EFFECT OF POTASSIUM BICARBONATE ON BONE AND MUSCLE

描述(申请人提供)：代谢性酸中毒导致骨质流失和肌肉萎缩。每天，正常西方饮食的成年人每天产生大约75-100meq/d的酸。随着年龄的增长，他们的肾功能和排酸能力下降，他们的酸性变得更强。补充碳酸氢钾(KHCO3)的碱性饮食显著减少了尿钙排泄，降低了骨转换率(骨吸收的生化标记物)，并显著减少了尿氮排泄(肌肉分解代谢的指标)。目前尚无关于钾(可增加肾钙滞留)和碳酸氢盐(显示可减少净酸排泄)在降低骨转换中的相对贡献的一致意见。我们推测，HCO3还可以减少老年人的氮气(肌肉)消耗。目前还没有证据表明KHCO3或其成分会在野外条件下对骨周转或氮素消耗产生持续影响。拟议的研究将确定钾和碳酸氢钠单独和联合使用对血清甲状旁腺素、骨转换生化标记物、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服用67.5 mmol KHC03、KCI或NaHCOS或每天服用安慰剂的治疗组，为期12周。受试者将在基线、3、7和12周访问该中心，以评估他们的饮食、服药依从性和体重。他们将在选定的研究访问中进行以下测量：肌肉功能测试、血清钙、钾、甲状旁腺激素和骨钙素以及24小时尿钙、N-端肽、钙吸收、钾、钠、肌酐、可滴定酸、肾净酸排泄量和氮。在分析中，最终值将是响应，基线值将是协变量。如果在减少钙的排泄、骨转换和/或氮的浪费方面有效，那么使用钾、碳酸氢钠或两者的组合治疗将值得进一步评估，作为一种潜在的廉价和安全的方法来减少老年人的骨丢失和肌肉损耗。

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.