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1.
CMAJ Open ; 9(2): E711-E717, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34162663

RESUMO

BACKGROUND: In Canada, decisions regarding osteoporosis pharmacotherapy are based on estimated 10-year risk of osteoporotic fracture. We aimed to determine how frequently 2 common approaches (Canadian Association of Radiologists and Osteoporosis Canada [CAROC] tool and Fracture Risk Assessment Tool [FRAX]) produced different estimates and to seek possible explanations for differences. METHODS: We conducted a cross-sectional chart review at a tertiary osteoporosis centre (Dr. David Hanley Osteoporosis Centre in Calgary). Included patients were women referred for consideration of osteoporosis pharmacotherapy who attended a consultation between 2016 and 2019 and whose charts contained 10-year osteoporotic fracture risk estimates using both the CAROC tool (based on bone mineral density [BMD] results) and FRAX (based on BMD results and clinically assessed fracture risk factors). Risk estimates provided on BMD reports (calculated with CAROC) and generated through osteoporosis clinic consultation (calculated with FRAX, including BMD) were categorized as low (< 10.0%), moderate (10.0%-19.9%) or high (≥ 20.0%). Estimates were considered discordant when they placed the patient in different risk categories. RESULTS: Of 190 patients evaluated, 99 (52.1%) had discordant risk estimates. Although a similar proportion were considered high risk by BMD reports using the CAROC tool (17.9%) and clinic charts using FRAX (19.5%), the 2 methods identified different patients as being high risk. Around the crucial high-risk (20.0%) treatment threshold, discordance was present in 37 patients (19.5%, 95% confidence interval [CI] 14.5%-25.7%); discordance around the moderate-risk (10.0%) threshold was present in 69 (36.3%, 95% CI 29.5%-43.2%) patients. Disagreement regarding fracture history between BMD reports and clinic charts was observed in 19.8% of patients. INTERPRETATION: Fracture risk estimates on BMD reports (using the CAROC tool) and those calculated in the clinical setting (using FRAX) frequently result in different risk classification. Osteoporosis treatment decisions may differ in up to half of patients depending on which estimate is used, highlighting the need for a consistent and accurate assessment process for fracture risk.


Assuntos
Osteoporose , Fraturas por Osteoporose , Sistemas de Informação em Radiologia/estatística & dados numéricos , Medição de Risco , Alberta/epidemiologia , Densidade Óssea , Tomada de Decisão Clínica , Estudos Transversais , Tratamento Farmacológico/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose/complicações , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Fraturas por Osteoporose/diagnóstico , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/prevenção & controle , Avaliação de Resultados em Cuidados de Saúde , Seleção de Pacientes , Medição de Risco/métodos , Medição de Risco/normas , Medição de Risco/estatística & dados numéricos
5.
Br J Gen Pract ; 70(700): e801-e808, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33020167

RESUMO

BACKGROUND: Delivery of patient-centred care is limited by physician time. Group medical consultations may save physician time without compromising patient experience. AIM: To assess patient experience and specialist physician time commitment in a group consultation for osteoporosis. DESIGN AND SETTING: Prospective pilot study at a tertiary osteoporosis centre in Canada between May 2016 and June 2019. METHOD: The authors evaluated women referred for osteoporosis who chose a 2-hour group consultation instead of a one-to-one consultation. Group consultations were led by an osteoporosis nurse and specialist physician, and consisted of individualised fracture risk assessment and education regarding osteoporosis therapies, followed by a decision-making exercise to choose a treatment plan. Patients then followed up with their GPs to implement this plan. Patient experience was assessed via a questionnaire immediately and 3 months post-consultation, at which time GP satisfaction and patient treatment status were also surveyed. RESULTS: Of 560 referrals received, 18 patients declined osteoporosis specialist assessment, 54 could not be contacted, 303 attended a one-to- one consultation, and 185 attended a group consultation. Mean participant age was 62.8 years (standard deviation [SD] 5.8) and the Fracture Risk Assessment Tool (FRAX) 10-year osteoporotic fracture risk was 13.0 (SD 7.0)%. Immediately post-consultation, 104 (97.2%) patients were satisfied and 102 (95.3%) felt included in decision making. Satisfaction was reported by 95/99 (96.0%) patients and 27/36 (75.0%) GPs. Treatment plans had been enacted by 90 (90.1%) patients. For a matched number of individual consultations, each group session conferred a specialist physician time savings of 5.5 hours. CONCLUSION: Group consultations represent a satisfactory and time-efficient alternative to one-to-one consultations for select patients with osteoporosis.


