Reductions in Bone Mineral Density Are Apparent Early in Children With Prevalent Osteonecrosis Lesions Following Leukemia Therapy

Abstract

Osteonecrosis (ON) is a serious complication of childhood acute lymphoblastic leukemia. We determined the prevalence of osteonecrotic lesions in our patient population by a one-time multisite magnetic resonance imaging (MRI) more than 1 year following leukemia therapy. MRI findings were evaluated in relationship to clinical factors (including longitudinal changes in bone mineral density [BMD]). Eighty-six children enrolled in the Steroid Associated Osteoporosis in the Pediatric Population (STOPP) study were evaluated for ON at 3.1 ± 1.3 years following therapy. Thirty children had a total of 150 confirmed ON lesions (35%). Lumbar spine (LS) BMD Z-scores (mean ± SD) were low at diagnosis and similar between patients with and without ON (−1.09 ± 1.53 versus −1.27 ± 1.25, p = 0.549). LS BMD Z-scores declined from baseline to 12 months in children with ON (−0.31 ± 1.02) but not in those without (0.13 ± 0.82, p = 0.035); the hip BMD Z-scores from baseline to 24 months declined in both groups, but to a greater extent in those with ON (−1.77 ± 1.22) compared to those without (−1.03 ± 1.07, p = 0.045). At the time of the MRI, mean total hip and total body (TB) BMD Z-scores were lower in children with ON (hip −0.98 ± 0.95 versus −0.28 ± 1.06, p = 0.010; TB −1.36 ± 1.10 versus −0.48 ± 1.50, p = 0.018). Pain occurred in 11/30 (37%) with ON versus 20/56 (36%) without, p = 0.841. In multivariable models, older age at diagnosis (odds ratio [OR] 1.57; 95% confidence interval [CI], 1.15–2.13; p = 0.004), and hip BMD Z-score at MRI (OR 2.23; 95% CI, 1.02–4.87; p = 0.046) were independently associated with ON. Overall, one-third of children demonstrated ON after leukemia therapy. Those with ON had greater reductions in spine and hip BMD Z-scores in the first 1 and 2 years of therapy, respectively. Older age and lower hip BMD Z-scores at MRI were significantly associated with prevalent, off-therapy ON. These data assist in identifying children at risk of ON. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).