solubility of bone in solutions of magnesium saltsthe results following oral ingestion of magnesium...

SOLUBILITY OF BONE IN SOLUTIONS OF MAGNESIUM SALTS

BY J. C. FORBES

(From the Department of Biochemistry, Medical College of Virginia, Richmond)

(Received for publication, June 24, 1931)

In receht years a number of investigators have shown that the administration of magnesium salts increases calcium excretion. Injections of magnesium salts, especially intravenous injections, have given more positive evidence of calcium loss than oral administration. This is of course to be expected, since injection of the salt would naturally lead to a greater concentration of magnesium in the blood stream than would be obtained by oral administration.

Mendel and Benedict (l), working with dogs, cats, and rabbits, noted an increased calcium elimination in the urine when aqueous solutions of magnesium salts were injected subcutaneously. Schiff (2), studying the effect of magnesium sulfate on infants, found that the subcutaneous administration of 0.2 ,gm. of magnesium sulfate per kilo of body weight greatly increased the calcium excretion in the urine and slightly increased that in the feces. Stransky (3) studied the calcium and magnesium content of the blood of rabbits after the subcutaneous administration of sufficient magnesium sulfate to produce narcosis, and found that the plasma magnesium was greatly increased but the calcium concentration was definitely diminished. Richter-Quittner (4) corroborated this work and also found that, although the total amount of calcium in the blood was decreased, the amount of diffusible calcium was definitely increased.

The results following oral ingestion of magnesium salts have been more variable than those obtained by injection of the salt. Mal- colm (5) produced a small increase in calcium excretion in dogs by feeding magnesium chloride. Hart and Steenbock (6) fed magnesium chloride and sulfate to swine and demonstrated an in-

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256 Bone Solubility in Mg Salt Solutions

creased calcium elimination in the urine but not in the feces. They also found that if soluble ph0sphat.e salts were fed with the magnesium salt, the calcium loss was considerably reduced. Palmer, Eckles, and Schutte (7) obtained similar results with cattle. Underhill, Honeij, and Bogert (8) found no material increase in calcium elimination in normal individuals, or in cases of leprosy, or of exostosis when the magnesium in the diet was increased. Bogert and McKittrick (9), however, obtained a slight, increase in the urinary and fecal calcium of women to whom 6 gm. of magnesium lactate were given daily.

Further evidence showing the antagonistic action of magnesium on calcium utilization is given by the experiments of Shipley and Holt (lo), and of Shelling, Kramer, and Orent (ll), on the calcification of rachitic cartilage in z&o. These experiments show that magnesium has a specific inhibitory action on the bone- forming elements in rachitic metaphyses and this inhibitory action may be overcome by increasing the phosphate concentration of the solution. The experimental results of Holt, La Mer, and Chown (12), and of Zorkendorfer (13), further emphasize this antagonistic action of magnesium. They have shown that the solubility of poorly soluble calcium salts, such as Ca3(P0& and CaHPO+ in water, is greatly increased by the addition of soluble magnesium salts.

Although these results of Halt, La Mer, and Chown, and of Zorkendorfer, as well as the experiments on the injection of magnesium salts might lead one to assume that magnesium salts would increase the solubility of bone, no experimental evidence is available to show that this is the case. This investigation was therefore carried out in order to determine the effect of magnesium salts on the solubility of bone calcium and phosphorus in vitq in the hope that further light might be thrown on the influence of magnesium salts on calcium metabolism.

Methods of Analyses-Calcium determinations were made by Kramer and Tisdall’s (14) method, except that 50 cc. conical centrifuge tubes were employed, and as large a volume of solution as feasible was taken for analysis. Since magnesium interferes with calcium precipitation, as shown by Zorkendorfer (13), all of the solutions containing more than 0.004 M magnesium salt were diluted with water before precipitating the calcium. The


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J. C. Forbes 257

final magnesium concentration after addition of the ammonium oxalate solution was always less than 30 mg. per 100 cc. of solution. Phosphorus was determined by Fiske and Subbarow’s (15) method. A quinhydrone hydrogen ion apparatus, unless other- wise stated, was used in all pH determinations.

