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Pamidronate and osteoporosis prevention in liver transplant recipients

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Abstract

Osteoporosis is a common complication in patients with end-stage liver disease and after orthotopic liver transplantation (LT), with resulting increasing fracture rate. In this study, we investigated the role of treatment with pamidronate in preventing further bone loss after LT. Eighty-five patients with end-stage liver disease were included in the study. Pamidronate 30 mg was given intravenously every 3 months after LT for the duration of 1 year to 43 patients with osteopenia or osteoporosis prior LT. The remainders served as controls. All patients received a supplementation of calcium and vitamin D. Bone mineral density (BMD) at the lumbar spine and the femoral neck, and markers of bone metabolism were measured before and 12 months after LT. Sixty-two BMD were available at 12 months; only paired BMD were evaluated. A significant increase in lumbar spine BMD was observed in pamidronate treated patients. No change was evident in controls. Femoral neck BMD decreased in both treated and untreated patients. Osteocalcin serum levels and deoxypyridinoline urinary excretion were significantly reduced by treatment. Our study suggests that pamidronate decreases bone turnover and is effective in preventing the course of bone loss after LT, however the efficacy, at the dosage regimen employed and in a follow-up of 12 months, appears to be limited to trabecular bone, with no effect on the cortical structure of the femur.

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References

  1. Leidig-Bruckner G, Hosch S, Dodidou P, Ritschel D, Conradt C, Klose C, Otto G, Lange R, Theilmann L, Zimmerman R, Pritsch M, Ziegler R (2001) Frequency and predictors of osteoporotic fractures after cardiac or liver transplantation: a follow-up study. Lancet 357:342–347

    Article  PubMed  CAS  Google Scholar 

  2. Monegal A, Navasa M, Guanabens N, Peris P, Pons F, Martinez de Osaba MJ, Rimola A, Rodes J, Munoz-Gomez J (1997) Osteoporosis and bone mineral metabolism disorders in cirrhotic patients referred for orthotopic liver transplantation. Calcif Tissue Int 60:148–154

    Article  PubMed  CAS  Google Scholar 

  3. Shane E, Mancini D, Aaronson K, Silverberg SJ, Seibel MJ, Addesso V, McMahon DJ (1997) Bone mass, vitamin D deficiency, and hyperparathyroidism in congestive heart failure. Am J Med 103:197–207

    Article  PubMed  CAS  Google Scholar 

  4. Trombetti A, Gerbase MW, Spiliopoulos A, Slosman DO, Nicod LP, Rizzoli R (2000) Bone mineral density in lung-transplant recipients before and after graft: prevention of lumbar spine post-transplantation-accelerated bone loss by pamidronate. J Heart Lung Transplant 19:736–743

    Article  PubMed  CAS  Google Scholar 

  5. Mikuls TR, Julian BA, Bartolucci A, Saag KG (2003) Bone mineral density changes within six months of renal transplantation. Transplantation 75:49–54

    Article  PubMed  CAS  Google Scholar 

  6. Kanis JA, Johansson H, Oden A, De Laet C, Johnell O, Eisman JA, Mc Closkey E, Mellstrom D, Pols H, Reeve J, Silman A, Tenenhouse A (2004) A meta-analysis of prior corticosteroid use and fracture risk. J Bone Miner Res 19:893–899

    Article  PubMed  Google Scholar 

  7. Abdelhadi M, Ericzon BG, Hultenby K, Sjoden G, Reinholt FP, Nordenstrom J (2002) Structural skeletal impairment induced by immunosuppressive therapy in rats: cyclosporine A vs tacrolimus. Transpl Int 15:180–187

    Article  PubMed  CAS  Google Scholar 

  8. Bikle DD, Sakata T, Halloran BP (2003) The impact of skeletal unloading on bone formation. Gravit Space Biol Bull 16:45–54

