(Pictured above:   Vana and her buddy Qai in the background.)

Panosteitis
By, Fred Lanting

One of the main reasons for a young dog to be "pulled" from a show, or excused from
the ring, is the sudden lameness of a condition known as panosteitis, familiarly labelled "
pano" by many breeders. Of some 130+ breeds recognized by the American Kennel Club and
hundreds more by some other registries, a dozen or so have been reported to be affected.
This mysterious disease causes sudden lameness in many younger dogs, but its
greatest potential may be in false diagnosis. The disease has been given various names:
hematogenic chronic osteomyelitis, enostosis, long-bone disease, panosteitis, and
eosinophilic panosteitis. It was first described by Gratzl, and by Baumann and Pommer in
1951 in Vienna. Since then it has been reported in Sweden, Germany, Hungary, what was then
Yugoslavia, and the United States, yet there is not as much information on this subject in
the early scientific literature; there was no reference in several texts on orthopedic
diseases, and Smith's otherwise comprehensive text on Veterinary Pathology had but a brief
note on enostosis as "a German Shepherd Dog disease", "analogous to eosinophilic
panosteitis". An obscure Yugoslavian doctoral thesis dated 1961 led to a couple of
references, and a dogged search (pardon the pun) of the international orthopedic literature
finally turned up a 1970 study published in the AVMA Journal. Personal contact with
orthopedic and radiology specialists brought the search to some work at Purdue.

SYMPTOMS AND DIAGNOSIS
Clinical signs are those which are obvious or apparent upon gross examination of the
entire dog, as opposed to microscopic or other types of study. Symptoms are determined by
means which may include gait and motion analysis, and comparison with other limbs by
manipulation and palpation. In humans such a case history would include a verbal report by
the patient of his complaint. Radiologic study involves the use of X-rays, and histologic
determination usually requires euthanasia and dissection of the tissues involved (long
bones). A similar term, pathologic, also refers to laboratory findings of functional and
structural aspects of the disease. Fortunately, a knowledgeable breeder can probably
diagnose pano faster and cheaper than can a vet, merely by knowing the breed and pinching in
the right places.
Panosteitis is probably a disease of the osteoblasts, which, you will remember, are
those bone cells that produce the organic osteoid and matrix vesicles needed for
ossification. It involves a necrosis of fat
cells in the marrow of long bones. It is a generalized (pan-) inflammation (-itis) of
certain bones (os-). Specifically, it occurs in five of the long bones of the appendicular
skeleton: the humerus, radius, and ulna of the foreleg, and the femur and tibia of the hind
limb. It has not been reported in the long but narrow fibula of the lower rear leg. More
often than not, the first sign is a sudden lameness in one foreleg. Exhibitors have claimed
it always occurs between the closing date for entries and the day of the show, after all
arrangements and plans have been made, but this is something that has not been substantiated
by unbiased scientific studies.
Intensity of discomfort varies not only with the progression of the lesion in the
individual, but with the difference in pain threshold between one dog and another. It may
be so minor that one has to press
and probe to elicit pain response, or it may be so bad that the dog will whimper and refuse
to put any weight on the limb. The degree of pain is not closely correlated with the stage
as seen on the radiographs. While lameness may sometimes be observed in only one limb, the
disease has been
radiographically discovered in at least two bones simultaneously in some 96% of affected
dogs. Further, the typical lameness-recovery cycle of one or two weeks will shift from one
leg to another, although there may actually be as many as seven bones involved at any one
time. Usually, an upper arm will be affected first, followed by a femur or ulna, and often
the problem will appear in another bone in the original limb or its partner. There may be a
lapse of several weeks between episodes, and more than one phase may be present in the
individual at any one time.
Partly because of the nature of the disease and the fact that the owner is not
likely to do any damage to his dog by withholding treatment if it is indeed pano, this may
be the easiest to diagnose at home with fair reliability. If you can elicit a definite pain
response by pinching the suspected affected bone in the middle of the shaft, it is most
likely panosteitis. If the pain is at the distal end of the long bone, it could
instead be HOD, in which case a trip to the vet is certainly in order.
Computing this simple test with the breed predilection and perhaps previous experience, the
owner may save himself some expense. If you have any doubt, though, be sure to ask the
doctor.
Whether it is very common for the same bone to be the site of recurrence is not a
matter of total agreement, although too many owners report it to be so, to ignore that
strong anecdotal evidence. One study of 100 consecutive cases at New York's Animal Medical
Center concluded that "after a bone has passed through all phases of the disease, it is
unlikely that it will be affected again", and reported only one incidence of return to a
previously-affected bone. Another study released 5 years later held that "recurrence in the
same bone was most frequently found in the radius, followed by the ulna...", but mentioned a
6-month or more interval between episodes in individual long bones.
Symptoms of panosteitis may be confused, by the novice or the vet with limited
experience, with OCD of the shoulder or one of the elbow dysplasias; if in the rear limb, it
could make someone think the dog has HD or cruciate ligament injury. A case history plus
information on the breed, family, and diet can give some diagnostic clues. UAP, for
example, is often brought to light via trauma such as jumping off a ledge, but pano shows up
regardless of traumatic occurrences. The most reliable and definitive diagnosis might
possibly be by a series of radiographs which can show the early, middle, and late phases of
the disease, but even then radiographic signs can be so minimal that they can be missed,
even if the animal exhibits clinical signs and a number of films are correctly exposed.
Radiographs in both major studies were taken every month from 5 to 30 months of age. This
type of approach is not feasible for the typical dog owner, nor is it necessary or best in
most cases, if experience is sufficient.
I find my own diagnostic method to be at least as reliable as a series of
radiographs: first, I take into account the breed, and the second thing is to watch the dog
walk, as other problems can give subtle
differences in gait. Since I have long bred GSDs, and the disorder was once known as "that
German Shepherd Dog disease", I have had much opportunity to witness its appearance in dogs
of my colleagues. As soon as my 1981 HD book was printed, and I had said that I had never
had a dog with pano, I found the worst case I had ever encountered, in one of my own dogs!
By then, I had already plenty of practice in palpation (feeling) diagnosis as a part-time
professional handler and consultant to other breeders. The third and most reliable physical
test is to pinch the dog in the middle of the shaft of each of those ten bones (all the long
leg bones except the fibula) and compare its reaction, bone to bone.
Almost always, the dog will yelp with pain if you pinch the affected bone in the limb it has
been favoring. Try to squeeze where there is very little muscle covering the bone, but only
in the middle, not at the ends. Pain upon pinching near the joints can possibly lead you to
suspect HOD or joint disorders, but possibly other than bone cancer there is nothing that
gives the same response to pinching the middle of the diaphysis (shaft) as pano does.

