title: Systemic treatment with telmisartan improves femur fracture healing in mice.
abstract: Recent clinical studies indicated that angiotensin receptor blockers (ARBs) would decrease the risk of bone fractures in the elderly populations. There is little known about the role of the ARBs in the process of fracture healing. The purpose of the present study was to verify the hypothesis that systemic treatment with telmisartan has the ability to promote fracture healing. In this study, femur fractures were produced in 96 mature male BALB/c mice. Animals were treated with the ARBs telmisartan or vehicle. Fracture healing was analysed after 2, 5 and 10 weeks postoperatively using X-ray, biomechanical testing, histomorphometry, immunohistochemistry and micro-computed tomography (micro-CT). Radiological analysis showed the diameter of the callus in the telmisartan treated animals was significantly increased when compared with that of vehicle treated controls after two weeks of fracture healing. The radiologically observed promotion of callus formation was confirmed by histomorphometric analyses, which revealed a significantly increased amount of bone formation when compared with vehicle-treated controls. Biomechanical testing further showed a significantly greater peak torque at failure, and a higher torsional stiffness in telmisartan-treated animals compared with controls. There was an increased fraction of PCNA-positive cells and VEGF-positive cells in telmisartan-treated group compared with vehicle-treated controls. From the three-dimensional reconstruction of the bony callus, telmisartan-treated group significantly increased the values of BV/TV by 21.7% and CsAr by 26.0% compared to the vehicle-treated controls at 5 weeks post-fracture. In summary, we demonstrate in the current study that telmisartan could promote fracture healing in a mice model via increasing mechanical strength and improving microstructure. The most mechanism is probably by an increase of cell proliferation and neovascularization associated with a decreased VEGF expression in hypertrophic chondrocytes.
authors.affiliation: Department of Orthopeadics, Xijing Hospital, The Fourth Military Medical University, Xi'an, PR China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, PR China; ICU, 309th Hospital of PLA, Beijing, PR China.
authors.forename: Jia-xing
authors.initials: JX
authors.lastname: Wang
authors.affiliation: Department of Orthopeadics, Xijing Hospital, The Fourth Military Medical University, Xi'an, PR China.
authors.forename: Ya-fei
authors.initials: YF
authors.lastname: Feng
authors.affiliation: Department of Orthopeadics, Xijing Hospital, The Fourth Military Medical University, Xi'an, PR China.
authors.forename: Zi-xiang
authors.initials: ZX
authors.lastname: Wu
authors.affiliation: Department of Orthopeadics, Xijing Hospital, The Fourth Military Medical University, Xi'an, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopeadics, Xijing Hospital, The Fourth Military Medical University, Xi'an, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Orthopeadics, Xijing Hospital, The Fourth Military Medical University, Xi'an, PR China.
authors.forename: Quan-chang
authors.initials: QC
authors.lastname: Tan
authors.affiliation: Department of Orthopeadics, Xijing Hospital, The Fourth Military Medical University, Xi'an, PR China.
authors.forename: Ya-bo
authors.initials: YB
authors.lastname: Yan
authors.affiliation: Department of Orthopeadics, Xijing Hospital, The Fourth Military Medical University, Xi'an, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lei
mesh_terms: D000284:Administration, Oral; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D002146:Bony Callus / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D017102:Fracture Healing / Q000187:drug effects*; D015870:Gene Expression; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D033081:Shear Strength; D000077333:Telmisartan; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D055114:X-Ray Microtomography
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D015415:Biomarkers; D018809:Proliferating Cell Nuclear Antigen; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D000077333:Telmisartan