Bones Metabolic - Pathology

Pituitary

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

Pituitary dwarfism

• Rare in animals, reported in German Shepherd Dogs
• Deficiency of growth hormone
• Proportionate dwarfism
• Growth plates remain open for up to 4 years
• Disorganised proliferating chondrocytes

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