Characterization of low bone mass in young patients with thalassemia by DXA, pQCT and markers of bone turnover

Abstract

Previous reports using dual x-ray absorptiometry (DXA) suggest that up to 70% of adults with thalassemia major (Thal) have low bone mass. However, few studies have controlled for body size and pubertal delay, variables known to affect bone mass in this population. In this study, bone mineral content and areal density (BMC, aBMD) of the spine and whole body were assessed by DXA, and volumetric BMD and cortical geometries of the distal tibia by peripheral quantitative computed tomography (pQCT) in subjects with Thal (n=25, 11 male, 10 to 30 yrs) and local controls (n=34, 15 male, 7 to 30 yrs). Z-scores for bone outcomes were calculated from reference data from a large sample of healthy children and young adults. Fasting blood and urine were collected, pubertal status determined by self-assessment and dietary intake and physical activity assessed by written questionnaires. Subjects with Thal were similar in age, but had lower height, weight and lean mass index Z-scores (all p<0.001) compared to controls. DXA aBMD was significantly lower in Thal compared to controls at all sites. Adult Thal subjects (>18 yrs, n=11) had lower tibial trabecular vBMD (p=0.03), cortical area, cortical BMC, cortical thickness, periosteal circumference and section modulus Z-scores (all p<0.01) compared to controls. Cortical area, cortical BMC, cortical thickness, and periosteal circumference Z-scores (p=0.02) were significantly lower in young Thal (≤18 yrs, n=14) compared to controls. In separate multivariate models, tibial cortical area, BMC, and thickness and spine aBMD and whole body BMC Z-scores remained lower in Thal compared to controls after adjustment for gender, lean mass and/or growth deficits (all p<0.01). Tanner stage was not predictive in these models. Osteocalcin, a marker of bone formation, was significantly reduced in Thal compared to controls after adjusting for age, puberty and whole body BMC (p=0.029). In summary, we have found evidence of skeletal deficits that cannot be dismissed as an artifact of small bone size or delayed maturity alone. Given that reduced bone density and strength are associated with increased risk of fracture, therapies focused on increasing bone formation and bone size in younger patients are worthy of further evaluation.

Bone Disease in Thalassemia: A Molecular and Clinical Overview

“…The classification of patients into normal, osteopenia and osteoporotic categories, using QCT Z scores, was in better agreement with the assignment based on trabecular number (k ϭ 0.209, P ϭ .053) than the classification using DXA Z scores (k ϭ 0.145, P ϭ .12) (186). Another study employing peripheral QCT showed lower tibial trabecular volumetric BMD, cortical area, cortical bone mineral content, cortical thickness, periosteal circumference and section modulus Z-scores in thalassemic patients compared to controls (52).…”

“…Multiple risk factors are implicated in bone loss and have been previously described (49,50). There have been many studies describing the prevalence of reduced bone mass in thalassemia but direct comparison of individual studies is difficult (49,(51)(52)(53). The problem lies in the inconsistent use of DXA Z score, T score and areal BMD to describe patient cohorts.…”

Body Composition in Adult Patients with Thalassemia Major

“…Our data also confirmed that the total BMD of patients is lower compared to controls. There are published data in the literature which prove that osteoporosis is a well-recognized side effect in thalassemic patients and explain the molecular paths that are implicated in this procedure [8, 11, 16, 25]. …”

Guidelines for the Standard Monitoring of Patients With Thalassemia

“…All patients should have a bone density assessment by dual energy x-ray absorptiometry (DXA) performed annually beginning at age 10 years to evaluate for low bone mass. Treatment options for low bone density include optimization of vitamin D and zinc levels, encouragement of weight bearing activity, and possibly a trial of bisphosphonates [34, 38, 39]. …”