TABLE I

Effect oj Magnesium Salts on Solubility of Bone Calcium Calcium values are expressed in mg. per 100 cc. of solution.

Exwri- merit

No.

rime of extrac-

tion -

0

_

1.008 M salt

0.4 M salt -

bra.

6 26 77

105

0.1 1.2 2.7 3.1 0.5 1.7 6.1 10.9 1.1 4.2 7.9 17.6 1.6 4.6 ii.i 19.8

6 1.0 2.1 4.7 8.6 26 1.1 2.5 8.1 20.2 77 1.9 3.7 13.9 35.0

105 1.2 2.6 19.6 52.8

6 1.1 1.1 3.3 8.6 26 1.9 3.1 8.6 21.6 77 2.0 3.0 14.5 45.5

105 1.2 2.4 20.4 66.0

6 2.9 4.6 8.5 25.4 26 3.4 5.0 10.8 31.5 77 3.9 6.5 15.6 51.2

105 3.4 5.9 17.9 66.8

6 0 0.1 26 0.4 0.8 77 0.5 0.7

105 0.3 0.6

0.3 3.7 5.7 6.2

--

2.3 11.6 22.0 29.0

I

-

Bone in klgSOc solutions in distilled water

Bone in MgSO, solutions in ~/15 phosphate buffer solution of pH 6.2

Bone in MgC% solutions in ~/15 phosphate buffer solution of pH 6.2

Bone in MgSO, solutions in M/15 KHzPO,

Bone in MgSO, solutions in ~/15 phosphate buffer solution of pH 7.4

As preliminary experiments, the effect of various concentrations of magnesium sulfate and chloride on the solubility of bone calcium was studied, in the first case in ~/15 phosphate buffer solutions of various hydrogen ion concentrations, and then in


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TABLE II

Effect of Magnesium Sulfate on the Solubility of Bone Calcium in Ringer’s Solution

-

Time of xtraotia

hrs.

0 16 24 24 24 48 24

0 26 24 48 24 48

0 24 24 48 24 48

0 24 24 24 24

0 24 24 24

7.8

7.2

6.0

7.9

0.7

Ca concentration

MogsMO, o.lKJ4 M M&O4

0.04 M MgS04

ml. 13.6 7.4 7.7 7.5 6.7 9.2 8.1

ml7.

13.6 11.6 11.7 11.5 12.9

12.2

ml.

13.6 24.1 22.6 21.7 21.8 23.1 27.2

11.9 11.9 11.2 5.8 9.1 20.7 5.1 9.8 19.5 6.3 13.2 18.3 7.8 11.7 18.3 6.1 9.6 18.1

10.6 6.9

6.6 7.3 6.5

10.6 10.6 10.9 22.5 10.1 18.9 11.1 19.1 11.8 18.0 10.8 20.0

5.0 4.0 3.7 4.3 4.0

5.0 4.8 3.5 4.0

5.0 5.0 5.5 20.2 5.6 21.5 6.2 22.1 6.1 21.8

5.0 5.0 7.1 21.4 7.0 21.8 7.8 20.8

_- Inorease in Cs

Mog&

ml.

0.004 M M&0(

fw.

0.04 Al MgS.04

WI.

-6.2 -5.9 -6.1 -6.9 -4.4 -5.5

-2.0 -1.9 -2.1 -0.7

-1.4

+10.5 +Q.O +8.1 +8.2 +9.5

+13.6

-6.1 -2.8 $9.5 -6.8 -2.1 +8.3 -5.6 +1.3 +7.1 -4.1 -0.2 +7.1 -5.8 -2.3 +6.9

-3.7

-4.0 -3.3 -4.1

-1.0 -1.3 -0.7 -1.0

-0.2 -1.5 -1.0

+0.3 +ll.Q -0.5 +a.3 +0.5 +8.5 +1.2 +7.4 +0.2 +9.4

+0.5 +15.2 +0.6 +16.5 +1.2 +17.1 +1.1 +16.8

f2.1 +16.4 +2.0 +16.8 +2.8 +15.s

Ringer’s solution containing various amounts of calcium chloride, and of different initial hydrogen ion concentrations. Beef rib bone was used in all experiments. It was first finely chopped, then washed, first with tap water and afterwards with distilled


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J. C. Forbes 259

water, until the supernatant fluid showed no visible signs of blood, and finally air-dried at room temperature.

