Osteoporosis

IntroductionTwocomponentofboneBonecells：

osteoblastsosteoclastsosteocyteBonematrix：

anorganic(2/3)

organic(

1/3)Twoformsofthebone

trabecularbone(spongybone)20%oftotalbonemass(vertebrae,epiphysisofthelongbones)80%ofboneturnoveroccursintrabecularbone.verysusceptibletotheeffectsofestrogendeficiency.corticalbone（compactbone）

diaphysisofthelongbonesmetabolicrelativeinactiveBoneremodelingprocessCFU-GM:colonyformingunitsforgranulocyte-macrophagesCFU-F:colonyformingunitsforfibroblastsChangesofbonemasswithageinmenandwomen

Osteoporosis(OP)Osteoporosisisametabolicbonediseasecharacterizedby:lowbonemassmicroarchitecturaldeterioration

ofbonetissueenhancedbonefragigilityandincreasedriskoffracture

Theunderlying:imbalancebetweenboneresorptionandboneformation.WHOdefinitionNormalOsteoporosis

ClinicalmanifestationOstealgiaandmyastheniaFragilityfracture

spinehipforearmSpinalOsteoporoticCompressionFractrurePathogenesis1.aninadequatepeakbonemass(PBM)2.excessiveboneresorption

1)sexhormonedeficiency(hypogonadism)2)PTHrelativeoverproductionresultedfrom1,25(OH)D3underproduction(aging,hyperparathyroidism)3.inadequateformation

1.vitamineDdeficiency2.aging

Typesofosteoporosis

1.primaryosteoporosis:1)Type1osteoporosis(postmenopausalosteoporosis)2)Type2primaryosteoporosis(senileOP)2.

Secondaryosteoporosis1)Genetic2)Endocinre3)Deficiencystates4)Inflammatorydiseases

5)Hematologicandneoplastic

6)Medications1)GeneticCysticfibrosisGlycogenstoragediseaseGaucherdiseaseHemochromatosisHomocystinuriaHypophosphatasiaIdiopathichypercalciuriaMarfansyndromePorphyria2)EndocrineCushingsyndromeGonadalinsufficiency(primaryandsecondary)HyperthyroidismPrimaryhyperparathyroidismType1diabetesmellitus3)Deficiencystates

CalciumdeficiencyMagnesiumdeficiencyProteindeficiencyVitaminDdeficiencyBariatricsurgeryCeliacdiseaseGastrectomyMalabsorptionMalnutritionParenteralnutritionPrimarybiliarycirrhosis4)Inflammatorydiseases

InflammatoryboweldiseaseAnkylosingspondylitisRheumatoidarthritis5)Hematologicandneoplastic

MultiplemyelomaHemochromatosisHemophiliaLeukemiaLymphomaSicklecellanemiaThalassemiaMetastaticdisease6)MedicationsglucocorticoidsCytotoxicagentsGnRHagonistsoranaloguesHeparinImmunosuppressives(eg,cyclosporine)anticonvulsants(eg,phenytoin)AromataseinhibitorsDignosticworkup1.Bonemineraldensity

(BMD)

detectionDual-energyX-rayabsorptiometry(DXA)

QCTorQMR。Quantitativeboneultrasound

Bonemorphometry2.Bonex-ray,CT,MRIDignosticworkup3.boneformationmarker：

b-ALP、osteocalcin4.boneresorptionmarker：

Urinecalcium/CrratioPyrD-pyrDXADignosticcluesofosteoporosis①postmenopauseorpostbilateralovariectomy②unclearchronicbackpain③heightgetshorterorSpinaldeformity(KyphoticThorax)；④fragilityfracturesorfamilyhistory⑤multipleriskfactors:advancedagesmokingimmobilisationunderweightusageofcorticosteroidsforalongtimeWHODiagnosticcriteriaofosteoporosisNormal:Notlessthan1SDbelowtheavg.foryoungadultsOsteopenia:-1to-2.5SDbelow…Osteoporosis:Morethan2.5SDbelow…Severeosteoporosis:Morethan2.5below…,withfracturesTreatment

Pharmacotherapy

(antiresorptivesandanabolics)AddressSecondaryFactors

(drugsanddiseases)LifestyleChanges

(nutrition,physicalactivity,andfallprevention)YatesAA,etal.JAmDietAssoc.1998;9:699-706.NIHConsensusConference.JAMA1994;272:1942-8.*600IU/dayforpatientsoverage70Non-pharmacologicalManagementCalcium:1200–1500mg/dayVitamin:D600-800IU/dayWeight-bearingandstrength-trainingexercises:increasebonemassiftheyincreasemusclemassandstrength.Fall-preventiontechniquesPharmacologicoptionsAntiresorptiveagent

Hormonereplacementtherapy(HRT)Selectiveestrogenreceptormodulator(Raloxifene)CalcitoninBisphosphonatesAnabolicagent

PTH1-34Inpostmenopausalwomenwithanintactuterus,HRT(estrogenplusprogestin)wasassociatedwith:29%increaseinCHDevents*41%increaseinstroke*111%increaseinVTEdisease*22%increaseintotalcardiovasculardisease*26%increaseininvasivebreastcancer*37%decreaseincolorectalcancer*34%decreaseinhipandclinicalvertebralfractures*resultsFromtheWomen'sHealthInitiativerandomizedcontrolledtrial.HRTNotfirstlinetherapyofosteoporossis.IndicatedjustbythepresenceofclimactericsyndromeandabsenceofcardiovasculareriskfactorsBreastcarcinomascreeningbeforeuseageandfollowupeveryyearlaterSERMs-Raloxifeneincreasetheriskofbloodclots.doesnotaffecttheuterusorbreasts.BisphosphonatesCalcitoninDecreasesboneresorptionAdvantage–MayprovideanalgesiceffectonbonepainassociatedwithfracturesDisadvantage–CardiacsideeffectParathyroidHormone(PTH)RANK=ReceptorActivatorofNuclearFactorκBRANKL=ReceptorActivatorforNuclearFactorκBLigand,isfoundonthesurfaceofstromalcells,osteoblasts,andTcells.OPG=Osteoprotegerin護(hù)骨素=osteoclastogenesisinhibitoryfactor(OCIF)RaloxifenePTHCalci