Metabolic/nutritional bone disease Flashcards
What is the metabolic activity directed towards in normal bone?
Maintenance of ionic equilibria (esp. Ca and PO4)
Repair of damaged structures
Reaction to external stimuli
What is the shapem, structure, and behaviour of bone governed by?
Genetic determinants
Hormonal factors
Mechanical factors
Nutritional factors
Hormonal factors governing bone growth and behaviour
Pituitary (growth hormone)
Thyroid
Gonads (oestrogen)
Adrenal cortex (hyperadrenocorticism)
Effects of growth hormone on bone growth and behaviour
Excess: Gigantisism (acromegaly) (acquired), often a female cat that develops a wider head and large feet
Deficiency: Pituitary dwarfism (congenital)
Effects of thyroid hormone on bone behaviour and growth
Deficiency: failure of growth and variety of skeletal deformities
Excess: osteoporosis secondary to increased metabolic rate
Effect of oestrogen on bone growth and behaviour
Association between hypoestrogenism and osteoporosis in women
Oestrogen is a regulator of bone mass in mature skeleton
Mild osteoporosis occurs in spayed bitches but is not clinically significant
Effects of hyperadrenocorticism on bone growth and behaviour
Can lead to osteoporosis in dogs.
Glucocorticoids also reduce the rate at which bone is formed
Intramembranous osteogenesis
In all bones
mesenchyme -> matrix -> mineralised matrix -> bone
Endochondral ossification
In long bones
Mesenchyme -> chondroblasts -> chondrocytes -> mineralised scaffold -> bone
Woven (trabecular) bone
Haphazardly-arranged fibres
As bone growth occurs at the periosteum - trabecular bone formed first that then becomes compact
Lamellar (compact) bone
Haversian systems with concentric fibres
Endochondral ossification
Chondrocytes proliferate
Then they hypertrophy and lay down some mineral
Then die by apoptosis (and, unusually, swell as do so)
Osteoclasts remove some mineralised areas to allow vascularisation (capillary loops)
Primary trabeculae develop - later remodelled to secondary
Bone modelling
When bone formation and resorption occur on separate surfaces
Bone remodelling
The replacement of old tissue by new. Mainly occurs in the adult skeleton to maintain bone mass.
Bone formation and resorption at the same sites
5 stages of bone remodelling
Activation: pre-osteoclasts differentiate into mature active osteoclasts
Resorption: osteoclasts digest mineral matrix (old bone)
Reversal of signals: end of resorption
Formation: osteoblasts synthesize new bone matrix
Quiescence: osteoblasts become resting bone-lining cells on the newly formed bone surface
Osteodystrophy
A general term for dystrophic growth of bone
Ca/P ratio of bone mineral
1.67 and 1.5
Chief factors affecting osteodystrophies
Calcium, phosphorus, Vitamin D
Times at which osteodystrophies are more prevalent
Young and growing, pregnancy, lactation, egg production
Evidence of disturbance to endochondral ossification
Growth arrest line
Growth retardation lattice
Four main types of nutritional osteodystrophy
Osteoporosis
Osteomalacia
Rickets
Osteodystrophia fibrosa
Osteoporosis
Decreased amounts of bone (but normal composition)
Osteomalacia
Decreased mineralisation of osteoid (softening of bone)
Usually due to failure of mineralisation of matrix
Rickets
Decreased mineralisation of osteoid and cartilage
A disease of growing bones
Osteodystrophia fibrosa
Osteoporosis or osteomalacia plus intertrabecular fibrosis (hyperparathyroidism)
What bones does osteoporosis affect?
Vertebrae
Flat bones
Metaphysis of long bone
Causes of osteoporosis
Malnutrition or simple starvation - often due to calcium deficit, combined with protein/calorie malnutrition
Disuse osteoporosis - following low muscular activity and reduced weight bearing
Senile osteoporosis - due to an increase in the numbers of dead osteocytes
Intestinal parasitism - due to malabsorption in the GI tract
Copper deficiency - due to deficiency of lysyl oxidase activity to cross link collagen and elastin
Clinical presentation of osteomalacia
Slow onset
Shifting lameness
Susceptibility to fractures
Osteophagia may occur (scavenging)
Fertility of affeced animals often depressed
Hypophosphataemia and anaemia are common
Causes of osteomalacia
Deficiency of phosphorus or vitamin D
Need prolonged vitamin D deficiency
Pathology of osteomalacia
Excess deposition of matrix at stress points
Bones break easily, cortex is thin and spongy
Deformities occur
Tendons separate from their attachments
Histology of osteomalacia
Active resorption of bone
Accumulation of excess unmineralised osteoid on trabecular surfaces
Cause of rickets
Dietary insufficiency/imbalance
Calcium, vitamin D, and phosphorus
What is the lesion in rickets?