In the experiments recorded in Table I approximately 10 gm. of this air-dried material were placed in 300 cc. Pyrex flasks and 200 cc. of the various buffer solutions added. Small amounts of

TABLE III

Solubility of Bone Calcium and Phosphorus in 0.04 x Magnesium sulfate Solution in Distilled Waler

Deter- mina-

tion No.

Concentration per 100 cc.

Solution 1 1 Solution 2 I Solution 3

Ca P Ca ~--

mg. mg. mg.

6.2 1.03 7.5

9.0 1.37 9.3

2.8 0.73 2.8 0.64 2.2

5.2 1.02 4.7 0.90 4.6

7.8 1.45 8.2

6.1 1.12 5.4

46.2 11.6

-

-- P Ca

-- V&Q. n&g.

1.13 7.1

1.37 8.7

1.46 7.7

1.20 5.8

-

P -

ml.

1.1:

1.3c

0.6:

0.9E

1.1:

l.W

AVW-

ctri? ratio

6.0

6.7

3.9

5.0

5.8

5.1

4.0

Remarks

Solutions shaken for 1 hr. then stood 18 hrs. at room temperature

Additional 4 hr. shaking and 18 hrs. standing at room temperature

Fresh solution added and shaken for 15 min. at room temperature

Additional 1 hr. shaking and 18 hrs. standing at room temperature

1 hr. additional shaking and 18 hrs. standing at room temperature

Fresh solution, left for 5 days at room temperature

0.4 M MgSO, solution added to large amount of bone and left in incu- bator for 3 days at 37”

chloroform and toluene were then added as preservatives, the flasks stoppered, and set aside at room temperature with occasional shaking. Samples for analysis were removed at intervals, filtered, and analyzed for calcium. The experimental results show that both magnesium sulfate and chloride exert a very great


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solvent action on bone calcium, and that this action increases with increase in magnesium concentration.

In Table II is shown the effect of magnesium sulfate on the solubility of bone calcium in Ringer’s solution containing various amounts of calcium. In order to obtain a maximum effect in a

Effect of Magnesium Sulfate on Solubility of Bone Calcium and Phosphorus in Calcium Phosphate Solutions

Calcium and phosphorus values are expressed in mg. per 106 cc. of solution.

Experi merit

NO.

1

2

3

4

5

6

- 1

--

-

Molar concentration of bIgSO I

Ca P PH

- - 0 -_

ml.

9.4 2.9 5.5

0

mg.

9.4 2.9 5.5

Ca P

1.1 1.0

1.7 1.2

Ca P

0.7 0.9

1.0 1.3

Ca 2.9 1.0 P 0.8 1.0 PH 7.5 7.5

Ca 1.8 0.8 P 0.5 0.7 PH 7.7 7.7

Ca P

3.8 0.3 ,

-

3.7 0.4

Remarka ~.004 0.094 0.04 0.04 ----

m9. mg. nag. mp.

9.4 9.4 9.4 9.4 Original solution 2.9 2.9 2.9 2.9 5.4 5.4 5.2 5.2

2.1 2.4 23.4 Bone in solution for 24 1.7 1.3 1.4 hours

2.9 20.5 20.5 ‘2.1 1.2 1.5 1.5

Bone in fresh solution for 24 hours

3.4 3.4 21.6 21.2 Bone in fresh solution for 1.0 0.9 1.3 1.4 72 hours 7.4 7.5 7.2 7.1

5.6 3.7 22.6 22.6 Bone in fresh solution for 0.6 0.6 1.2 1.4 48 hours 7.5 7.5 7.1 7.1

10.0 10.7 22.8 22.0 Bone in fresh splution for 0.7 0.8 0.9 0.6 120 hours

short time, these experiments were carried out in test-tubes, and a large amount of bone was used in comparison with that of the solution. At the end of each extraction period, the solutions were drained off and fresh solutions added for the next extraction. The results show that, in the absence of magnesium salts, some of the original solution calcium is removed by the bone; the greater the


