The Risk of Low Bone Mineral Density with Long-Term G-CSF Therapy for Severe Chronic Neutropenia.

Abstract 1484

Low bone mineral density (BMD) is a known risk factor for fractures. Low BMD has been reported in individuals with severe chronic neutropenia (SCN), and attributed both to the diseases causing neutropenia and to G-CSF therapy. However, given the rarity of SCN, few data exist regarding associations of BMD z-scores with disease characteristics such as type of neutropenia and duration of G-CSF therapy. We present data here obtained from BMD reports collected through the Severe Chronic Neutropenia International Registry (SCNIR).

We reviewed BMDs on 128 subjects [40 children (< 21 years of age), 87 females] having sufficient information about lumbar spine BMD by dual-xray absorptiometry (DXA) for evaluation. For subjects with multiple BMD measurements available, the most recent one was used for analysis. Mean age was 32.0 years (range 0.6–85 years).

57 subjects had idiopathic SCN (mean age 40 years), 40 had congenital (mean age 15 years), 28 were cyclic (mean age 41 years) and 3 were autoimmune (mean age 18 years). 122 subjects had received G-CSF at the time of the BMD assessment (mean 8.8 years, range 0.1–19.9 years). 11 of the adults were on bisphosphonate therapy for low BMD at the time of the BMD assessment; no children were on anti-resorptive therapy.

BMDs in these subjects were, on average, low. For the children, the BMD z-score (age matched mean ±1 standard deviation) was -1.0 ± 1.1, with 17.5% of children having BMDs that were low for age (Z-score < -2.0). For the adults the BMD t-score was -1.1 ± 1.4, with 46% of adults meeting t-score criteria for osteopenia (≤ -1.0) and 9% meeting criteria for osteoporosis (< -2.5). BMDs were lowest in those with congenital neutropenia, followed by those with cyclic neutropenia.

For children, BMDs were lower in those who had received longer G-CSF therapy (r= -0.506, p=0.002). This association was not seen in adults (r= 0.074, p= 0.5).

The low BMDs and the correlation of lower BMD with longer G-CSF treatment in children suggests there is an association of bone loss with the childhood diseases causing SCN. The data also suggest that regular assessments of bone health should be made in SCN patients, particularly those on long-term G-CSF therapy.