EFFECT OF POTASSIUM BICARBONATE ON BONE AND MUSCLE

描述（由申请人提供）：代谢性酸中毒导致骨质流失和肌肉萎缩。在正常的西方饮食中，成年人每天产生大约75-100毫当量的酸。随着个人年龄的增长，他们的肾功能和排泄酸的能力下降，他们变得更加酸中毒。在产酸代谢饮食的受试者中，添加碳酸氢钾（KHCO3）碱化饮食可显著减少尿钙排泄，降低骨更新率（骨吸收的生化指标），并减少尿氮排泄（肌肉分解代谢的指标）。目前，对于钾（可能增加肾钙潴留）和碳酸氢盐（显示减少净酸排泄）在减少骨更新方面的相对作用尚未达成共识。我们假设HCO3也可以减少老年人的N2（肌肉）消耗。目前没有证据表明，在野外条件下，KHCO3或其成分会对骨转换或氮消耗产生持续影响。拟议的研究将确定钾和碳酸氢盐单独或联合使用对血清甲状旁腺激素、骨转换生化指标、钙排泄、钙吸收和尿氮的影响。192名男性和女性将被随机分配到每天67.5 mmol KHC03、KCI或NaHCOS或安慰剂组，持续12周。受试者将在基线、3周、7周和12周访问中心，评估他们的饮食、服药依从性和体重。在选定的研究访问中，他们将接受以下测量：肌肉功能测试、血清钙、钾、甲状旁腺激素、骨钙素和24小时尿钙、n -末端肽、钙吸收、钾、钠、肌酐、可滴定酸、肾网酸排泄和氮。在分析中，最终值将是响应，基线值将是协变量。如果能有效减少钙排泄、骨转换和/或氮消耗，那么用钾、碳酸氢盐或两者联合治疗，作为一种潜在的廉价和安全的减少老年人骨质流失和肌肉消耗的方法，值得进一步评估。

DESCRIPTION (provided by applicant): Metabolic acidosis causes bone loss and muscle wasting. On a daily basis, adults on normal Western diets generate approximately 75-100 meq/d of acid. As individuals age, their renal function and ability to excrete acid decline and they become more acidotic. Alkalinizing the diet with supplemental potassium bicarbonate (KHCO3) reduces urinary calcium excretion, lowers bone turnover rates (biochemical markers of bone resorption) and reduces urinary nitrogen excretion (an indicator of muscle catabolism) acutely in subjects on acidogenic metabolic diets. Currently there is no concensus on the relative contributions of potassium (which may increase renal calcium retention) and bicarbonate (shown to reduce net acid excretion) on decreasing bone turnover. We postulate that HCO3 may also reduce N2 (muscle) wasting in older persons. There is no evidence at this time that KHCO3 or its components will have a sustained impact on bone turnover or nitrogen wasting under field conditions.The proposed study will determine the effect of potassium and bicarbonate, alone and in combination, on serum PTH, biochemical markers of bone turnover, calcium excretion, calcium absorption and urinary nitrogen. 192 men and women will be randomly assigned to treatment with 67.5 mmol of KHC03, KCI, or NaHCOS or with placebo daily for 12 weeks. Subjects will visit the Center at baseline, 3, 7, and 12 weeks for assessment of their diets, pill compliance, and weight. They will have the following measurements on selected study visits: muscle function tests, serum calcium, potassium, parathyroid hormone, and osteocalcin and 24-hr urinary calcium, N-telopeptide, calcium absorption, potassium, sodium, creatinine, titratable acid, renal net acid excretion, and nitrogen. In the analysis, the final value will be the response and the baseline value will be a covariate. If effective in reducing calcium excretion, bone turnover, and/or nitrogen wasting, then treatment with potassium, bicarbonate, or the two combined would warrant further evaluation as a potentially inexpensive and safe means to reduce bone loss and muscle wasting in the elderly.