Effect of risedronate on joint structure and symptoms of knee osteoarthritis: results of the BRISK randomized, controlled trial [ISRCTN01928173]

Tim D Spector, Philip G Conaghan, J Christopher Buckland-Wright, Patrick Garnero, Gary A Cline, John F Beary, David J Valent, Joan M Meyer, Tim D Spector, Philip G Conaghan, J Christopher Buckland-Wright, Patrick Garnero, Gary A Cline, John F Beary, David J Valent, Joan M Meyer

Abstract

To determine the efficacy and safety of risedronate in patients with knee osteoarthritis (OA), the British study of risedronate in structure and symptoms of knee OA (BRISK), a 1-year prospective, double-blind, placebo-controlled study, enrolled patients (40-80 years of age) with mild to moderate OA of the medial compartment of the knee. The primary aims were to detect differences in symptoms and function. Patients were randomized to once-daily risedronate (5 mg or 15 mg) or placebo. Radiographs were taken at baseline and 1 year for assessment of joint-space width using a standardized radiographic method with fluoroscopic positioning of the joint. Pain, function, and stiffness were assessed using the Western Ontario and McMaster Universities (WOMAC) OA index. The patient global assessment and use of walking aids were measured and bone and cartilage markers were assessed. The intention-to-treat population consisted of 284 patients. Those receiving risedronate at 15 mg showed improvement of the WOMAC index, particularly of physical function, significant improvement of the patient global assessment (P < 0.001), and decreased use of walking aids relative to patients receiving the placebo (P = 0.009). A trend towards attenuation of joint-space narrowing was observed in the group receiving 15 mg risedronate. Eight percent (n = 7) of patients receiving placebo and 4% (n = 4) of patients receiving 5 mg risedronate exhibited detectable progression of disease (joint-space width >or= 25% or >or= 0.75 mm) versus 1% (n = 1) of patients receiving 15 mg risedronate (P = 0.067). Risedronate (15 mg) significantly reduced markers of cartilage degradation and bone resorption. Both doses of risedronate were well tolerated. In this study, clear trends towards improvement were observed in both joint structure and symptoms in patients with primary knee OA treated with risedronate.

Figures

Figure 1
Figure 1
Disposition of patients with knee osteoarthritis in a controlled, randomized trial of risedronate.
Figure 2
Figure 2
Changes in mean values at 12 months from baseline measures in patients with osteoarthritis. Patients were given risodronate (Ris) or placebo. Scores were the weighted composite of the 24 question scores on the visual analogue scale (1 to 100 mm) of the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index or its subscales for pain, stiffness, and physical function. Vertical lines represent standard errors of the mean. P values refer to risedronate (15 mg) vs baseline values.
Figure 3
Figure 3
Changes in mean patient global assessment after risedronate or placebo in osteoarthritis. Vertical lines represent standard errors of the mean. Ris, risedronate.
Figure 4
Figure 4
Relation between WOMAC scores and minimum percentage change in JSW after 1 year in patients with osteoarthritis. Scores were the weighted composite (1 to 100 mm) of the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index or its subscales for pain and physical function. JSW, joint-space width.
Figure 5
Figure 5
Changes in urinary CTX-II levels after treatment of osteoarthritis patients with placebo or risedronate. Ris, risedronate.

