Bone Pathology

Front 1

Osteopetrosis: histology & pathogenesis

Back 1

>Persistence of primary and secondary spongiosa and continued formation of new trabecular bone
> Decreased remodeling of mature bone; rare osteoclasts
> Cartilage of the growth plate is normal or increased in width.
> Long bone trabeculae are thickened and much of the marrow cavity.
# Normal cortical bone

Hint 1

Osteoclasts can’t resorb and shape the primary trabeculae >spicules of bone with central cores of calcified cartilage fill medullary cavity > bones are dense with no medullary cavity

Front 2

Osteopetrosis dz in species & differentials

Back 2

Bovine congenital osteopetrosis (Angus, Simmental, Hereford inherit via autosomal recessive trait)

Avian Retroviral Osteopetrosis ( 8-12 week old (chronic), Thick shanks (lower metatarsal bones), Neoplastic)

Hint 2

osteopetrosis-like osteosclerosis lesions: treatment with parathyroid hormone, estrogen, diphosphonates, and hypercalcemia

Front 3

Osteogenesis Imperfect pathogenesis & histology

Back 3

Osteopenic disease > defect in osteoblastic production of type I collagen. Defective COL1A1 and COL1A2 genes that encode for alpha 1 and 2 chains of procollagen molecule result in qualitative and quantitative collagen defects

Hint 3

> Primary lesion is osteopenia.
> Growth plate and primary spongiosa are normal.
> Abrupt failure of secondary spongiosa and lamellar bone formation
> Metaphysis may have multiple growth arrest lines related to formation of transverse trabeculae.
> Trabeculae are not modeled (retention of cartilage cores), but are resorbed at the metaphyseal-diaphyseal junction.
> Paucity of endochondral and intramembranous ossification
>Marrow cavity contains loose mesenchymal tissue.
> Dentin is thin and lacks a tubular pattern.

Front 4

Causes of osteoporosis: bone & tooth lesions

Back 4

> Starvation
> Disuse: Loss of skeletal mass from inactivity and decreased weight bearing
> Senile: Physiologic loss of skeletal mass with age
> Intestinal parasitism: Trichostrongylus colubriformis; Ostertagia circumcincta
> Phosphorous deficiency (Rickets in young animals; osteomalacia in adults)
> Copper deficiency: Collagen defects due to decrease in activity of lysyl oxidase; involves growth plates
> Primary and secondary hyperparathyroidism: Resorption of bone with replacement by fibrous connective tissue

Hint 4

Fluoride toxicosis: Chalky, opaque enamel with increased susceptibility to chipping

Front 5

Congenital Cortical Hyperostosis

Back 5

Autosomal recessive inherited disease of pigs

Diaphyseal dysplasia

Abnormal periosteal bone formation on major long bones

May be due to disorganization of perichondral ossification groove

stillborn or die within 1 to 2 days

Hint 5

>Reactive periosteal hyperostosis secondary to infection, neoplasia, trauma, or metabolic disease

>Osteopetrosis: Thickening of spongiosa due to decreased osteoclast resorption

>Caffey's disease in children

Front 6

Craniomandibular Osteopathy: predisposed breeds, dz features

Back 6

Scottish, West Highland White and Cairn Terriers

Hint 6

Bilaterally symmetrical

Irregular thickening of mandibles, tympanic bullae, occipital and temporal bones

Less commonly affects appendicular bones

Apparent at 4-7mos of age

genetic basis; autosomal recessive inheritance is suggested in West Highland White terriers

Front 7

CMO histo & morph

Back 7

>Mosaic of reversal and resting lines
> Medullary spaces contain irregular trabeculae of woven bone and fibroblasts
> Random osteoclastic resorption involving lamellar and woven bone with production of abundant coarsely woven bone
> Increased osteoblastic activity on trabecular surfaces
> Lymphocytes, plasma cells, and neutrophils present in areas of remodeling and ossification
>Resolution of the disease involves replacement of woven trabeculae with lamellar bone and gradual resorption

Hint 7

Morph: hyperostosis with focally extensive neutrophilic osteitis and periostitis and marked periosteal fibrous tissue proliferation

Front 8

Chondrodystrophies - definition

Back 8

Disorders of bone growth due to primary lesions in growth cartilage (physis, AE complex, and epiphyseal cartilage)

widespread disorder of growth cartilage or expressed only in AE complex or in physis

Hint 8

Growth plates: normal or thin; chondrocytes can be arranged normally or very disorganized; cartilage matrix normal or rarefied

Trabecular bone: primary trabeculae can be reduced in amount with coarse and misshaped cartilage cores

