THE SKELETON AND ITS JOINTS
The bones with their articulations have been the subject of extensive
study and research by zoologists in the direction of classification and
evolution. Adaptation of the osseous construction to the needs of the
animal is well appreciated biological knowledge. For example, the keel
of the sternum in birds affords broad origins for the flying muscles,
the pectorals, which also insert on the alæ of this bone and on the
clavicle, and in addition use these latter formations as fulcra. So too
the extremities of quadrupeds are angular in their upper two segments
for the purpose of supplying a direct action of the flexors employed in
running and leaping. The thick masseter muscle of carnivores is
accommodated in the deep zygomatic fossa. Many other examples might be
cited, but these serve to direct attention to the adaptation of function
and construction. Pathological changes in our materials are however too
few to permit conclusions as to possible relation of zoological position
and development except such as may refer to deformity incident to the
degenerative processes—rickets, osteomalacia and osteogenesis
imperfecta, and in these conditions the alterations are merely passive
accommodations to weakened support in order to obtain comfort. To put
the matter in other words, it would seem that, aside from the diseases
just named, there is no outstanding change in the skeletal tissues
peculiar to zoological orders that might indicate vulnerability of the
system or the methods of response to injury or disease.
EFFECTS OF TRAUMA.
There must be considerable reserve or reconstructive power in the bones
of animals since it is a common thing at autopsy to see unmistakable
evidences of repair of fractures, dislocations and inflammations. Some
illustrations are introduced to exemplify this healing ability, one of
which was found in an animal shot by a hunter, the other an incidental
autopsy discovery. Even though there be no definite relationship between
the zoological order and osseous disease, it is interesting to record a
very simple observation. Animals with long extremities, especially when
the bones are quite near the skin, have a rather high incidence of
fractures and inflammations. Thus the ungulates have of all orders the
highest percentage of these traumatic and infective lesions; herons and
gallinaceous birds follow the ungulates. Marsupials, primates and
carnivores, in this order, are susceptible to inflammations but not to
fractures. Bones are often broken, among the Cervidæ, Bovidæ and
Camelidæ, when as they are chased by mates, they fall upon the slippery
floor of the cages; or again the mounting of a small animal by a large
buck may crush the former to the earth. Two cases of fractured pelvis
have been seen in antelopes from a fall with extended hind legs.
It would seem that repair is usually satisfactory if the animal has a
quiet retreat where callus may form and union occur. A heron is known to
have broken both bones of the leg; at autopsy a very insignificant
circumferential callus remained, the member being as straight and strong
as normal. Figure 40 shows the femur of a deer shot by a hunter; the
shortening was considerable, but function was doubtless good because the
hunter could perceive no limping as the animal ran. The most interesting
fracture among our records was an intracapsular fracture of the hip in a
Huanaco (_Lama huanacos_) shown in Figure 41. This animal slipped on the
ice in December and was thought to have broken something near the hip,
but it limped around without any great show of pain until the following
May, when it died of meningitis secondary to an _otitis media et
interna_. At autopsy an unhealed, complete fracture of the neck of the
right femur was found, apparently separating the head from the neck, the
former being dislocated to the upper angle of the obturator foramen.
Everywhere about the joint callus had been thrown out, but not in a
manner to effect a junction of the broken ends nor to seal the edge of
the acetabulum to the femoral neck. This was probably due in part to the
irregularity of the line of fracture and to the interposition of the
upper part of the dislocated head between the lower rim of the
acetabulum and the surgical neck of the bone. When the specimen was
fresh traces of capsule were found over the upper half of the
acetabulum. While it is usually difficult to decide the manner in which
these injuries effect their damage and deformity, it might be ventured
to explain this case as due to extreme posterolateral extension of the
leg driving the head of the femur downward and inward, rupturing the
capsule and the ligament bridging the acetabular notch, to rest on the
pubis at the upper edge of the obturator foramen where it could find a
sort of joint cavity made by the pubic and ischial segments of the old
acetabulum, but about an inch and a half below its normal location.
[Illustration:
FIG. 40.—HEALED FRACTURE OF FEMUR. FROM A DEER SHOT BY A HUNTER.
]
[Illustration:
FIG. 41.—PARTIALLY HEALED INTRACAPSULAR FRACTURE OF HEAD OF RIGHT
FEMUR. HUANACO (LAMA HUANACOS).
]
Another injury to the hip joint was noted in a Livingstone’s eland
(_Taurotragus oryx livingstonii_). This beast was not positively known
to have fallen, although it was suspected that such an accident had
occurred by reason of sudden inability to rise. At autopsy, death having
succeeded on signs of shock, a complete upward and backward dislocation
of the right femoral head was found; there was also an intracapsular
rupture of the left round ligament, but on this side the femoral head
had not left the acetabular cavity.
Many other fractures have been observed but generally without
interesting features. The conclusions which may be drawn from our
experience are that animals with long bones, and liable to chase have
the greatest liability to fractures, and that the healthy beast, given
seclusion and quietude, possesses great ability to heal its broken
bones. Pathological fractures are occasionally seen. (Consult notes on
cretin wolves.)
Before entering upon a discussion of the most important of osseous
lesions, rickets and osteomalacia, certain inflammatory states may be
appropriately described.
INFLAMMATIONS.
Hypertrophic osteoperiosteitis: A male lion (_Felis leo_) at the Garden
three years died, after being out of condition for a long time, from
chronic ulcerative pulmonary tuberculosis with terminal pneumonia,
nephritis and enteritis. Both hind feet had been observed as enlarged
and apparently painful for some weeks before death. Upon dissection the
bones of both hind feet are the seat of extensive hypertrophy, and the
periosseous fibrous tissues are thickened. A large mass about the size
of a small orange lies attached to the outer side of each ankle. The
hypertrophic periosteitis extends up the tibia a distance of about three
inches and the fibula for about the same distance. These two bones are
adherent to each other for about 1½ inches. The joint between them and
the tarsal bones is apparently perfectly free. The calcaneum is the bone
most severely involved; on this is a large rounded mass which extends on
the bone for a distance of about 2½ inches. The small bones of the foot
are more or less severely involved but are not bound together, the
joints being practically free. The terminal and next phalanges are
entirely free from disease while the metatarsals are severely involved
and grown together into one large mass. On section this appears as a
mass of spongy bone lying on top of the cortex. In the dried specimen
this looks very like old pumice stone. Histological section shows the
periosteum raised from the bone by mononuclear infiltration. The bone
marrow spaces are filled by a very delicate gelatinous material. The
lamellæ are thickened. A photograph of the foot with a normal example is
given. (Fig. 42.) (See also Tuberculosis section—Carnivora.)
