High Prevalence of Bone Pain and Fractures in Young Transfusion Dependent Patients with β-Thalassemia at Southern Pakistan

Abstract

Standard thalassemia management is focused primarily on blood transfusions and iron chelation. Thalassemia caregivers grossly underestimate chronic pain due to bone and mineral related disorders. This study aimed to determine the frequency of bone pain, fractures, performance status and biochemical bone markers in children having transfusion dependent β-thalassemia major. We recruited 367 patients between 5 to 17 years of age from Fatimid Foundation Karachi, Pakistan. A questionnaire regarding clinical details such as demography, frequency of transfusion, iron chelation and fractures was administered. Wong-Baker Faces® pain rating scale and Eastern Cooperative Oncology Group Performance Status were used for assessment of bone pain and performance status respectively. Biochemical bone-health markers estimated included vitamin D, corrected calcium, intact parathyroid hormone, phosphorous, magnesium, zinc and ferritin levels. Among 367 children, 33.5% (n=123) were taking regular chelation and 50% (n=184) were on calcium and or vitamin D supplements. Eighty-two percent (n=303) patients experienced variable intensity of recurrent bone pain in past two years, which increased in frequency with advancing age. Forty-six patients (12.5%) reported multiple or recurrent fractures. Median 25OHD level was deficient (13.09ng/ ml IQR 18.6-8.56) with normal corrected calcium (8.81mg/dl IQR 9.4-7.97) while serum phosphate was at upper limit of reference range (5.1 IQR 5.9-4.3). Logistic regression analysis showed significant association of pain with age (OR 1.1 95% CI 1.0-1.2 p 0.001). The patients with and without fractures showed significant differences in age, corrected calcium, ferritin and zinc levels. Higher median phosphorus and iPTH were noted in patients with fractures but the difference was not significant. Binary logistic regression analysis showed statistically significant association with low levels of corrected calcium (OR 0.77% CI 0.6-0.9 p<0.04) and zinc (OR 0.08% CI 0.97-1.0 p<0.04). High prevalence of bone pains, fractures and biochemical abnormalities including hypovitaminosis D, hypocalcaemia and hyperphosphatemia were noted in patients with thalassemia. We need more studies to determine the impact on peak bone mass, prevalence of osteopenia and osteoporosis so that preventive intervention strategies can be planned in addition to adherence with optimum care for improving bone health in thalassemia.