Abstract
The bone mineral density during childhood and the teen years is an important determinate of adult bone health. Decreased bone mineral density has been found to be a relatively common complication following adult hematopoietic cell transplantation (HCT), but has not been well studied after HCT among pediatric patients. Not surprisingly, an effective therapeutic approach to decreased bone mineral density has also not been developed for children.
Patients and Methods: The records of 196 children <18 years of age who received HCT between 1/97-6/03 who survived for 1 year or more after HCT were reviewed. Patients selected for analysis had decreased bone mineral density (Z-score of <-1 standard deviation (SD) corrected for patient sex and age) and 2 or more bone mineral density (DEXA) scans performed after HCT. Change in bone density was calculated as the difference in L2-4 lumbar spine SD score. Variables associated with change in bone density were analyzed.
Results: Among the 143 patients who had a DEXA scan performed, 82 (57%) demonstrated bone loss defined as <-1 SD Z-score. Fifty-six (68%) of these 82 patients had two or more DEXA scans and were analyzed. These 56 patients received an HCT when they were a median 10.8 (1.1–17.9) years of age, 33 were male, and 40 had chronic GVHD treated with corticosteroids and calcinurin inhibitor therapy. Patients were grouped according to treatment received for the bone loss. Nine patients changed therapy and were analyzed twice in separate treatment categories, hence there were 65 patients in 3 groups: 16 received a bisphosphonate or calcitonin (B/C), 37 calcium supplement only, and 12 no therapy. The B/C group included patients receiving pamidronate, zometa, fosamax, or calcitonin. Baseline median Z-scores were −2.6 SD for the B/C group, −2.2 SD for calcium, and −1.4 SD for no therapy. The median length of therapy was 446 days for the B/C group and 365 days for the calcium group. For the no therapy group, the time interval between DEXA scans was 324 days. Treatment with B/C or calcium compared with no therapy was significantly associated with improved bone density (p=0.0004). Corticosteroids, length of corticosteroid therapy (months), presence of chronic GVHD, gender, TBI received in preparative regimen, and patient age at therapy were not associated with change in bone mineral density. The mean change in bone mineral density per year was +1.16 SD for the B/C group, +0.16 for calcium, and +0.52 for no therapy. Although not statistically significant (p=0.44), concomitant steroid use for more than half the time interval between DEXA scans decreased therapeutic gains in the B/C group by −0.59 SD/year and −0.38 SD/year for the calcium group. The only observed side effect was hypocalcemia in one patient receiving pamidronate.
Conclusions: These data demonstrate that the greatest improvement in bone mineral density was observed in patients receiving a bisphosphonate or calcitonin. Minimal to no toxicity was observed.
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