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OBJECTIVE: Osteoporosis and fractures are frequently encountered in patients with Crohn's disease. In order to prevent fractures, treatment with bone protecting drugs appears warranted early in the course of bone disease when bone loss is not yet prominent. We therefore aimed to demonstrate a beneficial effect on bone density of the bisphosphonate risedronate in osteopenic Crohn's disease patients. METHODS: This double-blind, placebo-controlled randomised trial of risedronate with calcium and vitamin D supplementation was performed in osteopenic Crohn's disease patients. Patients were treated for 2â years with follow-up after 3 and after every 6â months. Disease characteristics and activity and bone turnover markers were assessed at all visits; dual x-ray absorptiometry was performed at baseline, 12 and 24â months; radiographs of the spine at baseline and 24â months. RESULTS: Of 132 consenting patients, 131 were randomised (67 placebo and 64 risedronate). Patient characteristics were similar in both groups, although the risedronate group was slightly heavier (body mass index 24.3 vs 23.0â kg/m(2)). Bone mineral density at lumbar spine increased 0.04â g/cm(2) on average in the risedronate group versus 0.01â g/cm(2) in the placebo group (p=0.007). The mean increase in total hip bone mineral density was 0.03 versus 0.01â g/cm(2), respectively (p=0.071). Fracture prevalence and incidence were similar. Change of T-scores and concentrations of bone turnover markers were consistent with a beneficial effect of risedronate when compared with placebo. The effect of risedronate was primarily demonstrated in the first 12â months of treatment. No serious unexpected suspected adverse events were observed. CONCLUSIONS: A 24-month treatment course with risedronate 35â mg once weekly, concomitant with calcium and vitamin D supplementation, in osteopenic Crohn's disease patients improved bone density at lumbar spine. NTR 163 Dutch Trial Register.
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Conservadores da Densidade Óssea/uso terapêutico , Doenças Ósseas Metabólicas/tratamento farmacológico , Cálcio/uso terapêutico , Doença de Crohn/complicações , Suplementos Nutricionais , Ácido Etidrônico/análogos & derivados , Vitamina D/uso terapêutico , Absorciometria de Fóton , Adulto , Densidade Óssea , Doenças Ósseas Metabólicas/diagnóstico por imagem , Doenças Ósseas Metabólicas/etiologia , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Ácido Etidrônico/uso terapêutico , Feminino , Seguimentos , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ácido Risedrônico , Resultado do TratamentoRESUMO
Fractures may be associated with higher morbidity in obese postmenopausal women than in nonobese women. We compared health-care utilization, functional status, and health-related quality of life (HRQL) in obese, nonobese, and underweight women with fractures. Information from the GLOW study, started in 2006, was collected at baseline and at 1, 2, and 3 years. In this subanalysis, self-reported incident clinical fractures, health-care utilization, HRQL, and functional status were recorded and examined. Women in GLOW (n = 60,393) were aged ≥55 years, from 723 physician practices at 17 sites in 10 countries. Complete data for fracture and body mass index were available for 90 underweight, 3,270 nonobese, and 941 obese women with one or more incident clinical fractures during the 3-year follow-up. The median hospital length of stay, adjusted for age, comorbidities, and fracture type, was significantly greater in obese than nonobese women (6 vs. 5 days, p = 0.017). Physical function and vitality score were significantly worse in obese than in nonobese women, both before and after fracture; but changes after fracture were similar across groups. Use of antiosteoporosis medication was significantly lower in obese than in nonobese or underweight women. In conclusion, obese women with fracture undergo a longer period of hospitalization for treatment and have poorer functional status and HRQL than nonobese women. Whether these differences translate into higher economic costs and adverse effects on longer-term outcomes remains to be established.
