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1.
Diabetes Care ; 46(8): 1477-1482, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37276529

RESUMO

OBJECTIVE: To compare the incidence of type 1 diabetes (T1D) before and during the coronavirus disease 2019 (COVID-19) pandemic and determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with T1D development. RESEARCH DESIGN AND METHODS: All Danish residents aged <30 years free of diabetes from 2015 to 2021 were included. Individuals were followed from 1 January 2015 or birth until the development of T1D, the age of 30, the end of the study (31 December 2021), emigration, development of type 2 diabetes, onset of any cancer, initiation of immunomodulating therapy, or development of any autoimmune disease. We compared the incidence rate ratio (IRR) of T1D using Poisson regression models. We matched each person with a SARS-CoV-2 infection with three control individuals and used a cause-specific Cox regression model to estimate the hazard ratio (HR). RESULTS: Among 2,381,348 individuals, 3,579 cases of T1D occurred. The adjusted IRRs for T1D in each quarter of 2020 and 2021 compared with 2015-2019 were as follows: January-March 2020, 1.03 (95% CI 0.86; 1.23); January-March 2021, 1.01 (0.84; 1.22), April-June 2020, 0.98 (0.80; 1.20); April-June 2021, 1.34 (1.12; 1.61); July-September 2020, 1.13 (0.94; 1.35); July-September 2021, 1.21 (1.01; 1.45); October-December 2020, 1.09 (0.91; 1.31); and October-December 2021, 1.18 (0.99; 1.41). We identified 338,670 individuals with a positive SARS-CoV-2 test result and matched them with 1,004,688 control individuals. A SARS-2-CoV infection was not significantly associated with the risk of T1D development (HR 0.90 [95% CI 0.60; 1.35]). CONCLUSIONS: There was an increase in T1D incidence during April-June 2021 compared with April-June 2015-2019, but this could not be attributed to SARS-CoV-2 infection.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 1/epidemiologia , COVID-19/epidemiologia , SARS-CoV-2 , Dinamarca/epidemiologia
2.
BMC Endocr Disord ; 22(1): 14, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34991581

RESUMO

BACKGROUND: Patients with primary hyperparathyroidism (pHPT) and impaired kidney function (estimated glomerular filtration rate (eGFR) < 60 mL/min) are offered parathyroidectomy (PTX) to protect them from further complications. Surprisingly, two recent uncontrolled cohort studies have suggested a further decrease in kidney function following PTX. We aimed to examine the effects of PTX compared to non-surgical surveillance on kidney function in pHPT patients. METHODS: Historic cohort study. From the Danish National Patient Registry (NPR) and major medical biochemistry laboratories in Denmark, we identified 3585 patients with biochemically confirmed pHPT among whom n = 1977 (55%) were treated with PTX (PTX-group) whereas n = 1608 (45%) were followed without surgery (non-PTX group). Baseline was defined as time of diagnosis and kidney function was re-assessed 9-15 months after PTX (PTX group) or 9-15 months after diagnosis (non-PTX group). RESULTS: At follow-up, eGFR had decreased significantly in the PTX- compared to the non-PTX-group (median - 4% vs. - 1%, p < 0.01). Stratification by baseline eGFR showed that the decrease was significant for those with a baseline eGFR value of 80-89 and > 90 mL/min, but not for those with lower eGFR values. Findings did not differ between patients with mild compared to moderate/severe hypercalcemia. However, after mutual adjustments, we identified baseline levels of calcium, PTH, and eGFR as well as age and treatment (PTX vs. no-PTX) as independent predictors for changes in kidney function. CONCLUSION: Compared to non-surgical surveillance, PTX is associated with a small but significant decrease in kidney function in pHPT patients with an initial normal kidney function.


