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

Kamal Jamil, Margaret Zacharin, Bruce Foster, Geoffrey Donald, Timothy Hassall, Aris Siafarikas, Michael Johnson, Elaine Tham, Colin Whitewood, Val Gebski, Chris T. Cowell, David Graham Little, Craig Frank Munns

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Article numberY
JournalBMJ Paediatrics Open
Volume1
Issue number1
DOIs
Publication statusPublished - Dec 2017

Fingerprint

zoledronic acid
Femur Head Necrosis
Legg-Calve-Perthes Disease
Diphosphonates
Thigh
Therapeutics
Observation
Outcome Assessment (Health Care)
Safety
Facial Pain
Bone Remodeling
Research Ethics Committees
Confidentiality
Bone Resorption
New Zealand
Ethics
Minerals
Hip
Arm
Nitrogen

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Protocol for a randomised control trial of bisphosphonate (zoledronic acid) treatment in childhood femoral head avascular necrosis due to Perthes disease. / Jamil, Kamal; Zacharin, Margaret; Foster, Bruce; Donald, Geoffrey; Hassall, Timothy; Siafarikas, Aris; Johnson, Michael; Tham, Elaine; Whitewood, Colin; Gebski, Val; Cowell, Chris T.; Little, David Graham; Munns, Craig Frank.

In: BMJ Paediatrics Open, Vol. 1, No. 1, Y, 12.2017.

Research output: Contribution to journalArticle

Jamil, K, Zacharin, M, Foster, B, Donald, G, Hassall, T, Siafarikas, A, Johnson, M, Tham, E, Whitewood, C, Gebski, V, Cowell, CT, Little, DG & Munns, CF 2017, 'Protocol for a randomised control trial of bisphosphonate (zoledronic acid) treatment in childhood femoral head avascular necrosis due to Perthes disease', BMJ Paediatrics Open, vol. 1, no. 1, Y. https://doi.org/10.1136/bmjpo-2017-000084
Jamil, Kamal ; Zacharin, Margaret ; Foster, Bruce ; Donald, Geoffrey ; Hassall, Timothy ; Siafarikas, Aris ; Johnson, Michael ; Tham, Elaine ; Whitewood, Colin ; Gebski, Val ; Cowell, Chris T. ; Little, David Graham ; Munns, Craig Frank. / Protocol for a randomised control trial of bisphosphonate (zoledronic acid) treatment in childhood femoral head avascular necrosis due to Perthes disease. In: BMJ Paediatrics Open. 2017 ; Vol. 1, No. 1.
@article{1b35be35672e4b1890b0ddf334fd0190,
title = "Protocol for a randomised control trial of bisphosphonate (zoledronic acid) treatment in childhood femoral head avascular necrosis due to Perthes disease",
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.",
author = "Kamal Jamil and Margaret Zacharin and Bruce Foster and Geoffrey Donald and Timothy Hassall and Aris Siafarikas and Michael Johnson and Elaine Tham and Colin Whitewood and Val Gebski and Cowell, {Chris T.} and Little, {David Graham} and Munns, {Craig Frank}",
year = "2017",
month = "12",
doi = "10.1136/bmjpo-2017-000084",
language = "English",
volume = "1",
journal = "BMJ Paediatrics Open",
issn = "2399-9772",
number = "1",

}

TY - JOUR

T1 - Protocol for a randomised control trial of bisphosphonate (zoledronic acid) treatment in childhood femoral head avascular necrosis due to Perthes disease

AU - Jamil, Kamal

AU - Zacharin, Margaret

AU - Foster, Bruce

AU - Donald, Geoffrey

AU - Hassall, Timothy

AU - Siafarikas, Aris

AU - Johnson, Michael

AU - Tham, Elaine

AU - Whitewood, Colin

AU - Gebski, Val

AU - Cowell, Chris T.

AU - Little, David Graham

AU - Munns, Craig Frank

PY - 2017/12

Y1 - 2017/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85049462437&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85049462437&partnerID=8YFLogxK

U2 - 10.1136/bmjpo-2017-000084

DO - 10.1136/bmjpo-2017-000084

M3 - Article

AN - SCOPUS:85049462437

VL - 1

JO - BMJ Paediatrics Open

JF - BMJ Paediatrics Open

SN - 2399-9772

IS - 1

M1 - Y

ER -