Delayed short-course treatment with teriparatide (PTH1-34) improves femoral allograft healing by enhancing intramembranous bone formation at the graft-host junction

Masahiko Takahata, Edward M. Schwarz, Tony Chen, Regis J. O'Keefe, Hani A. Awad

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Clinical management of critical bone defects remains a major challenge. Despite preclinical work demonstrating teriparatide (PTH1-34) effectiveness in small animals, inconclusive data from clinical trials have raised questions of dose and regimen. To address this, we completed a comprehensive study in the murine femoral allograft model, to assess the effects of dose (0.4, 4, and 40 μg/kg/day) and various treatment regimens on radiographic, histologic, and biomechanical healing at 2, 4, and 9 weeks. Only the high dose (40 μg/kg) of PTH1-34 demonstrated significant effects when given daily over 9 weeks. Remarkably, equivalent biomechanical results were obtained with delayed, short treatment from 2 to 6 weeks that did not induce a significant increase in endochondral bone formation and callus volume. In contrast, PTH1-34 treatment from 1 to 5 weeks postop demonstrated similar osteogenic effects as immediate daily treatment for 9 weeks, but failed to achieve a significant increase in biomechanics at 9 weeks. MicroCT and histologic analyses demonstrated that the 2-week delay in treatment allowed for timely completion of the endochondral phase, such that the prominent effects of PTH1-34 were enhanced intramembranous bone formation and remodeling at the graft-host junction. These findings support the potential use of PTH1-34 as an adjuvant therapy for massive allograft healing, and suggest that there may be an ideal treatment window in which a short course is administered after the endochondral phase to promote osteoblastic bone formation and remodeling to achieve superior union with modest callus formation.

Original languageEnglish
Pages (from-to)26-37
Number of pages12
JournalJournal of Bone and Mineral Research
Volume27
Issue number1
DOIs
StatePublished - Jan 1 2012
Externally publishedYes

Keywords

  • ALLOGRAFT
  • BIOMECHANICS
  • BONE
  • MICROCOMPUTED TOMOGRAPHY (MICROCT)
  • PARATHYROID HORMONE (PTH)

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