The application of FRAX in Ecuador

Introduction Intervention thresholds for the treatment of osteoporosis have been based historically on the measurement of bone mineral density. The development of FRAX® has permitted more accurate assessment of fracture risk. Objective The aim of the present study was to explore treatment paths and characteristics of women eligible for treatment in Ecuador based on FRAX. Methodology and methods A total of 2367 women aged 60–94 years were selected from the National Health, Welfare and Aging Survey (SABE) conducted in Ecuador. Probabilities of major osteoporotic and hip fracture were computed using the Ecuadorian FRAX model. The proportion of women eligible for treatment and bone mineral density assessment was determined based on age-specific intervention thresholds and a hybrid threshold was fixed from age 75 years. Results A total of 87 women (3.7%) had a prior fragility fracture and would be eligible for treatment for this reason. An additional 49 women were eligible for treatment in that MOF probabilities lay above the upper assessment threshold using age-specific thresholds. An BMD test would be recommended in 1131 women (48%) so that FRAX could be recalculated with the inclusion of femoral neck BMD. With the hybrid threshold, an additional 170 women were eligible for treatment and an BMD test recommended in 1218 women. Conclusions The hybrid threshold identifies more women eligible for treatment than age-specific thresholds. Although age-specific thresholds identify women at higher risk of fracture, the lower number of women identified results in fewer identified fracture cases. Resumen Introducción Los umbrales de intervención para el tratamiento de osteoporosis se han basado históricamente en la medición de la densidad ósea. El desarrollo del FRAX® ha permitido una evaluación más precisa del riesgo de fractura. Objetivo El objetivo del estudio fue explorar las rutas de tratamiento y las características de las mujeres elegibles para tratamiento en Ecuador con base en FRAX. Materiales y métodos Se seleccionó a 2.367 mujeres de 60 a 94 años de la encuesta SABE. Se calcularon las probabilidades de fracturas osteoporóticas principales y de cadera utilizando el modelo FRAX ecuatoriano. Se calculó la proporción de mujeres elegibles para tratamiento y evaluación de la densidad ósea, con base en umbrales de intervención específicos de la edad y de un umbral fijo a partir de los 75 años. Resultados Ochenta y siete mujeres (3,7%) tenían una fractura previa y eran elegibles para tratamiento. Utilizando umbrales específicos de edad, otras 49 mujeres eran elegibles para recibir tratamiento debido a que las probabilidades de fractura osteoporótica principal estaban por encima del umbral de evaluación superior. Se recomienda medir la densidad ósea en 1.131 mujeres para que el FRAX pueda ser recalculado con la inclusión de la densidad ósea del cuello femoral. Con el umbral híbrido, otras 170 mujeres fueron elegibles para tratamiento y la medición de la densidad ósea se recomendó a 1.218 mujeres. Conclusiones El umbral híbrido identifica a más mujeres elegibles para tratamiento que los umbrales específicos de la edad. Aunque estos últimos identifican a las mujeres con mayor riesgo de fractura, el menor número de mujeres identificadas resulta en menos casos de fractura identificados

Potential adverse effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on bisphosphonate efficacy : An exploratory post hoc analysis from a randomized controlled trial of clodronate

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to have weak but beneficial effects on bone health, including fracture risk, but many epidemiological studies are likely confounded. We explored the relationship between NSAIDs and fracture risk in a post hoc analysis of a well-documented, randomized, placebo-controlled study of the bisphosphonate, clodronate, in which treatment reduced osteoporotic fracture risk by 23%. Concurrent medication use at baseline was used to identify those prescribed oral NSAIDs. Only verified, incident fractures were included in the analysis. A total of 1082 (20.8%) women reported use of NSAIDs at baseline. They were slightly, but significantly, younger (mean 79 versus 80 years, p = 0.004), heavier (mean 66.7 versus 64.7 kg, p < 0.001) than nonusers, with slightly higher femoral neck bone mineral density (FN-BMD, 0.66 versus 0.64 g/cm2, p < 0.001). In an adjusted model, NSAID use was associated with a significant increase in osteoporotic fracture risk over the 3-year study period (hazard ratio [HR] 1.27; 95% confidence interval [CI], 1.01–1.62; p = 0.039). However, this increase in risk was not statistically significant in the placebo group (HR 1.11; 95% CI, 0.81–1.52). In women receiving clodronate, the effect of the bisphosphonate to reduce osteoporotic fracture risk was not observed in those receiving NSAIDs (HR 0.95; 95% CI, 0.65–1.41; p = 0.81) in contrast to those not using NSAIDs (HR 0.71; 95% CI, 0.58–0.89; p = 0.002). In a subset with hip BMD repeated at 3 years, BMD loss during clodronate therapy was greater in those women receiving NSAIDs than in nonusers (eg, total hip −2.75% versus −1.27%, p = 0.078; femoral neck −3.06% versus −1.12%, p = 0.028), and was not significantly different from that observed in women receiving placebo. The efficacy of the bisphosphonate, clodronate, to reduce fracture risk was largely negated in those receiving NSAIDs. Although the mechanism is unclear, this clinically significant observation requires exploration in studies of commonly used bisphosphonates. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)

