RESUMO
Vitamin D is important for musculoskeletal health. Concentrations of 25-hydroxyvitamin D, the most commonly measured metabolite, vary markedly around the world and are influenced by many factors including sun exposure, skin pigmentation, covering, season and supplement use. Whilst overt vitamin D deficiency with biochemical consequences presents an increased risk of severe sequelae such as rickets, osteomalacia or cardiomyopathy and usually warrants prompt replacement treatment, the role of vitamin D supplementation in the population presents a different set of considerations. Here the issue is to keep, on average, the population at a level whereby the risk of adverse health outcomes in the population is minimised. This position paper, which complements recently published work from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, addresses key considerations regarding vitamin D assessment and intervention from the population perspective. This position paper, on behalf of the International Osteoporosis Foundation Vitamin D Working Group, summarises the burden and possible amelioration of vitamin D deficiency in global populations. It addresses key issues including screening, supplementation and food fortification.
Assuntos
Suplementos Nutricionais , Saúde Global , Deficiência de Vitamina D , Vitamina D , Humanos , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/tratamento farmacológico , Vitamina D/sangue , Vitamina D/análogos & derivados , Vitamina D/uso terapêutico , Alimentos Fortificados , Programas de Rastreamento/métodos , Conservadores da Densidade Óssea/uso terapêuticoRESUMO
Guidelines for doctors managing osteoporosis in the Asia-Pacific region vary widely. We compared 18 guidelines for similarities and differences in five key areas. We then used a structured consensus process to develop clinical standards of care for the diagnosis and management of osteoporosis and for improving the quality of care. PURPOSE: Minimum clinical standards for assessment and management of osteoporosis are needed in the Asia-Pacific (AP) region to inform clinical practice guidelines (CPGs) and to improve osteoporosis care. We present the framework of these clinical standards and describe its development. METHODS: We conducted a structured comparative analysis of existing CPGs in the AP region using a "5IQ" model (identification, investigation, information, intervention, integration, and quality). One-hundred data elements were extracted from each guideline. We then employed a four-round Delphi consensus process to structure the framework, identify key components of guidance, and develop clinical care standards. RESULTS: Eighteen guidelines were included. The 5IQ analysis demonstrated marked heterogeneity, notably in guidance on risk factors, the use of biochemical markers, self-care information for patients, indications for osteoporosis treatment, use of fracture risk assessment tools, and protocols for monitoring treatment. There was minimal guidance on long-term management plans or on strategies and systems for clinical quality improvement. Twenty-nine APCO members participated in the Delphi process, resulting in consensus on 16 clinical standards, with levels of attainment defined for those on identification and investigation of fragility fractures, vertebral fracture assessment, and inclusion of quality metrics in guidelines. CONCLUSION: The 5IQ analysis confirmed previous anecdotal observations of marked heterogeneity of osteoporosis clinical guidelines in the AP region. The Framework provides practical, clear, and feasible recommendations for osteoporosis care and can be adapted for use in other such vastly diverse regions. Implementation of the standards is expected to significantly lessen the global burden of osteoporosis.
Assuntos
Osteoporose , Fraturas da Coluna Vertebral , Ásia/epidemiologia , Humanos , Programas de Rastreamento , Osteoporose/diagnóstico , Osteoporose/epidemiologia , Osteoporose/terapia , Padrão de CuidadoRESUMO
AIM: India contributes towards a large part of the worldwide epidemic of diabetes and its associated complications. However, there are limited longitudinal studies available in India to understand the occurrence of diabetes complications over time. This pan-India longitudinal study was initiated to assess the real-world outcomes of diabetes across the country. METHODS: The LANDMARC study is the first prospective, multicentre, longitudinal, observational study investigating a large cohort of people with type 2 diabetes mellitus across India over a period of 3 years. The primary objective of this ongoing study is to determine the proportion of people developing macrovascular diabetes complications over the duration of the study (36 months ± 45 days) distributed over seven visits; the secondary objective is to evaluate microvascular diabetes complications, glycaemic control and time-to-treatment adaptation or intensification. Overall, 6300 participants (aged 25-60 years) diagnosed with type 2 diabetes for at least 2 years will be included from 450 centres across India. Data will be recorded for baseline demographics, comorbidities, glycaemic measurements, use of anti-hyperglycaemic medications and any cardiovascular or other diabetes-related events occurring during the observational study period. CONCLUSIONS: The LANDMARC study is expected to reveal the trends in complications associated with diabetes, treatment strategies used by physicians, and correlation among treatment, control and complications of diabetes within the Indian context. The findings of this study will help to identify the disease burden, emergence of early-onset complications and dose titration patterns, and eventually develop person-centred care and facilitate public health agencies to invest appropriate resources in the management of diabetes. (Trial Registration No: CTRI/2017/05/008452).
