New Medications Being StudiedA Randomized, Double-Blind, Placebo-Controlled Study of Oral Alendronate Sodium 35 or 10 mg for the Prevention and Treatment of Periprosthetic Osteolysis.
1. To assess the effect of daily oral alendronate 35mg and 10 mg on the progression of femoral osteolysis (increase in total osteolytic lesion area) when administered for up to 6 months in patients with progressive femoral osteolysis.
2. To assess the effect of daily oral alendronate 35 mg and 10 mg on the progression of femoral osteolysis (maximum lesion depth of the primary osteolytic lesion and total osteolytic lesion interface length) when administered for up to 6 months in patients with progressive femoral osteolysis.
3. To assess the effect of daily oral alendronate 35mg/10mg and 10 mg on the progression of femoral osteolysis over an 18-month treatment period.
4. To assess the effect of 6 months versus 18 months of treatment with daily oral alendronate 35 mg and 10 mg on the progression of femoral osteolysis.
5. To assess the effect of daily oral alendronate 35 mg and 10 mg on the progression of acetabular osteolysis.
Male or female aged 18 to 80. The patient had a total hip arthroplasty (either cemented or uncemented, primary or revision) greater than or equal to 2 years prior to study entry.
The patient has at least on femoral osteolytic lesion evident on the baseline anteroposterior (AP) radiograph. For the purposes of this study all osteolytic lesions are defined as having a minimum area of 20mm, and a minimum depth (measured at the widest point of the lesion) of 2 mm. Patients with linear lesions may be included as long as the lesion(s) or part of the lesion(s) meet the above measurement criteria.
The patient has documented progressive femoral osteolysis defined as an increase in the total osteolytic lesion area (sum of all lesions) of at least 20 mm based upon a comparison of two AP radiographs taken on separate occasions within 3 years of entry into this study. Screening laboratories are either in or close to, the normal ranged provided by the central laboratory.
The patient has hip anatomy suitable for radiographic evaluation of the orthopedic hip and areas of osteolysis. The patient is able to tolerate the positioning necessary to allow for the acquisition of the standardized radiographs utilizing the positioning device as outlined in the standard operating procedures provided by the CRQAAC.
Exclusion CriteriaThe patient is either mentally or legally incompetent to give informed consent.
The patient has significant abnormalities or orthopedic hardware (such as screws or wires), other than the prosthesis, in the osteolytic area of interest which would interfere with the interpretation of the periprosthetic radiographs.
The patient is expected to need revision surgery of the total hip arthroplasty within 18 months of randomization.
Should not have an existing or impending periprosthetic fracture.
Should not be pregnant or lactating planning to become pregnant during the next year.
Should not have a current or recent (within the past 2 years) history of alcohol or drug dependence.
Should not have severe renal impairment (creatinine clearance <35 mL/minute) uncontrolled hypertension, decompensated heart failure, or unstable angina or has had a myocardial infarction within 6 months prior to study entry.
Should not have a history of, or evidence of, metabolic bone disease (other than osteoporosis).
Should not have a total daily calcium intake (dietary plus supplements) of <600ng,
Should not have a history of recent (within the past year) major upper GI disease.
Should not have a previous or current diagnosis of cancer or other malignant disease, with the exception of basal cell or epidermal skin cancer or carcinoma of the cervix, which has been cured by appropriate treatment or other malignancies curatively treated greater than or equal to 10 years ago without evidence recurrence.
Should not have evidence of hip infection (e.g. elevated ESR or WBC).
Should not be currently using or previously (within the last 2 years) bisphosphonate or floride (>1 mg/day).
Should not use of supraphysiologic doses of glucocorticoids at a prednisone-equivalent dose >7.5 mg/day for more than 30 days in the 1-year period immediately prior to, or following randomization.