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Recursos em Saúde/estatística & dados numéricos , Obesidade/epidemiologia , Osteoporose Pós-Menopausa/epidemiologia , Fraturas por Osteoporose/epidemiologia , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Feminino , Nível de Saúde , Humanos , Tempo de Internação/estatística & dados numéricos , Estudos Longitudinais , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/terapia , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/terapia , Fraturas por Osteoporose/complicações , Fraturas por Osteoporose/terapia , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: Patients with osteoarthritis have increased bone mass but no decrease in fractures. The association between self-reported osteoarthritis and incident falls and fractures was studied in postmenopausal women. METHODS: The Global Longitudinal Study of Osteoporosis in Women is a prospective multinational cohort of 60,393 non-institutionalised women aged ≥55 years who had visited primary care practices within the previous 2 years. Questionnaires were mailed at yearly intervals. Patients were classified as having osteoarthritis if they answered yes to the question, 'Has a doctor or other health provider ever said that you had osteoarthritis or degenerative joint disease?', and this was validated against primary care records in a subsample. Information on incident falls, fractures and covariates was self-reported. Cox and Poisson models were used for incident fractures and number of falls, respectively, to compute hazard ratios (HRs) and rate ratios (RRs) for baseline osteoarthritis status. RESULTS: Of 51 386 women followed for a median of 2.9 years (interquartile range 2.1-3.0), 20 409 (40%) reported osteoarthritis. The adjusted HR for osteoarthritis predicting fracture was 1.21 (95% CI 1.13 to 1.30; p<0.0001) and the adjusted RR for falls was 1.24 (95% CI 1.22 to 1.26; p<0.0001). However, the association between osteoarthritis and fracture was not significant after adjustment for incident falls (HR 1.06 (95% CI 0.98 to 1.15; p=0.13)). CONCLUSIONS: Postmenopausal women with self-reported osteoarthritis have a 20% increased risk of fracture and experience 25% more falls than those without osteoarthritis. These data suggest that increased falls are the causal pathway of the association between osteoarthritis and fractures.
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Acidentes por Quedas/estatística & dados numéricos , Fraturas Ósseas/epidemiologia , Osteoartrite/epidemiologia , Pós-Menopausa , Idoso , Estudos de Coortes , Feminino , Seguimentos , Humanos , Incidência , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Distribuição de Poisson , Prevalência , Modelos de Riscos Proporcionais , Estudos Prospectivos , Risco , Autorrelato , Inquéritos e QuestionáriosRESUMO
BACKGROUND & AIMS: Crohn's disease (CD) is associated with an increased prevalence of osteoporosis, but the pathogenesis of this bone loss is only partly understood. We assessed bone structure and remodeling at the tissue level in patients with quiescent CD. We also investigated the roles of osteocyte density and apoptosis in CD-associated bone loss. METHODS: The study included 23 patients with quiescent CD; this was a subgroup of patients from a large randomized, double-blind, placebo-controlled, multicenter trial. We obtained transiliac bone biopsy samples and performed histomorphometric analysis. Results were compared with data from age- and sex-matched healthy individuals (controls). RESULTS: Trabecular bone volume was decreased among patients with CD compared with controls (18.90% vs 25.49%; P < .001). The low bone volume was characterized by decreased trabecular thickness (120.61 vs 151.42 µm; P < .01). Bone formation and resorption were reduced, as indicated by a decreased mineral apposition rate (0.671 vs 0.746 µm/day; P < .01) and a low osteoclast number and surface area compared with controls and published values, respectively. In trabecular bone of patients with CD, osteocyte density and apoptosis were normal. The percentage of empty lacunae among patients was higher than that of published values in controls. CONCLUSIONS: In adult patients with quiescent CD, bone histomorphometric analysis revealed a reduction in bone mass that was characterized by trabecular thinning. The CD-associated bone loss was caused by reduced bone formation, possibly as a consequence of decreased osteocyte viability in the patients' past.
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Densidade Óssea , Reabsorção Óssea/patologia , Doença de Crohn/patologia , Osteogênese , Adulto , Apoptose , Biópsia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Osteoclastos/patologia , Osteócitos/patologia , Osteoporose/patologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Using [18F] Sodium Fuoride (NaF) Positron Emission Tomography (PET) it is not only possible to identify the ossifying potency of a flare-up, but also to identify an asymptomatic chronic stage of fibrodysplasia ossificans progressiva (FOP). The purpose of this study was to investigate the diagnostic role of a more widely available imaging modality, Magnetic Resonance Imaging (MRI), which is of special interest for studies in pediatric FOP patients. MRI and [18F]NaF PET/CT images at time of inclusion and subsequent follow-up CT scans of 4 patients were analyzed retrospectively. Presence, location, and intensity of edema identified by MRI were compared with activity on [18F]NaF PET. Occurrence or progression of heterotopic ossification (HO) was examined on the follow-up CT images. Thirteen different lesions in various muscle groups were identified: five lesions with only edema, five lesions with both edema and increased [18F]NaF uptake, one lesion with only increased [18F]NaF uptake, and two lesions with neither edema nor uptake of [18F]NaF. Mild edema, found in three lesions, was present at asymptomatic sites, which did not show increased [18F] NaF uptake or progression of HO on consecutive CT images. Moderate edema was found in three symptomatic lesions, with increased [18F]NaF on PET and progression of HO on CT. Severe edema was identified in four lesions. Interestingly, two of these lesions did not develop HO during follow-up; one of these two even gave obvious symptoms of a flare-up. MRI can identify whether symptoms are the result of an acute flare-up by the presence of moderate to severe edema. The occurrence of severe edema on MRI was not always related to an ossifying lesion. The additional diagnostic value of MRI requires further investigation, but MRI does not seem to fully replace the diagnostic characteristics of [18F]NaF PET/CT in FOP. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
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In the field of rare bone diseases in particular, a broad care team of specialists embedded in multidisciplinary clinical and research environment is essential to generate new therapeutic solutions and approaches to care. Collaboration among clinical and research departments within a University Medical Center is often difficult to establish, and may be hindered by competition and non-equivalent cooperation inherent in a hierarchical structure. Here we describe the "collaborative organizational model" of the Amsterdam Bone Center (ABC), which emerged from and benefited the rare bone disease team. This team is often confronted with pathologically complex and under-investigated diseases. We describe the benefits of this model that still guarantees the autonomy of each team member, but combines and focuses our collective expertise on a clear shared goal, enabling us to capture synergistic and innovative opportunities for the patient, while avoiding self-interest and possible harmful competition.