Assuntos
Diabetes Mellitus Tipo 2/terapia , Angiopatias Diabéticas/epidemiologia , Hipoglicemiantes/uso terapêutico , Adulto , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Angiopatias Diabéticas/etiologia , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/etiologia , Neuropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/etiologia , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/etiologia , Feminino , Hemoglobinas Glicadas/metabolismo , Controle Glicêmico , Humanos , Índia/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Estudos Observacionais como Assunto , Doenças Vasculares Periféricas/epidemiologia , Doenças Vasculares Periféricas/etiologia , Estudos Prospectivos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologiaRESUMO
BACKGROUND: Peri-operative glucocorticoids are routinely administered to patients undergoing trans-sphenoidal surgery for non-functional pituitary adenomas (NFPA) irrespective of hypothalamus-pituitary-adrenal (HPA) axis status. PURPOSE: Evaluation of HPA axis before and 12 weeks after endoscopic trans-sphenoidal adenomectomy (E-TSA) utilizing low-dose (1 µg) ACTH stimulation test (LDACTH) to determine the need for glucocorticoid administration in patients with NFPA. We also determined the factors that can predict occurrence of hypocortisolism at 12 weeks after surgery. METHODS: Sixty-three consecutive patients with NFPA requiring surgical excision were enrolled in this study. Glucocorticoids were administered to patients with demonstrable hypocortisolism [preoperative peak cortisol < 16 µg/dL during LDACTH test, postoperative day 3 (POD-3) 0800 hrs Cortisol < 8 µg/dL or stimulated cortisol (LDACTH) < 16 µg/dL at 12 weeks]. RESULTS: Hypocortisolism was present in 43 patients (68.2%) pre-operatively and persisted in 33 patients (52.4%) on POD-3. Thirty-three patients (52.4%) had hypocortisolism at 12 weeks after surgery. Eleven patients (17.4%) did not require glucocorticoids during the entire study period and 30 patients (47.6%) did not require glucocorticoids after 3 months. None of the patients developed adrenal crisis during the study. Hypocortisolism on the third post-operative day was the single significant predictor of hypocortisolism at 12 weeks after the surgery. There was a significant correlation between POD-3 0800 hrs cortisol ≥ 8µg/dL and stimulated cortisol (LDACTH) ≥16µg/dL at 12 weeks (r = 0.62, p < 0.0001). POD-3 0800 hrs cortisol ≥ 8 µg/dL had 73% sensitivity and 79% specificity in predicting eucortisolism at 12 weeks. CONCLUSIONS: HPA function is preserved in significant proportion of NFPA patients undergoing E-TSA. Perioperative glucocorticoids should be given only in patients with demonstrable preoperative hypocortisolism on 1 µg ACTH test. Postoperative day 3 0800 hrs cortisol is a reasonable predictor of HPA axis status at 12 weeks after surgery.
Assuntos
Adenoma/diagnóstico , Adenoma/cirurgia , Hormônio Adrenocorticotrópico/administração & dosagem , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/cirurgia , Testes de Função Adreno-Hipofisária/métodos , Adenoma/metabolismo , Adenoma/fisiopatologia , Hormônio Adrenocorticotrópico/farmacologia , Adulto , Assistência ao Convalescente/métodos , Idoso , Relação Dose-Resposta a Droga , Feminino , Humanos , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Índia , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/fisiopatologia , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/fisiopatologia , Cuidados Pré-Operatórios/métodos , Período Pré-Operatório , Prognóstico , Resultado do Tratamento , Adulto JovemRESUMO
The original Electronic Supplementary Material file 3 contained an erroneous reference for Mali. A link to the corrected file is provided here.
