Osteoporosis after solid organ or stem cell transplantation
- Elizabeth Shane, MD
Elizabeth Shane, MD
- Professor of Medicine
- Columbia University Medical Center
- Harold N Rosen, MD
Harold N Rosen, MD
- Associate Professor in Medicine
- Harvard Medical School
- Section Editors
- Peter J Snyder, MD
Peter J Snyder, MD
- Editor-in-Chief — Endocrinology
- Section Editor — Pituitary Disease; Male Reproductive Endocrinology
- Professor of Medicine
- University of Pennsylvania School of Medicine
- Marc K Drezner, MD
Marc K Drezner, MD
- Section Editor — Bone Disease
- Professor of Medicine
- University of Wisconsin Medical School
Transplantation has become an established therapy for end-stage kidney, heart, lung, and liver diseases, as well as for several hematologic disorders. Improved survival of transplant recipients has raised awareness of post-transplant complications, such as osteoporosis. Post-transplant osteoporosis and fracture occur in a substantial proportion of patients.
The pathogenesis, clinical manifestations, and management of bone loss after solid organ (with the exception of renal transplant) or stem cell transplantation will be reviewed here. Management of bone loss after renal transplantation is discussed elsewhere. (See "Bone disease after renal transplantation" and "Persistent hyperparathyroidism after renal transplantation".)
Transplant-related osteoporosis and fracture are due to both pretransplant and post-transplant factors (table 1).
Pretransplant bone status — Many patients undergoing transplantation already have low bone mineral density (BMD). The mechanism appears to vary with the underlying disease:
●In patients with severe heart failure (New York Heart Association [NYHA] classes III and IV) who are candidates for cardiac transplantation, chronic kidney disease, vitamin D deficiency, secondary hyperparathyroidism, hypogonadism, chronic use of heparin and/or loop diuretics, and reduced physical activity may contribute to low BMD .
- Shane E, Mancini D, Aaronson K, et al. Bone mass, vitamin D deficiency, and hyperparathyroidism in congestive heart failure. Am J Med 1997; 103:197.
- Compston JE. Osteoporosis after liver transplantation. Liver Transpl 2003; 9:321.
- Shane E, Silverberg SJ, Donovan D, et al. Osteoporosis in lung transplantation candidates with end-stage pulmonary disease. Am J Med 1996; 101:262.
- Shane E, Rivas M, McMahon DJ, et al. Bone loss and turnover after cardiac transplantation. J Clin Endocrinol Metab 1997; 82:1497.
- Spira A, Gutierrez C, Chaparro C, et al. Osteoporosis and lung transplantation: a prospective study. Chest 2000; 117:476.
- Ebeling, PR. Transplantation Osteoporosis. In: Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 7th, The American Society of Bone and Mineral Research, Washington, DC 2008. p.279.
- Kulak CA, Cochenski Borba VZ, Kulak J, Ribeiro Custódio M. Osteoporosis after solid organ transplantation. Minerva Endocrinol 2012; 37:221.
- Schulte CM, Beelen DW. Bone loss following hematopoietic stem cell transplantation: a long-term follow-up. Blood 2004; 103:3635.
- Tauchmanovà L, Colao A, Lombardi G, et al. Bone loss and its management in long-term survivors from allogeneic stem cell transplantation. J Clin Endocrinol Metab 2007; 92:4536.
- Shane E, Addesso V, Namerow PB, et al. Alendronate versus calcitriol for the prevention of bone loss after cardiac transplantation. N Engl J Med 2004; 350:767.
- Shane E, Cohen A, Stein EM, et al. Zoledronic acid versus alendronate for the prevention of bone loss after heart or liver transplantation. J Clin Endocrinol Metab 2012; 97:4481.
- Crawford BA, Kam C, Pavlovic J, et al. Zoledronic acid prevents bone loss after liver transplantation: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 2006; 144:239.
