Archives of Osteoporosis

, 13:107 | Cite as

Effects of anti-osteoporosis medications on total hip arthroplasty risks in osteoporotic patients with hip osteoarthritis in Taiwan: a nationwide cohort study

  • Chih-Chien Hung
  • Chen-Yu Wang
  • Shau-Huai Fu
  • Rong-Sen Yang
  • Fei-Yuan HsiaoEmail author
Original Article



This nationwide cohort study examined the potential disease-modifying effect of anti-osteoporosis medication on hip osteoarthritis. The results revealed that the usage of anti-osteoporosis medication is not associated with decreased risk in undergoing total hip arthroplasty in patient with hip osteoarthritis.


This study aimed to assess the association between use of anti-osteoporosis medications (AOMs) and the risk of undergoing total hip arthroplasty (THA) in patients with hip osteoarthritis (OA).


Using the 2008–2013 National Health Insurance Research Database, we identified patients who were first diagnosed as having hip OA. All identified patients were followed until THA, death of any cause, or December 31, 2013, whichever occurred first. All AOM exposures were divided into three categories: bisphosphonates use, non-bisphosphonates use, and no use of AOMs and assessed in a time-varying manners. The primary outcome was THA. The secondary outcome was the differences in the longitudinal utilization of NSAIDs between AOM users and non-users. Time-dependent Cox proportional hazards models were used to investigate the effect of AOM use on the risk of THA.


We identified 35,870 patients who were first diagnosed as having hip OA and had no history of AOM use between 2009 and 2012. Among them, 3162 and 1667 patients had their first prescription of bisphosphonates and other non-bisphosphonates AOMs during the follow-up period. Mean age of bisphosphonates users, non-bisphosphonates users, and non-users was 75.62, 76.84, and 67.39 years, respectively. Bisphosphonates or non-bisphosphonates users did not show significant change when compared to non-users in terms of risk of undergoing THA [adjusted hazard ratio (aHR) 0.972, 95% confidence interval (CI) 0.743–1.273; aHR 0.926, 95% CI 0.672–1.277].


Our results showed that the use of AOMs is not associated with decreased risk of THA in patients with hip OA.


Osteoporosis Hip osteoarthritis Total hip arthroplasty Anti-osteoporosis medications 



The study was funded by the National Taiwan University Hospital, Yun-Lin branch (grant number NTUHYL105.N002).

Compliance with ethical standards

Conflicts of interest


Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Research Ethics Committee of National Taiwan University Hospital (NTUH-REC-201510092W) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

For this retrospective type of study, formal consent is not required.


