The Efficacy of Denosumab in Decreasing Periprosthetic Bone Loss in Patients With Total Knee Arthroplasty

The Efficacy of Denosumab in Decreasing Periprosthetic Bone Loss in Patients With Total Knee Arthroplasty: A Randomised, Double Blind, Placebo Controlled Clinical Trial

This study evaluates the effect of Denosumab in decreasing the periprosthetic bone resorption after Total Knee Arthroplasty compared to placebo in 60 patients (30 placebo and 30 Denosumab) within a year after surgery.

Study Overview

• Status: Completed
• Conditions: Bone Resorption
• Intervention / Treatment: Drug: Denosumab; Drug: Placebo

Detailed Description

Periprosthetic bone resorption after Total Knee Arthroplasty occurs as a consequence of prosthetic implant on the bone. Some of this patients (up to 13%) develop an aseptic failure of the prosthesis needing revision surgery.

2 groups of patients are treated with Placebo and Denosumab in a double blind prospective trial. Densitometry, Knee society score (KSS), Western Ontario McMaster University Osteoarthritis Index (WOMAC) and the Medical Outcomes Study Short Form 36 (SF-36) were done in both groups at 0,3,6 and 12 months after surgery.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with Knee Osteoarthritis treated with Total Knee Arthroplasty

Exclusion Criteria:

• Patients allergies to Denosumab
• Patients with previous Osteoporosis treatment
• Patients with renal failure
• Patients with previous Bisphosphonate treatment for more than 5 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Denosumab; Patients treated with Denosumab	Drug: Denosumab; Denosumab treatment one year after surgery; Other Names: Prolia
Placebo Comparator: Placebo; Patients treated with placebo	Drug: Placebo; Serum one year after surgery; Other Names: Serum

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Bone Mass index	Bone Mass index in gr/cm3	Change in densitometry before surgery (0) and at three (3) months after surgery
Change in Bone Mass index	Bone Mass index in gr/cm3	Change in densitometry before surgery (0) and at six (6) months after surgery
Change in Bone Mass index	Bone Mass index in gr/cm3	Change in densitometry before surgery (0) and at twelve (12) months after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life (WOMAC)		WOMAC test before (0) and at three (3), six (6) and twelve (12) months after surgery
Quality of life (SF-36)		SF-36 test before (0) and at three (3), six (6) and twelve (12) months after surgery
Kidney function	Creatinine clearance	Before surgery and at three, six and twelve months after surgery
Liver function	ALT, AST	Before surgery and at three, six and twelve months after surgery
Bone turnover markers	Beta cross lap and Procollagen type 1 n-terminal propeptide (P1NP)	At three, six and twelve months after surgery

Collaborators and Investigators

• Sponsor: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
• Investigators: Principal Investigator: Jose Carlos Gonzalez, Orthopaedic Department-Hospital de la Santa Creu i Sant Pau

Publications and helpful links

General Publications

• Ishii Y, Yagisawa K, Ikezawa Y. Changes in bone mineral density of the proximal femur after total knee arthroplasty. J Arthroplasty. 2000 Jun;15(4):519-22. doi: 10.1054/arth.2000.4639.
• Sugita T, Umehara J, Sato K, Inoue H. Influence of tibial bone quality on loosening of the tibial component in total knee arthroplasty for rheumatoid arthritis: long-term results. Orthopedics. 1999 Feb;22(2):213-5. doi: 10.3928/0147-7447-19990201-10.
• Wang CJ, Wang JW, Weng LH, Hsu CC, Huang CC, Chen HS. The effect of alendronate on bone mineral density in the distal part of the femur and proximal part of the tibia after total knee arthroplasty. J Bone Joint Surg Am. 2003 Nov;85(11):2121-6. doi: 10.2106/00004623-200311000-00009.

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: April 28, 2016
• First Submitted That Met QC Criteria: May 2, 2016
• First Posted (Estimate): May 4, 2016

Study Record Updates

• Last Update Posted (Actual): August 11, 2017
• Last Update Submitted That Met QC Criteria: August 10, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: knee arthroplasty
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Bone Diseases; Bone Resorption; Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: IIBSP-DEN-2012-24; 2012-001285-15 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No