beijing China"},{"name":"Beijing Key Laboratory of Spinal Diseases  Beijing 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