Bone mineral density in patients with autosomal recessive osteopetrosis after hematopoietic cell transplantation

Anna Petryk; Lynda E Polgreen; Donald R Dengel; Todd E Defor; Paul Orchard

doi:10.1530/boneabs.4.P20

Objectives: Autosomal recessive osteopetrosis (OP) is a rare metabolic bone disease characterized by impaired osteoclast function resulting in defective bone resorption and generalized high bone mineral density (BMD). Excessive bone compromises bone marrow space, leading to marrow failure. The infantile malignant form is typically fatal within the first decade of life. The intermediate form presents later during childhood. Currently, the only potential curative therapy for OP is hematopoietic cell transplantation (HCT), which restores normal hematopoiesis and provides a source of functional donor-derived osteoclasts. Little is known about the effect of HCT on BMD in OP, particularly in intermediate form. The objective of this study was to examine long-term impact of HCT on BMD in patients with OP. We hypothesized that mean BMD Z-score will be lower in HCT recipients with malignant OP transplanted at a younger age than those with intermediate OP.

Methods: A cross-sectional study was conducted in five patients with OP (four males) transplanted at the University of Minnesota between 1995 and 2010. All patients received myeloablative conditioning. BMD Z-scores for L1–L4 (LBMD) and total body excluding head (TBMD) for patients <18 years, were measured by dual energy X-ray absorptiometry.

Results: BMD data are shown in Table 1. Patients with malignant OP (transplanted at age ≤1 year) had mean LBMD Z-score −1.8±1.1 compared to LBMD Z-score 12.5±3.2 in patients with intermediate OP at a median of 4.3 years after HCT (range 3.1–19.1 years). TBMD Z-score was −0.7±0.5 for patients with malignant OP.

Table 1
Patient	1	2	3	4	5
Sex	M	F	M	M	M
Age at HCT (years)	0.2	0.5	1	24	33.2
Age at recent evaluation (years)	19.3	4.8	5.3	27.9	36.3
Height SDS at recent evaluation	−5.0	−2.4	−0.9	−1.4	−2.6
Pre-HCT LBMD Z-score	–	–	–	10.1	14.5
Post-HCT LBMD Z-score	−0.5	−2.2	−2.6	9.3	15.6
Post-HCT TBMD Z-score	−1.3	−0.4	−0.5	–	–

Conclusion: Patients with malignant OP who were transplanted during the first year of life had a normal or even low LBMD at most recent follow up versus patients with intermediate OP, transplanted during young adulthood, who had high LBMD. The clinical significance of this persistently elevated LBMD in patients with intermediate OP is unknown. Future studies should address the effect of HCT on bone quality and fracture risk in these patients.

Disclosure: The authors declared no competing interests.

Bone Abstracts

P20