Assuntos
Taxa de Filtração Glomerular , Hiperparatireoidismo Primário/fisiopatologia , Hiperparatireoidismo Primário/cirurgia , Paratireoidectomia , Conduta Expectante , Idoso , Biomarcadores/análise , Dinamarca , Feminino , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos
3.
Bone ; 143: 115612, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32853851

RESUMO

CONTEXT: Menopause leads to an increased bone turnover associated with a high risk of fractures. Bone turnover is inhibited by meal intake, to some extent mediated by gut hormones, and interventions based on these endocrine changes may have potential in future prevention of osteoporosis. OBJECTIVE: To investigate whether postmenopausal women exhibit postprandial suppression of bone turnover markers to the same extent as premenopausal women, despite higher fasting levels. Furthermore, to assess whether menopausal differences in bone turnover markers are related to postmenopausal changes in plasma gut hormone levels. METHODS: A cross-sectional study of 21 premenopausal, 9 perimenopausal, and 24 postmenopausal women between 45 and 60 years of age. Serum/plasma levels of bone turnover markers and gut hormones were investigated during a 120 min oral glucose tolerance test. Bone turnover markers included N-terminal propeptide of type-I procollagen (PINP, bone formation marker) and carboxyterminal collagen I crosslinks (CTX-I, bone resorption marker). Gut hormone secretion was evaluated from responses of glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2) and glucose-dependent insulinotropic polypeptide (GIP). RESULTS: Fasting levels of s-CTX-I were increased in peri- and postmenopausal women compared to premenopausal women (p = 0.001). Despite higher fasting levels, the relative postprandial s-CTX-I suppression was comparable across menopausal status (p = 0.14). Fasting levels of s-PINP were also increased in postmenopausal women compared to premenopausal women (p < 0.001) with comparable and modest s-PINP suppression over menopause (p = 0.13). Postprandial plasma GLP-1 (p = 0.006) and GLP-2 (p = 0.01) were significantly increased in postmenopausal women compared to premenopausal women while GIP responses were slightly increased in the perimenopausal group (p = 0.02) but comparable between pre- and postmenopausal women. None of the postprandial gut hormone increases predicted postprandial bone turnover suppression in these women. CONCLUSIONS: Glucose-induced suppression of bone turnover markers is preserved in postmenopausal women, despite significantly higher fasting values, indicating that CTX-I lowering treatments based on these postprandial mechanisms might be a feasible strategy to prevent postmenopausal osteoporosis.


Assuntos
Osteoporose Pós-Menopausa , Pós-Menopausa , Biomarcadores , Remodelação Óssea , Colágeno Tipo I , Estudos Transversais , Jejum , Feminino , Humanos
4.
Calcif Tissue Int ; 107(2): 160-169, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32468187

RESUMO

Preclinical studies have shown a potential osteoanabolic effect of metformin but human studies of how metformin affects bone turnover are few. A post hoc sub-study analysis of an 18-month multicenter, placebo-controlled, double-blinded trial in type 2 diabetes mellitus (T2DM), randomizing participants to metformin versus placebo both in combination with different insulin analogue regimens (Metformin + Insulin vs. Placebo + Insulin). Patients were not treatment naive at baseline, 83% had received metformin, 69% had received insulin, 57.5% had received the combination of metformin and insulin before entering the study. Bone formation and resorption were assessed by measuring, N-terminal propeptide of type I procollagen (P1NP) and C-terminal telopeptide of type I collagen (CTX) at baseline and end of study. The influence of gender, age, smoking, body mass index (BMI), T2DM duration, glycosylated hemoglobin A1c (HbA1c), c-reactive protein (CRP) and insulin dosage was also included in the analyses. The levels of bone formation marker P1NP and bone resorption marker CTX increased significantly in both groups during the trial. P1NP increased less in the Metformin + Insulin compared to the placebo + insulin group (p = 0.001) (between group difference change), while the increases in CTX levels (p = 0.11) were not different. CRP was inversely associated (p = 0.012) and insulin dosage (p = 0.011) was positively related with change in P1NP levels. BMI (p = 0.002) and HbA1C (p = 0.037) were inversely associated with change in CTX levels. During 18 months of treatment with metformin or placebo, both in combination with insulin, bone turnover increased in both groups. But the pattern was different as the bone formation marker (P1NP) increased less during Metformin + Insulin treatment, while change in bone resorption (CTX) was not significantly different between the two groups.


