1. Traumatic diseases

2. Congenital diseases

3. Metabolic disturbances

4. Vascular disturbances

5. Infectious

6. Poorly characterized conditions

7. Neoplastic

1. Structural support

2. Protect organs

3. Attachment for tendon

4. Bone marrow (creation of RBCs and leukocytes)

5. Mineral metabolism (warehouse for calcium and phosphorous)

1. Cortical (AKA compact, Haversian, or cortex) bone

2. Cancellous (AKA trabecular, or spongy) bone

1. Diaphysis - in the middle

2. Metaphysis - area btwn diaphysis and growth plate

3. Epiphysis - area btwn articular cartilage and growth plate

Made up of osteons (=Haversian system) and circumferential lamellae

Haversian canal at the center of the osteon that is parallel to the long axis of the bone

Volkmann's canals run perpendicular to the long axis of the long bone

Blood vessels and nerve supplies run thru these canals

Based on maturity of bone

1. Lamellar bone (mature bone)

2. Woven bone (immature bone)

1. Nutrient arteries

2. Metaphyseal and epiphyseal arteries

3. Periosteal arteries

They are the cortex blood supply (plus nutrient/metaphyseal/ epiphyseal arteries)

Join the bone along w/fascial attachment

Arise from bone marrow mesenchymal stem cells

Used for bone formation

A monocyte-macrophage lineage cell

Used for bone resorption

1. The first site of ossification (formation of bone tissue)

2. Prenatal development

3. Diaphysis/medullary cavity

1. Second place of bone formation

2. Postnatal development

3. Epiphysis

Growth plate or Physis

1. Endochondral ossification

2. Interstitial growth

Resting chondrocytes --> Proliferative chondrocytes --> Mature chondrocytes --> Hypertrophic chondrocytes --> Calcified cartilage

How we grow in length

1. Primary spongiosum

2. Secondary spongiosum

1. Cartilaginous trabecula, calcified cartilage bars

2. Cartilaginous cores are rapidly replaced by woven bone (osteoid seam)

Cartilaginous bars of the physis tunnel into the metaphysis

1. Bony trabecula

2. Primary spongiosa being replaced by lamellar bone (no cartilaginous cores)

1. Line btwn hyaline and calcified cartilage

2. Adult animals

1. Line btwn calcified cartilage and subchondral bone (epiphysis)

2. Adult animals

1. Any disease that affects the progress of bone growth by killing bone tissue

2. Juvenile animal

No cartilage is involved

In the periosteum, there are many pleuripotent osteogenic cells.  They produce osteoblasts and osteoid trajectory w/o endochondrial ossification

1. Genetic information

2. Applied load - biomechanical stress is important in "bone remodeling"

Accomplished by BMUs in which bone resorption is coupled with bone formation

Bone formation and bone production occur at same location

Osteoclastic resorption is followed by osteoblastic bone production

Bone remodeling occurs in Basic Multicellular Units (BMU) - BMU consists of: osteoclasts, osteoblasts, vascular supply

Parathyroid hormone is important to instigate bone resorption

However, osteoclasts do not have receptors to sense PTH stimulus - osteoblasts sense PTH and give signals to osteoclasts for bone resorption

1. Transverse

2. Oblique

3. Spiral

4. Comminuted

5. Infraction

6. Salter-Harris fracture

1. Fracture thru a growth plate

2. May cause a stop in growth (endochondral ossification)

Ex: Radius-Ulna problem where one grows and the other stops

1. Direct bone healing

2. Secondary bone healing

1. Gap healing by bone cells migrating from fracture ends

2. Contact healing

3. BMU is organized into a "cutting cone" of osteoclasts resorbing bone followed by bone formation by osteoblasts which span the gap btwn fracture site

1. Employs a combination of intramembranous ossification and endochondrial ossification

2. Seen w/IM (intramedullary) pinning or casting

3. Wider gap w/callus formation

4. Interstitial bone formation due to involvement of periosteum

Hemorrhage, clot formation --> inflammatory cells appear.  Organization and resorption of blood clot --> Mesenchymal cell proliferation, neovascularization --> Callus = osteogenic/chondrogenic reparative granulation tissue

