LIVS

Panosteitis - a common bone marrow disease

By: Shadi Ireifej, DVM Staff Surgeon

Panosteitis is a common self-limiting bone marrow disease resulting in (1) long bone adipose and hematopoietic tissue replacement by fibrous tissue, (2) osseous changes to the trabeculae and endosteum, and (3) cortical and periosteal new bone formation. Panosteitis has also been called enostosis, eosinophilic enostosis, eosinophilic panosteitis, juvenile osteomyelitis, and osteomyelitis of young German shepherd dogs.

This is a condition that affects large and giant breed dogs 5 to 18 months of age; 89% to 95% are less than 2 years of age, 57% to 71% are between 6 and 12 months of age, 64% are less than 12 months of age, 82% are less than 18 months of age, 5 to 11% are older than 2 years of age, and 2% are older than 7 years of age. The peak reported age is 9 to 10 months of age. Smaller breed dogs are rarely affected (1.8% incidence) with Cardigan Welsh corgis, Blue heelers, American cocker spaniels, Malteses, Norwich terriers, miniature schnauzers, Shetland sheepdogs, Pembroke Welsh corgis, and Wirehaired pointing griffons having been reported. Smaller breed dogs are usually 2 months old or more. Males are over-represented with a 67 to 84% prevalence. Affected females are usually in estrus. Affected breeds and their associated risk factor ratios include the following: Basset hound (3.5x at risk, 8% incidence), Mastiff (3.5x at risk), Chinese shar pei (3.5x at risk), Giant schnauzer (3.4x at risk), German shepherd dog (3.3x at risk, 39% to 79% of cases), Bernese mountain dog (2.8x at risk), English springer spaniel (2.8x at risk), Dalmation (2.5x at risk), Saint Bernard (2.5x at risk), Great Dane (2.3x at risk, 2% of cases), Irish wolfhound (2.3x at risk), American Staffordshire terrier (2x at risk), Neapolitan mastiff (2x at risk), Rhodesian ridgeback (2x at risk), Afghan hound (1.9x at risk), Bulldog (1.9x at risk), Doberman pinscher (1.9x at risk, 2% of cases), English setter (1.9x at risk), Newfoundland (1.9x at risk), Weimaraner (1.9x at risk), Akitas (1.8x at risk), Boxer (1.8x at risk), Chesapeake bay retriever (1.8x at risk), West highland white terrier (1.7x at risk), Chow chow (1.7x at risk), Bull terrier (1.6x at risk), Labrador retriever (1.6x at risk, 11% of cases), German shorthaired pointer (1.6x at risk), golden retriever (1.5x at risk, 8% of cases), Rottweiler (1.4x at risk, 3% of cases), Shih tzu (1.4x at risk), and American cocker spaniel (1.3x at risk). Mix breeds have an 8% incidence.

 

 

Clinical signs of affected dogs include (1) weight-bearing lameness of up to 2 week duration, (2) bone pain centered at the nutrient foramen (the junction of the proximal third to the distal two thirds of long bones) and/or (3) pain anywhere along the diaphysis and metaphysis. The lameness is usually acute and progressive, but can be chronic over days to many months. Lameness in dogs greater than 2 years of age is seen in 10% of cases. One limb may be affected or the dog may shift limbs. Multiple limbs are affected in 49% of cases (50% are of the thoracic limbs, and 50% are of the pelvic limbs) and multiple bones are affected in 53% of cases. Lethargy, pyrexia, tonsillitis, muscle atrophy, anorexia, and reluctance to move are rarely seen.

 

The cause for panosteitis is unknown. The most accepted hypothesis is an osseous compartment syndrome that develops due to the osmotic effects of high protein and caloric levels (and maybe high calcium) from the diet. This results in an intraosseous protein-rich edema that causes an increased medullary pressure and compression of the vasculature, resulting in ischemia. This subsequent osseous ischemia leads to a deficient metabolic state (decreased oxygenation, inadequate influx of nutritive substances, local acidosis, decreased removal of metabolites, and disruption of local biochemical processes), and a vicious circle is created due to the resulting local inflammation (the fibroblastic reticular cells of the bone marrow). The subsequent increase in fibrous tissue is rich in osteoblasts, fibroblast, osteocytes, and osteoclasts. This disease is aggravated by an increased metabolism due to excessive physical activity of the patient. The osteoclasts remove trabeculae, which are replaced by unorganized woven bone, and the medullary canal is obliterated. This process occurs along the endosteum, cortex and periosteum in severe cases. Hyperemia of the periosteum and adjacent soft tissue provokes a periosteal reaction and subsequent periosteal new bone formation that is a few millimeters thick. With later stages, woven bone trabeculae are replaced by lamellar bone trabeculae that are fewer and thicker than normal. These changes may persist for months. Marrow may become aplastic depending in the amount of remodeling for a given patient. A genetic suspicion exists with German shepherd dogs due to their 86% incidence rate. Other suspected causes include bacterial infections (e.g., hematogenous  streptococcus), viral infections (e.g., distemper virus or live distemper vaccination), stress, metabolic disease, vascular anomalies, allergic disease, hyperestrinism (e.g., the first estrus), parasite migration, autoimmune reactions (due to viral infections), and hemophilia A (e.g., German shepherd dogs).

