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Osteoporosis in the adult solid organ transplant population: underlying mechanisms and available treatment options

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Abstract

The prevention and treatment of osteoporosis is an increasingly important topic in the solid organ transplant (SOT) population. Compared to the general population, these patients are at an elevated risk of developing osteoporosis due to progressive disease, lifelong immunosuppressant therapy, and malnutrition. As patients live longer after transplant, chronic disease management is increasingly more important. Supplementation with calcium and vitamin D is often necessary in the SOT population due to a high incidence of vitamin D deficiency. Bisphosphonate therapy is most commonly used for prevention and treatment of osteoporosis, but therapy can be limited by renal dysfunction which is common in transplant recipients. Alternative agents such as teriparatide and calcitonin have not been shown to provide a significant impact on the rate of fractures in this population. Additionally, denosumab may be a promising treatment option due to its novel mechanism of action, and is currently being studied in renal transplant patients. Timely initiation of supplementation and treatment, and minimizing glucocorticoid exposure prior to and after transplantation will aid in the prevention and proper management of osteoporosis in these patients.

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References

  1. Sayegh MH, Carpenter CB (2004) Transplantation 50 years later—progress, challenges, and promises. N Engl J Med 351:2761–2766

    Article  CAS  PubMed  Google Scholar 

  2. Yu TM, Lin CL, Chang SN, Sung FC, Huang ST, Kao CH (2014) Osteoporosis and fractures after solid organ transplantation: a nationwide population-based cohort study. Mayo Clin Proc 89:888–895

    Article  PubMed  Google Scholar 

  3. Kulak CA, Borba VZ, Kulak J Jr, Custodio MR (2012) Osteoporosis after transplantation. Curr Osteoporos Rep 10:48–55

    Article  PubMed  Google Scholar 

  4. Maalouf NM, Shane E (2005) Osteoporosis after solid organ transplantation. J Clin Endocrinol Metab 90:2456–2465

    Article  CAS  PubMed  Google Scholar 

  5. Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, Lindsay R (2014) Clinician's guide to prevention and treatment of osteoporosis. Osteoporos Int 25:2359–2381

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Wibaux C, Legroux-Gerot I, Dharancy S, Boleslawski E, Declerck N, Canva V, Mathurin P, Pruvot FR, Cortet B (2011) Assessing bone status in patients awaiting liver transplantation. Joint Bone Spine 78:387–391

    Article  PubMed  Google Scholar 

  7. Gal-Moscovici A, Sprague SM (2007) Osteoporosis and chronic kidney disease. Semin Dial 20:423–430

    Article  PubMed  Google Scholar 

  8. Wang TK, O'Sullivan S, Gamble GD, Ruygrok PN (2013) Bone density in heart or lung transplant recipients—a longitudinal study. Transplant Proc 45:2357–2365

    Article  CAS  PubMed  Google Scholar 

  9. Grossman JM, Gordon R, Ranganath VK et al (2010) American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res 62:1515–1526

    Article  Google Scholar 

  10. Costanzo MR, Dipchand A, Starling R et al (2010) The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients. J Heart Lung Transplant Off Publ Int Soc Heart Transplant 29:914–956

    Article  Google Scholar 

  11. Lucey MR, Terrault N, Ojo L, Hay JE, Neuberger J, Blumberg E, Teperman LW (2013) Long-term management of the successful adult liver transplant: 2012 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Liver Transplant Off Publ Am Assoc Study Liver Dis Int Liver Transplant Soc 19:3–26

    Google Scholar 

  12. Kidney Disease: Improving Global Outcomes Transplant Work G (2009) KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surgeons 9(Suppl 3):S1–155

    Google Scholar 

  13. Bia M, Adey DB, Bloom RD, Chan L, Kulkarni S, Tomlanovich S (2010) KDOQI US commentary on the 2009 KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Kidney Dis Off J Natl Kidney Found 56:189–218

