Prevalence and characterization of renal tubular acidosis in patients withosteopenia and osteoporosis and in non-porotic controls

Background. Chronic metabolic acidosis may increase alkali mobilization fro m the bone and thus promote the development of osteoporosis. The objective of the current study was to compare urinary acidification in patients with reduced bone mineral content with that in control subjects with normal bone density. Methods. Forty-six subjects (41 females, 5 males) with osteopenia or osteop orosis were studied. In none of the subjects were overt metabolic acidosis, derangement of potassium homeostasis, or renal insufficiency present. Dist al tubular acidification was studied by means of oral ammonium chloride loa ding test (0.1 g/kg body weight) and the oral frusemide test (40 mg). In ad dition the frusemide test was performed in 20 healthy age- and sex-matched controls (17 females, 3 males). Results. In all control subjects a urinary pH <5.5 was observed following t he ingestion of 40 mg frusemide. In contrast, in patients with reduced bone mineral density incomplete renal tubular acidosis type I (RTA I) was diagn osed in 10 of 46 subjects (22%) by oral ammonium chloride loading lest. Dis orders possibly related to RTA. I were detected in eight of these 10 patien ts. Thirty-six patients had a normal urinary pH response following oral amm onium chloride loading. Oral frusemide, 40 mg, failed to lower urinary pH < 5.5 in sixteen patients (35%), these included 10 subjects with incomplete R TA I, and six subjects with a normal oral ammonium chloride loading test. A n abnormal frusemide test was found in 35% of patients with reduced bone ma ss and in none of the normal controls (chi(2)=7.39; P<0.01). With the ammon ium chloride test as the gold standard for diagnosis of distal RTA, the fru semide test showed a sensitivity of 1.0 (95% CI, 0.69-1.0) and a specificit y of 0.89 (95% CI, 0.78-0.96) for the diagnosis of distal RTA. Patients wit h incomplete RTA I were younger than those without incomplete RTA I (42+/-1 6 vs 54+/-14 years; P=0.025; mean+/-SD). Basal serum bicarbonate concentrat ions and capillary pH did not differ between the groups. Conclusion. Incomplete RTA I may be prevalent in a significant proportion o f patients suffering from osteopenia or osteoporosis. The outcome of the fr usemide test suggests either a defect of the H+ ATPase in the cortical coll ecting tubule (CCT) or a defective Na+ reabsorption in the CCT. Prospective studies are needed to further elucidate the impact of incomplete RTA I on the development of reduced bone mineral content.