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Doenças Ósseas/terapia , Comportamento Cooperativo , Atenção à Saúde/organização & administração , Relações Interprofissionais , Equipe de Assistência ao Paciente/organização & administração , Melhoria de Qualidade/organização & administração , Doenças Raras/terapia , Humanos , Motivação , Países BaixosRESUMO
Steroid hormones have been implicated in the growth and/or development of meningiomas. A 46, XX male with untreated congenital adrenal hyperplasia who developed meningiomas is presented here. The meningiomas only expressed progesterone receptors, as most meningiomas do. The high 17-hydroxyprogesterone levels, resulting from his disease, could have played a role in the development and growth of his meningiomas.
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Hiperplasia Suprarrenal Congênita/complicações , Hiperplasia Suprarrenal Congênita/fisiopatologia , Neoplasias Meníngeas/etiologia , Meningioma/etiologia , Hiperplasia Suprarrenal Congênita/genética , Humanos , Masculino , Neoplasias Meníngeas/terapia , Meningioma/terapia , Pessoa de Meia-IdadeRESUMO
Population screening for fracture risk may reduce the fracture incidence. In this randomized pragmatic trial, the SALT Osteoporosis Study (SOS), we studied whether screening for fracture risk and subsequent treatment in primary care can reduce fractures compared with usual care. A total of 11,032 women aged 65 to 90 years with ≥1 clinical risk factor for fractures were individually randomized to screening (n = 5575) or usual care (n = 5457). Participants in the screening group underwent a screening program, including bone densitometry and vertebral fracture assessment. Participants with a high 10-year fracture probability (FRAX) or a vertebral fracture were offered treatment with anti-osteoporosis medication by their general practitioner. Incident fractures as reported by questionnaires were verified with medical records. Follow-up was completed by 94% of the participants (mean follow-up = 3.7 years). Of the 5575 participants in the screening group, 1417 (25.4%) had an indication for anti-osteoporosis medication. Screening and subsequent treatment had no statistically significant effect on the primary outcome fracture (hazard ratio [HR] = 0.97; 95% confidence interval [CI] 0.87-1.08), nor on the secondary outcomes osteoporotic fractures (HR = 0.91; 95% CI 0.81-1.03), major osteoporotic fractures (HR = 0.91; 95% CI 0.80-1.04), hip fractures (HR = 0.91; 95% CI 0.71-1.15), falls (odds ratio [OR] = 0.91; 95% CI 0.72-1.15), or mortality (HR = 1.03; 95% CI 0.91-1.17). Post hoc explorative finding suggested that screening might be most effective after a recent fracture (HR = 0.65; 95% CI 0.44-0.96 for major osteoporotic fractures and HR = 0.38; 95% CI 0.18-0.79 for hip fractures). The results of this study might have been compromised by nonparticipation and medication nonadherence in the screening group. Overall, this study does not provide sufficient indications to consider screening for fracture prevention. However, we cannot exclude its clinical relevance to reduce (major) osteoporotic fractures and hip fractures because of the relatively small number of women with a treatment indication in the intervention group. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.
