Fracture prevalence and relationship to endocrinopathy in iron overloaded patients with sickle cell disease and thalassemia

Ellen B. Fung; Paul R. Harmatz; Meredith Milet; Thomas D. Coates; Alexis A. Thompson; Mark Ranalli; Robert Mignaca; Charles Scher; Patricia Giardina; Shanda Robertson; Lynne Neumayr; Elliott P. Vichinsky

doi:10.1016/j.bone.2008.03.003

Fracture prevalence and relationship to endocrinopathy in iron overloaded patients with sickle cell disease and thalassemia

Ellen B. Fung^*, Paul R. Harmatz, Meredith Milet, Thomas D. Coates, Alexis A. Thompson, Mark Ranalli, Robert Mignaca, Charles Scher, Patricia Giardina, Shanda Robertson, Lynne Neumayr, Elliott P. Vichinsky

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

67 Scopus citations

Abstract

Transfusional iron overload leads to gonadal failure and low bone mass in patients with thalassemia (Thal). However, gonadal failure is rarely reported in transfused patients with sickle cell disease (SCD) and the literature regarding fracture prevalence in SCD is limited. The objective of this study was to assess self-reported fracture prevalence and its relationship to endocrinopathy in transfused Thal or SCD subjects and compare to non-transfused subjects with SCD (NonTxSCD). Eligibility was based on age ≥ 12 years and liver iron concentration ≥ 10 mg/g dry wt or serum ferritin ≥ 2000 ng/mL (Thal or TxSCD) or for NonTxSCD, ferritin < 500 ng/mL. Data were collected by patient interview and chart review at 31 clinical centers in the U.S., Canada and the U.K. 152 subjects with Thal (52% Male; 25.6 ±0.7 years), 203 subjects with TxSCD (44% Male, 24.7 ± 0.9 years: Mean ± SE), and 65 NonTxSCD (50% Male, 22.2 ±1.3 years) were enrolled. Overall, male subjects with Thal were more likely to have sustained a fracture in their lifetime (51%) compared to TxSCD (28%) or NonTxSCD (32%) (p = 0.005). There was no difference in fracture prevalence among women (Thal: 26%, TxSCD 17%, NonTxSCD: 16%). Fracture was most frequently reported in the upper extremities (53.3% of all fractures) while spine and pelvic fractures were relatively common for such a young cohort: 10.6%. Though overall fracture prevalence was not distinctly different from published healthy cohorts, fewer fractures occurred during the adolescent years. In multivariate analysis, the significant predictors of fracture prevalence were Thal diagnosis (Odds Ratio: 2.3; 1.2-4.6; 95%CI), male gender (OR: 2.6; 1.5-4.5), hypothyroidism (OR: 3.3; 1.1-9.8) and age (OR: 1.1; 1.03-1.08). These data suggest that despite similar iron burden, transfused patients with Thal are at greater risk for fracture than subjects with SCD. Male subjects with Thal and hypothyroidism are at particular risk for fracture, in contrast, transfused subjects with SCD had no greater risk of fracture compared to non-transfused SCD. Though ethnic differences in fracture risk cannot be ignored, endocrinopathy is rare in TxSCD which may also provide some protection from fracture.

Original language	English (US)
Pages (from-to)	162-168
Number of pages	7
Journal	Bone
Volume	43
Issue number	1
DOIs	https://doi.org/10.1016/j.bone.2008.03.003
State	Published - Jul 2008

Funding

Supported in part by the NIH grant R01 DK057778, the Pediatric Clinical Research Center at the Children's Hospital and Research Center Oakland (M01 RR01271) and the Southern California Thalassemia Center Grant (CDC) 1U01DD000309-01. The authors would like to thank our dedicated research nurse coordinators and clinical research associates at each of the 31 participating centers and of course the subjects and their families who participated in the Multi-Center Study of Iron Overload without whom this work would not be possible.

Keywords

Endocrinopathy
Fracture
Iron overload
Sickle cell disease
Thalassemia

ASJC Scopus subject areas

Physiology
Endocrinology, Diabetes and Metabolism
Histology

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10.1016/j.bone.2008.03.003

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@article{42cc6d509d1f4b579f6002ec5d826ba4,

title = "Fracture prevalence and relationship to endocrinopathy in iron overloaded patients with sickle cell disease and thalassemia",