    Article  Google Scholar 

  14. Schipper LG, Fleuren HW, van den Bergh JP, Meinardi JR, Veldman BA, Kramers C (2015) Treatment of osteoporosis in renal insufficiency. Clin Rheumatol (2015) 34:1341--1345. doi:10.1007/s10067-015-2883-4

  15. Jamal SA, West SL, Miller PD (2012) Bone and kidney disease: diagnostic and therapeutic implications. Curr Rheumatol Rep 14:217–223

    Article  CAS  PubMed  Google Scholar 

  16. Mitterbauer C, Oberbauer R (2008) Bone disease after kidney transplantation. Transplant Int Off J Eur Soc Organ Transplant 21:615–624

    Article  Google Scholar 

  17. Stein EM, Shane E (2011) Vitamin D in organ transplantation. Osteoporos Int A J Estab Result Coop Eur Found Osteoporos Natl Osteoporos Found USA 22:2107–2118

    Article  CAS  Google Scholar 

  18. Bitetto D, Fabris C, Falleti E et al (2010) Vitamin D and the risk of acute allograft rejection following human liver transplantation. Liver Int Off J Int Assoc Study Liver 30:417–444

    Article  CAS  Google Scholar 

  19. Obi Y, Hamano T, Ichimaru N et al (2014) Vitamin D deficiency predicts decline in kidney allograft function: a prospective cohort study. J Clinical Endocrinol Metabol 99:527–535

    Article  CAS  Google Scholar 

  20. Lowery EM, Bemiss B, Cascino T, Durazo-Arvizu RA, Forsythe SM, Alex C, Laghi F, Love RB, Camacho P (2012) Low vitamin D levels are associated with increased rejection and infections after lung transplantation. J Heart Lung Transplant Off Publ Int Soc Heart Transplant 31:700–707

    Article  Google Scholar 

  21. Grotz W, Nagel C, Poeschel D et al (2001) Effect of ibandronate on bone loss and renal function after kidney transplantation. J Am Soc Nephrol 12:1530–1537

    CAS  PubMed  Google Scholar 

  22. Coco M, Glicklich D, Faugere MC et al (2003) Prevention of bone loss in renal transplant recipients: a prospective, randomized trial of intravenous pamidronate. J Am SocNephrol 14:2669–2676

    CAS  Google Scholar 

  23. Schwarz C, Mitterbauer C, Heinze G, Woloszczuk W, Haas M, Oberbauer R (2004) Nonsustained effect of short-term bisphosphonate therapy on bone turnover three years after renal transplantation. Kidney Int 65:304–309

    Article  CAS  PubMed  Google Scholar 

  24. Fahrleitner-Pammer A, Piswanger-Soelkner JC, Pieber TR et al (2009) 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 Off J Am Soc Bone Miner Res 24:1335–1344

    Article  CAS  Google Scholar 

  25. Shane E, Cohen A, Stein EM et al (2012) Zoledronic acid versus alendronate for the prevention of bone loss after heart or liver transplantation. J Clin Endocrinol Metabol 97:4481–4490

    Article  CAS  Google Scholar 

  26. Nowacka-Cieciura E, Cieciura T, Baczkowska T, Kozinska-Przybyl O, Tronina O, Chudzinski W, Pacholczyk M, Durlik M (2006) Bisphosphonates are effective prophylactic of early bone loss after renal transplantation. Transplant Proc 38:165–167

    Article  CAS  PubMed  Google Scholar 

  27. Torregrosa JV, Fuster D, Pedroso S, Diekmann F, Campistol JM, Rubí S, Oppenheimer F (2007) Weekly risedronate in kidney transplant patients with osteopenia. Transpl Int 20:708–711

    Article  CAS  PubMed  Google Scholar 

  28. Omidvar B, Ghorbani A, Shahbazian H, Beladi Mousavi SS, Shariat Nabavi SJ, Alasti M (2011) Comparison of alendronate and pamidronate on bone loss in kidney transplant patients for the first 6 months of transplantation. Iran J Kidney Dis 5:420–424