Assuntos
Osteoporose , Canadá , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose/diagnóstico , Osteoporose/tratamento farmacológico , Avaliação de Resultados da Assistência ao Paciente , Satisfação do Paciente , Projetos Piloto , Estudos Prospectivos , Encaminhamento e Consulta , Atenção Terciária à Saúde
6.
Arch Osteoporos ; 15(1): 138, 2020 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-32888079

RESUMO

Many individuals prescribed osteoporosis pharmacotherapy either do not start or do not persist with treatment. In this study, women who attended a group medical visit at an osteoporosis center which involved fracture risk assessment and focused on autonomous decision-making made treatment decisions with high confidence. Those who started pharmacotherapy were highly persistent. PURPOSE: Adherence and persistence with osteoporosis pharmacotherapy is low, possibly reflecting lack of confidence in physicians' treatment recommendations. We evaluated treatment decisions, decisional confidence, and 12-month treatment adherence among women who attended a group bone health consultation that fostered autonomous decision-making. METHODS: We prospectively assessed postmenopausal women referred to an osteoporosis clinic who chose to attend a group medical visit in lieu of one-on-one consultation. The group visit was facilitated by a specialist physician and nurse, involving estimation of 10-year major osteoporotic fracture risk (using FRAX®) and extensive education regarding fracture consequences and potential advantages and disadvantages of pharmacotherapy. No direct advice was given by the specialist. Post-consult, participants made an autonomous decision regarding treatment intent and followed up with their family physician to enact their chosen plan. Intentions to initiate pharmacotherapy were assessed immediately post-consult. Treatment status and decisional confidence were evaluated 3 and 12 months later. Three-month treatment status was considered to reflect final treatment decision. Persistence was defined as proportion of participants on treatment at 3 months who remained treated at 12 months. RESULTS: One hundred one women (mean (SD) age, 62.7 years (5.8); median (IQR) FRAX®, 10.7% (8.3-17.6)) participated. Immediately post-consult, 27 (26.7%) intended to initiate treatment. At 3 months, 23 (22.8%) were treated, and at 12 months, 21 (91.3%) remained persistent. Of 89 questionnaire respondents at 12 months, 85 (95.5%) reported confidence in their treatment decision. CONCLUSION: When postmenopausal women are provided with individualized fracture risk estimates and enabled to make autonomous decisions regarding pharmacotherapy, ultimate decisions to receive treatment are made with confidence and result in high persistence at 12 months.


Assuntos
Conservadores da Densidade Óssea , Adesão à Medicação , Osteoporose Pós-Menopausa , Osteoporose , Fraturas por Osteoporose , Autonomia Pessoal , Conservadores da Densidade Óssea/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose/tratamento farmacológico , Osteoporose Pós-Menopausa/tratamento farmacológico , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/prevenção & controle , Probabilidade , Encaminhamento e Consulta , Medição de Risco , Inquéritos e Questionários
7.
J Bone Miner Res ; 35(12): 2404-2414, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32777104

RESUMO

Three years of high-dose vitamin D supplementation (400 IU, 4000 IU, 10,000 IU) in healthy vitamin D-sufficient individuals aged 55 to 70 years (serum 25(OH)D 30-125 nmol/L at baseline), resulted in a negative dose-response relationship for bone density and strength. This study examined whether response differed between males and females. A total of 311 participants (53% male) were randomized to 400 IU (male = 61, female = 48), 4000 IU (male = 51, female = 49), or 10,000 IU (male = 53, female = 49) daily vitamin D3 . Participants were scanned with high-resolution peripheral quantitative computed tomography (HR-pQCT) to measure total volumetric BMD (TtBMD) at baseline, 6, 12, 24, and 36 months. Finite element analysis estimated bone strength. Balance, physical function, and clinical biochemistry parameters were also assessed. Constrained linear mixed effects models determined time-by-treatment group-by-sex interactions. Baseline, 3-month, and 3-year levels of 25(OH)D were 76.3, 76.7, and 77.4 nmol/L (400 IU); 81.3, 115.3, and 132.2 (4000 IU); and 78.4, 188.0, and 144.4 (10,000 IU), respectively. There were significant time-by-treatment group-by-sex interactions for TtBMD at the radius (p = .002) and tibia (p = .005). Treatment with 4000 IU or 10,000 IU compared to 400 IU resulted in TtBMD losses in females, but this was not observed with males. After 3 years, females lost 1.8% (400 IU), 3.8% (4000 IU), and 5.5% (10,000 IU), whereas males lost 0.9% (400 IU), 1.3% (4000 IU), and 1.9% (10,000 IU) at the radius. At the tibia, losses in TtBMD were smaller, but followed a similar trend. There were no significant bone strength interactions. Vitamin D supplementation with 4000 IU or 10,000 IU, compared with 400 IU daily, resulted in greater losses of TtBMD over 3 years in healthy vitamin D-sufficient females, but not males. These results are clinically relevant, because vitamin D supplementation is widely administered to postmenopausal females for osteoporosis prevention. Our findings do not support a benefit of high-dose vitamin D supplementation for bone health, and raise the possibility of harm for females. © 2020 American Society for Bone and Mineral Research (ASBMR).