Cassie's notes from lecture

Hemorrhage/disruption of vascular supply (hypoxic condition) --> granulation tissue formation --> cartilage --> (if stable condition) --> neovascularization (oxygen/nutrient/growth factors/cytokines) --> endochondral ossification --> bone callus --> bone remodeling --> bone

1. Blood supply

2. Rigidity of fixation

3. Quality of reduction

4. Age

5. General health and nutrition

6. Local or systemic infection

1. Poor blood supply

2. Too much motion (instability)

3. Bone ends are excessively separated

4. Muscle/fascia is trapped btwn fracture ends

5. Poor nutrition

6. Infection

1. Delayed union

2. Malunion

3. Nonunion

Bone union won't occur. 

A fibrous bridge occurs btwn the fracture ends --> motion occurs at the fracture site "pseudoarthrosis"

Etiology is often not apparent

Perinatal factors:  in utero malposition, premature birth, perinatal joint trauma, joint laxity, congenital hypothyroidism --> improper development of cuboidal bones (carpus/tarsus)

Older foals: trauma, nutritional imbalance

Joint trauma --> premature closure of distal ulnar physis --> continuous growth of the adjacent radius --> asynchronous growth of the radius and ulna --> "bowing" (abnormal bone modeling) --> deformity

Cone shape of distal ulnar physis means it is easily injured and can be injured in many directions

"bad form" "abnormal formation"

Abnormal cartilage differentiation --> premature cessation of cartilage growth --> development abnormalities of cartilage structure

"abnormal nourishment"

= chondrodysplasia

breeds that have chondrodysplasia as a characteristic

e.g. dachshund, bulldog, bassett hound, corgi

1. Characterized by a generalized or localized lack of coordinated bone and joint development due to abnormal endochondral ossification

2. Familial chondrodysplasia is known in Alaskan malamutes

Common phenotype is shortened front limbs w/deformity (axial skeleton is normal)

A good animal model to study subset of human dwarfism

An autosomal recessive chondrodysplasia in Suffolk, Hampshire

Gross:  narrow chests, long limbs and neck w/poor muscling, kyphosis, scoliosis, "roman nose" (shortening of the maxilla w/dorsal rounding), limb deformity, pectus excavatum (concavity of sternum)

Histopathology: multiple centers of ossifications w/thickened and disorganized growth plate; haphazardly arranged growth plates (abnormal endochondral ossification)

1. Bone marrow stromal cells produce CFU-GM and RANKL --> monocyte + RANK --> osteoclast

2. Incomplete osteoclast function/anatomy/production

RANK and RANKL system: osteoblast delivers PTH stimulus to osteoclast.  If there is a problem w/system can't get bone resorption and osteoclast production

Unresorbed primary spongiosa (cartilaginous trabeculae) fills metaphysis and diaphysis

Said another way - bone marrow is filled w/primary spongiosa - no normal bone remodeling or turnover --> fracture

Fracture due to bone fragility

Anemia

Death

Bone is hard, but very fragile and breakable

In utero infection w/BVDV --> ? (possibly increase solube IL-1 inhibitor --> decrease IL-1 --> decrease osteoclastiogenesis) --> retained primary spongiosa

Seen in infectious diseases

Metaphysis and diaphysis is also filled with bone trabeculae

1. "Growth retardation lattices" - a band of denser metaphysis

2. Some viruses impaired remodeling by osteoclasts --> transient interruption of bone resorption --> zonal osteopetrotic changes in metaphysis

1. Cattle - BVDV, lead poisoning

2. Dog - Canine distemper virus

3. Cat - Feline infectious leukemia virus

4. Pig - Classical swine fever virus

1. Plumbism

2. Paint, batteries, and putty cans from rubbish dumps

1. Lead is resorbed by osteoclasts --> interfere w/osteoclastic activity --> metaphyseal osteosclerosis ("lead line" in radiograph)

