Skip to main content
Top
Published in: Osteoporosis International 7/2013

01-07-2013 | Original Article

Thalassemia bone disease: the association between nephrolithiasis, bone mineral density and fractures

Authors: P. Wong, P. J. Fuller, M. T. Gillespie, V. Kartsogiannis, B. J. Strauss, D. Bowden, F. Milat

Published in: Osteoporosis International | Issue 7/2013

Login to get access

Abstract

Summary

Thalassemia bone disease is well described, but the prevalence of nephrolithiasis has not been characterized. The association between nephrolithiasis, reduced bone density, and increased fractures has been demonstrated through this retrospective study of 166 participants with transfusion-dependent thalassemia. The findings support the need for increased vigilance of kidney and bone disease in this cohort.

Introduction

Previous studies have revealed that thalassemia is associated with reduced bone mineral density (BMD) and fractures. Many causes are implicated including hypogonadism, growth hormone deficiency, marrow expansion, and iron overload. Nephrolithiasis is associated with reduced BMD and increased fractures in the general population. However, the prevalence of nephrolithiasis and its association with bone density and fractures have not been characterized in thalassemia.

Methods

We have addressed this question by performing a retrospective cohort study of 166 participants with transfusion-dependent thalassemia who had undergone dual-energy X-ray absorptiometry between 2009 and 2011. Logistic regression modeling was used to adjust for potential confounders.

Results

We found a high prevalence of kidney stones (18.1 %) which was greater in males compared to females (28.7 vs 9.7 %, respectively). Renal stones were associated with reduced femoral neck Z-score and fractures in men after adjusting for potential confounders. These results indicate that nephrolithiasis is highly prevalent in patients with transfusion-dependent thalassemia and is significantly associated with reduced BMD and increased fractures.

