Intermittent Parathyroid Hormone (1–34) Treatment Increases Callus Formation and Mechanical Strength of Healing Rat Fractures

Andreassen, Troels T.; Ejersted, Charlotte; Oxlund, Hans

doi:10.1359/jbmr.1999.14.6.960

Cited by 315 publications

(223 citation statements)

References 31 publications

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“…Specifically administration of the amino terminal fragment PTH 1-34 demonstrated stimulatory effects on healing in various animal models including fracture-healing models [3,45,66,96] and bone-grafting models [1,35]. The mechanism by which PTH stimulates bone healing is not well understood.…”

Section: Design Considerations For Functional Tissue Engineering Of Pmentioning

confidence: 99%

“…The mechanism by which PTH stimulates bone healing is not well understood. Several recent studies suggest PTH exerts its anabolic actions at both the early stage and the late stage of bone healing [3,64]. Intermittent treatment of PTH altered the expression of IGFs and Wnt signaling in fracture-healing models [43,66].…”

Section: Design Considerations For Functional Tissue Engineering Of Pmentioning

confidence: 99%

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A Perspective: Engineering Periosteum for Structural Bone Graft Healing

Zhang

Awad

O’Keefe

et al. 2008

Clin Orthop Relat Res

206

169

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Autograft is superior to both allograft and synthetic bone graft in repair of large structural bone defect largely due to the presence of multipotent mesenchymal stem cells in periosteum. Recent studies have provided further evidence that activation, expansion and differentiation of the donor periosteal progenitor cells are essential for the initiation of osteogenesis and angiogenesis of donor bone graft healing. The formation of donor cell-derived periosteal callus enables efficient host-dependent graft repair and remodeling at the later stage of healing. Removal of periosteum from bone autograft markedly impairs healing whereas engraftment of multipotent mesenchymal stem cells on bone allograft improves healing and graft incorporation. These studies provide rationale for fabrication of a biomimetic periosteum substitute that could fit bone of any size and shape for enhanced allograft healing and repair. The success of such an approach will depend on further understanding of the molecular signals that control inflammation, cellular recruitment as well as mesenchymal stem cell differentiation and expansion during the early phase of the repair process. It will also depend on multidisciplinary collaborations between biologists, material scientists and bioengineers to address issues of material selection and modification, biological and biomechanical parameters for functional evaluation of bone allograft healing.

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Section: Design Considerations For Functional Tissue Engineering Of Pmentioning

confidence: 99%

Section: Design Considerations For Functional Tissue Engineering Of Pmentioning

confidence: 99%

A Perspective: Engineering Periosteum for Structural Bone Graft Healing

Zhang

Awad

O’Keefe

et al. 2008

Clin Orthop Relat Res

206

169

View full text Add to dashboard Cite

show abstract

“…Intermittent dosing of PTH is an osteoporosis treatment that can stimulate fracture healing [16][17][18][19] as well as implant fixation 20,21 in animals. However, in subsequent clinical trials only a modest effect on human fracture healing was detected with PTH.…”

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confidence: 99%

Efficacy of a sclerostin antibody compared to a low dose of PTH on metaphyseal bone healing

et al. 2013

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ABSTRACT:We compared the effect of a sclerostin antibody to that of a clinically relevant dose of parathyroid hormone (PTH) in a rat model for metaphyseal bone healing. Screws of steel or poly methyl methacrylate (PMMA) were inserted bilaterally into the proximal tibia of young male rats. During 4 weeks the animals then received injections of either phosphate buffered saline (control), sclerostin antibody (25 mg/kg, twice weekly) or PTH (5 mg/kg, daily). The healing response around the screws was then assessed by mechanical testing and X-ray microtomography (mCT). To distinguish between effects on healing and general effects on the skeleton, other untraumatized bone sites and serum biomarkers were also assessed. After 4 weeks of treatment, PTH yielded a 48% increase in screw pull-out force compared to control (p ¼ 0.03), while the antibody had no significant effect. In contrast, the antibody increased femoral cortical and vertebral strength where PTH had no significant effect. mCT showed only slight changes that were statistically significant for the antibody mainly at cortical sites. The results suggest that a relatively low dose of PTH stimulates metaphyseal repair (screw fixation) specifically, whereas the sclerostin antibody has wide-spread effects, mainly on cortical bone, with less influence on metaphyseal healing. ß

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“…However, when rhPTH (1-34) is administered therapeutically, the oncedaily bolus administration creates a pulsatile exposure and leads to increased osteogenesis 34,35 . Studies in models of fracture-healing have demonstrated that rhPTH (1-34), the active fragment of this polypeptide, consistently enhances the stiffness and strength of experimental fractures during the healing process [36][37][38][39] . In an investigation by Alkhiary et al 38 the effects of rhPTH (1-34) (teriparatide) on fracture-healing was studied in 270 rats that had undergone standard closed femoral fractures and received doses of teriparatide that are similar to those that are effective in the treatment of osteoporosis in postmenopausal women.…”

Section: Current Status Of Osteoinductive Agents For Spine Fusionmentioning

confidence: 99%