Locally Administered Clodronate in the Prevention of Aseptic Implant Loosening

Could the Intra-operative Clodronate Rinsing Improve the Integration of the Femoral Stem in a Prospective, Double-blinded, Randomized, Placebo-controlled Clinical RSA-study

Periprosthetic bone-loss after total hip arthroplasty (THA), detected as an early migration of the prosthesis, may predict later loosening. The investigators hypothesized that by reducing bone resorption after THA with bisphosphonates, it might be possible to achieve better early fixation of the implant.

Nineteen patients suffering arthrosis were recruited to a prospective, double-blinded, randomized, placebo-controlled clinical pilot trial. Patients were operated with an uncemented Bimetric stem with tantalum markers, the acetabular cup and liner were chosen by the surgeon. The femoral proximal intramedullary canal was rinsed with 1mM (millimole) clodronate, that was done by adding the clodronate to the 1000 ml 0.9% NaCl (sodium chloride) in nine patients and rinsing solution was the pure 0.9% NaCl for 10 patients. These rinsing packages were labeled only with the code from the pharmacy of the hospital. These patients were followed for two years using radiostereometric analysis (RSA), dual energy x-ray absorptiometry (DXA) and the Harris hip score (HHS).

The purpose of the investigator's study was to examine whether the local intraoperative administration of clodronate could reduce periprosthetic bone loss and further stem migration after primary THA.

Study Overview

• Status: Completed
• Conditions: Hip Arthrosis
• Intervention / Treatment: Drug: Clodronate; Drug: Saline

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Early Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 73 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• hip arthrosis and
• a primary THA was planned

Exclusion Criteria:

• renal insufficiency
• hypercalcemia
• malignant tumors
• contemporaneously treatment with another bisphosphonate or aminoglycoside

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Clodronate; 1 mM clodronate (60 mg in 1000 ml saline) was used intraoperatively during total hip arthroplasty: before installation of the prosthesis, the rinsing was performed with pulsatile lavage using the clodronate solution. The time for rinsing was about one minute.	Drug: Clodronate
Placebo Comparator: Saline; 1000 ml saline was used intraoperatively during total hip arthroplasty: before installation of the prosthesis, the rinsing was performed with pulsatile lavage using the saline solution. The time for rinsing was about one minute.	Drug: Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal total point motion (MTPM) - migration of the femoral stem	It represents the length of the translation vector of the point in a rigid body that has the greatest motion. It can only have positive values, and is not normally distributed. The reason for using MTPM is that in many cases, motion implies a biological effect of some kind and this effect is liable to be greatest at the point of maximum motion. The parameter has been measured by RSA-methods, which is an accurate method of determining the migration and wear of orthopaedic implants: it determine the precise location of two distinct objects relative to each other in three dimension such as the relative position of the femoral component and the proximal femur. In radiostereometric analysis the position in space of the original object is reconstructed from a two dimensional x-ray film using tantalum beads. Movement between segments is then calculated by localizing each segment in a coordinate system. Lower values represent a better outcome.	0 to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone mineral density (BMD) in 7 Gruen zones	BMD was measured by dual-energy X-ray absorptiometry, DXA. In clinical use, precision errors are < 5 %. To evaluate the horizontal linear distribution of the BMD, seven Gruen zones, peri-prosthetic sub-regions of interest, ROI (region of interest) were calculated by the software on the anteroposterior view of the proximal femur. The value of BMD is g/cm2 and it estimates the strength of the bone. Higher values/lesser decrease in values represent a better outcome.	0 to 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Migration of femoral stem	Subsidence and vertical movement of the femoral stem (scale micrometers), x-, y- and z-translations. Parameters were measured using RSA-methods and the scaling is linear. Lower values represent a better outcome.	0 to 24 months
The maximal (MTPM) maximal total point motion	The maximal MTPM value after 3 months when the expected integration of stem should have happened. Lower values represent a better outcome.	3 to 24 months
Correlation between baseline BMD and the maximal MTPM	This parameters summarize the BMD and RSA values together. The investigators have planned it to evaluate the correlation between the quality of periprosthetic bone in baseline and the migration of femoral stem during 2 years follow-up period between the study groups.	BMD (0 month) - the maximal MTPM 3 to 24 months
Harris Hip Score (HHS)	Harris Hip Score (HHS) is a clinician-based outcome measure, health status scale, that is frequently used to measure the outcome of total hip arthroplasty. It is measured by questionnaire that give points from 0 to 100. Higher values represent a better outcome.	0 to 24 months

Collaborators and Investigators

• Sponsor: University of Oulu

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2004
• Primary Completion (Actual): March 12, 2014
• Study Completion (Actual): March 12, 2014

Study Registration Dates

• First Submitted: January 4, 2019
• First Submitted That Met QC Criteria: January 14, 2019
• First Posted (Actual): January 15, 2019

Study Record Updates

• Last Update Posted (Actual): January 18, 2019
• Last Update Submitted That Met QC Criteria: January 16, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: DXA; RSA; Bisphosphonates; Migration of stem; Aseptic loosening of prosthesis
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Hip; Physiological Effects of Drugs; Bone Density Conservation Agents; Clodronic Acid
• Other Study ID Numbers: Ei tiedossa

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified individual participant data for all primary and secondary outcome data will be made available.
• IPD Sharing Time Frame: Data will be available after submitting the results to the scientific journals and five years after the publication.
• IPD Sharing Access Criteria: Data Access requests will be reviewed By an external Independent Review Panel. Requestors will be required to sign a Data Access Agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

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