Assuntos
Remodelação Óssea/efeitos dos fármacos , Diabetes Mellitus Tipo 2 , Insulina , Metformina , Biomarcadores , Proteína C-Reativa , Colágeno Tipo I , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas , Humanos , Insulina/análogos & derivados , Insulina/uso terapêutico , Metformina/uso terapêutico , Fragmentos de Peptídeos , Peptídeos , Pró-Colágeno
5.
Breast Cancer Res Treat ; 179(3): 699-708, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31707511

RESUMO

PURPOSE: Previous studies have shown that low levels of 25-hydroxyvitamin D (25(OH)D) are associated with a poorer breast cancer survival. The relationship between vitamin D status and breast cancer outcomes is however still debated. The aim of the present study was to investigate the association between 25(OH)D blood levels measured at time of diagnosis and event-free survival (EFS) and overall survival (OS) in a large cohort of patients with early-stage primary invasive breast cancer. METHODS: From April 2008 to April 2013, 25(OH)D status was measured at time of diagnosis in all women operated for early stage primary invasive breast cancer at Rigshospitalet, Copenhagen, Denmark. Associations between 25(OH)D and EFS and OS were investigated using a Cox Proportional hazards model, adjusting for age, disease characteristics, time period, and BMI. Differences in survival were evaluated by hazard ratios (HR). RESULTS: In the present study, 2510 women with primary invasive breast cancer were included. Women with the lowest 25(OH)D levels (≤ 52 nmol/L) had an inferior EFS with a HR of 1.63 (95% CI 1.21-2.19) compared to women in the third quartile (76-99 nmol/L). Women with the highest 25(OH)D levels (≥ 99 nmol/L) also had an inferior EFS with a HR of 1.37 (95% CI 1.02-1.83). Plotting 25(OH)D status against EFS, the association was inversely J-shaped. For OS, a similar association with 25(OH)D status was observed. CONCLUSION: We confirmed previous findings suggesting that a low 25(OH)D status is associated with an inferior breast cancer survival, but unlike previous findings, we found an indication of poorer breast cancer survival also among women with high 25(OH)D levels.


Assuntos
Biomarcadores , Neoplasias da Mama/sangue , Neoplasias da Mama/mortalidade , Vitamina D/análogos & derivados , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Cromatografia Líquida , Terapia Combinada/métodos , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Espectrometria de Massas em Tandem , Resultado do Tratamento , Carga Tumoral , Vitamina D/sangue
6.
Ugeskr Laeger ; 180(32)2018 Aug 06.
Artigo em Dinamarquês | MEDLINE | ID: mdl-30070630

RESUMO

This review discusses two methods of monitoring the effect of anti-osteoporotic treatment: bone mineral density (BMD) and bone turnover markers (BTMs). Both monitoring strategies are to some extent able to predict the treatment-induced change in risk of fracture. The use of BMD is commonplace, and clinicians are experienced in the interpretation of data. The use and knowledge of BTMs among clinicians is limited, but it allows for early testing while being practical and cheap. Further knowledge and implementation of BTMs in the clinical practice may improve the monitoring capabilities.


Assuntos
Biomarcadores/sangue , Conservadores da Densidade Óssea/farmacologia , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Monitoramento de Medicamentos/métodos , Osteoporose/tratamento farmacológico , Densidade Óssea/fisiologia , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea/fisiologia , Colágeno Tipo I/sangue , Humanos , Adesão à Medicação , Osteoporose/metabolismo , Fraturas por Osteoporose/metabolismo , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Pró-Colágeno/sangue , Medição de Risco
7.
Calcif Tissue Int ; 103(4): 359-371, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29909449