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Fraturas do Quadril , Programas de Rastreamento , Osteoporose , Fraturas por Osteoporose , Inquéritos e Questionários , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/prevenção & controle , Humanos , Osteoporose/diagnóstico , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/prevenção & controleRESUMO
Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder leading to progressive heterotopic ossifications (HO) of muscles, tendons, and ligaments, which can be induced by trauma or by surgery. Despite strong medical advice to the contrary, an FOP patient insisted on surgery to alleviate her complete trismus, which caused an unbearable impact on her quality of life (QOL). The entire trismus history of this FOP patient is presented. [18F]-NaF position emission tomography/computed tomography (PET/CT) scans were introduced as an imaging method for heterotopic bone formation activity. To place our findings into context, a systematic review on jaw surgery in FOP was performed. After falling down the stairs, a 9-year-old patient developed mobility impairment of her left-sided jaw. During the following 13 years bone scintigraphy showed persistent activity of the disease leading to progressive left-sided zygomatico-mandibular fusion by HO, resulting in complete trismus. Within 1 month after HO removal on the left side and a matching right coronoidectomy, [18F]-NaF PET/CT demonstrated a substantial flare-up activity followed by new HO in both masseter and temporalis muscles. Despite recurrent HO and trismus her QOL increased due to a stable increased interincisal opening of 5.5 mm. Although systematic review reveals a 100% risk of HO recurrence after jaw surgery, information on improved QOL is scarce. In conclusion, surgery in FOP may be beneficial for QOL despite new HO formation. Assessment of disease activity using [18F]-NaF PET/CT is possible before HO is evident on CT and may serve as a new and quantitative marker of the disease. © 2017 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
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CONTEXT: A middle-aged woman with recent-onset painful swollen fingers and widespread periostitis, elevated serum alkaline phosphatase (ALP) activity and erythrocyte sedimentation rate, and accelerated skeletal turnover was found not to have mutations in the gene sequences for exon 1 of receptor activator of nuclear factor-kappaB (RANK), osteoprotegerin (OPG), or sequestosome-1. INTRODUCTION: Hyperphosphatasia refers to disorders that feature elevated serum ALP activity (hyperphosphatasemia) usually from excesses of the bone isoform of ALP. Such conditions include familial expansile osteolysis, expansile skeletal hyperphosphatasia, and a familial form of early-onset Paget's disease of bone (PDB2), all from constitutive activation of RANK, and juvenile Paget's disease from OPG deficiency. PATIENT AND METHODS: A 38-yr-old woman developed painful swollen fingers and achy bones after an episode of unexplained pericarditis and restrictive lung disease. Sequence analysis of exon 1 of TNFRSF11A encoding RANK, TNFRSF11B encoding OPG, and SQSTM1 encoding sequestosome-1 searched for mutations responsible for familial expansile osteolysis, expansile skeletal hyperphosphatasia, or PDB2, juvenile Paget's disease, or Paget's disease of bone (PDB), respectively. RESULTS: Serum ALP and osteocalcin and urinary hydroxyproline were increased. Radiographs showed widespread, symmetric hyperostosis in the limbs where bone scintigraphy demonstrated enhanced radionuclide uptake. Iliac crest histology revealed accelerated skeletal turnover. No mutations were detected in the three genes examined. Three years of therapy with 70 mg alendronate orally once weekly improved symptoms, radiographic abnormalities, and biochemical markers. CONCLUSIONS: Our patient manifested a unique, sporadic hyperphosphatasia syndrome. Unexplained, transient inflammation seemed to cause her pericarditis, restrictive lung disease, and periostitis with accelerated skeletal turnover that responded well to antiinflammatory drugs and alendronate therapy.