abstract = "Transfusional iron overload leads to gonadal failure and low bone mass in patients with thalassemia (Thal). However, gonadal failure is rarely reported in transfused patients with sickle cell disease (SCD) and the literature regarding fracture prevalence in SCD is limited. The objective of this study was to assess self-reported fracture prevalence and its relationship to endocrinopathy in transfused Thal or SCD subjects and compare to non-transfused subjects with SCD (NonTxSCD). Eligibility was based on age ≥ 12 years and liver iron concentration ≥ 10 mg/g dry wt or serum ferritin ≥ 2000 ng/mL (Thal or TxSCD) or for NonTxSCD, ferritin < 500 ng/mL. Data were collected by patient interview and chart review at 31 clinical centers in the U.S., Canada and the U.K. 152 subjects with Thal (52% Male; 25.6 ±0.7 years), 203 subjects with TxSCD (44% Male, 24.7 ± 0.9 years: Mean ± SE), and 65 NonTxSCD (50% Male, 22.2 ±1.3 years) were enrolled. Overall, male subjects with Thal were more likely to have sustained a fracture in their lifetime (51%) compared to TxSCD (28%) or NonTxSCD (32%) (p = 0.005). There was no difference in fracture prevalence among women (Thal: 26%, TxSCD 17%, NonTxSCD: 16%). Fracture was most frequently reported in the upper extremities (53.3% of all fractures) while spine and pelvic fractures were relatively common for such a young cohort: 10.6%. Though overall fracture prevalence was not distinctly different from published healthy cohorts, fewer fractures occurred during the adolescent years. In multivariate analysis, the significant predictors of fracture prevalence were Thal diagnosis (Odds Ratio: 2.3; 1.2-4.6; 95%CI), male gender (OR: 2.6; 1.5-4.5), hypothyroidism (OR: 3.3; 1.1-9.8) and age (OR: 1.1; 1.03-1.08). These data suggest that despite similar iron burden, transfused patients with Thal are at greater risk for fracture than subjects with SCD. Male subjects with Thal and hypothyroidism are at particular risk for fracture, in contrast, transfused subjects with SCD had no greater risk of fracture compared to non-transfused SCD. Though ethnic differences in fracture risk cannot be ignored, endocrinopathy is rare in TxSCD which may also provide some protection from fracture.",

keywords = "Endocrinopathy, Fracture, Iron overload, Sickle cell disease, Thalassemia",

author = "Fung, {Ellen B.} and Harmatz, {Paul R.} and Meredith Milet and Coates, {Thomas D.} and Thompson, {Alexis A.} and Mark Ranalli and Robert Mignaca and Charles Scher and Patricia Giardina and Shanda Robertson and Lynne Neumayr and Vichinsky, {Elliott P.}",

note = "Funding Information: Supported in part by the NIH grant R01 DK057778, the Pediatric Clinical Research Center at the Children's Hospital and Research Center Oakland (M01 RR01271) and the Southern California Thalassemia Center Grant (CDC) 1U01DD000309-01. The authors would like to thank our dedicated research nurse coordinators and clinical research associates at each of the 31 participating centers and of course the subjects and their families who participated in the Multi-Center Study of Iron Overload without whom this work would not be possible.",

year = "2008",

month = jul,

doi = "10.1016/j.bone.2008.03.003",

language = "English (US)",

volume = "43",

pages = "162--168",

journal = "Bone",

issn = "8756-3282",

publisher = "Elsevier Inc.",

number = "1",

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TY - JOUR

T1 - Fracture prevalence and relationship to endocrinopathy in iron overloaded patients with sickle cell disease and thalassemia

AU - Fung, Ellen B.

AU - Harmatz, Paul R.

AU - Milet, Meredith

AU - Coates, Thomas D.

AU - Thompson, Alexis A.

AU - Ranalli, Mark

AU - Mignaca, Robert

AU - Scher, Charles

AU - Giardina, Patricia

AU - Robertson, Shanda

AU - Neumayr, Lynne

AU - Vichinsky, Elliott P.

N1 - Funding Information: Supported in part by the NIH grant R01 DK057778, the Pediatric Clinical Research Center at the Children's Hospital and Research Center Oakland (M01 RR01271) and the Southern California Thalassemia Center Grant (CDC) 1U01DD000309-01. The authors would like to thank our dedicated research nurse coordinators and clinical research associates at each of the 31 participating centers and of course the subjects and their families who participated in the Multi-Center Study of Iron Overload without whom this work would not be possible.