    PubMed  Google Scholar 

  29. Torregrosa JV, Fuster D, Monegal A, Gentil MA, Bravo J, Guirado L, Muxi A, Cubero J (2011) Efficacy of low doses of pamidronate in osteopenic patients administered in the early post-renal transplant. Osteoporos Int J Estab Result Coop Eur Found Osteoporos Natl Osteoporos Found USA 22:281–287

    Article  CAS  Google Scholar 

  30. Gilfraguas L, Guadalix S, Martinez G, Jodar E, Vara J, Gomez-Sanchez MA, Delgado J, De La Cruz J, Lora D, Hawkins F (2012) Bone loss after heart transplant: effect of alendronate, etidronate, calcitonin, and calcium plus vitamin D3. Prog Transplant (Aliso Viejo, Calif) 22:237–243

    Article  Google Scholar 

  31. 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 Transplant Off Publ Am Assoc Study Liver DisInt Liver Transplant Soc 11:960–966

    Google Scholar 

  32. Atamaz F, Hepguler S, Akyildiz M, Karasu Z, Kilic M (2006) Effects of alendronate on bone mineral density and bone metabolic markers in patients with liver transplantation. Osteoporos Int J Estab Result Coop Eur Found Osteoporos Natl Osteoporos Found USA 17:942–949

    Article  CAS  Google Scholar 

  33. Crawford BA, Kam C, Pavlovic J, Byth K, Handelsman DJ, Angus PW, McCaughan GW (2006) Zoledronic acid prevents bone loss after liver transplantation: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 144:239–248

    Article  CAS  PubMed  Google Scholar 

  34. Bodingbauer M, Wekerle T, Pakrah B et al (2007) Prophylactic bisphosphonate treatment prevents bone fractures after liver transplantation. Am J Transplant Off J Am Soc Transplant Am SocTransplant Surg 7:1763–1769

    Article  CAS  Google Scholar 

  35. Monegal A, Guanabens N, Suarez MJ et al (2009) Pamidronate in the prevention of bone loss after liver transplantation: a randomized controlled trial. Transplant Int Off J Eur Soc Organ Transplant 22:198–206

    Article  CAS  Google Scholar 

  36. Guadalix S, Martínez-Díaz-Guerra G, Lora D, Vargas C, Gómez-Juaristi M, Cobaleda B, González EM, Hawkins F (2011) Effect of early risedronate treatment on bone mineral density and bone turnover markers after liver transplantation: a prospective single-center study. Transpl Int 24:657–665

    Article  CAS  PubMed  Google Scholar 

  37. Kaemmerer D, Schmidt B, Lehmann G, Wolf G, Hommann M, Settmacher U (2012) Monthly ibandronate for the prevention of bone loss in patients after liver transplantation. Transplant Proc 44:1362–1367

    Article  CAS  PubMed  Google Scholar 

  38. Palmer SC, McGregor DO, Strippoli GF (2007) Interventions for preventing bone disease in kidney transplant recipients. Cochrane Database Syst Rev CD005015

  39. Alendronate [package insert]. Whitehouse Station, NJ: Merck & Co., Inc. 2012

  40. Ibandronate sodium injection [package insert] San Francisco, CA: Genentech, Inc. 2013

  41. Ibandronate sodium tablets [package insert] Research Triangle Park, NC: GlaxoSmithKline 2005

  42. Risedronate [package insert] Mason, OH: Warner Chilcott Pharmaceuticals Inc. 2010

  43. Zoledronic Acid [package insert] East Hanover, NJ: Novartis 2015

  44. Jamal SA, Bauer DC, Ensrud KE, Cauley JA, Hochberg M, Ishani A, Cummings SR (2007) Alendronate treatment in women with normal to severely impaired renal function: an analysis of the fracture intervention trial. J Bone Miner Res Off J Am Soc Bone Miner Res 22:503–508