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Proteínas Adaptadoras de Transdução de Sinal/genética , Fosfatase Alcalina/metabolismo , Osso e Ossos/metabolismo , Osteoprotegerina/genética , Periostite/complicações , Receptor Ativador de Fator Nuclear kappa-B/genética , Adulto , Fosfatase Alcalina/sangue , Biomarcadores , Conservadores da Densidade Óssea/uso terapêutico , Osso e Ossos/diagnóstico por imagem , Feminino , Dedos/diagnóstico por imagem , Dedos/patologia , Humanos , Inflamação/patologia , Dor/etiologia , Radiografia , Cintilografia , Proteína Sequestossoma-1 , SíndromeRESUMO
Increased fracture risk has been associated with weight loss in postmenopausal women, but the time course over which this occurs has not been established. The aim of this study was to examine the effects of unintentional weight loss of ≥10 lb (4.5 kg) in postmenopausal women on fracture risk at multiple sites up to 5 years after weight loss. Using data from the Global Longitudinal Study of Osteoporosis in Women (GLOW), we analyzed the relationships between self-reported unintentional weight loss of ≥10 lb at baseline, year 2, or year 3 and incident clinical fracture in the years after weight loss. Complete data were available in 40,179 women (mean age ± SD 68 ± 8.3 years). Five-year cumulative fracture rate was estimated using the Kaplan-Meier method, and adjusted hazard ratios for weight loss as a time-varying covariate were calculated from Cox multiple regression models. Unintentional weight loss at baseline was associated with a significantly increased risk of fracture of the clavicle, wrist, spine, rib, hip, and pelvis for up to 5 years after weight loss. Adjusted hazard ratios showed a significant association between unintentional weight loss and fracture of the hip, spine, and clavicle within 1 year of weight loss, and these associations were still present at 5 years. These findings demonstrate increased fracture risk at several sites after unintentional weight loss in postmenopausal women. This increase is found as early as 1 year after weight loss, emphasizing the need for prompt fracture risk assessment and appropriate management to reduce fracture risk in this population. © 2016 American Society for Bone and Mineral Research.
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Fraturas Ósseas/epidemiologia , Pós-Menopausa , Redução de Peso , Idoso , Feminino , Seguimentos , Fraturas Ósseas/etiologia , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Fatores de TempoRESUMO
OBJECTIVE: To compare the 2-year effects of raloxifene (Rlx) with oral postmenopausal hormone therapy (HT) on serum markers of brain and whole-body cholesterol metabolism. METHODS: In a randomized, double-blind, placebo-controlled trial, 95 healthy, non-hysterectomized, early postmenopausal women received either daily Rlx 60 mg (n = 24), Rlx 150 mg (n = 23), HT (conjugated equine estrogens 0.625 mg/medroxyprogesterone acetate 2.5 mg; n = 24), or placebo (n = 24). Fasting blood samples were collected at baseline and after 6, 12, and 24 months of treatment for measurement of serum concentrations of cholesterol by means of gas-liquid chromatography; 24S-hydroxycholesterol (cerebrosterol), lathosterol, and the plant sterol campesterol by means of gas-liquid chromatography-mass spectrometry. The analyses were performed retrospectively from serum samples stored at -70 degrees C for 5 years. RESULTS: Twenty-four months of treatment with raloxifene 150 mg was associated with a significant reduction in serum cholesterol concentrations (-10%, P = 0.007). The ratio of 24S-hydroxycholesterol to cholesterol, a serum marker of brain cholesterol metabolism, showed a significant increase after 6 and 12 months with raloxifene 150 mg but not after 24 months (P = 0.001). The ratio of lathosterol to cholesterol, a marker of whole-body cholesterol synthesis, increased with raloxifene 60 mg (P = 0.163), raloxifene 150 mg (P < 0.001), as well as with HT (P = 0.005). The ratio of campesterol to cholesterol, a marker of cholesterol absorption rate, was significantly reduced with HT (P = 0.002). CONCLUSION: Two-year treatment with raloxifene or HT had no influence on brain cholesterol metabolism, while whole-body cholesterol synthesis, assessed by the ratio of lathosterol to cholesterol, increased during raloxifene and HT.
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Doença de Alzheimer/prevenção & controle , Encéfalo/efeitos dos fármacos , Colesterol/metabolismo , Terapia de Reposição de Estrogênios , Cloridrato de Raloxifeno/farmacologia , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Doença de Alzheimer/sangue , Biomarcadores/sangue , Biomarcadores/metabolismo , Encéfalo/metabolismo , Colesterol/sangue , Método Duplo-Cego , Estrogênios Conjugados (USP)/administração & dosagem , Estrogênios Conjugados (USP)/farmacologia , Feminino , Humanos , Hidroxicolesteróis/sangue , Hidroxicolesteróis/metabolismo , Acetato de Medroxiprogesterona/administração & dosagem , Acetato de Medroxiprogesterona/farmacologia , Pessoa de Meia-Idade , Pós-Menopausa , Cloridrato de Raloxifeno/uso terapêutico , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Resultado do TratamentoRESUMO
The efficacy and safety of oral pamidronate was examined in a double-blind, placebo-controlled trial in women and men with established osteoporosis. Seventy-eight postmenopausal women and 23 men with at least one prevalent vertebral fracture were randomized separately to 150 mg/day of pamidronate or placebo for 3 years followed by 150 mg/day of pamidronate for an additional 2 years. In addition, all patients received 400 U/day of cholecalciferol and 500 mg/day of elemental calcium. Pamidronate increased significantly bone mineral density of the lumbar spine (LS-BMD) and of the femoral neck (FN-BMD). The total increase in BMD of the spine after 5 years of treatment was 14.3%. Lateral spine radiographs were obtained at baseline and after 3 years of treatment. Fractures of previously normal vertebrae occurred in 15 of 45 patients treated with placebo (33.3%) and in 5 of 46 patients treated with pamidronate (11%). The relative risk was 0.33 (95% CI, 0.14-0.77). Treatment was well tolerated and there was no difference in gastrointestinal toxicity between pamidronate and placebo-treated patients. One hundred fifty milligrams daily of pamidronate is an effective and safe treatment of women and men with established osteoporosis.
