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1.
Medicine (Baltimore) ; 100(7): e24839, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33607854

RESUMO

BACKGROUND: To systematically evaluate the efficacy of teriparatide and bisphosphonates in preventing fractures in postmenopausal women with osteoporosis. MATERIALS AND METHODS: We performed a systematic search of PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) that compared teriparatide and bisphosphonates for osteoporosis treatment. Searches were performed without language restrictions and included studies from beginning of time to March 2019. Two authors independently screened and extracted the selected article. The quality of the included studies was evaluated using the Cochrane system evaluation method. Data were extracted and analysed using RevMan 5.2 software. RESULTS: Nine RCTs were included for a total of 2990 postmenopausal women with osteoporosis. Of these, 1515 patients were treated with teriparatide and 1475 were treated with bisphosphonates. After pooling the data of 9 studies, there were significant differences between teriparatide and bisphosphonates [relative risk (RR): 0.61, 95% confidence interval (CI) (0.51, 0.74)] in the prevention of fractures according to different follow-up durations (P < .05), whatever alendronate [RR: 0.51, 95% CI (0.27, 0.95)] and other bisphosphonates [RR: 0.63, 95% CI (0.51, 0.77)]. In addition, we found significant differences between teriparatide and bisphosphonates in the prevention of vertebral fractures [RR: 0.47, 95% CI (0.35, 0.64)] and non-vertebral fractures [RR: 0.76, 95% CI (0.58,0.99)]. There were no significant differences in adverse effects between teriparatide and bisphosphonates [RR: 0.89, 95% CI (0.76, 1.03)]. CONCLUSIONS: Based on the results of our meta-analysis, teriparatide was better than bisphosphonates in preventing fractures in postmenopausal women with osteoporosis both in the short-term and long-term follow-up periods. Teriparatide was superior to bisphosphonates in preventing vertebral and non-vertebral fractures. These drugs did not differ in terms of their adverse effects. More high-quality studies are needed to compare other factors such as costs and adverse reactions.


Assuntos
Difosfonatos/uso terapêutico , Fraturas Ósseas/prevenção & controle , Osteoporose Pós-Menopausa/tratamento farmacológico , Teriparatida/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Alendronato/uso terapêutico , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Estudos de Casos e Controles , Difosfonatos/efeitos adversos , Feminino , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/etiologia , Humanos , Incidência , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/prevenção & controle , Teriparatida/efeitos adversos , Resultado do Tratamento
2.
N Engl J Med ; 383(8): 743-753, 2020 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-32813950

RESUMO

BACKGROUND: Bisphosphonates are effective in reducing hip and osteoporotic fractures. However, concerns about atypical femur fractures have contributed to substantially decreased bisphosphonate use, and the incidence of hip fractures may be increasing. Important uncertainties remain regarding the association between atypical femur fractures and bisphosphonates and other risk factors. METHODS: We studied women 50 years of age or older who were receiving bisphosphonates and who were enrolled in the Kaiser Permanente Southern California health care system; women were followed from January 1, 2007, to November 30, 2017. The primary outcome was atypical femur fracture. Data on risk factors, including bisphosphonate use, were obtained from electronic health records. Fractures were radiographically adjudicated. Multivariable Cox models were used. The risk-benefit profile was modeled for 1 to 10 years of bisphosphonate use to compare associated atypical fractures with other fractures prevented. RESULTS: Among 196,129 women, 277 atypical femur fractures occurred. After multivariable adjustment, the risk of atypical fracture increased with longer duration of bisphosphonate use: the hazard ratio as compared with less than 3 months increased from 8.86 (95% confidence interval [CI], 2.79 to 28.20) for 3 years to less than 5 years to 43.51 (95% CI, 13.70 to 138.15) for 8 years or more. Other risk factors included race (hazard ratio for Asians vs. Whites, 4.84; 95% CI, 3.57 to 6.56), height, weight, and glucocorticoid use. Bisphosphonate discontinuation was associated with a rapid decrease in the risk of atypical fracture. Decreases in the risk of osteoporotic and hip fractures during 1 to 10 years of bisphosphonate use far outweighed the increased risk of atypical fracture among Whites but less so among Asians. After 3 years, 149 hip fractures were prevented and 2 bisphosphonate-associated atypical fractures occurred in Whites, as compared with 91 and 8, respectively, in Asians. CONCLUSIONS: The risk of atypical femur fracture increased with longer duration of bisphosphonate use and rapidly decreased after bisphosphonate discontinuation. Asians had a higher risk than Whites. The absolute risk of atypical femur fracture remained very low as compared with reductions in the risk of hip and other fractures with bisphosphonate treatment. (Funded by Kaiser Permanente and others.).


Assuntos
Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Fraturas do Fêmur/induzido quimicamente , Fraturas do Quadril/prevenção & controle , Osteoporose Pós-Menopausa/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Americanos Asiáticos , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Grupo com Ancestrais do Continente Europeu , Feminino , Fraturas do Fêmur/epidemiologia , Fraturas do Fêmur/etnologia , Fraturas do Quadril/epidemiologia , Humanos , Incidência , Pessoa de Meia-Idade , Análise Multivariada , Osteoporose Pós-Menopausa/complicações , Fraturas por Osteoporose/induzido quimicamente , Fraturas por Osteoporose/epidemiologia , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Fatores de Tempo
3.
Arch Osteoporos ; 15(1): 109, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32700153

RESUMO

A consensus platform is provided by the experts of the Gulf Cooperation Council (GCC) countries' respective osteoporosis societies, on which specific guidelines can be developed further for regional use on the assessment and treatment of postmenopausal women at risk from fractures due to osteoporosis. INTRODUCTION: Guidance is provided in a Gulf Cooperation Council (GCC) country setting on the assessment and treatment of postmenopausal women at risk from fractures due to osteoporosis, which is an adaptation of the European guidance by Kanis et al., jointly published by the International Osteoporosis Foundation and the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). The respective osteoporosis societies of the Gulf Cooperation Council (GCC) countries assembled for a unifying consensus on the diagnosis and management of osteoporosis in postmenopausal women for the region. METHODS: The Chair for Biomarkers of Chronic Diseases (CBCD) in King Saud University (KSU), Riyadh, Kingdom of Saudi Arabia (KSA), in cooperation with the Saudi Osteoporosis Society (SOS), hosted regional experts and respective leaders from different GCC osteoporosis societies, together with an adviser from the ESCEO. An assembly of experts representing the different osteoporosis societies from Saudi Arabia, the UAE, Bahrain, Oman, and Kuwait gathered on February 15-16, 2019 in Riyadh, KSA for the formulation of a general osteoporosis consensus for the region. RESULTS: The following areas were covered: diagnosis of osteoporosis and assessment of fracture risk; general and pharmacological management of osteoporosis; and hip fractures, vitamin D, recommendation on which FRAX tool to follow, and the importance of country-specific FRAX® and fracture liaison services for secondary fracture prevention. CONCLUSIONS: A platform is provided on which specific guidelines can be developed for regional use in GCC.


