Impact of generic alendronate cost on the cost-effectiveness of osteoporosis screening and treatment

Introduction: Since alendronate became available in generic form in the Unites States in 2008, its price has been decreasing. The objective of this study was to investigate the impact of alendronate cost on the cost-effectiveness of osteoporosis screening and treatment in postmenopausal women. Methods: Microsimulation cost-effectiveness model of osteoporosis screening and treatment for U.S. women age 65 and older. We assumed screening initiation at age 65 with central dual-energy x-ray absorptiometry (DXA), and alendronate treatment for individuals with osteoporosis; with a comparator of "no screening" and treatment only after fracture occurrence. We evaluated annual alendronate costs of $20 through$800; outcome measures included fractures; nursing home admission; medication adverse events; death; costs; quality-adjusted life-years (QALYs); and incremental cost-effectiveness ratios (ICERs) in 2010 U.S. dollars per QALY gained. A lifetime time horizon was used, and direct costs were included. Base-case and sensitivity analyses were performed. Results: Base-case analysis results showed that at annual alendronate costs of $200 or less, osteoporosis screening followed by treatment was cost-saving, resulting in lower total costs than no screening as well as more QALYs (10.6 additional quality-adjusted life-days). When assuming alendronate costs of$400 through $800, screening and treatment resulted in greater lifetime costs than no screening but was highly cost-effective, with ICERs ranging from$714 per QALY gained through $13,902 per QALY gained. Probabilistic sensitivity analyses revealed that the cost-effectiveness of osteoporosis screening followed by alendronate treatment was robust to joint input parameter estimate variation at a willingness-to-pay threshold of$50,000/QALY at all alendronate costs evaluated. Conclusions: Osteoporosis screening followed by alendronate treatment is effective and highly cost-effective for postmenopausal women across a range of alendronate costs, and may be cost-saving at annual alendronate costs of $200 or less. © 2012 Nayak et al

Efficacy of weekly teriparatide does not vary by baseline fracture probability calculated using FRAX

Summary The aim of this study was to determine the efficacy of once-weekly teriparatide as a function of baseline fracture risk. Treatment with once-weekly teriparatide was associated with a statistically significant 79 % decrease in vertebral fractures, and in the cohort as a whole, efficacy was not related to baseline fracture risk. Introduction Previous studies have suggested that the efficacy of some interventions may be greater in the segment of the population at highest fracture risk as assessed by the FRAX® algorithms. The aim of the present study was to determine whether the antifracture efficacy of weekly teriparatide was dependent on the magnitude of fracture risk. Methods Baseline fracture probabilities (using FRAX) were computed from the primary data of a phase 3 study (TOWER) of the effects of weekly teriparatide in 542 men and postmenopausal women with osteoporosis. The outcome variable comprised morphometric vertebral fractures. Interactions between fracture probability and efficacy were explored by Poisson regression. Results The 10-year probability of major osteoporotic fractures (without BMD) ranged from 7.2 to 42.2 %. FRAX-based hip fracture probabilities ranged from 0.9 to 29.3 %. Treatment with teriparatide was associated with a 79 % (95 % CI 52–91 %) decrease in vertebral fractures assessed by semiquantitative morphometry. Relative risk reductions for the effect of teriparatide on the fracture outcome did not change significantly across the range of fracture probabilities (p = 0.28). In a subgroup analysis of 346 (64 %) participants who had FRAX probabilities calculated with the inclusion of BMD, there was a small but significant interaction (p = 0.028) between efficacy and baseline fracture probability such that high fracture probabilities were associated with lower efficacy. Conclusion Weekly teriparatide significantly decreased the risk of morphometric vertebral fractures in men and postmenopausal women with osteoporosis. Overall, the efficacy of teriparatide was not dependent on the level of fracture risk assessed by FRAX in the cohort as a whole

Association between renin and atherosclerotic burden in subjects with and without type 2 diabetes.

