ADDITIVE EFFECTS OF ACIDOSIS AND PARATHYROID-HORMONE ON MOUSE OSTEOBLASTIC AND OSTEOCLASTIC FUNCTION

Patients with end-stage renal disease are acidotic and often develop s econdary hyperparathyroidism. Whether acidosis contributes to the hone disease observed in these patients is not clear. To determine whether acidosis and parathyroid hormone (PTH) have additive effects on net c alcium efflux (J(Ca)(+)) from bone and on bone cell function, we measu red J(Ca)(+), osteoblastic collagen synthesis, and osteoclastic beta-g lucuronidase release from neonatal mouse calvariae cultured in control (Ctl, pH approximate to 7.4) or acidified (Met, pH approximate to 7.1 ) medium with or without a submaximal concentration of PTH (10(-10) M) for 48 h. Compared with Ctl, from 24 to 48 h J(Ca)(+) was increased w ith Met and with PTH, and the combination of Met + PTH increased J(Ca) (+) further. Compared with Ctl, collagen synthesis was decreased with Met and with PTH and decreased further with Met + PTR. There was an in verse correlation between percent collagen synthesis and J(Ca)(+). Com pared with Ctl, beta-glucuronidase release into the medium was increas ed with Met and with PTH and increased further with Met + PTH. There w as a direct correlation between medium beta-glucuronidase activity and J(Ca)(+). Osteoclastic beta-glucuronidase activity correlated inverse ly with osteoblastic collagen synthesis. During cultures to 96 h, ther e continued to be greater J(Ca)(+) from calvariae incubated with Met PTH than from those with either treatment alone. Thus acidosis and PT H independently stimulated J(Ca)(+), from bone, inhibited osteoblastic collagen synthesis, and stimulated osteoclastic beta-glucuronidase se cretion, whereas the combination had a greater effect on each of these parameters than either treatment alone. These findings indicate that acidosis and PTH can have an additive effect on bone cell function and suggest that uremic osteodystrophy may result from a combination of a low pH and an elevated PTH.