208
Pathology and Pathogenesis of Experimental Fluorosis in Cattle
Distal epiphysis of femur
The normal disposition of trabeculae im-
mediately below the epiphyseal line had dis-
appeared, giving place to irregularly disposed
trabeculae of normal structure.
These trabe-
culae apparently were of recent formation since
they showed slight clacification (Plate XIX, fig.
3). Some of the more recently-formed trabe-
culae showed accumulations of osteoblasts at the
surface, indicating their osteoblastic origin.
The usual process of breakdown and rebuilding
of bone had taken place through the activities
of osteoclasts and osteoblasts respectively; as
evidence of the former phenomenon, the osteo-
clasts presented a picture of 'dissecting resorp-
tion' (Plate XIX, fig. 2) of trabeculae.
The
intertrabecular spaces were occupied as a rule
by net-works of reticulum and osteoblasts, but
those immediately below the epiphyseal cartil-
age contained dilated cappillaries and collage-
nous fibrils, the latter presumably arising from
osteoblasts since these cells showed fibrillar pro-
jections at either end and contained elongated
nuclei. The collagenous fibrils at places show-
ed areas of condensation crowded with osteo-
blasts, some of which could be seen developing
lucunar spaces.
PATHOGENESIS
Chronic fluorine intoxication in animals is a
generalized chachectic condition, as the absorbed
fluorine compounds affect various organs of the
body.
In attempting to explain the patho-
genesis of the disease, attention has been direct-
ed especially to the mineral metabolism, to the
relation between fluorine and parathyroid and
thyroid, and finally to vitamins, particularly
vitamin C.
Further, the type of lesion
depends on such factors as dose and nature of
fluorine compounds ingested, duration of inges-
tion and the prevailing dietetic condition.
On
the basis of certain biochemical data and histo-
logical findings in affected bones, an attempt
may be made to explain certain features of the
pathogenesis.
As far as the symptoms and the gross osseous
changes are concerned, chronic fluorine intoxi-
cation may be looked upon as an osteodystro-
phia, but the question arises whether, as with
certain classical osteodystrophias, the osseous
changes in fluorosis also become manifest as a
result of disturbed calcium and phosphorous
metabolism.
Before attempting a complete
answer to this question the effects of a high
dose of NaF on the calcium and phos-
phorus contents of blood and bones of the
experimental animals may be examined.
TABLE I
Calcium and phosphorus in blood and thigh
bones of animals given high dose of NaF
(Majumdar et al 1943).
Hill Bull
No.
167
180
402
Control 89
Bone
(gm. per 100
gm. of ash)
Ca
41.5
40.0
39.5
41.0
P
17.3
17.3
17.4
17.3
Blood
Ca (mg. per 100 c.c. of
serum) and P (mg. per 100
c.c. of blood) after 7
months' fluorins feeding
Ca
9.9
9.6
8.6
10.4*
P
3.7
5.4
5.4
4.73*
*Average
The figures in Table I clearly indicate that
the high fluorine intake did not lower the cal-
cium and phosphorus values of the blood and
bone appreciably.
Metabolism studies on these
animals by Majumdar et al [1943] showed
slightly negative Ca and P values.
This
feature taken in conjunction with the slight
lowering of blood calcium might suggest that
the pathogenesis of fluorine intoxication is, to
some extent, connected with a fall in blood
calcium. Against this is the fact that by feed-
ing extra calcium as phosphate and carbonate
to another group of experimental animals,
which were getting the same quantity of fluo-
rine, symptoms and lesions of fluorine intoxi-
cation were not prevented. The negative Ca
and P balance observed by Majumdar et al
may, therefore, have been due to a generalized
toxic effect of NaF interfering with the animals'
appetites and so leading to lowered intake of Ca
and P.
Evidently fluorine has no direct effect
on the metabolism of these minerals, and its
effects on bone can hardly be explained solely
on the basis of negative Ca balance.
Histological examination of certain parts of
the skeleton, particularly the spongiosa, reveals
excessive resorption of trabeculae, indicating
a considerable withdrawal of Ca and P. This
would suggest a rise in output of Ca and P, but
in view of only a slight increase which has
already been accounted for, one might agree
with Roholm [1937] that the actual explana-
tion of the phenomenon lies not in the negative
Ca balance, but in the primary calcioprive
mechanism of fluorine affecting the usual
calcium depots of the bone.
The question
therefore, arises as to the fate of calcium with
drawn from these skeletal depots, and this can
be explained on the assumption that fluorine,