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Endogenous tissue engineering: PTH therapy for skeletal repair

Cell and Tissue Research volume 347, pages 545–552 (2012)Cite this article

Abstract

Based on its proven anabolic effects on bone in osteoporosis patients, recombinant parathyroid hormone (PTH1-34) has been evaluated as a potential therapy for skeletal repair. In animals, the effect of PTH1-34 has been investigated in various skeletal repair models such as fractures, allografting, spinal arthrodesis and distraction osteogenesis. These studies have demonstrated that intermittent PTH1-34 treatment enhances and accelerates the skeletal repair process via a number of mechanisms, which include effects on mesenchymal stem cells, angiogenesis, chondrogenesis, bone formation and resorption. Furthermore, PTH1-34 has been shown to enhance bone repair in challenged animal models of aging, inflammatory arthritis and glucocorticoid-induced bone loss. This pre-clinical success has led to off-label clinical use and a number of case reports documenting PTH1-34 treatment of delayed-unions and non-unions have been published. Although a recently completed phase 2 clinical trial of PTH1-34 treatment of patients with radius fracture has failed to achieve its primary outcome, largely because of effective healing in the placebo group, several secondary outcomes are statistically significant, highlighting important issues concerning the appropriate patient population for PTH1-34 therapy in skeletal repair. Here, we review our current knowledge of the effects of PTH1-34 therapy for bone healing, enumerate several critical unresolved issues (e.g., appropriate dosing regimen and indications) and discuss the long-term potential of this drug as an adjuvant for endogenous tissue engineering.

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Affiliations

  1. The Center for Musculoskeletal Research, University of Rochester, 665, 601 Elmwood Avenue, Rochester, NY 14642, USA

    Masahiko Takahata, Hani A. Awad, Regis J. O’Keefe, Susan V. Bukata & Edward M. Schwarz

  2. Department of Biomedical Engineering, University of Rochester, Rochester, NY, USA

    Hani A. Awad & Edward M. Schwarz

  3. Department of Orthopaedics, University of Rochester, Rochester, NY, USA

    Hani A. Awad, Regis J. O’Keefe, Susan V. Bukata & Edward M. Schwarz

Authors
  1. Masahiko Takahata
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  2. Hani A. Awad
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  3. Regis J. O’Keefe
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  4. Susan V. Bukata
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  5. Edward M. Schwarz
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Corresponding author

Correspondence to Edward M. Schwarz.

Additional information

This work was funded in part by grants from the Aircast Foundation and grants from the National Institutes of Health (AR056696, AR054041, DE019902).

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Takahata, M., Awad, H.A., O’Keefe, R.J. et al. Endogenous tissue engineering: PTH therapy for skeletal repair. Cell Tissue Res 347, 545–552 (2012). https://doi.org/10.1007/s00441-011-1188-4

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  • DOI: https://doi.org/10.1007/s00441-011-1188-4

Keywords

  • Parathyroid hormone (PTH)
  • Skeletal repair
  • Fracture insufficiency
  • Allograft