Published onlineJournal ArticleThis is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: Activation of the renin-angiotensin-aldosterone-system (RAAS) has been proposed to contribute to development of vascular complications in type 2 diabetes (T2D). The aim of the present study was to determine if plasma renin levels are associated with the severity of vascular changes in subjects with and without T2D. METHODS: Renin was analyzed by the Proximity Extension Assay in subjects with (n = 985) and without (n = 515) T2D participating in the SUMMIT (SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools) study and in 205 carotid endarterectomy patients. Vascular changes were assessed by determining ankle-brachial pressure index (ABPI), carotid intima-media thickness (IMT), carotid plaque area, pulse wave velocity (PWV) and the reactivity hyperemia index (RHI). RESULTS: Plasma renin was elevated in subjects with T2D and demonstrated risk factor-independent association with prevalent cardiovascular disease both in subjects with and without T2D. Renin levels increased with age, body mass index, HbA1c and correlated inversely with HDL. Subjects with T2D had more severe carotid disease, increased arterial stiffness, and impaired endothelial function. Risk factor-independent associations between renin and APBI, bulb IMT, carotid plaque area were observed in both T2D and non-T2D subjects. These associations were independent of treatment with RAAS inhibitors. Only weak associations existed between plasma renin and the expression of pro-inflammatory and fibrous components in plaques from 205 endarterectomy patients. CONCLUSIONS: Our findings provide clinical evidence for associations between systemic RAAS activation and atherosclerotic burden and suggest that this association is of particular importance in T2D.Innovative Medicines Initiative (the SUMMIT consortium, IMI-2008/115006, the Swedish Heart-Lung Foundation, the Swedish Research Council and Marianne and Marcus Wallenberg Foundation)

Selenium status is positively associated with bone mineral density in healthy aging European men

Objective It is still a matter of debate if subtle changes in selenium (Se) status affect thyroid function tests (TFTs) and bone mineral density (BMD). This is particularly relevant for the elderly, whose nutritional status is more vulnerable. Design and Methods We investigated Se status in a cohort of 387 healthy elderly men (median age 77 yrs; inter quartile range 75-80 yrs) in relation to TFTs and BMD. Se status was determined by measuring both plasma selenoprotein P (SePP) and Se. Results The overall Se status in our population was low normal with only 0.5% (2/387) of subjects meeting the criteria for Se deficiency. SePP and Se levels were not associated with thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroxine (T4), triiodothyronine (T3) or reverse triiodothyronine (rT3) levels. The T3/T4 and T3/rT3 ratios, reflecting peripheral metabolism of thyroid hormone, were not associated with Se status either. SePP and Se were positively associated with total BMD and femoral trochanter BMD. Se, but not SePP, was positively associated with femoral neck and ward's BMD. Multivariate linear analyses showed that these associations remain statistically significant in a model including TSH, FT4, body mass index, physical performance score, age, smoking, diabetes mellitus and number of medication use. Conclusion Our study demonstrates that Se status, within the normal European marginally supplied range, is positively associated with BMD in healthy aging men, independent of thyroid function. Thyroid function tests appear unaffected by Se status in this population

Vitamin D during pregnancy: why observational studies suggest deficiency and interventional studies show no improvement in clinical outcomes? A narrative review

International audienc

Fatores de risco para fratura por osteoporose e baixa densidade óssea em mulheres na pré e pós-menopausa