Assuntos
Osteoartrite , Osteoporose Pós-Menopausa , Idoso , Barein , Consenso , Feminino , Humanos , Kuweit , Pessoa de Meia-Idade , Omã , Osteoartrite/complicações , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/diagnóstico , Osteoporose Pós-Menopausa/terapia , Pós-Menopausa , Arábia Saudita
4.
Medicine (Baltimore) ; 99(29): e20773, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702821

RESUMO

BACKGROUND: The prevalence of postmenopausal osteoporosis is rapidly rising, with a high proportion of patients who are vulnerable to fractures and other chronic symptoms. The commonly applied Western medicine lacks cost-efficiency and tends to have various potential side effects. Guilu Erxian Glue (GEG), an orally taken traditional Chinese medicinal product, has been advocated to manage osteoporosis for a long period. However, the evidence of the efficacy of GEG on osteoporosis seems to be less convincing and conclusive. Therefore, the purpose of this study is to assess the effectiveness and safety of GEG on postmenopausal osteoporosis. METHODS: We will implement a systematic review and meta-analysis following the requests of the preferred reporting items for systematic reviews and meta-analyses protocols (PRISMA-P). The PubMed database, Scopus, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, VIP database, Sinomed, and grey literature sources will be retrieved for eligible studies. Randomized controlled trials investigating GEG in women with postmenopausal osteoporosis employing osteoporosis-associated outcomes measures will be eligible for inclusion. Two reviewers will independently complete the study selection procedure, data extraction, and risk of bias assessment. A third reviewer will mediate when irreconcilable discrepancies occur. Should sufficient clinical homogeneity exist, a meta-analysis will be conducted. Additionally, we will utilize the Grading of Recommendations Assessment, Development and Evaluation to assess the strength of quantitative outcomes. RESULTS: The current systematic review and meta-analysis will provide the effectiveness and safety of GEG on postmenopausal osteoporosis. CONCLUSION: The study will offer high-quality and explicit evidence for applying GEG on the treatment of postmenopausal osteoporosis. OSF REGISTRATION: DOI 10.17605/OSF.IO/JCVBH.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Fraturas Ósseas/prevenção & controle , Osteoporose Pós-Menopausa/terapia , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Protocolos Clínicos/normas , Estudos de Avaliação como Assunto , Feminino , Fraturas Ósseas/etiologia , Humanos , Medicina Tradicional Chinesa/métodos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/complicações , Prevalência , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Resultado do Tratamento
6.
Rev. osteoporos. metab. miner. (Internet) ; 12(2): 45-52, abr.-jun. 2020. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-193783

RESUMO

OBJETIVO: Valorar la asociación de las mediciones tridimensionales (3D) derivadas de la absorciometría de rayos X de energía dual (DXA) lumbar con las fracturas osteoporóticas en las vértebras dorsales. MATERIAL Y MÉTODOS: Analizamos retrospectivamente 32 mujeres postmenopáusicas: 16 con fracturas incidentes en las vértebras dorsales y 16 controles sin ningún tipo de fractura. Las DXA lumbares se adquirieron en la visita inicial (es decir, antes del evento de fractura) y se midió la densidad mineral ósea de área (DMOa) en las vértebras L1 a L4. Las mediciones 3D derivadas de la DXA se evaluaron utilizando un software de modelado 3D (3D-SHAPER). La densidad mineral ósea volumétrica (DMOv) se calculó en el hueso trabecular, cortical e integral. También se midió el grosor cortical y la DMO superficial (DMOs) cortical. Las diferencias en las mediciones derivadas de la DXA entre los grupos de fracturados y controles se evaluaron utilizando una prueba t de Student no pareada. También se calculó la razón de probabilidades (OR) y el área bajo la curva característica operativa del receptor (AUC). RESULTADOS: En el presente estudio caso-control ajustado por edad no se encontraron diferencias significativas entre los grupos de fracturados y controles en términos de peso (ρ = 0,44), altura (ρ = 0,25) y DMOa (ρ = 0,11). Sin embargo, sí se encontraron diferencias significativas (ρ < 0,05) en la DMOv integral y trabecular y en la DMOs cortical. La DMOv trabecular en el cuerpo vertebral fue la medida que mejor discriminó entre ambos grupos, con un AUC de 0,733, respecto a 0,682 para la DMOa. CONCLUSIÓN: Este estudio muestra la capacidad de los modelos 3D derivados de la DXA lumbar para discriminar entre sujetos con fracturas incidentes en las vértebras dorsales y controles. Es necesario analizar cohortes mayores para determinar si estas mediciones podrían mejorar la predicción del riesgo de fractura en la práctica clínica