PY - 2008/7

Y1 - 2008/7

N2 - Transfusional iron overload leads to gonadal failure and low bone mass in patients with thalassemia (Thal). However, gonadal failure is rarely reported in transfused patients with sickle cell disease (SCD) and the literature regarding fracture prevalence in SCD is limited. The objective of this study was to assess self-reported fracture prevalence and its relationship to endocrinopathy in transfused Thal or SCD subjects and compare to non-transfused subjects with SCD (NonTxSCD). Eligibility was based on age ≥ 12 years and liver iron concentration ≥ 10 mg/g dry wt or serum ferritin ≥ 2000 ng/mL (Thal or TxSCD) or for NonTxSCD, ferritin < 500 ng/mL. Data were collected by patient interview and chart review at 31 clinical centers in the U.S., Canada and the U.K. 152 subjects with Thal (52% Male; 25.6 ±0.7 years), 203 subjects with TxSCD (44% Male, 24.7 ± 0.9 years: Mean ± SE), and 65 NonTxSCD (50% Male, 22.2 ±1.3 years) were enrolled. Overall, male subjects with Thal were more likely to have sustained a fracture in their lifetime (51%) compared to TxSCD (28%) or NonTxSCD (32%) (p = 0.005). There was no difference in fracture prevalence among women (Thal: 26%, TxSCD 17%, NonTxSCD: 16%). Fracture was most frequently reported in the upper extremities (53.3% of all fractures) while spine and pelvic fractures were relatively common for such a young cohort: 10.6%. Though overall fracture prevalence was not distinctly different from published healthy cohorts, fewer fractures occurred during the adolescent years. In multivariate analysis, the significant predictors of fracture prevalence were Thal diagnosis (Odds Ratio: 2.3; 1.2-4.6; 95%CI), male gender (OR: 2.6; 1.5-4.5), hypothyroidism (OR: 3.3; 1.1-9.8) and age (OR: 1.1; 1.03-1.08). These data suggest that despite similar iron burden, transfused patients with Thal are at greater risk for fracture than subjects with SCD. Male subjects with Thal and hypothyroidism are at particular risk for fracture, in contrast, transfused subjects with SCD had no greater risk of fracture compared to non-transfused SCD. Though ethnic differences in fracture risk cannot be ignored, endocrinopathy is rare in TxSCD which may also provide some protection from fracture.

AB - Transfusional iron overload leads to gonadal failure and low bone mass in patients with thalassemia (Thal). However, gonadal failure is rarely reported in transfused patients with sickle cell disease (SCD) and the literature regarding fracture prevalence in SCD is limited. The objective of this study was to assess self-reported fracture prevalence and its relationship to endocrinopathy in transfused Thal or SCD subjects and compare to non-transfused subjects with SCD (NonTxSCD). Eligibility was based on age ≥ 12 years and liver iron concentration ≥ 10 mg/g dry wt or serum ferritin ≥ 2000 ng/mL (Thal or TxSCD) or for NonTxSCD, ferritin < 500 ng/mL. Data were collected by patient interview and chart review at 31 clinical centers in the U.S., Canada and the U.K. 152 subjects with Thal (52% Male; 25.6 ±0.7 years), 203 subjects with TxSCD (44% Male, 24.7 ± 0.9 years: Mean ± SE), and 65 NonTxSCD (50% Male, 22.2 ±1.3 years) were enrolled. Overall, male subjects with Thal were more likely to have sustained a fracture in their lifetime (51%) compared to TxSCD (28%) or NonTxSCD (32%) (p = 0.005). There was no difference in fracture prevalence among women (Thal: 26%, TxSCD 17%, NonTxSCD: 16%). Fracture was most frequently reported in the upper extremities (53.3% of all fractures) while spine and pelvic fractures were relatively common for such a young cohort: 10.6%. Though overall fracture prevalence was not distinctly different from published healthy cohorts, fewer fractures occurred during the adolescent years. In multivariate analysis, the significant predictors of fracture prevalence were Thal diagnosis (Odds Ratio: 2.3; 1.2-4.6; 95%CI), male gender (OR: 2.6; 1.5-4.5), hypothyroidism (OR: 3.3; 1.1-9.8) and age (OR: 1.1; 1.03-1.08). These data suggest that despite similar iron burden, transfused patients with Thal are at greater risk for fracture than subjects with SCD. Male subjects with Thal and hypothyroidism are at particular risk for fracture, in contrast, transfused subjects with SCD had no greater risk of fracture compared to non-transfused SCD. Though ethnic differences in fracture risk cannot be ignored, endocrinopathy is rare in TxSCD which may also provide some protection from fracture.

KW - Endocrinopathy

KW - Fracture

KW - Iron overload

KW - Sickle cell disease

KW - Thalassemia

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Fracture prevalence and relationship to endocrinopathy in iron overloaded patients with sickle cell disease and thalassemia

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