Longitudinal assessment of bone density and structure in childhood survivors of acute lymphoblastic leukemia without cranial radiation

Abstract

Purpose: Children with acute lymphoblastic leukemia (ALL) are at risk for impaired bone accrual. This peripheral quantitative computed tomography study assessed changes in bone mineral density (BMD) and structure after completion of ALL treatment.

Methods: Fifty ALL participants, ages 5-22 yr, were enrolled within 2 yr (median 0.8 yr) after completing ALL therapy. Tibia peripheral quantitative computed tomography scans were performed at enrollment and 12 months later. Age-, sex-, and race-specific Z-scores for trabecular BMD (TrabBMD), cortical BMD (CortBMD), and cortical area (CortArea) were generated based on more than 650 reference participants. Multivariable linear regression models examined determinants of changes in Z-scores.

Results: At enrollment, mean TrabBMD (-1.03±1.34) and CortBMD (-0.84±1.05) Z-scores were low (both P<0.001) compared with reference participants. TrabBMD and CortBMD Z-scores increased to -0.58±1.41 and -0.51±0.91 over 1 yr, respectively (both P<0.001). Changes in cortical outcomes varied according to the interval since completion of therapy. Among those enrolled less than 6 months after therapy, CortArea Z-scores increased and CortBMD Z-scores decreased (both P<0.01). Among those enrolled 6 months or more after therapy, CortArea Z-scores did not change and CortBMD Z-scores increased (P<0.01). Changes in CortArea and CortBMD Z-scores were inversely associated (r=-0.32, P<0.001). Cumulative glucocorticoid exposure, leukemia risk status, and antimetabolite chemotherapy were not associated with outcomes.

Conclusion: TrabBMD was low after completion of ALL therapy and improved significantly. Early increases in cortical dimensions were associated with declines in CortBMD; however, participants further from ALL therapy demonstrated stable cortical dimensions and increases in CortBMD, potentially reflecting the time necessary to mineralize newly formed bone.

Fig. 1.

The change in cortical BMD (milligrams per cubic centimeter) Z-score over the 12-month study was significantly and positively associated with the interval since completion of ALL therapy at enrollment. Cortical BMD Z-scores decreased a mean of 0.54 during follow-up among those enrolled within 6 months of completing ALL therapy (P < 0.01) and increased a mean of 0.77 for those enrolled at least 6 months after completing ALL treatment (P < 0.01). CI, Confidence interval.

Fig. 2.

The change in cortical BMD (milligrams per cubic centimeter) Z-score is shown relative to the change in cortical area (square millimeter) Z-score over study interval. Increases in cortical area Z-scores were significantly associated with declines in cortical BMD Z-score, independent of the interval since completing ALL therapy. CI, Confidence interval.

Fig. 3.

Changes in trabecular BMD (milligrams per cubic meter), cortical BMD (milligrams per cubic meter), and cortical area (square millimeters) Z-scores over the 12-month study interval in early (<6 months) vs. late (≥6 months) enrollees from the time of completing ALL therapy.