SECTION XII. The Skeleton and Its Joints

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.

FIG. 40.—HEALED FRACTURE OF FEMUR. FROM A DEER SHOT BY A HUNTER. ]

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.)

FIG. 42.—HYPERTROPHIC PERIOSTEITIS. RIGHT HIND FOOT WITH A NORMAL LEFT. LION (FELIS LEO). THIS CONDITION WAS ASSOCIATED WITH CHRONIC PULMONARY TUBERCULOSIS. ]

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.

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 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 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.

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 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 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 described typical examples of this condition in fowls. Jöst, 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 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 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 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 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:

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.

FIG. 47.—EXAMPLES OF LOCAL OSTEOMATA RESEMBLING OSTEOSARCOMA AND FIBROUS OSTEITIS; THEY PROBABLY BELONG TO THE DISEASE KNOWN AS LEONTIASIS OSSIUM. ]

FIG. 47B. A AND B, OPOSSUMS (DIDELPHYS VIRGINIANA). ]

FIG. 47C. C, ISABELLINE GAZELLE (GAZELLA ISABELLA). ]

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).