RESUMO

This study aimed to describe clinical outcomes in patients prescribed teriparatide and followed up for 18 months after stopping the drug in real-life conditions. The Extended Forsteo® Observational Study analysed incident clinical fractures in 6-month intervals using logistic regression with repeated measures. Changes in back pain (visual analogue scale) and health-related quality of life (HRQoL; EQ-5D questionnaire) were analysed using mixed models for repeated measures. Patients were analysed if they had a post-baseline visit, regardless of whether and for how long they took teriparatide. Of 1531 patients analysed (90.7% female, mean age: 70.3 years), 76 (5.0%) never took teriparatide. Median treatment duration was 23.6 months. The adjusted odds of clinical fracture decreased by 47% in the > 12- to 18-month treatment period (p = 0.013) compared with the first 6-month period, with no statistically significant reduction in the > 18- to 24-month interval. The clinical fracture rate remained stable during the 18 months' post-teriparatide, when approximately 98% of patients took osteoporosis medication (51% bisphosphonates). Clinical vertebral fractures were reduced at every time period compared with the first 6 months. Adjusted mean back pain scores decreased and EQ-5D scores increased significantly at each post-baseline observation. In a real-life clinical setting, the risk of clinical fractures declined during 24 months of teriparatide treatment. This reduction was maintained 18 months after stopping teriparatide. In parallel, patients reported significant improvements in back pain and HRQoL. The results should be interpreted in the context of the non-controlled design of this observational study.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Fraturas Ósseas/prevenção & controle , Osteoporose/tratamento farmacológico , Teriparatida/uso terapêutico , Idoso , Dor nas Costas/etiologia , Feminino , Seguimentos , Fraturas Ósseas/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/complicações , Qualidade de Vida
8.
Arch Osteoporos ; 13(1): 50, 2018 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-29717390

RESUMO

PURPOSE: Medical treatment of osteoporosis should preferably be both effective and have minimal side effects. The aim of the present study was to examine long-term benefits and risks of parathyroid hormone (PTH) treatment in compliant patients. METHODS: This is a nationwide retrospective cohort study based on national registers in which we identified 1739 patients treated with PTH (2003-2010) (index cases) for at least 18 months and with a medication possession rate of > 0.8. For comparison, patients treated with bisphosphonate (BP) (n = 13,131) and anti-osteoporotic treatment-naïve controls (n = 12,721) were selected. Incidence of fractures, drug consumption, and comorbidity were compared between the three cohorts. Mean follow-up of the PTH-treated patients was 4.3 years (range 1.8-8.7 years). RESULTS: Before initiation of treatment, PTH patients had a significantly higher Charlson comorbidity index score and more osteoporotic fractures than both BP patients and controls. No difference was detected in the incidence of fractures during PTH treatment or years after between PTH patients and BP patients. No significant difference in the use of drugs was seen between PTH and BP patients, except for PPI intake which was higher in PTH patients. No significant increases were found in the incidence of cancers or other ICD-10 diagnoses among PTH-treated patients in comparison with both BP and controls. CONCLUSION: Overall, PTH treatment is effective and safe. Following PTH treatment in compliant patients, neither fracture incidence nor drug consumption differed between PTH-treated and BP-treated patients, despite the fact that PTH-treated patients had more severe osteoporosis. No increased incidence of malignant diseases or other diseases was detected.


Assuntos
Hormônios e Agentes Reguladores de Cálcio/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/epidemiologia , Hormônio Paratireóideo/uso terapêutico , Idoso , Dinamarca/epidemiologia , Difosfonatos/uso terapêutico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Osteoporose/complicações , Fraturas por Osteoporose/etiologia , Sistema de Registros , Estudos Retrospectivos
9.
Ther Adv Musculoskelet Dis ; 7(4): 160-8, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26288666

RESUMO

Bisphosphonates (BPs) are widely used as the main treatment for osteoporosis. In vitro and animal studies suggest that use of BPs may have a potential for colorectal cancer (CRC) prevention. Safety and efficacy in terms of osteoporosis prevention have only been evaluated in randomized controlled trials (RCTs) of relatively short duration (3-5 years), with smaller extension studies. The evidence for a benefit beyond 5 years is limited and intake of BPs has not shown any relationship with CRC in intervention studies. Observational studies and meta-analysis have shown unchanged or decreased risk of CRC. BPs used for treatment and prevention of osteoporosis should not be applied for prevention of CRC in clinical practice.

