Clinical Rheumatology

, Volume 32, Issue 12, pp 1759–1766 | Cite as

Alendronate treatment for hip osteoarthritis: prospective randomized 2-year trial

  • Takashi NishiiEmail author
  • Satoru Tamura
  • Toshiyuki Shiomi
  • Hideki Yoshikawa
  • Nobuhiko Sugano
Original Article


We examined the clinical efficacy of alendronate treatment for hip osteoarthritis using multiple outcome measures. Fifty patients with symptomatic hip osteoarthritis were enrolled in this prospective trial. The patients were randomly assigned to an alendronate group (35 mg/week alendronate and 600 mg/day calcium lactate) or a control group (600 mg/day calcium lactate) for 2 years. The groups were compared with regard to the following five parameters. The primary outcome measures are the following: (1) the Western Ontario and McMaster Universities (WOMAC) osteoarthritis pain score and the visual analog score (VAS). The secondary outcome measures are the following: (2) joint space width (JSW) measured on radiographs using a semiautomatic computer software, (3) the biochemical markers urinary N-telopeptide of type I collagen (NTX-I) and C-terminal cross-linking telopeptide of type II collagen (CTX-II), (4) dual-energy X-ray absorptiometry of the hip and lumbar spine, and (5) bone marrow edema on magnetic resonance images. The alendronate group showed pain improvement trends in VAS and WOMAC scores, whereas the control group showed worsening of pain. The alendronate group showed significant improvement in WOMAC pain scores after 12 months (p = 0.031) but no significant prevention of structural osteoarthritis progression, defined as a decrease in JSW >0.30 mm or conversion to total hip arthroplasty. There was significantly larger decrease in the biochemical markers and significantly increased bone density in the alendronate group. Alendronate treatment by standard dose for osteoporosis showed clinical efficacy for decreasing pain but failed to show preventive effects for structural progression of hip osteoarthritis.


Alendronate Hip osteoarthritis Randomized controlled trial Structure-modifying effects Symptom-modifying effects 



We gratefully acknowledge Hidenobu Miki, Katsuya Nakata, Mitsuyoshi Yamamura, Shyunsaku Nishihara, and Kengo Yamamoto in the Osaka Osteoarthritis Forum group for their instructions of establishment in study design and analysis of the study outcomes. Part of this study was funded by Grant from Osaka Foundation for the Prevention of Cancer and Cardiovascular Disease and Grant-in-Aid for Scientific Research, the Ministry of Education, Science and Culture of Japan.




