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

描述（由申请人提供）：随着年龄的增长，男性和女性都会出现轻度进行性代谢性酸中毒。这是肾功能下降和摄入产酸饮食的结果。有大量证据表明，严重的代谢性酸中毒会导致骨骼和肌肉损失，但慢性轻度酸中毒对老年人骨骼和肌肉的影响尚未确定。在我们最近完成的美国国立卫生研究院资助的171名老年男性和女性的试验中，用碳酸氢盐补充剂每天碱化饮食3个月，显著减少了n -末端肽（NTX）的尿排泄，NTX是骨吸收的标志，尿氮是肌肉萎缩的标志。此外，碳酸氢盐补充剂显著改善了女性的肌肉表现。这些和其他数据支持碳酸氢盐作为减少肌肉骨骼衰退的一种潜在作用，这种衰退导致老年人广泛的发病率和死亡率。然而，在进行长期碳酸氢盐干预研究之前，重要的是确定最可能最佳的碳酸氢盐剂量，并确定从中受益最多的受试者的特征。拟议的剂量发现研究将通过评估安慰剂和两剂量碳酸氢盐对尿NTX和氮排泄以及下肢功能的影响来扩展我们之前在该领域的工作。我们计划测试的最低剂量与我们最近试验中显示的有效剂量相似。这项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名女性，年龄在60岁及以上，每天服用1.0或1.5 mmol/kg体重的碳酸氢钾或安慰剂，持续三个月。将比较三组患者尿中NTX和氮排泄的变化以及下肢性能的选择指标。还将评估干预措施的安全性和耐受性。这项研究应提供适当的给药方案和未来长期碳酸氢盐干预试验的研究人群所需的信息，以评估这种简单、低成本的干预对重要临床结果的长期影响，包括骨和肌肉质量的损失率、跌倒和骨折。

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.