英文医学ppt课件资料：Osteoporosis

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,6/6/2017,#,Osteoporosis,Uri yoel,M.D,endocrine unit,soroka university medical center,OsteoporosisUri yoel,M.D,end,1,Basic bone physiology,Basic bone physiology,2,英文医学ppt课件资料：Osteoporosis,3,Osteoclast express CSF1R(M-CSF Receptor)and RANK.,Attach to stromal/osteoblastic cells.,Osteoblasts express membrane-bound and soluble M-CSF,membrane-bound RANKL,and OPG under the influence of stimulators of resorption(i.e.,PTH,1,25-Vit D,IL-1,TNF,IL-6,IL-11,or PGs).,If osteoblastic cells produce more RANKL than OPG,osteoclasts are formed and activated,which increases bone resorption.,If osteoblastic cells produce more OPG than RANKL,OPG binds the available RANKL,and new osteoclast formation is prevented.,During states of inflammation,T lymphocytes are activated and produce membrane-bound and soluble RANKL,which can stimulate osteoclast-mediated bone resorption.,Osteoblast osteoclast interactions,Osteoclast express CSF1R(M-CS,4,Functional elements of the fully differentiated osteoclast,Osteoclasts attach to bone by means of podosomes containing,3,integrin.,Protons are generated through the actions of carbonic anhydrase II(CAII),which is transported into the resorption space by the vacuolar-type H,+,-ATPase proton pump.,A chloride channel coupled to the proton pump facilitates charge neutrality across the membrane.,Passive exchange of chloride(Cl,)for bicarbonate(HCO,3,)in the basolateral membrane removes excess bicarbonate.,Cathepsin K is an important enzyme for the removal of the organic components of bone in the acid environment of the resorption space.,Functional elements of the ful,5,The Wnt Signaling Pathway,The activation of the Wnt signalling pathway leads to an increased proliferation and differentiation of osteoblastic precursor cells,which favours the deposition of new bone and an increase of bone density.,Wnt signalling is triggered when the appropriate Wnt peptide binds to a coreceptor complex at the osteoblast cell membrane involving low-density lipoprotein receptor-related protein(LRP)5 or-6 and the Frizzled(Fz)receptor.,Sclerostin interacts with LRP5 and LRP6 and inhibits the binding of Wnt to its receptor,thus blocking bone formation.,The Wnt Signaling PathwayThe a,6,Mutations in the gene sclerostin,Sclerosteosis,is an AR disorder characterized by bone overgrowth,most prominent in the skull,Mandible.,van Buchem disease,is also an autosomal recessive skeletal disease characterized by bone overgrowth.Excessive bone formation is most prominent in the skull,mandible,clavicle,ribs and diaphysis of long bones and bone formation occurs throughout life.,Mutations in the gene sclerost,7,Pathophysiology of osteoporosis,Bone mass in older adults equals the peak bone mass achieved,by age 1825,minus,the amount of bone subsequently,lost.,Peak bone mass is determined largely by,genetic factors,with contributions from nutrition,endocrine status,physical activity,and health during,growth.,The process of,bone,remodelling,that maintains a healthy skeleton may be considered a preventive maintenance program,continually removing older bone and replacing it with new bone.,Bone,loss occurs when this,balance is altered,resulting in greater bone removal than replacement.,The,imbalance,occurs with,menopause,and,advancing,age.,The,loss of bone tissue leads to disordered skeletal architecture and an increase in,fracture risk,.,Pathophysiology of osteoporos,8,Changes,within cancellous bone as,a consequence of bone loss.Trabecular bone is,lost,leaving an architecturally weakened structure with significantly reduced mass.,Cosman et al.Osteoporosis int.2014,Changes within cancellous bone,9,英文医学ppt课件资料：Osteoporosis,10,Osteoporosis overview,Osteoporosis is a,silent,disease until it is complicated by,fractures.,These fractures occur,following,minimal,trauma,or,no,trauma,.,Fractures,are common and place an enormous medical and personal burden on the aging,individuals who suffer them.,Take a major economic toll on,the nation,.,Osteoporosis,can be,prevented,diagnosed,and treated,before fractures occur,.,Even,after the first fracture has occurred,there are effective treatments,to decrease the risk of further fractures,.,Osteoporosis overviewOsteoporo,11,The National Osteoporosis Foundation(NOF)estimates that 10.2 million Americans have osteoporosis and that an additional 43.4 million have low bone mass.More than 2 million osteoporosis-related fractures occur annually in the U.S.,more than 70%of these occur in,women.,ENDOCRINE PRACTICE Vol,22,2016,The National Osteoporosis Foun,12,英文医学ppt课件资料：Osteoporosis,13,英文医学ppt课件资料：Osteoporosis,14,英文医学ppt课件资料：Osteoporosis,15,英文医学ppt课件资料：Osteoporosis,16,英文医学ppt课件资料：Osteoporosis,17,英文医学ppt课件资料：Osteoporosis,18,In men-50 year old and older with clinical risk factors or fragility fracture,.,In men-50 year old and older,19,Treatment,Treatment,20,英文医学ppt课件资料：Osteoporosis,21,英文医学ppt课件资料：Osteoporosis,22