STIMULATED OSTEOCLASTIC AND SUPPRESSED OSTEOBLASTIC ACTIVITY IN METABOLIC BUT NOT RESPIRATORY-ACIDOSIS

When bone is cultured in acidic medium produced by a reduced bicarbonate concentration ([HCO3-]), a model of metabolic acidosis, there is greater net calcium efflux than when the same decrement in pH is produced by an increased partial pressure of carbon dioxide (Pco(2)), a model of respiratory acidosis. To determine the effects of metabolic and respiratory acidosis on bone cell function we cultured neonatal mouse calvariae for 48 h under control conditions (pH similar to 7.40, Pco(2) similar to 41 mmHg, [HCO3-] similar to 25 meg/I) or under isohydric acidic conditions simulating metabolic (pH similar to 7.09, [HCO3-] similar to 12) or respiratory (pH similar to 7.10, PC0(2) similar to 86) acidosis and measured osteoblastic collagen synthesis and alkaline phosphatase activity and osteoclastic beta-glucuronidase activity. Collagen synthesis was inhibited by metabolic (23.2 +/- 1.3 vs. 30.3 +/- 1.0% in control) but was not altered by respiratory (32.3 +/- 0.6) acidosis. Alkaline phosphatase activity was inhibited by metabolic (402 +/- 16 vs. 471 +/- 15 nmol P.min(-1.)mg protein(-1) in control) but not altered by respiratory (437 +/- 25) acidosis. beta-Glucuronidase activity was stimulated by metabolic (1.02 +/- 0.06 vs. 0.78 +/- 0.05 mu g phenolphthalein released bone(-1).h(-1) in control) but not altered by respiratory (0.73 +/- 0.06) acidosis. Net calcium efflux in control was increased by metabolic (783 +/- 57 vs. 20 +/- 57 nmol bone(-1).48 h(-1) in control) and by respiratory (213 +/- 45) acidosis; however, calcium efflux with metabolic was greater than with respiratory acidosis. Thus the Limited calcium efflux with respiratory acidosis appears to be the result of non-cell-mediated physicochemical mineral dissolution alone, whereas metabolic acidosis additionally inhibits osteoblastic bone formation and stimulates osteoclastic bone resorption.