Fracture Prevalence in Adults with Transfusion-Dependent Thalassemia Is Related to Osteoporosis and Age
Authors: Chapin John C. , Vogiatzi Maria , Kleinert Dorothy , DeFilippis Ersilia , Christos Paul , Giardina Patricia 
Published: October 2019

Abstract
Introduction: Adults with transfusion dependent thalassemia syndromes are living into later adulthood as a result of better transfusion therapy and chelation. Unfortunately, chronic health problems develop in these patients that persist into adulthood. Osteoporosis and osteopenia are significant co-morbidities in the thalassemia population as a result of impaired growth in childhood, extramedullary expansion of the marrow, iron deposition, vitamin D deficiencies, and hypogonadism. The morbidity of osteoporosis is significant in this population, leading to fractures and chronic pain.
The purpose of this study was to provide a cross-sectional descriptive analysis of bone disease in adult thalassemia patients with osteoporosis and fracture histories.
Methods: A retrospective review of electronic medical records was carried out from patients with transfusion-dependent thalassemia (>8 transfusions per year) seen at the Weill Cornell Comprehensive Thalassemia Center. Information on demographics, diagnosis, iron assessment, and co-existing medical conditions was collected. Results of dual-energy X-ray absorptiometry (DEXA) scans as well as urine and serum markers of bone turnover were also obtained (C-telopeptide (CTX), N-telopeptide (NTX), bone alkaline phosphatase (AP)). The prevalence of fractures was collected.
Results: We identified 65 adult patients with transfusion-dependent thalassemia (median age = 36.8, range 16-56; 41 female, 24 male). Thirteen patients had diagnosed thalassemia intermedia (TI), one patient had hemoglobin Lepore, one patient had alpha-thalassemia major, and one patient had Hemoglobin E/beta thalassemia. The remaining patients (n = 49) had thalassemia major. 98% of patients (n=64) were on chelation therapy, the median liver iron content (LIC) was 2.821 mg/g dw (range 0.5 – 135) with a median T2* on cardiac MRI of 34.5 msec (range 7-49 msec).
Based on T score <-2.5, 26/65 (40%) of adults were classified as having osteoporosis. The median DEXA T-score at the lumbar spine was -2.4, and -1.95 at the femoral neck. Median markers of bone turnover were CTX=439 pg/ml, range 48-1030; NTX=61 mg/dl, range 19-566; and AP= 18 ug/L, range 8.9-99. We identified 26 patients with fracture history. Comparing those patients with fractures (n=26) to those without fractures (n=39), the only significant difference was lumbar spine DEXA scores (median T-2.66 in those with fractures vs -1.91 in those without fractures; p=0.023). There was a non-significant trend toward significance in T scores differences in T scores of the hips (median T score -2.25 vs -1.7). There were no significant differences in markers of bone turnover between the two groups. When analyzing age groups in the adult population, there was a non-significant trend of decreased markers of bone turnover in older patients. Fracture history was significantly associated with age (patients <30 had a 20% fracture prevalence, 31-40 had a prevalence of 23.1%, and >41 had a prevalence of 66.7%; p=0.001).
Conclusions: Osteoporosis remains a significant problem in the adult transfusion-dependent thalassemia population, and often begins in young adulthood. A fracture history is significantly associated with decreased DEXA T scores. Bone turnover markers decrease with age, which may reflect decreased remodeling or increased use of bone-sparing treatments. A fracture history was far more common in patients over the age of 40. Improved treatments for transfusion-dependent thalassemia patients with osteoporosis should be a high priority for future research.

Disclosures
Chapin: Novo-Nordisk: Honoraria; Alexion: Honoraria. Kleinert:Apopharma: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.