Musculoskeletal benefits of bicarbonate in older adults - a dose-finding trial

碳酸氢盐对老年人的肌肉骨骼益处 - 剂量探索试验

基本信息

批准号：
8181797
负责人：
Bess Dawson-Hughes
金额：
$ 49.72万
依托单位：
TUFTS UNIVERSITY BOSTON
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8181797
关键词：
Acidosis Acids Activities of Daily Living Address Affect Age Aging Agreement Alkalies Animals Area Bicarbonates Biochemical Markers Body Weight Bone Resorption Chronic Clinical Clinical Research Clinical Trials Clinical Trials Design Data Diet Dose Double-Blind Method Elderly Enrollment Excretory function Food Fracture Funding Future Goals Health IGFBP3 gene Individual Ingestion Insulin-Like Growth Factor I Intervention Intervention Studies Intervention Trial Investigation Knowledge Lead Long-Term Effects Lower Extremity Measures Metabolic acidosis Morbidity - disease rate Muscle Muscle function Musculoskeletal N-telopeptide Nitrogen Observational Study Osteocalcin Outcome Participant Performance Physical Function Placebo Control Placebo Effect Placebos Population Population Study Postmenopause Process Proteins Randomized Recommendation Regimen Relative (related person)Renal function Research Research Design Research Personnel Risk Risk Factors Role Safety Serum Solid Staging Testing Tissues Translating United States National Institutes of Health Woman Work age related arm base bone bone loss bone mass bone turnover calcium intake cost economic impact falls fruits and vegetables improved men modifiable risk mortality muscle form older men older women potassium bicarbonate programs sex urinary wasting

项目摘要

DESCRIPTION (provided by applicant): With aging, men and women develop a mild and progressive metabolic acidosis. This occurs as a result of declining renal function and ingestion of acid-producing diets. There is extensive evidence that severe metabolic acidosis causes bone and muscle loss, but the impact of the chronic, mild acidosis on bone and muscle in older individuals has not been established. In our recently completed NIH-funded trial in 171 older men and women, alkalinizing the diet with a bicarbonate supplement daily for 3 months significantly reduced urinary excretion of N-telopeptide (NTX), a marker of bone resorption, and urinary nitrogen, a marker of muscle wasting. Moreover, bicarbonate supplements significantly improved muscle performance in the women. These and other data support a potential role for bicarbonate as a means of reducing the musculoskeletal declines that lead to extensive morbidity and mortality in the elderly. Before proceeding to a long-term bicarbonate intervention study, however, it is important to identify the dose of bicarbonate most likely to be optimal and to characterize the subjects who benefit most from it. The proposed dose-finding study will extend our previous work in this area by evaluating the effects of placebo and two doses of bicarbonate on urinary NTX and nitrogen excretion and on lower extremity performance. The lowest dose we plan to test is similar to the dose shown in our recent trial to be effective. The proposed study is a double blind, randomized, placebo-controlled, parallel-group trial in which 138 men and 138 women, age 60 and older, will take potassium bicarbonate in doses of 1.0 or 1.5 mmol/kg of body weight or placebo daily for three months. Changes in urinary excretion of NTX and nitrogen and in selected measures of lower extremity performance will be compared across the three groups. The safety and tolerability of the interventions will also be evaluated. This investigation should provide needed information on the appropriate dosing regimen and on the study population that should be enrolled in a future long-term bicarbonate intervention trial to assess the long-term effects of this simple, low cost intervention on important clinical outcomes including rates of loss in bone and muscle mass, falls, and fractures. PUBLIC HEALTH RELEVANCE: Despite recognition that mild metabolic acidosis contributes to muscle and bone wasting, most older men and women consume diets which aggravate the acidosis. This proposal describes a study designed to identify the dose of an alkali supplement likely to be needed to reverse the acidosis process. This dose of alkali can then be tested for its long-term effects on rates of bone and muscle loss, on falls, and fractures.

描述（由申请人提供）：随着老化，男人和女性会出现轻度和进行性代谢性酸中毒。这是由于肾功能下降和摄入酸性饮食的结果而发生的。有广泛的证据表明，严重的代谢性酸中毒会导致骨骼和肌肉丧失，但是尚未确定慢性，轻度酸中毒对骨骼和肌肉在老年人中的影响。在我们最近完成的NIH资助的试验中，在171名老年男性和女性中，每天用碳酸氢盐补充剂碱化饮食3个月，大大降低了N-甲状腺素（NTX）的尿液排泄，骨吸收的标志物，骨吸收的标志物，尿液氮，肌肉浪费的标志。此外，碳酸氢盐补充剂可显着改善女性的肌肉表现。这些数据和其他数据支持碳酸氢盐作为减少肌肉骨骼的一种潜在作用，从而导致老年人的广泛发病率和死亡率下降。但是，在进行长期碳酸氢盐干预研究之前，重要的是要确定最有可能最佳的碳酸氢盐剂量并表征从中受益最大的受试者。拟议的剂量调查研究将通过评估安慰剂和两剂碳酸氢盐对尿液NTX和氮排泄以及下肢性能的影响，扩展我们在该领域的先前工作。我们计划测试的最低剂量类似于我们最近试验中显示的有效剂量。拟议的研究是一项双盲，随机，安慰剂对照，平行组试验，其中138名男性和138名60岁及60岁的女性将以1.0或1.5 mmol/kg的体重或安慰剂或安慰剂的剂量服用碳酸氢钾，每天服用三个月。在这三组中，将比较NTX和氮的尿液排泄的变化以及下肢表现的选定度量。干预措施的安全性和耐受性也将进行评估。这项调查应提供有关适当给药方案的所需信息以及应在未来的长期碳酸氢盐干预试验中注册的研究人群，以评估这种简单的低成本干预对重要临床结果的长期影响，包括骨骼和肌肉质量，肌肉，下降和骨折的临床损失。公共卫生相关性：尽管人们认识到温和的代谢性酸中毒会导致肌肉和骨骼浪费，但大多数老年男女都会食用加剧酸中毒的饮食。该提案描述了一项旨在鉴定可能需要扭转酸中毒过程的碱补充剂剂量的研究。然后，可以对这种碱剂量的长期影响，对骨骼和肌肉损失率，跌倒和骨折的长期影响。