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Physicochemical effects of acidosis on bone calcium flux and surface ion composition
Author(s) -
Bushinsky David A.,
Wolbach Wendy,
Sessler Nelson E.,
Mogilevsky Radion,
LeviSetti Riccardo
Publication year - 1993
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650080112
Subject(s) - calcium , chemistry , medicine , endocrinology , acidosis , calcitonin , metabolic acidosis
Abstract Net calcium flux ( J Ca ) from bone in vitro is pH dependent. When pH falls below 7.40, through a reduction in [HCO 3 − ], there is both physicochemical and cell‐mediated J Ca . 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 J Ca 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, [HCO 3 − ] = 25 nM) or in medium that modeled metabolic acidosis (Met, pH = 7.10, [HCO 3 − ] = 12), each with or without calcitonin (CT, 3 × 10 −9 M). There was net calcium efflux in Ntl ( J Ca = 631 ± 36 nmol per bone per 48 h), which increased in Met (1019 ± 53, p < 0.01); CT inhibited J Ca 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 J Ca 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.