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3.
Osteoporos Int ; 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33768343

RESUMO

We describe variation across geographical regions of England in operations undertaken following presentation of hip fracture and in 30-day mortality. Some significant geographic variation in 30-day mortality was observed particularly for patients with trochanteric hip fractures and warrants further investigation of other aspects of post-hip fracture care INTRODUCTION: Mortality after hip fracture has improved considerably in the UK over recent decades. Our aim here was to describe geographical variation in type of operation performed and 30-day mortality amongst patients in England with hip fracture. METHODS: The National Hip Fracture Database was used to carry out a prospective cohort study of nearly all over-60 year olds with hip fracture in England. These data were linked to Hospital Episode Statistics (HES), allowing us to explore regional variation in the operations performed for three fracture types (intracapsular, trochanteric and subtrochanteric), and use logistic regression models adjusted for demographic and clinical factors to describe associated 30-day mortality. RESULTS: NHFD recorded data for 64,211 patients who underwent surgery in England during 2017. Most had an intracapsular (59%) or trochanteric fracture (35%), and we found significant geographical variation across regions of England in use of total hip replacement (THR) (ranging from 10.1 to 17.4%) for intracapsular fracture and in intermedullary nailing (ranging from 14.9 to 27.0%) of trochanteric fracture. Some geographical variation in mortality amongst intracapsular fracture patients was found, with slightly higher mortality in the East of England (adjusted odds ratio [aOR]: 1.22, 95% CI: 1.02-1.46). Trochanteric fractures showed slightly more variation, with higher 30-day mortality (aOR: 1.40, 95%CI: 1.05-1.88) in the East of England and significantly lower mortality in the North East (aOR: 0.65, 95%CI: 0.46-0.93). CONCLUSIONS: We have identified regional differences in operation type and 30-day mortality amongst hip fracture patients in England. The relationship between surgical approach and mortality has been explored, but the extent to which differential mortality reflects variation in approach to medical assessment, anaesthesia and other aspects of care warrants further investigation.

4.
Aging Clin Exp Res ; 33(4): 759-773, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33742387

RESUMO

Osteoporosis, a common chronic metabolic bone disease is associated with considerable morbidity and mortality. As the prevalence of osteoporosis increases with age, a paralleled elevation in the rate of incident fragility fractures will be observed. This narrative review explores the origins of bone and considers physiological mechanisms involved in bone homeostasis relevant to management and treatment. Secondary causes of osteoporosis, as well as osteosarcopenia are discussed followed by an overview of the commonly used pharmacological treatments for osteoporosis in older people.

5.
Calcif Tissue Int ; 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33661343

RESUMO

BACKGROUND: Biochemical bone turnover markers are useful tools to assess bone remodeling. C-terminal telopeptide of type I collagen (ß-CTX) has been recommended as a reference marker for bone resorption in research studies. METHODS: We describe the results of a multicenter study for routine clinical laboratory assays for ß-CTX in serum and plasma. Four centers (Athens GR, Copenhagen DK, Liege BE and Sheffield UK) collected serum and plasma (EDTA) samples from 796 patients presenting to osteoporosis clinics. Specimens were analyzed in duplicate with each of the available routine clinical laboratory methods according to the manufacturers' instructions. Passing-Bablok regressions, Bland-Altman plots, V-shape evaluation method, and Concordance correlation coefficient for ß-CTX values between serum and plasma specimens and between methods were used to determine the agreement between results. A generalized linear model was employed to identify possible variables that affected the relationship between the methods. Two pools of serum were finally prepared and sent to the four centers to be measured in 5-plicates on 5 consecutive days with the different methods. RESULTS: We identified significant variations between methods and between centers although comparison results were generally more consistent in plasma compared to serum. We developed univariate linear regression equations to predict Roche Elecsys®, IDS-iSYS, or IDS ELISA ß-CTX results from any other assay and a multivariable model including the site of analysis, the age, and weight of the patient. The coefficients of determination (R2) increased from approximately 0.80 in the univariate model to approximately 0.90 in the multivariable one, with the site of analysis being the major contributing factor. Results observed on the pools also suggest that long-term storage could explain the difference observed with the different methods on serum. CONCLUSION: Our results show large within- and between-assay variation for ß-CTX measurement, particularly in serum. Stability of the analyte could be one of the explanations. More studies should be undertaken to overcome this problem. Until harmonization is achieved, we recommend measuring ß-CTX by the same assay on EDTA plasma, especially for research purposes in large pharmacological trials where samples can be stored for long periods before they are assayed.

