Bone mineral density and histology in distal renal tubular acidosis

Abstract

Background. Chronic metabolic acidosis in distal renal tubular acidosis (RTA) has been implicated in the pathogenesis of enhanced bone resorption and osteopenia, resulting in a loss of bone mineral content. However, histomorphometric and bone densitometric studies of patients who suffered from longstanding distal RTA have rarely been done. Methods. A cross-sectional study to determine the alterations of bone mineral density (BMD) and histology was done in 14 nonazotemic RTA patients (11 females and 3 males) who had never received alkaline therapy before enrolling into this study. The mean age was 32.7 ± 11.9 years. BMD measurements and transiliac bone biopsy were done in all patients. Blood chemistries, intact parathyroid hormone level, and a 24-hour urine collection for the determination of urinary calcium, phosphate, sodium, and potassium were obtained from the RTA patients at the time of bone biopsy. Data from 28 age-, sex-, and body mass index-matched, normal controls who were residents in the same area were also obtained. Results. Urinary excretion of calcium was 2.05 ± 1.59 mmol/day. No patient had hypercalciuria. The serum intact parathyroid hormone level was 15.92 ± 8.48 pg/mL. RTA patients had lower BMD in most areas when compared with normal controls. There were two patients who suffered from a pathologic fracture at the femur. Bone histomorphometry from RTA patients shows a significantly decreased bone formation rate (0.02 ± 0.02 vs. 0.07 ± 0.045 μm3/μm2/day, P < 0.05), not significantly decreased osteoblastic surface (0.78 ± 1.03% vs. 2.6 ± 1.1%) and osteoclastic surface (0.05 ± 0.03 vs. 0.13 ± 0.23%), but significantly increased osteoid surface (31.47 ± 24.52 vs. 5.79 ± 4.39%, P < 0.05) and osteoid volume (2.95 ± 3.09 vs. 0.92 ± 1.05%, P < 0.05) when compared with those of normal controls. There was no difference in osteoid thickness (10.65 ± 6.10 vs. 8.69 ± 2.14 μm). Only one distal RTA patient who had a marked increase in osteoid thickness justified the diagnosis of osteomalacia. Conclusions. This study demonstrates that low bone mass is common in distal RTA patients. Chronic metabolic acidosis results in suppression of bone formation and resorption, which in turn may contribute to the development of low bone mass in distal RTA patients. Although minor elevations in osteoid surface and osteoid volume are found among distal RTA patients, overt osteomalacia is not the predominant bone lesion.