Three Phases
The first stage, the one most associated with acute pain, exhibits the least
evidence of the lesion's presence in radiographs. There is some blurring, and an
accentuation of the pattern of fibrous bands extending from the cortex (the hard, denser
portion of the bone) inward toward the center of the medullary canal, where the marrow is
located. Film contrast between the canal and cortex is diminished, and the radiodensities
of the medulla and its lining are slightly greater. The fatty connective tissue takes on an
appearance similar to eosinophilic granulomas (hence one of the early names for the disease)
and bone is added to those fibrous bands, called trabeculae. The great deal of congestion
in the medullary canal is almost undoubtedly the main reason for so much pain; if the poor
dog could reason, he might imagine his bones were about to burst from the increased
pressure! If a hole is drilled (a punch biopsy) for the purpose of testing some of the
marrow, pain is abruptly diminished.
The second phase is easily diagnosed in the clinic by the appearance of radiodense,
mottled medullary tissue, beginning in the vicinity of the nutrient foramen, that hole in
the side of the bone where blood vessels enter and leave. In pano's second phase, the
borders of this hole are characteristically accentuated, the cortex appears less dense, and
its inner lining becomes less roughened. In cases where the medullae are greatly affected,
a remodeling (new bone cell formation) takes place as a secondary response on the cortex's
outer layer, the periosteum, and it grows to several millimeters thick. This is the
swelling or inflammation of bone that gives panosteitis its name. In 6 to 8 weeks these
characteristics gradually merge into the third phase.
During the approach of the third phase, the fibrous bone which formed in the medulla
is resorbed, giving the radiologist a more normal picture again, and production of blood by
the marrow resumes a more normal procedure. It may take several months for the bone to
regain normal shape and appearance, especially if pano had struck in the more mature
youngster, but it generally does heal satisfactorily. Only a radiology specialist or a
general practitioner especially well-trained in this field will be able to tell later on if
a particular patient had had pano.
Interestingly, no fractures accompanying or following panosteitis which could be considered
related have been reported, despite temporary changes in the porosity and density of these
organs as found in histo-pathologic examinations of euthanized dogs. Perhaps this is due to
the dog's extreme reluctance to put weight on the afflicted limb during the first two
phases. Nor was there any evidence of acute infection or chronic (lasting) inflammation.
The disease and recovery reach a point of cessation, with some evidence of its having been
there observable upon dissection and microscopic examination of the tissues. A little of
the marrow typically seems to be permanently replaced by fibrous connective
tissue rather than bone, and the thickening of the outer surface gradually returns to
normal.

