With improved survival in patients with thalassemia major, the problem of bone disease has assumed greater importance. Approximately 50% to 80% of older thalassemia patients have an osteoporosis-osteopenia syndrome. The pathogenesis of bone disease is multifactorial including expansion of the medullary cavity due to IE, with subsequent thinning of the cortices, endocrinopathy, and iron overload. The widespread prevalence of osteoporosis in patients with thalassemia major was first observed across all ages in 1995. Subsequently, others reported a high frequency of abnormal Z scores in pediatric, adolescent, and adult patients. Abnormal bone mineral density has been reported in older studies of pediatric and adolescent patients with thalassemia major, though it is less likely that well transfused and chelated patients will have these complications at the same frequency. Vertebral fractures are associated with osteoporosis and cause significant morbidity in this population. Lumbar and thoracic vertebrae fractures are present in over 30% of thalassemia patients over the age of 30 years. The Thalassemia Clinical Research Network noted the overall fracture prevalence of 12% in a contemporary sample of 702 patients with α - and β -thalassemia. The fractures occurred more frequently in thalassemia major (17%) and intermedia (12%) compared with β -E (7%) and α -thalassemia (2%). Fracture prevalence increased with age and with sex hormone replacement therapy. An observational study by the Thalassemia Clinical Research Network has demonstrated a high prevalence of low bone mass across all the thalassemia syndromes, including β -thalassemia major, intermedia, β -E, HbH, H-Constant Spring, and homozygous α -thalassemia, which progresses with aging. In addition, increased serum and urine markers of bone turnover have been described in thalassemia patients with osteoporosis, which correlate with low dual-energy X-ray absorptiometry scores and improve with bisphosphonate therapy. It remains unclear if different chelation therapies and transfusions can alter the progression of osteo porosis. Bisphosphonates have been used with varying success to correct the osteopenia, not always being successful given the complex pathophysiology of the disease. Zinc supplementation may also improve bone density in younger patients with thalassemia.
Skeletal abnormalities are less common in patients receiving regular RBC transfusions but may still occur as a result of partially unchecked IE and expansion of the erythroid BM. These cause widening of the BM space and thinning of the cortex, with consequent osteoporosis. Changes in the skull and facial bones, including expansion of the frontal bone with prominent frontal bossing, may occur before the initiation of transfusion therapy. Radiographs reveal the diploic spaces to be widened. At first, the skull has a granular appearance, but later perpendicular bony trabeculae appear, giving the classic “hair on end” or “crewcut” appearance (Fig.1). Marked overgrowth of the maxilla results in severe malocclusion, jumbling of the upper incisors, and prominence of the molar eminences. These bone changes produce the classic thalassemic facies. Additional skeletal changes are observed in the metacarpals, metatarsals, and phalanges, where expanded medullary cavities produce a rectangular and then a convex shape. Irregular fusion of the epiphyses of the proximal humerus results in characteristic shortening of the upper arms. Marked osteoporosis and cortical thinning may predispose to pathologic fractures of the extremities and compression fractures of the vertebrae (Fig.2).
Fig1. MARKED EXPANSION OF THE DIPLOEIC SPACE IN THE SKULL BONES WITH THE “HAIR ON END” OR “CREW CUT” APPEARANCE ON X-RAY.
Fig2. COMPRESSION FRACTURE OF L2 VERTEBRA IN A PATIENT WITH SEVERE β-THALASSEMIA. (From Pearson HA, Benz EJ Jr. Thalassemia syndromes. In: Miller DR, Baehner RL, McMillan CW, eds. Smith’s Blood Diseases of Infancy and Childhood. 5th ed. St. Louis: CV Mosby; 1984:439.)
Several abnormalities in the ribs may occur, including notching and osteolytic lesions. The ribs become very wide, especially at the points of their attachment to the vertebral column. BM masses may extrude from these sites, creating the appearance of paravertebral masses and compressing the spinal cord.