7.
Osteoporos Int ; 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33758991

RESUMO

In a simulated population of older women, we demonstrate that an upward shift in the population distribution of BMD by approximately 0.3SD may decrease the risk of incident fractures to the same extent as an intervention targeted to those with T-score less than -2.5. INTRODUCTION: To investigate the impact of population level or targeted alterations to BMD on the incidence of fractures. METHODS: We used a simulated cohort of 49,242 women with age and body mass index distribution from the UK, and prevalence of other clinical risk factors based on European FRAX® cohorts. Using FRAX probabilities of major osteoporotic fracture (MOF: hip, clinical vertebral, distal forearm, proximal humerus) and hip fracture, calculated with femoral neck BMD, we determined the expected number of fractures over 10 years, stratified by 10-year age band from 50 years. We then investigated the effect of (i) uplifting all individuals with T-score below -2.5 to be exactly -2.5 (high-risk strategy) and (ii) shifting the entire BMD distribution upwards (population strategy). RESULTS: Overall, the high-risk strategy prevented 573 MOF including 465 hip fractures. Moving the BMD T-score distribution upward by 0.27SD gave an equivalent reduction in numbers of MOF; for hip fractures prevented, this was 0.35SD. A global upward 0.25SD BMD shift prevented 524 MOF including 354 hip fractures, with corresponding figures for an increase of 0.5SD being 973 MOF prevented and 640 hip fractures prevented. The ratio of hip fracture to MOF prevented differed by the two approaches, such that for the high-risk strategy, the ratio was 0.81, and for the population strategy was 0.68 (0.25SD BMD uplift) and 0.66 (0.5SD BMD uplift). The numbers of fractures prevented by the high-risk strategy increased with age. In contrast, the age-related increase in numbers of fractures prevented with the population strategy rose with age, but peaked in the 70-79-year age band and declined thereafter. CONCLUSIONS: Both strategies reduced the numbers of expected incident fractures, with contrasting relative impacts by age and fracture site. Whilst the current analysis used UK/European anthropometric/risk factor distributions, further analyses calibrated to the distributions in other settings globally may be readily undertaken. Overall, these findings support the investigation of both population level interventions and those targeted at high fracture risk groups.

8.
Osteoporos Int ; 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33721032

RESUMO

This study demonstrates a substantial and persistent anti-osteoporosis treatment gap in men and women ≥50 years old who sustained major osteoporotic fracture(s) between 2005 and 2014 in Denmark. This was not substantially reduced by including hospital-administered anti-osteoporosis treatments. Strengthened post-fracture organization of care and secondary fracture prevention is highly needed. INTRODUCTION: The purpose of this study was to evaluate the Danish anti-osteoporosis treatment gap from 2005 to 2014 in patients sustaining a major osteoporotic fracture (MOF), and to assess the impact of including hospital-administered anti-osteoporosis medications (AOM) on the treatment gap among these patients. METHODS: In this retrospective, registry-based study, we included men and women aged 50 years or older and living in Denmark, who sustained at least one MOF between 2005 and 2014. We applied a repeated cross-sectional design to generate cohorts of patients sustaining a first MOF, hip, vertebral, humerus, or forearm fracture, respectively, within each calendar year. We evaluated the treatment gap as the proportion of patients within each cohort not receiving treatment with AOM within 1 year of the fracture. Hospital-administered AOM was identified by SKS code. RESULTS: The treatment gap among MOF patients decreased from 85% in 2005 to 79% in 2014. The gap was smaller among hip and vertebral fracture patients as compared to humerus and forearm fracture patients, and it was smaller in women than in men. The use of hospital-administered AOM was relatively uncommon, with a maximum of 0.9% of MOF patients initiating hospital-administered AOM (in 2012). We observed substantial variations in this proportion between fracture types and gender. Hospital-administered AOM was most commonly used among vertebral fracture patients. CONCLUSION: A significant treatment gap among patients sustaining a major osteoporotic fracture was present throughout our analysis, and including hospital-administered AOM did not significantly improve the treatment gap assessment. Improved secondary fracture prevention is urgently needed.