SIMILAR DISORDERS AND SYMPTOMS
You have seen that the differential diagnosis which the owner can make with fairly
good accuracy (pinching the bone) will distinguish panosteitis from HOD and other disorders;
the vet can confirm it with
radiographs and examination. Another disorder which can give x-ray pictures very similar to
the "milky" or "cloudy" appearance of panosteitis is erythrocyte pyruvate kinase (PK)
deficiency. Some years
ago, a screening program to eliminate this hereditary enzyme metabolism disorder in Basenjis
was thought to have been successful, but around 1990, a few more were diagnosed. The
osteosclerosis, an abnormal
increased density of bone, is apparently a pleiotropic effect of the homozygous presence of
the deficiency gene. Pleiotropy means one gene (or identical gene pair, if recessive) gives
rise to more than one
disease or characteristic; Alaskan Malamute dwarfism/anemic blood disorder is another
example. In the Basenji disorder, the bone density that could take as much as two years to
develop might be one of the
evidences of the genetic problem, but only if accompanied by other tests.
Even then, it might be missed, as some affected dogs will show normally high erythrocyte PK
activity at the time of the tests. But if some of the other symptoms are looked for, the
diagnosis is easier. Affected
dogs often have heart murmurs, atrophied muscles, progressive anemia, stunted growth, rapid
heartbeats, and swollen livers, hearts, and spleens.

HEMOPHILIA WITH SIGNS OF PANOSTEITIS
Some dogs have shown such frank signs of panosteitis that a tentative but fairly
strong diagnosis of pano has been made, and then upon further tests run because of
additional symptoms, they were found to have Hemophilia A. Of course, it is possible that
some dogs can have both disorders at once, but based on the incidences of the two, the
coincidental appearance might be hard to imagine except in certain
isolated GSD families. Dr. Jean Dodd, a noted blood specialist, has seen some notable
connection between pano and von Willebrand's Disease (vWD), a different type of hemophilia.
I think that probably the signs of pano or the actual development of enostosis, as some
prefer to call it, in the hemophiliac dog come about via bleeding in the marrow with
osteoblast (bone depositing cells) activity.

CAUSE OF PANOSTEITIS
The cause or etiology is unknown, but fortunately the disease is self-limiting: it
follows a progressive pattern and generally the animal recovers with or without treatment to
a normal state or one so close that
you might not be able to tell it had occurred without cutting the bones for microscopic
examination. In worse cases, some permanent scarring can be identified by those especially
adept at reading the radiographs for this lesion. Since panosteitis is a disease of the
fatty bone marrow in the long leg bones of the adolescent or young adult dog, it may be that
research on bone marrow will lead to an understanding of the etiology and hence the best
treatments, cure, and prevention of the disease.
Panosteitis was originally designated as hematogenic chronic osteomyelitis
associated with fever and infection. Later work indicated these conditions, when present,
were coincidental rather than causative.
As mentioned earlier, infection is generally not associated, and malignancy is likewise
absent. Only one of the 100 dogs in the Animal Medical Center study had tonsillitis (the
tonsils are "traps" for infectious agents circulating throughout the body). Whenever
vaccines, flea powders, worm medicine, diet, and other environmental factors have been
implicated, rechecking has found that the only common denominator
was physiological stress. Bacteriologic cultures of marrow, and the histologic
examinations, rule out bacterial agents. White blood cell and eosinophil counts were within
normal in nearly all cases, the rare
exceptions being no doubt a result of some co-existing but unrelated problem. An
eosinophil, by the way, is a type of cell of the peripheral blood or bone marrow, and a high
level is an indication of some sort of
infection or attack by parasites.