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J. C. Forbes 261

original calcium concentration, the larger the amount removed. Magnesium sulfate, even in low concentrations, greatly inhibits this calcium deposition, and in high concentrations actually causes marked solution of the bone calcium. The relative effect of low concentrations of the magnesium salt is naturally influenced by the original calcium concentration of the solution. For example, when the original calcium concentration is 5 mg. per 100 cc. of solution and the magnesium concentration 0.004 M, slight solution of the bone calcium takes place, but when the original calcium concentration is 11.9 or above deposition of calcium takes place in the same magnesium concentration.

In Table III is shown the effect of magnesium sulfate on the solubility of bone calcium and phosphorus in distilled water. It will be seen that in all of the experiments the Ca:P ratio is considerably greater than the theoretical value for Ca3(PO&. This is especially true in Determinations 1 and 2. Calorimetric determinations of hydrogen ions were made on the solutions in Determinations 2, 5, and 6 and were found to be approximately pH 7.8, 7.6, and 7.6 respectively, showing that the bone markedly decreased the hydrogen ion concentration of the solutions. It therefore seems probable that the bone calcium may have gone into solution. in two ways, as a basic compound like Ca(OH), or CaC03 and as Cas(PO&.

In Table IV is shown the effect of magnesium sulfate on the solubility of bone calcium and phosphorus in a weak calcium phosphate solution. This solution was prepared by adding a small amount of calcium chloride to a weak solution of mono- potassium phosphate. As in the previous experiment, the bone caused a marked decrease in the hydrogen ion concentration of the solutions, both in the absence and presence of magnesium salt. Phosphorus concentration was also decreased in all solutions. The calcium concentration in the solutions containing no magnesium salt and those containing 0.004 M magnesium sulfate was decreased, but that of the solutions containing 0.04 M magnesium sulfat,e was markedly increased. The decrease in calcium and phosphorus, especially in the absence of magnesium salts, is likely due to a considerable extent to the conversion of the soluble Ca(HzPO& into the more insoluble CaHP04 and Ca3(PO& due to the decreased acidity of the solution.


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TABLE V

Effect of Magnesium Sulfate on Solubz’lity of Bone Calcium and Phosphorus in Weak Phosphate Buffer Solutions


-- 1 0 2 0.12

3 0.24

Deter- Molar concentration of ,MgSOd

mina- tion 0 I 0.004 0.04 No. - ~-

Cl3 P pH Ca --- 6.6 6.20

, 2.4 7.60.12

i 5.4 7.61.6

5.4 7.62.4

P pH Ca P pH -- ---

6.6 6.0 0 6.5 5.9 Original solution 1.1 7.511.3 1.6 7.4 Solution in contact with

bone for 75 min. at 37” 2.4 7.5 9.3 3.0 7.2 Freshsolution,incontact

with bone for 75 min. at 37”

4 3.0 7.4 9.4 4.6 7.1 Fresh solution, in contact with bone for 90 min. at 37”

5 0.6 5.0 7.42.4 1.9 7.2 9.8 3.5 7.0 Fresh solution, in contact with bone for 3 hrs. at 37”

6 0.54 L 4.4 7.42.4

3.4 7.72.3

2.0 7.3 7.6 3.6 7.2 Fresh solution, in contact with bone for 5 hrs. at 37”

7 0.7 1.8 7.4 12.4 2.2 7.3 Fresh solution, in contact with bone for 28 hrs. at 37”

8 0.4(

9 0.5

i 7.22.3

5.2 7.42.6



10 0.26

11 1.0

1 4.7 7.62.2

5.9 6.92.5


3.6 6.9 5.7 5.7 6.7 Fresh solution, in contact with bone for 150 min. at 37”

12 0.6 5.1 7.02.3 4.6 7.0 6.6 6.2 6.9 Fresh solution, in contact with bone for 15 hrs. at 37”

Remarks

-

25 cc. of solution were used for each extraction except in Determinations 11 and 12 where 75 cc. were used. Solutions were shaken occasionally during the extraction.