References

    1. Dixon T, Shaw M, Ebrahim S, Dieppe P. Trends in hip and knee joint replacement: socioeconomic inequalities and projections of need. Ann Rheum Dis. 2004;63:825–830. doi: 10.1136/ard.2003.012724.
    1. Millar WJ. Hip and knee replacement. Health Rep. 2002;14:37–50.
    1. Melzer D, Guralnik JM, Brock D. Prevalence and distribution of hip and knee joint replacements and hip implants in older Americans by the end of life. Aging Clin Exp Res. 2003;15:60–66.
    1. Quam JP, Michet CJ, Jr, Wilson MG, Rand JA, Ilstrup DM, Melton LJ, 3rd, Wallrichs SL. Total knee arthroplasty: a population-based study. Mayo Clin Proc. 1991;66:589–595.
    1. Buckland-Wright JC, Macfarlane DG, Lynch JA, Jasani MK, Bradshaw CR. Joint space width measures cartilage thickness in osteoarthritis of the knee: high resolution plain film and double contrast macroradiographic investigation. Ann Rheum Dis. 1995;54:263–268.
    1. Spector TD. Bisphosphonates: potential therapeutic agents for disease modification in osteoarthritis. Aging Clin Exp Res. 2003;15:413–418.
    1. Bettica P, Cline G, Hart DJ, Meyer J, Spector TD. Evidence for increased bone resorption in patients with progressive knee osteoarthritis: longitudinal results from the Chingford study. Arthritis Rheum. 2002;46:3178–3184. doi: 10.1002/art.10630.
    1. Li B, Aspden RM. Mechanical and material properties of the subchrondral bone plate from the femoral neck of patients with osteoarthritis or osteoporosis. Ann Rheum Dis. 1997;56:247–254.
    1. Bendele AM, Hulman JF. Spontaneous cartilage degeneration in guinea pigs. Arthritis Rheum. 1988;31:561–565.
    1. Meyer JM, Dansereau SM, Farmer RW, Jeans GL, Prenger MC. Bisphosphonates structurally similar to risedronate (actonel) slow disease progression in the guinea pig model of primary osteoarthritis [abstract] Arthritis Rheum. 2001. p. 5307. abstract 1527.
    1. Meyer J, Farmer R, Prenger MC. Risedronate but not alendronate slows disease progression in the guinea pig model of primary osteoarthritis [abstract] J Bone Miner Res. 2001. p. 5305. abstract SA472.
    1. Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, Christy W, Cooke TD, Greenwald R, Hochberg M, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum. 1986;29:1039–1049.
    1. Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol. 1988;15:1833–1840.
    1. Buckland-Wright JC. Protocols for precise radio-anatomical positioning of the tibiofemoral and patellofemoral compartments of the knee. Osteoarthritis Cartilage. 1995:71–80.
    1. Buckland-Wright JC, Bird CF, Ritter-Hrncirik CA, Cline GA, Tonkin C, Hangartner TN, Ward RJ, Meyer JM, Meredith MP. X-ray technologists' reproducibility from automated measurements of the medial tibiofemoral joint space width in knee osteoarthritis for a multicenter, multinational clinical trial. J Rheumatol. 2003;30:329–338.
    1. Hanson DA, Weis MA, Bollen AM, Maslan SL, Singer FR, Eyre DR. A specific immunoassay for monitoring human bone resorption: quantitation of type I collagen cross-linked N-telopeptides in urine. J Bone Miner Res. 1992;7:1251–1258.
    1. Garnero P, Delmas PD. Assessment of the serum levels of bone alkaline phosphatase with a new immunoradiometric assay in patients with metabolic bone disease. J Clin Endocrinol Metab. 1993;77:1046–1053. doi: 10.1210/jc.77.4.1046.
    1. Christgau S, Garnero P, Fledelius C, Moniz C, Ensig M, Gineyts E, Rosenquist C, Qvist P. Collagen type II C-telopeptide fragments as an index of cartilage degradation. Bone. 2001;29:209–215. doi: 10.1016/S8756-3282(01)00504-X.
    1. Bellamy N. WOMAC Osteoarthritis Index: A User's Guide. 2. London, Ontario: Victoria Hospital; 1995.
    1. Carbone LD, Nevitt MC, Wildy K, Barrow KD, Harris F, Felson D, Peterfy C, Visser M, Harris TB, Wang BW, et al. The relationship of antiresorptive drug use to structural findings and symptoms of knee osteoarthritis. Arthritis Rheum. 2004;50:3516–3525. doi: 10.1002/art.20627.
    1. Bingham C, Beary J, Cohen S, Clauw D, Cline G, Meyer J. Clinically significant placebo improvement occurs by 6 months and is maintained through 24 months in a study of knee OA pain and function [abstract] American College of Rheumatology Annual Meeting: October 16–21 2004; San Antonio, TX. 2004. Abstract 263.
    1. Reijman M, Hazes JM, Birma-Zeinstra SM, Koes BW, Christgau S, Christiansen C, Uitterlinden AG, Pols HA. A new marker for osteoarthritis: cross-sectional and longitudinal approach. Arthritis Rheum. 2004;50:2471–2478. doi: 10.1002/art.20332.
    1. Brandt KD, Mazzuca SA, Katz BP, Lane KA, Doxycycline Study Group The disease modifying effect of doxycycline (doxy) includes symptomatic benefit for patients with knee osteoarthritis [abstract] Arthritis Rheum. 2003;48:3643. doi: 10.1002/art.11017. Abstract LB1.
    1. Reginster JY, Deroisy R, Rovati LC, Lee RL, Lejeune E, Bruyere O, Giacovelli G, Henrotin Y, Dacre JE, Gossett C. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet. 2001;357:251–256. doi: 10.1016/S0140-6736(00)03610-2.
    1. Dieppe PA, Cushnaghan J, Shepstone L. The Bristol 'OA500' study: progression of osteoarthritis (OA) over 3 years and the relationship between clinical and radiographic changes at the knee joint. Osteoarthritis Cartilage. 1997;5:87–97.
    1. Buckland-Wright JC, Wolfe F, Ward RJ, Flowers N, Hayne C. Substantial superiority of semiflexed (MTP) views in knee osteoarthritis: a comparative radiographic study, without fluoroscopy, of standing extended, semiflexed (MTP), and schuss views. J Rheumatol. 1999;26:2664–2674.
    1. Mazzuca SA, Brandt KD, Dieppe PA, Doherty M, Katz BP, Lane KA. Effect of alignment of the medial tibial plateau and x-ray beam on apparent progression of osteoarthritis in the standing anteroposterior knee radiograph. Arthritis Rheum. 2001;44:1786–1794. doi: 10.1002/1529-0131(200108)44:8<1786::AID-ART315>;2-L.
    1. Mazzuca SA, Brandt KD, Buckland-Wright JC, Buckwalter KA, Katz BP, Lynch JA, Ward RJ, Emsley CL. Field test of the reproducibility of automated measurements of medial tibiofemoral joint space width derived from standard knee radiographs. J Rheumatol. 1999;26:1359–1365.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi