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D A Bushinsky

Publications and source records attributed to D A Bushinsky.

At least 55 records · Page 3Linked to original sources
PubMed1995

Stone formation in genetic hypercalciuric rats.

Our genetic hypercalciuric (GH) rats have been selected and inbred for 29 generations to maximize urine calcium (UCa) excretion compared to identical gender controls (Ctl). To determine the effect of the increased UCa on urinary supersaturation and stone formation, we pair fed 15 GH and 15 Ctl rats a standard 1.2% calcium diet for 18 weeks, measured urine supersaturation every two weeks, and examined the urinary tract of 1/3 of the rats for the presence of stones every six weeks. Any stones formed were studied by SEM, X-ray and electron diffraction and X-ray microanalysis. Over the entire study UCa was increased in the GH compared to Ctl, resulting in greater supersaturation with respect to calcium hydrogen phosphate (CaHPO4) at all times and calcium oxalate (CaOx) at most times. There was a progressive increase in the incidence of stone formation in GH rats with one of five rats having stones at six weeks, three of five with stones at 12 weeks and five of five with stones at 18 weeks. There were no stones formed in Ctl rats. SEM reveals discrete stones and not nephrocalcinosis. X-ray and electron diffraction and X-ray microanalysis reveal the stones to be poorly crystalline apatite which is a solid phase of calcium and phosphate. Compared to Ctl, in the GH rats the saturation ratio for CaHPO4 increased proportionally more than that for CaOx, perhaps explaining why the rats formed apatite and not oxalate stones. This is the first description of an animal model of spontaneous nephrolithiasis.

Animals↗
PubMed1995

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 ([HCO(3-)]), 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 (PCO2), 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 approximately 7.40, PCO2 approximately 41 mmHg, [HCO(3-)] approximately 25 meq/l) or under isohydric acidic conditions simulating metabolic (pH approximately 7.09, [HCO(3-)] approximately 12) or respiratory (pH approximately 7.10, PCO2 approximately 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 micrograms 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1995

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 bone disease observed in these patients is not clear. To determine whether acidosis and parathyroid hormone (PTH) have additive effects on net calcium efflux (JCa+) from bone and on bone cell function, we measured JCa+, osteoblastic collagen synthesis, and osteoclastic beta-glucuronidase release from neonatal mouse calvariae cultured in control (Ctl, pH approximately 7.4) or acidified (Met, pH approximately 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 JCa+ was increased with Met and with PTH, and the combination of Met + PTH increased JCa+ further. Compared with Ctl, collagen synthesis was decreased with Met and with PTH and decreased further with Met + PTH. There was an inverse correlation between percent collagen synthesis and JCa+. 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 JCa+. Osteoclastic beta-glucuronidase activity correlated inversely with osteoblastic collagen synthesis. During cultures to 96 h, there continued to be greater JCa+ from calvariae incubated with Met + PTH than from those with either treatment alone. Thus acidosis and PTH independently stimulated JCa+ 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.

Acidosis↗
PubMed1994

Proton-induced physicochemical calcium release from ceramic apatite disks.

When bone is cultured in acid medium there is net calcium efflux (JCa) and proton influx (JH) relative to the mineral. The acid medium appears to induce physicochemical mineral dissolution as well as cell-mediated bone resorption. To determine the independent effect of acid medium on physicochemical dissolution, we utilized cell-free synthetic ceramic apatite (CAP) disks, which contain carbonate (5.5%) in an apatite structure chemically similar to mammalian bone. CAP disks were cultured in control (Ctl, pH approximately equal to 7.44) or acid (Met, pH approximately equal to 7.11) medium for 48 h and compared to similarly treated neonatal (4-6 days old) mouse calvariae. Medium was changed and analyzed at 3, 24, and 48 h. At 3, 24, and 48 h there was significantly greater JCa from the CAP disks and calvariae incubated in Met compared to Ctl; over the entire 48 h time period there was a greater progressive increase in JCa from the CAP disks than the calvariae incubated in Met. There was no significant JCa at 3, 24, or 48 h from CAP disks or calvariae incubated in Ctl. At 3 h there was significantly greater JH into the CAP disks and calvariae incubated in Met compared to Ctl; JH was greater into the CAP disks than the calvariae. Utilizing a synthetic model of bone mineral we demonstrated that acid medium induces physicochemical calcium efflux and proton influx relative to the mineral.

Animals↗
PubMed1994

Hormonal regulation of Na(+)-Ca2+ exchange in osteoblast-like cells.

