Preliminary experience with the combined use of recombinant bone morphogenetic protein and bisphosphonates in the treatment of congenital pseudarthrosis of the tibia
Preliminary experience with the combined use of recombinant bone morphogenetic protein and bisphosphonates in the treatment of congenital pseudarthrosis of the tibia
复制标题
DOI：
10.1007/s11832-010-0293-3
复制
发表时间：
2010-12-01
影响因子：
1.4
通讯作者：
Little, David G.
中科院分区：
文献类型：
--
作者：
Birke, Oliver;Schindeler, Aaron;Little, David G.
目的先天性胫骨假关节(CPT)是一种少见但严重的儿童疾病。在手术程序、固定、最佳手术时间或辅助药物干预方面，没有一种单一的方法明显优于其他方法。CPT经常与1型神经纤维瘤病(NF1)有关，NF1是一种以骨合成代谢不足和过度分解代谢为特征的疾病。方法2002-2008年间，我们对8例Crawford IV型CPT患者在手术时应用BMP-7(OP-1)和BP(帕米膦酸盐或唑来膦酸)治疗，其中7例确诊为NF1，中位年龄7岁(2岁11个月至12岁)。结果8例中6例术后平均5.5个月(4-7个月)一期愈合。其中一例为CPT近端一期愈合后17个月，远端有新的骨折，需要多次手术才能在19个月时最终愈合。结论根据这些临床资料(6/8例一期愈合)和既往的临床前研究结果，我们认为BP疗法可能有助于通过抑制破骨细胞性骨丢失来保护BMP诱导的骨形成。在CPT中实现愈合的关键因素包括充分的固定，仔细切除发育不良的组织，以及建立一个有利于骨愈合的净合成代谢环境。我们用BMP和BP平衡合成代谢和分解代谢反应的生物学概念是否能在NF1 CPT的复杂治疗中提高治愈率仍不确定，需要进行更大规模的前瞻性多中心试验。
Purpose Congenital pseudarthrosis of the tibia (CPT) is a rare but serious disorder in children. No single approach has clearly emerged as superior in terms of operative procedure, fixation, optimal time for surgery or adjunctive pharmaceutical intervention. CPT is frequently associated with neurofibromatosis type 1 (NF1), a condition featuring deficient bone anabolism and excessive catabolism. We have therefore combined the use of bone morphogenetic proteins (BMP) with bisphosphonates (BP) as an adjunct to surgical intervention.Methods Between 2002 and 2008 we administered BMP-7 (OP-1) at the time of surgery followed by BP (pamidronate or zoledronic acid) in eight Crawford type IV CPT cases in seven patients (six with a confirmed diagnosis of NF1) with a median age of 7 years (range 2 years 11 months to 12 years) at surgery.Results In six of eight cases, this approach led to primary healing after a mean of 5.5 months (range 4-7 months). One of these cases represented 17 months after primary healing of a proximal CPT with a new further distal fracture that required multiple operations to finally unite at 19 months. The two remaining cases ultimately reached union after multiple operations at 14 and 30 months, respectively, but required recent treatment for refractures.Conclusion Based on these clinical data (primary healing in 6/8 cases) and prior pre-clinical findings, we propose that BP therapy may be helpful in preserving the BMP-induced bone formation by inhibiting the osteoclastic bone loss. Key factors to achieve union in CPT include sufficient fixation, meticulous resection of the dysplastic tissue and the establishment of a net anabolic environment for bone healing. Whether our biological concept of balancing the anabolic and catabolic responses with BMP and BP improves healing rates in the complex treatment of NF1 CPT remains uncertain and warrants larger prospective multicentre trials.