OBJECTIVE: To assess the relation between three-dimensional (3D) measurements obtained by lumbar dual energy X-ray absorptiometry (DXA) and osteoporotic fractures in dorsal vertebrae. MATERIAL AND METHODS: We analysed retrospectively 32 postmenopausal women, allocated to two groups: 16 women in the experimental group, who presented incident fractures of the dorsal vertebrae, and 16 women in the control group, who did not show any type of fracture. Measurements of the (aBMD) of vertebrae L1 through L4 were taken at the initial visit (i.e., prior to the fracture event) by lumbar dual-energy x-ray absorptiometries (DXA). 3D measurements obtained by DXA were evaluated using 3D modelling software (3D-SHAPER). Volumetric bone mineral density (vBMD) was calculated in the trabecular, cortical and integral bone. Cortical thickness and cortical surface BMD (sBMD) were also measured. Differences in measurements derived from the DXA between the experimental and control groups were assessed using an unpaired Student t-test. The odds ratio (OR) and the area under the receiver operating characteristic curve (AUC) were also determined. RESULTS: In the present age-adjusted case-control study, no significant differences were found between the experimental and control groups in terms of weight (ρ = 0.44), height (ρ = 0.25) and aBMD (ρ = 0.11). However, significant differences (ρ < 0.05) were found in the integral and trabecular vBMD and in the cortical sBMD. Trabecular vBMD in the vertebral body was the measure that best discriminated between both groups, with an AUC of 0.733, compared to 0.682 of the aBMD. CONCLUSION: This study shows the ability of 3D models resultant from lumbar DXAs to discern between subjects with incident fractures in the dorsal vertebrae and control subjects. It is necessary to analyse larger cohorts to establish if these measurements could improve the prediction of fracture risk in clinical practice


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/diagnóstico por imagem , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/etiologia , Estudos de Casos e Controles , Estudos Retrospectivos , Absorciometria de Fóton , Raios X
7.
Medicine (Baltimore) ; 99(15): e18964, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32282692

RESUMO

BACKGROUND: We performed a systematic review and meta-analysis of the efficacy and safety of teriparatide and bisphosphonates in managing postmenopausal osteoporosis. METHODS: PubMed, EMBASE, Web of Science, and China National Knowledge Infrastructure were searched for relevant randomized controlled trials that were published before April 2018 and compared teriparatide and bisphosphonates in treating postmenopausal osteoporosis. Stata 12.0 was used for the meta-analysis. The pooled risk ratio (RR) or weighted mean difference and 95% confidence interval (CI) were calculated using a fixed effects or random effects meta-analysis. RESULTS: A total of 14 randomized controlled trials were included in this meta-analysis. The teriparatide group was associated with a lower total occurrence of vertebral fractures (RR = 0.55, 95% CI: 0.40-0.77; P = .001) and nonvertebral fractures (RR = 0.65, 95% CI: 0.46-0.90; P = .009) than the bisphosphonate group. Moreover, compared with the bisphosphonate group, the teriparatide group had improved bone mineral density at the lumbar spine and femoral neck at the final follow-up (P < .05). There was no significant difference between the teriparatide and bisphosphonate groups in terms of complications (RR = 1.05, 95% CI: 0.90, 1.22, P = .516). CONCLUSIONS: Teriparatide significantly reduced the occurrence of vertebral and nonvertebral fractures in osteoporosis patients. More studies should focus on the quality of life of patients using these 2 drugs.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Difosfonatos/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Teriparatida/uso terapêutico , Conservadores da Densidade Óssea/farmacologia , Difosfonatos/farmacologia , Colo do Fêmur/efeitos dos fármacos , Humanos , Vértebras Lombares/efeitos dos fármacos , Osteoporose Pós-Menopausa/complicações , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/prevenção & controle , Teriparatida/farmacologia
8.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 55(3): 159-164, 2020 Mar 09.
Artigo em Chinês | MEDLINE | ID: mdl-32193911

RESUMO

Objective: To investigate the association between osteoporosis and severe periodontal attachment loss in postmenopausal women. Methods: One hundred and ninety-five postmenopausal women aged 50-65 years old were included in the present study. The participant were recruited from patients in the Peking University International Hospital and through website from March, 2017 to August, 2018. Periodontal examination, filling out a structured questionnaire and bone mass density (BMD) examination were completed to each of the participants. The clinical attachment loss (CAL), oral hygiene index simplified (OHI-S), and bleeding on probing (BOP) were examined and recorded as periodontal parameters. The structured questionnaire was used to collect information of the physical activity, socioeconomic status, marital status, oral health habits, and so on. Bone mass density of the lumbar spine and left hip were scanned by using standardized dual energy X-ray absorptiometry. Based on the T-score of BMD (difference between the measured BMD and the mean value of young white women in terms of standard deviations), osteoporosis was defined as T-score≤-2.5 (according to the World Health Organization criteria). Fourteen risk factors were preliminarily screened by chi-square test, including age, duration of menopause, body mass index (BMI), exercise habit, economic status, marital status, level of education, habit of dental visit, tooth brushing habit, usage of interdental tools, OHI-S, BOP(+)%, osteoporosis in hip and osteoporosis in lumbar. Factors with P<0.05 were selected for multivariate Logistic regression analysis. Logistic regression was used to analysis the risk factors of severe periodontal attachment loss. Results: The mean age of 195 postmenopausal women was (57.8±4.3) years. After adjusting for ages, the economic status, habit of dental visit, OHI-S and BOP(+)%, there was an association of osteoporosis in hip and severe periodontal attachment loss in postmenopausal women [odds ratios (OR)=2.466, 95% confidence intervals (CI) was 1.173-5.185, P=0.017]. Conclusions: Postmenopausal women with osteoporosis in hip has a greater chance of presenting severe periodontal attachment loss.


Assuntos
Osteoporose Pós-Menopausa/complicações , Perda da Inserção Periodontal/complicações , Absorciometria de Fóton , Idoso , Densidade Óssea , Feminino , Quadril/diagnóstico por imagem , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/diagnóstico por imagem , Pós-Menopausa
9.
Clin Interv Aging ; 15: 357-361, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32210546

RESUMO

Purpose: Sarcopenia and osteoporosis are both serious health problems in postmenopausal women. The Asia Working Group for Sarcopenia recommends using the skeletal muscle index (SMI), which is height-adjusted appendicular skeletal muscle mass (ASMM). However, loss of height has been shown to be a common clinical finding in patients with osteoporosis. This study examined the prevalence of presarcopenia using height and arm span, which is a predictor of height, and investigated the diagnostic accuracy for presarcopenia. Methods: A total of 55 post-menopausal osteoporotic patients aged 62-95 years underwent bioelectrical impedance analysis (BIA) for ASMM measurement and dual-energy X-ray absorptiometry (DXA) scan for bone mineral density (BMD). Anthropometric measurements, including height, weight, and arm span were taken, and body mass index (BMI), SMI, and arm span-adjusted SMI (Arm span SMI) were calculated. Presarcopenia was defined as SMI or Arm span SMI <5.7 kg/m2 in this study. Results: The prevalence of presarcopenia was 27.3% and 38.2% evaluated by SMI and Arm span SMI, respectively. The prevalence of presarcopenia was higher when evaluated by Arm span SMI than by SMI. In the presarcopenia group diagnosed only by Arm span SMI (n=11), the arm span-height difference was significantly higher (p<0.001) and the percentage of young adult mean (YAM) femoral neck-BMD was significantly lower (p=0.013) compared to the normal group diagnosed by both SMI and Arm span-SMI (n=29). Conclusion: These results indicated that Arm span SMI might be useful for the diagnosis of sarcopenia in patients with severe osteoporosis and kyphosis.