[Illustration:
FIG. 42.—HYPERTROPHIC PERIOSTEITIS. RIGHT HIND FOOT WITH A NORMAL
LEFT. LION (FELIS LEO). THIS CONDITION WAS ASSOCIATED WITH CHRONIC
PULMONARY TUBERCULOSIS.
]
[Illustration:
FIG. 43.—MARKED SCOLIOSIS IN A COCKATOO.
]
A cockatoo died from acute miliary tuberculosis; the upper thoracic and
lower cervical vertebræ are involved in an S-shaped scoliosis which
reduces the height of the thorax by perhaps a centimetre. Thorough
dissection was not made, the trunk being kept as a museum specimen and
for study in event another avian scoliosis occurred; but from palpation,
separation of the muscles and stretching of the spinal column it does
not appear that a tuberculous osteitis of the vertebra existed. It seems
that this may be due to congenital deformity or old injury.
A white-nosed coati (_Nasua narica_) suffered with generalized
tuberculosis which also affected the wrist joint with a caseous and
ulcerative arthritis.
Gouty arthritis has been recorded but three times, although on several
occasions small uratic deposits in tendon sheaths have been observed in
birds; gout has not been seen in mammals. An illustrative case in a
Boat-billed Heron (_Cancroma cochlearia_) will be given in the section
on gout.
Arthritis as an acute infectious disease such as rheumatism of the human
being, has not been observed, but copious examples of acute, subacute or
chronic monoarticular inflammation are recorded. Nearly all of these
have a definite explanation—traumatism or acute general disease, and
there are a few cases of polyarthritis with chronic disease. Notable
among the last are two instances of chronic dry ossifying arthritis and
synovitis, one with tuberculosis, the other with actinomycosis, both
occurring in ungulates. A third case similar in character deserves
special mention. The Indian elephant “Bolivar” (_Elephas indicus_) died
from pulmonary tuberculosis, myocarditis, nephritis and hepatic
cirrhosis. The joints of all extremities showed atrophic arthritis with
fluid, the synovial membranes being ulcerated or retracted and fibrotic.
The articulating surfaces where not roughened by erosion, were
flattened. It is perhaps worthy of mention that this old and familiar
animal was the occupant of the same enclosure, floored with cement, for
over thirty years, conditions which might be partly instrumental in the
arthritic changes as well as in the flattening of articular surfaces.
The Ungulata frequently suffer with wounds, ulcers and abscesses about
the lips, nose, and soft tissues of the jaws which may at times be
confusingly like actinomycosis. This disease we have seen in gazelles
and tapirs but have had to exclude it in several other members of this
order. A number have come to autopsy with osteitis of the lower
mandible, some evidently traumatic in origin, others probably due to
infection _via_ the teeth. Figure 44 represents the jaw bone of an
Isabelline gazelle (_Gazella isabella_) suffering with a rarefying
osteitis from a root abscess, and illustrates well the possibility of
focal infection from this source.
DEGENERATIVE SKELETAL DISEASES.
While the foregoing instances of disease in the osseous system are
interesting examples of individual pathological lesions, they are
insignificant in comparison with the forms of bony change known under
the names of rickets, osteomalacia, osteogenesis imperfecta and the
like—systemic conditions which are chiefly degenerative but have certain
evidences of inflammation in addition. The modern knowledge of the first
two named is so far from complete that it cannot be said that there is
any certainty of their identity. Indeed there seem to be some reasons to
think that there is more than one variety of rickets, that all cases are
not dependent upon the same cause, and that in essence it is the same
process as osteomalacia, the latter, however, occurring at a later age.
We shall show that in the same order, Primates, both diseases may occur
in animals fed upon the same diet, and that one family tends to have one
disease, another family the other.
[Illustration:
FIG. 44.—DENTAL ROOT ABSCESS AND OSTEITIS OF JAW BONE. ISABELLINE
GAZELLE (GAZELLA ISABELLA).
]
RICKETS.
Since the two conditions are diagnosed separately in veterinary practice
and each seems to have a distinct place in medical ideas, it may be well
to outline upon what criteria the two diagnoses have been made in this
Garden. Rickets is essentially a disease of early life. The animal is
noted as having a large head, squatty station, heavy extremities and a
prominent belly. Death occurs as the result of enteritis or pneumonia.
Occasionally such a young specimen seems to recover from the disease but
retains the distortion of his skeleton; this is important, for we
believe that osteomalacia, except the variety confined to periods of
pregnancy, rarely ends in recovery when once thoroughly established. At
autopsy the cranial bones are the seat of osteotabes, the face is broad,
the epiphyseal junctions are swollen by irregular osteogenesis and
granulation tissue, the periosteum shows an irregular fibrous tissue
overgrowth—the last two processes producing bones of irregular contour
and thickness. Section through the osteogenetic ends of the long bones
shows actively congested marrow up to the articular cartilages with very
tortuous strands of spongy bone or cartilage, and when considered
transversely, there is a bone-forming layer of many times the normal
thickness but bloody red instead of pink.
OSTEOMALACIA.
Osteomalacia appears in mature animals or at least those well able to
care for their own nourishment. The earliest observations are not
referable to the skeleton but to the change in the activity of the
beast. He will be noted as less active in running, jumping or searching
for his food. The customary position is a sitting or lying one. No
change is noted in the head or face. As the disease progresses, the
animal becomes quite inactive, seeks solitude but will eat well if the
food be conveniently available and he does not have to fight for it. The
movements are stiff and seem painful. About this time definite
alteration in the shape of the chest is perceptible, and in some cases
there is anterior curvature of the legs. Movement becomes so difficult,
probably from weakness and pain, that it seems as if paraplegia actually
existed. The inability of affected monkeys to climb has given rise to
the term “cage paralysis,” but this term should not be restricted to
weakness, the result of osteomalacia since it is used by dealers and
keepers to imply the cramped station and gait of an animal long housed
in quarters too small for it, an appropriate application because it
suggests cause and effect. However, the appellation is widely and
loosely used insuring its employment in diagnosis for entirely different
conditions such as degenerative bone disease and hind-quarter laming
from enteric intoxications; for these affections one might use the term
in an adjectival or descriptive sense.