    Article  CAS  Google Scholar 

  45. Hirschberg R (2012) Renal complications from bisphosphonate treatment. Curr Opin Supp Palliat Care 6:342–347

    Article  Google Scholar 

  46. Berenson JR, Boccia R, Lopez T, Warsi GM, Argonza-Aviles E, Lake S, Ericson SG, Collins R (2011) Results of a multicenter open-label randomized trial evaluating infusion duration of zoledronic acid in multiple myeloma patients (the ZMAX trial). J Support Oncol 9:32–40

    Article  CAS  PubMed  Google Scholar 

  47. Pamidronate [package insert] East Hanover, NJ: Novartis 2012

  48. Black DM, Schwartz AV, Ensrud KE et al (2006) Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA 296:2927–2938

    Article  CAS  PubMed  Google Scholar 

  49. Watts NB, Bilezikian JP, Camacho PM et al (2010) American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of postmenopausal osteoporosis. Endoc Pract Off J Am College Endocrinol Am Assoc Clin Endocrinol 16(Suppl 3):1–37

    Google Scholar 

  50. Teriparatide [package insert] Indianapolis, IN: Eli Lilly and Company 2012

  51. Saag KG, Zanchetta JR, Devogelaer JP, Adler RA, Eastell R, See K, Krege JH, Krohn K, Warner MR (2009) Effects of teriparatide versus alendronate for treating glucocorticoid-induced osteoporosis: thirty-six-month results of a randomized, double-blind, controlled trial. Arthritis Rheum 60:3346–3355

    Article  CAS  PubMed  Google Scholar 

  52. Cejka D, Benesch T, Krestan C, Roschger P, Klaushofer K, Pietschmann P, Haas M (2008) Effect of teriparatide on early bone loss after kidney transplantation. Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg 8:1864–1870

    Article  CAS  Google Scholar 

  53. Wang HH, Chang PC, Chu SH, Liu KL, Lai PC, Huang JY, Chiang YJ (2008) Osteoporosis after kidney transplantation: preliminary report from a single center. Transplant Proc 40:2412–2413

    Article  PubMed  Google Scholar 

  54. Kapetanakis EI, Antonopoulos AS, Antoniou TA, Theodoraki KA, Zarkalis DA, Sfirakis PD, Chilidou DA, Alivizatos PA (2005) Effect of long-term calcitonin administration on steroid-induced osteoporosis after cardiac transplantation. J heart Lung transplant Off Publ Int Soc Heart Transplant 24:526–532

    Article  Google Scholar 

  55. 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  CAS  PubMed  Google Scholar 

  56. Calcitonin-salmon [package insert] East Hanover, NJ: Novartis 2014

  57. Cummings SR, San Martin J, McClung MR et al (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361:756–765

    Article  CAS  PubMed  Google Scholar 

  58. Leder BZ, Tsai JN, Uihlein AV, Burnett-Bowie SA, Zhu Y, Foley K, Lee H, Neer RM (2014) Two years of Denosumab and teriparatide administration in postmenopausal women with osteoporosis (The DATA Extension Study): a randomized controlled trial. J Clin Endocrinol Metab 99:1694–1700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Denosumab [package insert] Thousand Oaks, CA: Amgen Inc. 2015

  60. Cohen SB, Dore RK, Lane NE et al (2008) Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. Arthritis Rheum 58:1299–1309

    Article  CAS  PubMed  Google Scholar 

  61. Bonani M, Serra AL, Fehr T, Brockmann J, Schiesser M, Frey DP, Wüthrich RP (2012) A randomized open label clinical trial examining the effect of denosumab on the prevention of first year bone mineral density loss after renal transplantation (POSTOP Study; NCT01377467): 1515. Transplantation 94(10S):887