We proposed a role for Na-Ca exchange in hormonally mediated bone resorption and recently characterized Na-dependent Ca transport in an osteoblast-like rat osteosarcoma cell line (UMR-106). To test whether calcemic agents alter Na(+)-Ca2+ exchange in osteoblasts, UMR cells were treated acutely or cultured in the absence or presence of calcemic agent for 24 h. Cells were then loaded with the Ca-sensitive dye fura-2 in the presence of 140 mM NaCl, no Ca, and the absence or presence of 0.3 mM ouabain. Cells were resuspended at 22 degrees C, and the fluorescence ratio at excitation wavelength of 340 and 380 nm was measured. An outward Na gradient was generated by removing extracellular Na and maintaining isotonicity with choline chloride. Na(+)-Ca2+ exchange was demonstrated by enhanced Ca uptake in ouabain-treated (Na-loaded) cells after the addition of 1.5 mM Ca. Acute addition of 10(-7) M PTH or 10(-6) M PGE2 had no effect on Na-dependent Ca uptake. However, 24 h treatment of cells with PTH, PGE2, or 1,25(OH)2D3 caused a dose-dependent inhibition of Na(+)-Ca2+ exchange. Using the Na-sensitive dye, SBFI, we also demonstrated that the effect was bidirectional; PTH inhibited Ca-dependent Na uptake comparably to its inhibition of Na-dependent Ca uptake. The effects of the calcemic agents were mimicked by 24 h treatment of the cells with 1 microM forskolin or 2 microM PMA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Greater inhibition of in vitro bone mineralization with metabolic than respiratory acidosis.

At a similar decrement in pH, acidosis produced by lowering the concentration of medium bicarbonate (metabolic acidosis) induces greater net calcium efflux from cultured neonatal mouse calvariae than acidosis produced by increasing the partial pressure of carbon dioxide (respiratory acidosis). This differential effect is due, at least in part, to enhanced cell-mediated bone mineral resorption during metabolic acidosis. To determine the effect of acidosis on osteoblastic bone formation we utilized primary cultures of neonatal mouse calvarial cells which produce calcified nodules in culture. Cells were plated at 4.5 x 10(4) cells/35 mm dish and incubated until confluent (day 9). Nodule formation was then induced by addition of beta-glycerophosphate and ascorbic acid and the cultures were randomly divided and then cultured in control (Ctl, N = 18) medium or in medium simulating metabolic (Met, N = 17) or respiratory (Resp, N = 19) acidosis. Medium was changed and calcium (Ca) measured every 48 hours until day 23. The mean initial medium pH of all Resp cultures (7.186 +/- 0.002) was lower than Met (7.243 +/- 0.006, P < 0.01), which was lower than Ctl (7.502 +/- 0.002, p < 0.01), yet the number of discrete nodules formed in Met (22 +/- 4 nodules/cm2) was lower than Resp (43 +2- 7, P < 0.01), and both were lower than Ctl (88 +/- 6, P < 0.01 vs. both Met and Resp).(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗
PubMed1994

Increased urinary saturation and kidney calcium content in genetic hypercalciuric rats.

We have established a colony of genetic hypercalciuric (IH) rats as a model of idiopathic hypercalciuria in humans. To test the hypothesis that hypercalciuria can cause crystallization in kidneys through increased supersaturation, in the absence of confounding effects of diet and whatever complex inhibitor disorders underlay stone disease, we fed males and females of the 21st generation of IH rats 13 g per day of a low calcium (LCD, 0.02% Ca), followed by a normal calcium (NCD, 0.6% Ca) and then a high calcium (HCD, 1.2% Ca) diet, each for seven days. During the last 24 hours of each period complete urine collections were obtained and analyzed for all substances known to affect urinary calcium oxalate (CaOx) and brushite (CaHPO4) supersaturation. Relative supersaturation with respect to the solid phases of CaOx and CaHPO4 were then calculated. Compared to same gender controls (Ctl) urine calcium excretion was higher in the female IH rats on all diets and in the male IH rats on NCD and HCD. The female and male IH rats on NCD and HCD were supersaturated with respect to CaOx; however, the male and female Ctl were supersaturated with respect CaOx only on HCD. The female IH rats on NCD and HCD and the male IH rats on NCD were supersaturated with respect to CaHPO4; however, neither the male nor female Ctl rats were supersaturated with respect to CaHPO4 on any diet. On NCD and HCD urine supersaturation with respect to CaHPO4 by females exceeded that of males.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Acidosis and bone.

Acidosis has important effects on the bone mineral which can be investigated utilizing neonatal mouse calvariae in organ culture. When calvariae are cultured for 3 h in physiologically acidic medium produced by a reduction of the bicarbonate concentration, a model of acute metabolic acidosis, there is net calcium efflux from bone in addition to net proton influx into bone which lessens the severity of the acidosis. Utilizing a high resolution scanning ion microprobe to study the bone during acidosis we have found that the protons exchange for sodium and potassium on the bone surface. In acute experiments the calcium efflux is the result of mobilization of carbonated apatite through an alteration in the physicochemical driving forces for bone mineral accretion and dissolution. In the more chronic cultures (greater than 48 h) metabolic acidosis induces calcium efflux by stimulating osteoclastic bone resorption and inhibiting osteoblastic bone formation. When calvariae are cultured for 3 h in acidic medium produced by an increase in the partial pressure of carbon dioxide, a model of respiratory acidosis, there is also calcium efflux; however, at the same decrement in pH the net flux is far less than that observed during metabolic acidosis. During acute respiratory acidosis there is no measurable influx of protons into bone and during chronic studies there is no measurable calcium efflux.

Acidosis↗
PubMed1993

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

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 x 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 physiochemical bone dissolution. The Ntl bone surface (approximately 2 nm in depth) was rich in Na compared to Ca (Na/Ca = 11.9, count/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).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Response of genetic hypercalciuric rats to a low calcium diet.

A fundamental mechanism for hypercalciuria in genetic hypercalciuric rats appears due to a primary increase in intestinal calcium absorption. However previous studies could not exclude additional mechanisms to account for the hypercalciuria. To determine if enhanced bone mineral dissolution either as a primary abnormality or secondary to a defect in renal tubule calcium reabsorption is responsible for a component of the augmented calcium excretion we studied rats continually inbred for hypercalciuria. Nineteenth generation adult female idiopathic hypercalciuric (IH) and non-inbred control (Ctl) rats were fed 13 g/day of a normal calcium diet (0.6% calcium, NCD) for 10 days. Urine calcium excretion over the last seven days was greater in IH (34 +/- 2 mg/7 day) than in Ctl (2.9 +/- 0.3, P < 0.01) rats. Some rats in each group were continued on the same diet while others were fed a low calcium diet (0.02% calcium, LCD) for an additional 10 days; balance measurements were made over the final seven days. With LCD, urine calcium excretion was approximately 8-fold higher in IH compared to Ctl (13 +/- 2 mg/7 day vs. 1.6 +/- 0.1, IH vs. Ctl, respectively, P < 0.01). In IH rats percent calcium absorption was greater (59 +/- 3% vs. 45 +/- 3, IH vs. Ctl, P < 0.01), however calcium retention was negative (-1.9 +/- 2.0 mg/7 day vs. 6.5 +/- 0.5, IH vs. Ctl, P < 0.01) compared to Ctl rats. The fall in urine calcium excretion when IH rats are fed LCD indicates that enhanced intestinal calcium absorption is a primary mechanism of the hypercalciuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Aluminum inhibits bone nodule formation and calcification in vitro.

Cells isolated from neonatal mouse calvariae can be induced to form mineralized nodules after exposure to ascorbic acid and beta-glycerophosphate. To determine whether aluminum inhibits nodule formation and subsequent mineralization, cells isolated from neonatal mouse calvariae were induced to form nodules and incubated with increasing concentrations of aluminum (10(-7) to 10(-5) M). Compared with control and 10(-7) M aluminum-supplemented cultures, the number of nodules formed and the number of nodules calcified were reduced in cells incubated with 10(-6) and 10(-5) M aluminum. The cumulative net calcium uptake into the nodules and their final calcium content were also decreased with 10(-6) and 10(-5) M aluminum. After 10 and 18 days of incubation, aluminum did not affect DNA synthesis or release of alkaline phosphatase but significantly inhibited collagen production. Thus aluminum induced a dose-dependent inhibition of nodule formation and calcification that may be related to its inhibition of collagen production.

Alkaline Phosphatase↗
PubMed1993

Decreased bone carbonate content in response to metabolic, but not respiratory, acidosis.

In vitro cultured neonatal mouse calvariae release calcium and buffer the medium proton concentration in response to a decrease in the medium pH caused by a reduction in bicarbonate concentration ([HCO3-]), a model of metabolic acidosis, but not to an equivalent decrease in pH caused by an increase in the partial pressure of carbon dioxide (PCO2), a model of respiratory acidosis. We have postulated that the medium is in equilibrium with the carbonated apatite in bone. To determine whether bone carbonate is depleted during models of acidosis, we cultured calvariae in control medium (pH approximately 7.4, PCO2 approximately 43, [HCO3-] approximately 26) or in medium in which the pH was equivalently reduced by either a decrease in [HCO3-] (metabolic acidosis, pH approximately 7.1, [HCO3-] approximately 13) or an increase in PCO2 (respiratory acidosis, pH approximately 7.1, PCO2 approximately 86) and determined net calcium flux (JCa) and bone carbonate content. We found that compared with control, after 3, 24, and 48 h there was a decrease in bone carbonate content during metabolic but not during respiratory acidosis. Compared with control, at 3 h JCa increased with both respiratory and metabolic acidosis; however, at 24 and 48 h JCa increased only with metabolic acidosis. JCa was correlated inversely with percent bone carbonate content in control and metabolic acidosis at all time periods studied (r = -0.809, n = 23, P < 0.001). Thus a model of metabolic acidosis appears to increase JCa from bone, perhaps due to the low [HCO3-] inducing bone carbonate dissolution.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1993

Increased intestinal vitamin D receptor in genetic hypercalciuric rats. A cause of intestinal calcium hyperabsorption.

In humans, familial or idiopathic hypercalciuria (IH) is a common cause of hypercalciuria and predisposes to calcium oxalate nephrolithiasis. Intestinal calcium hyperabsorption is a constant feature of IH and may be due to either a vitamin D-independent process in the intestine, a primary overproduction of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], or a defect in renal tubular calcium reabsorption. Selective breeding of spontaneously hypercalciuric male and female Sprague-Dawley rats resulted in offspring with hypercalciuria, increased intestinal calcium absorption, and normal serum 1,25(OH)2D3 levels. The role of the vitamin D receptor (VDR) in the regulation of intestinal calcium absorption was explored in 10th generation male genetic IH rats and normocalciuric controls. Urine calcium excretion was greater in IH rats than controls (2.9 +/- 0.3 vs. 0.7 +/- 0.2 mg/24 h, P < 0.001). IH rat intestine contained twice the abundance of VDR compared with normocalciuric controls (536 +/- 73 vs. 243 +/- 42 nmol/mg protein, P < 0.001), with no difference in the affinity of the receptor for its ligand. Comparable migration of IH and normal intestinal VDR on Western blots and of intestinal VDR mRNA by Northern analysis suggests that the VDR in IH rat intestine is not due to large deletion or addition mutations of the wild-type VDR. IH rat intestine contained greater concentrations of vitamin D-dependent calbindin 9-kD protein. The present studies strongly suggest that increased intestinal VDR number and normal levels of circulating 1,25(OH)2D3 result in increased functional VDR-1,25(OH)2D3 complexes, which exert biological actions in enterocytes to increase intestinal calcium transport. Intestinal calcium hyperabsorption in the IH rat may be the first example of a genetic disorder resulting from a pathologic increase in VDR.

Animals↗
PubMed1993

Effects of metabolic and respiratory acidosis on bone.

Acidosis had long been thought to influence the bone mineral; however, there was little direct evidence to support this impression. When neonatal mouse calvariae are cultured for 3 hours in medium with a reduced bicarbonate concentration, a model of acute metabolic acidosis, there is net calcium efflux from bone in addition to a net influx of protons into bone lessening the magnitude of the acidosis. The protons appear to exchange for sodium and potassium on the bone surface. In these acute experiments, the calcium efflux appears to be due to mobilization of carbonated apatite through an alteration in the physicochemical driving forces for bone accretion and dissolution. In more chronic cultures (greater than 48 hours) metabolic acidosis induces calcium efflux by stimulating osteoclastic bone resorption and inhibiting osteoblastic bone formation. When calvariae are cultured acutely in medium with an elevated partial pressure of carbon dioxide, a model of respiratory acidosis, there is also calcium efflux, but at the same decrement in pH the magnitude is far less than that observed during metabolic acidosis. There does not appear to be any measurable influx of protons into bone, and during chronic cultures there is no measurable calcium efflux. Thus, acidosis influences the bone mineral; however, for the same decrement in pH there is a marked difference in the response of bone to models of metabolic and respiratory acidosis.

Acidosis↗
PubMed1992

Greater unidirectional calcium efflux from bone during metabolic, compared with respiratory, acidosis.

There is a smaller net calcium efflux from bone in vitro during respiratory (increased PCO2) than metabolic (decreased [HCO3-] acidosis. This could be due to the elevated PCO2, which would lessen the driving force for mineral dissolution and increase the driving force for mineralization with respect to carbonated apatite in the bone mineral. To test this hypothesis, we injected neonatal mice with 45Ca and dissected the radiolabeled calvariae 24 h later. The live calvariae were then cultured for 24 h under conditions simulating respiratory acidosis (Resp, pH = 7.225 +/- 0.003, PCO2 = 87.5 +/- 0.1 mmHg), severe respiratory acidosis (SResp, pH = 7.072 +/- 0.004, PCO2 = 103.0 +/- 0.5 mmHg), metabolic acidosis (Met, pH = 7.212 +/- 0.003, HCO3- = 15.5 +/- 0.1 meq/l), or normal acid-base status (Ctl, pH = 7.452 +/- 0.003, PCO2 = 40.0 +/- 0.2 mmHg, HCO3- = 27.8 +/- 0.2 meq/l) and bidirectional net calcium flux (JCa) and unidirectional 45Ca release were determined. There was greater JCa from bone during Met than Resp, and JCa was not different from Met during SResp despite the latter having a significantly lower pH. There was greater unidirectional 45Ca release from bone during Met than Resp, SResp, or Ctl. There was a similar direct correlation between JCa and 45Ca efflux in the respiratory and metabolic groups. However, when calvarial osteoclast activity was inhibited with calcitonin,although there was again greater JCa and 45Ca release with a metabolic compared with respiratory acidosis, there was a greater proportion of 45Ca release than JCa from bone.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1992

Acidosis inhibits osteoblastic and stimulates osteoclastic activity in vitro.

Metabolic acidosis induces net calcium flux (JCa) from cultured neonatal mouse calvariae through physicochemical and cell-mediated mechanisms. To determine the role of osteoblasts in acid-induced JCa, collagen synthesis and alkaline phosphatase activity were assessed in calvariae incubated in reduced pH and bicarbonate medium, a model of metabolic acidosis (Met), and compared with controls (Ctl). Collagen synthesis fell from 30.5 +/- 1.1 in Ctl to 25.1 +/- 0.4% with Met, and alkaline phosphatase decreased from 403 +/- 25 in Ctl to 298 +/- 21 nmol Pi.min-1.mg protein-1 with Met. During acidosis JCa was correlated inversely with percent collagen synthesis (r = -0.743, n = 11, P = 0.009) and with alkaline phosphatase activity (r = -0.453, n = 22, P = 0.034). To determine the role of osteoclasts in acid-induced JCa, osteoclastic beta-glucuronidase activity was determined in Ctl and Met in the absence or presence of the osteoclastic inhibitor calcitonin (CT, 3 x 10(-9) M). Met increased beta-glucuronidase (5.9 +/- 0.2) compared with Ctl (4.6 +/- 0.3 micrograms phenolphthalein released.bone-1.h-1), whereas CT inhibited beta-glucuronidase in both Ctl and Met (3.1 +/- 0.2 and 3.5 +/- 0.3, respectively). During acidosis JCa was correlated directly with beta-glucuronidase activity (r = 0.683, n = 42, P less than 0.001). Thus the cell-mediated component of JCa during acidosis in vitro appears to result from a combination of inhibited osteoblastic and stimulated osteoclastic activity.

Acidosis↗
PubMed1992

Critical role of bicarbonate in calcium release from bone.

Calcium release from cultured bone is pH dependent; net calcium flux (JCa) from bone increases with decreasing pH. At a similar decrement in pH there is greater JCa when acidosis is produced by a low medium bicarbonate concentration ([HCO3-]), a model of metabolic acidosis (Met), compared with an increased medium PCO2, a model of respiratory acidosis (Resp). To separate the role of [HCO3-] from that of pH in inducing JCa we cultured calvariae for 3 h under three different neutral (pH approximately 7.4) isohydric environments [control (Ctl), fully compensated Met (C-Met), or fully compensated Resp (C-Resp)] and two different acid (pH approximately 7.1) isohydric environments (Met or Resp). During neutral pH (Ctl, C-Met, and C-Resp) there was JCa from bone during C-Met (decreased [HCO3-]), no net flux during Ctl (normal [HCO3-]), and JCa into bone during C-Resp (increased [HCO3-]); and JCa was correlated inversely with [HCO3-] (r = -0.824, n = 36, P less than 0.001). During acid pH there was greater JCa from bone during Met (decreased [HCO3-]) than during Resp (normal [HCO3-]); and JCa was again correlated inversely with [HCO3-] (r = -0.848, n = 22, P less than 0.001). JCa from bone during Met and Resp was greater than C-Met and C-Resp, respectively. The addition of the osteoclastic inhibitor salmon calcitonin did not alter the relative JCa results. Thus at a constant pH the magnitude of JCa from cultured neonatal mouse calvariae appears dependent on the [HCO3-]; the lower the [HCO3-], the greater the calcium efflux.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