OBJECTIVE: To estimate the prevalence and analyze risk factors associated to osteoporosis and low-trauma fracture in women. METHODS: Cross-sectional study including a total of 4,332 women older than 40 attending primary care services in the Greater São Paulo, Southeastern Brazil, between 2004 and 2007. Anthropometrical and gynecological data and information about lifestyle habits, previous fracture, medical history, food intake and physical activity were obtained through individual quantitative interviews. Low-trauma fracture was defined as that resulting from a fall from standing height or less in individuals 50 years or older. Multiple logistic regression models were designed having osteoporotic fracture and bone mineral density (BMD) as the dependent variables and all other parameters as the independent ones. The significance level was set at p<0.05. RESULTS: The prevalence of osteoporosis and osteoporotic fractures was 33% and 11.5%, respectively. The main risk factors associated with low bone mass were age (OR=1.07; 95% CI: 1.06;1.08), time since menopause (OR=2.16; 95% CI: 1.49;3.14), previous fracture (OR=2.62; 95% CI: 2.08;3.29) and current smoking (OR=1.45; 95% CI: 1.13;1.85). BMI (OR=0.88; 95% CI: 0.86;0.89), regular physical activity (OR=0.78; 95% CI: 0.65;0.94) and hormone replacement therapy (OR=0.43; 95% CI: 0.33;0.56) had a protective effect on bone mass. Risk factors significantly associated with osteoporotic fractures were age (OR=1.05; 95% CI: 1.04;1.06), time since menopause (OR=4.12; 95% CI: 1.79;9.48), familial history of hip fracture (OR=3.59; 95% CI: 2.88;4.47) and low BMD (OR=2.28; 95% CI: 1.85;2.82). CONCLUSIONS: Advanced age, menopause, low-trauma fracture and current smoking are major risk factors associated with low BMD and osteoporotic fracture. The clinical use of these parameters to identify women at higher risk for fractures might be a reasonable strategy to improve the management of osteoporosis.OBJETIVO: Estimar la prevalencia y analizar los factores de riesgo asociados con osteoporosis y fractura por bajo impacto entre mujeres. MÉTODOS: Estudio transversal realizado con 4.332 mujeres encima de 40 años de edad provenientes de atención primaria de salud en el área metropolitana de la gran São Paulo, SP, entre 2004 2007. Datos antropométricos y ginecológico y relativos a hábitos de vida, fractura previa, antecedentes personales, ingestión alimentaria y actividad física fueron evaluados por medio de entrevista individual y cuantitativa. Fractura por bajo impacto fue definida como decurrente de caída de la propia altura o menos en individuos con más de 50 años de edad. Modelos de regresión multivariada y logística analizaron, respectivamente, la densidad ósea y la fractura por osteoporosis, como variables dependientes y todas las otras como independientes. El nivel de significancia estadística establecido fue p<0,05. RESULTADOS: La prevalencia de osteoporosis y de fracturas por fragilidad ósea fue de 33% y 11,5%, respectivamente. Los principales factores de riesgo asociados con baja densidad ósea fueron edad (OR=1,07; IC 95%: 1,06;1,08), menopausia (OR=2,16; IC 95%: 1,49;3,14), fractura previa (OR=2,62; IC 95%: 2,08;3,29) y tabaquismo actual (OR=1,45; IC 95%: 1,13;1,85). Por otro lado, elevado IMC (OR=0,88; IC 95%: 0,86;0,89), actividad física regular (OR=0,78; IC 95%: 0,65;0,94) y terapia hormonal actual (OR=0,43; IC 95%: 0,33;0,56) desempeñaron papel protector. Los factores de riesgo significantemente relacionados con fractura por osteoporosis fueron edad (OR=1,05; IC 95%: 1,04;1,06), menopausia (OR=4,12; IC 95%: 1,79;9,48), historia familiar de fractura de cuadril (OR=3,59; IC 95%: 2,88;4,47) y baja densidad ósea (OR=2,28; IC 95%: 1,85;2,82). CONCLUSIONES: Edad avanzada, menopausia, fractura previa por bajo impacto y tabaquismo actual son los principales factores de riesgo asociados con baja densidad ósea y esta, con las fracturas por fragilidad ósea. El uso clínico de estos parámetros para identificar mujeres de mayor riesgo para fracturas puede ser una estrategia interesante para mejorar el abordaje de la osteoporosis.OBJETIVO: Estimar a prevalência e analisar os fatores de risco associados com osteoporose e fratura por baixo impacto entre mulheres. MÉTODOS: Estudo transversal realizado com 4.332 mulheres acima de 40 anos de idade provenientes de atendimento primário de saúde na área metropolitana da Grande São Paulo, SP, entre 2004 e 2007. Dados antropométricos e ginecológicos e relativos a hábitos de vida, fratura prévia, antecedentes pessoais, ingestão alimentar e atividade física foram avaliados por meio de entrevista individual e quantitativa. Fratura por baixo impacto foi definida como decorrente de queda da própria altura ou menos em indivíduos com mais de 50 anos de idade. Modelos de regressão multivariada e logística analisaram, respectivamente, a densidade óssea e a fratura por osteoporose como variáveis dependentes e todas as outras como independentes. O nível de significância estatística estabelecido foi p < 0,05. RESULTADOS: A prevalência de osteoporose e de fraturas por fragilidade óssea foi de 33% e 11,5%, respectivamente. Os principais fatores de risco associados com baixa densidade óssea foram idade (OR = 1,07; IC 95%: 1,06;1,08), menopausa (OR = 2,16; IC 95%: 1,49;3,14), fratura prévia (OR = 2,62; IC 95%: 2,08;3,29) e tabagismo atual (OR = 1,45; IC 95%: 1,13;1,85). Por outro lado, elevado IMC (OR = 0,88; IC 95%: 0,86;0,89), atividade física regular (OR = 0,78; IC 95%: 0,65;0,94) e terapia hormonal atual (OR = 0,43; IC 95%: 0,33;0,56) desempenharam papel protetor. Os fatores de risco significativamente relacionados com fratura por osteoporose foram idade (OR = 1,05; IC 95%: 1,04;1,06), menopausa (OR = 4,12; IC 95%: 1,79;9,48), história familiar de fratura de quadril (OR = 3,59; IC 95%: 2,88;4,47) e baixa densidade óssea (OR = 2,28; IC 95%: 1,85;2,82). CONCLUSÕES: Idade avançada, menopausa, fratura prévia por baixo impacto e tabagismo atual são os principais fatores de risco associados com baixa densidade óssea, a qual se associa com as fraturas por fragilidade óssea. O uso clínico desses parâmetros para identificar mulheres de maior risco para fraturas pode ser uma estratégia interessante para melhorar a abordagem da osteoporose.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP-EPM Instituto de Diagnóstico por ImagemUNIFESP-EPM Programa de Pós-Graduação em ReumatologiaUNIFESP-EPM Departamento de RadiologiaUNIFESP, EPM, Instituto de Diagnóstico por ImagemUNIFESP, EPM Programa de Pós-Graduação em ReumatologiaUNIFESP, EPM Depto. de RadiologiaSciEL