10.
Ugeskr Laeger ; 176(8A): V08130525, 2014 Feb 17.
Artigo em Dinamarquês | MEDLINE | ID: mdl-25350304

RESUMO

This article is based on a systematic literature search and meta-analyses of clinical data regarding effects of bisphosphonates (BP) and denosumab (DS) on preventing skeletal related events (SRE) in patients with bone metastases from solid tumours. Although there are pharmacological differences between the different types of BP no major differences were observed between BP in preventing SRE or in adverse events. Treatment with DS has in three randomised trials showed a greater effect than BP in preventing SRE. The optimal choice of bone-anti-resorptive agent should depend on the patient's general condition, renal function and treatment logistics.


Assuntos
Neoplasias Ósseas , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/complicações , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Denosumab/uso terapêutico , Difosfonatos/uso terapêutico , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Metanálise como Assunto , Neoplasias da Próstata/patologia , Radiografia
12.
J Clin Endocrinol Metab ; 99(10): 3527-30, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24971663

RESUMO

INTRODUCTION: Recent studies show an association between hyponatremia and osteoporosis. We have previously reported a case of severe male osteoporosis due to chronic syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Here, we provide a follow-up on this case after cure of the condition that further supports the causal relationship. THE CASE: A 38-year-old man had been diagnosed with severe osteoporosis most likely due to chronic SIADH. The SIADH was believed to be idiopathic. A magnetic resonance imaging scan, however, revealed a tumor in the sinus, and biopsies showed an esthesioneuroblastoma, immunohistochemically positive for antidiuretic hormone (ADH). After the tumor was removed, ADH and sodium levels normalized. A dual-energy x-ray absorptiometry scan performed 7 months after the patient's last surgery showed a significant spontaneous improvement in bone mineral density in the lumbar vertebrae. CONCLUSION: This case provides evidence for a causal relationship between SIADH and chronic hyponatremia and impaired bone metabolism that can lead to severe secondary osteoporosis. The effect on bone metabolism is at least partially reversible.


Assuntos
Estesioneuroblastoma Olfatório/complicações , Síndrome de Secreção Inadequada de HAD/complicações , Cavidade Nasal , Neoplasias Nasais/complicações , Osteoporose/etiologia , Adulto , Estesioneuroblastoma Olfatório/diagnóstico , Humanos , Hiponatremia/etiologia , Masculino , Imagem Multimodal , Neoplasias Nasais/diagnóstico
13.
Biomed Res Int ; 2014: 176190, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24800209

RESUMO

Background. The aim of this study was to investigate IL-6 and 25-hydroxyvitamin D (25-OH D) associations with muscle size and muscle function in dialysis patients. Methods. Patients were included in a 16-week control period followed by 16 weeks of high-intensity resistance training thrice weekly. IL-6 and 25-OH D were analysed after an over-night fast. Muscle fibre size was analysed in biopsies from m. vastus lateralis. Muscle power was tested using a Leg Extensor Power Rig. Results. Patients (n = 36) with IL-6 ≥ 6.49 pg/ml (median) were older and had decreased muscle power and a reduced protein intake (P < 0.05) compared with patients with IL-6 < 6.49 pg/ml. IL-6 was not associated with muscle fibre size. Vitamin D deficiency (25-OH D < 50 nmol/l) was present in 51% of the patients and not associated with muscle power. IL-6 remained unchanged during the training period, whilst muscle power increased by 20-23% (P < 0.001). Conclusion. Elevated IL-6 values were associated with decreased muscle power but not with decreased muscle fibre size. Half of the patients were suffering from vitamin D deficiency, which was not associated with muscle power. IL-6 was unchanged by high-intensity resistance training in dialysis patients in this study.


