Bone Density in Thalassemia Major Improves in Longterm Transplant Survivors.
Authors: Leung Ting Fan , Li Chi Kong , Lam Christopher W.K. , Chu Yvonne , Shing Matthew M.K. , Li Chung Yi , Chan Iris H.S. , Chik Ki Wai , Lee Vincent , Yuen Patrick M.P. 
Published: October 2019

Background: Bone-related complication is a major longterm morbidity for thalassemia major (TM), and osteoporosis significantly increases the risk of fractures. Up to 60% of adult TM patients suffer from osteoporosis. It remains unclear whether diminished bone mineral density (BMD) in TM can be reversed after bone marrow transplantation (BMT). Objective: This study investigates the effects of BMT on BMD measurement in TM patients by comparing BMD in those receiving regular blood transfusion (BT) with patients following BMT.

Patients and Methods: This study recruited all Chinese TM patients managed in the pediatric department of a university teaching hospital in Hong Kong. Medical history and details on BT or BMT and drug treatments were obtained from chart review. All BMT patients were ≥ 2 years post-transplant. They did not receive any medication or suffer from any transplant-related complication for ≥ one year. Pubertal development was assessed clinically by Tanner staging, and supplemented with hormonal studies if indicated. BMD at lumbar spine (L1-L4) and left hip were measured by dual-energy x-ray absorptiometry (DEXA). Osteoporosis was defined quantitatively as T-score for BMD < -2.5. Paired blood and urine samples were collected in the mornings of DEXA scan for biochemical markers, including serum osteocalcin and bone-specific alkaline phosphatase (ALP) levels for bone formation and serum beta-crossLap and urine cross-linking deoxypyridinoline (DPD) levels for bone resorption. Student t test was used to analyze numerical values and chi-square was used to compare proportions.

Results: 53 TM patients on regular BT and 33 post-BMT patients were recruited. Their mean (SD) ages were 14.4 (5.9) years and 15.6 (5.8) years (p=0.346). Patients in the latter group were 5.7 (1.9) years after BMT. Thirteen (25%) BT patients and 13 (39%) post-BMT patients suffered from endocrinopathy (p=0.144). Similar proportions of BT and BMT patients showed signs of puberty (62% versus 67%; p=0.679). The mean (SD) serum ferritin concentrations in these two groups were 7401 (3770) pmol/L and 1348 (1144) pmol/L, respectively (p<0.0001). BMD T-scores were < -2.5 at spine and hip in 62% and 35% of BT-dependent TM patients, and in 36% (p=0.063) and 6% (p=0.036) of post-BMT patients. Absolute BMD at spine in these two groups were 0.636 (0.115) g/cm2 and 0.684 (0.155) g/cm2 (p=0.102), whereas the respective values at hip were 0.651 (0.121) g/cm2 and 0.706 (0.149) g/cm2 (p=0.092). Sub-group analysis revealed that pubertal post-BMT patients had significantly higher hip BMD as compared to those on regular BT (p=0.044). Serum osteocalcin concentrations were significantly higher in BMT than BT patients (mean [SD]: 96.4 [72.7] μg/L versus 68.9 [40.3] μg/L; p=0.037). The other biochemical markers of bone turnover did not differ between the two groups of TM patients. Lastly, BMD values were not associated with the presence of endocrinopathy, extent of iron overload or dosage of desferrioxamine in BT-dependent TM patients.

Conclusions: Osteoporosis is common among Chinese teenagers and young adults with TM. Our results support that BMD measurement should form an integral part of longterm follow-up in TM patients. Transplant survivors of TM had significantly better BMD at left hips as compared to those on regular BT, and this may result from increased bone formation in the post-transplant patients.