Osteoporosis Secundaria Osteoporosis. ¿Cuál es tu causa?

Presentación del tema: "Osteoporosis Secundaria Osteoporosis. ¿Cuál es tu causa?"— Transcripción de la presentación:

1 Osteoporosis Secundaria Osteoporosis. ¿Cuál es tu causa?
Dr. Luis Elizondo Endocrinologo Hospital La católica Clinica Via san Juan Densitometrista Clínico certificado - ISCD

2 “Lo que llamamos casualidad NO ES ni puede ser sino la causa ignorada de un efecto desconocido”
Voltaire

3 Nuestra charla habla sobre “CAUSAS DE”
Rembrandt, 1632 Lecciókn de anatomía Nuestra charla habla sobre “CAUSAS DE”

4 Premisas

5 Reto Clínico: Osteoporosis
Asintomático, incluso en el contexto de fracturas vertebrales en 2/3 Reto del Clínico Identificar Población en Riesgo Prevenir la Primera Fractura 1. South-Paul JE. Am Fam Physician. 2001;63: 2. Lenchnik L, et al. AJR. 2004;183:

6 Osteoporosis – cambio de definición y paradigma
“Masa ósea disminuida, deterioro de la microarquitectura del tejido óseo que conlleva a un incremento en el riesgo de fractura.” (Conference Consenso OMS, 1991)

7 Osteoporosis Normal Osteoporosis
“Osteoporosis es un desorden esquelético caracterizado por el compromiso de la fortaleza ósea, que predispone a una persona a que se incremente su riesgo de fractura” The Consensus Development Conference, sponsored by the National Institute of Health, issued this new definition of osteoporosis last year which now focuses on decreased bone strength instead of just low BMD. In this way, the definition of osteoporosis has evolved so that it not only includes the traditional measures of bone quantity, such as mass, but it also includes measures of bone quality (architecture, for example) As you look at these visuals, you can see that the healthy bone is comprised of thick, inter-linking trabeculae, while the weakened bone is thin and some of the connectors have broken. Now that we have defined osteoporosis as a disease of decreased bone strength, it is important to understand what factors contribute to bone strength. Normal Osteoporosis Consensus Development Conference, JAMA 2001; 285:

8 Osteoporosis Fractura Factor de Riesgo EVENTO Arquitectura
Calidad Ósea DMO disminuida Fortaleza Ósea y Arquitectura Tasa de recambio Daño acumulativo Grado de mineralización Propiedades de la matriz mineral/colágena

9 Objetivo claro en Osteoporosis: Disminuir el riesgo relativo de fracturas La Densitometría Ósea es parte importante de la evaluación del riesgo de fractura, pero no la única determinación

10 Mayor Tasa de Fracturas Osteoporóticas son Osteopenia
Número de fracturas No. of fracturas 100 200 300 400 500 > 0.0 0.0 to -0.5 -0.5 to -1.0 -1.0 to -1.5 -1.5 to -2.0 -2.0 to -2.5 -2.5 to -3.0 -3.0 to -3.5 ≤ -3.5 Normal Osteo- penia Osteo- porosis Categoría T-score 60 50 40 30 20 10 Tasa de fracturas Tasa de fracturasr 1000 personas año Speaker notes Many individuals who experience a fracture (and even multiple fractures) have BMD scores in the low bone mass (formerly called osteopenia) range (T-score: -1 to -2.5).1,2 These individuals often do not receive treatment as they may not be appropriately identified as being at high risk of future fractures.1,2 Thus, there is a missed opportunity to prevent future fractures due to over reliance on BMD. The data in the graphs come from a Canadian historical cohort study with a mean observation period of 3.2 years.1 The study group (16,505 women 50 years of age or older) was drawn from the Manitoba Bone Density Program database, which includes all bone mineral density results for Manitoba. Baseline density measurements for the lumbar spine and hip were performed with dual-energy x-ray absorptiometry (DXA). The mean age was 65 years, and the mean T-scores for all sites fell within the osteopenic category. There were 765 incident fractures. Fracture rates were significantly higher among women 65 years or older than among women 50 –64 years old. Although fracture rates were significantly higher among women with osteoporotic T-scores, most fractures occurred in women with non-osteoporotic values (min – max: 59.7% – 67.8%). References 1. Cranney A, Jamal SA, Tsang JF, et al. Low bone mineral density and fracture burden in postmenopausal women. CMAJ 2007; 177(6): 2. Langsetmo L, Goltzman D, Kovacs CS, et al. Repeat low-trauma fractures occur frequently among men and women who have osteopenic BMD. J Bone Miner Res 2009; 24(9): Cranney A, et al. CMAJ 2007; 177(6):

11 OSTEOPOROSIS PRIMARIA
Ninguna enfermedad es aparentemente la causa Conforma el grupo más numeroso Relacionada con menopausia y el envejecimiento normal. Se pueden reconocer dos subgrupos: Osteoporosis Tipo I (Osteoporosis posmenopáusica) Osteoporosis Tipo II (Osteoporosis senil).

12 OSTEOPOROSIS SECUNDARIA
Entre el 20 % y 40% de las mujeres que consulta por osteoporosis tiene una enfermedad identificable como responsable de la misma.

13 Conceptos básicos Si desconocemos la causa no se ha investigado lo suficiente sobre la misma Manejar un paciente con osteoporosis es un estudio dinámico, en un futuro podremos determinar la causa Documentar la causa permite optimizar el tratamiento Evolucionar a un paciente sin mejoría puede relacionarse con causa secundaria

14 Balance del calcio

15 Metabolismo de la Vitamina D

16 Ciclo óseo: fisiología

17 Caso Clínico # 1 62 años, Recope
Madre: Fractura de cadera izquierda, con marcha afectada por incidente Trauma desde su propia altura con fractura en muñeca Resolución de fractura con artrosis de muñeca con discreta desviación ulnar pero funcional 10 años despúes llega al EBAIS de la Garita por Gastritis Intervention Threshold Major Fracture - 10 year fracture probabilityHip - 10 year hip fracture probability TreatLifestyle advice and reassure In elderly women with a prior fracture, treatment is needed without the need for a bone density scan. InterpretationThe intervention thresholds depicted by the lines between the green and red areas above are the 10 year probabilities of a major osteoporotic fracture (left graph) or a hip fracture (right graph) in women with a prior fracture. In individuals with probabilities of a major osteoporotic fracture and/or hip fracture AT or ABOVE the intervention threshold, treatment should be strongly considered. Where both probabilities fall below the treatment threshold, a further assessment is recommended in 5 years or less depending on the clinical context. NB - These thresholds are for guidance only and the final decision to initiate therapeutic intervention lies with the individual clinician. ManagementFor a more detailed description of investigations, supportive measures and treatments, please refer to the Executive Summary No trials have been designed and powered to detect differences in the magnitude of fracture reduction between different treatments. Thus the choice of agent is determined by the spectrum of anti-fracture effects across skeletal sites, side effects and cost. Treatments have been less extensively evaluated in men with osteoporosis than in women, though there is no evidence that skeletal metabolism in men differs fundamentally from that of women. Alendronate, risedronate, zoledronate and teriparatide are approved for the treatment of osteoporosis in men. Secondary causes of osteoporosis are commonly found amongst men, so this population requires thorough investigation. Consideration should be given to referring men with osteoporosis to specialist centres, particularly younger men or those with severe disease. The low cost of generic alendronate, which has a broad spectrum of anti-fracture efficacy, makes this the first line treatment in the majority of cases. In women who are intolerant of alendronate or in whom it is contraindicated, other bisphosphonates, denosumab, strontium ranelate or raloxifene may provide appropriate and cost-effective treatment options. The high cost of parathyroid hormone peptides restricts their use to those at very high risk, particularly for vertebral fractures. World Health Organization Collaborating Centre for Metabolic Bone Diseases, University of Sheffield, UK