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Difosfonatos/uso terapêutico , Osteoporose/tratamento farmacológico , Administração Oral , Idoso , Densidade Óssea , Difosfonatos/administração & dosagem , Difosfonatos/efeitos adversos , Método Duplo-Cego , Feminino , Quadril/patologia , Humanos , Vértebras Lombares/patologia , Masculino , Osteoporose/patologia , Pamidronato , PlacebosRESUMO
Estrogens may affect the essential n-6 and n-3 fatty acids arachidonic acid (AA; C20:4n-6) and docosahexaenoic acid (DHA; C22:6n-3). Therefore, we investigated the long-term effects of hormone replacement therapy and raloxifene, a selective estrogen-receptor modulator, in two randomized, double-blind, placebo-controlled studies. In study I, 95 healthy, non-hysterectomized, early postmenopausal women (age range 47-59 years) received one of the following treatments: daily raloxifene 60 mg (n=24), daily raloxifene 150 mg (n=23), 0.625 mg conjugated equine estrogens (CEE) plus 2.5 mg medroxyprogesterone acetate (MPA; n=24), or placebo (n=24). In study II, 30 men (age range 60-69 years) received daily 120 mg raloxifene (n=15) or placebo (n=15). In study I, plasma cholesteryl ester fatty acids were measured at baseline and after 6, 12, and 24 months in 83 (drop out rate 13%), 73 (23%), and 70 (25%) women respectively. In study II, fatty acids were measured at baseline and after 3 months in 29 men (drop out rate 3%). In postmenopausal women, administration of 150 mg raloxifene increased AA by a mean of +6.1% (P=0.055, not significant). Administration of CEE plus MPA increased AA by +14.1% (P<0.0005). Mean changes in DHA were +22.1% (P=0.003) and +14.9% (P=0.047) respectively, as compared with placebo. In men, 120 mg raloxifene for 3 months did not significantly affect AA (-5.2%; P=0.342) or DHA (+4.0%; P=0.755), but it increased testosterone levels by +19.8% (P=0.006). Administration of raloxifene 150 mg/day as well as CEE plus MPA to postmenopausal women increases the proportion of AA and DHA in plasma cholesteryl esters during a follow-up of 2 years. Short term administration of raloxifene in elderly men did not affect AA or DHA. The synthesis of AA and DHA from precursors may be enhanced through an estrogen receptor-dependent pathway.
Assuntos
Ácido Araquidônico/sangue , Ácidos Docosa-Hexaenoicos/sangue , Terapia de Reposição de Estrogênios , Pós-Menopausa/sangue , Cloridrato de Raloxifeno/uso terapêutico , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Idoso , Análise de Variância , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Hormônio Luteinizante/sangue , Masculino , Acetato de Medroxiprogesterona/uso terapêutico , Pessoa de Meia-Idade , Fatores Sexuais , Testosterona/sangue , Fatores de TempoRESUMO
OBJECTIVE: To investigate the effects of 1 mg 17beta-estradiol continuously combined with 2.5, 5, 10, or 20 mg dydrogesterone on the serum lipid profile of postmenopausal women. DESIGN: Serum lipid profile was measured in two 1-year studies performed in healthy, nonhysterectomized, postmenopausal women. One study (n = 182) had an open design and investigated oral 17beta-estradiol 1 mg daily continuously combined with dydrogesterone 2.5 mg daily; the other study (n = 326) had a double-blind, randomized design and investigated oral 17beta-estradiol 1 mg daily continuously combined with dydrogesterone at doses of 5, 10, or 20 mg daily. RESULTS: With all four dosages of dydrogesterone, serum total and low-density lipoprotein cholesterol were significantly reduced (-4.6% to -7.6% and -6.3% to -11.6%, respectively), whereas high-density lipoprotein cholesterol was significantly increased (+4.3% to +7.4%). Serum apolipoprotein A1 and B also improved significantly, reflecting the favorable changes in high-density lipoprotein and low-density lipoprotein cholesterol, as did lipoprotein(a). CONCLUSION: Oral 17beta-estradiol 1 mg daily continuously combined with dydrogesterone 2.5 to 20 mg daily has beneficial effects on serum lipid profile in postmenopausal women.