8.
Curr Osteoporos Rep ; 18(5): 587-596, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32734512

RESUMO

PURPOSE OF REVIEW: Recent evidence from clinical trials and observational studies raises the possibility that bisphosphonate use might confer a lower risk of cardiovascular disease and cancer, resulting in a mortality benefit. This review summarizes clinical and preclinical studies examining the non-skeletal effects of bisphosphonates. RECENT FINDINGS: Data from clinical trials are conflicting regarding whether or not bisphosphonates have beneficial effects on mortality, cardiovascular events, or cancer incidence. No clinical trials have assessed these outcomes as primary endpoints, and most trials were shorter than 4 years. Observational data suggest that bisphosphonate users may have lower mortality, delayed progression of vascular calcification and atherosclerotic burden, and reduced incidence of breast and colorectal cancer compared to non-users. Preclinical studies confirm that bisphosphonates can be taken up by macrophages and monocytes, and nitrogen-containing bisphosphonates have the ability to disrupt the mevalonate pathway within these cells. In this manner, bisphosphonates exert anti-atherogenic and anti-cancer effects. Bisphosphonates also appear to exert protective effects on vascular smooth muscle cells and endothelial cells and may have direct cytotoxic effects on cancer cells. The balance of evidence does not support bisphosphonate treatment for the primary purpose of improving non-skeletal outcomes, although appropriately designed controlled trials that further explore this possibility are both justified and required. Patients with skeletal indications for bisphosphonate therapy can be reassured that these agents are not associated with increased mortality, cardiovascular disease, or cancer incidence.

9.
Nutrients ; 12(2)2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32092887

RESUMO

Vitamin D supplementation is proposed as a fall prevention strategy, as it may improve neuromuscular function. We examined whether three years of vitamin D supplementation (400, 4000 or 10,000 IU daily) affects postural sway in older adults. Three hundred and seventy-three non-osteoporotic, vitamin D-sufficient, community-dwelling healthy adults, aged 55-70 years, were randomized to 400 (n = 124), 4000 (n = 125) or 10,000 (n = 124) IU daily vitamin D3 for three years. Sway index was assessed at baseline, 12-, 24- and 36-months using the Biosway machine. We tested participants under four conditions: eyes open or eyes closed with firm (EOFI, ECFI) or foam (EOFO, ECFO) surfaces. Secondary assessments examined sway in the anterior-posterior (AP) and medio-lateral (ML) directions. Linear mixed effects models compared sway between supplementation groups across time. Postural sway under EOFO and ECFO conditions significantly improved in all supplementation groups over time. Postural sway did not differ between supplementation groups at any time under any testing conditions in normal, AP or ML directions (p > 0.05 for all). Our findings suggest that high dose (4000 or 10,000 IU) vitamin D supplementation neither benefit nor impair balance compared with 400 IU daily in non-osteoporotic, vitamin D-sufficient, healthy older adults.


Assuntos
Colecalciferol/administração & dosagem , Suplementos Nutricionais , Equilíbrio Postural/efeitos dos fármacos , Vitaminas/administração & dosagem , Idoso , Feminino , Voluntários Saudáveis , Humanos , Vida Independente , Modelos Lineares , Masculino , Pessoa de Meia-Idade
10.
J Gen Intern Med ; 35(1): 276-282, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31625042

