Williams Textbook of Endocrinology, 12 Ed. Site www.gilbertodenucci.com Dúvidas denucci@ gilbertodenucci.com Arquivo Medicamentos utilizados na profilaxia e tratamento da osteoporose.
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Site www.gilbertodenucci.com Dúvidas denucci@gilbertodenucci.com Arquivo Medicamentos utilizados na profilaxia e tratamento da osteoporose
Effect of calcium supplements with or without vitamin D on cardiovascular events: based on patient-level data. The panels show the time to first event for 24869 participants in five trials of calcium supplements,1811-15 and the WHI CaD Study participants not taking personal calcium supplements at baseline Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women’s Health Initiative limited access dataset and meta-analysis - BMJ 2011;342:d2040 – Fig 3
Osso • É um órgão dinâmico que se remodela constantemente durante a vida. Este processo envolve remoção ou reabsorção de osso de uma superfície óssea e a subsequente deposição de osso novo em uma superfície próxima.
Osteoblastos • Células que formam o osso. Eles sintetizam a matrix orgânica e subsequentemente promovem a mineralização da mesma. A matrix orgânica sintetizada pelos osteoblastos é formada por colágeno tipo I e outras proteínas. A síntese é controlada por PTH (paratormônio) e 1,25-dihidroxi vitamina D.
Signals Determining Mesenchymal-Cell Differentiation toward Osteoblasts and Signals Acting on Mature Osteoblasts to Enhance Bone Formation. Mechanisms of Anabolic Therapies for Osteoporosis - n engl j med 357;9 www.nejm.org august 30, 2007
Elements of Wnt/β-catenin signaling. In the liganded state, binding of Wnt to the frizzled receptor inhibits GSK3 activity through mechanisms involving Axin, Frat-1, and Disheveled (Dsh). Regulation of bone mass by Wnt signaling - The Journal of Clinical Investigation http://www.jci.org Volume 116 Number 5 May 2006
Osteoclastos • São células responsáveis pela reabsorção óssea. Apresentam a mesma origem de macrófagos/monócitos. São estimuladas pelo PTH (não apresentam receptores para PTH), RANKL e são inibidas pela calcitonina.
Signals Determining Mesenchymal-Cell Differentiation toward Osteoblasts and Signals Acting on Mature Osteoblasts to Enhance Bone Formation. Mechanisms of Anabolic Therapies for Osteoporosis - n engl j med 357;9 www.nejm.org august 30, 2007
Elements of Wnt/β-catenin signaling. In the liganded state, binding of Wnt to the frizzled receptor inhibits GSK3 activity through mechanisms involving Axin, Frat-1, and Disheveled (Dsh). Regulation of bone mass by Wnt signaling - The Journal of Clinical Investigation http://www.jci.org Volume 116 Number 5 May 2006
Osteoporose • Doença esquelética sistêmica caracterizada por baixa massa óssea e deterioração da microarquitetura do tecido ósseo com consequente aumento da susceptibilidade a fraturas
Formation Resorption Normal Resorption Formation Formation Resorption High turnover Low turnover Pharmacological Topics of Bone Metabolism: Recent Advances in Pharmacological Management of Osteoporosis - J Pharmacol Sci 106, 530 – 535 (2008)4
Densitometria • Mulheres acima de 65 anos • Mulheres menopausadas que apresentaram fratura • Candidatas a tratamento de osteoporose • Mulheres utilizando reposição hormonal • Mulheres menopausadas abaixo de 65 anos mas que apresentam fatores de risco para osteoporose
Tratamento • Inibidores da reabsorção óssea • Promotores da formação óssea (anabólico)
Inibidores da reabsorção • Cálcio • Vitamina D • Terapia hormonal • Bifosfonados • Moduladores de receptores de estrógeno • Calcitonina
Activation of vitamin D3 to form 1,25-dihydroxycholecalciferol and role of vitamin D in controlling the plasma calcium concentration Textbook of Medical Physiology – Guyton & Hall – Fig. 79.6
Effect of calcium supplements with or without vitamin D on cardiovascular events: based on patient-level data. The panels show the time to first event for 24869 participants in five trials of calcium supplements,1811-15 and the WHI CaD Study participants not taking personal calcium supplements at baseline Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women’s Health Initiative limited access dataset and meta-analysis - BMJ 2011;342:d2040 – Fig 3
Effect of calcium supplements with or without vitamin D on cardiovascular events: based on patient-level data. The panels show the time to first event for 24869 participants in five trials of calcium supplements,1811-15 and the WHI CaD Study participants not taking personal calcium supplements at baseline Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women’s Health Initiative limited access dataset and meta-analysis - BMJ 2011;342:d2040 – Fig 3
Effect of calcium supplements with or without vitamin D on cardiovascular events: based on patient-level data. The panels show the time to first event for 24869 participants in five trials of calcium supplements,1811-15 and the WHI CaD Study participants not taking personal calcium supplements at baseline Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women’s Health Initiative limited access dataset and meta-analysis - BMJ 2011;342:d2040 – Fig 3
Inibidores da reabsorção • Cálcio • Vitamina D • Terapia hormonal • Bifosfonados • Moduladores de receptores de estrógeno • Calcitonina
Inibidores da reabsorção • Cálcio • Vitamina D • Terapia hormonal • Bifosfonados • Moduladores de receptores de estrógeno • Calcitonina • Inibidores de RANKL
A, Nitrogen-containing bisphosphonates selectively inhibit farnesyl pyrophosphate synthase (FPPS) within osteoclasts. B, Osteoclast endocytosis of bisphosphonate from the bone surface leads to FPPS inhibition and osteoclast apoptosis. BP = nitrogen-containing bisphosphonate; HMG-CoA = 3-hydroxy-3-methylglutaryl coenzyme A.
Effect of nitrogen-containing bisphosphonates on the mevalonate pathway by inhibiting farnesylpyrophosphate synthase. HMG-CoA, ydroxymethylglutaryl-coenzyme A; PP, pyrophosphate. Fleisch Breast Cancer Res 2002 4:30 doi:10.1186/bcr414
