Bisphosphonates combined with surgical treatment is better to inhibit bone resorption of long bones with fibrous dysplasia

doi:10.3969/j.issn.2095-4344.2015.15.006

Abstract

Abstract:

BACKGROUND: Bisphosphonates that can suppress osteoclast activity strongly is a powerful inhibitor for bone resorption, which has been reported to have good effects in the treatment of fibrous dysplasia.
OBJECTIVE: To evaluate the clinical effect of surgical treatment combined with bisphosphonate therapy in the treatment of fibrous dysplasia.
METHODS: Fifteen patients with fibrous dysplasia of the long bone were subjected to surgical treatment and oral bisphosphonate therapy postoperatively. Limb pain, limb function, local X-ray manifestations and blood alkaline phosphatase activity were observed before and at 3, 6, 12, 24 months after treatment. The therapeutic effects were evaluated using modified Macnab standards.
RESULTS AND CONCLUSION: All the 15 patients were followed up for more than 24 months, and their pain symptoms were significantly relieved after the combined treatment of surgery and bisphosphonates, excellent in 12 cases and effective in 1 case, and the total efficiency was 100%. X-ray films showed that the density slightly decreased in operation areas after 3 months, but at 6 months after treatment, the cortical bone was thickened and the marrow cavity density increased in the operation areas, and non-focal zone was continuously enlarged. No fractures and recurrence were found in all patients. At 6 months after treatment, the serum alkaline phosphatase activity decreased significantly (P < 0.05). The results suggest that surgical operation with bisphosphonate treatment for bone fibrous dysplasia can effectively inhibit the bone resorption, promote bone formation, increase the intensity of the lesion, reduce fractures and recurrence rate, so as to achieve a better therapeutic effect in clinic.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

全文链接：

Key words: Diphosphonates, Pain, Alkaline Phosphatase, Osteoclasts

CLC Number:

R318

Yang Hong-sheng, Yan Xiao-hu, Li Yu-gang, Cao Zong-rui, Liu Zhan-li, Xu Xiao-ping, Chang Shan. Bisphosphonates combined with surgical treatment is better to inhibit bone resorption of long bones with fibrous dysplasia[J]. Chinese Journal of Tissue Engineering Research, 2015, 19(15): 2325-2329.

Figures/Tables 1

2.1 参与者数量分析纳入15例患者，均获得2年以上随访，最长随访45个月，平均32.6个月。治疗及随访过程无脱落，全部进入结果分析。 2.2 双膦酸盐类药物对骨吸收抑制效果外科治疗后均采用至少4次双膦酸盐治疗，其中2例患者使用5次，4例患者使用6次。8例患者使用帕米膦酸，7例使用唑来膦酸。术后3个月患肢可部分负重，6个月可完全负重。其中14例患者随访结果显示，外科治疗后3个月X射线显示植骨区密度较术后有降低。 2.3 局部骨密度和骨质量变化外科治疗后6个月X射线显性局部骨密度和骨质量均较原病骨明显提高，12个月后病灶密度已经达到最高，甚至高于正常骨密度。且该密度在进一步随访中趋于稳定(见图1)。 2.4 治疗前后血碱性磷酸酶变化及Macnab疗效评定结果患者外科治疗前碱性磷酸酶均高于正常值平均为 (133.40±3.10) U/L；治疗后3个月该数值降低不明显平均为 (128.61±2.89) U/L，与治疗前相比差异无显著性意义(P > 0.05)；6个月后碱性磷酸酶数值大多降低至正常范围平均为(86.12±3.05) U/L，与治疗前相比明显降低，差异且有显著性意义(P < 0.05)；12个月较6个月时变化不明显平均为(87.51±2.65) U/L，与治疗前相比差异有显著性意义(P < 0.05)，但与6个月相比差异无显著性意义(P > 0.05)。采用改良的Macnab疗效评定标准进行评价，显效12例，有效3例，无效0例，总有效率100%(15/15)。 2.5 典型病例患者女性29岁，右股骨近端纤维结构不良行病灶清除、植骨融合。使用双膦酸盐药物治疗后3个月X射线片结果提示病灶区密度稍低，骨皮质较薄；6个月X射线片显示植骨愈合好，病灶区骨密度升高，周围骨皮质增厚，植骨愈合好；18个月与6个月相差不多，植骨愈合好，无病灶复发。见图1。 2.6 不良反应所有患者伤口均一期愈合，无人工骨、异体骨排斥反应。所有病灶在随访期间未见复发，无患肢病理性骨折/再骨折。使用双膦酸盐后，部分患者出现不适症状，最主要为流感样表现，多发生于首次使用后1-3 d，体温轻度升高，为37.3-38.1 ℃，经适当补液，对症处理后好转；其次为乏力症状，间断或偶发的不适等。无严重不良反应，随访期间，未出现下颌骨坏死及股骨不典型骨折的患者。1例股骨上段病损的患者，外科治疗后1个月时残留患肢疼痛，治疗后3个月时随访时出现髓腔病损区下方局部骨溶解，但对骨强度无影响，治疗3个月后部分负重，6个月后再复查时疼痛完全消失，X射线见病灶无进展，可完全负重。"

