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> or =12 years and liver iron concentration> or =10 mg/g dry wt or serum ferritin> or =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.
authors.affiliation: Department of Hematology at the Children's Hospital & Research Center, Oakland, CA, USA. Electronic address: efung@mail.cho.org.
authors.forename: Ellen B
authors.initials: EB
authors.lastname: Fung
authors.affiliation: Department of Gastroenterology at the Children's Hospital & Research Center, Oakland, CA, USA.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Harmatz
authors.affiliation: Pediatric Clinical Research Center at the Children's Hospital and Research Center at Oakland, CA, USA.
authors.forename: Meredith
authors.initials: M
authors.lastname: Milet
authors.affiliation: Departments of Hematology at the Children Hospital Los Angeles, CA, USA.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Coates
authors.affiliation: Children's Memorial Hospital, Chicago, IL, USA.
authors.forename: Alexis A
authors.initials: AA
authors.lastname: Thompson
authors.affiliation: Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Ranalli
authors.affiliation: Children's Hospital of Central California, CA, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Mignaca
authors.affiliation: Tulane University Medical Center, New Orleans, LA, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Scher
authors.affiliation: Weill Medical College of Cornell University, NY, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Giardina
authors.affiliation: Department of Hematology at the Children's Hospital & Research Center, Oakland, CA, USA.
authors.forename: Shanda
authors.initials: S
authors.lastname: Robertson
authors.affiliation: Department of Hematology at the Children's Hospital & Research Center, Oakland, CA, USA.
authors.forename: Lynne
authors.initials: L
authors.lastname: Neumayr
authors.affiliation: Department of Hematology at the Children's Hospital & Research Center, Oakland, CA, USA.
authors.forename: Elliott P
authors.initials: EP
authors.lastname: Vichinsky
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications / Q000378:metabolism*; D004700:Endocrine System Diseases / Q000150:complications*; D005260:Female; D050723:Fractures, Bone / Q000150:complications / Q000453:epidemiology*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008297:Male; D015995:Prevalence; D013789:Thalassemia / Q000150:complications / Q000378:metabolism*
chemical_list: D007501:Iron