18 Tasas de no tratamiento en Osteoporosis(1): 6 meses post fractura
Esta brecha es aún mayor en HOMBRES y en personas institucionalizadas2,3 Speaker notes Despite the high rate of fracture in the Canadian population, less than 20% of individuals receive therapies to reduce future fracture within the year following fracture.1-3 The therapeutic care gap is even wider in men; less than 10% of Canadian men with fragility fractures receive any osteoporosis therapy.4 Furthermore, treatment rates following a fracture are lower for those individuals who reside in long-term care.5 The undertreatment of patients following a fragility fracture1 stands in stark contrast to myocardial infarction treatment, which has overcome a significant care gap over the past 15 years; approximately 80% of individuals now receive beta blockers to help prevent recurrent myocardial infarction.6 No tratamiento. Undertreated: women meeting criteria for treatment2 15.7% not taking calcium 18.6% not taking vitamin D 52.7% not exercising >2 hrs per week 35.3% not receiving therapy References 1. Bessette L, Ste-Marie LG, Jean S, et al. The care gap in diagnosis and treatment of women with a fragility fracture. Osteoporos Int 2008; 19:79-86. 2. Bessette L, Jean S, Davison KS, et al. Factors influencing the treatment of osteoporosis following fragility fracture. Osteoporos Int 2009; 20(11): 3. Papaioannou A, Giangregorio L, Kvern B, et al. The osteoporosis care gap in Canada. BMC Musculoskelet Disord 2004; 5:11. 4. Papaioannou A, Kennedy CC, Ioannidis G, et al. The osteoporosis care gap in men with fragility fractures: the Canadian Multicentre Osteoporosis Study. Osteoporos Int 2008; 19(4): 5. Giangregorio L, Jantzi M, Papaioannou A, et al. Osteoporosis management among residents living in long-term care. Osteoporos Int 2009; 20(9): 6. Austin PC, Tu JV, Ko DT, et al. Factors associated with the use of evidence-based therapies after discharge among elderly patients with myocardial infarction. CMAJ 2008; 179(9): No diagnóstico Underdiagnosed: National Osteoporosis Risk Assessment (NORA) study (200,160 postmenopausal women)1 40% osteopenic 7% osteoporotic 11% ≥1 fracture after age 45 years 1. Siris ES, et al. JAMA. 2001;286: 2. Schnatz PF, et al. Menopause. 2011;18: FRACTURA:OSTEOPOROSIS::IAM:Enfermedad cardiovascular Pero Brecha de Tratamiento Post Evento es Mayor.1,4 1. Bessette L, et al. Osteoporos Int 2008; 19: Papaioannou A, et al. Osteoporos Int 2008; 19(4): Giangregorio L, Osteoporos Int 2009; 20(9): Austin PC, et al. CMAJ 2008; 179(9):

19 Fractura es Predictor de Fractura Futura
Riesgo de fractura en cadera* a 1 año: 5% – 10%1,2 Riesgo fractura vertebral a 1 año†: 20%3 Fracturas vertebrales prevalentes previenen fractura de cadera*4,5 Speaker notes A fracture remains one of the most significant risk factors for predicting future fractures.1 The risk of experiencing another fracture in the year following a hip fracture is 5% –10%2,3 and 20% following a vertebral fracture.4 Vertebral fractures also increase the risk for hip fractures.5,6 Forty percent of Canadians who experience a fracture have a history of prior fracture.7 References 1. Chen P, Krege JH, Adachi JD, et al. Vertebral fracture status and the World Health Organization risk factors for predicting osteoporotic fracture risk. J Bone Miner Res 2009; 24(3): 2. Papaioannou A, Wiktorowicz ME, Adachi JD, et al. Mortality, independence in living, and re-fracture, one year following hip fracture in Canadians. JOGC 2000; 22(8): 3. Colon-Emeric C, Kuchibhatia M, Pieper C, et al. The contribution of hip fracture to risk of subsequent fractures: data from two longitudinal studies. Osteoporos Int 2003; 14: 4. Lindsay R, Silverman SL, Cortet B, et al. Risk of new vertebral fracture in the year following a fracture. JAMA 2001; 285: 5. Ismail AA, Cockerill W, Cooper C, et al. Prevalent vertebral deformity predicts incident hip though not distal forearm fracture: results from the European Prospective Osteoporosis Study. Osteoporos Int 2001; 12(2):85-90. 6. Melton LJ 3rd, Atkinson EJ, Cooper C, et al. Vertebral fractures predict subsequent fractures. Osteoporos Int 1999; 10(3): 7. Hajcsar EE, Hawker G, Bogoch ER: Investigation and treatment of osteoporosis in patients with fragility fractures. CMAJ 2000, 163: 1. Papaioannou A, et al. JOGC 2000; 22(8): Colon-Emeric C, et al. Osteoporos Int 2003; 14: Lindsay R, et al. JAMA 2001; 285: Ismail AA, et al. Osteoporos Int 2001; 12(2): Melton LJ 3rd, et al. Osteoporos Int 1999; 10(3): * Hombre y mujer † Mujer Postmenopaúsica

20 Factores de Riesgo ¿Modificables?

21 Edad principal factor de riesgo
HR ajustados para la edad (comparados con la edad de 30 años) e IMC (comparado con IMC=25) para fractura osteoporótica (radio distal, cadera, o vértebra) y para fractura de cadera en hombres y mujeres en términos de fracciones polinómicasand for hip fracture in men and women with fractional polynomial terms. Fig 1 Adjusted hazard ratios for age (compared with age 30) and BMI (compared with BMI=25) for osteoporotic fracture (distal radius, hip, or vertebral) and for hip fracture in men and women with fractional polynomial terms Julia Hippisley-Cox, and Carol Coupland BMJ 2009;339:bmj.b4229

22 FACTORES DE RIESGO NO MODIFICABLES
Factores genéticos o constitucionales Edad avanzada Sexo femenino Historia personal de fractura por fragilidad Raza caucásica o asiática Historia familiar de OSTEOPOROSIS y/o fractura de cadera Kanis JA, Borgstrom F, De Laet C, et al. Assessment of fracture risk. Osteoporos Int 2005; 16:581.

23 Factores de Riesgo Modificables: Ingesta
Excesiva ingesta de alcohol, café y proteína Café se asocio a fracturas Dieta hiperproteica e hiponatrémica aumenta fracturas El alcohol inhibe la actividad osteoblástica y los niveles de Vit D. The excessive use of coffee, protein or alcohol largely relate to impairing the body’s management of calcium and vitamin D. Even if behavior modification fails, Vitamin D fortified milk and Vitamin D supplementation can offset these negative effects.

24 Hiponatremia como causa de factor de riesgo
5 Estudio de hiponatremia( 136 mmol/l) y su riesgo de fractura en la cohorte Rotterdam (n = pacientes, edad: > 55 edades, seguimieno : 7.7 años) Fracturas no vertebrales Numero de eventos RR (CI95) ajustado p Hiponatremia Normonatremia 93/399 (23.3 %) 833/4 809 (17.3 %) 1.34 ( ) Referencia 0.009 Incidencia y prevalencia de fracturas vertebrales 23/136 (16.9 %) 269/2 390 (11.3 %) 1.61 ( ) 0.049 Caídas reciemtes Hyiponatremia 95/399 (23.8 %) 787/4 809 (16.4 %) 1.34 ( ) 0.029 Hiponatremia leve se asocia con el riesgo de fractura ASBMR D’après Zillikens M et al., Rotterdam, Pays-Bas, abstr. 109

25 Café como Factor de Riesgo
Age Ageing Jan;21(1):20-6. Coffee drinking: a minor risk factor for bone loss and fractures. Johansson C1, Mellström D, Lerner U, Osterberg T. Author information Abstract The influence of coffee drinking as a possible risk factor for loss of bone mass was assessed in a cohort of year-old men and women who were examined with dual photon absorptiometry of the right calcaneum. A high consumption of coffee was significantly associated with a lower bone mass, deteriorated dental state, lower socio-economic level and a higher consumption of tobacco. In non-smoking women a bivariate relationship was found between the daily consumption of three or more cups of coffee and a low bone mass (p less than 0.01). However, in a stepwise logistic regression model, only tobacco smoking, body mass index, body height, physical activity and a deteriorated dental state were found to be significant predictive factors for a low bone mineral content. Bone mass and tobacco smoking were the only significant predictive factors for fractures before the ages of 70 and 76 years. Coffee drinking was not a contributory independent risk factor for loss of bone mass and fractures in this population study. JOHANSSON C, MELLSTRÖM D, LERNER U, ÖSTERBERG T. Coffee Drinking: A Minor Risk Factor for Bone Loss and Fractures. Age and Ageing 1992;21:20-6

