帕米膦酸二钠治疗累及股骨近端多发性纤维结构不良的24例报告

Pamidronate disodium for polyostotic fibrous dysplasia in the proximal femur:twenty-four cases report

目的：探讨帕米膦酸二钠对不同程度病情的累及股骨近端多发性纤维结构不良的治疗方法及临床疗效。方法2009年6月至2012年1月，我院收治的累及股骨近端的多发性纤维结构不良者24例，其中男14例，女10例，年龄8～61（平均24）岁。手术＋术后帕米膦酸二钠治疗组11例，其中肿瘤刮除植骨内固定术8例，不刮除病灶单纯行内固定者3例；单纯应用帕米膦酸二钠治疗组13例。术后或第一次治疗后，每3个月按疗程应用帕米膦酸二钠，共2年。所有病例于治疗前及每次给予帕米膦酸二钠前检测骨代谢指标骨钙素和I型胶原C端肽，并行影像学检查。采用VAS评分系统评价治疗前后的疼痛变化，Harris髋关节评分系统评价髋关节功能。观察有无药物不良反应。结果本组24例共接受了205次帕米膦酸二钠治疗。所有病例均获24～55个月的随访，中位随访时间42个月。治疗后第2年血清骨钙素水平（80.195±64.75）μg/L较治疗前（147.198±104.86）μg/L明显降低，差异有统计学意义（P＝0.000），血清I型胶原C端肽水平（0.672±0.61）μg/L较治疗前（1.396±0.6）μg/L也明显降低，差异有统计学意义（P＝0.000）。手术＋术后应用帕米膦酸二钠的11例中仅有1例出现病情恶化，再次骨折，其余10例内固定均牢靠，7例骨量增加，3例病情无变化。单纯应用帕米膦酸二钠治疗的13例仅有1例病情恶化，其余12例均有不同程度的骨量增加、溶骨区减少、骨皮质增厚。所有病例治疗后疼痛逐渐减轻，末次随访VAS评分平均为优，手术＋药物治疗组：末次随访VAS评分（1.33±1.1）明显小于治疗前VAS评分（7.25±1.7）；单纯药物治疗组：末次随访VAS评分（1.17±1.5）小于治疗前VAS评分（5.83±1.3），差异均有统计学意义（P＝0.002）。所有病例髋关节功能明显恢复，末次随访Harris评分平均为良，手术＋药物治疗组：末次随访Harris评分（79.58±5.2）大于治疗前Harris评分（43.67±31.8）；单纯药物治疗组：末次随访Harris评分（79.17±8.4）大于治疗前Harris评分（69.75±7.9），差异均有统计学意义（P＝0.002）。除5例在首次静滴帕米膦酸二钠后次日发热外，24例均未见其它不良反应。结论帕米膦酸二钠治疗累及股骨近端多发性纤维结构不良疗效确切，能减少溶骨性破坏、预防骨折风险、缓解疼痛、改善髋关节功能，不良反应轻微、短暂。对无症状的PFD、MAS无须手术治疗，可直接应用帕米膦酸二钠治疗；对病变范围局限、溶骨性破坏者须行刮除植骨内固定术，对于股骨近端病变范围大、骨强度不佳者可单纯内固定，二者术后均须应用帕米膦酸二钠治疗，以防止植骨吸收及病情恶化。

Objective To investigate the therapeutic methods and clinical effects of pamidronate disodium for polyostotic ifbrous dysplasia in the proximal femur in different degrees. Methods From June 2009 to January 2012, 24 patients with polyostotic ifbrous dysplasia in the proximal femur were adopted and treated. There were 14 males and 10 females, whose average age was 24 years old （ range;8-61 years ）. A combination of surgery and postoperative pamidronate disodium was performed on 11 patients, curettage, bone graft and internal ifxation on 8 patients, simple internal fixation on 3 patients and only pamidronate disodium on 13 patients. Pamidronate disodium was taken every 3 months after the operation or after the ifrst treatment, and the duration was 2 years. Before the treatment or before pamidronate disodium injection, bone metabolic markers were detected and the imaging examination was performed in all the patients, including osteocalcin （ OC ） and C-terminal telopeptides of type I collagen （ CTX-I ）.The Visual Analogue Scale （ VAS ） was used to evaluate the preoperative and postoperative pain. The hip function was systematically assessed based on the Harris hip score. The adverse effects were observed. Results A total of 205 times of pamidronate disodium injection were received. All the patients were followed up for 24-55 months, and the median follow-up time was 42 months. At the 2nd year after the treatment, the level of OC in the serum was （ 80.195±64.75 ）μg/L, which was obviously reduced when compared with the level of （ 147.198±104.86 ）μg/L before the treatment. The differences between them were statistically signiifcant （ P=0.000 ）. At the 2nd year after the treatment, the level of CTX-I in the serum was （ 0.672±0.61 ）μg/L, which was also obviously reduced when compared with the level of （ 1.396±0.6 ）μg/L before the treatment. The differences between them were statistically signiifcant （ P=0.000 ）. In the group of a combination of surgery and postoperative pamidronate disodium, disease progression of fracture again was noticed only in 1 case and ifrm internal ifxation in the other 10 cases, including 7 cases of increased bone mass and 3 cases of no disease progression. In the group of only pamidronate disodium, disease progression was noticed only in 1 case and increased bone mass, reduced osteolysis and cortical thickening of bone in different degrees in the other 12 cases. Pain was gradually relieved after the treatment in all the patients, with excellent VAS scores on average in the latest follow-up. In the group of a combination of surgery and pamidronate disodium, the VAS score was （ 1.33±1.1 ） points in the latest follow-up, which was obviously reduced when compared with the preoperative VAS score of （ 7.25±1.7 ） points. The differences between them were statistically signiifcant （ P=0.002 ）. In the group of only pamidronate disodium, the VAS score was （ 1.17±1.5 ） points in the latest follow-up, which was reduced when compared with the preoperative VAS score of （ 5.83±1.3 ） points. The differences between them were statistically signiifcant （ P=0.002 ）. The hip function was well restored in all the patients, with good Harris hip scores in the latest follow-up. In the group of a combination of surgery and pamidronate disodium, the Harris hip score was （ 79.58±5.2 ） points in the latest follow-up, which was greater than the preoperative Harris hip score of （ 43.67±31.8 ） points. The differences between them were statistically signiifcant （ P=0.002 ）. In the group of only pamidronate disodium, the Harris hip score was （ 79.17±8.4 ） points in the latest follow-up, which was greater than the preoperative Harris hip score of （ 69.75±7.9 ） points. The differences between them were statistically signiifcant （ P=0.002 ）. Except that fever was noticed in 5 patients at the 2nd day after the ifrst intravenous drip infusion of pamidronate disodium, no adverse reactions were found in the 24 patients. Conclusions Pamidronate disodium is effective in the treatment of polyostotic fibrous dysplasia in the proximal femur, with the advantages of inhibiting osteolytic bone destruction, preventing the risk of bone fractures, relieving pain, improving the hip function, reducing adverse reactions and minimizing the treatment time. For the patients with asymptomatic polyostotic fibrous dysplasia or McCune-Albright syndrome, surgery is unnecessary and pamidronate disodium is a good choice. Curettage, bone graft and internal ifxation should be performed on the patients with limited extent of lesions and osteolytic bone destruction. Simple internal ifxation should be performed on the patients with extensive lesions in the proximal femur, pathological fractures or severe deformities or on the verge of fractures. Both kinds of patients above should receive pamidronate disodium injection after the operation, so as to prevent bone absorption and disease progression.