RESUMO
Low calcium intake may adversely affect bone health in adults. Recognizing the presence of low calcium intake is necessary to develop national strategies to optimize intake. To highlight regions where calcium intake should be improved, we systematically searched for the most representative national dietary calcium intake data in adults from the general population in all countries. We searched 13 electronic databases and requested data from domain experts. Studies were double-screened for eligibility. Data were extracted into a standard form. We developed an interactive global map, categorizing countries based on average calcium intake and summarized differences in intake based on sex, age, and socioeconomic status. Searches yielded 9780 abstracts. Across the 74 countries with data, average national dietary calcium intake ranges from 175 to 1233 mg/day. Many countries in Asia have average dietary calcium intake less than 500 mg/day. Countries in Africa and South America mostly have low calcium intake between about 400 and 700 mg/day. Only Northern European countries have national calcium intake greater than 1000 mg/day. Survey data for three quarters of available countries were not nationally representative. Average calcium intake is generally lower in women than men, but there are no clear patterns across countries regarding relative calcium intake by age, sex, or socioeconomic status. The global calcium map reveals that many countries have low average calcium intake. But recent, nationally representative data are mostly lacking. This review draws attention to regions where measures to increase calcium intake are likely to have skeletal benefits.
Assuntos
Cálcio da Dieta/administração & dosagem , Saúde Global/estatística & dados numéricos , Fatores Etários , Inquéritos sobre Dietas , Humanos , Fatores Sexuais , Classe SocialRESUMO
AIMS: To provide a review of the available data and practical use of insulin degludec with insulin aspart (IDegAsp). Premixed insulins provide basal and prandial glucose control; however, they have an intermediate-acting prandial insulin component and do not provide as effective basal coverage as true long-acting insulins, owing to the physicochemical incompatibility of their individual components, coupled with the inflexibility of adjustment. The molecular structure of the co-formulation of IDegAsp, a novel insulin preparation, allows these two molecules to coexist without affecting their individual pharmacodynamic profiles. METHODS: Clinical evidence in phase 2/3 trials of IDegAsp efficacy and safety in type 1 and type 2 diabetes mellitus (T1DM and T2DM) have been assessed and summarised. RESULTS: In people with T2DM, once- and twice-daily dosing provides similar overall glycaemic control (HbA1c ) to current modern insulins, but with lower risk of nocturnal hypoglycaemia. In prior insulin users, glycaemic control was achieved with lower or equal insulin doses vs. other basal+meal-time or premix insulin regimens. In insulin-naïve patients with T2DM, IDegAsp can be started once or twice-daily, based on individual need. People switching from more than once-daily basal or premix insulin therapy can be converted unit-to-unit to once-daily IDegAsp, although this strategy should be assessed by the physician on an individual basis. CONCLUSIONS: IDegAsp offers physicians and people with T2DM a simpler insulin regimen than other available basal-bolus or premix-based insulin regimens, with stable daytime basal coverage, a lower rate of hypoglycaemia and some flexibility in injection timing compared with premix insulins.
Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina Aspart/administração & dosagem , Insulina de Ação Prolongada/administração & dosagem , Glicemia , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Esquema de Medicação , Substituição de Medicamentos , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/farmacologia , Insulina Aspart/efeitos adversos , Insulina Aspart/farmacologia , Insulina de Ação Prolongada/efeitos adversos , Insulina de Ação Prolongada/farmacologia , Resultado do TratamentoRESUMO
This pilot audit explored how bone health is assessed patients with diabetes in diverse centres across Asia. Only 343 of 1092 (31%) audited patients had a bone health assessment, 27% of whom were diagnosed with osteoporosis. Quality improvement strategies are needed to address gaps in patient care in this area. PURPOSE: The Asia Pacific Consortium on Osteoporosis (APCO) Framework outlines clinical standards for assessing and managing osteoporosis. A pilot audit evaluated adherence to clinical standard 4, which states that bone health should be assessed in patients with conditions associated with bone loss and/or increased fracture risk; this report summarises the audit findings in patients with diabetes. A secondary aim was to assess the practicality and real-world use of the APCO bone health audit tool kit. METHODS: Eight centres across Asia participated in the pilot audit, selecting diabetes as the target group. Participants reviewed their practice records for at least 20 consecutively treated patients with the target condition. Questions covered routine investigations, bone health assessment, osteoporosis diagnosis, and patient referral pathways. Data were summarised descriptively. RESULTS: The participants represented public hospitals, university medical centres, and private clinics from India, Malaysia, Pakistan, Singapore, Taiwan, and Vietnam that see an estimated total of 95,000 patients with diabetes per year. Overall, only 343 of 1092 audited patients (31%) had a bone health assessment. Osteoporosis was subsequently diagnosed in 92 of 343 (27%) patients. CONCLUSION: Bone health was not assessed in most patients with diabetes. The results provide insight into current practices across diverse Asian centres and demonstrate the practical value of the audit tool kit. Participant feedback has been used to improve the tool kit. Results of this pilot audit are being used in the respective centres to inform quality improvement projects needed to overcome the gap in patient care.
Assuntos
Fidelidade a Diretrizes , Osteoporose , Humanos , Projetos Piloto , Osteoporose/epidemiologia , Feminino , Masculino , Ásia/epidemiologia , Fidelidade a Diretrizes/estatística & dados numéricos , Pessoa de Meia-Idade , Idoso , Auditoria Médica , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , Densidade ÓsseaRESUMO
Muscle strength plays an important role in determining risk for falls, which result in fractures and other injuries. While bone loss has long been recognized as an inevitable consequence of aging, sarcopenia-the gradual loss of skeletal muscle mass and strength that occurs with advancing age-has recently received increased attention. A review of the literature was undertaken to identify nutritional factors that contribute to loss of muscle mass. The role of protein, acid-base balance, vitamin D/calcium, and other minor nutrients like B vitamins was reviewed. Muscle wasting is a multifactorial process involving intrinsic and extrinsic alterations. A loss of fast twitch fibers, glycation of proteins, and insulin resistance may play an important role in the loss of muscle strength and development of sarcopenia. Protein intake plays an integral part in muscle health and an intake of 1.0-1.2 g/kg of body weight per day is probably optimal for older adults. There is a moderate [corrected] relationship between vitamin D status and muscle strength. Chronic ingestion of acid-producing diets appears to have a negative impact on muscle performance, and decreases in vitamin B12 and folic acid intake may also impair muscle function through their action on homocysteine. An adequate nutritional intake and an optimal dietary acid-base balance are important elements of any strategy to preserve muscle mass and strength during aging.