Osteosclerotic change = white, dense bone

2. Retention of primary spongiosa, intranuclear inclusions

1. Miccrocytic hypochromic anemia, basophilic stippling: interfere w/sulfhydryl binding --> inhibit enzymes involved in heme synthesis (gamma-aminolevulinic acid dehydrase and ferrochelatase)

2. Increase nucleated RBC:  interfere w/5`-nucleotidase

3. Depression, blindness: competes w/Ca++ at the NMJ

4. Renal tubular necrosis:  lead accumulates in proximal renal tubules

5. Centriolobular hepatocellular necrosis: lead accumulates in hepatocytes > inhibit mitochondrial respiration

1. "Popeye pigs"

2. Congenital disease of unknown genesis.  Condition is lethal at birth

Gross - thickened limbs (joints are normal)

Histopathology - cortex is thickened by radiating proliferation of periosteal bone

Hyperostosis is pressure from inside to out - get blockage of lymphatic and venous return --> soft tissue is edematous (which is a secondary lesion)

Hyperostosis is the primary lesion - B in bottom picture of slide 38

1. Brittle Bone Disease

2. Hereditary defect of collagen type I production - autosomal recessive trait in Angus cattle

Gross - affected bones are thin and brittle (osteopenia); type I collagen is also the main type in skin and muscle so see lesions in these organs as weakness; rib cage - callous formation - in utero fracture of infected Angus calf

Histopathology - very thin cortical bone and trabecular bone

Growth plates are typically not affected - b/c cartilage is composed of type II collagen, not type I so growth plate is usually spared

A group of conditions affecting the entire skeleton that are of metabolic origin and generally cause a decrease in bone mass ("osteopenia") and a tendency to fracture.

General term for this group is "osteodystrophy"

The diseases imply specific pathologic changes but not specific causes.  In general, they are disorders of calcium, phosphorous, and/or vitamin D metabolism

"Deficiency"

Decrease in the amount of bone that does not imply if there is concomitant clinical disease

"Increased porosity"

Decrease in the amount of bone that results in clinical disease

"Softening"

Mineralization defect that results in the accumulation of unmineralized bone (osteoid)

"Hardening"

Excess mineralization

1. Osteoporosis/Osteopenia

2. Osteomalacia

3. Rickets

4. Fibrous osteodystrophy

Osteoporosis is the clinical condition

Osteopenia just describes the decreased amount of bone - patient may or may not have clinical symptoms associated w/osteopenia

1. Ca deficiency --> hypocalcemia --> increase PTH --> increase bone resorption

2. Malnutrition (e.g. inanition, inflammatory bowel disease) --> deficiency of protein and mineral, decrease IGF-1 --> decreased bone formation

3. Disuse atrophy: decrease piezoelectric stimuli, decrease mechanical stimuli

4. Glucocorticoid therapy --> decrease calcium absorption from the intestine and increase renal excretion + directly inhibit type I collagen synthesis and osteoblasts

5. [Estrogen deficiency: increase TNF, IL-1, etc. --> increase bone resorption]

Thin cortex, trabeculae and fracture

Expanded marrow cavity, increased porosity (due to imbalance of bone resorption > bone formation)

By wide, unmineralized osteoid seams covering trabecular bones.

Skeletal deformities due to abnormally soft bones.

Mature bones have no open physis so no physeal lesions but is commonly seen at the growth plate

Vitamin D deficiency

Ca/P imbalance

It is unknown why dietary Ca deficiency does not cause rickets/osteomalacia

1. Lack of UV light

2. Advanced liver disease

3. Advanced renal disease

4. Malabsorptive diarrhea

5. Poor diet

Gross - thick physis (growth plate); "Rachitic rosary" at costochondral junctions

Histopathology - physis is expanded by a thick zone of hypertrophy.  There are retained primary spongiosa (cartilaginous trabeculae)

"Rubber jaw"

"Big head"

The main clinical manifestations is in jaw/maxilla

Big head: symmetrical enlargement of jaw, but bone is resorbed and replaced by fibrous connective tissue which is soft and pliable

