Ronald Barr

and 5 more

Background. Low bone mineral density (osteopenia) is encountered in children with acute lymphoblastic leukemia (ALL) before, during and after treatment. Prior experience with alendronate, an oral bisphosphonate, demonstrated high tolerability and evident clinical efficacy. However, concerns have been expressed about the long-term safety and utility of such agents in children. Procedure. Of 217 children with ALL treated on Dana Farber Cancer Institute protocols 69 received alendronate for a mean of 87 weeks after dual energy X ray absorptiometry (DXA). DXA was repeated following completion of alendronate, and again 5-9 years later in a subgroup of 32 children. Lumbar spine areal bone mineral (LS aBMD) Z scores were obtained and values corrected for height, age and weight (HAW) were calculated for subjects 3-18 years of age. Results. Almost 80% (N=172) of the children remain in continuous complete remission at a mean of 14.5 years from diagnosis. Of those who receive alendronate, which was almost uniformly well tolerated, 7/69 (10.3%) relapsed compared to 19/89 (21.3%) who did not receive the drug. The mean unmodified LS aBMD Z score rose from -1.78 to -0.47. This gain was statistically significant for both unmodified (p <0.0001) and HAW corrected Z scores -1.32 to -0.42; p <0.0001). There was a modest median loss of LS aBMD (Z score 0.045) subsequently in the subgroup (N=32) of subjects on long-term follow up. Discussion. Alendronate appears to be well tolerated and moderately effective in osteopenic children with ALL. Whether it offers protection against relapse of leukemia needs further study.

Ronald Barr

and 5 more

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.