- Guichelaar MM, Kendall R, Malinchoc M, Hay JE. Bone mineral density before and after OLT: long-term follow-up and predictive factors. Liver Transpl 2006; 12:1390.
- Monegal A, Navasa M, Guañabens N, et al. Bone disease after liver transplantation: a long-term prospective study of bone mass changes, hormonal status and histomorphometric characteristics. Osteoporos Int 2001; 12:484.
- Krol CG, Dekkers OM, Kroon HM, et al. Longitudinal changes in BMD and fracture risk in orthotopic liver transplant recipients not using bone-modifying treatment. J Bone Miner Res 2014; 29:1763.
- Yu TM, Lin CL, Chang SN, et al. Osteoporosis and fractures after solid organ transplantation: a nationwide population-based cohort study. Mayo Clin Proc 2014; 89:888.
- Cohen A, Shane E. Osteoporosis after solid organ and bone marrow transplantation. Osteoporos Int 2003; 14:617.
- Rakel A, Sheehy O, Rahme E, Lelorier J. Does diabetes increase the risk for fractures after solid organ transplantation? A nested case-control study. J Bone Miner Res 2007; 22:1878.
- Shane E, Rivas M, Staron RB, et al. Fracture after cardiac transplantation: a prospective longitudinal study. J Clin Endocrinol Metab 1996; 81:1740.
- Ramsey-Goldman R, Dunn JE, Dunlop DD, et al. Increased risk of fracture in patients receiving solid organ transplants. J Bone Miner Res 1999; 14:456.
- Leidig-Bruckner G, Hosch S, Dodidou P, et al. Frequency and predictors of osteoporotic fractures after cardiac or liver transplantation: a follow-up study. Lancet 2001; 357:342.
- Premaor MO, Das TK, Debiram I, et al. Fracture incidence after liver transplantation: results of a 10-year audit. QJM 2011; 104:599.
- Monegal A, Navasa M, Guañabens N, et al. Bone mass and mineral metabolism in liver transplant patients treated with FK506 or cyclosporine A. Calcif Tissue Int 2001; 68:83.
- Maalouf NM, Shane E. Osteoporosis after solid organ transplantation. J Clin Endocrinol Metab 2005; 90:2456.
- Braith RW, Mills RM, Welsch MA, et al. Resistance exercise training restores bone mineral density in heart transplant recipients. J Am Coll Cardiol 1996; 28:1471.
- Braith RW, Conner JA, Fulton MN, et al. Comparison of alendronate vs alendronate plus mechanical loading as prophylaxis for osteoporosis in lung transplant recipients: a pilot study. J Heart Lung Transplant 2007; 26:132.
- Cohen A, Addesso V, McMahon DJ, et al. Discontinuing antiresorptive therapy one year after cardiac transplantation: effect on bone density and bone turnover. Transplantation 2006; 81:686.
- Kananen K, Volin L, Laitinen K, et al. Prevention of bone loss after allogeneic stem cell transplantation by calcium, vitamin D, and sex hormone replacement with or without pamidronate. J Clin Endocrinol Metab 2005; 90:3877.
- Grigg AP, Shuttleworth P, Reynolds J, et al. Pamidronate reduces bone loss after allogeneic stem cell transplantation. J Clin Endocrinol Metab 2006; 91:3835.
- Bianda T, Linka A, Junga G, et al. Prevention of osteoporosis in heart transplant recipients: a comparison of calcitriol with calcitonin and pamidronate. Calcif Tissue Int 2000; 67:116.
- Aris RM, Lester GE, Renner JB, et al. Efficacy of pamidronate for osteoporosis in patients with cystic fibrosis following lung transplantation. Am J Respir Crit Care Med 2000; 162:941.
- Atamaz F, Hepguler S, Akyildiz M, et al. Effects of alendronate on bone mineral density and bone metabolic markers in patients with liver transplantation. Osteoporos Int 2006; 17:942.