Assuntos
Fenômenos Fisiológicos da Nutrição do Idoso/fisiologia , Força Muscular/fisiologia , Sarcopenia/fisiopatologia , Idoso , Envelhecimento/fisiologia , Proteínas Alimentares/administração & dosagem , Humanos , Desnutrição/complicações , Estado Nutricional , Sarcopenia/etiologia , Sarcopenia/terapia , Vitamina D/administração & dosagemRESUMO
UNLABELLED: One thousand six hundred healthy subjects aged more than 50 years, residing in Delhi, were evaluated for bone mineral metabolic parameters. High prevalence of osteoporosis (35.1% subjects) was observed in this population. Bone mineral density (BMD) correlated positively with body mass index (BMI) and negatively with PTH levels. No correlation was observed with serum 25(OH)D levels. INTRODUCTION: To assess the bone health status in elderly Indians and compare peripheral DXA (pDXA) with central DXA in evaluation of osteoporosis. METHODS: The study involved 1,600 healthy subjects more than 50 years of age residing in Delhi, India, who underwent anthropometric, biochemical, and hormonal evaluation. BMD was measured by DXA at lumbar spine, hip, and distal radius; and by pDXA at forearm and calcaneum. RESULTS: Seven hundred ninety-two males and 808 postmenopausal females, with a mean age of 57.67 ± 9.46 years were evaluated. Osteoporosis was present in 35.1% subjects (M-24.6%, F-42.5%) and osteopenia in 49.5% (M-54.3%, F-44.9%). Prevalence of osteoporosis increased with age in females, but not in males. BMD at all sites, except distal radius, was positively correlated with BMI (r=0.037, p=0.14). Total body BMD was negatively correlated with alkaline phosphatase (r= -0.184, p<0.00001) and PTH levels (r= -0.099, p<0.00001), respectively. No significant correlation was observed between serum 25(OH)D levels and BMD at any site. BMD at forearm and calcaneum, measured using pDXA, showed strong positive correlation with BMD measured by central DXA. pDXA had sensitivity of 88%, specificity of 55%, and negative and positive predictive values of 89% and 52%, respectively, at T-score -2.5 at peripheral sites compared to central DXA. CONCLUSIONS: A high prevalence of osteoporosis was observed in elderly Indian subjects. pDXA has high negative predictive value, making it a useful tool in population screening for osteoporosis.
Assuntos
Densidade Óssea/fisiologia , Osteoporose/epidemiologia , Absorciometria de Fóton , Idoso , Índice de Massa Corporal , Doenças Ósseas Metabólicas/diagnóstico por imagem , Doenças Ósseas Metabólicas/epidemiologia , Calcâneo/diagnóstico por imagem , Feminino , Fêmur/diagnóstico por imagem , Humanos , Índia , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Osteoporose/diagnóstico por imagem , Hormônio Paratireóideo/sangue , Prevalência , Rádio (Anatomia)/diagnóstico por imagem , Fatores de Risco , Sensibilidade e Especificidade , Vitamina D/análogos & derivados , Vitamina D/sangueRESUMO
This position paper of the International Osteoporosis Foundation makes recommendations for vitamin D nutrition in elderly men and women from an evidence-based perspective.
Assuntos
Vitamina D/administração & dosagem , Acidentes por Quedas/prevenção & controle , Administração Oral , Idoso , Esquema de Medicação , Medicina Baseada em Evidências , Feminino , Fraturas Ósseas/etiologia , Fraturas Ósseas/prevenção & controle , Humanos , Masculino , Necessidades Nutricionais , Vitamina D/análogos & derivados , Vitamina D/sangue , Vitamina D/uso terapêutico , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/tratamento farmacológicoRESUMO
UNLABELLED: This review describes the vitamin D status in different regions of the world with the objective of understanding the scope of hypovitaminosis D and the factors related to its prevalence that may contribute to the pathogenesis of osteoporosis and fragility fractures. INTRODUCTION: Vitamin D status has been linked to the pathogenesis of hip fractures as well as other skeletal and non-skeletal disorders. The purpose of this review is to provide a global perspective of vitamin D status across different regions of the world and to identify the common and significant determinants of hypovitaminosis D. METHODS: Six regions of the world were reviewed-Asia, Europe, Middle East and Africa, Latin America, North America, and Oceania-through a survey of published literature. RESULTS: The definition of vitamin D insufficiency and deficiency, as well as assay methodology for 25-hydroxyvitamin D or 25(OH)D, vary between studies. However, serum 25(OH)D levels below 75 nmol/L are prevalent in every region studied whilst levels below 25 nmol/L are most common in regions such as South Asia and the Middle East. Older age, female sex, higher latitude, winter season, darker skin pigmentation, less sunlight exposure, dietary habits, and absence of vitamin D fortification are the main factors that are significantly associated with lower 25(OH)D levels. CONCLUSION: Reports from across the world indicate that hypovitaminosis D is widespread and is re-emerging as a major health problem globally.
