Ch 73 OCD Flashcards
Define osteochondrosis
- developmental condition of growth cartilages in skeletally immature
- a disorder of the ordered process of endochondral ossification (where cartilage in epiphyses and growth plates is gradually turned into bone through a sequence of matrix mineralization, chondrocyte death, vascularization, and ossification)
- A generalized disease process has been refuted based on the localized nature of the initial lesions, often at predictable sites
- therefore considered a focal or multifocal disorder, often with a bilaterally symmetric distribution
What are the widely accepted location of OCD? (4)
proposed areas?
Humeral head
Medial aspect of humeral condyle
Lateral or medial femoral condyle
Medial or lateral trochlear ridge of the talus
classification
- Given that endochondral ossification occurs in the growth cartilages at both the epiphyses and the growth plates, some authorsargued that osteochondrosis manifests clinically at both
- Others suggesting that in dogs (and presumably cats), the term should be reserved for conditions of the articular surfaces of the shoulder, elbow, stifle, and hock joints only
proposed method of classifying osteochondrosis of the articular–epiphyseal cartilage complex
based on dz stage:
- osteochondrosis latens: indicate an early, microscopic lesion
- osteochondrosis manifesta: subclinical lesions that are macroscopically and radiologically apparent
- osteochondrosis dissecans: if attached or loose cartilage flaps are present and typically result in clinical signs.
Although inflammation is not believed to be associated with the pathogenesis, dt synovitis, convention is to describe as osteochondritis dissecans.
Epidemiology
- 9% of dogs < 1 year that were presented with an orthopedic problem
- Male dogs (talus being an exception)
- Epidemiologic and genetic studies indicate strong breed predispositions (large- and giant-breed dogs) = genetic component for each of the different manifestations of osteochondrosis
- 0.001% of 8909 cats presented dx with OCD
How much longitudinal bone growth is formed from the growth plates and from the epiphysis?
Growth plate: 75 - 80%
Epiphysis: 20 - 25%
Skeletal developments
- cartilaginous bone model that enlarges through the formation of new cartilage at primary (diaphyseal) and secondary (epiphyseal) growth centers, and growth plates > cartilage converts into mature bone via endochondral ossification
- In dogs, most longitudinal bone growth takes place between 12 and 26 weeks of age
- Growth plates enlarge through the formation of new cartilage
What are the 4 zones of the growth plate?
Resting zone (epiphyseal side)
Proliferative zone
Hypertrophic zone
Mineralisation zone
Which is the only vascularised zone of the physis?
The resting zone
- Penetrated by chondro-epiphyseal blood vessels within cartilage canals
Describe the chondrocyte appearance in each of the physeal zones
Resting zone:
- Small, scattered, randomly organised. - Primarily slowly dividing stem cells
Proliferative zone:
- Flat, relatively small, organised into columns.
- They divide, slowly enlarge and produce matrix
Hypertrophic zone:
- Spheroid and relatively large.
- Rapidly swell and continue synthesis of matrix
Mineralisation zone:
- Newly formed matrix mineralises
- chondrocytes undergo apoptosis
WHat effect does growth hormone have on the resting zone?
Promotes differentiation into daughter cells capable of making IGF-1 which stimulates clonal expansion of chondrocytes
What substances (3) are involved in the local feed-back loop of chondrocyte proliferation?
PTHrP
IHH (Indian hedgehog)
TGF-B
Controls the irreversible differentiation of proliferative chondrocytes into hypertrophic chondrocytes. BMP, thyroid hormone and others are also needed for this phenotypic change to occur
How does physeal mineralised cartilage under endochondral ossification?
- Chondrocytes in the zone of mineralization undergo their terminal differentiation and secrete a specialized matrix that promotes calcification
- Chondrocytes juxtaposed to the metaphyseal vasculature (terminal hypertrophic chondrocytes) die abruptly by apoptosis.
- Clasts remove matrix separating apoptotic chondrocytes from the metaphyseal vasculature
- Clasts form void lacunae in a mineralised matrix scaffold
- Vasculature from the metaphysis and osteoprogenitor cells invade the lacunae under control of VEGF produced by hypertrophic zone chondrocytes
- Osteoprogenitor cells differentiate into osteoblasts, which lay down woven bone
- woven bone are replaced by lamellar bone (secondary spongiosa)
- transformation of cartilage to woven bone is complex, with genetic, nutritional, metabolic, and mechanical factors all appearing to play a role
What are the 2 layers of the articular-epiphyseal complex?
cartilaginous ends of developing bones
Relatively thin outer layer
- Specialised immature articular cartilage, avascular and takes no part in endochondral ossification
- Developes into mature cartilage with 4 zones: Superficial, transitional, radial and calcified cartilage
- Noncalcified radial zone seperated from calcified cartilage by the tidemark. This indicates completion of maturation process
Inner layer functionally similar to the growth plate with 2 main differences:
- Visually disorganised without ordered zonal and columnar arrangement of chondrocytes
- Abundant vasculature from the perichondral plexus and course through cartilage canals, forming glomeruli
- Most proliferation occurs at periphery whereas conversion into bone occurs at the center
Chondro-epiphysis
- vessels from perichondral plexus course within cartilage canals
- cartilage canal vessels play a role in nourishing epiphyseal chondrocytes, in forming and maintaining the epiphyseal ossification center, and in providing mesenchymal stem cells
- Just as in the growth plate, enlargement of the epiphysis is a function of chondrocyte proliferation, chondrocyte enlargement, matrix formation
- As the ossification front from the center of the epiphysis reaches newly formed epiphyseal cartilage, the redundant cartilage canals regress through a normal process called chondrification
- demonstrated that blood vessels from the epiphyseal bone marrow anastomose with cartilage canal vessels.
