title: Bisphosphonates in the management of thalassemia-associated osteoporosis: a systematic review of randomised controlled trials.
abstract: Bisphosphonates are potent inhibitors of bone resorption, widely used for the management of osteoporosis and fracture prevention. Recent evidence suggests that bisphosphonates may have beneficial effects in the treatment of thalassemia-associated osteoporosis, a complex and multifactorial condition. Here we summarise available data about the efficacy and tolerability of bisphosphonates in beta--thalassemic patients. Randomised controlled trials (RCTs) of bisphosphonates in beta-thalassemia were identified searching PubMed. Studies were reviewed to retrieve relevant clinical information. The following variables were considered to assess the safety and efficacy of bisphosphonates-bone mineral density (BMD), markers of bone turnover, incidence of fragility fracture, bone pain, back pain, and clinical adverse events. Five RCTs were identified, investigating alendronate, clodronate, zoledronic acid and neridronate. All bisphosphonates produced a significant decrease of the markers of bone turnover. Alendronate, neridronate, and zoledronic acid significantly improved BMD at the lumbar spine, femoral neck and total hip. Zoledronic acid and neridronate were also shown to reduce bone and back pain. Probably due to the small sample sizes and to the short duration of the trials, it was not possible to establish the anti-fracture efficacy of bisphosphonates; however, they were well tolerated and adverse events were rare but expected on the basis of previous studies. Sufficient evidence exists to support the use of bisphosphonates in the management of thalassemia-associated osteoporosis (to prevent bone loss and improve the BMD). Further research is warranted to establish their anti-fracture efficacy and long-term safety.
authors.affiliation: Department of Gerontology and Musculoskeletal Sciences, Galliera Hospital, ASL3, Genoa, Italy, andrea.giusti@galliera.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Giusti
mesh_terms: D000818:Animals; D004164:Diphosphonates / Q000627:therapeutic use*; D006801:Humans; D010024:Osteoporosis / Q000188:drug therapy* / Q000209:etiology*; D039781:PubMed; D016032:Randomized Controlled Trials as Topic; D017086:beta-Thalassemia / Q000150:complications* / Q000188:drug therapy*
chemical_list: D004164:Diphosphonates
references.citation: Bone. 2006 Apr;38(4):571-5
references.pmid: 16298178
references.citation: Bone. 2010 Aug;47(2):169-80
references.pmid: 20493982
references.citation: Calcif Tissue Int. 2006 Sep;79(3):138-44
references.pmid: 16969592
references.citation: Clin Breast Cancer. 2012 Feb;12(1):40-8
references.pmid: 22014381
references.citation: Orphanet J Rare Dis. 2010 May 21;5:11
references.pmid: 20492708
references.citation: J Bone Miner Res. 2004 May;19(5):722-7
references.pmid: 15068494
references.citation: Br J Haematol. 1998 Dec;103(4):897-901
references.pmid: 9886298
references.citation: Ann N Y Acad Sci. 2011 Feb;1218:15-32
references.pmid: 20946579
references.citation: Lancet. 1996 Dec 7;348(9041):1535-41
references.pmid: 8950879
references.citation: Haematologica. 2008 Oct;93(10):1588-90
references.pmid: 18698086
references.citation: Ann Oncol. 2013 Feb;24(2):398-405
references.pmid: 23047045
references.citation: Haematologica. 2006 Sep;91(9):1193-202
references.pmid: 16956818
references.citation: Bone. 2011 Mar 1;48(3):425-32
references.pmid: 21035575
references.citation: J Bone Miner Metab. 2003;21(6):402-8
references.pmid: 14586797
references.citation: J Bone Miner Res. 2012 Feb;27(2):243-54
references.pmid: 22161728
references.citation: N Engl J Med. 2007 May 3;356(18):1809-22
references.pmid: 17476007
references.citation: J Bone Miner Res. 2004 Aug;19(8):1241-9
references.pmid: 15231010
references.citation: N Engl J Med. 2001 Feb 1;344(5):333-40
references.pmid: 11172164
references.citation: Calcif Tissue Int. 2011 Aug;89(2):91-104
references.pmid: 21637997
references.citation: Osteoporos Int. 2002 Aug;13(8):644-9
references.pmid: 12181623
references.citation: Acta Haematol. 2008;119(1):40-4
references.pmid: 18253025
references.citation: N Engl J Med. 1995 Nov 30;333(22):1437-43
references.pmid: 7477143
references.citation: J Bone Miner Res. 2007 Oct;22(10):1479-91
references.pmid: 17663640
references.citation: JAMA. 2006 Dec 27;296(24):2927-38
references.pmid: 17190893
references.citation: Br J Haematol. 2012 Nov;159(4):462-71
references.pmid: 22966867
references.citation: JAMA. 1999 Oct 13;282(14):1344-52
references.pmid: 10527181
references.citation: Best Pract Res Clin Endocrinol Metab. 2008 Oct;22(5):831-47
references.pmid: 19028359
references.citation: J Bone Miner Res. 2004 May;19(5):728-36
references.pmid: 15068495
references.citation: Bone. 2008 Jul;43(1):162-168
references.pmid: 18430624
references.citation: Br J Haematol. 2012 Jul;158(2):274-282
references.pmid: 22571408
references.citation: Horm Metab Res. 2012 Nov;44(12):909-13
references.pmid: 22581647
references.citation: Br J Haematol. 2004 Oct;127(2):127-39
references.pmid: 15461618
references.citation: Osteoporos Int. 2010 Jan;21(1):183-7
references.pmid: 19242634
references.citation: Bone. 2012 Jun;50(6):1389-93
references.pmid: 22465268
references.citation: J Bone Miner Res. 2002 Jun;17(6):1057-64
references.pmid: 12054161
references.citation: JAMA. 1998 Dec 23-30;280(24):2077-82
references.pmid: 9875874
references.citation: N Engl J Med. 2007 Nov 1;357(18):1799-809
references.pmid: 17878149
references.citation: J Bone Miner Res. 2007 Jan;22(1):135-41
references.pmid: 17042717
references.citation: Reumatismo. 2013 Oct 31;65(4):143-66
references.pmid: 24192561
references.citation: Haematologica. 2009 May;94(5):725-8
references.pmid: 19407319
references.citation: J Pediatr Endocrinol Metab. 1998;11 Suppl 3:795-801
references.pmid: 10091149
references.citation: Osteoporos Int. 2000;11(1):83-91
references.pmid: 10663363
references.citation: J Bone Miner Res. 2009 Mar;24(3):543-57
references.pmid: 18505376
references.citation: Osteoporos Int. 1999;9(5):461-8
references.pmid: 10550467
references.citation: Am J Hematol. 2009 May;84(5):317-8
references.pmid: 19396857
references.citation: Cancer. 2012 Mar 1;118(5):1192-201
references.pmid: 21987386