  1. 1.
    Hiligsmann M, Cooper C, Arden N, Boers M, Branco JC, Brandi ML et al (2013) Health economics in the field of osteoarthritis: an expert's consensus paper from the European Society for Clinical and Economic Aspects of osteoporosis and osteoarthritis (ESCEO). Semin Arthritis Rheum 43(3):303–313. CrossRefPubMedGoogle Scholar
  2. 2.
    Litwic A, Edwards M, Dennison E, Cooper C (2013) Epidemiology and burden of osteoarthritis. Br Med Bull 105:185–199. CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Salmon JH, Rat AC, Sellam J, Michel M, Eschard JP, Guillemin F, Jolly D, Fautrel B (2016) Economic impact of lower-limb osteoarthritis worldwide: a systematic review of cost-of-illness studies. Osteoarthr Cartil 24(29):1500–1508. CrossRefPubMedGoogle Scholar
  4. 4.
    Berenbaum F (2013) Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthr Cartil 21(1):16–21. CrossRefPubMedGoogle Scholar
  5. 5.
    Scanzello CR, Goldring SR (2012) The role of synovitis in osteoarthritis pathogenesis. Bone 51(2):249–257. CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Kellgren JH, Lawrence JS (1957) Radiological assessment of osteo-arthrosis. Ann Rheum Dis 16(04):494–502. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Ahlbäck S (1968) Osteoarthrosis of the knee. A radiographic investigation. Acta Radiol Diagn (Stockh) Suppl 277:7–72Google Scholar
  8. 8.
    Geusens PP, van den Bergh JP (2016) Osteoporosis and osteoarthritis: shared mechanisms and epidemiology. Curr Opin Rheumatol 28(2):97–103. CrossRefPubMedGoogle Scholar
  9. 9.
    Neuprez A, Neuprez AH, Kurth W, Gillet P, Bruyère O, Reginster JY (2018) Profile of osteoarthritic patients undergoing hip or knee arthroplasty, a step toward a definition of the "need for surgery". Aging Clin Exp Res 30:315–321. CrossRefPubMedGoogle Scholar
  10. 10.
    Bruyère O, Cooper C, Arden N, Branco J, Brandi ML, Herrero-Beaumont G, Berenbaum F, Dennison E, Devogelaer JP, Hochberg M, Kanis J, Laslop A, McAlindon T, Reiter S, Richette P, Rizzoli R, Reginster JY (2015) Can we identify patients with high risk of osteoarthritis progression who will respond to treatment? A focus on epidemiology and phenotype of osteoarthritis. Drugs Aging 32:179–187. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Zhang W, Moskowitz RW, Nuki G, Abramson S, Altman RD, Arden NK, 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(2):137–162. CrossRefPubMedGoogle Scholar
  12. 12.
    Zhang W, Nuki G, Moskowitz RW, 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 (2010) OARSI recommendations for the management of hip and knee osteoarthritis: part III: changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthr Cartil 18(4):476–499. CrossRefPubMedGoogle Scholar
  13. 13.
    Fajardo M, Di Cesare PE (2005) Disease-modifying therapies for osteoarthritis: current status. Drugs Aging 22(2):141–161. CrossRefPubMedGoogle Scholar
  14. 14.
    Per Q, Bay-Jensen AC, Christiansen C, Dam EB, Pastoureau P, Karsdal MA (2008) The disease modifying osteoarthritis drug (DMOAD): is it in the horizon? Pharmacol Res 58(1):1–7. CrossRefGoogle Scholar
  15. 15.
    Hunter DJ (2011) Pharmacologic therapy for osteoarthritis—the era of disease modification. Nat Rev Rheumatol 7(1):13–22. CrossRefPubMedGoogle Scholar
  16. 16.
    Carbone LD, Nevitt MC, Wildy K, Barrow KD, Harris F, Felson D, Peterfy C, Visser M, Harris TB, Wang BW, Kritchevsky SB (2004) Health, aging and body composition study. The relationship of antiresorptive drug use to structural findings and symptoms of knee osteoarthritis Arthritis Rheum 50(11):3516–3525. CrossRefPubMedGoogle Scholar
  17. 17.
    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 two-year multinational knee osteoarthritis structural arthritis study. Arthritis Rheum 54(11):3494–3507. CrossRefPubMedGoogle Scholar
  18. 18.
    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(6):660–666. CrossRefPubMedGoogle Scholar
  19. 19.
    Hwang JS, Chan DC, Chen JF, Cheng TT, Wu CH, Soong YK, Tsai KS, Yang RS (2014) Clinical practice guidelines for the prevention and treatment of osteoporosis in Taiwan: summary. J Bone Miner Metab 32(1):10–16. CrossRefPubMedGoogle Scholar
  20. 20.
    Soong YK, Tsai KS, Huang HY, Yang RS, Chen JF, Wu PC, Huang KE (2013) Risk of refracture associated with compliance and persistence with bisphosphonate therapy in Taiwan. Osteoporos Int 24(2):511–521. CrossRefPubMedGoogle Scholar
  21. 21.
    Fu SH, Wang CY, Yang RS, Wu FL, Hsiao FY (2017) Bisphosphonate use and the risk of undergoing total knee arthroplasty in osteoporotic patients with osteoarthritis: a nationwide cohort study in Taiwan. J Bone Joint Surg Am 99(11):938–946. CrossRefPubMedGoogle Scholar
  22. 22.
    Olivier E, Bruyère O, Richy F, Dardennes C, Reginster JY (2004) Health-related quality of life in total hip and total knee arthroplasty: a qualitative and systematic review of the literature. J Bone Joint Surg Am 86-A(5):963–974Google Scholar
  23. 23.
    Jenkins PJ, Clement ND, Hamilton DF, Gaston P, Patton JT, Howie CR (2013) Predicting the cost-effectiveness of total hip and knee replacement. Bone Joint J 95-B(1):115–121. CrossRefPubMedGoogle Scholar
  24. 24.
    Karlson EW, Mandl LA, Aweh GN, Sangha O, Liang MH, Grodstein F (2003) Total hip replacement due to osteoarthritis: the importance of age, obesity, and other modifiable risk factors. Am J Med 114(2):93–98. CrossRefPubMedGoogle Scholar
  25. 25.
