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

描述(申请人提供)：随着年龄的增长，男性和女性会发展为轻度和进行性代谢性酸中毒。这是由于肾功能下降和摄入产酸饮食造成的。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的丧失，但这种慢性的、轻度的酸中毒对老年人骨骼和肌肉的影响尚未得到证实。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，连续3个月每天补充碳酸氢盐使饮食碱化，显著减少了尿中N-端肽(NTX)和尿氮的排泄，N-端肽(NTX)是骨吸收的标志，尿氮是肌肉萎缩的标志。此外，补充碳酸氢盐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一种手段的潜在作用，以减少导致老年人广泛发病率和死亡率的肌肉骨骼衰退。然而，在进行一项长期的碳酸氢盐干预研究之前，重要的是确定最有可能是最佳的碳酸氢盐剂量，并确定从中受益最大的受试者。拟议的剂量发现研究将通过评估安慰剂和两种剂量的碳酸氢盐对尿中NTX和氮排泄的影响以及对下肢功能的影响来扩展我们在这一领域的先前工作。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、安慰剂对照的平行组试验，年龄在60岁及以上的138名男性和138名女性将每天服用碳酸氢钾，剂量为1.0或1.5 mmol/kg体重或服用安慰剂，为期三个月。将比较三组患者尿中NTX和氮的排泄量以及选定的下肢功能指标的变化。还将评估干预措施的安全性和耐受性。这项研究应该提供关于适当的剂量方案和研究人群的必要信息，这些研究人群应该参加未来的长期碳酸氢盐干预试验，以评估这种简单、低成本干预对重要临床结果的长期影响，包括骨和肌肉质量损失、跌倒和骨折的比率。

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.