Cell and Tissue Research

, Volume 347, Issue 3, pp 545–552 | Cite as

Endogenous tissue engineering: PTH therapy for skeletal repair

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

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.

Keywords

Parathyroid hormone (PTH) Skeletal repair Fracture insufficiency Allograft 

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Masahiko Takahata
    • 1
  • Hani A. Awad
    • 1
    • 2
    • 3
  • Regis J. O’Keefe
    • 1
    • 3
  • Susan V. Bukata
    • 1
    • 3
  • Edward M. Schwarz
    • 1
    • 2
    • 3
  1. 1.The Center for Musculoskeletal ResearchUniversity of RochesterRochesterUSA
  2. 2.Department of Biomedical EngineeringUniversity of RochesterRochesterUSA
  3. 3.Department of OrthopaedicsUniversity of RochesterRochesterUSA

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