The effects of combined human parathyroid hormone (1-34) and zoledronic acid treatment on fracture healing in osteoporotic rats

Li, Y. F.; Zhou, Chenchen; Li, J. H.; Luo, En; Feng, Ge; Hu, Jing

doi:10.1007/s00198-011-1751-6

Cited by 56 publications

(36 citation statements)

References 43 publications

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“…Previous studies have demonstrated that combination with bisphosphonates such as alendronic acid and zoledronic acid does not exert additive effects on PTH-induced increase in BMD in the clinical setting (Black et al, 2003, Finkelstein et al, 2003, Cosman et al, 2011, Li et al, 2012). This is at least partly because suppression of bone resorption inhibits bone resorption-dependent release of coupling factors from bone matrix.…”

Section: Discussionmentioning

confidence: 99%

Individual and combining effects of anti-RANKL monoclonal antibody and teriparatide in ovariectomized mice

et al. 2015

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We examined the individual and combined effects of teriparatide and anti-RANKL (receptor activator of nuclear factor κB ligand) monoclonal antibody in ovariectomized mice. Three-month-old female C57BL/6 mice were ovariectomized (OVX) or sham operated. Four weeks after OVX, they were assigned to 3 different groups to receive anti-RANKL monoclonal antibody (Ab) alone (5 mg/kg single injection at 4 weeks after OVX, Ab group), teriparatide alone (80 μg/kg daily injection for 4 weeks from 4 weeks after OVX, PTH group), or mAb plus teriparatide (Ab + PTH group). Mice were sacrificed 8 weeks after OVX. Bone mineral density (BMD) was measured at the femur and lumbar spine. Hind limbs were subjected to histological and histomorphometric analysis. Serum osteocalcin and CTX-I levels were measured to investigate the bone turnover. Compared with Ab group, Ab + PTH group showed a significant increase in BMD at distal femur and femoral shaft. Cortical bone volume was significantly increased in PTH and Ab + PTH groups compared with Ab group. Bone turnover in Ab + PTH group was suppressed to the same degree as in Ab group. The number of TRAP-positive multinucleated cells was markedly reduced in Ab and Ab + PTH groups. These results suggest that combined treatment of teriparatide with anti-RANKL antibody has additive effects on BMD in OVX mice compared with individual treatment.

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Section: Discussionmentioning

confidence: 99%

Individual and combining effects of anti-RANKL monoclonal antibody and teriparatide in ovariectomized mice

et al. 2015

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“…This hypothesis was proven in an experimental study in rodents, where PTH (1-34) and zoledronic acid treatment resulted in an additive effect on callus formation [62].…”

Section: Pth Peptidesmentioning

confidence: 93%

Drugs for bone healing

Brandi

2012

Expert Opinion on Investigational Drugs

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“…Rats in the OVX group were bilaterally ovariectomized and rats in the sham group underwent a sham operation. After 3 months without any treatment for osteoporosis induction, 10 randomly selected animals in the OVX group and all 10 animals in the sham group were euthanized as previously described (23). The BW and uterus weight (UW) of rats were recorded, and femoral bone mineral density (BMD) was measured using dual energy X-ray absorptiometry (DXA).…”

Section: Methodsmentioning

confidence: 99%

Bone morphogenetic protein 9 stimulates callus formation in osteoporotic rats during fracture healing

Wang

Huang

Fan

et al. 2017

Molecular Medicine Reports

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Fracture healing involves the coordinated actions of multiple cytokines. Bone morphogenetic protein 9 (BMP9) is an important factor in bone formation. The present study aimed to investigate the osteogenic potential of bone marrow stem cells (BMSCs) in response to adenoviral (Ad)BMP9, and the early fracture repair properties of AdBMP9 in surgically-created fractures in osteoporotic rats. Alkaline phosphatase (ALP) activity was assayed and matrix mineralization was examined by Alizarin Red S staining. mRNA and protein expression levels of BMP9, runt-related transcription factor 2 (RUNX2) and type 1 collagen (COL-1) were detected in vitro and in vivo. Femoral bone mineral density was assessed for osteoporosis in ovariectomized rats. An open femora fracture was subsequently created, and gelatin sponges containing AdBMP9 were implanted. The femora were harvested for radiographical, micro-computed tomography, biomechanical and histological analysis 4 weeks later. BMP9 successfully increased ALP activity and induced mineralized nodule formation in BMSCs. BMP9 in gelatin sponges demonstrated marked effects on microstructural parameters and the biomechanical strength of bone callus. In addition, it upregulated the expression levels of RUNX2 and COL-1. AdBMP9 in gelatin sponges significantly mediated callus formation, and increased bone mass and strength in osteoporotic rats with femora fractures. The results of the present study suggested that BMP9 enhanced callus formation and maintained early mechanical stability during fracture healing in osteoporotic rats, implicating it as a potential novel therapeutic target for fracture healing.

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The effects of combined human parathyroid hormone (1-34) and zoledronic acid treatment on fracture healing in osteoporotic rats

Abstract: Findings in this study suggested an additive effect of ZA and PTH on fracture healing in OVX rats, and this additive effect was specific to callus formation, not to undisturbed bone tissue.

Cited by 56 publications

References 43 publications

Individual and combining effects of anti-RANKL monoclonal antibody and teriparatide in ovariectomized mice

Individual and combining effects of anti-RANKL monoclonal antibody and teriparatide in ovariectomized mice

Drugs for bone healing

Bone morphogenetic protein 9 stimulates callus formation in osteoporotic rats during fracture healing

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