9.
J Eur Acad Dermatol Venereol ; 35(4): 797-806, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33533553

RESUMO

Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2, a novel RNA virus that was declared a global pandemic on 11 March 2020. The efficiency of infection with SARS-CoV-2 is reflected by its rapid global spread. The SARS-CoV-2 pandemic has implications for patients with inflammatory skin diseases on systemic immunotherapy who may be at increased risk of infection or more severe infection. This position paper is a focused examination of current evidence considering the mechanisms of action of immunotherapeutic drugs in relation to immune response to SARS-CoV-2. We aim to provide practical guidance for dermatologists managing patients with inflammatory skin conditions on systemic therapies during the current pandemic and beyond. Considering the limited and rapidly evolving evidence, mechanisms of action of therapies, and current knowledge of SARS-CoV-2 infection, we propose that systemic immunotherapy can be continued, with special considerations for at risk patients or those presenting with symptoms.


Assuntos
/epidemiologia , Dermatite/terapia , Imunoterapia , /complicações , Humanos , Padrões de Prática Médica , Medição de Risco
10.
Osteoporos Int ; 32(4): 611-617, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33558957

RESUMO

The effects of COVID-19 have the potential to impact on the management of chronic diseases including osteoporosis. A global survey has demonstrated that these impacts include an increase in telemedicine consultations, delays in DXA scanning, interruptions in the supply of medications and reductions in parenteral medication delivery. INTRODUCTION: The COVID-19 pandemic has had profound effects on the health of the global population both directly, via the sequelae of the infection, and indirectly, including the relative neglect of chronic disease management. Together the International Osteoporosis Foundation and National Osteoporosis Foundation sought to ascertain the impact on osteoporosis management. METHODS: Questionnaires were electronically circulated to a sample of members of both learned bodies and included information regarding the location and specialty of respondents, current extent of face to face consultations, alterations in osteoporosis risk assessment, telemedicine experience, alterations to medication ascertainment and delivery and electronic health record (EHR) utilisation. Responses were collected, quantitative data analysed, and qualitative data assessed for recurring themes. RESULTS: Responses were received from 209 healthcare workers from 53 countries, including 28% from Europe, 24% from North America, 19% from the Asia Pacific region, 17% from the Middle East and 12% from Latin America. Most respondents were physicians (85%) with physician assistants, physical therapists and nurses/nurse practitioners represented in the sample. The main three specialties represented included rheumatology (40%), endocrinology (22%) and orthopaedics (15%). In terms of the type of patient contact, 33% of respondents conducted telephone consultations and 21% video consultations. Bone mineral density assessment by dual-energy X-ray absorptiometry (DXA) usage was affected with only 29% able to obtain a scan as recommended. The majority of clinicians (60%) had systems in place to identify patients receiving parenteral medication, and 43% of clinicians reported difficulty in arranging appropriate osteoporosis medications during the COVID-19 crisis. CONCLUSIONS: To conclude through surveying a global sample of osteoporosis healthcare professionals, we have observed an increase in telemedicine consultations, delays in DXA scanning, interrupted supply of medications and reductions in parenteral medication delivery.


Assuntos
Osteoporose , Ásia , Europa (Continente) , Humanos , Oriente Médio , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Pandemias , Inquéritos e Questionários
11.
Osteoporos Int ; 32(3): 607-608, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33495876
12.
Osteoporos Int ; 32(3): 399-411, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33475820

RESUMO

Vertebral fractures are independent risk factors for vertebral and nonvertebral fractures. Since vertebral fractures are often missed, the relatively new introduction of vertebral fracture assessment (VFA) for imaging of the lateral spine during DXA-measurement of the spine and hips may contribute to detect vertebral fractures. We advocate performing a VFA in all patients with a recent fracture visiting a fracture liaison service (FLS). Fracture liaison services (FLS) are important service models for delivering secondary fracture prevention for older adults presenting with a fragility fracture. While commonly age, clinical risk factors (including fracture site and number of prior fracture) and BMD play a crucial role in determining fracture risk and indications for treatment with antiosteoporosis medications, prevalent vertebral fractures usually remain undetected. However, vertebral fractures are important independent risk factors for future vertebral and nonvertebral fractures. A development of the DXA technology, vertebral fracture assessment (VFA), allows for assessment of the lateral spine during the regular DXA bone mineral density measurement of the lumbar spine and hips. Recent approaches to the stratification of antiosteoporosis medication type according to baseline fracture risk, and differences by age in the indication for treatment by prior fracture mean that additional information from VFA may influence initiation and type of treatment. Furthermore, knowledge of baseline vertebral fractures allows reliable definition of incident vertebral fracture events during treatment, which may modify the approach to therapy. In this manuscript, we will discuss the epidemiology and clinical significance of vertebral fractures, the different methods of detecting vertebral fractures, and the rationale for, and implications of, use of VFA routinely in FLS. • Vertebral fracture assessment is a tool available on modern DXA instruments and has proven ability to detect vertebral fractures, the majority of which occur without a fall and without the signs and symptoms of an acute fracture. • Most osteoporosis guidelines internationally suggest that treatment with antiosteoporosis medications should be considered for older individuals (e.g., 65 years +) with a recent low trauma fracture without the need for DXA. • Younger individuals postfracture may be risk-assessed on the basis of FRAX® probability including DXA and associated treatment thresholds. • Future fracture risk is markedly influenced by both site, number, severity, and recency of prior fracture; awareness of baseline vertebral fractures facilitates definition of true incident vertebral fracture events occurring during antiosteoporosis treatment. • Detection of previously clinically silent vertebral fractures, defining site of prior fracture, might alter treatment decisions in younger or older FLS patients, consistent with recent IOF-ESCEO guidance on baseline-risk-stratified therapy, and provides a reliable baseline from which to define new, potentially therapy-altering, vertebral fracture events.