RESUMO

BACKGROUND: Osteoporosis guidelines recommend pharmacologic therapy based on 10-year risk of major osteoporotic fracture (MOF) and hip fracture, which may fail to account for patient-specific experiences and values. OBJECTIVE: We aimed to determine whether patient decisions to initiate osteoporosis medication agree with guideline-recommended intervention thresholds. DESIGN AND PARTICIPANTS: This prospective cohort study included women aged ≥ 45 with age-associated osteoporosis who attended a group osteoporosis self-management consultation at a tertiary osteoporosis center. INTERVENTION: A group osteoporosis self-management consultation, during which participants received osteoporosis education and then calculated1 their 10-year MOF and hip fracture risk using FRAX and2 their predicted absolute fracture risk with therapy (assuming 40% relative reduction). Participants then made autonomous decisions regarding treatment initiation. MAIN MEASURES: We evaluated agreement between treatment decisions and physician-set intervention thresholds (10-year MOF risk ≥ 20%, hip fracture risk ≥ 3%). KEY RESULTS: Among 85 women (median [IQR] age 62 [58-67]), 27% accepted treatment (median [IQR] MOF risk, 15.1% [9.9-22.0]; hip fracture risk, 3.3% [1.3-5.3]), 46% declined (MOF risk, 9.5% [6.5-11.6]; hip fracture risk, 1.8% [0.6-2.3]), and 27% remained undecided (MOF risk, 14.0% [9.8-20.2]; hip fracture risk, 4.4% [1.7-4.9]). There was wide overlap in fracture risk between treatment acceptors and non-acceptors. Odds of accepting treatment were higher in women with prior fragility fracture (50% accepted; OR, 5.3; 95% CI, 1.9-15.2; p = 0.0015) and with hip fracture risk ≥ 3% (32% accepted; OR, 3.6; 95% CI, 1.4-9.2; p = 0.012), but not MOF risk ≥ 20% (47% accepted; OR, 3.0; 95% CI, 1.0-8.5; p = 0.105). CONCLUSIONS: Informed decisions to start osteoporosis treatment are highly personal and not easily predicted using fracture risk. Guideline-recommended intervention thresholds may not permit sufficient consideration of patient preferences.


Assuntos
Fraturas do Quadril , Osteoporose , Fraturas por Osteoporose , Médicos , Idoso , Densidade Óssea , Feminino , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/etiologia , Fraturas do Quadril/prevenção & controle , Humanos , Pessoa de Meia-Idade , Osteoporose/complicações , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/prevenção & controle , Estudos Prospectivos , Medição de Risco , Fatores de Risco
11.
J Clin Endocrinol Metab ; 105(4)2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31746327

RESUMO

CONTEXT: More than 3% of adults report vitamin D intakes of 4000 IU/day or more, but the safety of this practice is unknown. OBJECTIVE: The objective of this work is to establish whether vitamin D doses up to 10 000 IU/day are safe and well tolerated. DESIGN: The Calgary Vitamin D Study was a 3-year, double-blind, randomized controlled trial. SETTING: A single-center study was conducted at the University of Calgary, Canada. PARTICIPANTS: Participants included healthy adults (n = 373) ages 55 to 70 years with serum 25-hydroxyvitamin D 30 to 125 nmol/L. INTERVENTIONS: Participants were randomly assigned 1:1:1 to vitamin D3 400, 40 000, or 10 000 IU/day. Calcium supplementation was initiated if dietary calcium intake was less than 1200 mg/day. MAIN OUTCOME MEASURES: In these prespecified secondary analyses, changes in serum 25-hydroxyvitamin D, calcium, creatinine, 24-hour urine calcium excretion, and incidence of adverse events were assessed. Between-group differences in adverse events were examined using incident rate differences and logistic regression. RESULTS: Of 373 participants (400: 124, 4000: 125, 10 000: 124), 49% were male, mean (SD) age was 64 (4) years, and 25-hydroxyvitamin D 78.0 (19.5) nmol/L. Serum calcium, creatinine, and 24-hour urine calcium excretion did not differ between treatments. Mild hypercalcemia (2.56-2.64 mmol/L) occurred in 15 (4%) participants (400: 0%, 4000: 3%, 10 000: 9%, P = .002); all cases resolved on repeat testing. Hypercalciuria occurred in 87 (23%) participants (400: 17%, 4000: 22%, 10 000: 31%, P = .01). Clinical adverse events were experienced by 365 (97.9%) participants and were balanced across treatment arms. CONCLUSIONS: The safety profile of vitamin D supplementation is similar for doses of 400, 4000, and 10 000 IU/day. Hypercalciuria was common and occurred more frequently with higher doses. Hypercalcemia occurred more frequently with higher doses but was rare, mild, and transient.


