JPC SYSTEMIC PATHOLOGY

MUSCULOSKELETAL SYSTEM

April 2025

M-M15

 

SIGNALMENT (JPC #2314363): Eight-month-old miniature poodle

 

HISTORY: This dog presented with rear limb lameness

 

HISTOPATHOLOGIC DESCRIPTION: Femur: Affecting 50% of the epiphysis, extending from the subchondral aspect of the articular cartilage to the physis, is a focally extensive area of osteonecrosis characterized by brightly eosinophilic, irregular bony trabeculae that lack osteocytes within lacunae, osteoblasts are often completely absent or flattened and atrophic, and multiple bone fragments have scalloped margins with adjacent osteoclasts in Howship’s lacunae (osteolysis). The intertrabecular spaces contain a marked fibroblastic proliferation within loosely arranged myxomatous to collagenous matrix with numerous variably sized capillaries (neovascularization). There is multifocal accumulation of amphophilic to basophilic necrotic cellular debris, moderate numbers of macrophages (with erythrophagocytosis and intracytoplasmic hemosiderin), scatted neutrophils, and mild hemorrhage, fibrin, and edema. Trabeculae adjacent to the affected area have peripheral, scalloped, intensely basophilic reversal lines (resorptive activity) and are lined by numerous active osteoblasts (remodeling).

 

MORPHOLOGIC DIAGNOSIS: Femur, epiphysis: Osteonecrosis, chronic, focally extensive, with osteolysis, fibrosis, neovascularization, and bone remodeling, miniature poodle, canine.

 

CONDITION: Avascular necrosis of the femoral head 

 

SYNONYM: Legg-Calvé-Perthes Disease, Osteonecrosis of the femoral head (ONFH) 

 

GENERAL DISSCUSSION:

• Avascular necrosis of the femoral head in Legg-Calvé-Perthes disease (vs. avascular necrosis due to slipped capital femoral epiphysis) is a result of idiopathic disruption of a major portion of the blood supply to the capital epiphysis with subsequent ischemic necrosis; this is in contrast to and considered a separate entity from necrosis of the femoral head associated with femoral neck fractures or slipped capital femoral epiphysis
• Common in small and miniature dog breeds (Lakeland, Cairn, West Highland white, Yorkshire, and fox terriers, miniature and toy poodles, miniature pinschers, pugs, and Griffons); rare in cats
  • Most commonly occurs in adolescent dogs 4 to 8 months of age with no sex or leg predisposition
  • Usually unilateral, but can be bilateral

 

PATHOGENESIS:

• Unknown etiology; autosomal recessive inheritance is suggested 
• Disruption of vascular supply > ischemia > osteonecrosis of the epiphyseal spongiosa > repair with proliferation of fibrous tissue (as opposed to creeping substitution) and neovascularization at the margin of viable and necrotic bone, woven bone deposited on existing necrotic trabeculae; necrotic bone removed by osteoclasts; lamellar bone replaces woven bone > loss in bone mass > collapse of the relatively unsupported articular cartilage if the ischemic area is extensive > disruption of normal joint congruity > degenerative joint disease
• Possible causes of initial ischemic incident or recurrent incidences:
  • Transient synovitis > increased intra-articular pressure > inhibition of venous drainage > ischemia and osteonecrosis
  • Anatomic variations: Susceptible poodles have subsynovial veins whereas resistant poodles have mainly intraosseous veins
• Precocious sexual maturity as a predisposing factor
• Increased bone marrow pressure from smaller diameter of epiphyseal vessels
• Environmental, dietary, and exertional factors
• Undetermined trauma or thrombosis; no apparent deficiency in clotting factors
• Steroid administration

 

TYPICAL CLINICAL FINDINGS:

• Unilateral hind leg lameness (15% bilateral); leg painful upon abduction; shortening of limb, or disuse atrophy of gluteal/quadriceps muscles; eventual degenerative arthropathy
• Radiology: Early in disease, increased radiodensity in the lateral epiphyseal area of the femoral head followed by lysis, collapse, or structural failure of the femoral head