Assuntos
Interleucina-6/sangue , Músculo Esquelético/fisiopatologia , Nefrite/fisiopatologia , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/terapia , Treinamento Resistido/métodos , Vitamina D/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular , Músculo Esquelético/patologia , Nefrite/complicações , Nefrite/prevenção & controle , Tamanho do Órgão , Insuficiência Renal Crônica/complicações , Resultado do Tratamento
14.
J Bone Miner Res ; 28(3): 455-63, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23044864

RESUMO

Ocular inflammatory reactions have been described in patients on bisphosphonate treatment. We estimated the incidence rate of ocular inflammation at 3 and 12 months in patients treated for osteoporosis using a register-based cohort linked to prescription data (hospitals and private practice) and hospital data. From January 1, 1997 to December 31, 2007, a total of 88,202 patients beginning osteoporosis therapy were identified. Of those patients, 82,404 (93%) began oral bisphosphonates and 5798 (7%) nonbisphosphonates. Within the first year of treatment, 4769 (5.4%) of patients on osteoporosis therapy filled one or more prescriptions for topical eye steroids (TES). TES treatment rates (per 1000 patient-years) in the first year of osteoporosis treatment were 44 (95% confidence interval [CI] 42 to 46) for alendronate, 40 (95% CI 38 to 43) for etidronate, 45 (95% CI 35 to 57) for risedronate, 32 (95% CI 27 to 37) for raloxifene, and 64 (95% CI 49 to 83) for strontium ranelate. After adjustment for age, Charlson index, and the number of comedications, pulmonary disease in men was associated with an increased use of TES (odds ratio [OR] = 1.48; 95% CI 1.17 to 1.86; p = 0.001). In women, malignant disease (OR = 1.27; 95% CI 1.02 to 1.60; p = 0.04) and pulmonary disease (OR = 1.32; 95% CI 1.07 to 1.62; p = 0.01) were significant predictors at 3 months and rheumatic diseases at 12 months (OR = 1.20; 95% CI 1.10 to 1.31; p < 0.001). There was no significant difference between the different drug classes (bisphosphonates versus nonbisphosphonates, alendronate versus nonalendronate-bisphosphonates) for risk of ocular inflammation, with age and the number of comedications being the only significant predictors. Hospital-treated uveitis (48 patients, or 0.05%) showed a similar trend. In conclusion, after initiation of treatment for osteoporosis, the risk of inflammatory eye reactions requiring TES is relatively low and not significantly different between bisphosphonate and nonbisphosphonate users. Patients with a rheumatic or pulmonary disease are at increased risk.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Bases de Dados Factuais , Difosfonatos/uso terapêutico , Prescrições de Medicamentos , Oftalmopatias/induzido quimicamente , Osteoporose/tratamento farmacológico , Estudos de Coortes , Difosfonatos/efeitos adversos , Feminino , Humanos , Masculino
15.
Ugeskr Laeger ; 174(47): 2926-30, 2012 Nov 19.
Artigo em Dinamarquês | MEDLINE | ID: mdl-23171789

RESUMO

Both chronic kidney disease and osteoporosis are frequent conditions in the general population. Most drugs for treating osteoporosis seem safe in terms of affecting renal function for patients with mildly to moderate decreased renal function. There are very few data on the efficacy (reduction in fracture risk) or safety in patients with severely decreased renal function (glomerular filtration rate < 30 ml/min) or on dialysis.


Assuntos
Osteoporose/tratamento farmacológico , Insuficiência Renal/complicações , Idoso , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/farmacocinética , Cálcio/metabolismo , Difosfonatos/administração & dosagem , Difosfonatos/efeitos adversos , Difosfonatos/farmacocinética , Feminino , Fraturas Espontâneas/diagnóstico por imagem , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/metabolismo , Taxa de Depuração Metabólica , Osteoporose/complicações , Osteoporose/metabolismo , Fraturas por Osteoporose/diagnóstico por imagem , Hormônio Paratireóideo/administração & dosagem , Hormônio Paratireóideo/efeitos adversos , Hormônio Paratireóideo/farmacocinética , Ligante RANK/administração & dosagem , Ligante RANK/efeitos adversos , Ligante RANK/farmacocinética , Radiografia , Diálise Renal , Insuficiência Renal/metabolismo , Moduladores Seletivos de Receptor Estrogênico/administração & dosagem , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Moduladores Seletivos de Receptor Estrogênico/farmacocinética , Estrôncio/administração & dosagem , Estrôncio/efeitos adversos , Estrôncio/farmacocinética
16.
BMJ ; 345: e6409, 2012 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-23048011

