Background: The association between chronic metabolic acidosis and alterations in bone cell functions has been demonstrated in vitro and in animal studies. However, the causal role of acidosis and the effects of alkaline therapy on bone histology and bone mineral density in chronic metabolic acidosis have never been systematically demonstrated in humans. This study was conducted to examine the alterations in bone mineral density and bone histology before and after correction of acidosis among patients with distal renal tubular acidosis (dRTA) METHODS: Correction of metabolic acidosis by potassium citrate was done in non-azotemic dRTA patients, 6 females and 4 males, who had never received long-term alkaline therapy before enrolling into this study. Blood chemistries, serum intact parathyroid hormone, and 24-hour urine collection for the determination of urinary calcium, phosphate, sodium, potassium, bone mineral density determination, and transiliac bone biopsy were done in all patients at baseline and after one year of potassium citrate therapy.

Results: Significant elevations in serum bicarbonate (16.5 +/- 3.0 vs. 24.6 +/- 2.8 mEq/L, P < 0.05) and urinary potassium excretion (35.2 +/- 7.9 vs. 55.4 +/-3.5 mEq/L, P < 0.05) were observed after potassium citrate therapy. No significant alterations in other serum and urine electrolytes were found after the therapy. Serum intact parathyroid hormone level was also significantly elevated after one year of treatment (12.8 +/- 7.3 vs. 26.2 +/- 8.7 pg/mL, P < 0.05). Bone formation rate was significantly suppressed at baseline and was normalized by the treatment (0.02 +/- 0.02 vs. 0.06 +/- 0.03 microm(3)/microm(2)/day, P < 0.05). There were non-significant elevations in trabecular bone volume, osteoblastic and osteoclastic numbers. Bone mineral densities in dRTA patients were also significantly decreased below normal values in most studied areas at baseline and were significantly elevated at the trochanter of femur (0.677 +/- 0.136 vs. 0.748 +/- 0.144 g/c m(2), P < 0.05) and total femur (0.898 +/- 0.166 vs. 0.976 +/- 0.154 g/c m(2), P < 0.05) after the treatment.

Conclusions: This study demonstrates that alkaline therapy corrects abnormal bone cell function and elevates bone mineral density in dRTA patients, indicating the causal role of acidosis in the alterations of bone cell functions and reduction in bone mineral density. Parathyroid gland activity also may be involved in the adaptation of the body to chronic metabolic acidosis.