Assuntos
Braço/anatomia & histologia , Estatura , Músculo Esquelético/patologia , Osteoporose Pós-Menopausa/complicações , Sarcopenia/diagnóstico , Absorciometria de Fóton , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Densidade Óssea , Impedância Elétrica , Feminino , Humanos , Pessoa de Meia-Idade
10.
Niger J Clin Pract ; 23(2): 147-153, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32031087

RESUMO

Aim: The aim of this study was to examine long-term implant success and marginal bone loss (MBL) of dental implants in postmenopausal women with osteoporosis/osteopenia. Materials and Methods: Postmenopausal women who underwent dental implant treatment at least 3 years ago were divided into two study groups [Test (osteoporosis/osteopenia) Group and Control Group] according to bone mineral density (BMD) measurements. Besides clinical periodontal and radiographic examinations, any implant failures were also recorded. Results: A total of 52 patients with a mean age of 59.51 ± 5.66 years (Test Group; 26 patients, mean age: 60.61; Control Group; 26 patients, mean age: 58.42) were included in the study. Implant survival rates were 96.2% and 100% with a mean follow-up 60.84 ± 22.13 and 60.07 ± 20.93 months in Test and Control Groups, respectively (P > 0.05). While peri-implant PI (plaque index) and PD (probing depth) were not different between the groups, BoP (bleeding on probing) was significantly higher in Test Group (P = 0,026). Although MBL in Test Group was higher than Control Group (0.82 ± 0,63 mm and 0.44 ± 0,33 mm respectively), the difference was not found statistically significant (P = 0.069). Conclusion: Within the limits of this retrospective study, it can be concluded that postmenopausal osteoporosis/osteopenia does not affect MBL and long-term implant success. The findings suggest that dental implant therapy is a reliable treatment modality in these patients to improve the quality of life by increasing function and aesthetics.


Assuntos
Perda do Osso Alveolar/etiologia , Doenças Ósseas Metabólicas/complicações , Implantes Dentários , Osteoporose Pós-Menopausa/complicações , Pós-Menopausa , Idoso , Densidade Óssea , Doenças Ósseas Metabólicas/epidemiologia , Índice de Placa Dentária , Prótese Dentária Fixada por Implante , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento
11.
Arch Osteoporos ; 15(1): 25, 2020 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-32095943

RESUMO

This is a cross-sectional study to look at the utility of DXA-VFA in addition to bone mineral density (BMD) in the evaluation of postmenopausal osteoporosis. Vertebral fracture (VF) was detected in more than two-thirds of postmenopausal women referred for DXA-BMD. Addition of DXA-VFA detected additional 27% with VF whose BMD were in the non-osteoporotic range. INTRODUCTION: VFs are the hallmark of osteoporotic fractures. Prevalent vertebral fractures are an independent risk factor for future fragility fractures. This study was conducted to look at the prevalence of VF by DXA-vertebral fracture assessment (VFA) and to study the utility of DXA-VFA in addition to bone mineral density (BMD) in the evaluation of osteoporosis. METHODS: A cross-sectional study of the postmenopausal women above the age of 50 years who were referred for BMD assessment by DXA. All subjects underwent VFA and BMD assessment by Hologic DXA. RESULTS: Four hundred postmenopausal women with a mean age of 62.7 ± 6.2 years underwent BMD and VFA assessment by DXA. Prevalent VF was seen in 261 (65.2%) subjects, of which 114 (28.5%) subjects, 135 (33.7%) subjects, and 12 (3%) subjects had mild, moderate, and severe VF, respectively. Among subjects with VF, 136 (52.1%) and 90 (34.5%) had BMD-defined osteoporosis at the spine and femur neck, respectively. Overall, 59% with VF had osteoporosis at either the spine or femur neck. Forty-one-percent subjects with VF had BMD in non-osteoporotic range at both sites, of which 20% had moderate-to-severe VF. Addition of DXA-VFA to BMD assessment detected additional 27% with VF whose BMD was in the non-osteoporotic range. CONCLUSION: VF was seen in more than two-thirds of the postmenopausal women referred for osteoporosis evaluation. VFA identified additional patients with VF whose BMD was not in the osteoporotic range. Incorporation of VFA to BMD will assist in documenting prevalent vertebral fracture which is an independent risk factor for incident fragility fracture irrespective of the BMD.


Assuntos
Absorciometria de Fóton/métodos , Densidade Óssea , Osteoporose Pós-Menopausa/diagnóstico por imagem , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas da Coluna Vertebral/diagnóstico por imagem , Idoso , Estudos Transversais , Feminino , Colo do Fêmur/diagnóstico por imagem , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/complicações , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Prevalência , Fatores de Risco , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Coluna Vertebral/diagnóstico por imagem
12.
FASEB J ; 34(2): 3399-3412, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31925860

RESUMO

Osteoporotic osteoarthritis (OPOA) is a common bone disease mostly in the elderly, but the relationship between Osteoporotic (OP) and osteoarthritis (OA) is complex. It has been shown that knee loading can mitigate OA symptoms. However, its effects on OPOA remain unclear. In this study, we characterized pathological linkage of OP to OA, and evaluated the effect of knee loading on OPOA. We employed two mouse models (OA and OPOA), and conducted histology, cytology, and molecular analyses. In the OA and OPOA groups, articular cartilage was degenerated and Osteoarthritis Research Society International score was increased. Subchondral bone underwent abnormal remodeling, the differentiation of bone marrow mesenchymal stem cells (BMSCs) to osteoblasts and chondrocytes was reduced, and migration and adhesion of pre-osteoclasts were enhanced. Compared to the OA group, the pathological changes of OA in the OPOA group were considerably aggravated. After knee loading, however, cartilage degradation was effectively prevented, and the abnormal remodeling of subchondral bone was significantly inhibited. The differentiation of BMSCs was also improved, and the expression of Wnt/ß-catenin was elevated. Collectively, this study demonstrates that osteoporosis aggravates OA symptoms. Knee loading restores OPOA by regulating subchondral bone remodeling, and may provide an effective method for repairing OPOA.