RESUMO

OBJECTIVE: To investigate the long term effect of hormone replacement therapy on cardiovascular outcomes in recently postmenopausal women. DESIGN: Open label, randomised controlled trial. SETTING: Denmark, 1990-93. PARTICIPANTS: 1006 healthy women aged 45-58 who were recently postmenopausal or had perimenopausal symptoms in combination with recorded postmenopausal serum follicle stimulating hormone values. 502 women were randomly allocated to receive hormone replacement therapy and 504 to receive no treatment (control). Women who had undergone hysterectomy were included if they were aged 45-52 and had recorded values for postmenopausal serum follicle stimulating hormone. INTERVENTIONS: In the treatment group, women with an intact uterus were treated with triphasic estradiol and norethisterone acetate and women who had undergone hysterectomy received 2 mg estradiol a day. Intervention was stopped after about 11 years owing to adverse reports from other trials, but participants were followed for death, cardiovascular disease, and cancer for up to 16 years. Sensitivity analyses were carried out on women who took more than 80% of the prescribed treatment for five years. MAIN OUTCOME MEASURE: The primary endpoint was a composite of death, admission to hospital for heart failure, and myocardial infarction. RESULTS: At inclusion the women on average were aged 50 and had been postmenopausal for seven months. After 10 years of intervention, 16 women in the treatment group experienced the primary composite endpoint compared with 33 in the control group (hazard ratio 0.48, 95% confidence interval 0.26 to 0.87; P=0.015) and 15 died compared with 26 (0.57, 0.30 to 1.08; P=0.084). The reduction in cardiovascular events was not associated with an increase in any cancer (36 in treated group v 39 in control group, 0.92, 0.58 to 1.45; P=0.71) or in breast cancer (10 in treated group v 17 in control group, 0.58, 0.27 to 1.27; P=0.17). The hazard ratio for deep vein thrombosis (2 in treated group v 1 in control group) was 2.01 (0.18 to 22.16) and for stroke (11 in treated group v 14 in control group) was 0.77 (0.35 to 1.70). After 16 years the reduction in the primary composite outcome was still present and not associated with an increase in any cancer. CONCLUSIONS: After 10 years of randomised treatment, women receiving hormone replacement therapy early after menopause had a significantly reduced risk of mortality, heart failure, or myocardial infarction, without any apparent increase in risk of cancer, venous thromboembolism, or stroke. TRIAL REGISTRATION: ClinicalTrials.gov NCT00252408.


Assuntos
Insuficiência Cardíaca/mortalidade , Terapia de Reposição Hormonal/mortalidade , Infarto do Miocárdio/mortalidade , Neoplasias/mortalidade , Neoplasias da Mama/mortalidade , Anticoncepcionais Orais Sintéticos/uso terapêutico , Dinamarca/epidemiologia , Estradiol/uso terapêutico , Estrogênios/uso terapêutico , Feminino , Hormônio Foliculoestimulante/sangue , Seguimentos , Terapia de Reposição Hormonal/efeitos adversos , Terapia de Reposição Hormonal/métodos , Hospitalização , Humanos , Pessoa de Meia-Idade , Noretindrona/análogos & derivados , Noretindrona/uso terapêutico , Acetato de Noretindrona , Pós-Menopausa , Estudos Prospectivos , Risco , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo , Resultado do Tratamento , Trombose Venosa/mortalidade
17.
Eur J Endocrinol ; 167(4): 553-60, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22875588