Our Primate collection has suffered considerably with osteomalacia, and
we have devoted much time to the study of its cause and treatment.
However, the Garden is not alone in this experience, for wherever
certain species are kept the disease appears. The description of cases
in the New York Garden by Blair and Brooks[46] is excellent, and with
the exception of data concerning the nervous system, almost exactly
parallels our own observations. They lay much stress upon the changes in
the brain, cord and ganglia as constant in well developed cases but as
probably secondary to the osseous, hemic and metabolic disturbances. We
have been unable to find any pathological lesions in four thoroughly
studied brains and cords from well developed cases. As will appear
later, our most satisfactory findings were in the dietary and metabolic
chemistry and in the osseous pathology. The cases recorded by Campbell
and Cleland[47] would seem to be undoubted instances of myelitis, but
the osseous changes are not sufficiently discussed. In many cases it
would seem, therefore, that there is some change in the nervous system,
but there may be some examples without this and with predominant osseous
lesions. We are inclined to think that these two groups differ
qualitatively, and we look upon the confusion as demanding for its
ultimate solution the use of exact nomenclature, especially the
exclusion of “cage paralysis” as a diagnostic term. The only division we
can understand at the present time depends upon the gross changes in the
bones, those with and those without definite irregularities in contour
due to periosteal overgrowth. Certain of the former may show no
unevennesses at all, the deformity being due to softness of the
skeleton. The other group has shafts of irregular thickness, swellings
around the joints and much beading of the middle of the ribs.
Whether or not there be true paralysis is difficult to settle, but in
our cases we have decided always in the negative because of the ability
of the monkeys to grasp firmly with the hind digits. The animals tend to
lie in one position, determined probably by comfort, the result being
that they develop sores at the points of contact with their cage floor,
and deformities of the skeleton (see Fig. 45). These deformities are
especially well exhibited by the chest, the vertebræ and the pelvis and
are referable to the almost constant squatting of the animal; the long
bones may be bowed but not as much as in rickets, nor is the epiphyseal
junction so knobby as in that disease.
The foregoing description is based chiefly upon observations on monkeys
but may be closely paralleled in carnivores and rodents. These latter,
however, lie rather than sit during the development of the disease, so
that thoracic and pelvic deformity is relatively less than in monkeys.
Death is due to enteritis, anemia, shock from fractures and respiratory
inflammation.
In so far as the deformities of the skeleton may serve to distinguish
between rickets and osteomalacia, I can only point to the preponderance
of changes in the skull and extremities in the former and of the trunk
bones in the latter. Deformity of the chest, barrel-shape shortening and
pigeon breast, is due more to posture than to the essentially osseous
changes. “Rachitic rosary” may occur in both, but it is always better
exhibited in rickets; in this disease the swellings occur at the
costochondral junction, while in osteomalacia rosary-like nodules may
develop anywhere along the ribs.
Examination of the anatomical lesions is, however, somewhat more
helpful, and the following description for osteomalacia may be
contrasted with that already given for rickets. The peculiar change is a
thinning of the shaft of long bones and reduction of the subperiosteal
plates of flat bones.
In mammals the long bones are more affected than in birds whose sternum,
ribs and beak show the severest changes. The skull is frequently not
affected to a serious degree, but may, however, show advanced lesions,
the cranial plates being thinned in places so that they may be bent in,
or occasionally a periosteal thickening may be found; the head as a
whole is not misshapen. The ribs are softened and may be of paper
thickness although there may be found a periosteal overgrowth, perhaps a
kind of splinting, which makes the diameter variable. At costochondral
junctions, beading may be found, but without the active congestion seen
in rickets. Similar alterations may be found in the long bones, here in
characteristic degree in that the shaft walls are thin, by removal of
the endosteal and periosteal layers sometimes with definite retraction
of the marrow. Occasionally subperiosteal thickenings, made of
osteofibrous tissue are encountered. At the epiphyses there are strands
of gelatinous tissue, fibrous and cartilaginous, separating pink or
blood-red areas of marrow. These strands may contain calcareous matter
and are probably the remains of the cancellated tissue. Despite all this
activity at the ends of the long bones there is not the extreme
prominence of articulations so characteristic of rickets. Gelatinous or
cartilaginous islands may be seen in the deep red shaft marrow.
[Illustration:
FIG. 45.—OSTEOMALACIA. MODERATELY ADVANCED CASE WITH HOWEVER WELL
ESTABLISHED DEFORMITY OF THORAX AND PELVIS. THIS POSITION WAS
CONSTANT FOR THREE MONTHS BEFORE DEATH. BLACK HANDED SPIDER MONKEY
(ATELES GEOFFROYI).
]
Fractures may be found and around them may form a blood clot or loose
fibrous tissue entirely devoid of bone salts. If a break has existed for
some time a very pronounced fibrous overgrowth from the periosteum is
apt to occur, indeed an excessive fibrosis may exist, but this is
ineffective for healing of the fracture or splinting of the shaft.
Certain cases, notably in Carnivora, seem to have especial activity in
and around joints so that when the member is dissected one gets the
impression of osteoarthritis. In such cases the synovia may be fibrotic
and the articular surfaces dry. The pelvic deformities are similar to
those in the human being—lateral contraction with bending in of the
superior rami of the pubis with the production of a beak, to which the
name “duckbill” has been given. The anterior curvature of the lumbar
spine makes an acute angle at the upper end of the sacrum.
Histological examination of a number of our cases of osteomalacia and
rickets have failed to show any lesion different from those known for
the human being and for domesticated animals. It is noteworthy that not
all bones of a given case will show the changes to the same degree even
though grossly they may seem comparably affected. So too there is no
certain relation between the degree of deformity as shown by the body as
a whole and the advancement of osteoporosis as seen under the
microscope. These observations are in accord with those of Brooks and
Blair. Just why this is cannot be stated, but as the cause of these two
bone diseases may not always be the same, variations in gross and minute
anatomy are not remarkable.