Assuntos
Cartilagem Articular/metabolismo , Osteoartrite/terapia , Osteoporose Pós-Menopausa/terapia , Suporte de Carga , Via de Sinalização Wnt , Animais , Cartilagem Articular/patologia , Adesão Celular , Diferenciação Celular , Movimento Celular , Células Cultivadas , Condrócitos/citologia , Condrócitos/metabolismo , Condrócitos/fisiologia , Feminino , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Osteoartrite/etiologia , Osteoartrite/metabolismo , Osteoblastos/citologia , Osteoblastos/metabolismo , Osteoblastos/fisiologia , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/metabolismo
13.
Arch Osteoporos ; 15(1): 9, 2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31897621

RESUMO

Lumbar BMD and functional recovery in the acute period were independently strongly associated with subsequent new VCF after hospital conservative therapy for patients with new fragility VCFs. Functional recovery was related with age, pain intensity during first month after hospitalization, VCF past history and multiple new VCFs. PURPOSE: This study aimed to determine the factors independently associated with the subsequent vertebral compression fracture (VCF) after hospital conservative therapy in patients with new fragility VCFs and parameters related with functional recovery in the acute period. METHODS: Subsequent VCF (n = 37) was defined as patients who sustained a new VCF within 9 months after new VCF, whereas patients without a new VCF were classified as non-subsequent VCF (n = 179). Logistic regression analysis was performed to determine independent factors associated with the subsequent VCF, including patients' characteristics, past histories, number of new VCFs, bone mineral density (BMD), lumbar sagittal alignment, fractured vertebral body height, spine muscle mass, pain intensity, corset types, medications for osteoporosis and pain relief, recovery ratio of functional independence measure (FIM) and bone union. Correlation coefficients were accessed between the FIM recovery ratio and continuous variable parameters, while intergroup comparisons or analysis of variance was conducted to examine significant differences in the FIM recovery ratio for categorical variable parameters. RESULTS: Lumbar BMD, FIM recovery ratio at the first month after hospitalization and segmental Cobb angle were significantly independently associated with subsequent VCF (odds ratio: 27.8, 9.6 and 1.1, respectively). The FIM recovery ratio was moderately negatively correlated with age and pain intensity and was significantly worse in patients with multiple new VCFs or past history of VCF. CONCLUSIONS: Conservative therapies focused on lumbar BMD, functional recovery and pain relief in the acute period may be useful in preventing subsequent VCF.


Assuntos
Tratamento Conservador/métodos , Fraturas por Compressão/etiologia , Fraturas por Osteoporose/terapia , Fraturas da Coluna Vertebral/terapia , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea/fisiologia , Feminino , Fêmur/fisiologia , Fraturas por Compressão/fisiopatologia , Fraturas por Compressão/terapia , Hospitalização , Humanos , Vértebras Lombares/fisiologia , Masculino , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/fisiopatologia , Fraturas por Osteoporose/etiologia , Modalidades de Fisioterapia , Recidiva , Estudos Retrospectivos , Fatores de Risco , Fraturas da Coluna Vertebral/etiologia , Estenose Espinal/etiologia , Estenose Espinal/fisiopatologia
14.
Clin Drug Investig ; 40(1): 15-23, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31630338

RESUMO

BACKGROUND AND OBJECTIVE: The correlation between change in bone mineral density (BMD) and the incidence of new vertebral fracture has been drawing attention in regard to evaluation of fracture risk and drug efficacy. We investigated the impact of the prevalence of vertebral fracture on this correlation via a meta-regression analysis with a view to improving evaluation of the correlation. METHODS: A total of 19 postmenopausal osteoporosis clinical studies involving 62,432 patients in 46 placebo or treatment groups were identified through MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. We performed a multivariate meta-regression analysis to examine the correlation between the percentage change in lumbar spine BMD from baseline at 3 years and the proportion of subjects experiencing new vertebral fractures, with or without the proportion of subjects with prevalent vertebral fracture as a covariate. We also analyzed the interaction between the subgroups divided by the proportion of subjects with prevalent vertebral fracture and the percentage change in lumbar spine BMD from baseline at 3 years. RESULTS: A multivariate meta-regression analysis showed a significant correlation between the change in lumbar spine BMD and the proportion of subjects experiencing new vertebral fracture, and a lower Akaike information criterion was obtained when the proportion of subjects with prevalent vertebral fracture was added as an explanatory variable. Significant interaction between the proportion of subjects with prevalent vertebral fracture and the change in lumbar spine BMD was shown. CONCLUSIONS: The change in lumbar spine BMD, not BMD T-score at one timepoint, had a significant correlation with the incidence of vertebral fracture. The prediction of the fracture risk by change in lumbar spine BMD was improved by adjusting the proportion of subjects with prevalent vertebral fracture in the study population. The difference of prevalence of vertebral fracture among populations should be considered when the association between change in lumbar spine BMD and incidence of vertebral fracture is examined.


