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丢失和肌肉萎缩。在日常基础上，正常西方饮食的成年人产生约75-100 meq/d的酸。随着年龄的增长，他们的肾功能和排酸能力下降，他们变得更加酸中毒。补充碳酸氢钾（KHCO 3）碱化饮食可减少尿钙排泄，降低骨转换率（骨吸收的生化标志物），并减少产酸代谢饮食受试者的尿氮排泄（肌肉紧张症的指标）。目前，钾（可能增加肾钙潴留）和碳酸氢盐（显示减少净酸排泄）对降低骨转换的相对作用尚未达成共识。我们假设HCO 3也可以减少老年人的N2（肌肉）消耗。目前没有证据表明KHCO 3或其成分会对野外条件下的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PTH、骨转换生化标志物、钙排泄、钙吸收和尿氮的影响。将192名男性和女性随机分配至每天用67.5mmol的KHC 03、KCl或NaHC 03或用安慰剂治疗12周。受试者将在基线、第3、7和12周访视中心，以评估其饮食、服药依从性和体重。他们将在选定的研究访视时进行以下测量：肌肉功能检查、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将值得进一步评价，作为一种潜在的廉价和安全的手段，以减少老年人的骨丢失和肌肉消耗。

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.