26 Incidencia de cualquier fractura en Cohorte Sueva entre 1997 – 2008desplegado en curvas de Kaplan Meir respect a tazas de café (<1, 1, 2–3, or ≥4 tazas por dia). Age-adjusted incidences of any fracture (A) and hip fracture (B) in the Swedish Mammography Cohort (counties of Uppsala and Västmanland, Sweden, 1987–2008) in relation to follow-up time displayed as Kaplan-Meier failure curves for the 4 categories of coffee consumption (<1, 1, 2–3, or ≥4 cups per day). Numbers at risk during follow-up are presented in Appendix Table 2. High consumption of coffee has been suggested to reduce the risk of some late-onset diseases and death but also to contribute to the development of osteoporotic fractures. Results of previous fracture studies have been inconsistent, and a comprehensive study is needed. The longitudinal population-based Swedish Mammography Cohort, including 61,433 women born in , was followed up from 1987 through Coffee consumption was assessed with repeated food frequency questionnaires. During follow-up, 14,738 women experienced fracture of any type, and 3,871 had a hip fracture. In a subcohort (n = 5,022), bone density was measured and osteoporosis determined (n = 1,012). After multivariable adjustment, there was no evidence of a higher rate of any fracture (hazard ratio per 200 mL coffee = 0.99; 95% confidence interval: 0.98, 1.00) or hip fracture (hazard ratio per 200 mL coffee = 0.97, 95% confidence interval: 0.95, 1.00) with increasing coffee consumption. A high coffee intake (≥4 cups daily) versus a low intake (<1 cup daily) was associated with a 2%-4% lower bone density, depending on site (P < 0.001), but the odds ratio for osteoporosis was only 1.28 (95% confidence interval: 0.88, 1.87). Thus, high coffee consumption was associated with a small reduction in bone density that did not translate into an increased risk of fracture. Helena Hallström et al. Am. J. Epidemiol. 2013;178: © The Author Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please

27 No hay correlación con consumo
Sheng y colabores:Osteoporosis Int 2014 Jan;25(1):141-50 Metanalisis de 14 estudios en que no se documentaba relación. Hallstrom y colaboradores: Plos One May 15;9(5).Casi hombres en 11.2 años con fracturas Hallstrom y colaboradores: Osteporosis Int 2006;17(7): : Mujeres PLoS One May 15;9(5):e doi: /journal.pone eCollection 2014. Coffee consumption and risk of fracture in the Cohort of Swedish Men (COSM). Hallström H1, Wolk A2, Glynn A3, Michaëlsson K4, Byberg L4. Author information Abstract BACKGROUND: Recent research in a large cohort of women showed that coffee consumption is not associated with increased risk of fracture. Whether this is the case also among men is less clear. METHODS: In the Cohort of Swedish Men (COSM) study, 42,978 men aged years old at baseline in 1997 answered a self-administered food frequency questionnaire covering coffee consumption and a medical and lifestyle questionnaire covering potential confounders. Our main outcomes first fracture at any site and first hip fracture were collected from the National Patient Registry in Sweden. The association between coffee consumption and fracture risk was investigated using Cox's proportional hazards regression. RESULTS: During a mean follow-up of 11.2 years, 5,066 men had a first fracture at any site and of these, 1,186 (23%) were hip fractures. There was no association between increasing coffee consumption (per 200 ml) and rate of any fracture (hazard ratio [HR] 1.00; 95% confidence interval [CI] ) or hip fracture (HR 1.02; 95% CI ) after adjustment for potential confounders. For men consuming ≥ 4 cups of coffee/day compared to those consuming <1 cup of coffee/day, HR for any type of fracture was 0.91 (95% CI ) and for hip fracture: 0.89 (95% CI ). CONCLUSIONS: High coffee consumption was not associated with an increased risk of fractures in this large cohort of Swedish men. INTRODUCTION: Consumption of coffee and tea, and total intake of caffeine has been claimed to be associated with osteoporotic fracture risk. However, results of earlier studies lack consistency. METHODS: We examined this relation in a cohort of 31,527 Swedish women aged years at baseline in The consumption of coffee, caffeinated tea and the intake of caffeine were estimated from a self-administered food frequency questionnaire (FFQ). Multivariate-adjusted hazards ratios (HRs) of fractures with 95% confidence intervals (95% CIs) were estimated by Cox proportional hazards models. RESULTS: During a mean follow-up of 10.3 years, we observed 3,279 cases with osteoporotic fractures. The highest (>330 mg/day) compared with the lowest (<200 mg/day) quintile of caffeine intake was associated with a modestly increased risk of fracture: HR 1.20 (95% CI: ). A high coffee consumption significantly increased the risk of fracture (p for trend 0.002), whereas tea drinking was not associated with risk. The increased risk of fracture with both a high caffeine intake and coffee consumption was confined to women with a low calcium intake (<700 mg/day): HR 1.33 (95% CI: ) with > or =4 cups (600 ml)/day of coffee compared to <1 cup (150 ml)/day. The same comparison but risk estimated for women with a high propensity for fractures (> or =2 fracture types) revealed a HR of 1.88 (95% CI: ). CONCLUSIONS: In conclusion, our results indicate that a daily intake of 330 mg of caffeine, equivalent to 4 cups (600 ml) of coffee, or more may be associated with a modestly increased risk of osteoporotic fractures, especially in women with a low intake of calcium. Osteoporos Int. 2006;17(7): Epub 2006 May 4. Coffee, tea and caffeine consumption in relation to osteoporotic fracture risk in a cohort of Swedish women. Hallström H1, Wolk A, Glynn A, Michaëlsson K. INTRODUCTION: Consumption of coffee and tea, and total intake of caffeine has been claimed to be associated with osteoporotic fracture risk. However, results of earlier studies lack consistency. We examined this relation in a cohort of 31,527 Swedish women aged years at baseline in The consumption of coffee, caffeinated tea and the intake of caffeine were estimated from a self-administered food frequency questionnaire (FFQ). Multivariate-adjusted hazards ratios (HRs) of fractures with 95% confidence intervals (95% CIs) were estimated by Cox proportional hazards models. During a mean follow-up of 10.3 years, we observed 3,279 cases with osteoporotic fractures. The highest (>330 mg/day) compared with the lowest (<200 mg/day) quintile of caffeine intake was associated with a modestly increased risk of fracture: HR 1.20 (95% CI: ). A high coffee consumption significantly increased the risk of fracture (p for trend 0.002), whereas tea drinking was not associated with risk. The increased risk of fracture with both a high caffeine intake and coffee consumption was confined to women with a low calcium intake (<700 mg/day): HR 1.33 (95% CI: ) with > or =4 cups (600 ml)/day of coffee compared to <1 cup (150 ml)/day. The same comparison but risk estimated for women with a high propensity for fractures (> or =2 fracture types) revealed a HR of 1.88 (95% CI: ). In conclusion, our results indicate that a daily intake of 330 mg of caffeine, equivalent to 4 cups (600 ml) of coffee, or more may be associated with a modestly increased risk of osteoporotic fractures, especially in women with a low intake of calcium. Sheng y colabores: Osteoporos Int Jan;25(1):141-50 Osteoporos Int Jan;25(1): doi: /s Epub 2013 Nov 6. Coffee, tea, and the risk of hip fracture: a meta-analysis. Sheng J1, Qu X, Zhang X, Zhai Z, Li H, Liu X, Li H, Liu G, Zhu Z, Hao Y, Qin A, Dai K. The present meta-analysis shows no clear association between coffee consumption and the risk of hip fractures. There was a nonlinear association between tea consumption and the risk of hip fracture. Compared to no tea consumption, drinking 1-4 cups of tea daily was associated with a lower risk of hip fracture. Prospective cohort and case-control studies have suggested that coffee and tea consumption may be associated with the risk of hip fracture; the results have, however, been inconsistent. We conducted a meta-analysis to assess the association between coffee and tea consumption and the risk of hip fracture. We performed systematic searches using MEDLINE, EMBASE, and OVID until February 20, 2013, without limits of language or publication year. Relative risks (RRs) with 95% confidence intervals (CI) were derived using random-effects models throughout all analyses. We conducted categorical, dose-response, heterogeneity, publication bias, and subgroup analyses. Our study was based on 195,992 individuals with 9,958 cases of hip fractures from 14 studies, including six cohort and eight case-control studies. The pooled RRs of hip fractures for the highest vs. the lowest categories of coffee and tea consumption were 0.94 (95% CI ) and 0.84 (95% CI ), respectively. For the dose-response analysis, we found evidence of a nonlinear association between tea consumption and the risk of hip fracture (p(nonlinearity) < 0.01). Compared to no tea consumption, 1-4 cups of tea per day may reduce the risk of hip fracture by 28% (0.72; 95% CI for 1-2 cups/day), 37% (0.63; 95% CI for 2-3 cups/day), and 21% (0.79; 95% CI for 3-4 cups/day). We found no significant association between coffee consumption and the risk of hip fracture. A nonlinear association emerged between tea consumption and the risk of hip fracture; individuals drinking 1-4 cups of tea per day exhibited a lower risk of hip fractures than those who drank no tea. The association between 5 daily cups of tea, or more, and hip fracture risk should be investigated.