Ability of tropical forest soils of French Guiana and Reunion to depollute woods impregnated with biocides

Our study sought to fine-tune knowledge about those microorganisms, particularly wood-decaying fungi degrading pollutants in situ. With a view to the depollution or bioremediation of treated woods, wood-decaying microorganisms from tropical forest soils in French Guiana and the island of Reunion were assessed for their ability to degrade toxic biocides such as pentachlorophenol (PCP) or copper chromium arsenic compounds (CCA). The degradation of red pine (Pinus resinosa) test pieces was monitored and it was found that the soil from French Guiana was more efficient than the soil from Reunion in terms of microbial activity in relation to these two biocides. A significant difference in weight loss was found for the red pinetest pieces treated with CCA and PCP, varying in a ratio of one to two (18% and 30%, respectively). In addition, a study of wood and soil fungus communities using D-HPLC and CE-SSCP, then analysed by a PCA, showed that biocide products leached into the soil had an impact on the fungus communities, which differed depending on the sampling time and on the wood treatment. Lastly, these results confirmed that CCA was less leachable and less degradable by microorganisms in these soils than PCP. (Résumé d'auteur

Elevated circulating Sclerostin concentrations in individuals with high bone mass, with and without LRP5 mutations.

CONTEXT: The role and importance of circulating sclerostin is poorly understood. High bone mass (HBM) caused by activating LRP5 mutations has been reported to be associated with increased plasma sclerostin concentrations; whether the same applies to HBM due to other causes is unknown. OBJECTIVE: Our objective was to determine circulating sclerostin concentrations in HBM. DESIGN AND PARTICIPANTS: In this case-control study, 406 HBM index cases were identified by screening dual-energy x-ray absorptiometry (DXA) databases from 4 United Kingdom centers (n = 219 088), excluding significant osteoarthritis/artifact. Controls comprised unaffected relatives and spouses. MAIN MEASURES: Plasma sclerostin; lumbar spine L1, total hip, and total body DXA; and radial and tibial peripheral quantitative computed tomography (subgroup only) were evaluated. RESULTS: Sclerostin concentrations were significantly higher in both LRP5 HBM and non-LRP5 HBM cases compared with controls: mean (SD) 130.1 (61.7) and 88.0 (39.3) vs 66.4 (32.3) pmol/L (both P < .001, which persisted after adjustment for a priori confounders). In combined adjusted analyses of cases and controls, sclerostin concentrations were positively related to all bone parameters found to be increased in HBM cases (ie, L1, total hip, and total body DXA bone mineral density and radial/tibial cortical area, cortical bone mineral density, and trabecular density). Although these relationships were broadly equivalent in HBM cases and controls, there was some evidence that associations between sclerostin and trabecular phenotypes were stronger in HBM cases, particularly for radial trabecular density (interaction P < .01). CONCLUSIONS: Circulating plasma sclerostin concentrations are increased in both LRP5 and non-LRP5 HBM compared with controls. In addition to the general positive relationship between sclerostin and DXA/peripheral quantitative computed tomography parameters, genetic factors predisposing to HBM may contribute to increased sclerostin levels.This study was supported by The Wellcome Trust NIHR Clinical Research Network (portfolio number 5163); and the supporting Comprehensive Local Research Networks included Birmingham and the Black Country, North and East Yorkshire and Northern Lincolnshire, South Yorkshire, West Anglia, and Western. C.L.G. was funded through a Wellcome Trust Clinical Research Training Fellowship (080280/Z/06/Z) and is now funded by Arthritis Research UK (Grant 20000). K.E.S.P. acknowledges the support of Cambridge NIHR Biomedical Research Centre and the Medical Research Council Human Nutrition Research Unit, Cambridge.This is the author accepted manuscript. The final version is available from the Endocrine Society via http://dx.doi.org/10.1210/jc.2013-395

Sarcopenia definitions and their association with fracture risk in older Swedish women