- These anastomoses develop only toward the end of the growth period
What is chondroification?
The process of regression of cartilage canals as the ossification from the centre of the epiphysis reaches newly formed epiphyseal cartilage
What remains once the process of epiphyseal ossification is finished?
A thin layer of avascular articular cartilage and a crtilage disc between the epiphysis and metaphysis (growth plate)
Etiology and Risk Factors (4)
- multifactorial origin
- risk factors: heredity, rapid growth, dietary factors, and trauma
- breed predisposition has been demonstrated for all forms of osteochondrosis
- reported heritability for these conditions 10% to 45%.
- inherited as a polygenetic trait
- anatomic features of affected limbs and joints may play an etiologic role in the development of osteochondrosis (conformation are in part genetically determined)
- rapid growth increases the incidence of skeletal diseases > The predisposition of large- and giant-breed dogs with a rapid rate of skeletal growth is consistent with this notion.
- direct correlation of dietary factors (i.e high Calcium) with osteochondrosis has not been established (great dane puppy study results not replicated in other breeds)
- microtrauma (disruption of cartilage canal vessels at the chondro-osseous junction)
- local mechanical overload > BUT major loading area of the proximal humeral joint surface during locomotion only partially coincides with the area where OCD lesions > role of microtrauma not fully elucidated
- exercise
How has microtrauma been speculated to cause OCD?
Pathogenesis
Microtrauma can cause damage to cartilage canal vessels at the chondroosseous junction and subsequent necrosis of cartilage canals leading to areas of cartilage ischaemia and necrosis
- Infarcted cartilage focally prevents endochondral ossification however cartilage proliferation continues, resulting in focal thickening
- Thickened cartilage may be less resistant to mechanical stress and may be metabolically deprved and degenerate
- Weakened cartilage may deform, fissures can form and may propage along tidemark (osteochondral junction)
- If fissures extend to the joint surface, an OCD lesion develops
Pathogenesis and Pathology
Type I: center of the affected articular surface, away from vascular attachments > caudal humeral head, medial humeral condyle, and femoral condyles
Type II: occur at the joint margin and retain a vascular attachment, the medial or lateral trochlear ridges of the talus, which attach to the joint capsule and/or collateral ligaments
**Generalised **thoeries
- dyschondroplasia or osetopaenic subchondral bone (2ndry to overnutrision/rapid growth) does not address species-specific, site specific manifestation of OCD lesions
Focal theory
- result from vascular trauma and subsequent necrosis of subchondral bone or necrosis of epiphyseal cartilage canals during growth > resulting in areas of cartilage ischemia and necrosis as matures
- consistent with the site-specific and often bilaterally symmetric nature of osteochondrosis because the juvenile vascular supply has a consistent species-specific pattern and tends to demonstrate bilateral symmetry
focal theory
Beginning as avascular osteonecrosis, OCD forms a transitional zone that harbors the potential of restoration with complete healing or progression to an osseous defect. Mechanical and traumatic factors are etiologically dominant in OCD, but a predisposition seems to be a contributing factor
- Normal epiphyseal blood supply with cartilage canal vessels originating from the perichondral plexus.
- As the ossification front advances, anastomoses between the cartilage canal vessels and the subchondral vessels develop.
- Focal interruption of an anastomosis at the osteochondral junction may cause ischemic cartilage necrosis (osteochondrosis latens).
- Small areas may be resolved when reached by the ossification front, and normal growth may ensue.
- Larger areas, which resist vascular invasion, will persist during remaining growth and may be detectable and be less resistant to mechanical stress (osteochondrosis manifesta).
- The necrotic area may be replaced by fibrous tissue, which ultimately may undergo intramembranous ossification.
- If the overlying articular cartilage fissures, an osteochondrosis dissecans lesion develop (Elution of proinflammatory debris and mediators results in synovitis, effusion, lameness, and OA)
OATs
- osteochondral grafts (plugs) are harvested from healthy, non–weight-bearing portions of the same or another joint
- single vs mosaicplasty (permits better contouring and addresses the tissue scarcity)
- commercially available instrumentation (e.g., Osteochondral Autograft Transfer System [OATS], Arthrex
- STUDY: incorporated and maintained its normal hyaline composition and biomechanical properties
- Autograft incorporated into subchondral bone (second-look arthroscopy). lameness score improved in all, only 20% were pain- or lameness-free
- lined and partially filled with fibrocartilage, with synovial adhesions
allograft has been succesfully reported
Synthetic Osteochondral Resurfacing
- single-layered polycarbonate-urethane plug (SynACart, Arthrex), with a textured titanium base for in- and on-growth.
- Long-term function considered excellent in the majority of dogs. Septic loosening occurred in 1 animal
- large diameter of the receiving socket, there is concern that implant failure will result in significant revision challenges
- osseous integration in 83% of cases (murphy 2018)
Osteochondrodysplasia in a Scottish Fold Cat Treated with Radiation Therapy and Samarium-153-1,4,7,10-Tetraazacyclododecane-1,4,7,10-Tetramethylene-Phosphonic Acid
Kim A. Selting, DVM, 2019
a heritable missense mutation in the TRPV4 gene
Radiation therapy administered using either external beam or bone-seeking radioisotopes can be effective at palliating clinical signs
OCD C5 lesion french bulldog