  1. 1.
    Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, Gabriel S, Hirsch R, Hochberg MC, Hunder GG, Jordan JM, Katz JN, Kremers HM, Wolfe F (2008) Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum 58:26–35PubMedCrossRefGoogle Scholar
  2. 2.
    Yoshimura N, Campbell L, Hashimoto T, Kinoshita H, Okayasu T, Wilman C, Coggon D, Croft P, Cooper C (1998) Acetabular dysplasia and hip osteoarthritis in Britain and Japan. Br J Rheumatol 37:1193–1197PubMedCrossRefGoogle Scholar
  3. 3.
    Della Valle CJ, Mesko NW, Quigley L, Rosenberg AG, Jacobs JJ, Galante JO (2009) Primary total hip arthroplasty with a porous-coated acetabular component. A concise follow-up, at a minimum of 20 years, of previous reports. J Bone Joint Surg Am 91:1130–1135PubMedCrossRefGoogle Scholar
  4. 4.
    Takatori Y, Ninomiya S, Nakamura S, Morimoto S, Moro T, Nagai I, Mabuchi A (2001) Long-term results of rotational acetabular osteotomy in patients with slight narrowing of the joint space on preoperative radiographic findings. J Orthop Sci 6:137–140PubMedCrossRefGoogle Scholar
  5. 5.
    Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis Rheum 2000; 43:1905–1915Google Scholar
  6. 6.
    Zhang W, Moskowitz RW, Nuki G, Abramson S, Altman RD, Arden N, Bierma-Zeinstra S, Brandt KD, Croft P, Doherty M, Dougados M, Hochberg M, Hunter DJ, Kwoh K, Lohmander LS, Tugwell P (2008) OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthr Cartil 16:137–162PubMedCrossRefGoogle Scholar
  7. 7.
    Bettica P, Cline G, Hart DJ, Meyer J, Spector TD (2002) Evidence for increased bone resorption in patients with progressive knee osteoarthritis: longitudinal results from the Chingford study. Arthritis Rheum 46:3178–3184PubMedCrossRefGoogle Scholar
  8. 8.
    Burr DB (1998) The importance of subchondral bone in osteoarthrosis. Curr Opin Rheumatol 10:256–262PubMedCrossRefGoogle Scholar
  9. 9.
    Carbone LD, Nevitt MC, Wildy K, Barrow KD, Harris F, Felson D, Peterfy C, Visser M, Harris TB, Wang BW, Kritchevsky SB (2004) The relationship of antiresorptive drug use to structural findings and symptoms of knee osteoarthritis. Arthritis Rheum 50:3516–3525PubMedCrossRefGoogle Scholar
  10. 10.
    Garnero P, Aronstein WS, Cohen SB, Conaghan PG, Cline GA, Christiansen C, Beary JF, Meyer JM, Bingham CO 3rd (2008) Relationships between biochemical markers of bone and cartilage degradation with radiological progression in patients with knee osteoarthritis receiving risedronate: the Knee Osteoarthritis Structural Arthritis randomized clinical trial. Osteoarthr Cartil 16:660–666PubMedCrossRefGoogle Scholar
  11. 11.
    Spector TD, Conaghan PG, Buckland-Wright JC, Garnero P, Cline GA, Beary JF, Valent DJ, Meyer JM (2005) Effect of risedronate on joint structure and symptoms of knee osteoarthritis: results of the BRISK randomized, controlled trial. Arthritis Res Ther 7:R625–R633PubMedCrossRefGoogle Scholar
  12. 12.
    Buckland-Wright JC, Messent EA, Bingham CO 3rd, Ward RJ, Tonkin C (2007) A 2-year longitudinal radiographic study examining the effect of a bisphosphonate (risedronate) upon subchondral bone loss in osteoarthritic knee patients. Rheumatology 46:257–264PubMedCrossRefGoogle Scholar
  13. 13.
    Laslett LL, Doré DA, Quinn SJ, Boon P, Ryan E, Winzenberg TM, Jones G (2012) Zoledronic acid reduces knee pain and bone marrow lesions over 1 year: a randomised controlled trial. Ann Rheum Dis 71:1322–1328PubMedCrossRefGoogle Scholar
  14. 14.
    Kellgren JH, Lawrence JS (1957) Radiological assessment of osteo-arthrosis. Ann Rheum Dis 16:494–502PubMedCrossRefGoogle Scholar
  15. 15.
    Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW (1988) 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 15:1833–1840PubMedGoogle Scholar
  16. 16.
    Rosen HN, Dresner-Pollak R, Moses AC, Rosenblatt M, Zeind AJ, Clemens JD, Greenspan SL (1994) Specificity of urinary excretion of cross-linked N-telopeptides of type I collagen as a marker of bone turnover. Calcif Tissue Int 54:26–29PubMedCrossRefGoogle Scholar
  17. 17.
    Reijman M, Hazes JM, Bierma-Zeinstra SM, Koes BW, Christgau S, Christiansen C, Uitterlinden AG, Pols HA (2004) A new marker for osteoarthritis: cross-sectional and longitudinal approach. Arthritis Rheum 50:2471–2478PubMedCrossRefGoogle Scholar
  18. 18.
    Garnero P, Ayral X, Rousseau JC, Christgau S, Sandell LJ, Dougados M, Delmas PD (2002) Uncoupling of type II collagen synthesis and degradation predicts progression of joint damage in patients with knee osteoarthritis. Arthritis Rheum 46:2613–2624PubMedCrossRefGoogle Scholar
  19. 19.
    Peterfy CG, Ermazi A, Zaim S, Tirman PF, Miaux Y, White D, Kothari M, Lu Y, Fye K, Zhao S, Genant HK (2004) Whole-organ magnetic resonance imaging score (WORMS) of the knee in osteoarthritis. Osteoarthr Cartil 12:177–190PubMedCrossRefGoogle Scholar