Routine biochemistry and complete blood count panels will rarely reveal eosinophilia (1 to 5% of cases) and leukocytosis (1% incidence). Affected dogs may have elevations in 11 of the 23 serum amino acids.

Radiographs depict four stages of abnormalities, in order of progression; (1) medullary canal radiolucency (changes in medullary adipose tissue, seen 10-14 days after the onset of clinical signs), (2) medullary canal radio-opacity (Figures 1 and 2, patchy or mottled pattern in the region of the nutrient foramen due to proliferating stromal and adventitial cells with calcification and intramembranous bone formation, seen 10 to 14 days after the onset of clinical signs and lasts 4 to 6 weeks), (3) endosteal, cortical, and periosteal reaction (the formation of woven bones begins to affect the cortical bone with progression of the patchy radio-densities from stage (2), cortical thickening is seen in 33% of cases), and (4) recovery (decreased number of granular densities, cortical remodeling, trabecular remodeling, and normal medullary canal seen in 2 to 3 months). Other stage (2) changes may include the following; a loss of the trabecular pattern, accentuation of the trabecular pattern, blurring, loss of medullary-cortical contrast, intramedullary granular densities, cortical changes around the nutrient foramen, patchy or mottled sclerotic densities, rough endosteal surfaces, coarse trabeculae, periosteal roughening, endosteal bone formation, periosteal new bone formation (15 to 25% of cases), subperiosteal bone production, a widened nutrient foramen, and cortical thickening. Persistent changes seen in stage (4) include increased medullary canal density, granular densities, fewer coarse trabeculae, roughened endosteum, and cortical thickening. Radiographic changes may be present for up to 90 days. Typically the diaphysis is affected (75% of cases) but these signs may extend to metaphyseal region of the affected bone (25% of cases). Radiographic changes may lag days to weeks behind the patient’s clinical signs, as 5% of cases will show no radiological abnormalities. The appendicular skeleton is always affected and rarely does this disease affect same bone twice. Usually multiple long bones are involved over weeks to months and patients may be affected bilaterally. More than one bone is affected during one episode in almost 100% of cases and up to 7 bones may be affected at one time.55 The affected anatomic location and frequencies are as follows; ulna 42% to 54%, radius 25% to 27%, humerus 14% to 68%, femur 11% to 68%, and tibia 8% to 24%. Contralateral bone involvement is seen in 31% (humerus) to 60% (tibia) of cases. Concurrent orthopedic diseases are seen in 26% of cases.

 

Nuclear scintigraphy using 99mTechnetium methylene diphosphonate (99mTc-MDP) may be a more sensitive and relatively specific diagnostic test for localization and characterization of exclusion of skeletal disease (especially for conditions that are multifocal or difficult to localize). Approximately 80% of dogs with panosteitis were diagnosed using nuclear scintigraphy, where radiographs and synovial fluid analyses were unremarkable.

 

Histopathological findings (in order of progression) include the following; loss of medullary adipose tissue, medullary canal fibrosis, intramembranous ossification, osteoclastic removal of trabeculae,  endosteum and periosteum osteoblast infiltration, and endosteal, cortical and periosteal new bone formation. With resolution of the disease, comes resolution of these histopathological abnormalities. These changes cycle every 60 to 90 days but may be as long as 190 days.

 

Therapy is not needed. Non-steroidal anti-inflammatories or corticosteroids along with exercise restriction may be required in select cases, for up to several months. Antibiotics, vitamin supplementation, mineral supplementation, diet changes, and irradiation of diseased bone and the adrenal glands have had no effect on clinical outcome. Clinical remission has been seen with the use of a proteolytic substance called benzopyron (Cumartrin).

 

The prognosis is excellent. Recurrence is possible, but rare after 18 to 20 months of age (18% incidence). Recurrence is rare for a given bone (1% incidence), and recurrence will always affect the other bones. The initial episode usually affects a thoracic limb followed by a pelvic limb, then recurring to a thoracic limb. This shifting pattern is seen every 2 to 4 weeks with lapses up to one month or more.

Prevention has been aimed at diet alterations. Use of puppy mild replacer in pre-weaning Dutch German Shepherd dogs results in excessive calcium, phosphorus and vitamin D that may contribute to this condition. Prevention with the use of killed distemper or adenovirus vaccine rather than modified live vaccinations has been advocated.

 

Figure 1. Lateral antebrachial plain radiograph depicting medullary canal radio-opacities of the radius.

Figure 2. Single-view antebrachial plain radiograph depicting medullary canal radio-opacities.

 
You are here: Home NEWS Panosteitis - a common bone marrow disease

After Hours:  Should a problem arise after normal business hours, all departments are covered by the Animal Emergency and Critical Care Center at Long Island Veterinary Specialists. It is always best to call in advance when possible, however, if problems arise, do not hesitate to bring your pet in immediately. This facility is staffed 24-hours by veterinarians and technicians ready to assist you and your pet.