Effect of Denosumab on Osteolytic Lesion Activity in THA
Research type
Research Study
Full title
Effect of Denosumab on Osteolytic Lesion Activity in Total Hip Arthroplasty (THA)
IRAS ID
77734
Contact name
Jemima Clarke
Sponsor organisation
Sheffield Teaching Hospitals NHS Trust
Eudract number
2011-000541-20
ISRCTN Number
N/A
Clinicaltrials.gov Identifier
Research summary
Research Summary
Although hip replacement surgery is a successful way of dealing with the pain and immobility caused by hip arthritis, 10% of the hip replacements carried out in the UK fail within 10 years. The main reason for this is the development periprosthetic osteolysis, that is, loss of bone around the site of the hip replacement. The osteolysis is thought to be due to the small particles of debris worn from the surfaces of the hip implant. These particles cause a reaction in the blood cells around the joint which in turn affects bone cells and leads to a loss of bone around the implant. The joint implant will then eventually become loose and unstable, a condition known as aseptic loosening. At present the only way to treat aseptic loosening is to have another operation to secure the hip joint, known as revision surgery. Revision surgery is not always successful and exposes the patient to the risk of major surgery.In this study we explore the potential for giving a medication (denosumab) that may prevent the loss of bone around the hip replacement implant. We will recruit patients who have been listed for revision surgery. One group of patients will be given a single dose of denosumab; another group will be given a placebo (dummy drug). At the time of the revision surgery a small sample of the bone from around the hip replacement will be taken and examined under the microscope. Comparisons will be made between the patients having the denosumab and those having placebo to find out whether the denosumab is having a beneficial effect on the bone surfaces. If successful, this study will lead to further studies to develop the use of denosumab to prevent aseptic loosening.
Summary of Results
In this phase 2 clinical trial we studied the effect of a single dose of the drug denosumab on osteolytic lesion activity in patients with osteolysis after hip replacement. We found that the drug inhibited osteoclast activity, as measured by surgical biopsy and by sysytemic biomarker measurements and was safe to administer in the single dose format. This evide gives support for the conduct of larger scale phase 3 clinical trials of this treatment using clinical endpoints for the disease.
REC name
Yorkshire & The Humber - Leeds West Research Ethics Committee
REC reference
11/YH/0252
Date of REC Opinion
20 Sep 2011
REC opinion
Further Information Favourable Opinion