Conclusions

The findings from this study strongly support the need for ongoing surveillance of BMD, fractures, and nephrolithiasis in the management of transfusion-dependent thalassemia.
Literature
1.
go back to reference Lauderdale DS, Thisted RA, Wen M, Favus MJ (2001) Bone mineral density and fracture among prevalent kidney stone cases in the third national health and nutrition examination survey. J Bone Miner Res 16:1893–1898PubMedCrossRef Lauderdale DS, Thisted RA, Wen M, Favus MJ (2001) Bone mineral density and fracture among prevalent kidney stone cases in the third national health and nutrition examination survey. J Bone Miner Res 16:1893–1898PubMedCrossRef
2.
go back to reference Melton Iii LJ, Crowson CS, Khosla S, Wilson DM, O’Fallon WM (1998) Fracture risk among patients with urolithiasis: a population-based cohort study. Kidney Int 53:459–464CrossRef Melton Iii LJ, Crowson CS, Khosla S, Wilson DM, O’Fallon WM (1998) Fracture risk among patients with urolithiasis: a population-based cohort study. Kidney Int 53:459–464CrossRef
3.
go back to reference Vogiatzi MG, MacKlin EA, Trachtenberg FL et al (2009) Differences in the prevalence of growth, endocrine and vitamin D abnormalities among the various thalassaemia syndromes in North America. Br J Haematol 146:546–556PubMedCrossRef Vogiatzi MG, MacKlin EA, Trachtenberg FL et al (2009) Differences in the prevalence of growth, endocrine and vitamin D abnormalities among the various thalassaemia syndromes in North America. Br J Haematol 146:546–556PubMedCrossRef
4.
go back to reference Quinn CT, Johnson VL, Kim HY et al (2011) Renal dysfunction in patients with thalassaemia. Br J Haematol 153:111–117PubMedCrossRef Quinn CT, Johnson VL, Kim HY et al (2011) Renal dysfunction in patients with thalassaemia. Br J Haematol 153:111–117PubMedCrossRef
5.
go back to reference Ponticelli C, Musallam KM, Cianciulli P, Cappellini MD (2010) Renal complications in transfusion-dependent beta thalassaemia. Blood Rev 24:239–244PubMedCrossRef Ponticelli C, Musallam KM, Cianciulli P, Cappellini MD (2010) Renal complications in transfusion-dependent beta thalassaemia. Blood Rev 24:239–244PubMedCrossRef
6.
go back to reference Vogiatzi MG, Macklin EA, Fung EB, Vichinsky E, Olivieri N, Kwiatkowski J, Cohen A, Neufeld E, Giardina PJ (2006) Prevalence of fractures among the thalassemia syndromes in North America. Bone 38:571–575PubMedCrossRef Vogiatzi MG, Macklin EA, Fung EB, Vichinsky E, Olivieri N, Kwiatkowski J, Cohen A, Neufeld E, Giardina PJ (2006) Prevalence of fractures among the thalassemia syndromes in North America. Bone 38:571–575PubMedCrossRef
7.
go back to reference Vogiatzi MG, Macklin EA, Fung EB et al (2009) Bone disease in thalassemia: a frequent and still unresolved problem. J Bone Miner Res 24:543–557PubMedCrossRef Vogiatzi MG, Macklin EA, Fung EB et al (2009) Bone disease in thalassemia: a frequent and still unresolved problem. J Bone Miner Res 24:543–557PubMedCrossRef
8.
go back to reference Jensen CE, Tuck SM, Agnew JE, Koneru S, Morris RW, Yardumian A, Prescott E, Hoffbrand AV, Wonke B (1998) High prevalence of low bone mass in thalassaemia major. Br J Haematol 103:911–915PubMedCrossRef Jensen CE, Tuck SM, Agnew JE, Koneru S, Morris RW, Yardumian A, Prescott E, Hoffbrand AV, Wonke B (1998) High prevalence of low bone mass in thalassaemia major. Br J Haematol 103:911–915PubMedCrossRef
9.
go back to reference Fung EB, Vichinsky EP, Kwiatkowski JL, Huang J, Bachrach LK, Sawyer AJ, Zemel BS (2011) Characterization of low bone mass in young patients with thalassemia by DXA, pQCT and markers of bone turnover. Bone 48:1305–1312PubMedCrossRef Fung EB, Vichinsky EP, Kwiatkowski JL, Huang J, Bachrach LK, Sawyer AJ, Zemel BS (2011) Characterization of low bone mass in young patients with thalassemia by DXA, pQCT and markers of bone turnover. Bone 48:1305–1312PubMedCrossRef
10.
go back to reference Ladis V, Raptou P, Rigatou E, Chouliaras G, Galanos A, Korres D, Kattamis C (2008) Study of bone density by pQCT analysis in healthy adults and patients with B-thalassemia major and intermedia. Pediatr Endocrinol Rev 6:127–131PubMed Ladis V, Raptou P, Rigatou E, Chouliaras G, Galanos A, Korres D, Kattamis C (2008) Study of bone density by pQCT analysis in healthy adults and patients with B-thalassemia major and intermedia. Pediatr Endocrinol Rev 6:127–131PubMed