Lack of bone = mandible and maxilla are very flexible

Decreased bone mass due to excessive bone resorption and replacement by fibrous tissue

There is very strong osteoclastic bone resorption w/replacement by fibrosis

Lots of osteoclasts

Little cortical bone left due to excessive resorption

1. Renal secondary hyperparathyroidism:  renal failure --> Ca/P imbalance --> stimulates PTH production --> increased osteoclast activity

2. Nutritional secondary hyperparathyroidism:  low Ca, high P (e.g. bran), Vitamin D deficiency; GI issues --> can't absorb Ca --> can't absorb Vitamin D; unknown why some animals w/this develop FOD while others osteoporosis

3. Primary hyperparathyroidism:  hyperplasia or neoplasia

4. Pseudohyperparathyroidism: Parathyroid hormone-related peptide (PTHrP) from neoplasia (lymphosarcoma, anal sac adenocarcinoma) "hypercalcemia of malignancy"; function is the same as PTH but unlikely b/c animal usually doesn't live long enough to be seen clinically

1. Lead poisoning

2. Vitamin D deficiency - osteomalacia, rickets, fibrous osteodystrophy

3. Vitamin D toxicity

4. Vitamin C deficiency (Scurvy)

5. Vitamin A toxicity

1. Humans, non-human primates, and guinea pigs

2. Won't see it in dogs, horses, cows, etc. b/c they have L-gulonolactone oxidase in their livers which is the enzyme necessary to produce endogenous Vitamin C

No L-gulonolactone oxidase

Vitamin C deficiency --> impaired hydroxylation of procollagen --> improper cross linking of collagen fibrils --> hemorrhage, thin physis w/inadequate synthesis of cartilage and osteoid

Essential for collagen formation

Collagen fibers: Gly-X-Y triplets with HYP in the Y position (essentially, collagen fiber is repeating Glycine-X-Y amino acid)

All collagen fibers including Type I and Type II

Growing animals have very thin growth plates; can see many other clinical symptoms such as hemorrhage b/c vessels are very fragile (vessels are formed by collagen)

Excessive Vitamin A (enriched grains, sweet potatoes, liver) can cause closure of growth plate (pathogenesis is not known) --> shortening of limbs and vertebral bone deformity

"Hyena disease" - short legs and curved neck w/head tilted to the ground

Vitamin A toxicity w/periarticular exostosis and osteosclerosis

Pathogenesis is unknown but possibly (increase retinoic acid --> increase ets1, a transcription factor --> bone proliferation?)

1. Legg-Calve-Perthes disease

2. Dry gangrene

3. Hypertrophic (pulmonary) osteopathy

1. Unknown etiology

2. Young (4-11 months), growing toy/miniature breeds (about 85% of reported cases are unilateral)

Vascular compromise to the proximal femoral epiphysis --> necrosis of the trabeculae and marrow tissue

What he said:

Disturbance of vascular supply to femoral neck epiphysis --> necrosis --> won't see osteoblast lining on trabecular bone, won't see osteoclasts or fat in bone marrow cavity (on radiograph) --> causes overlying cartilage collapse --> loss of normal round contour of femoral head

Infarction of an extremity (too tight a bandage on a limb, etc.) --> coagulative necrosis --> mummification

Pyknotic nuclei in the lacunae are all dead b/c the digit was tied down tightly - inhibited normal blood supply

Thoracic lesions thought to lead to chronic hypoxia and/or altered vagal regulation --> increase periosteal blood flow to the extremities

Exostosis goes away when the primary cause is removed

1. Infectious osteomyelitis:

Hematogenous osteomyelitis

Direct inoculation osteomyelitis

2. Noninfectious osteomyelitis:

Canine hypertrophic osteodystrophy = Metaphyseal osteopathy

1. Most commonly seen in young animals - probably b/c their host immune response is not very sufficient yet; rare to see in adult animals (except when receiving long-term chemo or glucocorticoids)