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J. C. Forbes 263

In Tables .V and VI are presented experimental data showing the effect of magnesium sulfate on the solubility of bone in weak phosphate buffer solutions. The results are in agreement with

TABLE VI

Effect of Magnesium Sulfate on’the Solubility of Bone Calcium and Phos- phorus in Weak Phosphate Bufer Solutions


4ndy- sis I-

Ca P PH

Concentration of Mg salt

ox O.oil16M --

0 0 6.6 6.6 6.1 6.1

0 0 6.6 6.6 6.0 5.8

Ca 1.3 2.3 3.1 13.4 P 4.6 4.2 4.2 4.6 PH 7.3 7.1 7.0 6.9

Ca 1.1 1.4 2.4 9.8 P 6.2 5.8 5.9 6.2 PH 7.0 7.0 6.7 6.5

CfL 0.6 1.2 2.8 8.5 P 5.4 5.5 5.4 6.0 PH 7.0 6.9 6.6 6.6

Ca 0.4 0.4 2.1 10.3 P 4.8 5.0 3.9 4.6 PH 7.5 7.3 7.3 6.8

Crt 0.7 1.1 2.8 7.4 P 5.7 5.9 6.4 6.6 PH 6.9 6.9 6.8 6.7

Ca 0.9 1.3 3.2 8.3 P 5.7 5.8 6.6 6.6 PH 7.1 7.0 6.9 6.9

Remarks

0 Original solution 6.6 5.3

23.5 10 bone added to 25 gm. 7.2 cc. respective solution 6.1 and left 2 hrs. at 37”

12.1 Fresh solution added and 8.8 left 2 hrs. at 37” 6.4



14.2 75 cc. fresh solution added 8.7 and left 24 hrs. at 37” 6.6

15.7 75 cc. fresh solution added 8.8 and left 24 hrs. at 37” 6.9

those obtained in the previous experiments. The decrease in acidity was very marked in all cases. The rapidity of this decrease will of course depend on various facfors, such as the size of


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the bone particles and the relative amounts of bone and solution. In an unrecorded experiment it was found that when only sufficient solution to cover the bone was used, 10 minutes at 37” sufficed to raise the pH of a ~/450 phosphate buffer solution from 6.2 to 7.2. The speed with which this change is brought about, as shown by Tztble V, decreases with increased extraction. This is, of course, to be expected since a certain amount of the basic compounds of the bone are removed with each extraction. The calcium solubility, as in the previous experiments, increased with increase in magnesium concentration. The phosphate concentration was

TABLE VII

Solutility of Bone Calcium and Phosphorus in 0.0#8 dl Magnesium Lactate in ~/460 Phosphate Bu$er Solution of pH 6.9

D&r- minntiol

NO.

I- ‘I - --

/

-

Gmcentratiou per 100 cc.

Solution 1

Ca

mg.

0 2.1

mg.

6.8 7.3

Ca P Ca P

fw. ma. wig. ma.

0 6.8 0 6.8 2.1 7.3 2.6 7.2

4.7 6.8 4.2 6.7 3.8 6.7 3.6 7.0 3.8 6.8 4.4 6.5

5.0 6.9 5.1 6.6 5.7 6.5

Solution 2 Solution 3

Original solution 2 hrs. shaking at room tem-

perature 14 hrs. additional shaking Fresh solution, shaken 2 hrs.

then stood 18 hrs. at room temperature

13 hrs. additional shaking then 18 hrs. standing at room temperature

diminished in all solutions except the 0.2 M magnesium sulfate solutions in which a slight increase was obtained. In several unrecorded experiments it has been found that, even in this concentration, a definite decrease in the phosphate concentration of the solution is obtained, if the extraction period is sufficiently prolonged.

A somewhat similar experiment showing the effect of magnesium lactate on the solubility of bone is shown in Table VII. It will be seen that t,he lactate has the same general effect on the bone calcium and phosphorus as the other magnesium salts. The experi-


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J. C. Forbes

ments were not sufficiently prolonged to show the maximum calcium solubility, but they show definitely a great increase in calcium solubility over that obtained in similar buffer solutions in the absence of magnesium salts, as shown inTables I to VI and VIII. The decrease in phosphorus after the preliminary rise was not as marked as in the other experiments. This, however, is likely primarily due to the short extraction periods.