Assuntos
Biomarcadores/sangue , Suplementos Nutricionais , Deficiência de Vitamina D/prevenção & controle , Vitamina D/análogos & derivados , Idoso , Cálcio/sangue , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , Vitamina D/administração & dosagem , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia
12.
JAMA ; 322(8): 736-745, 2019 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-31454046

RESUMO

Importance: Few studies have assessed the effects of daily vitamin D doses at or above the tolerable upper intake level for 12 months or greater, yet 3% of US adults report vitamin D intakes of at least 4000 IU per day. Objective: To assess the dose-dependent effect of vitamin D supplementation on volumetric bone mineral density (BMD) and strength. Design, Setting, and Participants: Three-year, double-blind, randomized clinical trial conducted in a single center in Calgary, Canada, from August 2013 to December 2017, including 311 community-dwelling healthy adults without osteoporosis, aged 55 to 70 years, with baseline levels of 25-hydroxyvitamin D (25[OH]D) of 30 to 125 nmol/L. Interventions: Daily doses of vitamin D3 for 3 years at 400 IU (n = 109), 4000 IU (n = 100), or 10 000 IU (n = 102). Calcium supplementation was provided to participants with dietary intake of less than 1200 mg per day. Main Outcomes and Measures: Co-primary outcomes were total volumetric BMD at radius and tibia, assessed with high resolution peripheral quantitative computed tomography, and bone strength (failure load) at radius and tibia estimated by finite element analysis. Results: Of 311 participants who were randomized (53% men; mean [SD] age, 62.2 [4.2] years), 287 (92%) completed the study. Baseline, 3-month, and 3-year levels of 25(OH)D were 76.3, 76.7, and 77.4 nmol/L for the 400-IU group; 81.3, 115.3, and 132.2 for the 4000-IU group; and 78.4, 188.0, and 144.4 for the 10 000-IU group. There were significant group × time interactions for volumetric BMD. At trial end, radial volumetric BMD was lower for the 4000 IU group (-3.9 mg HA/cm3 [95% CI, -6.5 to -1.3]) and 10 000 IU group (-7.5 mg HA/cm3 [95% CI, -10.1 to -5.0]) compared with the 400 IU group with mean percent change in volumetric BMD of -1.2% (400 IU group), -2.4% (4000 IU group), and -3.5% (10 000 IU group). Tibial volumetric BMD differences from the 400 IU group were -1.8 mg HA/cm3 (95% CI, -3.7 to 0.1) in the 4000 IU group and -4.1 mg HA/cm3 in the 10 000 IU group (95% CI, -6.0 to -2.2), with mean percent change values of -0.4% (400 IU), -1.0% (4000 IU), and -1.7% (10 000 IU). There were no significant differences for changes in failure load (radius, P = .06; tibia, P = .12). Conclusions and Relevance: Among healthy adults, treatment with vitamin D for 3 years at a dose of 4000 IU per day or 10 000 IU per day, compared with 400 IU per day, resulted in statistically significant lower radial BMD; tibial BMD was significantly lower only with the 10 000 IU per day dose. There were no significant differences in bone strength at either the radius or tibia. These findings do not support a benefit of high-dose vitamin D supplementation for bone health; further research would be needed to determine whether it is harmful. Trial Registration: ClinicalTrials.gov Identifier: NCT01900860.


Assuntos
Densidade Óssea/efeitos dos fármacos , Colecalciferol/administração & dosagem , Suplementos Nutricionais , Vitaminas/administração & dosagem , Absorciometria de Fóton , Administração Oral , Idoso , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Análise de Elementos Finitos , Resistência à Flexão , Humanos , Masculino , Pessoa de Meia-Idade , Rádio (Anatomia)/anatomia & histologia , Rádio (Anatomia)/diagnóstico por imagem , Tíbia/anatomia & histologia , Tíbia/diagnóstico por imagem , Falha de Tratamento , Vitamina D/análogos & derivados , Vitamina D/sangue
13.
Clin Endocrinol (Oxf) ; 91(1): 87-93, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30943313

RESUMO

OBJECTIVE: Levels of fibroblast growth factor 23 (FGF23) have been positively associated with measures of adiposity, cardiovascular disease and mortality. It is unclear whether the relationship of FGF23 with cardiovascular disease and mortality is confounded by obesity. We aimed to determine whether FGF23 concentrations decline following a reduction in adiposity after sleeve gastrectomy (SG). DESIGN: The effect of SG on FGF23 was evaluated in 22 obese adults (59% male) with type 2 diabetes. Fat mass, weight, BMI, plasma intact FGF23, parathyroid hormone (PTH) and leptin were determined at baseline and at 12 months following SG. RESULTS: At baseline, median (IQR) age was 51 (43-54) years, fat mass 47.8 (41.0-59.4) kg, BMI 40.9 (36.9-46.9) kg/m2 and FGF23 66.2 (55.3-82.9) pg/mL. Significant changes in median BMI (-10.8 kg/m2 , 95% CI: -12.9 to -7.2, P < 0.0001), fat mass (-20.0 kg, 95% CI: -26.7 to -12.4, P < 0.0001) and weight (-34.7 kg, 95% CI -40.0 to -23.1, P < 0.0001) were observed after SG. FGF23 (-12.4 pg/mL, 95% CI: -19.5 to 2.0, P = 0.005), PTH (-1.1 pmol/L, 95% CI: -1.7 to 0.2, P = 0.009) and leptin (-1687 pg/mL, 95% CI -4524 to -563, P = 0.01) declined following SG. Change in FGF23 was not significantly associated with change in measures of adiposity, PTH or leptin. CONCLUSIONS: FGF23 concentrations decline in the setting of significant weight loss following SG, implying that increased FGF23 concentrations are a downstream consequence of obesity, which may confound its association with cardiometabolic dysfunction. Mediators of the relationship between adiposity and FGF23 require further elucidation.