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Estradiol/administração & dosagem , Lipídeos/sangue , Pós-Menopausa/sangue , Congêneres da Progesterona/administração & dosagem , Administração Oral , Apolipoproteína A-I/sangue , Apolipoproteínas B/sangue , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Método Duplo-Cego , Quimioterapia Combinada , Estradiol/uso terapêutico , Terapia de Reposição de Estrogênios , Feminino , Humanos , Lipoproteína(a)/sangue , Pessoa de Meia-Idade , Congêneres da Progesterona/uso terapêuticoRESUMO
OBJECTIVE: The aim of this study was to compare the long-term effects of two dosages of raloxifene with oral hormone therapy (HT; conjugated equine estrogens combined with medroxyprogesterone acetate) on procarboxypeptidase U. DESIGN: In a randomized, double-blind, placebo-controlled, 2-year study, 95 healthy, nonhysterectomized, early postmenopausal women received either daily raloxifene 60 mg (n = 24), raloxifene 150 mg (n = 23), HT (conjugated equine estrogens 0.625 mg + medroxyprogesterone acetate 2.5 mg, n = 24), or placebo (n = 24). At baseline and after 6, 12, and 24 months, fasting plasma procarboxypeptidase U concentrations were measured. RESULTS: Six months of treatment with raloxifene 60 mg and raloxifene 150 mg were associated with significant decreases in plasma procarboxypeptidase U concentrations, which were sustained after 12 and 24 months. Raloxifene 60 mg: t = 0, 619 +/- 89 U/L (mean +/- SD); t = 6, 574 +/- 87 U/L; t = 12, 571 +/- 96 U/L; t = 24, 568 +/- 92 U/L; ANCOVA versus placebo, P = 0.026. Raloxifene 150 mg: t = 0, 608 +/- 67 U/L; t = 6, 580 +/- 73 U/L; t = 12, 578 +/- 70 U/L; t = 24, 562 +/- 61 U/L; ANCOVA versus placebo, P = 0.039. No significant changes were found in the HT group. CONCLUSION: Long-term treatment with raloxifene reduced procarboxypeptidase U plasma concentrations.
Assuntos
Carboxipeptidase B2/sangue , Fibrinólise , Pós-Menopausa/sangue , Cloridrato de Raloxifeno/farmacologia , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Análise de Variância , Biomarcadores/sangue , Anticoncepcionais Femininos/farmacologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Terapia de Reposição de Estrogênios , Estrogênios/farmacologia , Estrogênios Conjugados (USP)/farmacologia , Feminino , Humanos , Acetato de Medroxiprogesterona/farmacologia , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: Lipoprotein(a) (Lp(a)) and homocysteine (Hcy) are independent cardiovascular risk factors, which have been shown to be lowered by hormone replacement therapy (HRT). In this 2-year study, the long-term effects of raloxifene (Rlx) in two doses, on Lp(a) and Hcy, were studied and compared with the effects of continuously combined hormone replacement therapy (ccHRT). METHODS: In a prospective, randomized, double-blind, placebo-controlled 2-year study, 95 healthy, non-hysterectomized, early postmenopausal women, received daily either oral Rlx 60 mg (N=24) or 150 mg (N=23), ccHRT (conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg; N=24) or placebo (N=24). Fasting serum Lp(a) and plasma Hcy concentrations were measured at baseline and at 6, 12 and 24 months. RESULTS: The mean individual changes compared to baseline after 24 months were for Lp(a): Rlx 60: - 5%, Rlx 150: -7%, ccHRT: -34%, placebo: +1% and for Hcy: Rlx 60: -3%, Rlx 150: -4%, ccHRT: -4%, placebo: +6%. ANCOVA was significant for Lp(a) under ccHRT versus placebo (P=0.001) and for Lp(a) under ccHRT versus each of the two Rlx groups (P<0.05). CONCLUSIONS: Long-term treatment with Rlx was not as effective as ccHRT in lowering Lp(a). Although not significant and without an obvious dose-related response, the Hcy values showed the same trend for each treatment arm, which is in line with data reported earlier.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Homocisteína/sangue , Terapia de Reposição Hormonal , Lipoproteína(a)/sangue , Cloridrato de Raloxifeno/uso terapêutico , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Doenças Cardiovasculares/sangue , Método Duplo-Cego , Estrogênios Conjugados (USP)/administração & dosagem , Feminino , Humanos , Acetato de Medroxiprogesterona/administração & dosagem , Pessoa de Meia-Idade , Estudos Prospectivos , Cloridrato de Raloxifeno/administração & dosagem , Moduladores Seletivos de Receptor Estrogênico/administração & dosagemRESUMO
