类固醇诱发的骨质疏松.ppt

Corticosteroid-Induced Osteoporosis2012第一页，共四十九页。OsteoporosisSystemic 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 CIOMost common form of drug-related osteoporosis in men and womenOccurs 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 OsteoporosisCommon,iatrogenic form of secondary osteoporosisAssociated with corticosteroid use in chronic,noninfectious 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 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 CorticosteroidsRelative risk of fracture by dosages of corticosteroids of prednisolone.van Staa TP,et al,1998.01234562.5 mg/d2.5-7.5 mg/d7.5 mg/dRelative risk of fracture compared with controlHip fractureVertebral fracture第六页，共四十九页。CIO in Patients With AsthmaRelationship of percentage predicted bone density to duration of corticosteroid use in 44 corticosteroid-treated asthmatic patients.Schatz M,Dudl J,Zeiger RS,et al.Allergy Proc.1993;14:341-345.Reprinted with permission.Percent predicted bone densityr=-0.39(P=0.009)Duration of corticosteroid use(years)1201008060402 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36第七页，共四十九页。CIO in Patients With Rheumatoid ArthritisCS=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 of 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 DiseaseCorticosteroidsVitamin 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 CIO:OverviewBone 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 calciumAltered 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 urinary 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 globulin第十五页，共四十九页。Bone formation and bone resorptionOsteoblast-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,prostaglandin E第十六页，共四十九页。Osteoclastincrease osteoclast activityincrease apoptosis of mature osteoclastBone 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 resorptionOsteoclast formationPTHCalcium and phosphate absorption(gut and kidney)Glucocorticoid第十八页，共四十九页。Diagnosis of CIO:Initial Clinical Work-UpMedical 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,muscle 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 falling -Patient education:prevention of falling,exercise General health and prognosis第二十页，共四十九页。Patient EvaluationPhysical 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,estradiol,testosterone(male)24 hr-Urinary calcium and creatinine BMD of spine and hip X-rays of appropriate areaslaboratory第二十二页，共四十九页。Diagnostic Criteria*ClassificationT=0 to-1 SD NormalT=-1 to-2.5 SDOsteopeniaT -2.5 SDOsteoporosisT -2.5 SD+fragility fracturesSevere osteoporosis*Measured in“T scores,”ie,the number of standard deviations below or above the peak bone mass in a young adult reference population of the same sex;SD=standard deviation.WHO Criteria for Assessing Disease Severity第二十三页，共四十九页。Guidelines for BMD MeasurementBaseline BMD prior to/within 6 months of initiating therapyAntero-posterior measurement of lumbar spine and femoral neckFollow-up at 6 and 12 months,annually thereafter until bone mass stabilizesMeasuring hip alone may miss more rapid loss in spine第二十四页，共四十九页。Management of CIO:Goals of TreatmentReduce fracture riskMaintain current BMD,prevent additional bone lossAlleviate pain associated with existing fracture(s)Maintain/increase muscle strengthInitiate lifestyle changes as needed第二十五页，共四十九页。BMD,Vitamin D,and CalciumAdachi JD,et al,1996.-12-10-8-6-4-206 months12months18months24months30months36monthsChange in lumbar spine BMD from baseline(%)Vitamin D&calcium Placebo第二十六页，共四十九页。TreatmentHormonal replacement therapyCalcitoninBisphosphonatesAction Inhibit bone resorption Prevent apoptosis of osteoblasts Partially reverse bone loss Prevent early resorptive phase of bone loss Inhibit bone resorption Maintain or increase bone massPharmacologic Treatment of CIO:Overview第二十七页，共四十九页。