The purpose of this study was to investigate the prevalence of three sarcopenia definitions and their associations with fracture risk in older Swedish women when adjusted for fracture risk assessment (FRAX)-based risk factors; 2,883 women with a mean age of 77.8 years were included. Sarcopenia was defined based on the Sarcopenia Definitions and Outcomes Consortium (SDOC; low handgrip strength [kg] and gait speed (m/s)), revised European Working Group on Sarcopenia in Older People (EWGSOP2; low appendicular lean mass index, appendicular lean mass [ALM]/height; kg/m2], and hand grip strength [kg]), and Asian Working Group for Sarcopenia (AWGS; low ALM (kg), and hand grip strength [kg]) definitions. Femoral neck T-score was obtained from dual-energy X-ray absorptiometry. All fractures, confirmed by X-ray or medical record review, were subsequently categorized as major osteoporotic fractures (MOFs) and hip fractures. Deaths were verified through regional registers. The total follow-up time was 6.4 ± 1.3 (mean ± SD) yr. Cox regression (hazard ratios [HR] and 95% CIs) analyses were performed with adjustment for age, FRAX variables, and femoral neck T-score. Sarcopenia prevalence was 4.5% (n = 129) according to SDOC, 12.5% (n = 360) for EWGSOP2, and 10.3% (n = 296) defined by AWGS. Individuals with sarcopenia defined by SDOC had a higher mortality risk than individuals without sarcopenia (HR: 3.41; 95% CI: 2.51, 4.62) after adjusting for age and FRAX variables. Sarcopenia according to EWGSOP2 and AWGS was not associated with an increased fracture risk after adjusting for age and FRAX variables. Individuals with sarcopenia defined by SDOC had a higher risk for any fractures (HR: 1.48; 95% CI: 1.10, 1.99) and MOF (HR: 1.42; 95% CI: 1.03, 1.98) compared with individuals without sarcopenia after adjusting for clinical risk factors used in FRAX. In conclusion, sarcopenia defined by SDOC, incorporating muscle function/strength, was the only sarcopenia definition associated with fracture risk in older women

Menopausal hormone therapy reduces the risk of fracture regardless of falls risk or baseline FRAX probability — Results from the Women’s Health Initiative hormone therapy trials

Summary In a combined analysis of 25,389 postmenopausal women aged 50–79 years, enrolled in the two Women’s Health Initiative hormone therapy trials, menopausal hormone therapy vs. placebo reduced the risk of fracture regardless of baseline FRAX fracture probability and falls history. Introduction The aim of this study was to determine if the anti-fracture efficacy of menopausal hormone therapy (MHT) differed by baseline falls history or fracture risk probability as estimated by FRAX, in a combined analysis of the two Women’s Health Initiative (WHI) hormone therapy trials. Methods A total of 25,389 postmenopausal women aged 50–79 years were randomized to receive MHT (n = 12,739) or matching placebo (n = 12,650). At baseline, questionnaires were used to collect information on falls history, within the last 12 months, and clinical risk factors. FRAX 10-year probability of major osteoporotic fracture (MOF) was calculated without BMD. Incident clinical fractures were verified using medical records. An extension of Poisson regression was used to investigate the relationship between treatment and fractures in (1) the whole cohort; (2) those with prior falls; and (3) those without prior falls. The effect of baseline FRAX probability on efficacy was investigated in the whole cohort. Results Over 4.3 ± 2.1 years (mean ± SD), MHT (vs. placebo) significantly reduced the risk of any clinical fracture (hazard ratio [HR] 0.72 [95% CI, 0.65–0.78]), MOF (HR 0.60 [95% CI, 0.53–0.69]), and hip fracture (0.66 [95% CI, 0.45–0.96]). Treatment was effective in reducing the risk of any clinical fracture, MOF, and hip fracture in women regardless of baseline FRAX MOF probability, with no evidence of an interaction between MHT and FRAX (p > 0.30). Similarly, there was no interaction (p > 0.30) between MHT and prior falls. Conclusion In the combined WHI trials, compared to placebo, MHT reduces fracture risk regardless of FRAX probability and falls history in postmenopausal women

Increased development of radiographic hip osteoarthritis in individuals with high bone mass: a prospective cohort study.

BACKGROUND: Individuals with high bone mass (HBM) have a greater odds of prevalent radiographic hip osteoarthritis (OA), reflecting an association with bone-forming OA sub-phenotypes (e.g. osteophytosis, subchondral sclerosis). As the role of bone mineral density (BMD) in hip OA progression is unclear, we aimed to determine if individuals with HBM have increased incidence and/or progression of bone-forming OA sub-phenotypes. METHODS: We analysed an adult cohort with and without HBM (L1 and/or total hip BMD Z-score > + 3.2) with pelvic radiographs collected at baseline and 8-year follow-up. Sub-phenotypes were graded using the OARSI atlas. Superior/inferior acetabular/femoral osteophyte and medial/superior joint space narrowing (JSN) grades were summed and Δosteophyte and ΔJSN derived. Pain and functional limitations were quantified using the WOMAC questionnaire. Associations between HBM status and change in OA sub-phenotypes were determined using multivariable linear/logistic regression, adjusting for age, sex, height, total body fat mass, follow-up time and baseline sub-phenotype grade. Generalised estimating equations accounted for individual-level clustering. RESULTS: Of 136 individuals, 62% had HBM at baseline, 72% were female and mean (SD) age was 59 (10) years. HBM was positively associated with both Δosteophytes and ΔJSN (adjusted mean grade differences between individuals with and without HBM βosteophyte = 0.30 [0.01, 0.58], p = 0.019 and βJSN = 0.10 [0.01, 0.18], p = 0.019). Incident subchondral sclerosis was rare. HBM individuals had higher WOMAC hip functional limitation scores (β = 8.3 [0.7, 15.98], p = 0.032). CONCLUSIONS: HBM is associated with the worsening of hip osteophytes and JSN over an average of 8 years, as well as increased hip pain and functional limitation