Clinical efficacy of alendronate treatment in patients with hip osteoarthritis: a 2-year randomized controlled trial

Abstract

Purpose: Degeneration and loss of cartilage is the main pathogenesis of hip and knee osteoarthritis, but periarticular bone alteration such as subchondral bone changes and osteophyte formation also plays an important role on disease progression and clinical symptom. Regulation of those bone turnovers by antiresorptive drugs may be effective approach for osteoarthritis treatment. Clinical trials of bisphosphonate treatments have not been conducted in hip osteoarthritis. Our objectives were to examine clinical efficacy of alendronate treatment in hip osteoarthritis by a 2-year randomized controlled study. Methods: We prospectively enrolled 51patients with symptomatic hip osteoarthritis who met the following criteria; the Kellgren-Lawrence (KL) osteoarthritis grade of 2 or more on anteroposterior radiographs, age between 30 and 90 years, and no history of bisphosphonate administration. All participants provided informed consent to the study which was approved by the Institutional Review Board. The patients were randomly assigned to either the alendronate group (alendronate 35mg/week and calcium lactate 600mg/day) or the control group (calcium lactate 600mg/day) for 2 years in 1:2 ratios. All patients were scheduled to receive the following assessments; (1) WOMAC pain score and visual analogue score (VAS) at 6-month intervals, (2) anteroposterior pelvic radiographs at 6-month intervals, (3) biochemical markers of urinary NTX-I and CTX-II at 0, 6,12,24 months, (4) DEXA of the hip at 0, 6,12,24 months, and (5) MRI of the hip at 0, 12 months. Between the alendronate and control groups, changes of the pain scores, NTX-I and CTX-II values, bone mineral density were compared using Mann-Whitney test. Osteoarthritis progression and change of bone marrow edema (BME) on MRI were compared using Fisher's exact test. Osteoarthritis progression was defined as worsening of joint space narrowing on radiographs or conversion to total hip arthroplasty. If the patient had osteoarthritis in both hips, only one hip with more severe osteoarthritis was included. Results: Thirty-three patients in the alendronate group and 18 patients in the control group were enrolled. During the follow-up, 8 patients were excluded due to abdominal discomfort and transfer of the residence, and remaining 30 patients in the alendronate group and 13 patients in the control group were analyzed. At the entry, there were no significant differences of age, gender, BMI, KL grades, VAS, urinary NTX-I and CTX-II values between the two groups. At 24 months, VAS pain reduction was significantly better in the alendronate group (p<0.05). Radiographic osteoarthritis progression was seen in 14 hips (47%) of the alendronate group and in 5 hips (38%) in the control group, without significant difference. NTX-I values were significantly lower at all times, and CTX-II values were significantly lower at 24 months in the alendronate group (Fig 1). Among each group, however, there was no significant difference of CTX-II values between the hips with and without osteoarthritis progression. On MRI, the alendronate group showed higher frequency of BME reduction at 12 moths (31%), as compared with 0% in the control group. Conclusions: Alendronate treatment had clinical efficacy of pain reduction but failed to show preventing effect of hip osteoarthritis progression. These findings were in accordance with previous clinical trials of bisphosphonate treatment in knee osteoarthritis. In knee osteoarthritis, early reduction of CTX-II by bisphosphonate treatment was assumed a prognostic index for prevention of osteoarthritis progression, however, those associations were not found in hip osteoarthritis. Further investigations regarding development of potent surrogates for disease progression and detection of optimal responders of bisphosphonate treatments are required.