TABLE VIII

Efect of Phosphate Concentration on Solubilitg of Bone Calcium in 0.004 M Magnesium Sulfate

Calcium values are expressed in mg. per 100 cc. of solution; pH of solutions 6.2.

Experi- ment NO.

T Phosphate concentration T OM

2.4

M/750

2.2

- - M/150

. 1.9

3.1 2.9 1.7 2.3 2.1 1.1 2.8 2.1 1.4

3.6 3.8 2.6

4.9 5.0 3.0 5.0 4.6 2.9 4.9 4.0 2.6

2.9

2.7 2.5

2.2

2.2 2.0

1.9

1.9 1.4

M/15

1.6

1.3 1.0 1.1

1.6

1.6 1.1

Remarks

6 hrs. extraction with occasional shaking at 37”

Additional 24 hrs. at 37” I‘ 24 *‘ “ 37” ‘I 24 “ “ 37”


Additional 24 hrs. at 37” “ 24 ‘I “ 37” I‘ 24 “ “ 37”


Additional 24 hrs. at 37” I‘ 24 ” ” 37”

The bone used in Experiment 2 was heated in an oven at 100” for several days. This may explain the greater solubility.

Since an increase in phosphate concentration decreases the antagonistic action of magnesium both on calcification in vitro and calcium retention in experimental animals, it was decided to study the effect of variations in phosphate concentrations on the solubility of bone calcium in magnesium solutions. The experimental data are recorded in Table VIII. It will be seen that the


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266 Bone Solubility in ll/g Salt Solutions

phosphate concentration has a slight but very definite effect; i.e.,

the greater the phosphate concentration the less the calcium solubility.

DISCUSSION

The experimental results show that soluble magnesium salts great,ly increase the solubility of bone calcium in water solutions; the greater the magnesium concentration the greater the calcium solubility. The effect of the magnesium salts is, however, more or less influenced by the calcium and phosphate concentration of the original solution. It will be seen, for example, in Table III that magnesium sulfate in distilled water causes bone calcium to go into solution probably as a phosphate and as some other calcium compound having basic properties, possibly the hydroxide or carbonate. That such is likely the case is evident from the fact that the Ca:P ratio of the solutions is in all cases at least double that of t,he theoretical value for Cas(PO&, and also from the fact that the bone markedly decreased the hydrogen ionconcentration of the solutions. If, on the other hand, calcium is present in the original solution, either solution of the bone calcium or deposition of the solution calcium on the bone may take place, depending on the calcium, phosphate, and magnesium concentration of the solu!ion. For example, from the results recorded in Table II, it will be seen that in the 0.004 M magnesium solutions, deposition of calcium took place when the original calcium concentration was 11.9 mg. per 100 cc., or over, but solution of bone calcium took place when it was only 5 mg. per 100 cc. At the higher magnesium concentrations, solution of bone calcium took place at all calcium concentrations employed. In a similar manner, variations in the phosphate concentration of the solution influence the effect of magnesium on calcium solubility, especially in solutions of low magnesium concentrations. This effect of phosphates may be seen by comparing the results obtained with the 0.004 M magnesium sulfate in Ringer’s solution with those obtained with a weak phosphate solut.ion containing the same amount of magnesium and approximately the same calcium concentration. For example, in Experiment 3, Table II, there is a slight but definite incrense in the solubility of the bone calcium in the 0.004 M

mngnrsium sulfat’e solution over that in the Ringer’s solution


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J. C. Forbes 267

itself. On the other hand, as shown in Table IV, in solutions containing the same magnesium concentration and approximately the same calcium concentration but containing 2.9 mg. of phosphorus per 100 cc., definite deposition of solution calcium took place. Further evidence showing the effect of phosphates on the calcium solution action of magnesium salts is given in Table VIII. It will be seen from Table VIII that although there is no very definite difference between the calcium solubility in distilled water and the ~/750 phosphate buffer solution (4.1 mg. of phosphorus per 100 cc.), there is a very marked difference when one compares the calcium solubility in the solutions of higher phosphate concentrations with that in distilled water containing the same amount of magnesium salt.