    Flugsrud GB, Nordsletten L, Espehaug B, Havelin LI, Meyer HE (2002) Risk factors for total hip replacement due to primary osteoarthritis: a cohort study in 50,034 persons. Arthritis Rheum 46(3):675–682. CrossRefPubMedGoogle Scholar
  26. 26.
    Hsiao FY, Yang YC, Huang YT, Huang WF (2007) Using Taiwan’s National Health Insurance Research Databases for pharmacoepidemiology research. J Food Drug Anal 15:99–108Google Scholar
  27. 27.
    Chen YC, Yeh HY, Wu JC, Haschler I, Chen TJ, Wetter T (2011) Taiwan’s National Health Insurance Research Database: administrative health care database as study object in bibliometrics. Scientometrics 86:365–380. CrossRefGoogle Scholar
  28. 28.
    Hsing AW, Ioannidis JP (2015) Nationwide population science: lessons from the Taiwan National Health Insurance Research Database. JAMA Intern Med 175(9):1527–1529. CrossRefPubMedGoogle Scholar
  29. 29.
    Zhou Z, Rahme E, Abrahamowicz M, Pilote L (2005) Survival bias associated with time-to-treatment initiation in drug effectiveness evaluation: a comparison of methods. Am J Epidemiol 162(10):1016–1023. CrossRefPubMedGoogle Scholar
  30. 30.
    Lévesque LE, Hanley JA, Kezouh A, Suissa S (2010) Problem of immortal time bias in cohort studies: example using statins for preventing progression of diabetes. BMJ 340:b5087. CrossRefPubMedGoogle Scholar
  31. 31.
    Austin PC (2011) An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivariate Behav Res 46(3):399–424. CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Caro JJ, Ishak KJ, Huybrechts KF, Raggio G, Naujoks C (2004) The impact of compliance with osteoporosis therapy on fracture rates in actual practice. Osteoporos Int 15(12):1003–1008. CrossRefPubMedGoogle Scholar
  33. 33.
    Cramer JA, Gold DT, Silverman SL, Lewiecki EM (2007) A systematic review of persistence and compliance with bisphosphonates for osteoporosis. Osteoporos Int 18(8):1023–1031. CrossRefPubMedGoogle Scholar
  34. 34.
    Karlsson L, Lundkvist J, Psachoulia E, Intorcia M, Ström O (2015) Persistence with denosumab and persistence with oral bisphosphonates for the treatment of postmenopausal osteoporosis: a retrospective, observational study, and a meta-analysis. Osteoporos Int 26(10):2401–2411. CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Cremers SC, Pillai GC, Papapoulos SE (2005) Pharmacokinetics/pharmacodynamics of bisphosphonates. Clin Pharmacokinet 44(6):551–570. CrossRefPubMedGoogle Scholar
  36. 36.
    Beaudart, C., Biver, E., Bruyère, O., Cooper, C., Al-Daghri, N., Reginster, J. Y., & Rizzoli, R. (2017). Quality of life assessment in musculo-skeletal health. Aging clinical and experimental research, 1–6. doi:
  37. 37.
    Abrahamsen B, van Staa T, Ariely R, Olson M, Cooper C (2009) Excess mortality following hip fracture: a systematic epidemiological review. Osteoporos Int 20(10):1633–1650. CrossRefPubMedGoogle Scholar
  38. 38.
    Hallberg I, Rosenqvist AM, Kartous L, Löfman O, Wahlström O, Toss G (2004) Health-related quality of life after osteoporotic fractures. Osteoporos Int 15(10):834–841. CrossRefPubMedGoogle Scholar
  39. 39.
    Kanis JA, Bianchi G, Bilezikian JP, Kaufman JM, Khosla S, Orwoll E, Seeman E (2011) Towards a diagnostic and therapeutic consensus in male osteoporosis. Osteoporos Int 22(11):2789–2798. CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Lin TC, Yang CY, Yang YH, Lin SJ (2013) Comparative effectiveness of osteoporosis drugs in preventing secondary nonvertebral fractures in Taiwanese women. J Clin Endocrinol Metab 98(12):4717–4726. CrossRefPubMedGoogle Scholar
  41. 41.
    Shabestari M, Vik J, Reseland JE, Eriksen EF (2016) Bone marrow lesions in hip osteoarthritis are characterized by increased bone turnover and enhanced angiogenesis. Osteoarthr Cartil 24(10):1745–1752. CrossRefPubMedGoogle Scholar
  42. 42.
    Ahedi H, Aitken D, Blizzard L, Cicuttini F, Jones G (2014) A population-based study of the association between hip bone marrow lesions, high cartilage signal, and hip and knee pain. Clin Rheumatol 33(3):369–376. CrossRefPubMedGoogle Scholar
  43. 43.
    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. Skelet Radiol 37(5):423–431. CrossRefGoogle Scholar
  44. 44.
    Nishii T, Tamura S, Shiomi T, Yoshikawa H, Sugano N (2013) Alendronate treatment for hip osteoarthritis: prospective randomized 2-year trial. Clin Rheumatol 32(12):1759–1766. CrossRefPubMedGoogle Scholar
  45. 45.
    Reginster JY, Reiter-Niesert S, Bruyère O, Berenbaum F, Brandi ML, Branco J, Devogelaer JP, Herrero-Beaumont G, Kanis J, Maggi S, Maheu E, Richette P, Rizzoli R, Cooper C (2015) Recommendations for an update of the 2010 European regulatory guideline on clinical investigation of medicinal products used in the treatment of osteoarthritis and reflections about related clinically relevant outcomes: expert consensus statement. Osteoarthr Cartil 23(12):2086–2093. CrossRefPubMedGoogle Scholar
  46. 46.
    Lai YS, Wei HW, Cheng CK (2008) Incidence of hip replacement among national health insurance enrollees in Taiwan. J Orthop Surg Res 3(1):42. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2018

Authors and Affiliations

  1. 1.Department of OrthopedicsNational Taiwan University Hospital Yun-Lin BranchYun-Lin CountyTaiwan
  2. 2.Graduate Institute of Clinical Pharmacy, College of MedicineNational Taiwan UniversityTaipeiTaiwan
  3. 3.School of Pharmacy, College of MedicineNational Taiwan UniversityTaipeiTaiwan
  4. 4.Department of OrthopedicsNational Taiwan University HospitalTaipeiTaiwan
  5. 5.Department of PharmacyNational Taiwan University HospitalTaipeiTaiwan

Personalised recommendations