Bone health in long‐term survivors of pediatric acute lymphoblastic leukemia. An assessment by peripheral quantitative computed tomography

Background – Loss of bone mineral is a common concomitant of the treatment of acute lymphoblastic leukemia (ALL) due mainly to chemotherapy, especially with corticosteroids. Osteopenia/osteoporosis may persist long into survivorship. Measurement of bone mineral density (BMD) by dual energy X-ray absorptiometry is limited to two-dimensionality and cannot distinguish trabecular from cortical bone. Methods – A sample of 74 subjects, more than 10 years from diagnosis, underwent peripheral quantitative computed tomography (pQCT) at metaphyseal (trabecular bone) and diaphyseal (cortical bone) sites in the radius and tibia. pQCT provides three-dimensional assessment of bone geometry, density and architecture. Results – Similarities of average values in multiple metrics with those in healthy subjects obscured deficits in both trabecular and cortical bone, as well as bone strength, revealed by Z scores using an ethnically comparable sample of healthy individuals. Connectivity, a measure of bone architecture and a surrogate measure of bone strength, was lower in females than males. Survivors of standard risk ALL had greater connectivity in and more compact trabecular bone than high risk survivors who had received more intensive osteotoxic chemotherapy. There were no statistically significant differences in any of the metrics at any of the sites between subjects who had or had not a history of fracture, cranial irradiation or use of a bisphosphonate. Conclusions – These long-term survivors of ALL have somehat compromised bone health, but data in comparable healthy populations are limited. Longitudinal studies in larger and more ethnically diverse cohorts will provide greater insight into bone health in this vulnerable population.

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Nutritional intake of long-term survivors of childhood acute lymphoblastic leukemia: Evidence for bone health interventional opportunities

Pediatric Blood & Cancer ◽

10.1002/pbc.22737 ◽

2010 ◽

Vol 55 (7) ◽

pp. 1362-1369 ◽

Cited By ~ 38

Author(s):

Frances A. Tylavsky ◽

Karen Smith ◽

Harriet Surprise ◽

Sarah Garland ◽

Xiaowei Yan ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Bone Health ◽

Lymphoblastic Leukemia ◽

Nutritional Intake ◽

Childhood Acute Lymphoblastic Leukemia ◽

Long Term Survivors

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Longitudinal Assessment of Bone Density and Structure in Childhood Survivors of Acute Lymphoblastic Leukemia without Cranial Radiation

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2012-2393 ◽

2012 ◽

Vol 97 (10) ◽

pp. 3584-3592 ◽

Cited By ~ 49

Author(s):

Sogol Mostoufi-Moab ◽

Jill Brodsky ◽

Elizabeth J. Isaacoff ◽

Anne Tsampalieros ◽

Jill P. Ginsberg ◽

...

Keyword(s):

Computed Tomography ◽

Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia ◽

Quantitative Computed Tomography ◽

Peripheral Quantitative Computed Tomography ◽

Longitudinal Assessment ◽

Linear Regression Models ◽

Mineral Density ◽

Z Scores ◽

Childhood Survivors

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.

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