Physicochemical effects of acidosis on bone calcium flux and surface ion composition

Abstract

Net calcium flux (JCa) from bone in vitro is pH dependent. When pH falls below 7.40, through a reduction in [HCO3−], there is both physicochemical and cell‐mediated JCa. To characterize the physicochemical effect of acidosis on bone we inhibited the bone‐resorbing cells (osteoclasts) with the specific inhibitor calcitonin and studied the effect of acidosis on JCa and bone ion composition using an analytic high‐resolution scanning ion microprobe. Neonatal mouse calvariae were cultured for 48 h in physiologically neutral pH medium (Ntl, pH = 7.41, [HCO3−] = 25 nM) or in medium that modeled metabolic acidosis (Met, pH = 7.10, [HCO3−] = 12), each with or without calcitonin (CT, 3 × 10−9 M). There was net calcium efflux in Ntl (JCa = 631 ± 36 nmol per bone per 48 h), which increased in Met (1019 ± 53, p < 0.01); CT inhibited JCa in Ntl (‐54 ± 11, p < 0.01 versus Ntl), which increased in Met (197 ± 15, p < 0.01 versus Ntl + CT). In the presence of CT the increase in JCa in Met versus Ntl represents physicochemical bone dissolution. The Ntl bone surface (∼2 nm in depth) was rich in Na compared to Ca (Na/Ca = 11.9, counts/s of detected secondary ions), which fell in Met (Na/Ca = 6.0, p < 0.05); CT caused a further reduction of Na/Ca (3.1, p < 0.01 versus Ntl and versus Met), which was not altered in Met (2.6, p ≥ 0.05 versus Ntl + CT). The subsurface of the Ntl bone, eroded to a depth of = 100 nm with the microprobe, was also rich in Na/Ca (11.0), which fell in Met (4.1, p < 0.05); CT caused a further fall in Na/Ca (3.8, p < 0.01 versus Ntl), which again was not altered in Met (3.5, p ≥ 0.05 versus Ntl + CT). Acidosis causes a release of bone Ca and a fall in the ratio of bone Na/Ca, indicating a greater release of Na. Inhibition of osteoclastic function with calcitonin causes an influx of Ca to bone and a marked fall in bone Na/Ca, indicating little change in Na. Acidosis plus calcitonin causes Ca release with no change in Na/Ca, indicating that physicochemical bone mineral dissolution causes relatively equal Ca and Na release. Thus, the cell‐mediated effect of acidosis‐induced bone resorption appears responsible for the excess Na efflux. Copyright © 1993 ASBMR