  20. 20.
    Taljanovic MS, Graham AR, Benjamin JB, Gmitro AF, Krupinski EA, Schwartz SA, Hunter TB, Resnick DL (2008) Bone marrow edema pattern in advanced hip osteoarthritis: quantitative assessment with magnetic resonance imaging and correlation with clinical examination, radiographic findings, and histopathology. Skeletal Radiol 37:423–431PubMedCrossRefGoogle Scholar
  21. 21.
    Roemer FW, Hunter DJ, Winterstein A, Li L, Kim YJ, Cibere J, Mamisch TC, Guermazi A (2011) Hip Osteoarthritis MRI Scoring System (HOAMS): reliability and associations with radiographic and clinical findings. Osteoarthr Cartil 19:946–962PubMedCrossRefGoogle Scholar
  22. 22.
    Nishii T, Shiomi T, Sakai T, Takao M, Yoshikawa H, Sugano N (2012) Computational measurement of joint space width and structural parameters in normal hips. Arch Orthop Trauma Surg 132:591–598PubMedCrossRefGoogle Scholar
  23. 23.
    Langford R, McKenna F, Ratcliffe S, Vojtassák J, Richarz U (2006) Transdermal fentanyl for improvement of pain and functioning in osteoarthritis: a randomized, placebo-controlled trial. Arthritis Rheum 54:1829–1837PubMedCrossRefGoogle Scholar
  24. 24.
    Hayami T, Pickarski M, Wesolowski GA, McLane J, Bone A, Destefano J, Rodan GA, le Duong T (2004) The role of subchondral bone remodeling in osteoarthritis: reduction of cartilage degeneration and prevention of osteophyte formation by alendronate in the rat anterior cruciate ligament transection model. Arthritis Rheum 50:1193–1206PubMedCrossRefGoogle Scholar
  25. 25.
    Shirai T, Kobayashi M, Nishitani K, Satake T, Kuroki H, Nakagawa Y, Nakamura T (2011) Chondroprotective effect of alendronate in a rabbit model of osteoarthritis. J Orthop Res 29:1572–1577PubMedCrossRefGoogle Scholar
  26. 26.
    Van Offel JF, Dombrecht EJ, Bridts CH, Schuerwegh AJ, Ebo DG, Stevens WJ, De Clerck LS (2005) Influence of bisphosphonates on the production of pro-inflammatory cytokines by activated human articular chondrocytes. Cytokine 31:298–304PubMedCrossRefGoogle Scholar
  27. 27.
    Bingham CO 3rd, Buckland-Wright JC, Garnero P, Cohen SB, Dougados M, Adami S, Clauw DJ, Spector TD, Pelletier JP, Raynauld JP, Strand V, Simon LS, Meyer JM, Cline GA, Beary JF (2006) Risedronate decreases biochemical markers of cartilage degradation but does not decrease symptoms or slow radiographic progression in patients with medial compartment osteoarthritis of the knee: results of the 2-year multinational knee osteoarthritis structural arthritis study. Arthritis Rheum 54:3494–3507PubMedCrossRefGoogle Scholar
  28. 28.
    Tubach F, Ravaud P, Baron G, Falissard B, Logeart I, Bellamy N, Bombardier C, Felson D, Hochberg M, van der Heijde D, Dougados M (2005) Evaluation of clinically relevant changes in patient reported outcomes in knee and hip osteoarthritis: the minimal clinically important improvement. Ann Rheum Dis 64:29–33PubMedCrossRefGoogle Scholar
  29. 29.
    Nagae M, Hiraga T, Wakabayashi H, Wang L, Iwata K, Yoneda T (2006) Osteoclasts play a part in pain due to the inflammation adjacent to bone. Bone 39:1107–1115PubMedCrossRefGoogle Scholar
  30. 30.
    Ornetti P, Brandt K, Hellio-Le Graverand MP, Hochberg M, Hunter DJ, Kloppenburg M, Lane N, Maillefert JF, Mazzuca SA, Spector T, Utard-Wlerick G, Vignon E, Dougados M (2009) OARSI-OMERACT definition of relevant radiological progression in hip/knee osteoarthritis. Osteoarthr Cartil 17:856–863PubMedCrossRefGoogle Scholar
  31. 31.
    van Spil WE, Drossaers-Bakker KW, Lafeber FP (2013) Associations of CTX-II with biochemical markers of bone turnover raise questions on its tissue origin: data from CHECK, a cohort study of early osteoarthritis. Ann Rheum Dis 72:29–36PubMedCrossRefGoogle Scholar
  32. 32.
    Suka M, Yoshida K (2009) The national burden of musculoskeletal pain in Japan: projections to the year 2055. Clin J Pain 25:313–319PubMedCrossRefGoogle Scholar
  33. 33.
    Shiraki M, Kushida K, Fukunaga M, Kishimoto H, Taga M, Nakamura T, Kaneda K, Minaguchi H, Inoue T, Morii H, Tomita A, Yamamoto K, Nagata Y, Nakashima M, Orimo H (1999) A double-masked multicenter comparative study between alendronate and alfacalcidol in Japanese patients with osteoporosis: The Alendronate Phase III Osteoporosis Treatment Research Group. Osteoporos Int 10:183–192PubMedCrossRefGoogle Scholar

Copyright information

© Clinical Rheumatology 2013

Authors and Affiliations

  • Takashi Nishii
    • 1
    Email author
  • Satoru Tamura
    • 1
  • Toshiyuki Shiomi
    • 1
  • Hideki Yoshikawa
    • 2
  • Nobuhiko Sugano
    • 1
  1. 1.Department of Orthopaedic Medical EngineeringOsaka University Graduate School of MedicineSuita, OsakaJapan
  2. 2.Department of Orthopaedic SurgeryOsaka University Graduate School of Medicine, 2–2 YamadaokaSuita, OsakaJapan

Personalised recommendations