系统性红斑狼疮的骨质疏松与皮质激素的相关性.PPT

GC induced osteoporosis 北京协和医院风湿免疫科 张 烜 Introduction GCs are effective in many rheumatic diseases But GC induced OP is a common side effect Trabecular rich sites eg spine ribs are especially at risk Effective Rx can prevent or reverse GC bone loss OP in RA on GC Rx 多因素 RA Osteoclast 活化 ( TNFa，RANK) Physical inactivity GC Rx Menopause 不同部位骨丢失不同 Hand Femur Spine 腰椎骨丢失与GC强相关 Pathophysiology Most of the biological activities mediated via Passage across cell membrane attachment to cytosolic GC receptor binding to GC response element regulating gene transcription May act via other transcription factors: activated protein (AP)-1 NF?B GC receptor binding Effects of GC on bone metabolism ? Bone formation Most important ? Bone resorbtion Probably only during 1st 6 – 12 months of Rx ? OC production postponed apoptosis Longterm, ? bone turnover ? Intestinal absorbtion of calcium ? Urinary phosphate calcium loss Direct effect on kidney Secondary Hyperparathyroidism ? Bone loss Early but temporary ? Bone formation Most important Direct effects on osteoblasts ? cell replication ? osteocyte apoptosis ? type 1 collagen gene expression Indirect effects ? synthesis, release, receptor binding or binding proteins of growth factors eg IGF I II related to sex steroid production Effects of GC on bone metabolism Epidemiology Common First recognised by Cushing Risk of OP with GC Rx unclear Reported in up to 50% on longterm Rx Fracture risk Prospective data lacking Retrospective cohort study 244 236 pts on GC Rx vs 244 235 control pts ( UK GP registry) RR of vertebral # 2.6, hip # 1.6, nonvertebral # 1.3 Estimated vertebral fracture incidence 13 – 22% in first yr of Rx from calcium treated control arms of recent randomised control trials Cumulative prevalence of vertebral fractures : Up to 28% (cross sectional studies) Factors associated with fracture risk with GC Rx Age BMD Initial subsequent to GC Rx Postmenopausal women – highest risk