11.
go back to reference Ladis VA, Gandaifis N, Papadopoulos EC, Gavras GM, Papassotiriou I, Korres DS, Kattamis CA (2004) Bone density study at the distal radius, using pQCT analysis, in Greek thalassemic patients. Pediatr Endocrinol Rev 2:307–309 Ladis VA, Gandaifis N, Papadopoulos EC, Gavras GM, Papassotiriou I, Korres DS, Kattamis CA (2004) Bone density study at the distal radius, using pQCT analysis, in Greek thalassemic patients. Pediatr Endocrinol Rev 2:307–309
12.
go back to reference Knowelden J, Buhr AJ, Dunbar O (1964) Incidence of fractures in persons over 35 years of age. A report to the M.R.C. working party on fractures in the elderly. Br J Prev Soc Med 18:130–141PubMed Knowelden J, Buhr AJ, Dunbar O (1964) Incidence of fractures in persons over 35 years of age. A report to the M.R.C. working party on fractures in the elderly. Br J Prev Soc Med 18:130–141PubMed
13.
go back to reference Mahachoklertwattana P, Pootrakul P, Chuansumrit A, Choubtum L, Sriphrapradang A, Sirisriro R, Rajatanavin R (2006) Association between bone mineral density and erythropoiesis in Thai children and adolescents with thalassemia syndromes. J Bone Miner Metab 24:146–152PubMedCrossRef Mahachoklertwattana P, Pootrakul P, Chuansumrit A, Choubtum L, Sriphrapradang A, Sirisriro R, Rajatanavin R (2006) Association between bone mineral density and erythropoiesis in Thai children and adolescents with thalassemia syndromes. J Bone Miner Metab 24:146–152PubMedCrossRef
14.
go back to reference Stamatelou KK, Francis ME, Jones CA, Nyberg LM Jr, Curhan GC (2003) Time trends in reported prevalence of kidney stones in the United States: 1976–1994. Kidney Int 63:1817–1823PubMedCrossRef Stamatelou KK, Francis ME, Jones CA, Nyberg LM Jr, Curhan GC (2003) Time trends in reported prevalence of kidney stones in the United States: 1976–1994. Kidney Int 63:1817–1823PubMedCrossRef
15.
go back to reference Taylor EN, Stampfer MJ, Curhan GC (2005) Obesity, weight gain, and the risk of kidney stones. JAMA 293:455–462PubMedCrossRef Taylor EN, Stampfer MJ, Curhan GC (2005) Obesity, weight gain, and the risk of kidney stones. JAMA 293:455–462PubMedCrossRef
16.
go back to reference Daudon M, Lacour B, Jungers P (2006) Influence of body size on urinary stone composition in men and women. Urol Res 34:193–199PubMedCrossRef Daudon M, Lacour B, Jungers P (2006) Influence of body size on urinary stone composition in men and women. Urol Res 34:193–199PubMedCrossRef
17.
go back to reference Jackson RD, LaCroix AZ, Gass M et al (2006) Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 354:669–683PubMedCrossRef Jackson RD, LaCroix AZ, Gass M et al (2006) Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 354:669–683PubMedCrossRef
18.
go back to reference Curhan GC, Willett WC, Knight EL, Stampfer MJ (2004) Dietary factors and the risk of incident kidney stones in younger women: nurses’ health study II. Arch Intern Med 164:885–891PubMedCrossRef Curhan GC, Willett WC, Knight EL, Stampfer MJ (2004) Dietary factors and the risk of incident kidney stones in younger women: nurses’ health study II. Arch Intern Med 164:885–891PubMedCrossRef
19.
go back to reference Heaney RP (2008) Calcium supplementation and incident kidney stone risk: a systematic review. J Am Coll Nutr 27:519–527PubMed Heaney RP (2008) Calcium supplementation and incident kidney stone risk: a systematic review. J Am Coll Nutr 27:519–527PubMed
20.
go back to reference Curhan GC, Willett WC, Speizer FE, Spiegelman D, Stampfer MJ (1997) Comparison of dietary calcium with supplemental calcium and other nutrients as factors affecting the risk for kidney stones in women. Ann Intern Med 126:497–504PubMedCrossRef Curhan GC, Willett WC, Speizer FE, Spiegelman D, Stampfer MJ (1997) Comparison of dietary calcium with supplemental calcium and other nutrients as factors affecting the risk for kidney stones in women. Ann Intern Med 126:497–504PubMedCrossRef
21.