28 Acido fosfórico inhibe absorción de calcio
Datos del Framingham Osteoporosis Study Colas en algunos estudios Bebidas carbonatadas en otros. Tucker et al.Am J Clin Nutr October :(4)

29 Factores de Riesgo Modificables: Niveles de Vit D
Niveles adecuados de exposición Solar La suplementación con Vitamina D a dosis de 400 a 2000 UI por dia ha sido sugerida en las guías de tratamiento [i] NIH Consensus Conference JAMA 1994, [ii] Trivedi DP et. al. BMJ March 2003;326: [iii] Feskanich D, Willet W, et. al.. JAMA 2002;288:2300- Assuring adequate sunlight is necessary for the skin to make Vitamin D. This can be a problem in the homebound or institutionalized individual. If sun exposure cannot be obtained, individuals should seek to boost their Vitamin D by diet (for example in Vitamin D fortified milk and juice. For the elderly, the basic nutritional support for good bone health includes; Calcium at 1500 mg/day, Vitamin D at 800 IU per day and the use of weight bearing exercises. We will look at exercise on the next slide

30 Vitamina D Efectos diversos en la fisiología
Debe de recordarnos que la sobredosis provoca hipercalcemia Los niveles séricos son más importantes. Existe mayor correlación entre nivel sérico y DMO. Los estudios clínicos con bifosfonatos todos se han realizado con vitamina D Vía oral sola y sin calcio no ha documentado disminución en fracturas, aparentemente solo en combinación con calcio RR ,87  In many of these trials, it is difficult to differentiate the effect of calcium from that of vitamin D. Randomized trials of calcium only [68,69] or vitamin D only [70-74] have shown mixed results, likely due to differences in patient populations and study design. A meta-analysis of five trials comparing vitamin D (400 to 1370 units/day) with placebo in over 14,500 older men and women reported that vitamin D supplementation alone did not reduce fracture risk (relative risk [RR] 1.03, 95% CI ) (figure 1) [75]. In the same review, a separate meta-analysis of nine trials comparing calcium (500 to 1200 mg/day) plus vitamin D (400 to 1000 units/day) with placebo showed that combined supplementation reduced the risk for total fractures (RR 0.91, 95% CI ) [75,76]. In a subgroup analysis, the risk reduction was larger among institutionalized older individuals than community-dwelling individuals (RR 0.71 versus 0.92) (figure 2). Other meta-analyses of trials comparing calcium, vitamin D, or both with placebo or no treatment reported a beneficial reduction in fracture with calcium [77] and calcium plus vitamin D [77-81], but not with vitamin D alone [79-81]. Relative risk reductions for hip fracture ranged from 0.81 to 0.87 for combined calcium plus vitamin D supplementation [77,79,81]. These findings suggest that supplementation with vitamin D does not reduce the risk of fracture unless there is adequate calcium. ______________________---- Serum 25-hydroxyvitamin D concentrations and risk for hip fractures. AU Cauley JA, Lacroix AZ, Wu L, Horwitz M, Danielson ME, Bauer DC, Lee JS, Jackson RD, Robbins JA, Wu C, Stanczyk FZ, LeBoff MS, Wactawski-Wende J, Sarto G, Ockene J, Cummings SR SO Ann Intern Med. 2008;149(4):242. BACKGROUND: The relationship between serum 25-hydroxyvitamin D [25(OH) vitamin D]concentration and hip fractures is unclear. OBJECTIVE: To see whether low serum 25(OH) vitamin D concentrations are associated with hip fractures in community-dwelling women. DESIGN: Nested case-control study. SETTING: 40 clinical centers in the United States. PARTICIPANTS: 400 case-patients with incident hip fracture and 400 control participants matched on the basis of age, race or ethnicity, and date of blood draw. Both groups were selected from postmenopausal women who were not using estrogens or other bone-active therapies and who had not had a previous hip fracture. MEASUREMENTS: Serum 25(OH) vitamin D was measured and patients were followed for a median of 7.1 years (range, 0.7 to 9.3 years) to assess fractures. RESULTS: Mean serum 25(OH) vitamin D concentrations were lower in case-patients than in control participants (55.95 nmol/L [SD, 20.28]vs nmol/L [SD, 18.05]; P = 0.007), and lower serum 25(OH) vitamin D concentrations increased hip fracture risk (adjusted odds ratio for each 25-nmol/L decrease, 1.33 [95% CI, 1.06 to 1.68]). Women with the lowest 25(OH) vitamin D concentrations (<or =47.5 nmol/L) had a higher fracture risk than did those with the highest concentrations (>or =70.7 nmol/L) (adjusted odds ratio, 1.71 [CI, 1.05 to 2.79]), and the risk increased statistically significantly across quartiles of serum 25(OH) vitamin D concentration (P for trend = 0.016). This association was independent of number of falls, physical function, frailty, renal function, and sex-steroid hormone levels and seemed to be partially mediated by bone resorption. LIMITATIONS: Few case-patients were nonwhite women. Bone mineral density and parathyroid hormone levels were not accounted for in the analysis. CONCLUSION: Low serum 25(OH) vitamin D concentrations are associated with a higher risk for hip fracture. AD University of Pittsburgh, Department of Epidemiology, 130 DeSoto Street, Crabtree A524, Pittsburgh, PA 15261, USA. PMID 89 PubMed TI Association between 25-hydroxy vitamin D levels, physical activity, muscle strength and fractures in the prospective population-based OPRA Study of Elderly Women. Gerdhem P, Ringsberg KA, Obrant KJ, Akesson K Osteoporos Int. 2005;16(11):1425. Vitamin D supplements have been used to prevent fractures. The effect may be mediated through increased bone mass, but also through reduced falling propensity. The aim of this study was to evaluate the association between 25-hydroxy vitamin D levels (25OHD), fall-associated variables (including tests of functional performance), and fracture in ambulatory women. At baseline 25OHD was measured in 986 women. Fall-associated variables were investigated at baseline. Fractures were recorded during a 3-year follow-up. Four percent of the women had 25OHD levels below 20 ng/ml (50 nmol/l), and 26% had 25OHD levels below 30 ng/ml (75 nmol/l). 25OHD correlated with gait speed (r =0.17, P<0.001), the Romberg balance test (r =0.14, P<0.001), self-estimated activity level (r =0.15, P<0.001), and thigh muscle strength (r =0.08, P =0.02). During the 3-year follow-up, 119 out of the 986 women sustained at least one fracture. The Cox proportional hazard ratio (HR) (95% confidence interval) for sustaining a fracture during the follow-up was 2.04 ( ) for the group of women with 25OHD below 20 ng/ml, in which 9 out of 43 women sustained a fracture. Thirty-two of the 256 women with 25OHD levels below 30 ng/ml sustained a fracture during the follow-up, with a non-significant HR of 1.07 ( ). This cohort ofelderly, ambulatory women had a high mean 25OHD. A low 25OHD was associated with inferior physical activity level, gait speed and balance. A 25OHD level below 30 ng/ml was not associated with an increased risk of fractures in this study. However, a subgroup of women with 25OHD levels below 20 ng/ml had a tendency to an increased risk of fractures, which may be associated with an inferior physical activity and postural stability. Department of Orthopedics, MalmöUniversity Hospital, Lund University, Malmö, Sweden. 90 Serum 25-hydroxyvitamin D and risk of major osteoporotic fractures in older U.S. adults. Looker AC J Bone Miner Res May;28(5): Results from previous prospective studies linking serum 25-hydroxyvitamin D (25OHD) with fracture risk have been inconsistent. The present study examined the relationship between serum 25OHD and risk of incident major osteoporotic fracture (hip, spine, radius, and humerus) in older U.S. adults. The study used a pooled cohort of 4749 men and women ages 65 years and older from the third National Health and Nutrition Examination Survey (NHANES III, ) and NHANES Incident fractures were identified using linked mortality and Medicare records that were obtained for participants from both surveys. Serum 25OHD values were measured by radioimmunoassay in both surveys. Cox proportional hazards models were used to estimate the relative risk (RR) of fracture by serum 25OHD level. There were 525 incident major osteoporotic fractures (287 hip fractures) in the sample. Serum 25OHD was a significant linear predictor of major osteoporotic fracture and significant quadratic predictor of hip fracture in the total sample and among those with less than 10 years of follow-up, but it was not related to risk of either fracture type among those with≥10 years of follow-up. Major osteoporotic fracture risk was increased by 26% to 27% for each SD decrease in serum 25OHD among those with less than 10 years of follow-up. Serum 25OHD was significantly related to risk of major osteoporotic fractures as a group and to hip fracture alone in this cohort of older U.S. adults from NHANES III and NHANES However, the predictive utility of serum 25OHD diminished after 10 years. In addition, the relationship appeared to be linear when major osteoporotic fracture risk was considered but quadratic when hip fracture risk was assessed. National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, MD 20782, USA. 91 Occult vitamin D deficiency in