2. Caused by bacteria

Umbilical infection (omphalophlebitis) + FPT --> sepsis --> embolization to blind capillary loops --> osteomyelitis

Terminal branch of the metaphyseal artery makes a hairpin curve subjacent to the growth plate --> common location to see bacterial emboli; reason why you see osteomyelitis foci subjacent to the growth plate

Hematogenous route is probably very common

1. Extension:  horse - chronic laminitis, rotation of P3 w/perforation of sole

2. Fracture w/skin penetration

3. Surgery - surgical plate

4. Bite wounds

5. Periodontal disease: cow "lumpy jaw" - granulomatous osteomyelitis and osteolysis w/Actinomyces bovis

NEITHER HYPERTROPHIC NOR OSTEODYSTROPHIC!

NOT AN INFECTIOUS BONE DISEASE

DISEASE NAME IS MISLEADING!

Unknown etiology!

Usually bilaterally symmetric, a self-limiting disease

Occurence in diverse breeds - genetic, vascular abnormalities

Usually seen in young (2-8 mo) growing large/giant breed dogs

Gross: metaphysis of long bones - osteomyelitis w/infarction; open physis, growth plate is normal; lesion only in metaphysis - subjacent to growth plate (suppurative inflammation and necrosis in metaphysis, sometimes have microfracture b/c of inflammation and necrosis)

Histopathology: metaphysis infiltrated by suppurative inflammation w/necrosis (necrosis of capillary loops)

Yes! - once maturation is completed

Prognosis is good if pain can be monitored

1. Canine (eosinophilic) Panosteitis

2. Craniomandibular Osteopathy "Lion Jaw"

Unknown etiology!

Young (5-12 mo) growing large/giant breeds

75% of reported cases involve German Shepherd dogs

Self-limiting disease in single or multiple bones

Will go away

Bone marrow is replaced by fibrovascular tissue w/woven bone

Increase activity of osteoblasts and fibroblasts

Growing dogs - Westies, Scotties, Cairn terriers

Unknown etiology but autosomal recessive is suggested in westies

Usually recognized at 4-7 months old, self-limiting by 11-13 month b/c once animal matures to adult do not see condition; hyperostosis and pain will go away

Usually see pain and discomfort while chewing

1. Osteosarcoma

2. Osteoma

3. Chondrosarcoma

4. Chondroma

5. Multilobular tumor of bone

6. Multiple myeloma

7. Other tumors arise from bone

8. Metastatic bone tumors

A malignant tumor

Most common (malignant) bone tumor (dogs)

Does NOT cross the joint space

Several histologic types but all will make osteoid - must see this to diagnose osteosarcoma

Differentiation of chondrocytes and also osteoblastic differentiation w/osteoid production

(if no osteoid - chondrosarcoma)

Looks like fibrosarcoma w/fibular matrix; must see osteoid to diagnose

(if no osteoid, diagnose as fibrosarcoma)

Telangiectatic

Giant cell type

Poorly differentiated

 True/False:  In dogs, more than 80% of primary bone tumors are osteosarcomas

Appendicular (long bones) > axial skeleton

General rule - away from the elbow and close to the knee

Proximal humor, distal radius/ulna (distal radius is a very common location)

Distal femur, proximal tibia

FALSE!!

By the time it is diagnosed in dogs, 90% of cases have microscopic metastasis in lungs

Poor prognosis w/frequent metastasis

FALSE - 70%

Appendicular ~ Axial skeleton

Locally invasive - but slow to metastasis

Counterpart of osteosarcoma

A benign tumor

Rare but most common in the jaws of horses and cows - hard, rounded, disfiguring mass

Accounts for 10% of primary bone tumors in dogs

Neoplasm is composed of disorganized cartilaginous tissue - chondrocyte proliferation

Most common in large/giant breeds

Flat bones (ribs, nasal cavity, pelvis) are often affected - more common in flat bones, but can be seen in any location

Locally invasive, but slow to metastasize

Uncommon benign tumor

Neoplasm is composed of well-differentiated cartilage - composed of mature chondrocytes

Usually well-demarcated