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Decreased Periprosthetic Bone Loss in Patients Treated with Clodronate: A 1-Year Randomized Controlled Study

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Abstract

The efficacy of clodronate to reduce bone loss around uncemented stems after total hip arthroplasty (THA) was evaluated. Ninety-one patients operated with uncemented THA were randomized to receive either intramuscular clodronate at a dose of 100 mg weekly for 12 months or no treatment. Periprosthetic and contralateral bone mineral density (BMD) scans were performed and biochemical markers of bone turnover measured at baseline and at 3, 6, and 12 months. At month 12, with the exception of Gruen zones 4 and 5, patients treated with clodronate showed less bone loss at all zones, reaching statistical significance (P < 0.05) in Gruen zones 2 and 6 (difference of 6.6 and 5.9%, respectively). Analysis of data according to gender revealed sex-related differences in bone loss and efficacy of treatment. After 12 months, the difference in bone loss between treated and untreated women in five out of seven Gruen zones ranged from 6.2 to 13.3% (SS at zones 2 and 6), whereas comparison between treated and untreated men showed no BMD differences in all zones (P > 0.05). Median percent changes in serum levels of markers of bone metabolism by gender were consistent with BMD changes. A 1-year treatment with intramuscular clodronate determined a significant reduction of bone loss after THA. This was mainly attributed to its greater efficacy in the female population, which is at higher risk for bone loss. This observation suggests the need for the characterization of high-risk subjects as potential candidates for prevention strategies.

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References

  1. Chang RW, Pellisier JM, Hazen GB (1996) A cost–effectiveness analysis of total hip arthroplasty for osteoarthritis of the hip. JAMA 275:858–865

    Article  CAS  PubMed  Google Scholar 

  2. Furnes O, Lie A, Espehaug B, Vollset E, Engesaeter LB, Havelin I (2001) Hip disease, the prognosis of total hip replacements. A review of 53, 698 primary total hip replacements reported to the Norwegian Arthroplasty Register 1987–99. J Bone Joint Surg Br 83:579–586

    Article  CAS  PubMed  Google Scholar 

  3. Harris WH (2001) Wear and periprosthetic osteolysis: the problem. Clin Orthop 393:66–70

    Article  PubMed  Google Scholar 

  4. Sundfeldt M, Carlsson LV, Johansson CB, Thomsen P, Gretzer C (2006) Aseptic loosening, not only a question of wear: a review of different theories. Acta Orthop 77:177–197

    Article  PubMed  Google Scholar 

  5. Ries MD (2003) Complications in primary total hip arthroplasty: avoidance and management: wear. Instr Course Lect 52:257–265

    PubMed  Google Scholar 

  6. Haynes DR, Crotti TN, Potter AE, Loric M, Atkins GJ, Howie DW, Findlay DM (2001) The osteoclastogenic molecules RANKL and RANK are associated with periprosthetic osteolysis. J Bone Joint Surg Br 83-B:902–911

    Article  Google Scholar 

  7. Trevisan C, Bigoni M, Randelli G, Marinoni EC, Peretti G, Ortolani S (1997) Periprosthetic bone density around fully hydroxyapatite coated femoral stem. Clin Orthop 340:109–117

    Article  PubMed  Google Scholar 

  8. Massari L, Bagni B, Biscione R, Traina GC (1996) Periprosthetic bone density in uncemented femoral hip implants with proximal hydroxyapatite coating. Bull Hosp Jt Dis 54:206–210

    CAS  PubMed  Google Scholar 

  9. Brodner W, Bitzan P, Lomoschitz F, Krepler P, Jankovsky R, Lehr S, Kainberger F, Gottsauner-Wolf F (2004) Changes in bone mineral density in the proximal femur after uncemented total hip arthroplasty: a five-year longitudinal study. J Bone Joint Surg Br 86-B:20–26

    Google Scholar 

  10. Aldinger PR, Sabo D, Pritsch M, Thomsen M, Mau H, Ewerbeck V, Breusch SJ (2003) Pattern of periprosthetic bone remodelling around stable uncemented tapered hip stems: a prospective 84-month follow-up study and a median 156-month cross-sectional study with DXA. Calcif Tissue Int 73:2115–2121

    Article  Google Scholar 

  11. Yamaguchi KY, Masuhara K, Yamasaki S, Nakai T, Fuji T (2003) Predictive value of a preoperative biochemical bone marker in relation to bone remodelling after cementless total hip arthroplasty. J Clin Densitom 6:259–265

