JPC SYSTEMIC PATHOLOGY
MUSCULOSKELETAL SYSTEM
April 2025
M-M17
Signalment (JPC #2984970): Great Dane
HISTORY: This 15-week-old female puppy presented with a 3-day history of generalized pain and reluctance to walk followed by lateral recumbency.
HISTOPATHOLOGIC DESCRIPTION: Long bone, metaphysis, physis, and epiphysis: Diffusely, the metaphyseal primary spongiosa is characterized by elongated mineralized spicules of cartilage devoid of osteoid and lined by decreased numbers of osteoblasts. These calcified cartilage spicules extend well into the metaphysis and are frequently discontinuous and fragmented with sharp angular borders (microfractures) which coalesce and form a large infraction resulting in separation of the proximal and distal metaphysis. Within the medullary cavity separating the calcified spicules of the primary spongiosa and bony trabeculae of the secondary spongiosa are abundant mature neutrophils, reactive fibroblasts (fibrosis), fibrin, hemorrhage, and necrotic debris. Multifocally, scattered vessels within the epiphysis, metaphysis, and periosteum are variably occluded by fibrin thrombi and vessel walls are expanded by small amounts of necrotic debris and fibrin (vascular necrosis).
MORPHOLOGIC DIAGNOSIS: Long bone, metaphysis: Osteomyelitis, necrosuppurative, acute, focally extensive, severe, with microfractures, infraction, and fibrin thrombi, Great Dane, canine.
CONDITION: Metaphyseal osteopathy
SYNONYMS: Hypertrophic osteodystrophy (HOD); osteodystrophy II; skeletal scurvy; juvenile scurvy; Moller-Barlow's disease
GENERAL DISCUSSION:
- Inflammatory bone disease of unknown etiology that primarily affects growing, young (usually 3-6 months of age), large & giant breed dogs
- Nutritional or infectious etiology is suspected
- Highest incidence in Weimaraner, Irish Setter, Great Dane, German Shepherd, and Boxers
- Most dogs recover with anti-inflammatory therapy and pain management; relapses and bone malformations can occur
- All fast-growing bones are susceptible, but the distal radius and ulna are usually most severely affected; lesions are usually bilaterally symmetrical; bones distal to the carpus and tarsus are usually spared
PATHOGENESIS:
- Intense suppurative inflammation results in necrosis of osteoblasts and primary spongiosa throughout the metaphysis
- Mineralized cartilaginous trabeculae are fragile and are easily fractured
- Periosteal and extraperiosteal woven bone develop in areas of periosteal inflammation and hemorrhage
- Cause is unknown, no etiologies have been proven
- Therapeutic response to corticosteroids is better than NSAIDs, suggesting a possible immune-mediated etiology
- Irish setter littermates: Canine leukocyte adhesion deficiency has been linked to occurrence of metaphyseal osteopathy
- Proposed etiology: Neutrophil entrapment leads to autoinflammation and necrosis
- Weimaraner: Granulocytopathies suspected to be cause of metaphyseal osteopathy in some affected litters
TYPICAL CLINICAL FINDINGS:
- Pain, lameness, pyrexia, anorexia
- Swelling and hyperthermia of metaphysis; usually bilateral
- Radiographic findings: Alternating metaphyseal dense and lucent lines parallel to the growth plate (“double physis line”), lipping of metaphyseal margins; periosteal new bone growth in chronic cases
TYPICAL GROSS FINDINGS:
- Early: 1-5mm wide, pale yellow, soft, crumbly zone in metaphysis with an irregular line parallel to the physis
- Chronic: Metaphysis thickened by widened periosteum, and deposition of extraperiosteal bone and cartilage; can involve 2/3 of the length of the affected bone, excluding mid-diaphysis and epiphyses
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Early metaphyseal spongiosa: Bilaterally symmetrical, acute, fibrinosuppurative osteomyelitis; necrosis of osteoblasts and primary spongiosa; trabecular microfractures; hemorrhage; defective bone formation; elongation of zone of mineralized cartilage (primary spongiosa) with lack of osteoid deposition; neutrophils and hemorrhage within periosteum; active osteoclasts; fibrin thrombi may occlude small blood vessels
- Chronic: Periosteal thickening with subperiosteal new bone formation and extraperiosteal dystrophic calcification
- Extraskeletal lesions (variable; often not present): Enamel hypoplasia associated with dental crypt inflammation
DIFFERENTIAL DIAGNOSIS:
- Bacterial osteomyelitis: Typically starts in metaphyses where capillaries make sharp bends resulting in slowing and turbulence of blood flow and where there is decreased phagocytic capacity and discontinuous endothelial cells; differentiated from metaphyseal osteopathy by clinical signs, presence of bacteria, and involvement beyond metaphyseal bone
- Hypovitaminosis C (scurvy): Similar histologic appearance, no inflammation
- Panosteitis: No metaphyseal swelling; radiographs reveal cottony intramedullary densities in long bones
COMPARATIVE PATHOLOGY:
- Feline: Idiopathic bilateral metaphyseal necrosis of the femoral neck in young male cats (<2 years old); some clinical and radiographic similarities with canine hypertrophic osteodystrophy
REFERENCES:
- Craig LE, Dittmer KE, Thompson K. Bones and joints. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier Saunders; 2016:105-106.
- 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; 2022:1092-1093.