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Flashcards in Musculoskeletal Deck (64):

What area of the embryological animal does bone arise from?

Mesenchyme - mesoderm


Which type of ossification forms flat bones?



Describe intramembranous ossification.

  1. Remember it must be an area of high oxygen tension.
  2. OBs cluster in the fibrous membrane forming a COO, start secreting osteoid
  3. OBs secrete collagen and ECM into which Ca is secreted leading to trabeculae formation
  4. Appositional growth occurs as woven bone is replaced by lamellar bone
  5. OBs become trapped in lacunae and become OCs 
    1. ​Progenitor cells on the surface differentiate to OBs
  6. Bone marrow fills spaces between trabeculae
  7. The fibrous membrane from 2 becomes the periosteum


Describe the difference between appositional and interstitial growth.

Appositional = change in width

Interstitial = change in length


Describe Endochondral ossification.

  1. Originates from hypoxic mesechyme
  2. A cartilage model is laid down covered by perichondrium
  3. Blood vessels penetrate model mid-shaft, this stimulates differentiation to OBs 
  4. OBs form a collar around the bone diaphysis 
  5. Capillary beds penetrate diaphysis cause chondrocyte hypertrophy - cells burst increasing pH and intracellular calcification
  6. Intracellular substance degenerates and leaves cavities - forms marrow cavity when infiltrated by blood vessels


True or false

Bones grow in width by endochondral ossification

False, they grow in length by endochondral and in width by intramembranous


How do joint cavities develop?

By apoptosis.



Which structures of the joint are covered by synovium?

Surfaces of ligaments.

Not covered are articular surfaces and synovium


Osteoid seam

The layer of superficial non-mineralised osteoid.



Unmineralised bone matrix initially deposited by a layer of osteoblasts.


Primary mineralisation

Occurs around 8-10 days after osteoid secretion. The initial 70-75% of mineralisation. 


Secondary mineralisation

Complete bone mineralisation to final bone density. Occurs over several months


Name and describe the four cell types found in bone.

  1. Osteoblasts - Osteoid formation, initial mineralisation and reg factors production
  2. Osteocytes - Produce and absorb immediately local bone. Communication
  3. Osteoclasts - Reabsorption of bone. Produce low pH acid which dissolves bone salts, and proteolytic enzymes which dissolve osteoid
  4. Bone marrow stromal cells - haematopoietic growth factors, OB progenitor cells, PTH, strain gauge (activate remodelling)


Describe the morphological features of active and inactive OBs.

Active = Pear shaped, cuboidal cells, abundant RER and golgi, basophilic, granular cytoplasm.

Inactive = flat, similar to squamous cells, line bone surface


Describe the morphology of osteocytes.

Minimal cytoplasm, projections which communicate with immediately adjacent cells through canaliculi of bone


Describe the morphology of an osteoclast.

Large, multinucleated cells, eosinophilic cytoplasms, found on bone surface.

Found within Howship's lacunae when actively reabsorbing bones.


Describe the morphology of bone marrow stromal cells.

What four functions do they serve?

Spindle cells, margin of bone marrow, immediately above the osteoblast layer.

  1. Hematopoietic growth factors Eg: EPO and CSF
  2. Progenitor cells of the OB
    1. Provide vertical orientation of bone cell
    2. Establish the canalicular-lacunar system.
  3. React to parathyroid hormone stimulation
    1. Attract and stimulate OCl to remove bone
    2. Proliferate and form fibro-osseous matrix
  4. Strain gauges which activate bone remodelling.


What is the embryological origin of OCls?

Monomyelocytic stem cells


What are the organic components of the bone matrix?

  1. Osteoid - T1 collagen 
  2. Other proteins - proteoglycans, osteonectin, osteopontin, etc
  3. Growth factors - FGF & TGFbeta - cause mitogenic responses in cells


Name the two main inorganic components of the bone matrix.

  1. Hydroxyapatite - Calcium and phosphorous
  2. Carbonate, Mg, Na, Zn, F also


Cancellous bone

aka Spongy

Tarbeculae surrounded by large spaces filled with marrow. Found along entire of flat bones and in the diaphysis of long bones.

Provides support and marrow storage.


Dense bone

aka compact bone.

Trabeculae are densely packed with few spaces. Deposited in layers over cancellous bone.

They layers of compact bone are thicker at the diaphysis.

Forms osteons in thick cortex


Cancellous and compact bones are both examples of which category of bone?

Lamellar - mature - layers of lamellae


Woven bone


Randomly oriented lamellae - becomes lamellar through remodelling.


Outline the process of OCl bone reabsorption.

An acid environment is created between the cell and the bone surface. Hydrogen and bicarbonate ions are generated from CO₂ and water by carbonic anhydrase on the brush border.

An ATP-mediated proton pump actively transfers hydrogen ions into the extracellular space. The acidity of the local environment induces demineralisation of bone and enhances the activity of acid hydrolases released from osteoclasts.

Fragments of degraded matrix are endocytosed by the osteoclast.


Outline the process of OB bone production.

A thin layer of un-mineralised osteoid, the osteoid seam covers the surface where bone is being formed.

Mineralisation of osteoid does not occur until 5-10 days after deposition.

Histologically, it is more eosinophilic than the mineralised bone, and in lamellar bone, it is separated from it by a basophilic line (The mineralisation front).


Which four processes are characteristic of bone remodelling?

  • Activation of OB by external signals such as hormones, cytokines or growth factors.
  • OCl activation, attachment to bone surface and resorption of the bone
  • OCl inactivation: osteoclasts detach from the bone and undergo apoptosis
  • OB recruitment to the resorption site, where they deposit new bone


Name the regulatory factors of bone growth.

