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，男性和女性会出现轻度和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NIH资助的171名老年男性和女性的试验中，每天用碳酸氢盐补充剂碱化饮食3个月，显著减少了N-端肽（NTX）的尿排泄，这是骨吸收的标志物，尿氮是肌肉萎缩的标志物。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下降的一种手段的潜在作用，肌肉骨骼下降导致老年人的广泛发病率和死亡率。然而，在进行长期碳酸氢盐干预研究之前，重要的是要确定最有可能是最佳的碳酸氢盐剂量，并确定受益最大的受试者的特征。拟议的剂量探索研究将通过评估安慰剂和两种剂量的碳酸氢盐对尿NTX和氮排泄以及下肢功能的影响，扩展我们以前在这方面的工作。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。该研究是一项双盲、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60岁及以上，将每天服用1.0或1.5 mmol/kg体重的碳酸氢钾或安慰剂，持续3个月。将比较三组间尿NTX和氮排泄的变化以及下肢功能的选定指标。还将评估干预措施的安全性和耐受性。本研究应提供关于适当给药方案和未来长期碳酸氢盐干预试验应招募的研究人群的必要信息，以评估这种简单、低成本干预对重要临床结局的长期影响，包括骨和肌肉质量丢失率、福尔斯和骨折。

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.