 

TYPICAL GROSS FINDINGS:

• Midsagittal section: Necrotic bone is yellow white; large, pale areas of infarction surrounded by a zone of hemorrhage
• Cortical bone: Dry and chalky appearing large areas of necrosis, periosteum easily removed 
• Articular cartilage: Pannus, cartilaginous fissures and clefts in chronic cases

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Subchondral epiphyseal osteonecrosis characterized by trabeculae with empty lacunae (i.e. lacking osteocytes)
• Repair involves revascularization and proliferation of mesenchymal tissue from the margin of necrosis
• Woven bone is deposited on remnants of necrotic trabeculae; “sandwich” (reactive woven bone covers central necrotic bone)
• Degenerative joint disease is a common sequela with chronicity
• The physis (resting and proliferative zones) may or may not be affected depending on how extensive the necrosis is in the femoral head
• Cortical bone: Sequestra with inflammation 

 

DIFFERENTIAL DIAGNOSIS: 

Hind limb lameness

 

COMPARATIVE PATHOLOGY:

• Cats: Slipped capital femoral epiphysis associated with physeal dysplasia due to underlying weakness of the growth plate in young (2.4-24 month-old), overweight (90%) male (85%) cats; especially Siamese cats
  • Calves and foals: Reports of femoral capital epiphysis separation from trauma (i.e., birth trauma in calves, growing foals) a sequel is avascular necrosis of the femoral head 
  • Pigs and deer: Separation of femoral capital epiphysis due to osteochondrosis
  • Poultry: Femoral head separation (FHS) is a degenerative skeletal problem in fast-growing poultry and is associated with diseases that causes lesions in the musculoskeletal system (i.e., Enterococcus cecorum)
  • Galliformes and Columbiformes can have femoral head necrosis associated with E. cecorum
  • Free ranging, juvenile, yellow-eyed penguin: Diagnosed with age related, degenerative changes at necropsy (no evidence of infection) 
  • Suspected pathogenesis: Osteonecrosis and osteochondrosis with subsequent bilateral, aseptic degenerative changes of the femoral head 
  • Primates: 
  • Legg-Calve Perthes disease has been described in lowland gorillas
  • Juvenile cynomolgus macaques: Idiopathic chondrolysis rare condition of coxofemoral joint articular cartilage is replaced by fibrocartilage
  • Spontaneous osteonecrosis of the knee (SONK) is a condition reported in middle-aged humans and three rhesus macaques 

 

REFERENCES:

1. Crespo R, Franca MS, Fenton H, Shivaprasad HL. Galliformes and Colubriformes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:763. 
2. Fletcher OJ, Barnes HJ, Abdul-Aziz T. Chapter 3: Skeletal System. In: Abdul-Aziz T, Fletcher OJ, Barns HJ, eds. Avian Histopathology. 4th ed. Madison, WI: Omnipress; 2016: 75, 94-95.
3. Myers EA, Sander JE. Diseases with lesions in the Musculoskeletal System. In: Boulianne M et al., eds. Avian Disease Manual. 8^th ed. Jacksonville, FL: American Association of Avian Pathologists, Inc.; 2019:202.  
4. Olson EJ, Dykstra JA, Armstrong AR, Carlson CS. Bones, Joints, Tendons, and Ligaments. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:10631073-1074.
5. Pritzker KPH, Keesler MJ. Arthritis, Muscle, Adipose Tissue, and Bone Diseases of Nonhuman Primates. In: Abee CR et al, ed. Nonhuman Primates in Biomedical Research. Vol 2, 2nd ed. Waltman, MA: Elsevier Inc.; 2012:632, 638- 639. 
6. Stidworthy MF, Denk D. Sphenisciformes, Gaviiformes, Podicipediformes, Procellariiformes, and Pelecaniformes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals, Cambridge, MA: Academic Press; 2018:660.
7. Thompson K. Bones and joints. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6^th ed. Philadelphia, Pennsylvania: Saunders Elsevier; 2016:31,96-97,143.

 

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