    PubMed  Google Scholar 

  9. Boutsen Y, Jamart J, Esselinckx W, Stoffel M, Devogelaer JP (1997) Primary prevention of glucocorticoid-induced osteoporosis with intermittent intravenous pamidronate: a randomized trial. Calcif Tissue Int 61:266–271

    Article  PubMed  CAS  Google Scholar 

  10. Saag KG, Emkey R, Schnitzer TJ, Brown JP, Hawkins F, Goemaere S, Thamsborg G, Liberman UA, Delmas PD, Malice MP, Czachur M, Daifotis AG (1998) Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. Glucocorticoid-Induced Osteoporosis Intervention Study Group. N Engl J Med 339:292–299

    CAS  Google Scholar 

  11. Millonig G, Graziadei IW, Eichler D, Pfeiffer KP, Finkenstedt G, Muehllechner P, Koenigsrainer A, Margreiter R, Vogel W (2005) Alendronate in combination with calcium and vitamin D prevents bone loss after orthotopic liver transplantation: a prospective single-center study. Liver Transpl 11:960–966

    Article  PubMed  Google Scholar 

  12. Riemens SC, Oostdijk A, van Doormaal JJ, Thijn CJ, Drent G, Piers DA, Groen EW, Meerman L, Slooff MJ, Haagsma EB (1996) Bone loss after liver transplantation is not prevented by cyclical etidronate, calcium and alphacalcidol. The Liver Transplant Group, Groningen. Osteoporos Int 6:213–218

    CAS  Google Scholar 

  13. Fan SL, Almond MK, Ball E, Evans K, Cunningham J (2000) Pamidronate therapy as prevention of bone loss following renal transplantation. Kidney Int 57:684–690

    PubMed  CAS  Google Scholar 

  14. Bianda T, Linka A, Junga G, Brunner H, Steinert H, Kiowski W, Schmid C (2000) Prevention of osteoporosis in heart transplant recipients: a comparison of calcitriol with calcitonin and pamidronate. Calcif Tissue Int 67:116–121

    Article  PubMed  CAS  Google Scholar 

  15. Reeves HL, Francis RM, Manas DM, Hudson M, Day CP (1998) Intravenous bisphosphonate prevents symptomatic osteoporotic vertebral collapse in patients after liver transplantation. Liver Transpl Surg 4:404–409

    Article  PubMed  CAS  Google Scholar 

  16. Ninkovic M, Love S, Tom BD, Bearcroft PW, Alexander GJ, Compston JE (2002) Lack of effect of intravenous pamidronate on fracture incidence and bone mineral density after orthotopic liver transplantation. J Hepatol 37:93–100

    Article  PubMed  CAS  Google Scholar 

  17. Dodidou P, Bruckner T, Hosch S, Haass M, Klar E, Sauer P, Ziegler R, Leidig-Bruckner G (2003) Better late than never? Experience with intravenous pamidronate treatment in patients with low bone mass or fractures following cardiac or liver transplantation. Osteoporos Int 14:82–89

    Article  PubMed  CAS  Google Scholar 

  18. Krieg MA, Seydoux C, Sandini L, Goy JJ, Berguer DG, Thiebaud D, Burckhardt P (2001) Intravenous pamidronate as treatment for osteoporosis after heart transplantation: a prospective study. Osteoporos Int 12:112–116

    Article  PubMed  CAS  Google Scholar 

  19. Fromm GA, Vega E, Plantalech L, Galich AM, Mautalen CA (1991) Differential action of pamidronate on trabecular and cortical bone in women with involutional osteoporosis. Osteoporos Int 1:129–133

    Article  PubMed  CAS  Google Scholar 

  20. Giannini S, Nobile M, Ciuffreda M, Iemmolo RM, Dalle Carbonare L, Minicuci N, Casagrande F, Destro C, Gerunda GE, Sartori L, Crepaldi G (2000) Long-term persistence of low bone density in orthotopic liver transplantation. Osteoporos Int 11:417–424

