1、Corticosteroid-Induced Osteoporosis,2012,第一页，共四十九页。,Osteoporosis,Systemic skeletal diseaseLow bone massMicroarchitectural deterioration of bone tissueIncrease in bone fragility and fracture susceptibility,第二页，共四十九页。,Clinical Burden of CIO,Most common form of drug-related osteoporosis in men and wome
2、nOccurs at any age,in both genders,across racesUp to 50%of patients on chronic steroid therapy sustain osteoporotic fractures and/or develop osteonecrosis,第三页，共四十九页。,Corticosteroid-Induced Osteoporosis,Common,iatrogenic form of secondary osteoporosisAssociated with corticosteroid use in chronic,noni
3、nfectious medical conditionsAsthma-Nephrotic syndromeChronic lung disease-TransplantationRheumatologic disorders-etcInflammatory bowel disease,第四页，共四十九页。,Clinical significant,-Increase bone loss and fracture:6 Mo.-Trabecular cortical bone-7.5 mg of prednisolone(equivalent)-Incidence of osteoporosis
4、30-50%-Vertebral fracture 30-35%,hip fracture 50%-Rate of bone loss 2-4%per year-Alternate day regimen,inhale steroids,第五页，共四十九页。,Fracture Risk and Dose of Corticosteroids,Relative risk of fracture by dosages of corticosteroids of prednisolone.van Staa TP,et al,1998.,0,1,2,3,4,5,6,2.5 mg/d,2.5-7.5 m
5、g/d,7.5 mg/d,Relative risk of fracture,compared with control,Hip fracture,Vertebral fracture,第六页，共四十九页。,CIO in Patients With Asthma,Relationship of percentage predicted bone density to duration of corticosteroid use in 44 corticosteroid-treated asthmatic patients.Schatz M,Dudl J,Zeiger RS,et al.Alle
6、rgy Proc.1993;14:341-345.Reprinted with permission.,第七页，共四十九页。,CIO in Patients With Rheumatoid Arthritis,CS=corticosteroid;therapy=7 mg prednisone equivalent per day.Density change measured as change in absolute or Z score(difference in standard deviation compared with healthy age-matched controls o
7、f the same race and sex)compared to baseline.Verhoeven AC,et al,1997.,第八页，共四十九页。,*P0.001;*P=0.002.Percentage of SLE patients(N=97)with low BMD,as measured by DXA.Kipen Y,et al,1997.,CIO and Systemic Lupus Erythematosus,*,*,*,*,第九页，共四十九页。,Potential Factors Causing Bone Loss in Inflammatory Bowel Dise
8、ase,CorticosteroidsVitamin D/Calcium deficiencyPoor nutritional statusInflammationPhysical inactivityConcurrent medications(immunosuppressive agents),第十页，共四十九页。,CIO and Chronic Obstructive Pulmonary Disease,*P0.05 vs.ISU or NSU;*P0.005 vs ISU.McEvoy CE,et al,1998.,*,*,第十一页，共四十九页。,Pathophysiology of
9、CIO:Overview,Bone remodeling occurs throughout adulthoodOsteoporosis results from an imbalance between osteoclast and osteoblast activityTwo metabolic abnormalities contribute to increased bone resorptionSecondary hyperparathyroidism due to decreased GI absorption and urinary excretion of calciumAlt
10、ered gonadal function and decreased adrenal production of androgens,第十二页，共四十九页。,Pathophysiology of CIO,Calcium homeostasis Gonadal hormone Inhibit bone formation Increase bone resorption other,第十三页，共四十九页。,Calcium homeostasis,Decrease calcium and phosphate from GI tractsunknown mechanism Increase uri
11、nary calcium excretiondecrease calcium reabsorption at distal tubules Stimulatiom PTH secretion,第十四页，共四十九页。,Gonadal hormone effects,Decrease sex hormone:direct&indirectDecrease LH from pituitary gland:estrogen and testosteroneDecrease synthesis from adrenal glandsDecrease sex hormone binding globuli
12、n,第十五页，共四十九页。,Bone formation and bone resorption,Osteoblast-inh.Osteoblast proliferation-decrease matrix synthesis-increase apoptosis-decrease protein synthesis(type 1 collagen and noncollagenous protein-decrease osteocalcin,IGF1,IGFBP3,5,insulin-like growth factors,transforming growth factor B,pros
13、taglandin E,第十六页，共四十九页。,Osteoclastincrease osteoclast activityincrease apoptosis of mature osteoclast,Bone formation and bone resorption,第十七页，共四十九页。,Osteoblast proliferationApoptosis OB numberProtein synthesis Bone formationDifferentiation Bone mass Fracture RiskAndrogenOsteoclast apoptosisBone reso
14、rptionOsteoclast formationPTHCalcium and phosphate absorption(gut and kidney),Glucocorticoid,第十八页，共四十九页。,Diagnosis of CIO:Initial Clinical Work-Up,Medical historyRisk factors for bone lossPhysical examClinical signs and symptoms,第十九页，共四十九页。,Patient Evaluation,History Documentation of height,weight,m
15、uscle strength,balance,vision Documentation of medical historyDocumentation of menstrual history,infertility in menFracture history and Family history of fracturesOther risk factors for osteoporosis:-Lifestyles influences:calcium and vitamin D intake,smoking,alcohol intake,medications,prevention of
16、falling-Patient education:prevention of falling,exercise General health and prognosis,第二十页，共四十九页。,Patient Evaluation,Physical examinationEvidence of osteoporosis:evidence of fracture,kyphosis,loss of height,muscle strength and sizeGeneral physical findings:assessment of underlying disorder,other medical conditions,第二十一页，共四十九页。,Patient Evaluation,Complete blood count and erythrocyte sedimentation rate(ESR)Serum calcium,phosphate,creatinine,electrolyte,alkaline phosphatase,25-hydroxyvitamin D,estr