Transmission
In an experiment to discover possible genetic, infectious, or contagious modes of
transmittal, German Shepherd Dogs with a history of panosteitis were crossed with Pointers
from a family in which it had not been observed. Also, purebred Pointers and German
Shepherd Dogs were kennelled side-by-side separated only by a wire fence, and pups of both
breeds were raised together in the same pen. Regardless of contact, the Pointers remained
free of the disease while the Shepherds routinely developed it. The crossbreeding results
were inconclusive, even though only one incident of panosteitis showed up as late as the
fourth generation of back-crossing the female crossbreds to male German Shepherd Dogs.
Panosteitis does not appear to be related in any way to other radiographically
similar diseases. It has no bearing on, nor is it affected by, other bone or joint diseases
such as hip dysplasia or the various manifestations of osteochondrosis. Although
radiographically panosteitis resembles some human bone conditions, there is no real
counterpart in man.
It has previously been thought that nutrition might not have anything to do with the
lesion, despite it occurring mostly in large, fast-growing breeds. Calcium intake did not
seem to have any bearing on it, as
evidenced in bone healing studies. However, more testimonial evidence has since been
mounting among "breeders and feeders" that diet can indeed make it much worse or more likely
to appear in families predisposed to it. When I was preparing the article on panosteitis
for the AKC Gazette, I undertook a review of my first 140 German Shepherd Dogs, and until my
1981 book was in publication, I had encountered only one case of panosteitis in the
bloodlines I was using and developing. It happened
seven months after the dog was sold to a home where his diet was considerably "richer" than
the balanced commercial dry dog food he was used to. Clinical symptoms ended about ten days
after onset, and we
really don't know if the administration of prednisone had anything to do with alleviating it
(cause and effect relationship with this corticosteroid on pano not established), but no
further episodes occurred. It was some time later that one of my pups at home developed the
worst case I have personally encountered, and I did not record what diet we had been using
about that time, but he was produced by a
different sire than any of my other dogs.
A question of nutritional impact on the disease can be raised when comparing the
dog's change in diet with the predominant diet of those in the 100-dog study: raw or cooked
beef, eggs, cereal, and milk. Perhaps most of those 100 patients were from "pet homes"
where a dog is more likely to have been "overnourished". There are other question which can
only be answered through research, but there is no current active project regarding the
cause and environmental control of panosteitis. From personal experience as well as
speaking with scores of breeders, I am almost totally convinced that those dogs with breed
and/or family susceptibility for pano, who are fed very "rich" (high protein, especially)
diets are the ones most likely to come up limping with the disorder. One after another,
people have told me that by going to a lower-protein but still highly-digestible food, and
not feeding very liberally, they have stopped the course of pano in their kennels.

BREED, AGE, AND SEX CORRELATION
When first described, one of the names given the disease was "chronic osteomyelitis
of young German Shepherd Dogs", but as it was studied in subsequent years, other breeds were
found to be affected, including the Rottweiler, Airedale, Irish Setter, German Shorthaired
Pointer, Doberman
Pinscher, Great Dane, Basset Hound, and Saint Bernard. One observer has seen panosteitis in
all of the better-known large and giant breeds, but it has also been found in the Miniature
Schnauzer,the Scottish Terrier, and the Beagle.
The apparent prevalence in the German Shepherd Dog may partly be due to the large
population of this breed (worldwide, it is number one), though we cannot overlook the very
strong genetic aspect. Clinics such as the one in which the data on 100 consecutive cases
were collected have a preponderance of GSDs as patients. Body size is correlated with the
number of cases seen in a veterinary hospital or educational institution.
Growth rate is a possible factor, as it seems to be with HD. Most of the large and giant
breeds have a rapid early growth pattern, though the commonalities of growth rate and large
size with panosteitis may not be as closely related as they are with HD. If breeds such as
the Dobe and Collie, with their relatively flatter growth rate curve continue to have low
incidence of pano in relation to their populations, it still might not be conclusive
evidence of cause-and-effect, but may point to a connection.
If one subtracts the extremes of a very few diagnosed after full maturity, the curve
of ages at time of episodes rises from about 5 months to a peak around 10 months, and
rapidly diminishes, with very few cases after 18 months of age. In the one study mentioned
earlier the extraordinary number (10) found at age 24 months may not be representative. The
first German Shepherd Dog to win Best In Show at
Westminster, Covy-Tucker Hill's Manhattan, reportedly had at least one episode of pano at 4
years of age, but this was not documented.
There is a nearly 4:1 ratio of males to females affected by panosteitis; the
clinical signs are more severe and the disease more nearly chronic in males. This echoes a
pattern seen elsewhere. Early in the U.S. space program it was discovered that women could
withstand the stress of G-forces (acceleration) better than men. The U.S. Army determined
that female dogs can run 26% longer and swim 46% longer than males. Bitches lead many
racing teams of sled dogs because they can run smoother and calmer, some racing enthusiasts
claim. And females are much less prone to non-specific lameness (presumably this included
pano) according to the records of Zero (racing) Kennel. It appears the stress of estrus
(bitch's season is her highest stress period) or pregnancy contributes somewhat to
susceptibility.