Analysis of the bones shows a loss of calcium and an excess of sulphur
and magnesium. The loss of the first is chiefly _via_ the intestinal
discharges but also _via_ the urine. The metabolism of one monkey showed
a high calcium and phosphorus loss with moderate retention of sulphur
and magnesium.
Because of the importance of osteomalacia and rickets in cebus monkeys
and certain other animals, Dr. E. P. Corson-White has been investigating
its etiology. I shall refer briefly to her results as they affect our
present subject but shall leave for discussion in the chapter on diet,
which she has written, the broader question of food and systemic
disease.
It must be understood that the instances included in this general
discussion of degenerative osseous disease are cases of definite
character and development. There may have been, in addition to the
numbers cited in the list on page 357, many more animals at autopsy with
early or unrecognized constructive or destructive abnormalities, and we
are thoroughly familiar with the imperfect skeletal development of
specimens, inbred or reared in captivity or even those adult when caught
yet under Park conditions for many years. In these latter groups the
changes vary from incomplete construction (an example of atrophy was
quoted on page 24) to actual degeneration as in osteomalacia. Inbreeding
seems to be a potent factor in many cases, a well known fact in human
and veterinary medicine. The importance of inactivity in the causation
of degenerative bone disease, the unused muscles giving the bones
nothing to do, is certainly admitted but it is immeasurable. It is
probably not great in a cage of mixed varieties of monkeys. The effect
of the absence of sunlight in osseous degeneration is no factor in our
material. The exhibition house is well lighted and many animals are out
of doors all year around.
The ductless glands have repeatedly been accused of responsibility for
these disorders. In our seventy-nine cases of osteomalacia and thirty-
four of rickets, no abnormality has been observed in ovary, testes or
adrenals except for moderate congestions. Two cases were associated with
pancreatic disease, once acute, once chronic. The thyroid body has been
found to have been definitely abnormal only once—secondary hyperplasia
with colloid in a carnivore. In the Primates this body was frequently
congested and has shown small colloid cysts but was not uniformly
enlarged or atrophic. As a therapeutic measure I have administered
adrenalin to two monkeys, one for a few weeks, one for nearly six
months; this treatment was without any perceptible effect upon the
process.
Dr. Corson-White has, by the study of some cases during the life of the
monkey, confirmed the decreased alkalinity of the blood in connection
with the increased output of calcium in the feces and urine.
Since the explanation of the disease by blaming the ductless glands has
failed, Dr. Corson-White has undertaken a study of the diet given our
monkeys to see if any fault in it were a part of the etiology. Analysis
of this diet (see list page 426) computed from Atwater’s table, and by
actual analysis of the amounts of food consumed by the animal in four
four-day periods, gave:
1. Protein—low in quantity and poor in quality; especially low in
phosphorus content.
2. Fat—very low.
3. Carbohydrate—very high, almost eleven times the value of all other
ingredients.
4. Ash—decidedly low and predominatingly acid. Further analysis of this
ash showed a trace only of calcium and phosphorus and iron and only a
small amount of sodium; potassium, sulphur and magnesium were slightly
higher.
5. Vitamines A, B, C, were present in extremely small amounts—A was
exceptionally deficient, and in the rations of some days was entirely
lacking.
There are in this monkey diet several factors of importance. 1. Low
vitamine contents—especially Vitamine A—factors which are essential for
life and growth. 2. A high carbohydrate diet—which in oxidation yields
an acid ash and which favors the growth of intestinal bacteria producing
acid and gas. The acid from these two sources must be neutralized either
by the alkali derived from food, or from the body storage. This diet,
however, is abnormally low in ash and especially in the alkaline salts
of the ash, therefore making it an ideal diet for the production of
osteomalacia.
The following table shows the additions necessary for corrections of the
separate ingredients of the diet:
Monkey diet Corrected by
Rice Casein, Salt mixture, Carrots, or Lettuce.
Bread Casein, Butter fat, Salt mixture, especially Phosphorus.
Potato Salt mixture, especially NaCl and CaCO_{3}.
Raw peanuts Salt mixture.
Bananas Casein, Yeast, or Carrots.
Corn Casein, Tryptophan, Lacto-albumin.
Apple Casein, Gelatin, Butter fat.
Onion Casein, Gelatin, Butter fat.
The complete diet may therefore be rendered adequate by the addition
of fresh, whole milk and leafy vegetables, or by butter fat, salt
mixtures and leafy vegetables.
It would seem from these data that in this inefficient diet we have, if
not the cause of osteomalacia, at least a very potent factor in its
production. The disturbance of the calcium and phosphorus metabolism may
be due primarily to the deprivation of the alkaline salts from the diet
(famine osteomalacia) or to a drain from the alkaline storage of the
body, associated with a deficient diet (as in the cases of osteomalacia
of pregnancy and lactation) or in the combined action of a diet faulty
in more than its salt content, which by the production of acid in its
oxidation and by favoring the development of acid-forming bacteria,
causes the drain of the body alkali for the neutralization of this acid,
or it is due to the combination of all these factors acting through
their influence on the ductless glands.
It is important also that while this disease is very common among the
Cebidæ it has never been found among the macaques. This may be due to
the fact that, owing to the storage sacs in the mouth of the macaques,
more food proportional to body weight is consumed, or there may be an
essential difference in the basal metabolism of the families and
individuals. All the factors enumerated do tax the metabolic resources
of the body and depress the functions of the endocrine glands. Only
detailed and accurate quantitative studies of normal metabolism and the
effect of alterations of it on the ductless glands will give a more
definite answer to the problem.
This work indicates clearly the alterations to be made in the diets to
meet the requirements of the Cebidæ and is to be followed by
investigations along similar lines for other families.
TABLE 17.