Assuntos
Saúde Global , Deficiência de Vitamina D/epidemiologia , Vitamina D/sangue , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Pré-Escolar , Comparação Transcultural , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fatores Sexuais , Deficiência de Vitamina D/etiologia , Adulto JovemRESUMO
OBJECTIVES: Vitamin D is known to play an important role in bone mineral metabolism. Its deficiency may affect growth and status of bone markers in children. Hence, we undertook to study the status of bone markers in children with vitamin D deficiency (VDD) and impact of vitamin D3 supplementation on them. MATERIALS AND METHODS: Total 468 out of 615 children and adolescents with VDD, who were given either of the three doses (600, 1000, and 2000) of vitamin D supplementation, were included in the study. These 468 children with pre- and postsupplementation preserved samples with available anthropometry, serum biochemistry, 25-hydroxy-vitamin D, and parathormone were evaluated for bone formation (procollagen type 1 amino-terminal propeptide [P1NP]) and resorption (ß-cross laps [CTx]) markers. RESULTS: The mean age and body mass index of these children were 11.3 ± 2.3 years (boys: 11.5 ± 2.4; girls: 12.2 ± 1.2 years; P = 0.03) and 18.1 ± 3.8 kg/m2 (boys: 18.2 ± 3.9; girls: 17.6 ± 3.2 kg/m2; P = 0.208), respectively. There were 8.8% subjects with severe, 42.7% with moderate, and 48.5% with mild VDD. There was a significant decline in serum P1NP (from 691 ± 233 ng/ml to 640 ± 259 ng/ml, P < 0.001) and CTx (from 1.67 ± 0.53 ng/ml to 1.39 ± 0.51 ng/ml, P < 0.001) following supplementation. Though decline in serum P1NP and CTx levels was observed in both boys and girls, among all three supplementation groups and VDD categories, the effect was more marked in serum CTx than P1NP levels. CONCLUSIONS: Vitamin D supplementation in VDD children resulted in decrease in both bone formation (P1NP) and resorption (CTx). The impact, however, was more marked on bone resorption than bone formation.
RESUMO
The recent cloning of a [Ca2+]o-sensing receptor from several different tissues in several species directly demonstrates that a variety of cells can directly recognize and respond to small changes in their ambient level of [Ca2+]o through a G protein-coupled, cell surface receptor. This finding directly documents that [Ca2+]o can act as an extracellular, first messenger in addition to subserving its better known role as an intracellular second messenger. Several of the tissues expressing the CaR are important elements in the calcium homeostatic system that have long been known to be capable of sensing [Ca2+]o, such as parathyroid and thyroidal C cells. The presence of the receptor in the kidney, however, provides strong evidence that several of the long-recognized but poorly understood direct actions of [Ca2+]o on renal function could be mediated by the CaR. These actions include the up-regulation of urinary calcium and magnesium excretion in the setting of hypercalcemia, which complements the indirect inhibition of renal tubular reabsorption of calcium that results from high [Ca2+]o-mediated inhibition for PTH secretion. The impaired renal concentrating capacity in hypercalcemia is likely a manifestation of a homeostatically important interaction between the regulation of renal calcium and water handling that reduces the risk of pathological deposition of calcium in the kidney when there is a need to dispose of excess, calcium in the urine. In this regard, the availability of human syndromes of [Ca2+]o "resistance" or "overresponsiveness" due to loss-of-function or gain-of-function mutations in the CaR, respectively, have provided useful experiments in nature that have clarified the importance of the receptor in both abnormal and normal physiology. Much remains to be learned, however, about the role of the CaR in locations, such as the brain, where it likely responds to local rather than systemic levels of [Ca2+]o. In such sites, it may represent an important modulator of neuronal function, responding to [Ca2+]o as a neuromodulator or even neurotransmitter. The development of therapeutics that either activate or inhibit the function of the CaR may be useful for treating a variety of conditions in which the receptor is either under- or overactive. Finally, it would not be surprising to discover additional receptors for [Ca2+]o or for other ions (the CaR may, in fact, be an important [Mg2+]o-sensor) that could function abnormally in certain disease states and be amenable to pharmacological manipulation with ion receptor-based therapeutics.
