Wenstrup Richard J, Kacena Katherine A, Kaplan Paige, Pastores Gregory M, Prakash-Cheng Ainu, Zimran Ari, Hangartner Thomas N
Cincinnati Children's Hospital Research Foundation, Ohio, USA.
J Bone Miner Res. 2007 Jan;22(1):119-26. doi: 10.1359/jbmr.061004.
The effect of ERT with imiglucerase on BMD in type 1 GD was studied using BMD data from the International Collaborative Gaucher Group Gaucher Registry. Data were analyzed for 160 untreated patients and 342 ERT-treated patients. Imiglucerase significantly improves BMD in patients with GD, with 8 years of ERT leading to normal BMD.
The objective was to determine the effect of enzyme replacement therapy (ERT; Cerezyme, imiglucerase) on BMD in type 1 Gaucher disease (GD).
The study population included all adults (men, 18-70 years; women, 18-50 years) enrolled in the International Collaborative Gaucher Group (ICGG) Gaucher Registry for whom lumbar spine BMD measurements were available. BMD data with up to 8 years of follow-up were analyzed for 160 patients who received no ERT and 342 patients treated with ERT alone. BMD was assessed by DXA of the lumbar spine. Z scores for patients with GD were compared with a reference population. From the model's estimate, percent of patients by age and sex with osteoporosis (T score < or = -2.5) were calculated.
DXA Z scores for patients with GD in the no ERT (untreated) group were significantly below normal (y intercept = -0.80 Z score units, p < 0.001) and remained approximately 1 SD below the reference population over time (slope = -0.010 Z score units per year, p = 0.68). The DXA Z scores for patients with GD who received ERT at a dose of 60 U/kg/2 weeks were significantly lower than the reference population at baseline (y-intercept = -1.17 Z score units, p < 0.001), but improved significantly over time (slope = +0.132 Z score units per year, p < 0.001). A significant dose-response relationship was noted for the ERT group, with the slopes for the three main dosing groups of 15, 30, and 60 U/kg/2 weeks of +0.064, +0.086, and +0.132 Z score units per year, respectively. The BMD of patients with GD treated with ERT increased to -0.12 (60 U/kg/2 weeks), -0.48 (30 U/kg/2 weeks), and -0.66 (15 U/kg/2 weeks) SD of the mean of the reference population after 8 years of ERT, approaching the reference population. Estimated risk of osteoporosis of this GD population, if left untreated, ranged from approximately 10 to 30% in women and 10% to 25% in men.
ERT with imiglucerase (Cerezyme) may increase BMD in patients with GD. Response to treatment with imiglucerase is slower for BMD than for hematologic and visceral aspects of GD. A normal (age- and sex-adjusted) BMD should be a therapeutic goal for patients with type 1 GD.
使用国际协作戈谢病研究组戈谢病登记处的骨密度数据，研究了用伊米苷酶进行酶替代疗法（ERT）对1型戈谢病（GD）骨密度的影响。对160例未治疗患者和342例接受ERT治疗的患者的数据进行了分析。伊米苷酶显著改善了戈谢病患者的骨密度，ERT治疗8年后骨密度恢复正常。
目的是确定酶替代疗法（ERT；思而赞，伊米苷酶）对1型戈谢病（GD）骨密度的影响。
研究人群包括所有纳入国际协作戈谢病研究组（ICGG）戈谢病登记处且可获得腰椎骨密度测量值的成年人（男性，18至70岁；女性，18至50岁）。对160例未接受ERT的患者和342例仅接受ERT治疗的患者长达8年的随访骨密度数据进行了分析。通过腰椎双能X线吸收法（DXA）评估骨密度。将戈谢病患者的Z评分与参考人群进行比较。根据模型估计，计算不同年龄和性别的骨质疏松症患者（T评分≤ -2.5）的百分比。
未接受ERT（未治疗）组戈谢病患者的DXA Z评分显著低于正常水平（截距 = -0.80 Z评分单位，p < 0.001），且随时间推移仍比参考人群低约1个标准差（斜率 = -0.010 Z评分单位/年，p = 0.68）。接受每2周60 U/kg剂量ERT治疗的戈谢病患者的DXA Z评分在基线时显著低于参考人群（截距 = -1.17 Z评分单位，p < 0.001），但随时间显著改善（斜率 = +0.132 Z评分单位/年，p < 0.001）。ERT组呈现显著的剂量反应关系，每2周15、30和60 U/kg三个主要给药组的斜率分别为+0.064、+0.086和+0.132 Z评分单位/年。ERT治疗8年后，接受ERT治疗的戈谢病患者的骨密度增加到参考人群平均值的-0.12（每2周60 U/kg）、-0.48（每2周30 U/kg）和-0.66（每2周15 U/kg）标准差，接近参考人群。该戈谢病群体若不治疗，估计骨质疏松症风险在女性中约为10%至30%，在男性中为10%至25%。
用伊米苷酶（思而赞）进行ERT可能会增加戈谢病患者的骨密度。伊米苷酶治疗对骨密度的反应比对戈谢病血液学和内脏方面的反应慢。正常（年龄和性别校正后）骨密度应成为1型戈谢病患者的治疗目标。