_A List of the Orders Exhibiting Definite Lesions of Osteomalacia and
Rachitis._
═══════════════════════╤═══════════════════════╤═══════════════════════
│ Osteomalacia │ Rachitis
───────────────────────┼───────────────────────┼───────────────────────
Primates │ 29 │ 10
Lemures │ 4 │ 2
Carnivora │ 3 │ 8
Hyracoidea │ 2 │ 1
Rodentia │ 5 │ 3
Marsupialia │ 1 │ 10
│ 44 │ 34
Passeres │ 3 │
Psittaci │ 9 │
Accipitres │ 2 │
Columbæ │ 12 │
Galli │ 9 │
│ 35 │
───────────────────────┼───────────────────────┼───────────────────────
│ 79 │ 34 = 113
───────────────────────┴───────────────────────┴───────────────────────
Having discussed the nature of these diseases and some of the factors in
their causation, analysis of their distribution may be appropriately
added. The accompanying list (Table 17) illustrates the orders in which
the two diseases have been found. Veterinarians are familiar with
systemic osseous diseases in all the domesticated herbivores, but Hutyra
and Marek note them as uncommon in dogs and birds. Among the Primates,
osteomalacia occurs almost exclusively in New World monkeys, Cebidæ and
Hapalidæ, whereas rickets is much more common among macaques
(Cercopithecidæ). Eight of the ten cases of rickets in monkeys seem to
have arrived at the Garden with evidences of this disease. Half of the
cases were arrested, or at least not florid, when the beast came to
autopsy. All of the osteomalacic lemurs belonged to the ring tailed
species, born in the Garden and dying at ages from three to seven years.
The cases of rickets among the Carnivora were four Felidæ, three Canidæ
and one Procyonidæ while all the osteomalacia cases were in the last
family. Six of the eight cases among the rodents affected squirrels. The
large number of cases of rickets among the marsupials is due to a litter
of small opossums thrown by an apparently healthy mother and dying in
from six weeks to three months.
The avian varieties which show the most definite osteomalacic changes
are the pigeons and pheasants, with the parrakeets presenting nearly as
characteristic lesions. Birds when affected with this disease, may come
to autopsy in fairly good plumage and without any very marked
emaciation. This is remarkable, for when the _cresta sterni_ is palpated
this ridge may sometimes be bent enough laterally to touch the _alæ
sterni_. How the bird can sit upon a perch when it is possible to bend
the femora almost double, is difficult to understand. Deformity is by no
means so frank as in mammals although periosteal overgrowth may be quite
marked at times. Anemia is undoubted in nearly every instance, the
pallor of the muscles seeming to be as great as if the specimen were
intentionally bled to death.
OSTEITIS DEFORMANS.
Dr. Corson-White was fortunate enough, during the course of her work
upon osteomalacia of monkeys, to detect a specimen which did not show
the usual excessive excretion of calcium but on the other hand retained
this element and evinced alkali hunger. The general appearance of the
specimen was similar to that of monkeys having osteomalacia but at
autopsy a definite picture of Paget’s disease or osteitis deformans was
discovered. This led to a search for cases in the literature and to the
following study, which I paraphrase and condense from Doctor Corson-
White’s notes.
Osteitis deformans is a chronic constitutional affection characterized
by the absorption of compact bone, chiefly in the cranium and long
bones, and the laying down of fibro-osteoid tissue in such an excess as
to enlarge the affected bones. This material, which is soft and cuts
with reasonable ease, has calcareous matter in it as shown by Röntgen-
ray examination. Paget described it in a classical article in 1876[48]
since which time the reported cases have mounted to three hundred and
fifty. Because it has only been recognized in its best developed stages,
it may be that early mild or arrested cases have been overlooked.
Judging by the instances claimed to have been found in museum
collections of bones, it is probably an affection dating to antiquity.
So far these remarks apply only to man but in lower animals the reports
are very few and those are not available in the original. The abstracts
and references show considerable confusion. The names osteitis
deformans, osteoporosis, osteitis fibrocystica, osteodystrophia
deformans and osteosarcoma, leontiasis ossei, etc., are used almost
interchangeably. In 1901 Barthelemy[49] described a condition (_Maladie
du Son_) in horses in which there was a marked enlargement of the head
and of the epiphyses of the long bones. His cases were more allied to
osteitis fibrosa cystica. Paget’s disease always attacks the diaphyses
of the bones and not the epiphyses. Goldman[50] described typical
examples of this condition in fowls. Jöst[51], in one communication,
described a case in a horse which he says was identical with that
condition described by Paget as osteitis deformans and by Virchow as
leontiasis ossei; he also refers to similar cases in goats and monkeys.
Rossweg[52] found it in goats. In wild animals the only suggestive
article found was by Jöst but the description was probably of an
osteoporosis and a craniosclerosis which occurred in a young lion and a
monkey. All the communications deal with either domesticated animals or
those in captivity.
The etiology of this condition is as obscure to-day as it was at the
time of Paget’s first description. Prince thought it might be due to a
defect in some peripheral nerve or nerve centre or to a tract
degeneration. Cases have been reported in conjunction with a myelitis.
There has been however little on which to base these suppositions. Paget
felt that the process was at least upon an inflammatory basis and
deduced this from the enlargement and the excessive production of an
imperfectly developed structure with increased blood supply. Many felt
that rickets, osteomalacia and osteitis deformans were all
manifestations of the same disease. A bacterial cause was proposed by
Arcangelli who claimed the discovery of diplococci and improvement from
a vaccine. Lancereaux[53] and Richards felt that focal infection played
a profound rôle in the etiology. However all other observers fail to
isolate an organism from the bones or to get improvement from removal of
infectious foci. Heredity has been held responsible in seven per cent.
of the cases in human beings.
That some inflammatory factor is partly responsible seems plausible when
one considers the active growth of fibrocellular tissue in the endo- and
periosteum. The more interesting theories go back to perversions of
internal secretions, pituitary, parathyroid etc., (Macallum & Vogtlein).
Higbee and Ellis[54] say in relation to the neurotrophic theory that if
the neurotrophic mechanism governs metabolism and is influenced by the
activity of the ductless glands, there is considerable likelihood that
its disturbance may possibly be found to be the cause.
Da Costa[55] believed the disease to be a disorder of bone metabolism
probably dependent on the absence or perversion of some internal
secretion. There is much evidence on hand to indicate that disorders of
the ductless glands do influence bone metabolism, and changes in these
glands have been reported in cases of Paget’s disease, although the
findings and lesions have been far from uniform or distinctive or even
confined to one gland. Eight cases were reported as possibly due to a
hypothyroid condition; pituitary changes were found in three; adrenal
changes in one; parathyroid reported missing in two; three had sclerotic
thyroids. Many case reports make no mention whatever of the glands of
internal secretion.