Failure of mineralisation of (calcification) of bone and cartilage and failure of development of cartilaginous matrix, which then accumulates
Results in failure of vascularisation
Normal remodelling does not occur as the bone is protected from the action of osteoclasts by the unmineralised osteoid
Clinical rickets
Bone cortex is soft - curvature/fractures
Distortion of ribs
At PM bones can be easily cut with a knife
Weakening of osteochondral junction
Irregular overgrowth of cartilage
Enlargement of joints
Normal alignment of teeth often disrupted
Vitamin D refractory rickets
Signs of rickets can occur in the presence of a normal diet and the absence of uraemia (chronic renal failure)
plasma Calcitriol is found to be inappropriately low and there is loss of phosphorus in the urine and poor intestinal absorption.
Inherited X linked dominant condition
Vitamin D dependent rickets
refractory to physiological dose of Vitamin D but responds to pharmacological doses
Underlying metabolic changes in osteodystrophia fibrosa
Extensive osteoclastic resorption of bone and replacement with fibro-osseous tissue
Causes of osteodystrophia fibrosa
Primary hyperparathyroidism due to hyperplasia or neoplasia
Secondary hyperparathyroidism much more common - nutritional or renal in aetiology
Pathology of osteodystrophia fibrosa
Exatensive osteoclastic resorption of bone and replacement with fibro-osseous tissue
Nutritional secondary hyperparathyroidism
Deficiency of Vitamin D/calcium and excess phosphorus
Seen in young fast growing animals
Commonly in puppies - poor bone density, increased fragility, epiphyseal cartilage not affected
Renal secondary hyperparathyroidism
In animals with chronic renal failure
Plasma phosphorus increases, plasma calcium decreases
Stimulates release of PTH
Stimulates bone resoprtion
Clinical signs of bone resorption
Loss of appetite, shifting lameness and anaemia.
The jaws swell, together with the maxilla and this swelling may spread to other bones of head - rubber jaw.
osteodystrophy is, in fact, generalised but it affects bones of skull most severely
Histology of osteodystrophia fibrosa
Bone removed by osteoclasts
replaced by cellular connective tissue - becomes fibrillar with time
Articular cartilage may collapse - leads to DJD
Toxic osteodystrophies
VItamin D poisoning
Vitamin A poisoning
Vitamin D poisoning- lethal dose and toxic dose in dogs
88mg/kg
2-3mg/kg
Acute vitamin D poisoning
Gastric and small intestinal haemorrhages and microscopically focal myocardial necrosis, plus mineralisation of multiple organs
Chronic vitamin D toxicity
Mineralisation is more prominent, occuring on fibroeleastic tissue in many organs
Death usually due to renal failure
Skeletal changes in vitamin D poisoning
Osteosclerosis or rarefaction of bone
Types of lesions caused by vitamin A poisoning
- Cartilage damage
- Osteoporosis
- Exostoses
Characterisation of vitamin A poisoning
Injury to growth cartilage
Osteoporosis
Deveolpment of exostoses or osteophytes
Vitamin A toxicity
Most commonly seen in the cat - usually associated with a high liver diet
Chronic vitamin A poisoning
Deforming cervical spondylosis
Periarticular osteophytes also develop about the proximal joints of forelimb
Vitamin A deficiency
Abnormalities of modelling of membranous bones of skull
Volume of skull and spinal canal too small
Foraminae of spinal nerves too small and compress nerve (in cattle optic foramen affected - blindness, in puppies auditory foramen - deafness)
Osteoclasts are responsive to vitamin A and in its abscence there is inadequate resorption of endosteal bone - excessive deposition of periosteal bone secondary to reduced osteoclastic acitivity
