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Protocol for a randomised control trial of bisphosphonate (zoledronic acid) treatment in childhood femoral head avascular necrosis due to Perthes disease

Jamil K 1 , Zacharin M 2 , Foster B 3 , Donald G 4 , Hassall T 5 , Siafarikas A 6 Show all authors , Johnson M 7 , Tham E 8 , Whitewood C 9 , Gebski V 10 , Cowell CT 1 , Little DG 1 , Munns CF 1

Affiliations 

  • 1 Discipline of Child and Adolescent Health, The Children's Hospital at Westmead Clinical School, University of Sydney, Sydney, New South Wales, Australia
  • 2 Department of Endocrinology, Murdoch Children's Research Institute, The Royal Children's Hospital Melbourne, Melbourne, Victoria, Australia
  • 3 Department of Orthopaedic Surgery, Women's and Children's Hospital, North Adelaide, South Australia, Australia
  • 4 Department of Orthopaedic, Lady Cilento Children's Hospital, South Brisbane, Queensland, Australia
  • 5 Department of Oncology, Lady Cilento Children's Hospital, South Brisbane, Queensland, Australia
  • 6 Department of Endocrinology and Diabetes, Princess Margaret Hospital for Children, Perth, Western Australia, Australia
  • 7 Department of Orthopaedics, The Royal Children's Hospital Melbourne, Melbourne, Victoria, Australia
  • 8 Department of Endocrinology and Diabetes, Women's and Children's Hospital Adelaide, North Adelaide, South Australia, Australia
  • 9 Department of Orthopaedic Surgery, Princess Margaret Hospital for Children, Perth, Western Australia, Australia
  • 10 NHRMC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia
BMJ Paediatr Open, 2017;1(1):e000084.
PMID: 29637122 DOI: 10.1136/bmjpo-2017-000084

Abstract

Introduction: Perthes disease (PD) is an idiopathic disorder presenting with avascular necrosis to the femoral head, which frequently results in flattening. Long-term function is directly related to the subsequent femoral head sphericity. Current treatment includes mechanical modalities and surgical procedures, which are therapeutic but are not uniformly able to prevent collapse. The use of the nitrogen-containing bisphosphonate zoledronic acid (ZA) to inhibit osteoclastic bone resorption is aimed at preserving femoral head strength, reducing collapse and thus maintaining shape. The proposed multicentre, prospective, randomised controlled trial intends to evaluate the efficacy of ZA treatment in PD.

Methods and analysis: An open-label randomised control trial recruiting 100 children (50 each treatment arm) 5 to 16 years old with unilateral PD. Subjects are randomly assigned to either (a) ZA and standard care or (b) Standard care. The primary outcome measure is deformity index (DI), a radiographic parameter of femoral head roundness assessed at 24 months, following 12 months of ZA treatment (3-monthly doses of ZA 0.025 mg/kg at baseline, 3, 6, 9 and 12 months) plus 12 months observation (group A) or 24 months of observation (group B). Secondary outcome measures are femoral head subluxation, Faces Pain scale, Harris hip score and quality of life. Assessments are made at baseline, 3 monthly during the first year of follow-up and then 6 monthly, until the 24th month.

Ethics and dissemination: The study commenced following the written approval from the Human Research Ethics Committee. Safety considerations regarding the effects of ZA are monitored which include the subject's symptomatology, mineral status, bone mass and turnover activity, and metaphyseal modelling. Data handling plan requires that all documents, clinical information, biological samples and investigation results will be held in strict confidence by study investigators to preserve its safety and confidentiality.

Trial registration number: Australian and New Zealand Clinical Trials ACTRN12610000407099, pre-results.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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