Da Costa interprets the retention of calcium, phosphorus and magnesium,
with the sulphur loss found in these cases, as indicating a stimulated
osseous or osseoid formation accompanying the resorption of a highly
sulphurized organic matrix. In the course of this calcification
procedure we suppose a certain quota of the sulphur of the matrix is
replaced by other elements, a process which must entail retention of
calcium, phosphorus and magnesium and increased elimination of sulphur.
He shows the close parallelism between the mineral metabolism of a
growing boy, a case after parathyroidectomy and a case of osteitis
deformans, and suggests that this depends in some way either on the
absence or perversion of some internal secretion, possibly of the
parathyroids, which controls calcium exchange in the body. Substances
from some cause arise which have the power to abstract calcium from the
body tissues, the abstraction of these salts being the first step in the
production of the disease.
The example which is reported in full was the first to be encountered in
our 5,365 autopsies but shortly after this series was concluded two more
came to autopsy and Dr. Corson-White’s studies were made to embrace
these.
A reddish woolly monkey (_Lagothrix infumatus_) received November 25,
1919, was a particularly active specimen and as far as we could
determine a perfectly healthy adult animal. He passed the tuberculin
test and was placed on exhibition. In April, 1920, he was first reported
as crippled and was removed to the laboratory in June, 1920. At that
time the long bones of the legs and arms were bowed anteriorly and
laterally, the degree of curvature making the hands and feet seem
disconnected. The monkey could stand but made no voluntary effort to do
so. There was evidently some pain although it could not have been at all
severe. He resented handling, especially of his arms and legs. The head
was rounded, resembling that of a baby, and the eyes were protuberant
suggesting an exophthalmos. The maxillary bones were so excessively
thick that the mouth could not close and the monkey drooled saliva. His
blood on admission to the infirmary in May was—Hg eighty-nine per cent.,
R. B. C. 4,370,000, W. B. C. 5,800; one week before death it was Hg
fifty-four per cent., R. B. C. 2,860,000, W. B. C. 6,000. Routine urine
examination showed a constant trace of albumin, hyaline and granular
casts. There was at no time a Bence-Jones protein reaction, excess of
indican, indol, or diacetic acid. He had a constant slight diarrhœa with
some flatulence, the semifluid, constantly acid feces presenting a
preponderance of Gram-positive coccoid organisms. His appetite was fair
and he showed marked craving for lime, eating plaster from the walls
when he could get it. Because of this desire for lime he was given a
salt mixture to see if it would have any effect on the bone condition.
The mixture used was the following:
[Illustration:
FIG. 46.—OSTEITIS DEFORMANS. SKELETON SHOWING GENERAL THICKENING OF
ALL BONES, BUT ESPECIALLY OF THE SKULL, JAWS AND LONG BONES. NOTE
THICKNESS OF CALVARIUM, 10 mm.; NORMAL IS ABOUT 3–4 mm. THE HUMERUS
IS TWICE NORMAL SIZE. THE WIDTH OF THE ULNAR CORTEX IS SHOWN BY A
TRANSVERSE SECTION NEAR THE ELBOW JOINT. REDDISH WOOLLY MONKEY
(LAGOTHRIX INFUMATUS).
]
NaCl 0.874 grams
KCl 0.548 grams
CaH(PO) H_{2}O 3.608 grams
Ca lactate 0.386 grams
Mg citrate 0.848 grams
K citrate 1.953 grams
This mixture the animal ate with avidity and seemed more comfortable;
other than that no change was noted.
An inorganic metabolism examination was attempted on the ordinary diet
and the diet plus the salt mixture. Under the circumstances at our
disposal this was not entirely accurate but showed such marked variation
from the control animals examined—normal and osteomalacic—and such
marked correspondence on the four separate four-day periods of each
intake that it seemed acceptable. The result of this investigation on
the first series of four four-day periods was:
═══════════╤═════════╤═══════════════════╤═════════════════════════════
│ Intake │ Output │ Total
───────────┼─────────┼─────────┬─────────┼─────────────────────────────
„ │ „ │ Feces │ Urine │ „
───────────┼─────────┼─────────┼─────────┼─────────────────────────────
Calcium │0.0280 │0.014 │0.0022 │0.0162 = 0.0118 retention
Magnesium │0.0640 │0.034 │0.0123 │0.0463 = 0.0177 retention
Phosphorus │0.1540 │0.027 │0.0430 │0.07 = 0.084 retention
Sulphur │0.1440 │0.002 │0.1680 │0.17 = 0.026 loss
───────────┴─────────┴─────────┴─────────┴─────────────────────────────
The result on the higher salt content was practically the same, the
retention being in proportion slightly less. The diet for these small
monkeys is two apples, two bananas, six small sweet potatoes, with a
lump of boiled rice about the size of an egg. The content of this diet
has been found very low in calcium, phosphorus, sodium, chlorine and
iron, while potassium, magnesium and sulphur were high. To this diet
lime water was added to increase its inorganic content.
This Reddish Woolly Monkey died August 20, 1920, and was immediately
posted. There was marked thickening of the frontal, occipital and
parietal bones, upper and lower jaws. The increase in the size of the
alveolar margins prevented the closing of the mouth; only the last four
teeth could be brought into apposition. The enlargement of the mandibles
reduced the capacity of the mouth cavity. The skull while decidedly
thickened did not enlarge at the expense of the cranial cavity. There
was a cervical and dorsal kyphosis. The chest was increased
anteroposteriorly and contracted laterally. The long bones were thick,
bulky and deformed. (Fig. 46.)
A Black Spider Monkey (_Ateles ater_) showed a general hyperplasia of
the whole shaft of the long bones. She was much deformed by curvatures
and swellings of the skeleton—head enlarged, face deformed by the
swelling of the upper and lower alveolar processes, jaws do not close
and the palatal bones were flattened, skull irregularly thickened,
elastic but not soft, slight subperiosteal growth. Thickening of the
long bones was largely due to subperiosteal growth; section of the ulna
showed a subperiosteal osseoid layer surrounding the old shaft. This
tissue seemed to be very poor in lime salts, cutting without any grit.
Marrow cavity was filled with a fairly firm, deep red marrow which did
not bleed on section. The third monkey, a Brown cebus (_Cebus
fatuellus_) showed exactly the same general picture but was less
severely affected than the other two.