Assuntos
Osteoporose , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Absorciometria de Fóton , Idoso , Densidade Óssea , Humanos , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia
13.
J Chem Inf Model ; 60(12): 5832-5852, 2020 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-33326239

RESUMO

We present a supercomputer-driven pipeline for in silico drug discovery using enhanced sampling molecular dynamics (MD) and ensemble docking. Ensemble docking makes use of MD results by docking compound databases into representative protein binding-site conformations, thus taking into account the dynamic properties of the binding sites. We also describe preliminary results obtained for 24 systems involving eight proteins of the proteome of SARS-CoV-2. The MD involves temperature replica exchange enhanced sampling, making use of massively parallel supercomputing to quickly sample the configurational space of protein drug targets. Using the Summit supercomputer at the Oak Ridge National Laboratory, more than 1 ms of enhanced sampling MD can be generated per day. We have ensemble docked repurposing databases to 10 configurations of each of the 24 SARS-CoV-2 systems using AutoDock Vina. Comparison to experiment demonstrates remarkably high hit rates for the top scoring tranches of compounds identified by our ensemble approach. We also demonstrate that, using Autodock-GPU on Summit, it is possible to perform exhaustive docking of one billion compounds in under 24 h. Finally, we discuss preliminary results and planned improvements to the pipeline, including the use of quantum mechanical (QM), machine learning, and artificial intelligence (AI) methods to cluster MD trajectories and rescore docking poses.


Assuntos
Antivirais/química , /efeitos dos fármacos , Proteínas não Estruturais Virais/química , Inteligência Artificial , Sítios de Ligação , Simulação por Computador , Bases de Dados de Compostos Químicos , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Humanos , Simulação de Acoplamento Molecular , Conformação Proteica , Glicoproteína da Espícula de Coronavírus/química , Relação Estrutura-Atividade
14.
Artigo em Inglês | MEDLINE | ID: mdl-33246159

RESUMO

OBJECTIVES: Knee osteoarthritis (KOA) progression is frequently monitored by calculating the change in knee joint space width (JSW) measurements. Such differences are small and sensitive to measurement error. We aimed to assess the utility of two alternative statistical modelling methods for monitoring KOA. MATERIAL AND METHODS: We used JSW on radiographs from both the control arm of the Strontium Ranelate Efficacy in Knee Osteoarthritis trial (SEKOIA), a 3-year multicentre, double-blind, placebo-controlled phase three trial, and the Osteoarthritis Initiative (OAI), an open-access longitudinal dataset from the USA comprising participants followed over 8 years. Individual estimates of annualised change obtained from frequentist linear mixed effect (LME) and Bayesian hierarchical modelling, were compared with annualised crude change, and the association of these parameters with change in WOMAC pain was examined. RESULTS: Mean annualised JSW changes were comparable for all estimates, a reduction of around 0.14 mm/y in SEKOIA and 0.07 mm/y in OAI. The standard deviation (SD) of change estimates was lower with LME and Bayesian modelling than crude change (SEKOIA SD = 0.12, 0.12 and 0.21 respectively; OAI SD = 0.08, 0.08 and 0.11 respectively). Estimates from LME and Bayesian modelling were statistically significant predictors of change in pain in SEKOIA (LME P-value = 0.04, Bayes P-value = 0.04), while crude change did not predict change in pain (P-value = 0.10). CONCLUSIONS: Implementation of LME or Bayesian modelling in clinical trials and epidemiological studies, would reduce sample sizes by enabling all study participants to be included in analysis regardless of incomplete follow up, and precision of change estimates would improve. They provide increased power to detect associations with other measures.