References

[1] Bieniasz J, Maj A, Noczynska A. Fibrous dysplasia of bone in a 12 year old girl. Endokrynol Diabetol Chor Przemiany Materii Wieku Rozw.2006;12(1):69．
[2] Chow LT, Griffith J, Chow WH, et al.Monostotic fibrous dysplasia of the spine: report of a case involving the lumbar transverse process and review of the literature.Arch Orthop Trauma Surg.2000; 120(7-8):460-464.648-658.
[3] Campanacci M. Bone and soft tissue tumors: clinical features,imaging, pathology and treatment, 2nd edn. New York.Springer.1999.
[4] Parekh SG, Donthineni-Rao R, Ricchetti E,et al.Fibrous dysplasia.J Am Acad Orthop Surg.2004,12(5):305-313．
[5] Parisi MS, Oliveri B, Mautalen CA. Efect of intravenous pamidronate on bone markers and local bone mineral density in fibrous dysplasia. Bone.2003;33:582-588．
[6] Isaia GC, Lala R, Defilippi C, et al. Bone turnoverin children and adolescents with McCune-Albright syndrome treated with pamidronate for bone fibrous dysplasia. Calcif Tissue Int. 2002;71:121-128．
[7] Chapurlat RD．Medical therapy in adults with fibrousdysplasia of bone. J Bone Miner Res.2006;21,21:114-119．
[8] Riminucci M, Fisher LW, Shenker A，et al. Fibrous dysplasia of bone in the McCune-Albright syndrome: abnormalities in bone formation.Am J Pathol.1997;151(6):1587-1600.
[9] Bianco P, Kuznetsov SA, Riminucci M, et al. Reproduction of human fibrous dysplasia of bone in immunocompromised mice by transplanted mosaics of normal and Gsalpha- mutated skeletal progenitor cells. Clin Invest. 1998;101: 1737-1744．
[10] Candeliere GA, Glorieux FH, Prud’ homme J, et al. Increased expression of the c-fos protooncogene in bone from patients with fibrous dysplasia. N Engl J Med.1995;332:1546-1551．
[11] 李恩超.BMP-2、IL-6在骨的纤维结构不良中的表达及临床意义[J].中国骨肿瘤骨病,2005,4(3):162-166
[12] Jung ST, Chung JY, Seo HY,et al.Multiple osteotomies and intramedullary nailing with neck cross-pinning for Shepherd’s crook deformity in polyostotic fibrous dysplasia:7 femurs with a minimum of 2 years follow-up.Acta Orthop. 2006;77(3): 469-473.
[13] Dunstan E, Tilley S, Briggs TW, et al. A customised replacement for polyostotic fibrous dysplasia of the upper femur. A 51-year follow-up. J Bone Joint Surg (Br).2005;87(1): 114-115.
[14] Chen WJ, Chen WM, Chiang CC, et al. Shepherd’s crook deformity of polyostotic fibrous dysplasia treated with corrective osteotomy and dynamic hip screw. J Chin Med Assoc.2005;68(7):343-346.
[15] Watanabe K, Tsuchiya H, Sakurakichi K, et al. Double-level correction with the Taylor Spatial Frame for shepherd’s crook deformity in fibrous dysplasia. J Orthop Sci.2007;12(4): 390-394
[16] 牛艳辉,王臻.98例四肢骨纤维结构不良临床分析[J.中国矫形外科杂志,1998,5(4):329．
[17] 郭卫. 纤维异样增殖症//徐万鹏,冯传汉.骨科肿瘤学[M].北京:人民军医出版社,2001:331-332．
[18] Arpornchayanon O, Leerapun T. Effectiveness of intravenous bisphosphonates in treatment of giant cell tumour: a case report and review of the literature. J Med Assoc Thai.2008; 91:1609-1612.
[19] Plotkin H，Ranch F，Zeitlin L, et al. Effect of pamidronate treatment in children with polyostotie fibrous dysplasia of bone. J Clin Endocrinol Metab.2003;88(10):4569-4575．
[20] Collins MT, Chebli C, Jones J, et al. Renal phosphate wasting in fibrous dysplasia of bone is part of a generalized renal tubular dysfunction similar to that seen in tumor induced osteomalacia. J Bone Miner Res.2001;16(5):806-813．
[21] Khadikar VV, Khadikar AV, Maskati GB. Oral bispho-sphonmes in polyostotic fibrous dysplasia．Indian Pediatr.2004;41(9):1069-1070.
[22] 胥少汀,朱兵.骨的纤维结构不良的临床特点和处理(附38例分析)[J].中国骨肿瘤骨病杂志,2004,3(6):325-329.