“The more minute study of the bones of these monkeys shows a variety of
pictures while preserving one general form. The skull was smooth,
mottled by irregularly placed areas of congestion; it was asymmetrically
thickened; differentiation between cortex and diploe, internal and
external tables was lost; calcareous matter was absorbed and the
resultant bone was soft, elastic and porous; lacunæ enlarged and lined
with bone corpuscles and giant cells. Other areas show more dense bone,
the reparative processes being more active in that the lamellæ are wide
and the vascular spaces narrower. As a rule the compact bone is
absorbed, the Haversian canals are more or less confluent and there is
generally a marked increase of newly formed osseoid tissue. The
ossifying periosteitis obliterates the depressions for the cranial
arteries and the sutures. The skull cap becomes finely porous,
cancellous and even cavernous. The spaces are filled with a soft, red
marrow-like material. The bones at the base of the skull are much less
involved; the pericranium, dura and brain are normal.
“The long bones show interlacing narrow strands which are in some
regions wide, in others narrow or thin as in spongy bone. Large
irregular cavities are present and there is a disappearance of the
compact bone and an encroachment on the medullary canal of a relatively
dense new bone with small irregular trabeculæ surrounded by osteoblasts
and a fibrous connective tissue which fills the outer trabecular spaces.
The new bone is often both subperiosteal and subendosteal, the latter
often gaining on the former. It is always soft and irregularly
calcified. The general arrangement of the strands in the deep layers is
longitudinal but in the subperiosteal bone they are very irregular and
almost at right angles with the central strands. In this new osseoid
tissue cysts are frequent, varying in size from very small to rather
large cavities filled with a cloudy gelatinous material. The picture
here is very like osteitis fibrosa cystica. Endosteal cells proliferate
and may fill up the marrow spaces so that solid masses of fibrous tissue
result. Frequently the osteoid material shows fibrillæ. The compact bone
may be irregular with well marked Haversian systems. Toward the
periosteum the cells may become scanty, the bone dense in structure
while toward the interior the cells are more numerous and in the more
cancellous portions, the trabeculæ become slender and far apart; here
they may be covered by a single row of osteoblastic cells. The
intertrabecular spaces are large, irregular and filled with a delicate
alveolar tissue containing only a minimal number of normal bone marrow
cells, large capillaries and no giant cells. Periosteum may be of usual
thickness; the bone immediately beneath is spongy. The sclerosis of the
bone in its densest areas is entirely due to the ossification of spindle
cells which have remained in the place of the original marrow of the
bone. As a whole the bone is nowhere normal in amount or proportion but
the small Haversian systems are properly made, the abnormality being
chiefly due to cellular and fibrous growth around the large lamellæ
which at times is normal in amount but usually much in excess. In places
this consists wholly of fibroblasts, at others of giant and round cells
very suggestive of sarcoma. All histologists apparently agree that
Paget’s disease starts as a resorption of already calcified bone.”
These data seem to supply ample evidence that the autopsy diagnosis of
Paget’s osteitis deformans was correct. While the anatomy and course and
chemical changes presented by these monkeys do not settle the causation
of the disease, they offer very definite suggestions which Dr. Corson-
White summarizes in the following cautious conclusions.
“Many of the cases of Paget’s disease first came under the observation
for fractures, accidents common in osteomalacia but very rare in
developed cases of osteitis deformans. Early cases all presented
diarrhœa, which was present in all the early human cases seen, and in
all the cases reported in monkeys. This symptom was mentioned in
fourteen of the cases from the literature. It was also a constant
symptom in primate osteomalacia. The diet of these monkeys was
exceedingly low in those substances essential to bone development, and
Sherman has shown that the calcium balance is regulated to a certain
extent by the calcium ingested, and that when the diet was poor in this
element, the output materially exceeds the intake, a fact which is
immediately changed where the animal is put on a diet high in calcium.
So far as we could find there are no studies on the mineral metabolism
of beginning cases of Paget’s disease. It seems possible from the
osteomalacic animals previously studied, that the low mineral and
otherwise faulty content of the diet might so disturb the chemical
equilibrium directly, through the neurotrophic mechanism or through the
perversion of the ductless glands, that the mere addition of lime water
might entirely change the pathological picture. This is in accord with
the histology. The initial histological picture is always resorption of
bone, a general decalcification which later presents an irregular
proliferation. The disease then progresses along different lines ending
as osteitis fibrosa cystica, Paget’s or Von Recklinghausen’s diseases,
etc., dependent upon the strength of the reparative stimulus and the
organism upon which it acts.
“These cases are of interest (1) because they are typical examples of
Paget’s disease as it has been described in man both clinically and
pathologically, (2) because the disease shows the same general type of
inorganic metabolism that was exhibited in man, (3) because of the
alkali hunger shown by one monkey, and by two human cases, a hunger
which was severe, which preceded the deformity and disappeared after the
deformity was established, (4) because the disease developed in animals
fed on a diet insufficient in its inorganic and vitamine content to
which an excess of calcium was added.
“From this study it seems possible that Paget’s disease may be just one
stage in a deficiency disease, a reparative response through a
neurotrophic mechanism or through the perversion of the glands governing
calcium metabolism which has been perverted by an improperly balanced
diet.”
TUMORS.
Neoplastic diseases of the bones have yet to be classified to everyone’s
satisfaction. All gradations of hyperplasia of osteogenetic cells and
fibres and of the marrow elements, from simple inflammation to true
sarcoma, are recognized. As one reviews a large series of lesions,
clearly defined types may be found, but there are transition stages to
which an exact name is difficult or impossible to apply. Nor does the
pathological diagnosis always fit with the clinical course. Thus, for
example, the giant cell tumor of bones looks malignant, and is not, and
its structure may be simulated in such diseases as fibrous osteitis and
Paget’s disease. As we have seen in the discussion of the latter of
these two, abnormalities of fibre and cell growth simulate neoplasms
very closely. In addition it might be mentioned here that actinomycosis
may produce bony growths resembling sarcoma. When osteitis deformans
affects the facial bones especially, it has been called leontiasis
ossium, and it is then a more nodular, tumor-forming process, the
enlargement consisting of fleshy masses occupying the whole bone, but
especially the marrow cavity. Histologically the lesion is
fibrocellular, frequently with numerous giant cells; accumulations of
small sarcoma-like alveoli may be found. We have encountered four cases
among common opossums (_Didelphys virginiana_) and one in an Isabelline
Gazelle (_Gazella isabella_) and, because of the localization and fleshy
consistency of the tumor, we have called them osteosarcomata for
descriptive purpose, but not for classification among neoplasms (where
they will not be found). Two of the opossums had osteoporosis and
gelatinous marrow in the ribs. All these animals had been in the
exhibition under a year, and as far as known are not related. Figure 47
shows the gross character, while the following is the description from
one protocol.
