Additive effects of acidosis and parathyroid hormone on mouse osteoblastic and osteoclastic function

Patients with end-stage renal disease are acidotic and often develop secondary 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 calcium efflux (J(Ca)(+)) from bone and on bone cell function, we measured J(Ca)(+), osteoblastic collagen synthesis, and osteoclastic beta-glucuronidase 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 with 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 inverse correlation between percent collagen synthesis and J(Ca)(+). Compared with Ctl, beta-glucuronidase release into the medium was increased with Met and with PTH and increased further with Met + PTH. There was a direct correlation between medium beta-glucuronidase activity and J(Ca)(+). Osteoclastic beta-glucuronidase activity correlated inversely with osteoblastic collagen synthesis. During cultures to 96 h, there continued to be greater J(Ca)(+) from calvariae incubated with Met + PTH than from those with either treatment alone. Thus acidosis and PTH independently stimulated J(Ca)(+), from bone, inhibited osteoblastic collagen synthesis, and stimulated osteoclastic beta-glucuronidase secretion, 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.