  1. PTH - parathryoid hormone - > blood Ca2+
  2. 1,25-dihydroxy vit D3 - > blood Ca2+
  3. Calcitonin - < blood Ca2+


Describe the action of PTH

  • OCl activation via RANK-L pathway
  • Inhibits activation of OBs 
  • Increases Ca2+ reabsorption from the kidney
  • Increased vit D3 synthesis
  • Decreased P reabsorption from the kidneys


Describe the action of vit D3

  • Increases Ca2+ and P+ absorption from the gut
  • Increases P+ reabsorption from the kidney
  • Increases OCl activity


Describe the action of Calcitonin

  • Inhibits OCls
    • Loss of ruffled border and detachment from bone suraace
  • Inhibits OCl formation 
  • Inhibits PTH bone resorption


Name and describe the three layers of the growth plate.

What type of ossification is occuring here?

  1. Resting - zone of reserve chondrocytes
  2. Proliferating/ maturing - Chondrocytes are proliferating and producing molecules which modify matrix and allow cap invasion and initiate mineralisation
  3. Hypertrophy - Enlargement and lysis of chondrocytes. Minerals from caps and trabeculae are formed by osteoprogenitors differentiating into OBs


What is the difference between the primary and secondary spongiosum?

Primary - rapidly mineralised osteoid formed on top of calcified cartilage.

Secondary - Primary remodelled to lamellar bone


Growth arrest line

Characterises something going wrong at the level of bone matrix production. eg insufficient nutrition.

Seen histologically as a transverse calcified line parallel to the growth plate.


Growth retardation lattice

Persistence of non-formed areas of endochondral ossification at the growth plate.

Persistence of non-mineralised cartilage

Impaired OCls or OBs 


Resting lines

Longitudinal straight basophilic line within mineralised bone matrix. Evidence of OB resting at some point.


Reversal lines

Scalloped matrix lines, evidence of past bone remodelling 



Absence of cartilage development



Name and describe a form of this abnormality in calves.

Disorder of cartilage development

Eg Bulldog calf

Gross: Abort ~7m, micromelia, brachygnathia, domed head, abdominal hernia, 

Histo: Lack of distinct growth plates, densely packed, disorganised chondrocytes


Less severe buldog calves who are born unable to stand.

Telemark lethal


Describe a snorter.


Short broad heads, bulging forehead, prognathia

Histo: Shorter, irregular columns of hypertrophied chondrocytes


Point mutation in FGR3 which causes long limbs/ neck, shallow bodied and spinal abnormalities in lambs

What histological changes are seen with this?

Spider lamb syndrome

Histo: Small ossification centres within hypertrophic cartilage, lack of subchondral bone, irregular chondrocyte columns in growth plates. Very thin diphysis


What musculoskeletal abnormalities are seen with dwarfism?

Reduced longitudinal growth despite normal apositional growth.

Epiphyseal growth plate abnormality



Cleft palate


What is the difference between kyphosis, lordosis and scoliosis?

Kyphosis - dorsal curvature of the spine

Lordosis - ventral curvature of the spine

Scoliosis - lateral deviation of the spine


Complete or partial fusion of the hindlimbs.



Congenital deformity and shortening of the limbs




pertaining to digits



Incomplete duplication of the head


Spina Bifida

Defective closure of dorsal vertebral laminae in a segment of the vertebral column


Which genes are affected with Osteogenesis imperfecta?

COL1A1/ COL1A2 mutation

Gross: Brittle bones, bowed limbs

Histo: Calcified cartilage, lined with basophilic bone matrix



ACAN mutation is associated with which disorder?

What histological changes are observed?


Histo: avascular metaphyses, cartilage matrix, thin woven bone fills medulla


Marie's disease

Hypertrophic osteopathy - periosteal growth secondary to neoplastic/ inflammatory growth in the thorax



AKA pink tooth disease 

An inherited haemaglobin disorder which results in brown discolouration of bone



Pale tan discolouration of bone, dry periosteum

Caused by reduced bone blood supply/ foreign body (bone)


Legg-calve-perthes disease

Femoral head necrosis

Ischemia due to abnormal blood vessel formation leading to necrosis

Flattening of the femoral head and fracture



Decreased blood calcium - increased PTH activity (OCl, vitD3, kidney and gut absorption increased)

Reduced bone quality


  • Parasitic
  • Starvation
  • Steroids - collagen synthesis inhibited
  • Disuse


Rickets/ osteomalacia

Hypovitaminosis D3 - reduced absorption of Ca2+ leading to increased PTH activity (reduced mineralisation of bone)


Fibrous osteodystrophy


  • Primary secreting tumour
  • Renal failure
  • Nutritional
  • PTH-like secreting tumour AS carcinoma

Excessive bone resorption, fibroblastic replacement with collagen


What conditions can lead to poor bone healing after a fracture?

Inadequate blood supply = necrosis

Instability = Pseudoarthritis (poor union)


Describe this lesion

Focal pale tan discolouration 3x3cm, affected bone appears soft. 

Focal severe acute suppurative osteomyelitis


  • Foal - E.coli, Klebs, Salmonella, Rhodococcus
  • Calf - A. pyogenes, Salmonella
  • Dog - penetrating injury (E.coli, staph, strep)



Describe this lesion

Vertebrae - Focal acute severe suppurative osteomyelitis

Due to failure of passive transfer and systemic bacterial infection

  • F. necrophorum
  • A. pyogenes
  • R. equi
  • M. haemolytica

Predisposes bone to fracture


Lumpy jaw

Mandibular osteomyelitis - Actinomyces bovis

Multifocal round abscesses which distorts the external anatomy of the face