go back to reference Favus MJ (2011) The risk of kidney stone formation: the form of calcium matters. Am J Clin Nutr 94:5–6PubMedCrossRef Favus MJ (2011) The risk of kidney stone formation: the form of calcium matters. Am J Clin Nutr 94:5–6PubMedCrossRef
22.
go back to reference Pak CY (1969) Physicochemical basis for formation of renal stones of calcium phosphate origin: calculation of the degree of saturation of urine with respect to brushite. J Clin Invest 48:1914–1922PubMedCrossRef Pak CY (1969) Physicochemical basis for formation of renal stones of calcium phosphate origin: calculation of the degree of saturation of urine with respect to brushite. J Clin Invest 48:1914–1922PubMedCrossRef
23.
go back to reference Prié D, Ravery V, Boccon-Gibod L, Friedlander G (2001) Frequency of renal phosphate leak among patients with calcium nephrolithiasis. Kidney Int 60:272–276PubMedCrossRef Prié D, Ravery V, Boccon-Gibod L, Friedlander G (2001) Frequency of renal phosphate leak among patients with calcium nephrolithiasis. Kidney Int 60:272–276PubMedCrossRef
24.
go back to reference Prié D, Huart V, Bakouh N et al (2002) Nephrolithiasis and osteoporosis associated with hypophosphatemia caused by mutations in the type 2a sodium-phosphate cotransporter. N Engl J Med 347:983–991PubMedCrossRef Prié D, Huart V, Bakouh N et al (2002) Nephrolithiasis and osteoporosis associated with hypophosphatemia caused by mutations in the type 2a sodium-phosphate cotransporter. N Engl J Med 347:983–991PubMedCrossRef
25.
go back to reference Yacobovich J, Stark P, Barzilai-Birenbaum S, Krause I, Pazgal I, Yaniv I, Tamary H (2010) Acquired proximal renal tubular dysfunction in β-thalassemia patients treated with deferasirox. J Pediatr Hematol Oncol 32:564–567PubMedCrossRef Yacobovich J, Stark P, Barzilai-Birenbaum S, Krause I, Pazgal I, Yaniv I, Tamary H (2010) Acquired proximal renal tubular dysfunction in β-thalassemia patients treated with deferasirox. J Pediatr Hematol Oncol 32:564–567PubMedCrossRef
26.
go back to reference Milat F, Wong P, Fuller PJ, Johnstone L, Kerr PG, Doery JCG, Strauss BJ, Bowden DK (2012) A case of hypophosphatemic osteomalacia secondary to deferasirox therapy. J Bone Miner Res 27:219–222PubMedCrossRef Milat F, Wong P, Fuller PJ, Johnstone L, Kerr PG, Doery JCG, Strauss BJ, Bowden DK (2012) A case of hypophosphatemic osteomalacia secondary to deferasirox therapy. J Bone Miner Res 27:219–222PubMedCrossRef
27.
go back to reference Borgna-Pignatti C, Rugolotto S, De Stefano P et al (2004) Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica 89:1187–1193PubMed Borgna-Pignatti C, Rugolotto S, De Stefano P et al (2004) Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica 89:1187–1193PubMed
28.
go back to reference Cappellini MD, Cohen A, Piga A et al (2006) A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with β-thalassemia. Blood 107:3455–3462PubMedCrossRef Cappellini MD, Cohen A, Piga A et al (2006) A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with β-thalassemia. Blood 107:3455–3462PubMedCrossRef
29.
go back to reference Rheault MN, Bechtel H, Neglia JP, Kashtan CE (2011) Reversible Fanconi syndrome in a pediatric patient on deferasirox. Pediatr Blood Cancer 56:674–676PubMedCrossRef Rheault MN, Bechtel H, Neglia JP, Kashtan CE (2011) Reversible Fanconi syndrome in a pediatric patient on deferasirox. Pediatr Blood Cancer 56:674–676PubMedCrossRef
30.
go back to reference Wei HY, Yang CP, Cheng CH, Lo FS (2011) Fanconi syndrome in a patient with β-thalassemia major after using deferasirox for 27 months. Transfusion 51:949–954PubMedCrossRef Wei HY, Yang CP, Cheng CH, Lo FS (2011) Fanconi syndrome in a patient with β-thalassemia major after using deferasirox for 27 months. Transfusion 51:949–954PubMedCrossRef
Metadata
Title
Thalassemia bone disease: the association between nephrolithiasis, bone mineral density and fractures
Authors
P. Wong
P. J. Fuller
M. T. Gillespie
V. Kartsogiannis
B. J. Strauss
D. Bowden
F. Milat
Publication date
01-07-2013
Publisher
Springer-Verlag
Published in
Osteoporosis International / Issue 7/2013
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-012-2260-y

Other articles of this Issue 7/2013

Osteoporosis International 7/2013 Go to the issue