postmenopausal US women with acute hip fracture. LeBoff MS, Kohlmeier L, Hurwitz S, Franklin J, Wright J, Glowacki J JAMA. 1999;281(16):1505. CONTEXT: Low vitamin D levels may contribute to hip fractures in women, although limited data are available on vitamin D levels in US women admitted with acute hip fractures. OBJECTIVE: To determine whether postmenopausal women with hip fractures have low vitamin D and high parathyroid hormone levels compared with nonosteoporotic and osteoporotic women admitted for elective joint replacement. DESIGN: Comparative case series conducted between January 1995 and June 1998. SETTING AND PATIENTS: Ninety-eight postmenopausal community-dwelling women with no secondary causes of bone loss admitted for hip replacement, of whom 30 women had acute hip fractures and 68 women were admitted for elective joint replacement. Of the women admitted for elective joint replacement, 17 had osteoporosis and 51 did not. Women with comorbid conditions or who were taking medications that affect bone density and turnover were excluded. MAIN OUTCOME MEASURES: Primary measures were levels of vitamin D and parathyroid hormone; secondary measures were body composition and markers of bone turnover. RESULTS: Women with hip fractures had lower levels of 25-hydroxyvitamin D than women without osteoporosis admitted for elective joint replacement (P = .02) and than women with osteoporosis admitted for elective joint replacement (P = .01) (medians, 32.4, 49.9, and 55.0 nmol/L, respectively; comparisons adjusted for age and estrogen intake). Parathyroid hormone levels were higher in women with fractures than women in the nonosteoporotic control group (P<.001) or than elective osteoporotic women (P = .001) (medians, 5.58, 3.26, and 3.79 pmol/L, respectively; comparisons adjusted for age and estrogen intake). Fifteen patients (50.0%) with hip fractures had deficient vitamin D levels (<or =30.0 nmol/L) and 11 (36.7%) had a parathyroid hormone level greater than 6.84 pmol/L. Levels of N-telopeptide, a marker of bone resorption, were greater in the women with hip fractures than in the elective nonosteoporotic controls (P = .004). CONCLUSIONS: Postmenopausal community-living women who presented with hip fracture showed occult vitamin D deficiency. Repletion of vitamin D and suppression of parathyroid hormone at the time of fracture may reduce future fracture risk and facilitate hip fracture repair. Because vitamin D deficiency is preventable, heightened awareness is necessary to ensure adequate vitamin D nutrition, particularly in northern latitudes. Department of Internal Medicine, Brigham and Women's Hospital, Boston, Mass 02115, USA. 92 Secondary contributors to bone loss in osteoporosis related hip fractures. Edwards BJ, Langman CB, Bunta AD, Vicuna M, Favus M Osteoporos Int. 2008;19(7):991. UNLABELLED: Osteoporosis treatment of patients with hip fractures is necessary to prevent subsequent fractures. Secondary causes for bone loss are present in more than 80% of patients with hip fractures, and therefore, assessment of Vitamin D status, disorders in calcium absorption and excretion, monoclonal gammopathies, and renal function should be performed. Identifying and managing these disorders will improve detection and enhance treatment aimed at reducing the risk of recurrent fractures in older adults. INTRODUCTION: The purpose of this study was to determine the prevalence of disorders affecting bone and mineral metabolism in individuals with osteoporotic hip fractures. METHODS: Community dwelling individuals with hip fractures (HFx) 50 years of age and older. Assessment for vitamin D, renal and parathyroid status, calcium absorption, and plasma cell disorders. RESULTS: Of 157 HFx, mean age 70 +/- 10 years, HFx had higher creatinine (p = 0.002, 95% C.I , 0.05); lower 25 OH vitamin D (p = 0.019, 95% C.I. 6.5, 2.7), albumin (p = 0.007, 95% C.I. 0.36, 0.009), and 24-h urine calcium (p = 0.024, 95% CI 51, 21) as compared to controls. More than 80% of HFx had at least one previously undiagnosed condition, with vitamin D insufficiency (61%), chronic kidney disease (16%) (CKD), monoclonal gammopathy (6%), and low calcium absorption (5%) being the most common. One case each of multiple myeloma and solitary plasmocytoma were identified. CONCLUSIONS: Osteoporosis treatment of HFx is necessary to prevent subsequent fractures. Secondary causes for bone loss are remarkably common in HFx; therefore, assessment of vitamin D status, disorders in calcium absorption and excretion, protein electrophoresis, and renal function should be performed. Identifying and correcting these disorders will improve detection and enhance treatment aimed at reducing the risk of recurrent fractures in older adults. Bone Health and Osteoporosis Center, Department of Medicine, Feinberg School of Medicine, Northwestern University, 645 N Michigan, suite 630, Chicago, IL 60611, USA. 93 Serum 25-hydroxyvitamin D and the risk of hip and nonspine fractures in older men. Cauley JA, Parimi N, Ensrud KE, Bauer DC, Cawthon PM, Cummings SR, Hoffman AR, Shikany JM, Barrett-Connor E, Orwoll E, Osteoporotic Fractures in Men (MrOS) Research Group J Bone Miner Res. 2010;25(3):545. The association between vitamin D levels and incident fractures in older men is uncertain. To test the hypothesis that low serum 25-hydroxyvitamin D [(25(OH)D]levels are associated with an increased risk of fracture, we performed a case-cohort study of 436 men with incident nonspine fractures, including 81 hip fractures, and a random subcohort of 1608 men; average follow-up time 5.3 years. Serum vitamin D(2) and vitamin D(3) were measured on baseline sera using mass spectrometry and summed for total vitamin D. Modified Cox proportional hazards models were used to estimate the hazard ratio (HR) of fracture with 95% confidence intervals (CIs). Multivariable models included age, clinic, season, race, height, weight, and physical activity. The mean (SD) total 25(OH)D was 24.6 (7.8) ng/mL in nonspine fracture subjects, 21.5 (7.9) ng/mL in hip fracture subjects, and 25.2 (7.8) ng/mL in controls (nonspine fracture subjects versus nonpatients, p = .14; hip fracture subjects versus controls, p<.0001). 25(OH)D levels were unrelated to nonspine fractures. One SD decrease in total 25(OH)D was associated with an increased risk of hip fracture (multivariate HR = 1.60; 95% CI ). Compared with men in the top quartile of total 25(OH)D (>or =28), the HR of hip fracture was 2.36 (95% CI ) for men in the lowest quartile (<20) (p = .009 for trend). Adjusting for hip bone mineral density attenuated the association by more than 50% (p = .065 for trend). Low serum 25(OH)D concentrations are associated with a higher risk of hip fracture in older men. Measurement of 25(OH)D may be useful in identifying men at high risk of hip fracture. University of Pittsburgh, Department of Epidemiology, Pittsburgh, Pennsylvania 15261, USA. 94 Plasma 25-hydroxyvitamin D levels and fracture risk in a community-based cohort of elderly men in Sweden. Melhus H, et al J Clin Endocrinol Metab. 2010;95(6):2637. CONTEXT: Blood levels of 25-hydroxyvitamin D [25(OH)D]is the generally accepted indicator of vitamin D status, but no universal reference level has been reached. OBJECTIVE: The objective of the study was to determine the threshold at which low plasma 25(OH)D levels are associated with fractures in elderly men and clarify the importance of low levels on total fracture burden. DESIGN AND PARTICIPANTS: In the Uppsala Longitudinal Study of Adult Men, a population-based cohort (mean age, 71 yr, n = 1194), we examined the relationship between 25(OH)D and risk for fracture. Plasma 25(OH)D levels were measured with high-pressure liquid chromatography-mass spectrometry. SETTING: The study was conducted in the municipality of Uppsala in Sweden, a country with a high fracture incidence. MAIN OUTCOME MEASURE: Time to fracture was measured. RESULTS: During follow-up (median 11 yr), 309 of the participants (26%) sustained a fracture. 25(OH)D levels below 40 nmol/liter, which corresponded to the fifth percentile of 25(OH)D, were associated with a modestly increased risk for fracture, multivariable-adjusted hazard ratio 1.65 (95% confidence interval ). No risk difference was detected above this level. Approximately 3% of the fractures were attributable to low 25(OH)D levels in this population. CONCLUSIONS: Vitamin D insufficiency is not a major cause of fractures in community-dwelling elderly men in Sweden. Despite the fact that cutaneous synthesis of previtamin D during the winter season is undetectable at this northern latitude of 60 degrees, only one in 20 had 25(OH)D levels below 40 nmol/liter, the threshold at which the risk for fracture started to increase. Genetic adaptations to limited UV light may be an explanation for our findings. Department of Medical Sciences, Uppsala University, SE Uppsala, Sweden. Melhus H, et al J Clin Endocrinol Metab. 2010;95(6):2637.Cauley. J Bone Miner Res. 2010;25(3):545.Edwards et al. Osteoporos Int. 2008;19(7):991.LeBoff et al.JAMA. 1999;281(16):1505. Looker. J Bone Miner Res May;28(5): Gerdhem. Osteoporos Int. 2005;16(11):1425. Cauley et al. Ann Intern Med. 2008;149(4):242.

