（医学课件）糖皮质激素致股骨头坏死.ppt

糖皮质激素致股骨头坏死 风险预测进展,1,.,2,.,1、每日剂量与股骨头坏死的关系,3,.,2、激素暴露时间与股骨头坏死的关系,Glucocorticoid exposure was associated with osteonecrosis regardless of how recent the drug use was: Within 1 to 90 days, OR 5.8 (95% CI 1.6 to 21.2) Between 180 and 365 days earlier, OR 8.9 (95% CI 2.5 to 32.5) More than 730 days earlier, OR 4.3 (95% CI 2 to 9) When the researchers conducted a separate analysis limited to remote users patients whose exposure was more than a year before the index date they found persistent high risks: Between 30 and 90 days, OR 9.3 (95% CI 2.5 to 34.9) Between 90 and 180 days, OR 4.1 (95% CI 0.4 to 47.9) More than 365 days, OR 165.4 (95% CI 7 to 999.9) Primary source: American College of Rheumatology Vlad S, et al “Short periods of glucocorticoid use are associatd with a prolonged risk of osteonecrosis“ ACR 2011; Abstract 802.,4,.,5,.,6,.,1、纤溶酶原激活物抑制物-1（PAI-1）： 内源性纤溶活性的关键调节因子， 4G4G allele carriers always have higher plasma PAI-1 activity than 4G5G and 5G5G carriers 2、ABCB1 3435： p糖蛋白家族，药物转运蛋白，MDR1基因,7,.,SARS患者基因型与股骨头坏死发生,8,.,PAI-1 4G5G基因型频率与股骨头坏死(%),9,.,ABCB1 3435CT基因型频率与股骨头坏死(%),注：CT、TT者，均为PAI-1 4G5G,10,.,PAI-1与ABCB1 3435基因型组合在ON与NO-ON中的频率,11,.,基因型与股骨头坏死发生概率,12,.,基因型风险度与股骨头坏死发生概率,13,.,PAI-1 4G/5G ： 4G 高风险， 5G低风险 ABCB1 C3435T： CC高风险 ， C T/TT低风险 测基因，主要判断口服及注射激素的风险，给出用药建议,风险基因,14,.,风险度 风险较高： PAI-1及ABCB1均为高风险，即两个高风险，则风险度高。 需高度关注骨骼反应，同时配伍用双膦酸盐。 降低激素剂量并换用其他药物。 风险度中等：PAI-1及ABCB1中，有一个高风险，则风险度中等， 需要关注骨骼反应，一旦有不良反应征象，即配伍用双磷酸盐。 风险度低：PAI-1及ABCB1均为低风险，则风险度低。 但仍需关注骨骼反应，一旦有不良反应征象，即配伍用双磷酸盐。,Robert S. Glucocorticoid-induced osteonecrosis. Endocrine 2011. DOI 10,1007/s 12020-011-9580-0,15,.,糖皮质激素致股骨头坏死副作用的预防性治疗 分子量250-320Da的双膦酸盐，可以容易到达骨腔隙小管系统，保护成骨细胞，抑制糖皮质激素诱导的凋亡【1】。 依替膦酸二钠 分子量：250Da 唑来膦酸（择泰）分子量：290Da,Robert S. Glucocorticoid-induced osteonecrosis. Endocrine 2011. DOI 10,1007/s 12020-011-958