Pharmacologic treatment of CIOThiazide diuretics increase calcium absorption from GI tract decrease urinary calcium excretionFluorides stimulate osteoblast activityAnabolic steroids increase bone formation第二十八页，共四十九页。Patient groupPostmenopausal women Premenopausal women w/intact ovarian functions(ages 13-50)Men RecommendationEstrogen+progestin for women with intact uteriBisphosphonate or calcitonin if HRT contraindicated Estrogen-containing OCs(50 g estradiol)or equivalentBisphosphonate or calcitonin ifestrogen contraindicatedTestosterone(if serum testosterone levels low)Bisphosphonate or calcitonin if testosterone contraindicatedHormone Replacement Therapy in the Treatment of CIO:ACR GuidelinesAmerican College of RheumatologyTask Force on Osteoporosis Guidelines,1996.第二十九页，共四十九页。-0.06-0.04-0.0200.020.040.06Group 1 PrednisoneonlyGroup 2 Prednisone +ERTGroup 3 Control Group 4 ERT onlyChanges in lumbar spine BMD(g/cm2)at 1 yearEstrogen Replacement Therapy in the Treatment of CIO*P=0.008 vs.baseline;P=0.027 between groups 1 and 2.Lukert BP,et al,1992.*第三十页，共四十九页。Testosterone Replacement Therapy in the Treatment of CIO*P=0.005 vs control;P=0.05 between-group difference.Reid IR,et al,1996.*-5.0-2.50.02.55.0Testosterone therapyperiodControl periodChanges in lumbar spine BMD(%)at 1 year第三十一页，共四十九页。Cyclical Etidronate and Prevention of Corticosteroid-Induced Bone Loss*P0.05 between-group difference.Adachi JD,et al,1997.Roux C,et al,1998.*-4-3-2-1012LumbarspineFemoralneckTrochanterLumbarspineFemoralneckTrochanterChanges in BMD from baseline(%)at 1 yearEtidronateControl第三十二页，共四十九页。0246Lumbar spine*Femoral neckTrochanterChange in BMD from baseline(%)MenPre-menopausal womenPost-menopausal womenEtidronate:Pooled Results from Three Randomized Trials*P0.05 between-group difference.Roux C,et al,1998.第三十三页，共四十九页。Efficacy of Pamidronate in the Prevention of Bone LossBoutsen Y,et al,1997.-6-4-202466 months12 months6 months12 monthsChanges in BMD from baseline(%)Pamidronate+calciumCalcium only第三十四页，共四十九页。Efficacy of Alendronate in Increasing BMD*P 0.001 vs.control;*P 0.01 vs.control;P 0.001 vs.baseline,P 0.01 vs.baseline;Saag KG,et al,1998.-1.5-0.50.51.52.53.5Lumbar spine Femoral neckTrochanterTotal bodyChange in BMD from baseline(%)at 48 weeksControlAlendronate 5 mgAlendronate 10 mg*第三十五页，共四十九页。Efficacy of Alendronate:Two Years Follow-Up*P0.001 vs.control;*P0.01 vs.control;P0.05 vs.control.Saag KG,et al,1998.*-4-3-2-101234Lumbar spineFemoral neckTrochanterChange in BMD from baseline(%)ControlAlendronate 10 mgAlendronate 5 mgAlendronate 2.5 mg year 1,10 mg year 2第三十六页，共四十九页。Effect of Risedronate on BMD inPatients Initiating Corticosteroid Therapy*P0.05 vs control.Cohen S,et al,1998.*-4.0-2.00.02.04.0Lumbar spineFemoral neckTrochanterChange in BMD from baseline(%)at 12 monthsControlRisedronate 2.5 mgRisedronate 5 mg第三十七页，共四十九页。Effect of Risedronate on BMD in Patients on Long-Term Corticosteroid Therapy*P0.05 vs.control.Devogelaer JP,et al,1998.*-3.0-2.0-1.00.01.02.03.0Lumbar spineFemoral neckTrochanterChange in BMD from baseline(%)at 12 monthsControlRisedronate 2.5 mgRisedronate 5 mg第三十八页，共四十九页。05101520Pooled control patientsPooled risedronatepatientsPatients with vertebral fractures(%)Effect of Risedronate on Vertebral Fracture RatesPooled vertebral fracture rates from 518 patients on steroid therapy.*P=0.016 vs.control.Reid D,et al,1998.*第三十九页，共四十九页。TreatmentNumber of Change in lumbar pooled trials spine BMD(%)*Vitamin D18+1.96 Calcitonin11+2.11 Bisphosphonates18+5.31Bisphosphonates in the Management of CIO:A Meta-Analysis*Compared with no treatment or with calcium aloneP=0.0001 compared with calcitonin or vitamin D第四十页，共四十九页。