31 Niveles séricos de vitamina D y DMO
Percentage change in BMD from baseline during bisphosphonate treatment at the lumbar spine and total hip in the study population divided into 2 groups based on their serum 25 (OH) D concentration (cut-off value: 70 nmol/L). The % change in BMD at the hip was less in the group with sub-optimal vitamin D. Values are shown as the mean [SEM], # p = 0.08. Dean et al. BMC Musculoskeletal Disorders 2007, 8:3

32 (D3) y Reducción de Riesgo de Fractura No vertebral
Speaker notes A meta-analysis that combined data five trials (N = 9829) that used 17.5 – 20 µg (700 – 800 IU) of vitamin D3 reported a 23% reduction in non-vertebral fractures. A fracture risk reduction was associated with higher serum 25-OH-D levels, particularly when these exceeded 75 nmol/L. Reference Bischoff-Ferrari HA, Willett WC, Wong JB, et al. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA 2005; 293(18): Bischoff-Ferrari HA, et al. JAMA 2005; 293(18):

33 Asociación de Ingesta de Calcio y Riesgo de Fractura de Cadera
Speaker notes In a meta-analysis, it was concluded that calcium, with or without vitamin D, resulted in fewer fractures (both hip [shown] and vertebral). Reference Tang BM, Eslick GD, Nowson C, et al. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet 2007; 370(9588): Tang BM, et al. Lancet 2007; 370(9588):

34 Calcio y enfermedad cardiovascular?
Meta-analisis de 15 RCT : pacientes con ingesta de calico como monoterapia con 30% increment del riesgo de IAM (p = to 0.038). BMJ 2010;341:c3691 High-dose calcium supplementation has been associated with Renal calculi in older women Cardiovascular events in older women Prostate cancer in older men

35 Calcio y enfermedad cardiovascular
Kaplan.Meier survival curves for time to incident myocardial infarction or stroke by treatment allocation in a meta-analysis of patient-level data from five trials of calcium supplements used as monotherapy (n=8,151) and in women in the Women's Health Initiative (WHI) calcium and vitamin D trial not using personal calcium supplements at randomization (n=16,718). The magnitude and time-course of the effects of calcium supplements on the two classes of vascular events were very similar in these independent databases. CI, confidence interval; HR, hazard ratio. [Reprinted from "Subgroup analysis for the risk of cardiovascular disease with calcium supplements", by Radford LT, Bolland MJ, Gamble GD, Grey A, Reid IR, 2013, Bonekey Rep, 77(1), pp Copyright 2013 by the Nature Publishing Group. Reprinted with permission]. Reid. J Bone Metab Feb; 21(1): 21–28

36 Factores de Riesgo Modificables: Ejercicio
Recomendación se extiende por Ejercicio contra la gravedad Coordinación Fuerzas Nunca es tarde para empezar Promoting exercise through mechanical loading, will stimulate bone formation. In addition the strength, coordination, and balance achieved will decrease the risk of falls. Exercise can help achieve by BMD, by middle age, and this slows the density decline in later life.

37 Ejercicio. Metanalisis de 10 estudios
Kemmlet et al. Osteoporosis Int 2013 Jul;24(7):

38 Gráfica de forest de metanalisis de 10 estudios en los que se demuestra la importancia del ejercio en evitar caídas que finalizaban en fracturas. Fig 2 Forest plots of studies for four injurious fall categories: A, all injurious falls; B, falls resulting in medical care; C, falls resulting in serious injuries; and D, falls resulting in fractures Fabienne El-Khoury. BMJ 2013; 347 ©2013 by British Medical Journal Publishing Group

39 Habitos de Vida: Fumado y alcohol
Smoking is a risk factor that is both common and correctable. Nicotine decreases intestinal calcium absorption. It is associated with earlier menopause and lower spinal bone density. There is good research on smoking cessation aides. And for this and many other important reasons cessation should be a goal for our patient management.