Assuntos
Densidade Óssea , Osteoporose Pós-Menopausa/complicações , Fraturas da Coluna Vertebral/patologia , Feminino , Humanos , Incidência , Vértebras Lombares , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
J Clin Endocrinol Metab ; 105(3)2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674641

RESUMO

CONTEXT: In the Denosumab and High-Dose Teriparatide Administration (DATA-HD) study, we reported that 15 months of combined high-dose (HD) teriparatide and denosumab increased mean areal bone mineral density (aBMD) at the hip and spine more than combined denosumab and standard-dose (SD) teriparatide. OBJECTIVE: In the current analysis, we compare the individual rates of aBMD response between the treatment groups. DESIGN: Single-site, open-label, randomized controlled trial in which postmenopausal women received either teriparatide 20-µg daily (SD) or 40-µg daily (HD) given months 0 through 9, overlapped with denosumab 60 mg, given months 3 through 15 (15 months' total duration). The proportion of participants in the SD and HD groups experiencing total hip, femoral neck, and lumbar spine aBMD gains of >3%, >6%, and >9% were compared. PARTICIPANTS: Postmenopausal women with osteoporosis completing all study visits (n = 60). MAIN OUTCOME MEASURE(S): aBMD (dual x-ray absorptiometry). RESULTS: At the end of the 15-month treatment period, a higher proportion of women in the HD group had aBMD increases >3% (83% vs. 58%, P = .037) and >6% (45% vs. 19%, P = .034) at the total hip, and >3% at the femoral neck (86% vs. 63%, P = .044). At the lumbar spine, >3% response rates were similar, whereas the >6% and >9% response rates were greater in the HD group (100% vs. 79%, P = .012 and 93% vs. 59%, P = .003, respectively). CONCLUSION: Compared with the SD regimen, more women treated with the HD regimen achieved clinically meaningful and rapid gains in hip and spine aBMD. These results suggest that this approach may provide unique benefits in the treatment of postmenopausal osteoporosis.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Densidade Óssea/efeitos dos fármacos , Denosumab/administração & dosagem , Osteoporose Pós-Menopausa/tratamento farmacológico , Teriparatida/administração & dosagem , Absorciometria de Fóton , Idoso , Relação Dose-Resposta a Droga , Quimioterapia Combinada/métodos , Feminino , Colo do Fêmur/diagnóstico por imagem , Colo do Fêmur/efeitos dos fármacos , Colo do Fêmur/fisiopatologia , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/fisiopatologia , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/diagnóstico , Osteoporose Pós-Menopausa/fisiopatologia , Resultado do Tratamento
16.
J Clin Endocrinol Metab ; 105(3)2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674644

RESUMO

CONTEXT: The ACTIVE study demonstrated the antifracture efficacy of abaloparatide in postmenopausal women with osteoporosis. ACTIVExtend demonstrated sustained fracture risk reduction with alendronate in abaloparatide-treated participants from ACTIVE. A direct comparison of the efficacy of abaloparatide and antiresorptive therapies has not been performed. OBJECTIVE: The objective of this analysis is to compare the antifracture efficacy of abaloparatide in ACTIVE with that of alendronate in ACTIVExtend. DESIGN: In this post hoc analysis, the rate of new vertebral fractures for women in ACTIVExtend (N = 1139) was calculated based on baseline and endpoint radiographs for placebo or abaloparatide in ACTIVE and alendronate in ACTIVExtend. Vertebral fracture rates between abaloparatide and alendronate were compared in a Poisson regression model. Fracture rates for nonvertebral and clinical fractures were compared based on a Poisson model during 18 months of abaloparatide or placebo treatment in ACTIVE and 18 months of alendronate treatment in ACTIVExtend. RESULTS: The vertebral fracture rate was lower during abaloparatide treatment in ACTIVE (0.47 fractures/100 patient-years) than alendronate treatment in ACTIVExtend (1.66 fractures/100 patient-years) (relative risk reduction 71%; P = .027). Although the comparisons did not meet statistical significance, after switching from placebo (ACTIVE) to alendronate (ACTIVExtend), the rate of new vertebral fractures decreased from 2.49 to 1.66 fractures per 100 patient-years, and after switching from abaloparatide to alendronate from 0.47 to 0.19 fractures per 100 patient-years. The rates of nonvertebral fractures and clinical fractures were not significantly different. CONCLUSION: Initial treatment with abaloparatide may result in greater vertebral fracture reduction compared with alendronate in postmenopausal women with osteoporosis.


Assuntos
Alendronato/administração & dosagem , Conservadores da Densidade Óssea/administração & dosagem , Osteoporose Pós-Menopausa/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Proteína Relacionada ao Hormônio Paratireóideo/administração & dosagem , Fraturas da Coluna Vertebral/prevenção & controle , Idoso , Alendronato/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Densidade Óssea/fisiologia , Conservadores da Densidade Óssea/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Colo do Fêmur/diagnóstico por imagem , Colo do Fêmur/efeitos dos fármacos , Colo do Fêmur/fisiopatologia , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/fisiopatologia , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/diagnóstico , Osteoporose Pós-Menopausa/fisiopatologia , Fraturas por Osteoporose/diagnóstico , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Proteína Relacionada ao Hormônio Paratireóideo/efeitos adversos , Placebos/administração & dosagem , Placebos/efeitos adversos , Radiografia , Fatores de Risco , Fraturas da Coluna Vertebral/diagnóstico , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Resultado do Tratamento
17.
Orthop Surg ; 12(1): 116-123, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31880071