Assuntos
Fatores de Crescimento de Fibroblastos/sangue , Gastrectomia , Hormônio Paratireóideo/sangue , Adulto , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Adulto Jovem
14.
Hepatology ; 69(6): 2683-2695, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30468515

RESUMO

Healthy sexual function is important to maintain a good quality of life but is frequently impaired in patients with cirrhosis. The degree of sexual dysfunction appears to be linked with the degree of hepatic dysfunction. In men, sexual dysfunction can be related to the hyperestrogenism of portal hypertension and/or to decreased testosterone resulting from testicular dysfunction. In women, suppression of the hypothalamic-pituitary-gonadal axis appears to be a principal contributor, with no significant effect of portal hypertension. There is also a huge psychological barrier to break through as there is a component of depression in many patients with cirrhosis. Sexual dysfunction is often underdiagnosed in the cohort with cirrhosis. Management of sexual disorders in patients with cirrhosis can be challenging as they are often multifactorial. A multidisciplinary approach is key in managing these patients. We review the current literature on the pathogenesis of sexual dysfunction in patients with cirrhosis and propose a stepwise algorithm to better manage these patients.


Assuntos
Hormônios Esteroides Gonadais/sangue , Cirrose Hepática/epidemiologia , Cirrose Hepática/patologia , Disfunções Sexuais Fisiológicas/epidemiologia , Disfunções Sexuais Fisiológicas/terapia , Adulto , Fatores Etários , Comorbidade , Gerenciamento Clínico , Feminino , Humanos , Cirrose Hepática/fisiopatologia , Cirrose Hepática/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Disfunções Sexuais Fisiológicas/diagnóstico
15.
Contemp Clin Trials ; 67: 68-73, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29471124

RESUMO

The optimum dose of vitamin D and corresponding serum 25-hydroxyvitamin D (25OHD) concentration for bone health is still debated and some health practitioners are recommending doses well above the Canada/USA recommended Dietary Reference Intake (DRI). We designed a three-year randomized double-blind clinical trial investigating whether there are dose-dependent effects of vitamin D supplementation above the Dietary Reference Intake (DRI) on bone health. The primary aims of this study are to assess, whether supplementation of vitamin D3 increases 1) volumetric bone mineral density measured by high-resolution peripheral quantitative computed tomography (HR-pQCT); 2) bone strength assessed by finite element analysis, and 3) areal bone mineral density by dual X-ray absorptiometry (DXA). Secondary aims are to understand whether vitamin D3 supplementation improves parameters of bone microarchitecture, balance, physical function and quality of life. Participants are men and women aged 55-70 years, with women at least 5-years post-menopause. The intervention is daily vitamin D3 supplementation doses of 400, 4000 or 10,000 IU. Participants not achieving adequate dietary calcium intake are provided with calcium supplementation, up to a maximum supplemental dose of 600 mg elemental calcium per day. Results from this three-year study will provide evidence whether daily vitamin D3 supplementation with adequate calcium intake can affect bone density, bone microarchitecture and bone strength in men and women. Furthermore, the safety of high dose daily vitamin D3 supplementation will be explored.