TREATMENT
A great number of treatments have been proposed and tried, but all have had very
limited or extremely questionable success, and then only as partial palliatives; nothing has
been conclusively shown to have a cause-and-effect relationship.. Since the cause is
unknown, treatment is indicated and routinely prescribed only for the symptoms. Aspirin,
sulfa compounds, other antibiotics, vitamin C, prednisolone or similar steroids, and calcium
supplements have been most commonly attempted. Of the analgesics and other medications
tried, buffered aspirin (less irritating to the canine digestive tract) probably has the
greatest effect and widest application in relieving some pain in some dogs. It and the
corticosteroids have the largest number of proponents, but it has been my observation that
most dogs with panosteitis do not respond to these anymore than they do to anything else.
Corticosteroids do have an anti-inflammatory action and can give remarkable relief in many
ailments (and by some reports do a little good in alleviating some pain in pano), but as in
the case of all drugs and foreign substances, there are cautions. Prolonged or excessive
use of aspirin can cause stomach bleeding in dogs; steroids can bring on cardiovascular
problems including ruptured capillaries, and can damage the immune system at least
temporarily. If you decide to try a pain reliever in spite of my advice, if there is
overwhelming compunction to do something, make sure you discuss with your veterinarian the
possible side effects and contraindications. For every "cure" or "successful" treatment,
you can find a score or more cases in which it did not work at all.
One orthopedist said to me, "It's sort of like treating a cold in a human patient
where, if you give medicine it takes about seven days to get over it, and if you do nothing
it takes about a week." In the case of this disease, however, it may take anywhere from 2
days to 7 weeks for the pain to leave one site with 1 to 2 weeks quite common.
Radiologically and histologically, it can be 2 months between onset and the beginning of the
late phase, and then several more months before cortex and endosteum (inner lining of the
marrow cavity) regain normal appearance. It may take considerably longer for the disease to
run its course in all the bones which may become affected. I have observed that most cases
are outgrown by age 18 months to 2 years, with most initial episodes coming around 8 to 10
months of age; in many dogs the disease will strike at a much later age than in others. It
is rarely a chronic situation in regard to pain; in most cases symptoms appear only
intermittently in many bones, and many dogs will have but one episode in one bone.
Many of us experienced breeders believe that nothing you do will likely make a fig's
worth of difference in either pain relief or remission. One private practitioner with much
experience in orthopedic disorders claimed that Zyloprime relieved clinical and radiographic
symptoms within 5 days, but we know that many cases self-resolve in that period of time
anyway, and the experiments were not duplicated elsewhere. It appears that nothing gives
completely satisfactory results, so the best course of action is no action at all; let the
dog decide how much weight to put on the limb and just wait. Perhaps the best treatment
regimen for dogs with pano is in the nursery rhyme, "Leave them alone, and they'll come
home,
wagging their tails behind them." It may be best to let the dog restrict his exercise by
himself, give him emotional support so he doesn't go without food to the extent of exposing
himself to diseases or stresses he can't handle, and simply wait it out.

CONCLUSIONS
In summary, panosteitis is a self-limiting disease affecting many of the long leg
bones, predominately in large dogs between 5 and 18 months old.
It is apparently unrelated to other lesions of the skeletal or blood systems, and occurs
only in the canine, more in some breeds than others. Cause is unknown, but high-protein
diets may make symptoms worse or last longer. Panosteitis is "self-limiting", i.e., it will
"go away" whether one treats it or not. Since afflicted dogs "outgrow" the disease with
little or no expense, it is unlikely much research funding will become available to study
it. The dog owner should consult his veterinarian to rule out other problems which may be
more serious.


All information contained in this article is authored by Fred Lanting, Mr.GSD@juno.com
Fred Lanting is also the author of the Total German Shepherd Dog

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