Effect of Adjustment for Height on Bone Mineral Density in Fanconi Anemia

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 224-247-Osteoporosis I
Clinical
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-244
Roopa Kanakatti Shankar*1, Neelam Giri2, Maya Beth Lodish3, Ninet Sinaii4, James Reynolds5, Blanche P Alter2 and Constantine A Stratakis6
1NICHD, NIH, Bethesda, MD, 2National Cancer Institute, National Institutes of Health, Rockville, MD, 3NIH, 4National Institutes of Health, Bethesda, MD, 5CC-NIH, Bethesda, MD, 6National Institutes of Health (NIH), Bethesda, MD
Introduction: Previous studies suggested that Fanconi anemia (FA) is associated with decreased bone mineral density (BMD) (1) but did not account for short stature seen in these patients. BMD was reported to be normal in children with FA after correcting for height age (2).

Methods: We retrospectively analyzed data on patients with FA evaluated in the NCI’s Inherited Bone Marrow Failure Syndromes Study. BMD was measured by dual-energy X-ray absorptiometry scan (Hologic) at the lumbar spine and femoral neck. Data were re-interpreted after adjusting for height.  We calculated height-adjusted BMD Z-scores (HAZ) in children (≤20 years) using the online Bone Mineral Density Childhood Study calculator (3). In adults, bone mineral apparent density (BMaD) Z-scores were calculated to adjust for the effect of stature on bone size and BMD (4).

Results: Data from 24 patients (8 male): 9 children (median age 11.9y; 8.1-18.4) and 15 adults (median age 31.8y; 20.6-56.6) were analyzed. FA was diagnosed by chromosomal breakage study and confirmed by complementation studies and/or mutation analysis. Seven patients (4 adults) had undergone hematopoietic cell transplantation (HCT) with a median duration of 9.1y (6.7-17.4) since transplant. Several patients were on medications known to affect BMD including androgens (4/24), glucocorticoids (1/24), estrogens (4/11 women, 1 child) and bisphosphonates (4/24). In children, mean height Z-score was -1.25 (SD 1); mean BMD Z-score at the lumbar spine was -0.52 (SD 1.4); mean HAZ was 0.58 (SD 0.8). At the femoral neck mean BMD Z-score was -1.49 (SD 0.8); mean HAZ was -0.68 (SD 1.2). In the adults, mean height Z-score was -1.55 (SD 1.4); mean BMD Z-score was -1.52 (SD 1.3) at the lumbar spine and -1.22 (SD 1.3) at the femoral neck. BMaD Z-scores were -0.78 (SD 1.5) and -0.83 (SD 1.1) respectively. Excluding patients on bisphosphonates and using cut-offs established by Melton et al. (4), for BMD values that define osteoporosis in the adults, 3/12 met criteria for osteoporosis either at the spine or femoral neck. Using cutoffs based on BMaD values instead, only 1/12 met criteria for osteoporosis.

Conclusions: Children with FA have normal HAZ consistent with previous reports. While adults tend to have lower BMD, fewer patients meet criteria for osteoporosis using BMaD.  Correction for height must be considered in the interpretation of BMD in FA patients. Further study is needed on fracture risk and the effect of HCT on BMD in this population.

(1) Giri N, Batista DL, Alter BP, Stratakis CA. Endocrine Abnormalities in Patients with Fanconi Anemia. J Clin Endocrinol Metab 2007; 92(7):2624-31   (2) Rose SR, Rutter MM, Mueller R, Harris M et al. Bone mineral density is normal in children with Fanconi Anemia. Pediatr Blood Cancer. 2011 Dec 1;57(6):1034-82    (3) Zemel BS, Kalkwarf HJ, Gilsanz V, Lappe JM et al. Revised reference curves for bone mineral content and areal bone mineral density according to age and sex for black and non-black children: Results of the Bone Mineral Density in Childhood Study. J Clinic Endocrinol Metab. 2011 Oct; 96(10):3160-9.    (4) Melton LJ 3rd, Atkinson EJ, O’Connor MK, O’Fallon WM et al. Bone density and Fracture Risk in Men. J Bone Mineral Res 1998; 13(12):1915-23

Nothing to Disclose: RK, NG, MBL, NS, JR, BPA, CAS

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