骨坏死临床研究的现状、进展与前景

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四、干细胞治疗骨坏死

骨坏死的病理生理学研究发现,股骨头坏死患者股骨近端成骨细胞的增殖活性降低^{[ 30 ]} ,骨髓造血间室和基质部分基质干细胞的活性降低、数量减少,骨坏死可能是一种骨细胞和基质细胞相关性疾病^{[ 31} ^]。骨髓干细胞是人们迄今研究最多、认识最深刻的干细胞类型,其中包含具有成骨特性的成体干细胞,如造血干细胞、基质干细胞、多能干细胞等。因此,骨髓干细胞移植治疗可能是治疗骨坏死的一种有效方法。自体骨髓移植治疗骨坏死,最先报道是应用于1例肱骨头坏死患者的治疗^{[ 32 ]} ,然后才逐步应用到股骨头坏死的治疗领域。Gangji等^{[ 33 ]}对13例( 18髋) Ⅰ和Ⅱ期股骨头坏死患者进行对照双盲研究,将患髋分为单纯髓心减压组(对照组)和髓心减压加骨髓单核细胞移植组(骨髓移植组) ,评估其安全性、临床症状及疾病的进展情况。24个月的随访发现:骨髓移植组患者疼痛及其它关节症状明显减轻,骨坏死容量减少35% ,仅有1髋(1 /10)进展到Ⅲ期;而对照组骨坏死容量增加23% ,有5髋( 5 /8)进展到Ⅲ期骨坏死;生存率分析提示,两组患者进展到关节塌陷的时间有明显差异。Hernigou等^{[ 34 ]}回顾性分析了116例(189髋)患者行髓心减压及骨髓移植术的疗效。患者获得5～11年随访,平均随访7年。研究评价指标为临床症状的改变、影像学分期进展和关节置换的必要性。在塌陷前期( Ⅰ和Ⅱ期)进行治疗的145髋,只有9髋需要再次手术行髋关节置换术;在塌陷后期( Ⅲ和Ⅳ期)行治疗的55髋,有25髋需要再次手术行全髋关节置换术。以上两项研究提示骨髓移植对早期骨坏死的治疗是有效的,但其疗效及安全性还需要大规模的临床实验进一步验证。随着干细胞技术的日臻成熟、股骨头坏死发病机制和骨修复生理学研究的不断深入,利用骨髓干细胞移植治疗股骨头坏死将呈现出良好的发展前景。

五、研究前景展望

经过适当的治疗,大多数骨坏死患者能恢复到正常生活状态。但是,目前对骨坏死的掌握还十分有限,笔者期待随着研究的深入,在骨坏死的预防、诊断和治疗方面能有更新、更大的突破。当前及今后相当长的一段时间内,骨坏死的研究重点应集中体现以下几个方面: (1)筛查高危人群,调查骨坏死的发生率及流行病学特征; (2)鉴定疾病发生的危险因素,如明确凝血功能障碍性疾病是否为骨坏死发生的危险因素; (3)建立合适的骨坏死动物模型,以利于疾病的研究;(4)深入研究激素与骨坏死发生发展的关系和致病机理;(5)机械力学的研究,如髋、膝、踝关节的力线,因为力学因素是影响治疗效果的重要内容; (6)开发新的、更有效的骨坏死诊断方法,以便于早期诊断,提高疗效; (7)生物制剂疗法是骨坏死治疗的新方向,有广阔的应用前景,也是当前的研究热点; (8)在研发新治疗方法的同时,不要忽视现有治疗方法,这些旧方法经改造还有很大的提升空间,值得进一步的研究和探讨; (9)提高关节置换的手术技术、改进人工关节的材料,这样年轻患者将可能避免再次行关节置换术; ( 10)探寻骨坏死可能的预防措施,预防高于治疗。

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