OsteoporosisTargetingPathwaysthatLeadtoOsteoporosisandFractures课程.pptVIP

Resorbing Osteoclast Weekly Dosing of Odanacatib See Clinical Pharmacology Therapeutics 2009;Vol.86:175-182 for line graph-Figure 3A Slide Not Available New SERMs for Postmenopausal Osteoporosis Efficacy Increases BMD Reduces BTMs Decreases risk of VFs and NVFs Decreases risk of ER+ breast cancer Improves signs and symptoms of vulvovaginal atrophy Safety Increases risk of venous thromboembolisms (VTEs), hot flushes, muscle spasm, and vaginal bleeding Efficacy Increases BMD Reduces BTMs Decreases risk of VFs Safety Increases risk of VTEs, hot flushes, muscle cramps Cummings SR, et al. J Bone Miner Res. 2008;23:S81. Silverman SL, et al. J Bone Miner Res. 2008;23:1923-1934. Eastell R, et al. J Bone Miner Res. 2008;23:S81. Lasofoxifene Bazedoxifene Wnt Signaling With permission from Baron R, et al. Endocrinol. 2007;148:2633-2644. Sclerostin MAb Increases BMD in Rats Warmington K, et al. J Bone Miner Res. 2005;20(suppl 1):S22. Li X, et al. J Bone Miner Res. 2009;24:578-588. 1.5-year-old rats 1 year post-ovariectomyMAb 25 mg/kg 2x/wk x 5 wkPTH 1-34 100 mcg/kg 5x/wk x 5 wk Strontium Description Soft silvery white metallic element occurring naturally as celestine or strontianite Atomic weight = 87.62 Calcium atomic weight = 40.078 History First found 1790 in lead mines near Strontian, Scotland Radioactive Sr-90 discovered 1940s (nuclear weapons) DIFFERENTIATION OB OB BONE FORMATION Pre-OB REPLICATION OB BONE RESORPTION OC - BONE RESORBING ACTIVITY Pre-OC Strontium ranelate Strontium ranelate + BONE MATRIX + BONE-FORMING ACTIVITY Strontium ranelate With permission from Marie PJ, et al. Calcif Tiss Int. 2001;69:121-129. Strontium Ranelate—Mechanism of Action? - - Strontium Reduces VF Risk in SOTI Trial Spinal Osteoporosis Therapeutic Intervention With permission from Meunier PJ, et al. N Engl J Med. 2004;350:459-468. 49% (P .001) ? 41%(P .001) Strontium Reduces Nonvertebral Fractures (NVFs) in TROPOS Trial TReatment Of Peripheral Osteoporosis