    Article  PubMed  CAS  Google Scholar 

  21. Vedi S, Ninkovic M, Garrahan NJ, Alexander GJ, Compston JE (2002) Effects of a single infusion of pamidronate prior to liver transplantation: a bone histomorphometric study. Transpl Int 15:290–295

    Article  PubMed  CAS  Google Scholar 

  22. Compston JE, Greer S, Skingle SJ, Stirling DM, Price C, Friend PJ, Alexander G (1996) Early increase in plasma parathyroid hormone levels following liver transplantation. J Hepatol 25:715–718

    Article  PubMed  CAS  Google Scholar 

  23. Floreani A, Fries W, Luisetto G, Burra P, Fagiuoli S, Boccagni P, Della Rovere GR, Plebani M, Piccoli A, Naccarato R (1998) Bone metabolism in orthotopic liver transplantation: a prospective study. Liver Transpl Surg 4:311–319

    Article  PubMed  CAS  Google Scholar 

  24. Hay JE, Dickson ER, Weisner RH, Kron RAF (1990) Long-term effect of orthotopic liver transplantation on the osteopenia of primary biliary cirrhosis (abstract). Hepatology 12:838

    Google Scholar 

  25. Valero MA, Loinaz C, Larrodera L, Leon M, Moreno E, Hawkins F (1995) Calcitonin and bisphosphonates treatment in bone loss after liver transplantation. Calcif Tissue Int 57:15–19

    Article  PubMed  CAS  Google Scholar 

  26. Watson RG, Coulton L, Kanis JA, et al (1990) Circulating osteocalcin in primary biliary cirrhosis following liver transplantation and during treatment with ciclosporin. J Hepatol 11:354–358

    Article  PubMed  CAS  Google Scholar 

  27. Diamond T, Stiel D, Lunzer M, Wilkinson M, Roche J, Posen S (1990) Osteoporosis and skeletal fractures in chronic liver disease. Gut 31:82–87

    PubMed  CAS  Google Scholar 

  28. McDonald JA, Dunstan CR, Dilworth P, Sherbon K, Sheil AG, Evans RA, McCaughan GW (1991) Bone loss after liver transplantation. Hepatology 14:613–619

    Article  PubMed  CAS  Google Scholar 

  29. Cohen A, Ebeling P, Sprague S, Shane E (2003) Transplantation osteoporosis. In: Favus MJ (eds) Primer on the metabolic bone diseases and disorders of mineral metabolism. American Society for Bone and Mineral Research, Washington, pp 370–379

    Google Scholar 

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Acknowledgements

We thank the team of the service of nuclear medicine for the BMD measurements, and the whole group of solid organ transplantation for patients care.

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Authors and Affiliations

  1. Service of Bone Diseases [WHO Collaborating Center for Osteoporosis Prevention], Department of Rehabilitation and Geriatrics, University Hospital of Geneva, 1211, Geneva 14, Switzerland

    Pietra Pennisi, Andrea Trombetti & René Rizzoli

  2. Service of Transplantation, Department of Surgery, University Hospital of Geneva, 1211, Geneva 14, Switzerland

    Emiliano Giostra & Gilles Mentha

  3. Clinica Medica OVE, University of Catania, Via Plebiscito 628, 95124, Catania, Italy

    Carmelo E. Fiore

Authors
  1. Pietra Pennisi
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  2. Andrea Trombetti
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  3. Emiliano Giostra
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  4. Gilles Mentha
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  5. René Rizzoli
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  6. Carmelo E. Fiore
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Correspondence to Carmelo E. Fiore.

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Pennisi, P., Trombetti, A., Giostra, E. et al. Pamidronate and osteoporosis prevention in liver transplant recipients. Rheumatol Int 27, 251–256 (2007). https://doi.org/10.1007/s00296-006-0196-2

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  • DOI: https://doi.org/10.1007/s00296-006-0196-2

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