Cortical bone: highly variable lesions; mostly due to abnormal shape or size

Front 9

Spider lamb syndrome - pathogenesis, histo features

Back 9

Autosomal recessive condition resulting in generalized chondrodysplasia that occurs primarily in Suffolk and Hampshire sheep and their crosses

genetic mutation has been localized to the telomeric end of chromosome 6; mutation may involve fibroblast growth factor receptor 3

Hint 9

>Irregular growth plates
>Paucity of osteoblasts and osteoclasts
>Thin & discontinuous cortical bone
>Zone of proliferation is mildly expanded by chondrocytes forming irregular, non-parallel columns and nests
>Cartilage tongues extend into metaphysis and epiphysis
>Paucity of primary and secondary spongiosa
>Degenerative cartilage in growth plate

Front 10

Osteochondrosis

Back 10

>Heterogenous group of lesions in growth cartilage of young animals characterized by focal or multifocal failure (or delay) of endochondral ossification
>Involve metaphyseal growth plate and AE complex
>Focal or multifocal retention of growth cartilage due to its failure to become mineralized and replaced by bone

Hint 10

>Growth plate: well-demarcated wedge of white firm hyaline cartilage at AE complex or physis (hypertrophic, occ. poorly aligned, chondrocytes w/o evidence of vascular invasion or mineralization
>Trabecular bone: subjacent to dysplastic area, the trabeculae are course, modeled, and w/o cartilage cores; may be some discontinuity between retained cartilage and bone – space contains some fibrosis
>Cortical bone: no lesions except may see angular limb deformities

Front 11

Osteochondritis Dissecans (OCD): lesion, common sites for dog, horse, & pig

Back 11

Dysplasias of AE complex that form clefts in retained cartilage w/ secondary fracture of overlying articular cartilage > cartilaginous or osteochondral flap > if detaches and is free in joint then called a joint mouse

Hint 11

Dog: humeral head

Horse: anterior aspect of intermediate ridge of distal tibia (DIRT)

Pigs: medial condyles of distal femur and distal humerus in pigs

Front 12

Epiphysiolysis - definition, species affected (what is it called in the dog?)

Back 12

Separation of epiphysis from metaphysis due to fissure formation horizontally through physis

Hint 12

Only form of osteochondrosis found in the cat

Ununited anconeal process in dog

Front 13

Cervical Vertebral Myelopathy

Back 13

static or intermittent compression of SC by abnormal cervical vertebrae

Hint 13

Dogs – usually due to stenosis of canal

Quarter horses – localized hyperplasia and fibrocartilaginous metaplasia of ligamentum flavum can protrude into spinal canal

Front 14

Causes of Failure of Ossification

Back 14

Dogs with congenital hypothyroidism

Hint 14

Lambs after fetal thyroidectomy

Front 15

Metabolic Bone Disease - presentations, causes

Back 15

osteoporosis
fibrous osteodystrophy
rickets
osteomalacia

Hint 15

Nutritional, toxic, and endocrine causes

Front 16

Osteoporosis - definition/locations, mechanism

Back 16

Disease of bone pain and fracture due to decreased bone density or mass

flat bones of the skull, scapula, ileum, and metaphysis of long bones, vertebral bodies

Hint 16

Protein calorie malnutrition, immobilization, dietary Ca deficiency, GC excess, menopause (humans)

Deficiencies of Ca, P, or Vitamin D

Front 17

Osteoporosis - histo

Back 17

Growth plate: no lesions, unless due to pituitary dysfxn or protein calorie malnutrition, then plate is thin
Trabecular bone: thin, fewer in #, perforations within plate; normal anastomosing structure replaced by rodlike bone > decreased ability to withstand stress

Cortical bone: thin due to increased endosteal osteoclastic resorption; porous due to increased intracortical resorption and decreased osteoblastic activity

Hint 17

Osteoid seams are of normal width and frequency

Mineralization is usually normal

Front 18

Rickets/Osteomalacia

Back 18

Failure of mineralization with secondary bone deformities and fractures – rickets in growing animals and osteomalacia in adults

Rickets: Disease of bone and cartilage undergoing endochondral ossification

Osteomalacia: Disease only of bone

Hint 18

Most common is Vitamin D or phosphorus deficiency:
↓ vitamin D > ↓Ca and P > ↑ PTH > ↑ Ca resorption and ↓P resorption

* Vit D is required for mineralization of the zone of hypertrophied chondrocytes, which is in turn necessary for capillary invasion and subsequent ossification*

Renal disease

Chronic fluorosis

Front 19

Rickets lesions

Back 19

Growth plates: thickened due to failure of mineralization; prominent and nodular costal-chondral junctions “rachitic rosary” – retained cartilage