RESUMO

OBJECTIVE: To investigate the clinical significance of the detection of bone mineral density (BMD) and bone turnover markers (BTM) in older women with osteoporosis, and to compare their predictive power for osteoporotic fractures (OF). METHODS: In this retrospective study, 96 patients with OF and 107 patients with osteoporosis who were hospitalized in the Department of Orthopedics at the First Affiliated Hospital of Chengdu Medical College were examined from October 2017 to February 2019. All selected patients were divided into either the fracture group (96 cases, 47.3%) or the non-fracture group (107 cases, 52.7%). BMD was measured by dual-energy X-ray absorptiometry (DXA). BTM were detected by electrochemical luminescence: aminoterminal propeptide of type I procollagen (PINP), ß-cross-linked C-telopeptide of type I collagen (ß-CTX), and molecular fragment of osteocalcin N terminal (N-MID). Bone metabolism-related indicators were detected, including alkaline phosphatase (ALP), calcium (Ca), and phosphorus (P). Independent-samples t-tests were used to compare the measurement data between the two groups, one-way ANOVA to compare the gaps between groups, and binary logistic regression to analyze the correlation of BMD and BTM with OF. RESULTS: There were no significant differences in age, weight, height, body mass index, age, and time of menopause between the two groups. There were a total of 71 cases (35.0%) in group A (60-70 years), 80 cases (39.4%) in group B (71-80 years), and 52 cases (25.6%) in group C (81-90 years). The fracture group was compared with the non-fracture group for BMD in the lumbar (0.75 ± 0.05 vs 0.88 ± 0.13, 0.75 ± 0.16 vs 0.87 ± 0.09, 0.74 ± 0.21 vs 0.87 ± 0.12 g/cm2 ; P < 0.05), BMD in the hip (0.62 ± 0.16 vs 0.74 ± 0.14, 0.61 ± 0.15 vs 0.73 ± 0.0, 0.58 ± 0.13 vs 0.73 ± 0.08 g/cm2 ; P < 0.05), PINP (83.7 ± 5.7 vs 74.8 ± 5.0, 80.7 ± 4.1 vs 72.1 ± 5.1, 81.2 ± 7.0 vs 68.7 ± 6.3 ng/mL, P < 0.05), and ß-CTX (829.7 ± 91.5 vs 798.8 ± 52.2, 848.1 ± 71.2 vs 812.4 ± 79.0, 867.3 ± 53.1 vs 849.1 ± 67.2 pg./mL, P < 0.05). N-MID (19.0 ± 6.7 vs 21.3 ± 9.7, 16.2 ± 7.0 vs 18.0 ± 5.3 ng/mL, P < 0.05) in the fracture cases was lower than in the non-fracture cases for groups B and C, and there was statistical significance. Among the fracture cases, PINP in group A was higher than in group B and C, and ß-CTX in group C was higher than in group A and B (P < 0.05). There was no significant difference in the ALP, P, and Ca between the two groups (P > 0.05). Binary logistic regression analysis showed that for BMD in the lumbar and hip, ß-CTX and OF were significantly correlated (respectively, odds ratio [OR] = -4.182, 95% confidence interval [CI] 1.672-3.448; OR = 6.929, 95% CI 2.586-12.106; OR = 7.572, 95% CI 1.441-3.059), and the differences were statistically significant. PINP and N-MID were correlated with OF (respectively, OR = 4.213, 95% CI 0.978-1.005; OR = 2.510, 95% CI 1.070-1.134, P > 0.05), the difference was not statistically significant. CONCLUSION: Osteoporotic older women, with lower bone density and higher ß-CTX, are more likely to incur OF. ß-CTX is better than BMD at predicting OF and can help in its management and in implementing interventions in high-risk populations.


Assuntos
Biomarcadores/metabolismo , Densidade Óssea , Remodelação Óssea , Osteoporose Pós-Menopausa/complicações , Fraturas por Osteoporose/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/metabolismo , Fraturas por Osteoporose/metabolismo , Estudos Retrospectivos
18.
J Nutr ; 150(3): 599-605, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31825069

RESUMO

BACKGROUND: The direct association between intake of Japanese fermented soybeans, namely natto, and bone mineral density (BMD) is known. However, the association with osteoporotic fractures has not been studied. OBJECTIVE: This study aimed to investigate whether habitual natto intake is associated with a risk of osteoporotic fractures. METHODS: This prospective cohort study included 1417 postmenopausal Japanese women who were enrolled in the Japanese Population-Based Osteoporosis cohort study in 1996, 1999, 2002, and 2006 and were aged ≥45 y at baseline. The intake of natto, tofu, and other soybean products was surveyed with use of a FFQ at baseline. Fractures were ascertained in follow-up surveys conducted in 1999, 2002, 2006, and 2011/2012. Osteoporotic fracture was the primary outcome and was defined as a clinical fracture occurring without strong external force, diagnosed with radiographs by a medical doctor. HRs with 95% CIs were estimated with Cox proportional hazard models. RESULTS: During the 17,699 person-years of follow-up (median, 15.2 y), 172 women experienced osteoporotic fractures. After adjustment for age and BMD at the total hip, the HRs compared with those of < 1 pack (approximately 40 g)/wk natto intake were 0.72 (95% CI: 0.52, 0.98) and 0.51 (95% CI: 0.30, 0.87) for 1-6 and ≥7 packs/wk, respectively. After further adjustment for BMI, history of osteoporotic fractures, history of myocardial infarction or stroke, diabetes mellitus, current smoking, alcohol intake, frequency of tofu and other soybean product intakes, and dietary calcium intake, the HRs were 0.79 (95% CI: 0.56, 1.10) and 0.56 (95% CI: 0.32, 0.99) for 1-6 and ≥7 packs/wk, respectively. Frequency of tofu or other soybean product intakes had no association with the risk of osteoporotic fractures. CONCLUSIONS: Habitual natto intake may be associated with a reduced risk of osteoporotic fractures independent of confounding factors, including BMD, in Japanese postmenopausal women. This trial was registered at umin.ac.jp as UMIN 000032869.


Assuntos
Fraturas Ósseas/complicações , Osteoporose Pós-Menopausa/complicações , Pós-Menopausa , Alimentos de Soja , Adolescente , Adulto , Idoso , Densidade Óssea , Feminino , Fraturas Ósseas/epidemiologia , Humanos , Japão/epidemiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
19.
Lancet Diabetes Endocrinol ; 7(12): 899-911, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31676222

