Efficacy of Zoledronic Acid in Enhancement of Early Stability of Cementless Primary Hip Prosthesis
This is a randomized, double-blind and placebo-controlled study to evaluate the efficacy of zoledronic acid on the biologic incorporation of cementless hip prosthesis in postmenopausal female patients.The study population consists of postmenopausal female patients scheduled for total hip replacement because of degenerative hip osteoarthritis. The patients will receive either a single dose of 5 mg zoledronic acid or placebo intravenously after surgery before hospital discharge. The patients will be followed-up for 1 year. Zoledronic acid therapy has been shown to promote bone ingrowth into porous implants in pre-clinical models. The investigators hypothesis is that zoledronic acid, given as a single intravenous infusion after hip replacement surgery, enhances bone ingrowth into porous surface of cementless hip prostheses. As a primary outcome, the therapy is expected to reduce periprosthetic bone loss measured by DXA. Enhancement of bone ingrowth is expected to increase primary stability of the hip prosthesis and this effect can be detected with high-precision three-dimensional RSA imaging modality and in a faster functional recovery of the patients.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy of Zoledronic Acid in Enhancement of Early Stability of Cementless Primary Hip Prosthesis|
- The primary objective of this study is to test whether a single infusion of zoledronic acid reduces periprosthetic bone loss measured by DXA. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- RSA outcome, functional recovery and metabolic treatment response [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
- to demonstrate that the treatment can enhance biologic incorporation of cementless hip prostheses as shown by reduced prosthetic migration measured by RSA (radiostereometry)
- to demonstrate that enhanced incorporation of the hip prostheses following the therapy lead to faster functional recovery and better subjective outcome of the procedure.
- to demonstrate that the treatment suppresses biochemical markers of bone resorption.
|Study Start Date:||May 2007|
|Study Completion Date:||June 2011|
|Primary Completion Date:||December 2010 (Final data collection date for primary outcome measure)|
Drug: zoledronic acid
All the patients enrolled in the study will receive the standard of care with respect to surgical prosthetic replacement of the diseased hip. The patients will receive a custom-modified (RSA marked) hydroxyapatite-coated prosthesis with ceramic-on-ceramic bearing surfaces (SYMAX-TRIDENT, Stryker). The prosthesis modification provided by the manufacturer has a CE mark. The patients in the active-treatment group will receive a single 5 mg dose of zoledronic acid intravenously just prior to release from the hospital (about 5th day post-surgery) as an adjunct therapy. The control group will receive a placebo (saline) infusion. The active and placebo infusion vials will be provided by Norvartis Pharmaceutical. After surgery, before the administration of zoledronic acid or placebo, each patient will be re-screened for the level of serum calcium. In the case of postoperative hypocalcemia, the infusion will be postponed for a minimum of 3-4 weeks and the infusion will be given after the repeated measurements of serum calcium. All patients will receive calcium and D-vitamin supplementation throughout the study period. Efficacy will be assessed on the basis of clinical, radiographic (RSA, DXA, Spiral CT, conventional radiography) and laboratory criteria. The clinical benefit of zoledronic acid therapy is defined in terms of faster functional recovery, which will be analyzed in two ways: (1) the functional outcome (muscle strength, gait analysis and pedometry) will be repeatedly evaluated before and after surgery, and (2) the subjective outcome of the procedure as well as the general health assessment will be determined at each follow-up visits using standardized outcome measures. The primary objective of this study is to test whether a single infusion of zoledronic acid reduces periprosthetic bone loss measured by DXA at 12 months. Statistical significance of differences in periprosthetic bone mineral density between active-treatment and placebo groups will be analyzed using repeated analysis of variance.
|Turku University Hospital|
|Turku, Finland, 20520|
|Principal Investigator:||Hannu T Aro, MD, PhD||Turku University Hospital|