Trabecular bone: metaphyses are flared due to failure of bone and cartilage removal in the cutback zones; poorly mineralized matrixes cannot be resorbed because osteoclasts cannot bind to an unmineralized matrix

Cortical bone: soft; normal appearance or deformed because of wt-bearing on soft bone

Hint 19

Hallmark: persistence of hypertrophic chondrocytes at sites of endochondral ossification, both at physes and beneath articular cartilage

Front 20

Fibrous Osteodystrophy

Back 20

Increased, widespread osteoclastic resorption of bone and replacement by fibrous CT

Hint 20

Primary hyperparathyroidism
>Ca usually high
>May see metastatic calcification of tissues

Secondary hyperparathyroidism
>Nutritional (aka simian bone disease in NHP)
>Renal
>may also see osteomalacia due to low Ca

Front 21

Fibrous osteodystrophy - mechanism, histo

Back 21

Persistently high PTH: stimulate receptors on bone marrow stromal cells > differentiate into fibroblasts

stimulate receptors on osteoblasts > up-regulate production of osteoclast differentiation factor and down regulate secretion of osteoprotegerin

Hint 21

Trabecular bone: thin trabeculae due to osteoclastic resorption (large numbers of osteoclasts in Howship’s lacunae); osteoblastic proliferation can be marked but ineffectual (produce little osteoid), marked decrease of mature bone; marrow space filled by fibrous connective tissue (amount varies on stage)

Cortical bone: resorption and replaced by fibrous CT; osteoclastic resorption begins on endocortical bone surface but any vascular spaces w/in wall of bone can become enlarged due to osteoclastic resorption and replacement by fibrous CT; advanced cases – cortex can be replaced by reactive woven bone and fibrous CT

Front 22

Toxic Osteodystrophies

Back 22

Fluoride
Lead
Vitamin A
Vitamin D

Hint 22

Fluoride: Pathogenesis: Fluoride toxic to developing ameloblasts => production of poor enamel => odontoblasts produce addition dentin => dentin oxidized to a dark brown color

Lead:acid-fast lead inclusions,
“Lead Line”: osteosclerotic band of bone parallel to growth plate, Osteoporosis

Vit A:mf premature closures of growth plates w/ secondary growth deformity, osteoporosis, degeneration and necrosis of chondrocytes and osteoblasts in growing animals and paradoxically are stimulatory to osteoblasts in adults

Vit D: Acute high dose: widespread soft tissue mineralization, osteosclerosis with formation of abnormal woven bone matrix w/ increased basophilia

Front 23

Scurvy pathogenesis & histo

Back 23

Collagen Synthesis

* Ascorbic acid required for hydroxylation of proline and lysine, essential in the formation of collagen's helical structure, rigidity and strength

* Ascorbic acid deficiency results in decreased secretion and deposition of collagen, or deposition of collagen that is fragile and prone to degradation

* Defective collagen synthesis causes inadequate support of blood vessel walls and loose attachment of periosteum to bone, resulting in hemorrhage

Lack L-Gulonolactone Oxidase > dietary Vit C defic > ↓ lysine & proline hydroxylation > impaired Type 1 & 4 collagen synthesis > weakened vessel walls > periarticular hemorrhage

Hint 23

> dilation of metaphyseal vessels
> Irregular columnization, hypertrophy and mineralization of physeal cartilage
> Reduced or absent deposition of bone on the mineralized template
> Microfractures of the trabeculae and metaphyseal hemorrhage
>Marked proliferation of fusiform mesenchymal cells in the medullary cavity with displacement of hematopoietic cells
> Decreased osteoclasts, with reduced matrix remodeling
>Subperiosteal hemorrhage
> Resorption of dentin and derangement of odontoblasts in teeth

Front 24

Hypertrophic Osteopathy

Back 24

Formation of periosteal new bone along diaphysis of long bones

distal spread then proximal

Hint 24

Most often associated with concurrent intrathoracic space-occupying lesions in dogs> vagus nerve stimulation > increased blood flow to periosteum of distal limbs

>reduced peripheral oxygenation secondary to lung lesions or venoarterial shunting of blood

>neurogenic causes due to reflex or inappropriate stimulation of vagus nerve

>due to a hormone-like factor either produced by the primary lesion or whose catabolism is diminished due to underlying disease

Front 25

Osteochondromas

Back 25

Multiple cartilaginous exostoses

Defect in skeletal development

Hint 25

Outer cap of hyaline cartilage that undergoes orderly endochondral ossification to give rise to trabecular bone that forms base

Medullary cavity of mass communicates with that of underlying bone