15.
16.
Osteoporos Int ; 2020 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-32948904

RESUMO

Low body mass index (BMI) is an established risk factor for fractures in postmenopausal women but the interaction of obesity with bone microarchitecture is not fully understood. In this study, obesity was associated with more favourable bone microarchitecture parameters but not after parameters were normalised for body weight. INTRODUCTION: To examine bone microarchitecture in relation to fat mass and examine both areal bone mineral density (aBMD) and microarchitecture in relation to BMI categories in the UK arm of the Global Longitudinal Study of Osteoporosis in Women. METHODS: Four hundred and ninety-one women completed questionnaires detailing medical history; underwent anthropometric assessment; high-resolution peripheral quantitative computed tomography (HRpQCT) scans of the radius and tibia and DXA scans of whole body, proximal femur and lumbar spine. Fat mass index (FMI) residuals (independent of lean mass index) were derived. Linear regression was used to examine HRpQCT and DXA aBMD parameters according to BMI category (unadjusted) and HRpQCT parameters in relation to FMI residuals (with and without adjustment for anthropometric, demographic and lifestyle covariates). RESULTS: Mean (SD) age was 70.9 (5.4) years; 35.0% were overweight, 14.5% class 1 obese and 7.7% class 2/3 obese. There were significant increasing trends according to BMI category in aBMD of whole body, hip, femoral neck and lumbar spine (p ≤ 0.001); cortical area (p < 0.001), thickness (p < 0.001) and volumetric density (p < 0.03), and trabecular number (p < 0.001), volumetric density (p < 0.04) and separation (p < 0.001 for decreasing trend) at the radius and tibia. When normalised for body weight, all HRpQCT and DXA aBMD parameters decreased as BMI increased (p < 0.001). FMI residuals were associated with bone size and trabecular architecture at the radius and tibia, and tibial cortical microarchitecture. CONCLUSION: Significant trends in HRpQCT parameters suggested favourable bone microarchitecture at the radius and tibia with increasing BMI but these were not proportionate to increased weight.

17.
Placenta ; 99: 101-107, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32784052

RESUMO

OBJECTIVES: To investigate associations between placental volume (PV) at 11 weeks' gestation and offspring bone outcomes at birth, 6 years and 8 years. METHODS: 3D ultrasound scanning was used to assess 11 week PV in a subset (n = 236) of the Southampton Women's Survey (a prospective mother-offspring cohort). Maternal anthropometric measures and lifestyle information were obtained pre-pregnancy and at 11 weeks' gestation. Offspring dual-energy x-ray absorptiometry scanning was performed within 2 weeks postnatally and at 6 and 8 years. Linear regression was used to assess associations between PV and bone outcomes, adjusting for offspring age at DXA and sex, and maternal age, height, smoking status, walking speed and triceps skinfold thickness. ß are SD change in bone outcome per SD change in PV. RESULTS: In adjusted models, 11 week PV was positively associated with bone area (BA) at all time points, with evidence of persisting associations with increasing childhood age (birth: n = 80, ß = 0.23 [95%CI = 0.03, 0.42], 6 years: n = 110, ß = 0.17 [-0.01, 0.36], 8 years: n = 85, ß = 0.13 [-0.09, 0.36]). Similar associations between 11 week PV and bone mineral content (BMC) were observed. Associations with size-corrected bone mineral content were weaker at birth but strengthened in later childhood (birth: n = 78, ß = 0.07 [-0.21, 0.35], 6 years: n = 107, ß = 0.13 [-0.08, 0.34], 8 years: n = 71, ß = 0.19 [-0.05, 0.43]). CONCLUSIONS: 11 week PV is associated with DXA bone measures at birth, with evidence of persisting associations into later childhood. Further work is required to elucidate the contributions of placental morphology and function to gestational influences on skeletal development.

