Intermittent PTH accelerates stress fracture remodelling more effectively with cessation of bisphosphonate, than with concurrent bisphosphonate treatment. — ASN Events
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Intermittent PTH accelerates stress fracture remodelling more effectively with cessation of bisphosphonate, than with concurrent bisphosphonate treatment. (#62)

Mahmoud M Bakr 1 2 , Wendy L Kelly 1 , Athena Brunt 1 , Gemma Diessel 1 , Ward Massey 2 , Helen Massa 1 , Nigel Morrison 1 , Mark Forwood 1
  1. School of Medical Science, Griffith University, Gold Coast, Queensland, Australia
  2. School of Dentistry and Oral Health, Griffith University, Gold Coast, Queensland, Australia

Introduction/Background: Stress fractures (SFx) account for about 1%-7% of all athletic injuries, and underlie atypical femoral fractures following long-term bisphosphonate (BP) therapy. Parathyroid hormone (PTH) regulates calcium homeostasis, and has an anabolic action on bone when administered intermittently (iPTH). Combination therapy of iPTH plus Alendronate (ALN) impairs the anabolic function of iPTH and its ability to enhance bone mineral density (BMD). Our aim was to determine the efficacy of iPTH to accelerate SFx healing in the presence or absence of ALN.

Study design: 120 female Wistar rats were pre-treated with Alendronate (1.0 ug/kg/d s.c) for 14 days before inducing SFx. SFx was induced by end-loading of the right ulna in a single loading session. Sixty rats received ALN that was either continued (ALN1, n=30) or ceased (ALN2, n=30) after SFx induction. Sixty rats received daily PTH (8 Ī¼g/100g/day) for 14 days with concurrent (ALN-PTH1, n=30) or ceased ALN treatment (ALN-PTH2, n=30). Ulnae were collected after 2 or 6 weeks and two sections stained with Toluidine Blue and TRAP were examined for histomorphometric analysis using Osteomeasureā„¢ software.

Results: Woven bone parameters were greater with combined ALN-PTH treatment (P<0.05). Osteoclast number and perimeter increased significantly in the ALN-PTH groups when compared to ALN groups after two weeks (P=0.009 and 0.021 respectively). As a result of increased osteoclast number and perimeter, erosion perimeter increased significantly in ALN-PTH2 when compared to ALN-PTH1 after two weeks (p=0.002), and ALN2 group within the same timeframe (P=0.05). Healing percentage increased significantly in ALN-PTH2 after six weeks when compared to ALN-PTH1 (P=0.098).

Conclusion: We conclude that, in the presence of BP, activation of remodelling during SFx healing is more effective when BP therapy ceases, than when it continues concurrently with iPTH.