40 FACTORES DE RIESGO Visión inadecuada Escasa exposición solar
Hábitos Visión inadecuada Escasa exposición solar Nutrición no balanceada, exceso de alcohol, café, proteínas, dieta vegetariana. Tabaquismo Bajo índice de masa corporal (delgadez), menos de 58 kg Sedentarismo o fragilidad Inmovilización prolongada (> 3 meses) Kanis JA, Borgstrom F, De Laet C, et al. Assessment of fracture risk. Osteoporos Int 2005; 16:581.

41 Caso Clínico Don Sigilfredo, se presenta a la edad de 45 años al servicio de Emergencias con una fractura de cadera mientras levantaba una caja

42 Evaluación inicial Calcio, Fósforo, Albúmina y eventualmente PTH
TSH, T4 libre Calciuria en Orina de 24 horas Marcadores Óseos Vitamina D Antecedentes Ginecoobstétricos Historia Clínica que oriente a la solicitud de otros laboratorios: hipogonadismo, menopausia prematura, síndrome de malabsorción, insuficiencia hepática crónica, síndrome intestino irritable, hiperparatiroidismo, condiciones asociadas con pérdida de masa osea acelerada Fármacos: Prednisona, Inhibidores de la aromatasa

43 Condiciones Médicas

44 Causas endocrinológicas
Amenorreas funcionales (anorexia, por stress, por ejercicio físico intenso) Hiperprolactinemia Hipopituitarismo congénito o adquiridoFalla ovárica precoz Síndrome de Turner y Kalman Insuficiencia suprarrenal Síndrome de Cushing Diabetes mellitus tipo 1 Hiperparatiroidismo primario y secundario Hipertiroidismo Osteomalacia Diabetes tipo 1

45 Describió efecto de huesos como “comidos por gusanos”
Friedrich Daniel von Recklinghausen 1891 Describió efecto de huesos como “comidos por gusanos” Friedrich Daniel von Recklinghausen von Recklinghausen FD. Die Fibröse oder deformierende Ostitis, die Osteomalazie und die osteoplastische Carzinose in ihren gegenseitigen Beziehungen, Festchrift Rudolf Virchow (Ed), George Reimer, Berlin p.1.

46 Acción directa sobre los osteoblastos y osteoclastos
Fisiopatología Acción directa sobre los osteoblastos y osteoclastos Efecto sobre el receptor del TSH Finalmente existe un aumento de resorción ósea Efecto sobre marcadores óseos Ross et. Al. Bone disease with hyperthyroidism and thyroid hormone therapy. Uptodate 2014

47 Hipertiroidismo abierto
Constituye un antecedente que se toma en cuenta como factor de riesgo en el futuro para riesgo de fractura Cohorte 686 mujeres > 65 años Seguimiento 3,7 años Estados Unidos 3,6 veces más en cadera 4,5 veces más en vertebra Ross et. Al. Bone disease with hyperthyroidism and thyroid hormone therapy. Uptodate 2014

48 HSC: fracturas Efecto menos contundente que hipertiroidismo abierto en estudios En una cohorte que tomaba levotiroxina con TSH suprimida de 1180 pacientes TSH < 0,05 – 59% 5 años 2,5 % tasa de fracturas en TSH suprimido vs 0,9 % con TSH normal No estadísticamente significativo In a study of 1180 patients taking T4, 59 percent had a suppressed serum TSH concentration (<0.05 mU/L) [70]. Over a five-year period, the overall fracture rate in the women over age 65 years was 2.5 percent in those with suppressed TSH values versus 0.9 percent in those with normal serum TSH values; this difference did not reach statistical significance. ●In the Cardiovascular Health Study of 3567 individuals over age 65 years, hip fracture incidence was increased (hazard ratio 3.3) in men with subclinical hyperthyroidism, but not women [71]. There were only 29 men with subclinical thyrotoxicosis, and 45 percent were taking thyroid medications. Ross et. Al. Bone disease with hyperthyroidism and thyroid hormone therapy. Uptodate 2014

49 En California, en pacientes institucionalizados Sobre 65 años
HSC: fracturas En California, en pacientes institucionalizados Sobre 65 años Solo 29 pacientes de documentaron un incremento de fractura de cadera Significa un Hazard Ratio de 3,3 In a study of 1180 patients taking T4, 59 percent had a suppressed serum TSH concentration (<0.05 mU/L) [70]. Over a five-year period, the overall fracture rate in the women over age 65 years was 2.5 percent in those with suppressed TSH values versus 0.9 percent in those with normal serum TSH values; this difference did not reach statistical significance. ●In the Cardiovascular Health Study of 3567 individuals over age 65 years, hip fracture incidence was increased (hazard ratio 3.3) in men with subclinical hyperthyroidism, but not women [71]. There were only 29 men with subclinical thyrotoxicosis, and 45 percent were taking thyroid medications. Ross et. Al. Bone disease with hyperthyroidism and thyroid hormone therapy. Uptodate 2014

50 Causas nutricionales y gastrointestinales
Deficit calcio y vitamina D Enfermedad celíaca Síndromes de malabsorción Gastrectomía Cirugía bariátrica Enfermedad hepática grave y cirrosis biliar primaria Enfermedad inflamatoria intestinal Nutrición parenteral Malnutrición crónica

51 Causas Genéticas Hemocromatosis Hipofosfatasia Osteogénesis imperfecta
Síndrome de Marfan Síndrome de Ehlers-Danlos Porfirias Enfermedad de Gaucher

52 Causas Hematológicas y transplante
Mieloma múltiple Linfomas y leucemias Mastocitosis Anemia perniciosa Transplante

53 Otras causas Enfermedades crónicas: insuficiencia cardíaca congestiva, EPOC, IRC. Hipercalciuria idiosteoporosisática. Litiasis renal SIDA Alcoholismo Enfermedades infiltrativas: amiloidosis, sarcoidosis Fibrosis quística Fármacos

54 Caso Clínico Don Sigilfredo, se presenta a la edad de 45 años al servicio de Emergencias con una fractura de cadera mientras levantaba una caja

55 Aumento de marcadores Óseos

56 Marcadores Óseos

57 Condiciones de alto recambio Óseo
Hipertiroidismo IRC Metástasis neoplásicas Acromegalia Hiperparatiroidismo Fármacos

58 HIPERPARATIROIDISMOPR IMARIO
Bilezikian JP 2004

59 Marcadores oseos son factores de riesgo independiente para fractura
Epidos Prospective Study. J Bone Mineral Res 1996; 11:1531 Epidos Prospective Study. J Bone Mineral Res 1996; 11:1531

60 Marcadores Óseos y Riesgo de Fractura
4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 Q1 Q2 Q3 Q4 Sérico BAP Marcadores óseos por cuartiles Urinario CTX Relative risk 2.1 ( ) 1.3 ( ) 1.2 ( ) 1.8 ( ) 0.7 ( ) 3.2 ( ) Speaker notes A number of prospective population-based studies have reported that increased levels of BTMs are associated with an approximately two-fold increased risk of fracture (vertebral and non-vertebral) compared to those with normal BTM levels, both in women 65 years of age or older1,2 and in those younger than 65 years (shown).3 The ability of BTMs to predict fracture was largely independent of, and complementary to, BMD. References 1. Ross PD, Kress BC, Parson RE, et al. Serum bone alkaline phosphatase and calcaneus bone density predict fractures: a prospective study. Osteoporos Int 2000; 11(1):76-82. 2. Garnero P, Sornay-Rendu E, Chapuy MC, et al. Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J Bone Miner Res 1996; 11(3): 3. Garnero P, Sornay-Rendu E, Claustrat B, et al. Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: the OFELY study. J Bone Miner Res 2000; 15(8): Garnero P, et al. J Bone Miner Res 2000; 15(8):

61 Fármacos

62 45 años y con antecedente de AR con PDN por 10 años
Doña Blanca 45 años y con antecedente de AR con PDN por 10 años ¿Tiene su riesgo para fractura de osteoporosis?

