Metabolic/nutritional bone disease

Question 1

What is the metabolic activity directed towards in normal bone?

Answer 1

Maintenance of ionic equilibria (esp. Ca and PO4)

Repair of damaged structures

Reaction to external stimuli

Question 2

What is the shapem, structure, and behaviour of bone governed by?

Answer 2

Genetic determinants
Hormonal factors
Mechanical factors
Nutritional factors

Question 3

Hormonal factors governing bone growth and behaviour

Answer 3

Pituitary (growth hormone)
Thyroid
Gonads (oestrogen)
Adrenal cortex (hyperadrenocorticism)

Question 4

Effects of growth hormone on bone growth and behaviour

Answer 4

Excess: Gigantisism (acromegaly) (acquired), often a female cat that develops a wider head and large feet

Deficiency: Pituitary dwarfism (congenital)

Question 5

Effects of thyroid hormone on bone behaviour and growth

Answer 5

Deficiency: failure of growth and variety of skeletal deformities

Excess: osteoporosis secondary to increased metabolic rate

Question 6

Effect of oestrogen on bone growth and behaviour

Answer 6

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

Question 7

Effects of hyperadrenocorticism on bone growth and behaviour

Answer 7

Can lead to osteoporosis in dogs.

Glucocorticoids also reduce the rate at which bone is formed

Question 8

Intramembranous osteogenesis

Answer 8

In all bones

mesenchyme -> matrix -> mineralised matrix -> bone

Question 9

Endochondral ossification

Answer 9

In long bones

Mesenchyme -> chondroblasts -> chondrocytes -> mineralised scaffold -> bone

Question 10

Woven (trabecular) bone

Answer 10

Haphazardly-arranged fibres

As bone growth occurs at the periosteum - trabecular bone formed first that then becomes compact

Question 11

Lamellar (compact) bone

Answer 11

Haversian systems with concentric fibres

Question 12

Endochondral ossification

Answer 12

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

Question 13

Bone modelling

Answer 13

When bone formation and resorption occur on separate surfaces

Question 14

Bone remodelling

Answer 14

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

Question 15

5 stages of bone remodelling

Answer 15

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

Question 16

Osteodystrophy

Answer 16

A general term for dystrophic growth of bone

Question 17

Ca/P ratio of bone mineral

Answer 17

1.67 and 1.5

Question 18

Chief factors affecting osteodystrophies

Answer 18

Calcium, phosphorus, Vitamin D

Question 19

Times at which osteodystrophies are more prevalent

Answer 19

Young and growing, pregnancy, lactation, egg production

Question 20

Evidence of disturbance to endochondral ossification

Answer 20

Growth arrest line
Growth retardation lattice

Question 21

Four main types of nutritional osteodystrophy

Answer 21

Osteoporosis
Osteomalacia
Rickets
Osteodystrophia fibrosa

Question 22

Osteoporosis

Answer 22

Decreased amounts of bone (but normal composition)

Question 23

Osteomalacia

Answer 23

Decreased mineralisation of osteoid (softening of bone)

Usually due to failure of mineralisation of matrix

Question 24

Rickets

Answer 24

Decreased mineralisation of osteoid and cartilage

A disease of growing bones

Question 25

Osteodystrophia fibrosa

Answer 25

Osteoporosis or osteomalacia plus intertrabecular fibrosis (hyperparathyroidism)

Question 26

What bones does osteoporosis affect?

Answer 26

Vertebrae Flat bones Metaphysis of long bone

Question 27

Causes of osteoporosis

Answer 27

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

Question 28

Clinical presentation of osteomalacia

Answer 28

Slow onset Shifting lameness Susceptibility to fractures Osteophagia may occur (scavenging) Fertility of affeced animals often depressed Hypophosphataemia and anaemia are common

Question 29

Causes of osteomalacia

Answer 29

Deficiency of phosphorus or vitamin D Need prolonged vitamin D deficiency

Question 30

Pathology of osteomalacia

Answer 30

Excess deposition of matrix at stress points Bones break easily, cortex is thin and spongy Deformities occur Tendons separate from their attachments

Question 31

Histology of osteomalacia

Answer 31

Active resorption of bone Accumulation of excess unmineralised osteoid on trabecular surfaces

Question 32

Cause of rickets

Answer 32

Dietary insufficiency/imbalance Calcium, vitamin D, and phosphorus

Question 33

What is the lesion in rickets?

Answer 33

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

Question 34

Clinical rickets

Answer 34

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

Question 35

Vitamin D refractory rickets

Answer 35

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

Question 36

Vitamin D dependent rickets

Answer 36

refractory to physiological dose of Vitamin D but responds to pharmacological doses

Question 37

Underlying metabolic changes in osteodystrophia fibrosa

Answer 37

Extensive osteoclastic resorption of bone and replacement with fibro-osseous tissue

Question 38

Causes of osteodystrophia fibrosa

Answer 38

Primary hyperparathyroidism due to hyperplasia or neoplasia Secondary hyperparathyroidism much more common - nutritional or renal in aetiology

Question 39

Pathology of osteodystrophia fibrosa

Answer 39

Exatensive osteoclastic resorption of bone and replacement with fibro-osseous tissue

Question 40

Nutritional secondary hyperparathyroidism

Answer 40

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

Question 41

Renal secondary hyperparathyroidism

Answer 41

In animals with chronic renal failure Plasma phosphorus increases, plasma calcium decreases Stimulates release of PTH Stimulates bone resoprtion

Question 42

Clinical signs of bone resorption

Answer 42

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

Question 43

Histology of osteodystrophia fibrosa

Answer 43

Bone removed by osteoclasts replaced by cellular connective tissue - becomes fibrillar with time Articular cartilage may collapse - leads to DJD

Question 44

Toxic osteodystrophies

Answer 44

VItamin D poisoning Vitamin A poisoning

Question 45

Vitamin D poisoning- lethal dose and toxic dose in dogs

Answer 45

88mg/kg 2-3mg/kg

Question 46

Acute vitamin D poisoning

Answer 46

Gastric and small intestinal haemorrhages and microscopically focal myocardial necrosis, plus mineralisation of multiple organs

Question 47

Chronic vitamin D toxicity

Answer 47

Mineralisation is more prominent, occuring on fibroeleastic tissue in many organs Death usually due to renal failure

Question 48

Skeletal changes in vitamin D poisoning

Answer 48

Osteosclerosis or rarefaction of bone

Question 49

Types of lesions caused by vitamin A poisoning

Answer 49

1. Cartilage damage 2. Osteoporosis 3. Exostoses

Question 50

Characterisation of vitamin A poisoning

Answer 50

Injury to growth cartilage Osteoporosis Deveolpment of exostoses or osteophytes

Question 51

Vitamin A toxicity

Answer 51

Most commonly seen in the cat - usually associated with a high liver diet

Question 52

Chronic vitamin A poisoning

Answer 52

Deforming cervical spondylosis Periarticular osteophytes also develop about the proximal joints of forelimb

Question 53

Vitamin A deficiency

Answer 53

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