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1、 OsteoporosisLi Mei2015.10.8Osteoporosis8 million Osteoporotic Women and 2.5 million Osteoporotic Men in USAExpected to increase by about 40% by 2020Mortality increased 2-3 fold in women and women after all types of Osteoporotic fractures1 Surgeon-Generals Report2 Canadian and US census data3 Access
2、 Economics, 4 Center 1999Impact of osteoporosis on the quality offragile fractureWhat is the status of diagnose and treat?In study of 4 Midwestern health systems:1/8 1/4 of hip fracture pts received BMD testing were given calcium/D supplements1/10 treated with antiresorptive medicationsUS Department
3、 of Health and Human Services: Bone Health and Osteoporosis: A Report of the Surgeon General, Office of the Surgeon General, 2004.DefinitionSigns and SymptomsMechanismRisk FactorsDiagnosisImportance of BMD testingWho should be tested?BMD testing and interpretationWho should be treated?How to treatme
4、ntOutlineWhat is the definition ? A condition of skeletal fragility characterized by compromised bone strength predisposing to an increased risk of fractureNormal BoneOsteoporosisWhat are the signs and symptoms?Back painLoss of height over timeFractureWhat is the mechanism?Imbalance in bone remodeli
5、ng as a result of: bone breakdown by osteoclasts bone formation by osteblastsBiochemical Markers of Bone TurnoverFormationosteoblastsResorptionosteoclastsFormation Markers Osteocalcin (OC) Bone-specific alkaline phosphatase (BAP) Amino terminal propeptide of type I collagen (PINP) Carboxyl terminal
6、propeptide of type I collagen (PICP)Resorption Markers Pyridinoline (Pyr) Deoxypyridinoline (dPyr) Amino terminal telopeptide of type I collagen (NTX) Carboxyl terminal telopeptide of type I collagen (CTX)How to measure bone mass?FemurWorld Health Organization. Guidelines for Preclinical Evaluation
7、and Clinical Trials in Osteoporosis. Geneva, Switzerland: World Health Organization; 1998.T Score What is the diagnosis criteria?MIBI ScanningMultiple MyolemaBone Biopsy可見大量、增殖的漿細(xì)胞MetastasesMetastasesMetastasisType I Collagen, Osteogenesis Imperfectacollagen“blue” eyes in OIfractures in OICollagen i
8、s the major protein of bone encoded by COLIA1 and COLIA2 genes Collagen genes produce alpha 1 and alpha 2 chains Chains assemble to form collagen fibresMutations cause extreme bone fragility and severeOsteoporosis“brittle bone disease” osteogenesis imperfecta (OI) Antiresorptive Bisphosphonates alen
9、dronate, risedronate, ibandronate, etidronate SERMs (Selective estrogen receptor modulators) raloxifene Estrogen Calcitonin Anabolic PTH Both: Renalate strontiumWhat is the treatments for Osteoporosis?Lifestyle AdviceDietBalanced diet containing adequate calcium1000 mg/dayExerciseRegular weight bear
10、ing exercise 3 times a week for 20 minutes minimumSmokingStop smokingAlcoholWithin safe limits2u/day women3u/day menSunlight Exposure15-20 minutes on face, hands and forearms twice weekly form April to October 基礎(chǔ)用藥 骨吸收抑制劑 骨形成促進(jìn)劑鈣劑 雙膦酸鹽 維生素D 降鈣素 甲狀旁腺素片段 雌激素 合成類固醇雷尼酸鍶鹽 雷尼酸鍶鹽 選擇性雌激素受體調(diào)節(jié)劑 維生素K骨質(zhì)疏松防治藥物Ho
11、w to prevent and treat?AgeHormonal ReplacementBisphosphonates StrontiumSERM20406080Vitamin DPTHLife StyleTreatmentchoice* with prev vert fracture(s) * without prev vert fractures * with or without prev verfractures Antifracture efficacy of antiosteoporotic agents 0.61.00.2Incident nonvertebral fract
12、ures Relative risk RLX 60, 120(MORE)*CT 200 (PROOF)* Teriparatide 20g*ALN 5/10 (FIT1)*ALN 5/10 (FIT2)*RIS 5 (VERT-NA)*RIS 5 (VERT-MN)*RIS 2.5/5 (Hip Study)*Incident vertebral fractures Relative risk 0.61.00.2RLX 60 (MORE)*RLX 60 (MORE)*CT 200 (PROOF)* Teriparatide 20g*ALN 5/10 (FIT1)*ALN 5/10 (FIT2)*RIS 5 (VERT-NA)*RIS 5 (VERT-MN)*Strontium ranelate(SOTI)*Strontium ranelate(SOTI +TROPOS)*Strontium ranelate(TROPOS)*Strontium ranelate(SOTI)*Updated from Delmas, Lancet 2002RR 95% CI骨質(zhì)疏松癥治療新藥抗骨吸收藥物DenosumabOdanacatibLasofoxifeneBazedoxifene口服鮭魚降鈣素 促進(jìn)骨形成藥物骨硬化素抑制劑PTH制劑 經(jīng)皮PTH內(nèi)源性PTH刺激劑 鈣敏感
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