RESUMO

BACKGROUND: Odanacatib, a cathepsin K inhibitor, reduces bone resorption while maintaining bone formation. Previous work has shown that odanacatib increases bone mineral density in postmenopausal women with low bone mass. We aimed to investigate the efficacy and safety of odanacatib to reduce fracture risk in postmenopausal women with osteoporosis. METHODS: The Long-term Odanacatib Fracture Trial (LOFT) was a multicentre, randomised, double-blind, placebo-controlled, event-driven study at 388 outpatient clinics in 40 countries. Eligible participants were women aged at least 65 years who were postmenopausal for 5 years or more, with a femoral neck or total hip bone mineral density T-score between -2·5 and -4·0 if no previous radiographic vertebral fracture, or between -1·5 and -4·0 with a previous vertebral fracture. Women with a previous hip fracture, more than one vertebral fracture, or a T-score of less than -4·0 at the total hip or femoral neck were not eligible unless they were unable or unwilling to use approved osteoporosis treatment. Participants were randomly assigned (1:1) to either oral odanacatib (50 mg once per week) or matching placebo. Randomisation was done using an interactive voice recognition system after stratification for previous radiographic vertebral fracture, and treatment was masked to study participants, investigators and their staff, and sponsor personnel. If the study completed before 5 years of double-blind treatment, consenting participants could enrol in a double-blind extension study (LOFT Extension), continuing their original treatment assignment for up to 5 years from randomisation. Primary endpoints were incidence of vertebral fractures as assessed using radiographs collected at baseline, 6 and 12 months, yearly, and at final study visit in participants for whom evaluable radiograph images were available at baseline and at least one other timepoint, and hip and non-vertebral fractures adjudicated as being a result of osteoporosis as assessed by clinical history and radiograph. Safety was assessed in participants who received at least one dose of study drug. The adjudicated cardiovascular safety endpoints were a composite of cardiovascular death, myocardial infarction, or stroke, and new-onset atrial fibrillation or flutter. Individual cardiovascular endpoints and death were also assessed. LOFT and LOFT Extension are registered with ClinicalTrials.gov (number NCT00529373) and the European Clinical Trials Database (EudraCT number 2007-002693-66). FINDINGS: Between Sept 14, 2007, and Nov 17, 2009, we randomly assigned 16 071 evaluable patients to treatment: 8043 to odanacatib and 8028 to placebo. After a median follow-up of 36·5 months (IQR 34·43-40·15) 4297 women assigned to odanacatib and 3960 assigned to placebo enrolled in LOFT Extension (total median follow-up 47·6 months, IQR 35·45-60·06). In LOFT, cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 3·7% (251/6770) versus 7·8% (542/6910), hazard ratio (HR) 0·46, 95% CI 0·40-0·53; hip fractures 0·8% (65/8043) versus 1·6% (125/8028), 0·53, 0·39-0·71; non-vertebral fractures 5·1% (412/8043) versus 6·7% (541/8028), 0·77, 0·68-0·87; all p<0·0001. Combined results from LOFT plus LOFT Extension for cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 4·9% (341/6909) versus 9·6% (675/7011), HR 0·48, 95% CI 0·42-0·55; hip fractures 1·1% (86/8043) versus 2·0% (162/8028), 0·52, 0·40-0·67; non-vertebral fractures 6·4% (512/8043) versus 8·4% (675/8028), 0·74, 0·66-0·83; all p<0·0001. In LOFT, the composite cardiovascular endpoint of cardiovascular death, myocardial infarction, or stroke occurred in 273 (3·4%) of 8043 patients in the odanacatib group versus 245 (3·1%) of 8028 in the placebo group (HR 1·12, 95% CI 0·95-1·34; p=0·18). New-onset atrial fibrillation or flutter occurred in 112 (1·4%) of 8043 patients in the odanacatib group versus 96 (1·2%) of 8028 in the placebo group (HR 1·18, 0·90-1·55; p=0·24). Odanacatib was associated with an increased risk of stroke (1·7% [136/8043] vs 1·3% [104/8028], HR 1·32, 1·02-1·70; p=0·034), but not myocardial infarction (0·7% [60/8043] vs 0·9% [74/8028], HR 0·82, 0·58-1·15; p=0·26). The HR for all-cause mortality was 1·13 (5·0% [401/8043] vs 4·4% [356/8028], 0·98-1·30; p=0·10). When data from LOFT Extension were included, the composite of cardiovascular death, myocardial infarction, or stroke occurred in significantly more patients in the odanacatib group than in the placebo group (401 [5·0%] of 8043 vs 343 [4·3%] of 8028, HR 1·17, 1·02-1·36; p=0·029, as did stroke (2·3% [187/8043] vs 1·7% [137/8028], HR 1·37, 1·10-1·71; p=0·0051). INTERPRETATION: Odanacatib reduced the risk of fracture, but was associated with an increased risk of cardiovascular events, specifically stroke, in postmenopausal women with osteoporosis. Based on the overall balance between benefit and risk, the study's sponsor decided that they would no longer pursue development of odanacatib for treatment of osteoporosis. FUNDING: Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc, Kenilworth, NJ, USA.


Assuntos
Compostos de Bifenilo/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Compostos de Bifenilo/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/efeitos adversos , Método Duplo-Cego , Feminino , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/prevenção & controle , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/prevenção & controle , Humanos , Osteoporose Pós-Menopausa/complicações , Fraturas por Osteoporose/prevenção & controle , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/prevenção & controle , Resultado do Tratamento
20.
Biom J ; 61(6): 1448-1461, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31652011

RESUMO

In randomized clinical trials, it is often of interest to estimate the effect of treatment on quality of life (QOL), in addition to those on the event itself. When an event occurs in some patients prior to QOL score assessment, investigators may compare QOL scores between patient subgroups defined by the event after randomization. However, owing to postrandomization selection bias, this analysis can mislead investigators about treatment efficacy and result in paradoxical findings. The recent Japanese Osteoporosis Intervention Trial (JOINT-02), which compared the benefits of a combination therapy for fracture prevention with those of a monotherapy, exemplifies the case in point; the average QOL score was higher in the combination therapy arm for the unfractured subgroup but was lower for the fractured subgroup. To address this issue, principal strata effects (PSEs), which are treatment effects estimated within subgroups of individuals stratified by potential intermediate variable, have been discussed in the literature. In this paper, we describe a simple procedure for estimating the PSEs using marginal structural models. This procedure utilizes SAS code for the estimation. In addition, we present a simple sensitivity analysis method for examining the resulting estimates. The analyses of JOINT-02 data using these methods revealed that QOL scores were higher in the combination therapy arm than in the monotherapy arm for both subgroups.


Assuntos
Biometria/métodos , Ensaios Clínicos como Assunto , Fraturas Ósseas/prevenção & controle , Modelos Estatísticos , Idoso , Alendronato/farmacologia , Interações Medicamentosas , Feminino , Fraturas Ósseas/complicações , Humanos , Hidroxicolecalciferóis/farmacologia , Osteoporose Pós-Menopausa/complicações
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