Since an increase in either the calcium or phosphate concentration of the solution decreases t,he solution effect of magnesium salts, it is probable that the magnesium acts by increasing the solubility product constant of the calcium salts rather than by the formation of complex calcium-magnesium salts as suggested by Zorkendorfer (13). This would also explain how, as shown in many experiments, marked solution of bone calcium may take place with an actual decrease in the phosphate concentration of the solutjion. It is probable that this decrease is due to precipitation of Ca3(P0&; consequently the calcium and phosphate concentrations at equi- librium are determined by the solubility product constant of t,his compound under the conditions of the experiment. The fact t,hat the bone calcium passes into solution in some other form beside Ca3(PO& makes it possible to obtain marked solution of bone calcium in spite of an actual decrease in the phosphate concentration of the solution.

SUMMARY

The solubility of bone in various solutions of magnesium salts has been studied and it has been found that:

1. The solubility of bone calcium in water solutions is greatly increased by magnesium salts; the greater the magnesium concentration the greater the calcium solubility.

2. In the absence of phosphates from the original solution the calcium goes into solution as a phosphate and as some other compound, possibly a basic compound like the hydroxide or carbonate.


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3. When phosphates are present to even a moderate extent in the original solution, marked solution of bone calcium may take place with an actual decrease in the phosphate concentration of the solution.

4. Increasing the calcium or phosphate concentration of the original solution decreases the solution action of magnesium salts, especially when these are present in low concentrations.

5. Bone has been found to have a marked neutralizing action against acids, the pH of all weakly acid solutions being rapidly increased to over 7 by the neutralizing action of the bone.

It is a pleasure to acknowledge a grant from the Virginia Academy of Science to meet some of the expense of this investigation. My thanks are also due Miss Hazelwood Irving for carrying out some of the analytical work.

BIBLIOGRAPHY

1. hlendel, L. B., and Benedict, S. R., Am. J. Physiol., 26, 1 (1909). 2. Schiff, E., Jahrb. Kinderheilk., 91,43 (1920). 3. Stransky, E., Arch. exp. Path. u. Pharmakol., 76, 122 (1915). 4. Richter-Quittner, M., 2. ges. exp. Med., 46, 479 (1925). 5. Malcolm, J., J. Physiol., 32,183 (1905). 6. Hart, E. B., and Steenbock, H., J. Biol. Chem., 14,75 (1913). 7. Palmer, L. S., Eckles, C. H., and Schutte, D. J., Proc. Sot. Exp. Biol.

and Med., 26, 58 (1928). 8. Underhill, F. P., Honeij, J. A., and Bogert, L. J., J. Exp. Med., 32,

41 (1920). 9. Bogert, L. J., and McKittrick, E. J., J. Biol. Chem., 64,363 (1922).

10. Shipley, P. G., and Holt, L. E., Bull. Johns Hopkins Hosp., 41, 437 (1927).

11. Shelling, D. H., Kramer, B., and Orent, E. R., J. Biol. Chem., 77, 157 (1928); Kramer, B., Shelling, D. H., and Orent, E. R., Bull. Johns Hopkins Hosp., 41, 426 (1927).

12. Holt, L. E., Jr., La Mer, V. I~., and Chown, H. B., J. Biol. Chem., 64, 509 (1925).

13. Zorkendorfer, W., Biochem. Z., 221, 33 (1930). 14. Kramer, B., and Tisdall, F. F., J. Biol. Chem., 47, 475 (1921). 15. Fiske, C. H., and Subbarow, Y., J. Biol. Chem., 66, 375 (1925).


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J. C. ForbesOF MAGNESIUM SALTS

SOLUBILITY OF BONE IN SOLUTIONS

1931, 93:255-268.J. Biol. Chem.

http://www.jbc.org/content/93/2/255.citation

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solubility of bone in solutions of magnesium saltsthe results following oral ingestion of magnesium...

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