Munns Craig F J, Rauch Frank, Travers Rose, Glorieux Francis H
Genetics Unit, Shriners Hospital for Children and McGill University, Montréal, Québec, Canada.
J Bone Miner Res. 2005 Jul;20(7):1235-43. doi: 10.1359/JBMR.050213. Epub 2005 Feb 21.
Clinical and histomorphometric outcome was compared between children with OI who had received pamidronate since infancy and age-matched patients who had never received pamidronate. Pamidronate was associated with improved vertebral shape and mass, higher cortical width, increased cancellous bone volume, and suppressed bone turnover.
Observations in small patient series indicate that infants with severe osteogenesis imperfecta (OI) benefit from treatment with cyclical intravenous pamidronate. However, detailed analyses of outcome are lacking for this age group.
Clinical outcome was evaluated in 29 children with OI types I (n = 3), III (n = 14), or IV (n = 12) who started pamidronate therapy before 2 years of age (age at treatment onset: median, 6 months; range, 2 weeks to 23 months) and who had completed 3 years of treatment (total annual pamidronate dose, 9 mg/kg). They were compared with a historical control group of 29 untreated children with severe OI who were matched for OI type and age at the 3-year treatment time-point. In addition, iliac bone histomorphometry was compared between 24 pamidronate-treated patients and 24 age-matched OI patients who had not received pamidronate.
Morphometric evaluation of lumbar vertebrae (L(1)-L(4)) showed that the shape of vertebral bodies was better preserved in pamidronate-treated patients. This was accompanied by significantly higher lumbar spine areal and volumetric BMD (+110 and +96%, respectively) and a larger vertebral bone volume (+26%) on densitometry. Regarding mobility function, the Pediatric Evaluation of Disability Inventory gross motor score was 50% greater in the pamidronate group (p < 0.001). Iliac bone histomorphometry showed 61% higher cortical width and 89% higher cancellous bone volume in pamidronate-treated patients. Bone formation rate per bone surface in the pamidronate group was only 17% that of untreated patients.
In conclusion, this study suggests that cyclical pamidronate treatment started in infancy leads to improved bone strength and better gross motor function but also suppresses bone turnover markedly. It is therefore prudent to reserve pamidronate treatment to infant OI patients who present with a moderate to severe phenotype.
比较自婴儿期起接受帕米膦酸盐治疗的成骨不全症（OI）患儿与年龄匹配的从未接受过帕米膦酸盐治疗的患者的临床和组织形态计量学结果。帕米膦酸盐与改善椎体形状和质量、增加皮质宽度、增加松质骨体积以及抑制骨转换有关。
在小样本患者系列中的观察表明，患有严重成骨不全症（OI）的婴儿从周期性静脉注射帕米膦酸盐治疗中获益。然而，该年龄组的详细结果分析尚缺乏。
对29例I型（n = 3）、III型（n = 14）或IV型（n = 12）的OI患儿进行临床结果评估，这些患儿在2岁之前开始帕米膦酸盐治疗（治疗开始时的年龄：中位数为6个月；范围为2周至23个月），并且已完成3年的治疗（帕米膦酸盐的年总剂量为9 mg/kg）。将他们与29例未经治疗的严重OI患儿的历史对照组进行比较，这些对照组在3年治疗时间点的OI类型和年龄相匹配。此外，比较了24例接受帕米膦酸盐治疗的患者和24例年龄匹配的未接受帕米膦酸盐治疗的OI患者的髂骨组织形态计量学。
腰椎（L(1)-L(4)）的形态计量学评估显示，接受帕米膦酸盐治疗的患者椎体形状保存得更好。这伴随着腰椎区域骨密度和体积骨密度显著更高（分别增加110%和96%），并且在骨密度测量中椎体骨体积更大（增加26%）。关于运动功能，帕米膦酸盐组的儿童残疾评估量表粗大运动评分高50%（p < 0.001）。髂骨组织形态计量学显示，接受帕米膦酸盐治疗的患者皮质宽度高61%，松质骨体积高89%。帕米膦酸盐组每骨表面的骨形成率仅为未治疗患者的17%。
总之，本研究表明婴儿期开始的周期性帕米膦酸盐治疗可改善骨强度和粗大运动功能，但也显著抑制骨转换。因此，谨慎起见，应将帕米膦酸盐治疗保留给具有中度至重度表型的婴儿OI患者。