Assuntos
Proteínas de Ligação ao Cálcio/fisiologia , Cálcio/metabolismo , Animais , Proteínas de Ligação ao Cálcio/química , Proteínas de Ligação ao Cálcio/genética , Células/metabolismo , Resistência a Medicamentos , Homeostase , Humanos , Recém-Nascido , Mutação , SíndromeRESUMO
Osteoporosis is characterized by low bone mass with micro architectural deterioration of bone tissue leading to enhance bone fragility, thus increasing the susceptibility to fracture. Although exact numbers are not available, based on available data and clinical experience, on estimated 25 million Indians may be affected. Osteoporotic fractures in India occur commonly in both sexes, and may occur at a younger age than in the West. Recently published data have clearly demonstrated widespread vitamin D deficiency across India, at all ages and in both sexes, particularly in the urban areas. Poor sunlight exposure, skin pigmentation and a vitamin D-deficient diet are some obvious causes for this finding. Indians have low BMD as compared to the western Caucasians. This could be attributed to differences in skeletal size; however, the high prevalence of vitamin D deficiency is a major factor in the low BMD and poor bone health of Indians. Healthy lifestyle (diet, exercise and sunlight exposure) can have a major positive impact on the bone metabolism and bone health of Indians. These public health measures are recommended for the population at large as they are efficacious, safe and cost-effective. The peak bone mass of the population can be increased significantly by appropriate and timely intervention in children. Pharmacological interventions are expensive and should therefore be targeted to only those at high risk of fractures.
Assuntos
Densidade Óssea , Osteoporose/epidemiologia , Deficiência de Vitamina D/epidemiologia , Humanos , Índia/epidemiologia , Estilo de Vida , Osteoporose/diagnóstico , Osteoporose/terapia , Fatores de Risco , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/terapiaRESUMO
OBJECTIVE: To compare the adequacy and efficacy of different doses of vitamin D3 in pre-pubertal girls. DESIGN: Cluster Randomized controlled trial. SETTING: Public school in Delhi, India, between August 2015 and February 2016. PARTICIPANTS: 216 healthy pre-pubertal girls, aged 6.1-11.8 years. INTERVENTION: Daily supplementation with 600 IU (n=74), 1000 IU (n=67) or 2000 IU (n=75) of vitamin D3 under supervision for 6 months. OUTCOME MEASURES: Primary: Rise in serum 25 hydroxy Vitamin D (25(OH)D); Secondary: Change in bone formation and resorption markers. RESULTS: Following 6 months of supplementation, the mean (SD) rise in serum 25(OH)D was maximum with 2000 IU (24.09 (8.28) ng/mL), followed by with 1000 IU (17.96 (6.55) ng/mL) and 600 IU (15.48 (7.00) ng/mL). Serum 25(OH)D levels of ≥20 ng/mL were seen in 91% in 600 IU group , 97% in 1000 IU group and 100% in 2000 IU group. The overall mean (SD) rise in urinary calcium creatinine ratio (0.05 (0.28) to 0.13 (0.12) mg/mg), and serum procollagen type I N-terminal propeptide (538.9 (199.78) to 655.5 (218.24) ng/mL), and reduction in serum carboxy-terminal telopeptide (0.745 (0.23) to 0.382 (0.23) ng/mL) was significant (P<0.01). The change in the above parameters was comparable among the three groups after adjustment for age. CONCLUSIONS: Daily vitamin D supplementation with 600 IU to 2000 IU for 6 months results in Vitamin D sufficiency in >90% of pre-pubertal girls.