    Article  Google Scholar 

  62. Vasikaran S, Eastell R, Bruyere O et al (2011) Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int J Estab Result Coop Eur Found Osteoporos Natl Osteoporos Found USA 22:391–420

    Article  CAS  Google Scholar 

  63. Ettinger B, Black DM, Mitlak BH et al (1999) Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 282:637–645

    Article  CAS  PubMed  Google Scholar 

  64. Hernandez E, Valera R, Alonzo E, Bajares-Lilue M, Carlini R, Capriles F, Martinis R, Bellorin-Font E, Weisinger JR (2003) Effects of raloxifene on bone metabolism and serum lipids in postmenopausal women on chronic hemodialysis. Kidney Int 63:2269–2274

    Article  CAS  PubMed  Google Scholar 

  65. Isoniemi H, Appelberg J, Nilsson CG, Makela P, Risteli J, Hockerstedt K (2001) Transdermal oestrogen therapy protects postmenopausal liver transplant women from osteoporosis. A 2-year follow-up study. J Hepatol 34:299–305

    Article  CAS  PubMed  Google Scholar 

  66. Stempfle HU, Werner C, Echtler S, Wehr U, Rambeck WA, Siebert U, Uberfuhr P, Angermann CE, Theisen K, Gartner R (1999) Prevention of osteoporosis after cardiac transplantation: a prospective, longitudinal, randomized, double-blind trial with calcitriol. Transplantation 68:523–530

    Article  CAS  PubMed  Google Scholar 

  67. Fleischer J, McMahon DJ, Hembree W, Addesso V, Longcope C, Shane E (2008) Serum testosterone levels after cardiac transplantation. Transplantation 85:834–839

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Pereira S, Pedroso S, Martins L et al (2010) Bone mineral density after simultaneous kidney-pancreas transplantation: four years follow-up of 57 recipients. Transplant Proc 42:555–557

    Article  CAS  PubMed  Google Scholar 

  69. Vincenti F, Schena FP, Paraskevas S, Hauser IA, Walker RG, Grinyo J, Group FS (2008) A randomized, multicenter study of steroid avoidance, early steroid withdrawal or standard steroid therapy in kidney transplant recipients. Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg 8:307–316

    Article  CAS  Google Scholar 

  70. Woodle ES, First MR, Pirsch J, Shihab F, Gaber AO, Van Veldhuisen P, Astellas Corticosteroid Withdrawal Study G (2008) A prospective, randomized, double-blind, placebo-controlled multicenter trial comparing early (7 day) corticosteroid cessation versus long-term, low-dose corticosteroid therapy. Ann Surg 248:564–577

    PubMed  Google Scholar 

  71. Edwards BJ, Desai A, Tsai J, Du H, Edwards GR, Bunta AD, Hahr A, Abecassis M, Sprague S (2011) Elevated incidence of fractures in solid-organ transplant recipients on glucocorticoid-sparing immunosuppressive regimens. J Osteoporos 2011:591793

  72. Westenfeld R, Schlieper G, Woltje M, Gawlik A, Brandenburg V, Rutkowski P, Floege J, Jahnen-Dechent W, Ketteler M (2011) Impact of sirolimus, tacrolimus and mycophenolate mofetil on osteoclastogenesis--implications for post-transplantation bone disease. Nephrol Dial Transplant Off Publ Eur Dial Transplant Assoc Eur Renal Assoc 26:4115–4123

    CAS  Google Scholar 

  73. Red Book Online [database online]. Greenwood Village, CO: Truven Health Analytics, Inc. Updated periodically. Accessed 3 March 2015

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Caitlin Rose Early, Linda Stuckey, and Sarah Tischer declare they have no conflict of interest.

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Early, C., Stuckey, L. & Tischer, S. Osteoporosis in the adult solid organ transplant population: underlying mechanisms and available treatment options. Osteoporos Int 27, 1425–1440 (2016). https://doi.org/10.1007/s00198-015-3367-8

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