[Illustration:
FIG. 47.—EXAMPLES OF LOCAL OSTEOMATA RESEMBLING OSTEOSARCOMA AND
FIBROUS OSTEITIS; THEY PROBABLY BELONG TO THE DISEASE KNOWN AS
LEONTIASIS OSSIUM.
]
[Illustration:
FIG. 47B. A AND B, OPOSSUMS (DIDELPHYS VIRGINIANA).
]
[Illustration:
FIG. 47C. C, ISABELLINE GAZELLE (GAZELLA ISABELLA).
]
[Illustration:
FIG. 48.—FIBRO-OSTEOMA, A LOCAL SINGLE TUMOR OF THE UPPER JAW. THIS
DID NOT RESEMBLE THE CHANGES IN ACTINOMYCOSIS, BUT THE INFECTION WAS
NEVERTHELESS EXCLUDED BY BACTERIOLOGICAL SEARCH. ISABELLINE GAZELLE
(GAZELLA ISABELLA).
]
Common Opossum (_Didelphys virginiana_) ♀ . Osteosarcoma of alveolus,
rarefying osteitis deformans of skull, hypertrophy of thyroid, acute
catarrhal enteritis, acute hyperplasia of spleen. About the middle of
both lower rami and involving the posterior half of each upper maxilla
is a uniform elliptical growth apparently emanating from alveolus.
Teeth not loose, but can be moved in tumor to be described. On section
a white glistening homogeneous growth is seen apparently originating
in the body of the alveolus and around the teeth. The shaft of bone is
soft and easily broken. What remains of marrow is irregularly
injected. In upper jaw there is a distinct porosis of facial bones;
they and the enclosed sinuses are deeply injected. Lower four ribs on
both sides show distinct nodulations of pale color along a bluish
bone. All ribs are very soft and section shows osteoporosis of shaft
with injected marrow and distinct cartilaginous periosteal bone
formation. The skull is everywhere soft and the bone is apparently
increased in thickness, rich in blood, but porotic. Rest of skeleton
seems well calcified. Microscopic section of tumor shows practically
the same picture. Bone is nowhere normal in amount and proportion but
the Haversian systems seem properly made, the abnormality consisting
chiefly of cellular and fibrous growth around larger lamellæ, which at
times is normal in amount but usually much in excess. In places this
consists wholly of fibroblasts, at others of giant and round cells
very suggestive of sarcoma; indeed all areas must be called giant cell
sarcoma. There is an attempt to lay down osteoid tissue at places
particularly beneath periosteum. The giant cells are in great numbers
and some seem osteoclastic. As the lamellæ disappear young connective
tissue seems to take their place but giant cells do not remain
numerous at such places. Despite its atypical nature it must probably
be looked upon as an osteosarcoma. The tooth socket is not much
involved save for hyalinization of root matrix immediately about
dentinal zone.
In another Isabelline Gazelle (_Gazella isabella_) there was a fibro-
osteoma localized to one side of the superior maxilla (Fig. 48); this
has been included among the tumors, while the above mentioned cases have
not been so grouped.
True osteosarcoma seems not to have occurred. One tumor was seen upon
the wing of a Cuvier’s Toucan (_Rhamphastos cuvieri_) which was formerly
diagnosed as sarcoma, but later examination reveals some giant cells in
arrangement suggestive of tuberculous osteitis; since this is the only
case and not unequivocally a tumor its record is hardly warranted.
Osteomata of the hard variety have been seen on the ribs of a pigeon and
a pheasant as small rounded compact well outlined tumors. It is thought
that they represent products of healing after osteomalacia or rickets.
An osteochondroma growing from the nasal cartilage was found in a
caracal (_Felis caracal_), a fibro-osteoma was found on the vertebra and
clavicle of a Beechy’s spermophile (_Citellus grammurus beecheyi_) and a
fibroma occurred on the clavicle of a lesser snow goose (_Chen
hyperboreus hyperboreus_). The only other tumor from a bone was an
endothelioma from the periosteum of the clavicle in a moorhen
(_Gallinula chloropus_). It corresponds to the usual idea of this tumor.
It probably caused death by cachexia, and by its size, interference with
respiration. The only secondary tumor was a metastasis in the tibia from
a spindle cell sarcoma of the kidney in a scaly ground dove
(_Scardapella squamosa_).
THE MUSCLES.
The skeletal muscles of the wild animals of our collection have been
quite free of pathological lesions such as atrophies and dystrophies and
indeed seem relatively seldom affected by disease. Occasionally
hyalinization will accompany infectious disease or local suppurations
will spread into the muscles. Much more often filaria, sarcocystis,
flukes and larval insects will be found resident within or between
muscle bundles; this will be discussed at a later time. Six tumors have
been found, three of which certainly developed in a muscle, while for a
fourth case no primary growth was discovered. This last one, to dispose
of it at once because of its peculiarity, was an adenocarcinoma found as
a firm, conglomerate, encapsulated mass in the sheath of the gluteal
muscles of a waltzing mouse (_Mus wagneri rotans_). No other growth was
discovered although it must be admitted the body was not exhaustively
searched for some tiny nodule to which primary focus this muscle mass
could have been secondary. That metastases may be larger than original
growths is well known. The gross diagnosis was sarcoma. If this be an
original tumor it might be explained as arising from ectopic mammary
tissue.
The five other tumors were sarcomata, one of large cells almost
syncytial in size, shape and number of nuclei, two definite spindle cell
growths and two of fibrosarcoma type. The first occurred in an all green
parrakeet (_Brotogerys tirica_), the second in an undulated grass
parrakeet (_Melopsittacus undulatus_), the third in a larger Egyptian
gerbille (_Gerbillus pyramidum_), the fourth in a white-footed mouse
(_Peromyscus leucopus_), and the last in a bean goose (_Anser fabalis_).