Bones Metabolic - Pathology

Pituitary

Growth hormone
- Secreted by the anterior pituitary
- Influences the size of the skeleton and soft tissue

Pituitary dwarfism

Pituitary gigantism (Acromegaly)

Occurs in humans with pituitary adenoma
Due to pituitary hyperfunction
Overgrowth of cranial bones, chin, hands and feet
Reported in dogs ?(and cats)?

Thyroid

Thyroid hormones affect maturation of growth of cartilage

Hypothyroidism

In young animals
Retardation of growth and development of endochondral bone
Stunted growth
Skeletal abnormalities
In neonatal foals, Giant Schnauzers and Scottish Deerhounds

Hyperthyroidism

In young animals causes accelerated maturation of growth plate
In adults causes osteoporosis

Gonadal Effect on Bones

Oestrogen and androgens
- Affect growth of skeleton
- Accelerate epiphyseal closure
Oestrogen
- Stimulates osteoblasts to produce matrix
- Inhibits osteoclasts
Hypogonadism in growing skeleton -> delayed epiphyseal closure and skeletal maturation

Adrenal glands

Hyperadrenocorticism
- Causes osteoporosis
- Reported in dogs with Cushing's disease

Hyperparathyroidism

Can arise in a number of ways but single common factor is elevated PTH
Results in increased resorption of bone and replacement by fibrous connective tissue

Primary hyperparathyroidism

This is increased production of PTH not related to calcium or phosphorus levels
Due to parathyroid neoplasia or bilateral idiopathic parathyroid hyperplasia
Rare

Secondary hyperparathyroidism

Regardless of pathogenesis, the result is:
- Increased osteoclastic resorption of bone and deposition of fibro-osteoid matrix that fails to mineralise
- Flat bones of the skull swell, including maxillary and nasal bones
- Long bones become soft with thin cortices which fracture easily

Renal osteodystrophy (Image sourced from Bristol Biomed Image Archive with permission)

Renal hyperparathyroidism
- Pathogenesis:
  - Chronic renal failure
    - -> Retention of phosphate (due to reduced glomerular filtration) and inadequate production of vitamin D by kidneys
      - -> Hyperphosphataemia and hypocalcaemia (high P depresses Ca)
        -> Increased PTH output
        -> Increased bone resorption
        -> Fibrous osteodystrophy - increased osteoclastic resorption of cancellous and cortical bone + proliferation of fibrous tissue
- Mainly in dogs
- Affects whole skeleton but mainly skull
- Bones soft and pliable
- Canine teeth easily removed - rubber jaw
- Microscopically - Osteodystrophia fibrosa (above = fibrous osteodystrophy) +/- osteomalacia

Nutritional hyperparathyroidism (nutritional osteodystrophy)
- Also called fibrous osteodystrophy, “rubber jaw” or “bran disease”
- More common in young, fast-growing animals
- Pathogenesis:
  - Low calcium / high phosphate diets
    - -> Decreased calcium levels in serum
      - -> Parathyroid gland stimulated (may become enlarged)
        -> Increased PTH
        -> Increased bone resorption
- Caused by poor diet
  - Cattle and sheep - usually mild disease
  - Swine fed un-supplemented cereal grain, usually mild disease
  - Dogs/cats fed all-meat or offal diets (Ca:P often as high as 1:20)
    - Few weeks after weaning
    - Provision of calcium alone correct the problem
    - Very brittle bones -> sponataneous fractures
    - Extreme porosity of the whole skeleton on radioghraphs
  - Horses fed bran
    - Very susceptible to high phosphorus diet
    - Any time after weaning, susceptibility declines after seventh year
    - Early signs:
      - Mild changes of gait
      - Stiffness
      - Transient shifting lameness
    - Advanced signs:
      - Swelling of mandible and maxilla - 'Big head'
      - Dyspnoea caused by swelling of nasal and frontal bones
      - Teeth lost or buried in softened jaw
      - Fractures from mild trauma
      - Detached tendons and ligaments
      - Histologically:
        Marked loss of bone
        
        Replacement by proliferative tissue
    - Often called Osteodystrophia fibrosa

Rickets

Rickets in dog (Image sourced from Bristol Biomed Image Archive with permission)

Essentially the same disease as osteomalacia
Caused by Vitamin D and phosphorus deficiency
In young animals
Failure of:
- Mineralisation of osteoid at sites of membranous growth
- Cartilage vascularisation and mineralisation at sites of endochondral ossification
Osteoid and catilage build up at those sites