Assuntos
Densidade Óssea/efeitos dos fármacos , Osso e Ossos , Vitamina D , Absorciometria de Fóton/métodos , Idoso , Disponibilidade Biológica , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/efeitos dos fármacos , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevenção Primária , Tomografia Computadorizada por Raios X/métodos , Vitamina D/administração & dosagem , Vitamina D/farmacocinética , Vitaminas/administração & dosagem , Vitaminas/farmacocinética
16.
Eur J Clin Invest ; 47(7): 486-493, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28517037

RESUMO

BACKGROUND: Inorganic phosphate is a crucial component of cellular energy metabolism. We have identified an inverse relationship between serum phosphate concentration and fat mass in a cohort of healthy men. This study reports those data and determines whether this association is present in two female populations. METHODS: Cross-sectional data from three independent cohorts, consisting of healthy adult males (Male Cohort, n = 323) and healthy postmenopausal women (Female Cohort 1, n = 185; and Female Cohort 2, n = 1471), are reported. Associations between serum phosphate and weight, body mass index (BMI), fat mass and bone mineral density (BMD) were assessed. In a fourth cohort of postmenopausal women (FGF23 Cohort, n = 20), associations between fibroblast growth factor 23 (FGF23), weight and BMI were assessed. RESULTS: Serum phosphate correlated inversely with weight, BMI and fat mass across all three cohorts (r = -0·13 to -0·31, P < 0·0001-0·02). Associations were diminished after adjustment for PTH, but remained significant. In the FGF23 Cohort, FGF23 was positively correlated with weight (r = 0·60, P = 0·007) and BMI (r = 0·49, P = 0·03). Phosphate was inversely associated with BMD in Female Cohorts 1 and 2 (r = -0·08 to -0·29, P < 0·0001-0·02). This relationship was attenuated, but remained significant at most sites, following adjustment for age, fat mass, renal function and 25-hydroxyvitamin D. CONCLUSIONS: Serum phosphate is inversely associated with measures of adiposity in both women and men, largely independently of PTH. FGF23 might mediate these associations. This relationship may be an unrecognized confounder in some of the correlates of serum phosphate already described.


Assuntos
Adiposidade/fisiologia , Fosfatos/sangue , Adulto , Idoso , Índice de Massa Corporal , Densidade Óssea , Cálcio/administração & dosagem , Estudos de Coortes , Estudos Transversais , Suplementos Nutricionais , Diuréticos/administração & dosagem , Feminino , Humanos , Hidroclorotiazida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Pós-Menopausa , Vitamina D/análogos & derivados , Vitamina D/metabolismo
17.
Bonekey Rep ; 5: 852, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28018585

RESUMO

Hyperparathyroidism may be associated with skeletal and cardiovascular abnormalities, but it is unclear whether these associations exist for high-normal levels of parathyroid hormone (PTH). We assessed relationships between PTH and anthropometric, skeletal and cardiometabolic indices in normal men. Body composition, blood pressure, biochemistry and bone mineral density (BMD) were evaluated in 151 healthy men. BMD was reassessed at 2 years, and coronary artery calcium (CAC) was measured at 3.5 years. Relationships between PTH and other baseline characteristics, CAC scores and change in BMD were evaluated. PTH correlated positively with baseline body mass index, fat mass, diastolic blood pressure, triglycerides, total and low-density lipoprotein (LDL) cholesterol, (r=0.19-0.25, P=0.02-0.002), and with category of CAC score. Relationships between PTH and cardiometabolic indices remained significant after adjustment for age, 25-hydroxyvitamin D and estimated glomerular filteration rate. Men in the top PTH tertile (⩾4.4 pmol l-1, n=51) were more likely to have LDL cholesterol ⩾3.5 mmol l-1, diastolic blood pressure ⩾85 mm Hg, and CAC score >0 than men in lower tertiles. PTH was not associated with history of fracture, baseline BMD, or change in BMD over 2 years. In summary, in this cohort of healthy men, PTH levels are linearly related to adiposity and to cardiometabolic indices, but not to BMD or bone loss. These findings suggest that adiposity should be considered as an independent cause of secondary hyperparathyroidism, and they may be relevant to patients with normocalcemic hyperparathyroidism, in whom high PTH levels may be a marker of adiposity and cardiometabolic risk rather than always indicating parathyroid autonomy.

18.
Gynecol Endocrinol ; 32(9): 728-732, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26984343

RESUMO

Pulsatile GnRH is used to induce ovulation in women with hypothalamic amenorrhea (HA), but tools to predict response are lacking. We assessed whether baseline AMH levels are associated with response to pulsatile GnRH in 16 women with HA. AMH levels were compared between non-responders and women who achieved follicular development or pregnancy. Median AMH for the cohort was 2.2 ng/mL. AMH levels were undetectable or low in four women, normal in nine and high in three. Follicular development was observed in 13 (81%) women (82% of cycles) and pregnancy achieved in 10 (63%) women (29% of cycles). All four women with low or undetectable AMH had follicular response and three achieved pregnancy. Of the 12 women with normal or high AMH, 10 had a follicular response and seven achieved pregnancy. Median AMH levels were comparable in those who achieved follicular development and those who did not (2.2 ng/mL versus 1.3 ng/mL, p = 0.78) and in those who became pregnant and those who did not (2.2 ng/mL versus 1.9 ng/mL, p = 0.52). In summary, low AMH does not preclude response to ovulation induction in women with HA, suggesting that ovarian potential may not be the primary determinant of AMH concentrations in this population.


