Effect of Enzyme Replacement Therapy on Bone Mineral Density in Type 1 Gaucher Disease.

Objective: To determine the effect of enzyme replacement therapy (ERT; Cerezyme®, imiglucerase for injection) on bone mineral density (BMD) in patients with type 1 Gaucher disease (GD).

Methods: The GD population included all adults (males 18–70y, females 18–50y) with type 1 GD enrolled in the International Collaborative Gaucher Group (ICGG) Gaucher Registry for whom serial spine BMD measurements were submitted. BMD data with up to 12 years of follow-up were analyzed for 111 patients not on ERT, 218 patients on ERT only and 34 patients on ERT plus bisphosphonates. BMD was measured by dual energy X-ray absorptiometry (DXA) Z-scores (age and sex-adjusted) in the lumbar spine of each patient. All measurements were compared to a reference population (Hologic reference standard).

Results: DXA Z-scores for GD patients not on ERT were significantly lower than the reference population and remained approximately one standard deviation below the reference population over time (y intercept = −1.01, p<0.001; slope= +0.012, p=0.63). The DXA Z-scores for GD patients receiving ERT-only were also significantly lower than the reference population at baseline, but improved significantly over time, and the model suggests that on average patients do achieve the same values as the reference population after approximately 12 years of ERT (y-intercept = −1.21, p<0.001; slope= +0.092, p<0.001). The DXA Z-scores for GD patients receiving ERT plus bisphosphonates had an even more rapid increase, on average approaching the reference population after approximately 6 years of treatment (y-intercept = −1.23, p<0.001; slope = +0.202, p=.0003).

Discussion and Conclusion: Osteopenia and osteoporosis are common manifestations of type 1 GD. ERT with Cerezyme® significantly improves BMD in patients with GD. Response to treatment with ERT for BMD may be slower than other aspects of GD. On average, GD patients achieve age- and sex-adjusted normal BMD after approximately 12 years of ERT. The addition of bisphosphonates to ERT may produce an additive effect, with patients achieving a normal BMD more rapidly. A normal (age- and sex-adjusted) BMD should be a therapeutic goal for patients with type 1 GD.