    Article  PubMed  Google Scholar 

  12. Ohta H, Kobayashi S, Saito N, Nawata M, Horiuchi H, Takaoka K (2003) Sequential changes in periprosthetic bone mineral density following total hip arthroplasty: a 3-year follow-up. J Bone Miner Metab 21:229–233

    PubMed  Google Scholar 

  13. Rahmy AIA, Gosens T, Blake GM, Tonino A, Fogelman GM (2004) Periprosthetic bone remodelling of two types of uncemented femoral implant with proximal hydroxyapatite coating: a 3-year follow-up study addressing the influence of prosthesis design and preoperative bone density on periprosthetic bone loss. Osteoporos Int 15:281–289

    Article  CAS  PubMed  Google Scholar 

  14. Venesmaa PK, Kröger HP, Miettinen HJ, Jurvelin JS, Suomalainen OT, Alhava EM (2001) Monitoring of periprosthetic BMD after uncemented total hip arthroplasty with dual-energy X-ray absorptiometry-a 3-year follow-up study. J Bone Miner Res 16:1056–1061

    Article  CAS  PubMed  Google Scholar 

  15. Bhandari M, Bajammal S, Guyatt GH, Griffith L, Busse JW, Schünemann H, Einhorn TA (2005) Effect of bisphosphonates on periprosthetic bone mineral density after total joint arthroplasty. A meta-analysis. J Bone Joint Surg Am 87:293–301

    Article  PubMed  Google Scholar 

  16. Arabmotlagh M, Rittmeister M, Hennigs T (2006) Alendronate prevents femoral periprosthetic bone loss following total hip arthroplasty: prospective, randomized, double-blind study. J Orthop Res 24:1836–1841

    Article  Google Scholar 

  17. Venesmaa PK, Kröger HPJ, Miettinen HJA, Jurvelin JS, Suomalainen OT, Alhava EM (2001) Alendronate reduces periprosthetic bone loss after uncemented primary total hip arthroplasty: a prospective randomized study. J Bone Miner Res 16:2126–2131

    Article  CAS  PubMed  Google Scholar 

  18. Yamaguchi K, Masuhara K, Yamasaki S, Nakai T, Fuji T (2003) Cyclic therapy with etidronate has a therapeutic effect against local osteoporosis after uncemented total hip arthroplasty. Bone 33:144–149

    Article  CAS  PubMed  Google Scholar 

  19. Fokter SK, Komadina R, Repse-Fokter A, Yerby SA, Kocijancic A, Marc J (2005) Etidronate does not suppress periprosthetic bone loss following cemented hip arthroplasty. Int Orthop 29:362 336

    Article  CAS  PubMed  Google Scholar 

  20. Wilkinson JM, Stockley I, Peel NFA, Hamer AJ, Elson RA, Barrigton NA, Eastell R (2001) Effects of pamidronate in preventing local bone loss after total hip arthroplasty: a randomized, double-blind, controlled trial. J Bone Miner Res 16:556–564

    Article  CAS  PubMed  Google Scholar 

  21. Yamasaki S, Masuhara K, Yamaguchi K, Nakai T (2007) Risedronate reduces postoperative bone resorption after cementless total hip arthroplasty. Osteoporos Int 18:1009–1015

    Article  CAS  PubMed  Google Scholar 

  22. Wilkinson JM, Eagleton AC, Stockley I, Peel NFA, Hamer AJ, Eastell R (2005) Effect of pamidronate on bone turnover and implant migration after total hip arthroplasty: a randomized trial. J Orthop Res 23:1–8

    Article  CAS  PubMed  Google Scholar 

  23. Rossini M, Braga V, Gatti D, Gerardi D, Zamberlan N, Adami S (1999) Intramuscular clodronate therapy in postmenopausal osteoporosis. Bone 24:125–129

    Article  CAS  PubMed  Google Scholar 

  24. McCloskey E, Selby P, Davies M, Robinson J, Francis RM, Adams J, Kayan K, Beneton M, Jalava T, Pylkkänen L, Kenraali J, Aropuu S, Kanis JA (2004) Clodronate reduces vertebral fracture risk in women with postmenopausal or secondary osteoporosis: results of a double-blind, placebo-controlled 3-year study. J Bone Miner Res 19:728–736

