Denosumab for treating periprosthetic osteolysis; study protocol for a randomized, double-blind, placebo-controlled trialReport as inadecuate




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BMC Musculoskeletal Disorders

, 17:174

Orthopedics and biomechanics

Abstract

BackgroundWear-induced osteolysis is the main factor in reducing the longevity of total hip arthroplasty THA. The transmembrane Receptor Activator of Nuclear Factor κ B RANK and its corresponding ligand RANKL is an important regulator of osteoclast activity and bone resorption and is associated with osteolysis around implant. Inhibiting RANKL with denosumab is effective in vivo in preventing osteoporosis-related fractures. In vitro, osteoclasts can be blocked in animal models of osteolysis. We hypothesize that denosumab is effective in reducing wear-induced osteolysis around uncemented acetabular implants in THA.

Methods-designA randomized, double-blind, placebo-controlled trial will be conducted. We will include 110 patients, 40–85 years of age, with a known osteolytic lesion around an uncemented acetabular component ≥7 years after the primary operation. The patients will be randomized in a 1:1 ratio to subcutaneous injections of 60 mg denosumab or placebo for a total of 6 doses with start on day one and every 6 months with last treatment at 30 months. The primary endpoint will be the change in volume of the osteolytic lesion at 3 years measured with three-dimensional computed tomography 3D-CT. Secondary endpoints include functional outcome scores, change in bone mineral density of the lumbar spine, serological markers of bone turnover and adverse events.

DiscussionIn vitro results of both bisphosphonates and RANKL inhibitors have been promising, showing reduced osteolysis with treatment. This is, to our knowledge, the first clinical trial testing the efficacy of denosumab in reducing wear-induced osteolysis. The study is an academic, phase II trial from an independent center and is designed to demonstrate efficacy in reducing volume of osteolytic lesions around a total hip arthroplasty.

Trial registrationClinicalTrials.gov NCT02299817 2014-11-20

KeywordsTotal hip arthroplasty Osteolysis Denosumab Randomized clinical trial Outcome Computed tomography Abbreviations3D-CTthree-dimensional computed tomography

ADRAdverse drug reaction

AEadverse event

ANCOVAanalysis of co-variance

BMDBone mineral density

CONSORTconsolidated standards of reporting trials

CRFCase report form

CTcomputed tomography

DXAdual x-ray absorptiometry

ECGelectrocardiogram

EOSEnd of study

EQ-5Da standardised instrument for use as a measure of health outcome

EuroQoLEuropean quality of life scale

HHSHarris hip score

ICH-GCPinternational conference on harmonisation-good clinical practice

IMPinvestigational medicinal product

MCPmonocyte chemoattractant protein

MIGmonokine induced by interferon-β

MRImagnetic resonance imaging

P1NPProcollagen type 1 amino-terminal propeptide

PIprincipal investigator

PNRSPain Numeric Rating Scale

RANKreceptor activator of nuclear factor kappa B

RANKLreceptor activator of nuclear factor kappa B ligand

SADRSerious drug reaction

SAESerious adverse event

SCTxSerum C-terminal telopeptide of type I collagen

THAtotal hip arthroplasty

WOMACWestern Ontario and McMaster Universities arthritis index

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Author: Olof Sköldenberg - Agata Rysinska - Thomas Eisler - Mats Salemyr - Henrik Bodén - Olle Muren

Source: https://link.springer.com/



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