Prevention of Periprosthetic Bone Loss After Total Hip Replacement by Annual Bisphosphonate Therapy

Investigation on the Prevention of Periprosthetic Bone Loss After Total Hip Replacement by Annual Bisphosphonate Therapy: A Prospective Randomized Clinical Trial

Periprosthetic bone loss caused by stress-shielding effect, a phenomenon of bone atrophy under mechanical unloading after THR implantation, further compromises the longevity of implant. The prospective randomized study is aimed to investigate the periprosthetic bone loss after primary total hip replacements.

Study Overview

• Status: Completed
• Conditions: Functional Outcomes; Prevention of BMD Loss After THR; Serum Markers of Bone Turnover
• Intervention / Treatment: Drug: Aclasta; Drug: Placebo

Detailed Description

This study is a prospective, randomized, open-label clinical trial. The study will be performed in patients after obtaining informed consent. Group assignment is by drawing a sealed envelops based on random table. (1) Group 1: Experimental group 30 cases, Aclasta® (Zoledronic acid 5mg/100ml) is given intravenously on the 4th postoperative day and one year after the total hip replacement, (2) Group 2: Control group, 30 cases, no bisphosphonate is given to the patients. Only the unilateral coxarthrosis will be recruited for the study. Patients will be analyzed with (1) DXA study (2) Clinical assessment (Harris hip score and SF-12) (3) X-ray (4) serum marker of bone turnover. Patients will be scheduled for specified examinations preoperatively, postoperatively 6 weeks, 3 months, 6 months, 12 months, and 24 months.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 3

Contacts and Locations

Study Locations

• Taiwan
  • Taoyuan
    • Kweishan, Taoyuan, Taiwan, 333
      • Chang Gung Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female,between 35 and 85 years of age
2. Indicated for Total hip replacement for various hip diseases
3. Has preoperative DXA study within 3 months before the total hip replacement procedure or willing to receive preoperative DXA study as a baseline comparison
4. Signed written informed consent
5. Standard transgluteal approach for total hip replacement using Zimmer Triology Cup and Versys Fiber Metal Taper Stem with metal to highly cross-linked polyethylene bearing surface

Exclusion Criteria:

1. Any prior use of intravenous bisphosphonate within the last 2 years
2. Uncontrolled seizure disorders associated with falls
3. A history of invasive malignancy of any organ system, treated or untreated, within the past five years; excluding, basal cell or squamous cell carcinoma of the skin, colonic polyps with non-invasive malignancy which have been removed
4. Carcinoma in situ of the uterine cervix
5. History of osteogenesis imperfecta, multiple myeloma, or Paget's disease
6. Active primary hyperparathyroidism
7. History of iritis or uveitis
8. Self-reported history of diabetic nephropathy or retinopathy
9. AST or ALT more than twice the upper limit of normal
10. Alkaline phosphatase more than twice the upper limit of normal
11. Serum calcium 2.75 mmol/L (11.0 mg/dL)
12. Baseline renal insufficiency (calculated creatinine clearance 35 ml/min)
13. History of hypersensitivity to bisphosphonates
14. Use of any investigational drug(s) and/or devices within 30 days prior to randomization
15. Any medical or psychiatric condition which, in the Investigator's opinion, would preclude the participant from adhering to the Protocol or completing the trial per protocol
16. Use of hip protectors
17. With implant or prosthesis on the contralateral hip joint

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Placebo group	Drug: Placebo; No IV aclasta
EXPERIMENTAL: Aclasta; Aclasta IV once annual for 2 years	Drug: Aclasta; Aclasta once annually for 2 years

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
bone mineral density [g/cm2] of the 7 Gruen zones	bone mineral density measured by dual energy x-ray absorptiometry	5 years
bone mineral density change relative to the baseline values of the 7 Gruen zones	bone mineral density measured by dual energy x-ray absorptiometry	5 years
implant loosening or migration	check the implant position by serial standard X ray follow-up	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
serum alkaline phosphatase		5 years
serum calcium level		5 years
serum phosphate level		5 years
serum osteocalcin level		5 years
serum N-telopeptide procollagen level		5 years
serum creatinine level	renal function and glomerular filtration rate	5 years
serum alanine aminotransferase level	liver function	5 years
serum aspartate aminotransferase level	liver function	5 years
harris hip score	hip function measurement	5 years
short form-12	life quality measurement	5 years
University of California Los Angeles Activity Score	functional and activity evaluation, 10 point scale	5 years

Collaborators and Investigators

• Sponsor: Mel Shiuann-Sheng Lee
• Collaborators: Novartis

Publications and helpful links

Helpful Links

• American Academy of Orthopaedic Surgeons
• Chang Gung Memorial Hospital

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (ACTUAL): January 1, 2013
• Study Completion (ACTUAL): June 1, 2016

Study Registration Dates

• First Submitted: July 7, 2016
• First Submitted That Met QC Criteria: July 15, 2016
• First Posted (ESTIMATE): July 20, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): July 20, 2016
• Last Update Submitted That Met QC Criteria: July 15, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: bone mineral density; bisphosphonate; Total hip replacement; functional outcomes
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Bone Density Conservation Agents; Zoledronic Acid
• Other Study ID Numbers: 98-1150A3

Plan for Individual participant data (IPD)

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