18.
Eur J Neurol ; 27(10): 1805-1820, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32713125

RESUMO

BACKGROUND AND PURPOSE: Dementia is one of the most common disorders and is associated with increased morbidity, mortality and decreased quality of life. The present guideline addresses important medical management issues including systematic medical follow-up, vascular risk factors in dementia, pain in dementia, use of antipsychotics in dementia and epilepsy in dementia. METHODS: A systematic review of the literature was carried out. Based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework, we developed a guideline. Where recommendations based on GRADE were not possible, a good practice statement was formulated. RESULTS: Systematic management of vascular risk factors should be performed in patients with mild to moderate dementia as prevention of cerebrovascular pathology may impact on the progression of dementia (Good Practice statement). Individuals with dementia (without previous stroke) and atrial fibrillation should be treated with anticoagulants (weak recommendation). Discontinuation of opioids should be considered in certain individuals with dementia (e.g. for whom there are no signs or symptoms of pain or no clear indication, or suspicion of side effects; Good Practice statement). Behavioral symptoms in persons with dementia should not be treated with mild analgesics (weak recommendation). In all patients with dementia treated with opioids, assessment of the individual risk-benefit ratio should be performed at regular intervals. Regular, preplanned medical follow-up should be offered to all patients with dementia. The setting will depend on the organization of local health services and should, as a minimum, include general practitioners with easy access to dementia specialists (Good Practice statement). Individuals with dementia and agitation and/or aggression should be treated with atypical antipsychotics only after all non-pharmacological measures have been proven to be without benefit or in the case of severe self-harm or harm to others (weak recommendation). Antipsychotics should be discontinued after cessation of behavioral disturbances and in patients in whom there are side effects (Good Practice statement). For treatment of epilepsy in individuals with dementia, newer anticonvulsants should be considered as first-line therapy (Good Practice statement). CONCLUSION: This GRADE-based guideline offers recommendations on several important medical issues in patients with dementia, and thus adds important guidance for clinicians. For some issues, very little or no evidence was identified, highlighting the importance of further studies within these areas.

19.
Drugs ; 80(15): 1537-1552, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32725307

RESUMO

The incidence of osteoporosis and cardiovascular disease increases with age, and there are potentially shared mechanistic associations between the two conditions. It is therefore highly relevant to understand the cardiovascular implications of osteoporosis medications. These are presented in this narrative review. Calcium supplementation could theoretically cause atheroma formation via calcium deposition, and in one study was found to be associated with myocardial infarction, but this has not been replicated. Vitamin D supplementation has been extensively investigated for cardiac benefit, but no consistent effect has been found. Despite findings in the early 21st century that menopausal hormone therapy was associated with coronary artery disease and venous thromboembolism (VTE), this therapy is now thought to be potentially safe (from a cardiac perspective) if started within the first 10 years of the menopause. Selective estrogen receptor modulators (SERMs) are associated with increased risk of VTE and may be related to fatal strokes (a subset of total strokes). Bisphosphonates could theoretically provide protection against atheroma. However, data from randomised trials and observational studies have neither robustly supported this nor consistently demonstrated the potential association with atrial fibrillation. Denosumab does not appear to be associated with cardiovascular disease and, although parathyroid hormone analogues are associated with palpitations and dizziness, no association with a defined cardiovascular pathology has been demonstrated. Finally, romosozumab has been shown to have a possible cardiovascular signal, and therefore post-market surveillance of this therapy will be vital.

20.
Osteoporos Int ; 31(12): 2271-2286, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32642851

RESUMO

We provide an evidence base and guidance for the use of menopausal hormone therapy (MHT) for the maintenance of skeletal health and prevention of future fractures in recently menopausal women. Despite controversy over associated side effects, which has limited its use in recent decades, the potential role for MHT soon after menopause in the management of postmenopausal osteoporosis is increasingly recognized. We present a narrative review of the benefits versus risks of using MHT in the management of postmenopausal osteoporosis. Current literature suggests robust anti-fracture efficacy of MHT in patients unselected for low BMD, regardless of concomitant use with progestogens, but with limited evidence of persisting skeletal benefits following cessation of therapy. Side effects include cardiovascular events, thromboembolic disease, stroke and breast cancer, but the benefit-risk profile differs according to the use of opposed versus unopposed oestrogens, type of oestrogen/progestogen, dose and route of delivery and, for cardiovascular events, timing of MHT use. Overall, the benefit-risk profile supports MHT treatment in women who have recently (< 10 years) become menopausal, who have menopausal symptoms and who are less than 60 years old, with a low baseline risk for adverse events. MHT should be considered as an option for the maintenance of skeletal health in women, specifically as an additional benefit in the context of treatment of menopausal symptoms, when commenced at the menopause, or shortly thereafter, in the context of a personalized benefit-risk evaluation.

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