Histologically:
- Lines of hypertrophic cartilage cells are lenghtened and disorganised
- Ossification at metaphysis is poor
- Persisting osteoid and cartilage -> shaft modelling failure
- Thuckened physes due to normal chondrocyte proliferation but defective removal
Ends of bones enlarge -> club-like thickening of metaphysis + compression of epiphysis
- Most affected:
  - Proximal humerus
  - Distal radius
  - Ulna
  - Ribs
    - Enlargement of costochondral junction - called 'rachitic rosary'

Weight bearing leads to:
- Thickening of the physis and
- Flaring of the excess matrix at the metaphysis
Histological lesions heal whn diet corected
Minor deformities correct but major deformities remain
Occurs after weaning because:
- In utero and in milk - adeqaute nutrients obtained at expense of dam
In Foals
- Rare - long nursing period and relatively slow rate of growth
In Calves and lambs
- When diet deficeint of phosphorus and poor exposure to sunlight
In Puppies, Kittens and Piglets
- Rapid growth, weaned early -> fulminating rickets if poor exposure to sunlight and lack of vitamin D in diet

Osteomalacia

Failure of mineralisation of osteoid / softening of the bones
Active resorption of bone replaced by excess osteoid on trabeculae, endosteum of cortices and Haversian canals
Decreased resistance to tension -> osteoid build-up at tendon insertions
In advanced disease
- Bones break easily and become deformed
- Tendons may separate from bones
Caused by prolonged phosphorus and Vitamin D deficiency
- Vitamin D maintains normal plasma levels of calcium and phosphorus through acting on the intestines, bones and kidneys
In mature animals
Mainly grazing ruminants following gestation and lactation
- Sunlight is important for production of vitamin D in the skin of ruminants
- Vitamin d is also present in sun-dried hay
- Mostly seen where there is long grass growing season with poor sunlight

Hypovitaminosis A

Vitamin A is essential for normal bone growth in foetus and neonates
Hypovitaminosis from dietary deficiency of dam -> teratogenic in pigs and large cats
More commonly, deficiency in neonates (puppies, kittens, calves, piglets) on vitamin-deficient diets
Dietary deficiency -> failure of osteoclastic remodelling resulting in bone overgrowth and nerve compression
Optic nerves particularly affected

Hypervitaminosis A

Hypervitaminosis A (Image sourced from Bristol Biomed Image Archive with permission)

Main lesions:
- Injury to growth cartilage -> premature closure of growth plate
- Osteoporosis
- Exostoses
- Osteophyte formation in prolonged exposure
In cats fed bovine liver for prolonged periods
- Rich in vitamin A in grazing animals
- Vertebrae fuse with each other due to bone proliferation - cervical spondylosis (ankylosing exostosis of the vertebral column), especially in the neck
Can also be teratogenic, especially in pigs (cleft plate and abortions)

Hypervitaminosis D

May be of dietary or iatrogenic origin (has narrow safety margin)
Key features are hypercalcaemia with metastatic calcification of soft tissues
Acute poisoning
- In dogs and cats often from rodenticides containing cholecalciferol
- Grossly:
  - Gastrointestinal haemorrhage
  - Foci of myocardial discoloration
- Microscopically:
  - Mucosal haemorrhage
  - Necrosis of crypts
  - Focal myocardial necrosis
  - Mineralisation of intestinal mucosa, blood vessel walls, lungs and kidneys
Chronic poisoning
- Grossly:
  - Intense osteoclastic activity -> active resorption of bone, especially trabecular
- Microscopically:
  - Excessive production of osteoid - appears both eosinophilic and basophilic in different places
  - Marrow cavity may be obliterated
  - Mineralisation of soft tissues, especially blood vessel walls
- Due to inhibition of Parathyroid Hormone (PTH)|PTH and increase of calcitonin

Fluorine poisoning

F is widespread in nature
Pastures may be contaminated by industrial processes (e.g. brick manufacture)
Acute poisoning:
- Gastroenteritis
- Nephrosis
Chronic poisoning:
- Dental abnormalities
  - Intoxication during teeth development
  - Foci of poor enamel formation - yellow, dark brown/black, chalky
  - Irregular wear of teeth, chip easily
- Osteodystrophy = Fluorosis
  - Generalised skeletal disturbance
  - Most affected are metatarsals and mandibles
  - Periosteal hyperostosis + endosteal bone resorption -> thickened bones with enlarged marrow cavities

Lead poisoning

Lead can bind to mineral portion of bone and cartilage
In young animals ingesting large dose at once
- -> Lead induced malfunction of osteoclasts
- -> Transverse band of increased density on radiographs of metaphysis = "lead line" = growth retardation lattice