RANKL靶向抑制对骨纤维结构不良治疗的研究进展

doi:10.13591/j.cnki.kqyx.2023.11.012

摘要/Abstract

摘要：

骨纤维结构不良(fibrous dysplasia, FD)是一种由骨骼干细胞内GNAS突变引发的骨组织被纤维组织代替的罕见骨病,临床上缺乏有效的药物治疗手段。近年,有研究发现FD病变区域内核因子κB受体配体(receptor activator for nuclear factor-κB ligand, RANKL)呈高表达,介导破骨细胞功能亢进,严重者可导致病理性骨折。因此,RANKL成为FD的潜在治疗靶点。目前,国内外有关FD的RANKL靶向抑制治疗研究尚处于初步探索阶段,已有临床病例报道和实验室研究成果支持RANKL靶向抑制对FD骨骼症状的有效缓解作用。本文就国内外关于RANKL靶向抑制对FD治疗进展作一综述。

关键词: 骨纤维结构不良, RANKL, 靶向治疗

Abstract:

Fibrous dysplasia (FD)is a rare bone disease in which fibrous tissue replaces bone tissue, and is caused by a GNAS mutation in skeletal stem cells.Currently, there is no cure for FD. Receptor activator for nuclear factor-κB ligand (RANKL)has been discovered to be highly expressed in FD lesions, which mediates osteoclast hyperfunction and causes pathological bone fractures in severe cases. RANKL is thus a possible therapeutic target for FD. RANKL inhibition in FD treatment draws attention from researchers at home and abroad. Clinical case studies and laboratory studies have validated the relieving effect of RANKL inhibition on skeletal symptoms of FD. The current progress of RANKL inhibition in the management of FD is reviewed in this article.

Key words: fibrous dysplasia, RANKL, targeted therapy

中图分类号:

R739.82

刘钟毓, 白丁, 赵雪峰. RANKL靶向抑制对骨纤维结构不良治疗的研究进展[J]. 口腔医学, 2023, 43(11): 1028-1033.

LIU Zhongyu, BAI Ding, ZHAO Xuefeng. Research progress of RANKL inhibition in the treatment of fibrous dysplasia[J]. Stomatology, 2023, 43(11): 1028-1033.

图/表 2

表1

表2

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发表年份	通信作者	研究对象	治疗效果			停药反应			副作用^§
发表年份	通信作者	研究对象	疼痛缓解	骨转换率降低	骨质量改善	疼痛复发	骨转换率回弹	高钙血症	副作用^§
2012	Collins^[17]	9岁,男	√	√	√^#	N	√	√	影响生长发育
2013	Seibel^[24]	44岁,女	√	√	N	√	√	×
2013	Seibel^[24]	48岁,男	N	√	N	√	√	×
2014	Benhamou^[23]	46岁,男	√	√	N	√	√	×
2016	Chiodini^[25]	20岁,男	√	×^?	N	√	×^?	×
2019	Ohshika^[38]	37岁,女	×^?	√	√	N	N	N
2020	Paul^[26]	45岁,女	√	√	N	N	N	N
2021	Ikuta^[29]	27岁,女	√	√	√	√	N	×	低钙血症
2021	Boyce^[28]	13岁,女	√	√	√	√	√	√	致密性骨炎
2021	Meier^[27]	37岁,女	√	√	√	N	N	N
2021	Meier^[27]	68岁,女	√	√	√	N	N	N
2022	Upadhyay^[37]	21岁,女	×	N	N	N	N	N
2019	Riminucci^[34]	小鼠^*		√	√		√	√
2020	Riminucci^[32]	小鼠^*		N	√		N	N
2021	Zhao^[39]	小鼠^*		√	√		N	N
2019	Appelman^[30]	12人	√	√	N	N	N	N
2021	Meier^[35]	37人	√	√	N	√	√	×	颌骨骨坏死
2023	Boyce^[40]	8人	√	√	N	N	√	√

发表年份	通信作者	研究对象	给药频率	每次给药剂量
2012	Collins^[17]	9岁,男	共给药7次。每月给药1次。	初始剂量1 mg/kg;每3月剂量增加1次,依次为1.25 mg/kg,1.5 mg/kg
2013	Seibel^[24]	44岁,女	共给药3次。第1、2剂间隔9个月,第2、3剂间隔时间6个月。	60 mg
		48岁,男	共给药2次。两次给药间隔4个月。	60 mg
2014	Benhamou^[23]	46岁,男	共给药2次。两次给药间隔6个月。	60 mg
2016	Chiodini^[25]	20岁,男	共给药10次。每次给药间隔75~90 d,给药时机依据患者主观的疼痛复发。	60 mg
2019	Ohshika^[38]	37岁,女	共给药2次。每次给药间隔6个月。	60 mg
2020	Paul^[26]	45岁,女	共给药3次。每次给药间隔6个月。	初始剂量60 mg;后续提升剂量至120 mg
2021	Ikuta^[29]	27岁,女	在第1、8、15和29天给药,此后的每月给药;治疗3个月后,减为每2个月给药1次;治疗12个月后,减少到每3个月给药1次;在治疗18个月时,停药。共给药12次。	120 mg
2021	Boyce^[28]	13岁,女	先每月给药,持续18个月;而后给药频率逐渐减少到每6周、7周、8周和每3个月给药1次。在3.5年期间共31次。	初始剂量53 mg(1 mg/kg),维持18个月;后续逐渐增加至70 mg
2021	Meier^[27]	37岁,女	每3个月给药1次,已持续5.5年。	60 mg
		68岁,女	每3个月给药1次,已持续5.3年。	60 mg
2022	Upadhyay^[37]	21岁,女	共给药2次。每次给药间隔6个月。	120 mg
2023	Boyce^[40]	共8人	共给药6次,每次间隔1个月。	120 mg