Assuntos
Amenorreia/sangue , Amenorreia/tratamento farmacológico , Hormônio Antimülleriano/sangue , Hormônio Liberador de Gonadotropina/farmacologia , Hipotálamo/fisiopatologia , Infertilidade Feminina/sangue , Infertilidade Feminina/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde , Indução da Ovulação/métodos , Adulto , Amenorreia/etiologia , Feminino , Hormônio Liberador de Gonadotropina/administração & dosagem , Humanos , Infertilidade Feminina/etiologia , Gravidez
19.
Maturitas ; 85: 11-8, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26857874

RESUMO

OBJECTIVES: Both the FRAX and Garvan calculators are used to estimate absolute risk of fracture, but they sometimes produce different estimates. We sought to determine which patient characteristics contribute to these discrepancies. STUDY DESIGN: Ten-year hip fracture risk was estimated for 122 women, using both FRAX and Garvan with bone mineral density (BMD). MAIN OUTCOME MEASURES: Differences in estimates of hip fracture were assessed, both in absolute terms and with respect to a treatment threshold of 3%. RESULTS: Garvan estimates were higher than FRAX estimates across the range of ages and BMDs studied. A history of falls or of multiple fractures increased risk calculated by Garvan 3-6-fold, but did not account for all differences between calculators. Discrepancies around a 3% treatment threshold occurred in 31/122 (25%). Women aged 70-74 years, and women with osteopenia were most likely to have discordant estimates. Most discordant estimates (29/31) had a Garvan estimate ≥ 3% and FRAX <3%. Falls, multiple fractures, ethnicity and a history of parental hip fracture contributed to some discordant estimates. CONCLUSIONS: Hip fracture risk estimates are usually higher with Garvan than FRAX, and these differences could impact on treatment decisions in about a quarter of patients. Falls and multiple fractures have a strong influence on Garvan risk estimates, when present. Clinically important discrepancies tend to occur in patients who are at borderline fracture risk. In patients with hip fracture risks near the treatment threshold with one calculator, use of the other calculator should be considered to help guide treatment decisions.


Assuntos
Fraturas do Quadril , Acidentes por Quedas , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea , Doenças Ósseas Metabólicas/complicações , Feminino , Fraturas do Quadril/etiologia , Humanos , Pessoa de Meia-Idade , Medição de Risco/métodos , Fatores de Risco
20.
Diabetologia ; 58(10): 2238-46, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26109213

RESUMO

AIMS/HYPOTHESIS: Thiazolidinediones (TZDs) are associated with an increased risk of fracture but the mechanism is unclear. We sought to determine the effect of TZDs on bone mineral density (BMD) and bone turnover markers. METHODS: PubMed, EMBASE and Cochrane CENTRAL databases were searched from inception until January 2015 for randomised controlled trials comparing TZDs with metformin, sulfonylureas or placebo, and those reporting changes in BMD and/or bone turnover markers. The primary outcome was percentage change in BMD from baseline and results were pooled with random effects meta-analyses. RESULTS: In all, 18 trials were included in the primary analyses and another two were included in the sensitivity analyses (n = 3,743, 50% women, mean age 56 years, median trial duration 48 weeks). TZDs decreased BMD at the lumbar spine (difference -1.1% [95% CI -1.6, -0.7]; p < 0.0001), total hip (-1.0% [-1.4, -0.6]; p < 0.0001) and forearm (-0.9% [-1.6, -0.3]; p = 0.007). There were statistically non-significant decreases in BMD at the femoral neck (-0.7% [-1.4, 0.0]; p = 0.06) and total body (-0.3% [-0.5, 0.0]; p = 0.08). Five trials (n = 450) showed no statistically significant difference in percentage change in BMD between the TZD group and controls up to 1 year following TZD withdrawal. In 14 trials, the effect of TZD treatment on turnover markers varied considerably between individual studies. CONCLUSIONS/INTERPRETATION: Treatment with TZDs results in modest bone loss that may not be reversed 1 year after cessation of treatment.


Assuntos
Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Fraturas Ósseas/etiologia , Tiazolidinedionas/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tiazolidinedionas/efeitos adversos , Tiazolidinedionas/uso terapêutico
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