Glucocorticoid therapy evaluationPlan-at start of glucocorticoid therapy1.Minimize glucocorticoid dose 2.Use alternate day therapy,topical steroid or bone sparing steroid if possible 3.Prescribe exercise(weight baring),physical therapy,prevent falling 4.Avoid smoking and excess alcohol5.Assure adequate calcium intake 6.Add supplement calcium up to 1000-15000 mg calcium/day7.Add multivitamin containing 400-800 IU vitamin D 8.BMD measurement of the spine and hip:if T-score lower than 1 SD start HRT and if more than 1 SD start HRT only in postmenopausal woman第四十一页，共四十九页。Glucocorticoid therapy evaluationReassessment at 2-3 mo1.Review glucocorticoid therapy:attempt to decrease or discontinue2.Assess exercise and calcium intake3.Measure serum calcium,24 hr urinary calcium if more than 4 mg/kg/d use hydrochlorothiazide 25-50 mg twice daily Reassessment at 6 mo 1.Review glucocorticoid therapy and minimize 2.Assess exercise and calcium intake 3.Repeat serum calcium and 24 hr urinary calcium measurement4.Alter calcium/vitamin D/thiazide therapy if necessary 5.If pateint is to continue glucocorticoid ,consider to repeat BMD 6.Consider HRT/bisphosphonate/calcitonin第四十二页，共四十九页。Glucocorticoid therapy evaluationReassessment at 1 yr 1.Review glucocorticoid therapy and minimize2.Assess exercise and calcium intake 3.Repeat serum calcium and 24 hr urinary calcium measurement4.BMD measurement(spine and hip)5.Alter calcium/vitamin D/thiazide therapy if necessary6.Alter further thereapy if bone loss if continuesReassessment thereafter if glucocorticoids continue1.Repeat annual assessment as above 2.Change therapy as needed3.Consider newer drugs as they become available第四十三页，共四十九页。ACR Task Force on Osteoporosis:Initiating Long-Term Corticosteroid TherapyInitial history&physical,lab/DXA measurementsCalcium/vitamin D supplementationPatient educationT score -1Monitor regularlyOne month follow-up:Obtain 24h urine to measure calciumIf 300 mg/d:add thiazide diureticAdjust dosage of calcium and vitamin D supplementation6-12 months follow-up:Repeat BMDDecrease 5%:change/add medicationIncrease,no change,or decrease 5%young adults or Lower than 1 SD below the Screen for hypogonadism bone loss mean for aged-match controls NoIf hypogonadism present:Calcium 1000 mg/dayAdd hormone replacement with Vitamin D 400-800 IU/day Estrogen in woman and testosterone in men ExerciseCheck BMD in one year:add anti-resorptive Repeat bone mineral density in 1 yr.Therapy if 2 percent bone lossIf hypogonadism absent:5%bone lossAdd bisphosphanate if no fracture painAdd calcitonin if fracture pain Continue conservative therapy as long as bone density criteria above not met第四十五页，共四十九页。Corticosteroid-Induced Osteoporosis:ConclusionsMost common form of drug-related osteoporosisImbalance in bone formation and resorptionResultant bone loss and fracture Bone densitometry is recommended for all patients on chronic steroid therapyT scores -2.5 indicate osteoporosisT scores -1 indicate osteopeniaEach standard deviation change in bone density is associated with at least a two-fold change in fracture risk 第四十六页，共四十九页。Corticosteroid-Induced Osteoporosis:Conclusions Primary treatment goalsReduce fracture riskMaintain or increase bone massVitamin D and calcium may slow early resorptive changesHRT is recommended for patients with T scores 1 to prevent bone resorption(use bisphosphonates or calcitonin if HRT is contraindicated)Bisphosphonates are an efficacious treatmentInhibit bone resorptionMaintain or increase bone massAdvanced generation bisphosphonatesIncrease BMD of hip,spine,and total bodyMay lower risk for vertebral,hip,and forearm fractures第四十七页，共四十九页。第四十八页，共四十九页。内容(nirng)总结Corticosteroid-Induced Osteoporosis。r=-0.39(P=0.009)。Osteoclast apoptosisBone resorption。Vitamin D18+1.96。Calcitonin11+2.11。Bisphosphonates18+5.31。No第四十九页，共四十九页。