RESUMO

OBJECTIVE: To investigate the relationship between vitamin D status in healthy women and cardiovascular outcome. DESIGN AND METHODS: Between 1990 and 1993, 2016 healthy, recently postmenopausal women were enrolled in the Danish Osteoporosis Prevention Study. Serum levels of 25-hydroxyvitamin D (25(OH)D, nmol/l) were measured at baseline. Participants were followed for 16 years. The primary end point was a combination of death, heart failure, myocardial infarction (MI) and stroke. Vitamin D deficiency was defined as serum 25(OH)D<50 nmol/l. The primary end point was adjusted for other risk factors of adverse cardiovascular events (age, smoking, blood pressure, hip-waist ratio, education and family history of MI). RESULTS: At baseline, mean age was 50 years and BMI 25. Women with vitamin D deficiency (n=788) had more cardiovascular risk factors than vitamin D-replete women (n=1225). Compared with vitamin D-replete women, women with low 25(OH)D levels had significantly higher BMI and triglycerides, lower HDL and hip-waist ratio and less education. More were smokers among the vitamin D deficient (47 vs 38%). A primary end point was experienced by 118 (15%) with vitamin D deficiency and by 125 (10%) of the vitamin D replete. Hazard ratio (HR) was 1.49 (95% confidence interval: 1.16-1.92; P=0.002) in the vitamin D deficient. Adjusted HR was 1.32 (1.02-1.71; P=0.03). In total, 135 women died; of these, 65 (8%) were of the vitamin D deficient and 70 (6%) in the vitamin D-replete group; unadjusted HR was 1.44 (1.02-2.01; P=0.04) for vitamin D deficiency. CONCLUSION: Healthy women with vitamin D deficiency have increased risk of adverse cardiovascular outcome.


Assuntos
Doenças Cardiovasculares/diagnóstico , Pós-Menopausa , Deficiência de Vitamina D/complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Ensaios Clínicos como Assunto , Terapia de Reposição de Estrogênios , Feminino , Seguimentos , Saúde , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/sangue , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/epidemiologia , Osteoporose Pós-Menopausa/prevenção & controle , Pós-Menopausa/fisiologia , Prognóstico , Fatores de Risco , Análise de Sobrevida , Fatores de Tempo , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia
18.
J Bone Miner Res ; 27(3): 679-86, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22113985

RESUMO

Recent studies have reached conflicting conclusions regarding the risk of esophageal cancer with oral bisphosphonates. Prior studies did not record the number of cancer deaths or endoscopy rates, which could be higher in bisphosphonate users and lead to more cancers being diagnosed at a stage when their esophageal or gastric location could be accurately distinguished. We conducted a register-based, open cohort study using national healthcare data for Denmark. Upper endoscopy frequency, cancer incidence and mortality was examined in 30,606 alendronate users (female, age 50+) and 122,424 matched controls. Primary outcomes were esophageal cancer incidence and death because of esophageal cancer. The analysis showed that alendronate users were more likely to have undergone recent upper endoscopy (4.1 versus 1.7%, p < 0.001). Alendronate users had a lower risk of incident gastric cancer [odds ratio (OR) 0.61; 95% confidence interval (CI): 0.39-0.97) and no increased risk of esophageal cancer (OR 0.71; 95% CI: 0.43-1.19). Risk reductions were greater in users with 10+ prescriptions. The risk of dying of esophageal cancer was significantly reduced in alendronate users after 3 years OR 0.45 (95% CI: 0.22-0.92) but not after 9 years (OR 1.01; 95% CI: 0.52-1.95). An additional comparison with etidronate users revealed no statistically significant difference in outcomes. In conclusion, we found no excess in esophageal cancer deaths or incidence. The early decrease in esophageal cancer rates may relate to the greater use of endoscopy before starting alendronate. Longer term observations also indicated no excess risk of esophageal cancer death and a significantly decreased risk of gastric cancer death.


Assuntos
Alendronato/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Esofágicas/epidemiologia , Neoplasias Gástricas/epidemiologia , Adulto , Idoso , Alendronato/efeitos adversos , Conservadores da Densidade Óssea/efeitos adversos , Dinamarca/epidemiologia , Neoplasias Esofágicas/mortalidade , Ácido Etidrônico/uso terapêutico , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Neoplasias Gástricas/mortalidade
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