63 Glucocorticoides Incrementan resorción Inhiben formación
A dosis de 21 mg/día: pérdidad de 27% en columna lumbar en 1 año T3 and PTH increase both resorption and formation, the latter to a lesser extent Loss appears closer to 7% in 20wks on low dose pred (10mg/d) without Ca+ supplementation (Laan, et al 1993)

64 FÁRMACOS Furosemida hipercalciuria
Fenitoína y Barbitúricos incrementan metabolism hepático y de Vitamina D Heparina, promueve pérdida ósea Levotiroxina, incrementa resorción Glucocorticoids are well recognized as a cause, it can be seen in both men and women who use these drugs chronically for disease such as COPD, or rheumatoid arthritis. Furosemide is known to promote urinary calcium loss. (Thiazides, on the other hand, improve calcium balance by reabsorption.) Phenytoin/barbiturates are 2 anticonvulsants that enhance hepatic metabolism of Vitamin D through the cytochrome 450 system. Heparin-long standing use, is known to cause osteoporosis. Thyroxine- when doses are excessive, bone resorption can result. Care must be taken not to overtreat hypothyroidism.

65 Ciclosporina y tacrolimus Metrotexate Letrozole Litio Aluminio
Fármacos Tiazolidinedionas Estatinas Drogas citotóxicas Ciclosporina y tacrolimus Metrotexate Letrozole Litio Aluminio Leuprolide Glucocorticoides Anticonvulsivantes Anticoagulantes Tiazolidinedionas Estatinas Furosemida Drogas citotóxicas Ciclosporina y tacrolimus Metrotexate Letrozole

66 Adherencia

67 Pacientes con baja adherencia se fracturan más que pacientes con buena adherencia
Cumplimiento cubrir 80% del tiempo 16% reduccion† en tasa de Fx 0.6 0.7 0.8 0.9 1 1.1 Baja adherencia Alta adherencia * Riesgo de Fx Hazard Ratio †p<0.005 Caro JJ, et al. Osteoporos Int 2004;15:

68 Conclusiones La evaluación de los factores de riesgo es críticamente importante en identicar personas con alto riesgo de desarrollo de osteoporosis. Los factores de riesgo son para modificar Intervención temprana tiene alto impacto In summary, risk factor assessment is critical in identifying at risk patients. Although many powerful non-modifiable risk factors exist, several other risk factors are modifiable. Although it is difficult to elicit behavioral changes in a patient only in anticipation of a disease that may occur in the future, this is where our patient education must come in to play. As practitioners, we know that identifying at-risk patients early can help prevent or slow the development of this disease.

69 Conclusión Utilice las herramientas para identificar pacientes alto riesgo Cualquier paciente con fractura debe ser evaluado Asegure la ingesta de calico y vitamin D Promueva la actividad físca Discuta las opciones farmacológicas en pacientes de alto riesgo Elimine las barreras documentadas que provocan baja adherencia

70 Gracias! drluiselizondo@gmail.com
Centro Médico Palmares Clinica Vía San Juan

71

72

73

74 Primary Osteoporosis-Two Types
Type I: A primary bone loss from estrogen deficiency (post menopausal osteoporosis) affecting primarily trabecular bone. Type II: An age related bone loss, affecting trabecular and cortical bone. There are two types of primary osteoporosis, Types I and II. Type I relates to estrogen loss as an etiology and affects primarily trabecular bone. Type II is age related and affects both trabecular and cortical bone.

75 Osteoporosis Types and Associated Fractures
Vertebrae is mostly trabecular bone Affected most by Type I primary osteoporosis. Fractures seen most commonly in post-menopausal women Femoral bone is more cortical bone Affected most by Type II primary osteoporosis. Hip fractures occur with increasing frequency in older adults (both men and women). The trabecular bone of the vertebrae is affected most by Type I primary osteoporosis and therefore seen mostly in women. The hip, on the other hand is more cortical bone and fractures occur both men and women as they age.

76 Potential Risks of Calcium Supplementation
High-dose calcium supplementation has been associated with Renal calculi in older women Cardiovascular events in older women Prostate cancer in older men Speaker notes There is controversy regarding the potential adverse effects of high-dose calcium supplementation on renal calculi and cardiovascular events in older women and prostate cancer in older men.1-3 References 1. Bolland MJ, Grey AB, Gamble GD, et al. Effect of osteoporosis treatment on mortality: A meta-analysis. J Clin Endocrinol Metab 2010; 95(3): 2. Bolland MJ, Barber AP, Doughty RN, et al. Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. BMJ 2008; 336(7638): 3. Reid IR, Bolland MJ, Grey A, et al. Effect of calcium supplementation on hip fractures. Osteoporos Int 2008; 19(8): 1. Bolland MJ, et al. J Clin Endocrinol Metab 2010; 95(3): 2. Bolland MJ, et al. BMJ 2008; 336(7638): 3. Reid IR, et al. Osteoporos Int 2008; 19(8): Return to main presentation

77 INCIDENCIA 40 a 100% de individuos mayores residentes en U.S.A. y Europa no institucionalizados son deficientes Más del 50% de mujeres posmenopáusicas que reciben tratamiento para la osteoporosis tienen niveles subóptimos de 25(OH)D (menor de 30 ng/ml) Holick MF 2007

78 INCIDENCIA El 93% de individuos entre 10 y 60 años que ingresan en el hospital por dolor muscular y dolor óseo con una gran variedad de diagnósticos como fibromialgia, fatiga crónica o depresión son deficientes Holick MF 2007

79 INCIDENCIA 32% de estudiantes, médicos y residentes en un hospital de Boston fueron deficientes, a pesar de tomar una copa de leche diaria, ingerir salmón una vez a la semana y suplementos vitamínicos Holick MF 2007

80 Prevalencia de deficiencia/insuficiencia de 25OHD en jóvenes sanos Buenos Aires
25OHD <20 ng/ml sujetos sanos de 25 a 35 años años de residencia en Buenos Aires 42 mujeres ± 2.6 años varones ± 2.23 años mujeres varones invierno 42,6% 50% verano 5.4% 5.3% p=0.007 p=0.002 Div. Endocrinología Hospital Durand 2006

81 INCIDENCIA 73 de las mujeres que lactan y 80 % los recién nacidos son deficientes (menos de 20ng/ml)** a pesar de que toman suplemento vitamínico(70%) o comen pescado(90%) o ingieren 2 a 3 vasos de leche por día(93%) Holick MF 2007

82 Percent Adherent on Weekly Months Following Therapy Initiation
Most Patients Discontinue Oral Bisphosphonates Soon After Treatment Initiation 100 Rapid drop in persistence due to nonacceptance 80 Further decrease in persistence due to multiplicity of factors 60 Percent Adherent on Weekly Bisphosphonate 40 20 3 6 9 12 Months Following Therapy Initiation With permission from Springer Science+Business Media: Weycker D, et al. Compliance with drug therapy for postmenopausal osteoporosis, Osteoporos Int, 2006;17: Figure 1. © International Osteoporosis Foundation and National Osteoporosis Foundation 2006.

83 Adherence With Osteoporosis Therapies
Clinical trials Good adherence (usually >80%) Significant reduction in risk of vertebral, nonvertebral, and hip fractures1 Real-world adherence is poor Up to 83% of patients nonadherent with prescribed osteoporosis Rx2-4 Poor correlation was reported between patient and physician perceptions of compliance Consequences of poor adherence Magnitude of risk reduction for hip and vertebral fractures lower than expected4,5 1. Siris ES, et al. Am J Med. 2009;122(2 suppl):S3-S Hamilton B, et al. Osteoporos Int. 2003;14: 3. Yood RA, et al. Osteoporos Int. 2003;14: Caro JJ, et al. Osteoporos Int. 2004;15: 5. Eastell R, et al. Calcif Tissue Int. 2003;72:408. Abstract P-297.

84 Why Do Patients Resist Change?
Historically, several notions have been proposed as to why patients struggle with adherence to treatment plans: Denial or lack of insight Lack of knowledge Lack of skills Lack of caring Butterworth SW. J Manag Care Pharm. 2008;14(6 Suppl S-b):S21-S25.

85 Improving Adherence Assess patient beliefs/understanding
Understand current medication use patterns Identify patients likely to be nonadherent