    Article  CAS  PubMed  Google Scholar 

  25. McCloskey EV, Beneton M, Charlesworth D, Kayan K, deTakas D, Dey A, Orgee J, Ashford R, Forster M, Cliffe J, Kersh L, Brazier J, Nichol J, Aropuu S, Jalava T, Kanis JA (2007) Clodronate reduces the incidence of fractures in community-dwelling elderly women unselected for osteoporosis: results of a double-blind, placebo controlled randomized study. J Bone Miner Res 22:135–141

    Article  CAS  PubMed  Google Scholar 

  26. Makkonen N, Salminen A, Rogers MJ, Frith JC, Urtti A, Azhayeva E, Monkkonene J (1999) Contrasting effects of alendronate and clodronate on RAW 264 macrophages: the role of bisphosphonate metabolite. Eur J Pharm Sci 8:109–118

    Article  CAS  PubMed  Google Scholar 

  27. Bonabello A, Galmozzi MR, Bruzzese T, Zara GP (2001) Analgesic effect of bisphosphonates in mice. Pain 91:269–275

    Article  CAS  PubMed  Google Scholar 

  28. Hilding M, Aspenberg P (2006) Postoperative clodronate decreases prosthetic migration: 4-year follow-up of a randomized radiostereometric study of 50 total knee patients. Acta Orthop 77:912–916

    Article  PubMed  Google Scholar 

  29. Gruen TA, McNeice GM, Amstutz HC (1979) “Modes of failure” of cemented stem-type femoral components: a radiographic analysis of loosening. Clin Orthop 141:17–27

    PubMed  Google Scholar 

  30. Schneider U, Schmidt-Rohlfing B, Knopf U, Breusch SJ (2002) Effects upon bone metabolism following total hip and total knee arthroplasty. Pathobiology 70:26–33

    Article  CAS  PubMed  Google Scholar 

  31. Arabmotlagh M, Sabljic R, Rittmeister M (2006) Changes of the biochemical markers of bone turnover and periprosthetic bone remodelling after cemented hip arthroplasty. J Arthrop 21:129–134

    Article  Google Scholar 

  32. Kröger H, Vanninen E, Overmyer M, Miettinen H, Rushton N, Suomalainen O (1997) Periprosthetic bone loss and regional bone turnover in uncemented total hip arthroplasty: a prospective study using high resolution single photon emission tomography and dual-energy X-ray absorptiometry. J Bone Miner Res 12:487–492

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The study was funded by SPA-Società Prodotti Antibiotici (Milan, Italy). The authors are grateful to Patrizio Sala, BSc, of Data Management & Biometry (Cremona, Italy) for his support in data management and statistics.

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Authors and Affiliations

  1. Department of Orthopedics, University of Milano-Bicocca, Milan, Italy

    C. Trevisan

  2. Center for Metabolic Bone Disease, Istituto Auxologico Italiano, Milan, Italy

    S. Ortolani & R. Cherubini

  3. Medical Department, SPA-Società Prodotti Antibiotici, Via Biella 8, 20143, Milan, Italy

    P. Romano

  4. Department of Internal Medicine, University of Turin, Turin, Italy

    G. Isaia

  5. I Orthopedic Division, CTO/Maria Adelaide Hospital, Turin, Italy

    L. Agnese

  6. VII Orthopedic Division, Rizzoli Orthopedic Institute, Bologna, Italy

    D. Dallari

  7. Chirurgia Protesica Ospedale Santa Corona di Pietra Ligure, Savona, Italy

    G. Grappiolo

  8. Department of Orthopedics, University of Ferrara, Ferrara, Italy

    L. Massari

  9. Department of Rheumatology, Ospedale La Colletta, Arenzano, GE, Italy

    G. Bianchi

Authors
  1. C. Trevisan
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  2. S. Ortolani
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  3. P. Romano
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  4. G. Isaia
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  5. L. Agnese
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  6. D. Dallari
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  7. G. Grappiolo
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  8. R. Cherubini
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  9. L. Massari
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  10. G. Bianchi
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Corresponding author

Correspondence to P. Romano.

Additional information

P. Romano is employed by SPA-Società Prodotti Antibiotici. All other authors have stated that they have no conflict of interest.

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Trevisan, C., Ortolani, S., Romano, P. et al. Decreased Periprosthetic Bone Loss in Patients Treated with Clodronate: A 1-Year Randomized Controlled Study. Calcif Tissue Int 86, 436–446 (2010). https://doi.org/10.1007/s00223-010-9356-1

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  • DOI: https://doi.org/10.1007/s00223-010-9356-1

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