Locally harvested foods support serum 25-hydroxyvitamin D sufficiency in an indigenous population of Western Alaska

Background: Low serum vitamin D is associated with higher latitude, age, body fat percentage and low intake of fatty fish. Little documentation of vitamin D concentrations is available for Alaska Native populations. Objective: This study was undertaken to investigate serum 25-hydroxyvitamin D (25(OH)D) concentrations of the Yup'ik people of southwestern Alaska in relation to demographic and lifestyle variables, particularly with the use of locally harvested (local) foods. Design: Cross-sectional study. Methods: We estimated 25(OH)D, dietary vitamin D and calcium, percent of energy from local foods and demographic variables in 497 Yup'ik people (43% males) aged 14–92 residing in southwestern Alaska. Sampling was approximately equally divided between synthesizing and non-synthesizing seasons, although the preponderance of samples were drawn during months of increasing daylight. Results: Mean vitamin D intake was 15.1±20.2 µg/d, while local foods accounted for 22.9±17.1% of energy intake. The leading sources of vitamin D were local fish (90.1%) followed by market foods. Mean 25(OH)D concentration was 95.6±40.7 nmol/L. Participants in the upper 50th percentile of 25(OH)D concentration tended to be older, male, of lower body mass index, sampled during the synthesizing season, and among the upper 50th percentile of local food use. Conclusions: A shift away from locally harvested foods will likely increase the risk for serum 25(OH)D insufficiency in this population

Dual Energy X-Ray Absorptiometry Body Composition Reference Values from NHANES

In 2008 the National Center for Health Statistics released a dual energy x-ray absorptiometry (DXA) whole body dataset from the NHANES population-based sample acquired with modern fan beam scanners in 15 counties across the United States from 1999 through 2004. The NHANES dataset was partitioned by gender and ethnicity and DXA whole body measures of %fat, fat mass/height2, lean mass/height2, appendicular lean mass/height2, %fat trunk/%fat legs ratio, trunk/limb fat mass ratio of fat, bone mineral content (BMC) and bone mineral density (BMD) were analyzed to provide reference values for subjects 8 to 85 years old. DXA reference values for adults were normalized to age; reference values for children included total and sub-total whole body results and were normalized to age, height, or lean mass. We developed an obesity classification scheme by using estabbody mass index (BMI) classification thresholds and prevalences in young adults to generate matching classification thresholds for Fat Mass Index (FMI; fat mass/height2). These reference values should be helpful in the evaluation of a variety of adult and childhood abnormalities involving fat, lean, and bone, for establishing entry criteria into clinical trials, and for other medical, research, and epidemiological uses

Reference Ranges for Bone Mineral Density and Prevalence of Osteoporosis in Vietnamese Men and Women

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to examine the effect of different reference ranges in bone mineral density on the diagnosis of osteoporosis.</p> <p>Methods</p> <p>This cross-sectional study involved 357 men and 870 women aged between 18 and 89 years, who were randomly sampled from various districts within Ho Chi Minh City, Vietnam. BMD at the femoral neck, lumbar spine and whole body was measured by DXA (Hologic QDR4500). Polynomial regression models and bootstraps method were used to determine peak BMD and standard deviation (<it>SD</it>). Based on the two parameters, we computed T-scores (denoted by <it>T</it>_VN) for each individual in the study. A similar diagnosis was also done based on T-scores provided by the densitometer (<it>T</it>_DXA), which is based on the US White population (NHANES III). We then compared the concordance between <it>T</it>_VNand <it>T</it>_DXAin the classification of osteoporosis. Osteoporosis was defined according to the World Health Organization criteria.</p> <p>Results</p> <p>In post-menopausal women, the prevalence of osteoporosis based on femoral neck <it>T</it>_VNwas 29%, but when the diagnosis was based on <it>T</it>_DXA, the prevalence was 44%. In men aged 50+ years, the <it>T</it>_VN-based prevalence of osteoporosis was 10%, which was lower than <it>T</it>_DXA-based prevalence (30%). Among 177 women who were diagnosed with osteoporosis by <it>T</it>_DXA, 35% were actually osteopenia by <it>T</it>_VN. The kappa-statistic was 0.54 for women and 0.41 for men.</p> <p>Conclusion</p> <p>These data suggest that the <it>T-</it>scores provided by the Hologic QDR4500 over-diagnosed osteoporosis in Vietnamese men and women. This over-diagnosis could lead to over-treatment and influence the decision of recruitment of participants in clinical trials.</p