- Fahrleitner-Pammer A, Piswanger-Soelkner JC, Pieber TR, et al. Ibandronate prevents bone loss and reduces vertebral fracture risk in male cardiac transplant patients: a randomized double-blind, placebo-controlled trial. J Bone Miner Res 2009; 24:1335.
- Sambrook P, Henderson NK, Keogh A, et al. Effect of calcitriol on bone loss after cardiac or lung transplantation. J Bone Miner Res 2000; 15:1818.
- Stein EM, Ortiz D, Jin Z, et al. Prevention of fractures after solid organ transplantation: a meta-analysis. J Clin Endocrinol Metab 2011; 96:3457.
- Monegal A, Guañabens N, Suárez MJ, et al. Pamidronate in the prevention of bone loss after liver transplantation: a randomized controlled trial. Transpl Int 2009; 22:198.
- Bodingbauer M, Wekerle T, Pakrah B, et al. Prophylactic bisphosphonate treatment prevents bone fractures after liver transplantation. Am J Transplant 2007; 7:1763.
- Kaemmerer D, Lehmann G, Wolf G, et al. Treatment of osteoporosis after liver transplantation with ibandronate. Transpl Int 2010; 23:753.
- Fleischer J, McMahon DJ, Hembree W, et al. Serum testosterone levels after cardiac transplantation. Transplantation 2008; 85:834.
- Tauchmanovà L, Selleri C, De Rosa G, et al. Endocrine disorders during the first year after autologous stem-cell transplant. Am J Med 2005; 118:664.
- Tauchmanovà L, Selleri C, De Rosa G, et al. Gonadal status in reproductive age women after haematopoietic stem cell transplantation for haematological malignancies. Hum Reprod 2003; 18:1410.
- Trombetti A, Gerbase MW, Spiliopoulos A, et al. 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 2000; 19:736.
- Stempfle HU, Werner C, Echtler S, et al. Prevention of osteoporosis after cardiac transplantation: a prospective, longitudinal, randomized, double-blind trial with calcitriol. Transplantation 1999; 68:523.
- Isoniemi H, Appelberg J, Nilsson CG, et al. Transdermal oestrogen therapy protects postmenopausal liver transplant women from osteoporosis. A 2-year follow-up study. J Hepatol 2001; 34:299.
- Cejka D, Benesch T, Krestan C, et al. Effect of teriparatide on early bone loss after kidney transplantation. Am J Transplant 2008; 8:1864.
- Välimäki MJ, Kinnunen K, Tähtelä R, et al. A prospective study of bone loss and turnover after cardiac transplantation: effect of calcium supplementation with or without calcitonin. Osteoporos Int 1999; 10:128.
- Välimäki MJ, Kinnunen K, Volin L, et al. A prospective study of bone loss and turnover after allogeneic bone marrow transplantation: effect of calcium supplementation with or without calcitonin. Bone Marrow Transplant 1999; 23:355.
- Krieg MA, Seydoux C, Sandini L, et al. Intravenous pamidronate as treatment for osteoporosis after heart transplantation: a prospective study. Osteoporos Int 2001; 12:112.
- Ippoliti G, Pellegrini C, Campana C, et al. Clodronate treatment of established bone loss in cardiac recipients: a randomized study. Transplantation 2003; 75:330.
- Dodidou P, Bruckner T, Hosch S, et al. Better late than never? Experience with intravenous pamidronate treatment in patients with low bone mass or fractures following cardiac or liver transplantation. Osteoporos Int 2003; 14:82.
- Pretransplant bone status
- Post-transplant bone loss
- Effects of immunosuppressive regimens
- BONE MINERAL DENSITY ASSESSMENT
- General recommendations
- Candidates for medical therapy
- Medical therapy
- - Bisphosphonates
- - Calcitriol
- - Hormone replacement therapy
- - Other
- - Duration of therapy
- - Monitoring
- SUMMARY AND RECOMMENDATIONS
- Pretransplantation osteoporosis
- Prevention of post-transplantation osteoporosis