Assuntos
Colecalciferol/administração & dosagem , Suplementos Nutricionais/estatística & dados numéricos , Deficiência de Vitamina D/tratamento farmacológico , Vitamina D/análogos & derivados , Biomarcadores/metabolismo , Osso e Ossos/fisiologia , Criança , Feminino , Humanos , Índia , Vitamina D/sangue , Deficiência de Vitamina D/sangueRESUMO
The purpose of this study was to describe the impact of gastrointestinal events on patient-reported outcomes and health care resource use among Asia-Pacific women with postmenopausal osteoporosis. The results of this study show that gastrointestinal events decreased adherence, treatment satisfaction, and quality of life in Asia-Pacific women with postmenopausal osteoporosis. PURPOSE: This study aimed to describe the impact of gastrointestinal (GI) events on patient-reported outcomes and health care resource use among Asia-Pacific women with postmenopausal osteoporosis. METHODS: The MUSIC OS-AP study included an observational cohort study of postmenopausal women with osteoporosis. Women were classified as untreated or treated, with treated patients further classified as new or experienced users. Adherence was measured by the Adherence Evaluation of Osteoporosis treatment (ADEOS) questionnaire, treatment satisfaction by the Osteoporosis Patient Satisfaction Questionnaire (OPSAT) while general health-related and osteoporosis-specific quality of life were measured by the European Quality of Life-5 Dimensions (EQ-5D) questionnaire and the Osteoporosis Assessment Questionnaire (OPAQ), respectively. The association of GI events with these outcomes was determined by covariate-adjusted regression analysis of least squares mean differences in the scores of treated patients with and without GI events. Resource utilization was measured as the number of physician visits over the past 3 months, and multivariate regression analysis was used to assess the association of GI events with the likelihood of a visit. RESULTS: The GI event profile, quality of life scores, and resource use were numerically similar in untreated and treated women. The rate of adherence among treated women was higher in experienced than in new users. As indicated by mean scores, experienced users had better quality of life and slightly higher treatment satisfaction and fewer physician visits than new users. Except for adherence in new users, all measures were similarly adversely affected by GI events in both new and experienced users. CONCLUSIONS: GI events decreased adherence, treatment satisfaction, and quality of life in Asia-Pacific women with postmenopausal osteoporosis.
Assuntos
Conservadores da Densidade Óssea/efeitos adversos , Gastroenteropatias/induzido quimicamente , Osteoporose Pós-Menopausa/tratamento farmacológico , Idoso , Australásia/epidemiologia , Conservadores da Densidade Óssea/uso terapêutico , Estudos de Coortes , Ásia Oriental/epidemiologia , Feminino , Gastroenteropatias/epidemiologia , Recursos em Saúde/estatística & dados numéricos , Humanos , Índia/epidemiologia , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/epidemiologia , Medidas de Resultados Relatados pelo Paciente , Satisfação do Paciente , Estudos Prospectivos , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The objectives of the physician survey component of the MUSIC OS-AP study were to describe physicians' approaches to treatment of women with postmenopausal osteoporosis and to understand the influence of gastrointestinal (GI) events on treatment in clinical practice. METHODS: Physicians were recruited from 5 Asia-Pacific countries. Questionnaires collected information about physicians' standard practices for treatment of patients with osteoporosis, as well as their perspectives on the influence of GI events on osteoporosis treatment approaches. RESULTS: A total of 59 physicians participated in the study. The most frequently prescribed or recommended treatments were vitamin D (84% of patients), calcium (82%), and oral bisphosphonates (59%). When choosing a medication for treatment-naïve patients, GI sensitivity was often or always a factor for 79% of physicians. Among physicians not prescribing pharmacologic treatment, a mean of 18% of non-prescriptions were due to GI sensitivity. For patients with pre-existing GI conditions, physicians most frequently ranked use of non-oral osteoporosis medication as the first treatment strategy (47%), followed by co-prescription with a proton pump inhibitor or other gastro-protective agent (31%). For patients developing GI symptoms after starting pharmacologic treatment, the most frequently first-ranked management strategy was to check if patients were taking their osteoporosis medication correctly as prescribed (64%), followed by temporary discontinuation of the medication (i.e., a drug holiday) until GI events have resolved (31%) and co-prescription with a proton pump inhibitor or other gastroprotective agent (24%). CONCLUSIONS: These results suggest that GI events influence the prescribing practices of physicians in the Asia-Pacific region and sometimes result in non-treatment of women with osteoporosis.