Abstract
Bone disease is a common cause of morbidity in Gaucher disease (GD). 60% of adult patients (pts) have decreased bone mineral density (BMD). However, in elderly pts, statistically “normal” BMD may not indicate functionally normal bone strength. Here we report serial dual energy x-ray absorptiometry (DXA) scores and fracture (Fx) occurrence for 29 GD pts age 57–88 (9M, 20F) treated with enzyme replacement therapy (ERT) with imiglucerase, often in conjunction with bisphosphonates.
Results: Lumbar (L) spine Z-scores were mostly normal during 9.2 ± 4.9 y on ERT: median −0.50; mean (SD) −0.05 (0.41); centiles 10–90: −1.81 - 1.21. Nonetheless, new Fxs occurred in 13 of 29 (44.8%) pts: hip (6), spine (4), other location (11), multiple sites (7). Fx occurred in 5/8 (62.5%) pts with splenectomy v 8/21 (38.1%) pts without and in 7/20 (35%) N370S homozygotes v 6/9 (67%) with other genotypes. 10y Fx probability: 42% (CI 17–55). L spine T-scores were < −1 for 18/29 pts, indicating persistent osteopenia/osteoporosis in 62%, and < −2.68 in 25%. New Fx occurred in 8/15 (53.0%) pts with T-scores ≤ the median of −1.60 v 5/14 (35.7%) with T-scores > −1.60. Pts with low T scores were predominantly women (13/15F v 7/14M) and had higher use of bisphosphonates (86.7% v. 35.7%). Fx were not restricted to pts with the lowest T-scores. Findings were similar for femoral neck T-scores.
Conclusions: Normal DXA Z-scores in elderly GD pts do not indicate low Fx risk. Low T-scores, as seen in our pts, do confer an important Fx risk. The 42% 10y Fx probability in our elderly GD pts is higher than expected for comparably aged individuals without GD. Because other risk factors such as Fx history, nutritional status, and concurrent illness were similar in our pts regardless of Fx status, cumulative pathophysiology from long-standing, untreated GD may independently increase Fx risk. Treatment with ERT may allow pts to achieve normal Z-scores. However, starting ERT late in life, even in conjunction with bisphosphonates, may not reverse established osteopenia/osteoporosis sufficiently to avoid future Fx. Therefore, detection of bone loss in young pts and early therapeutic intervention to achieve and maintain normal BMD is an important component of GD management.
Author notes
Disclosure: Research Funding: Research grant from Genzyme Corporation, Cambridge MA. Participating in clinical trials with Genzyme Corporation, Shire Therapeutics Inc and Amicus Corporation Inc. Honoraria Information: Honoraria for speaking and for attendance at meetings from Genzyme Corporation and from Shire Therapeutics Inc. Membership Information: Member of speaker bureau for Genzyme Corporation and member and chairperson of the Board fo Scientific Advisors for the International Collaborative Gaucher Group Registry that is sponsored by Genzyme Corporation.