Low body mass index (BMI) is a well-established risk factor for fracture in postmenopausal women. Height and obesity have also been associated with increased fracture risk at some sites. We investigated the relationships of weight, BMI, and height with incident clinical fracture in a practice-based cohort of postmenopausal women participating in the Global Longitudinal study of Osteoporosis in Women (GLOW). Data were collected at baseline and at 1, 2, and 3 years. For hip, spine, wrist, pelvis, rib, upper arm/shoulder, clavicle, ankle, lower leg, and upper leg fractures, we modeled the time to incident self-reported fracture over a 3-year period using the Cox proportional hazards model and fitted the best linear or nonlinear models containing height, weight, and BMI. Of 52,939 women, 3628 (6.9%) reported an incident clinical fracture during the 3-year follow-up period. Linear BMI showed a significant inverse association with hip, clinical spine, and wrist fractures: adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) per increase of 5 kg/m(2) were 0.80 (0.71-0.90), 0.83 (0.76-0.92), and 0.88 (0.83-0.94), respectively (all p < 0.001). For ankle fractures, linear weight showed a significant positive association: adjusted HR per 5-kg increase 1.05 (1.02-1.07) (p < 0.001). For upper arm/shoulder and clavicle fractures, only linear height was significantly associated: adjusted HRs per 10-cm increase were 0.85 (0.75-0.97) (p = 0.02) and 0.73 (0.57-0.92) (p = 0.009), respectively. For pelvic and rib fractures, the best models were for nonlinear BMI or weight (p = 0.05 and 0.03, respectively), with inverse associations at low BMI/body weight and positive associations at high values. These data demonstrate that the relationships between fracture and weight, BMI, and height are site-specific. The different associations may be mediated, at least in part, by effects on bone mineral density, bone structure and geometry, and patterns of falling.
Assuntos
Índice de Massa Corporal , Peso Corporal , Osso e Ossos , Fraturas Ósseas , Modelos Biológicos , Pós-Menopausa/metabolismo , Fatores Etários , Idoso , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Feminino , Seguimentos , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/metabolismo , Fraturas Ósseas/fisiopatologia , Humanos , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Antiosteoporosis medication (AOM) does not abolish fracture risk, and some individuals experience multiple fractures while on treatment. Therefore, criteria for treatment failure have recently been defined. Using data from the Global Longitudinal Study of Osteoporosis in Women (GLOW), we analyzed risk factors for treatment failure, defined as sustaining two or more fractures while on AOM. GLOW is a prospective, observational cohort study of women aged ≥55 years sampled from primary care practices in 10 countries. Self-administered questionnaires collected data on patient characteristics, fracture risk factors, previous fractures, AOM use, and health status. Data were analyzed from women who used the same class of AOM continuously over 3 survey years and had data available on fracture occurrence. Multivariable logistic regression was used to identify independent predictors of treatment failure. Data from 26,918 women were available, of whom 5550 were on AOM. During follow-up, 73 of 5550 women in the AOM group (1.3%) and 123 of 21,368 in the non-AOM group (0.6%) reported occurrence of two or more fractures. The following variables were associated with treatment failure: lower Short Form 36 Health Survey (SF-36) score (physical function and vitality) at baseline, higher Fracture Risk Assessment Tool (FRAX) score, falls in the past 12 months, selected comorbid conditions, prior fracture, current use of glucocorticoids, need of arms to assist to standing, and unexplained weight loss ≥10 lb (≥4.5 kg). Three variables remained predictive of treatment failure after multivariable analysis: worse SF-36 vitality score (odds ratio [OR] per 10-point increase, 0.85; 95% confidence interval [CI], 0.76-0.95; p = 0.004); two or more falls in the past year (OR, 2.40; 95% CI, 1.34-4.29; p = 0.011), and prior fracture (OR, 2.93; 95% CI, 1.81-4.75; p < 0.0001). The C statistic for the model was 0.712. Specific strategies for fracture prevention should therefore be developed for this subgroup of patients.