Biochemistry

Question 1

what is osteoporosis?

Answer 1

a quantitative defect = reduced bone mineral density and increased porosity
it results in fragility and increased fracture risk (little/no trauma)

bone mineral density less than 2.5 SD below the mean peak value of young adults of the same race and sex

Question 2

what is osteopenia?

Answer 2

one mineral density between 1-2.5 SD below mean peak value

Question 3

when does physiologyic loss of bone density begin?

Answer 3

starts around 30 - slowdown of osteoblastic activity

Question 4

menopause effect of bone density

Answer 4

loss of protective effects of oestrogen - increase in osteoclastic bone resorption - loss of bone mineral density

Question 5

types of primary osteoporosis

Answer 5

post-menopausal osteoporosis

osteoporosis of old age

Question 6

what is post menopausal osteoporosis?

Answer 6

exacerbated loss of bone in the post-menopausal period

Question 7

what are the risk factors for post-menopausal osteoporosis?

Answer 7

early menopause
environmental factors - white caucasian 
smoking 
alcohol abuse 
lack of exercise 
poor diet

Question 8

what is the presentation of post-menopausal osteoporosis?

Answer 8

Colles fracture and vertebral insufficiency

Question 9

what is osteoporosis of old age?

Answer 9

greater decline in bone density than expected

Question 10

what are the risk factors for osteoporosis of old age?

Answer 10

greater decline in bone density than expected

Question 11

what are the risk factors for osteoporosis of old age?

Answer 11

early menopause 
environmental factors -white Caucasian 
smoking 
alcohol abuse 
lack of exercise 
poor diet 
chronic disease
inactivity 
reduced sunlight exposure Vitamin D

Question 12

causes of secondary osteoporosis

Answer 12

corticosteroid use 
alcohol abuse 
malnutrition 
chronic disease - CKD, malignancy, RA
endocrine disorders - Cushing's, hyperthyroidism, hyperparathyroidism

Question 13

how is osteoporosis diagnosed?

Answer 13

DEXA - measure of bone mineral density
compare DEXA with standard peak values for race, sex and age
Serum Ca and P are normal

Question 14

How is bone mineral density increased?

Answer 14

no treatment to increase bone mineral density

Question 15

what is the aim of osteoporosis treatment?

Answer 15

slow any further deterioration and decrease risk of subsequent fracture

Question 16

what are the pharmacological treatments which help prevent fragility in osteoporosis?

Answer 16

Calcium and vitamin D supplements
Bisphosphonates: reduce osteoclastic resorption
o alendronate - oral
o risedronate - oral
o etidronate – oral
o oral bisphosphonates have greatest evidence for efficacy, cost-effectiveness, and low side effect profile
o zoledronic acid – 1/year IV, more expensive than oral forms
Desunomab: monoclonal antibody which reduces osteoclast activity
Strontium: increase osteoblast replication & reduce resorption

Question 17

how to reduce risk of osteoporosis - build up bone mineral density?

Answer 17

exercise
good diet
healthy levels of sunlight
healthy lifestyle

Question 18

prevention of osteoporosis after menopause?

Answer 18

HRT not 1st line
can be considered if side effects with other medications occur
risks:
o breast cancer
o endometrial cancer
o DVT
raloxifene (oestrogen receptor modulator) can also be considered – risk of DVT

Question 19

what is osteomalacia?

Answer 19

a qualitative defect = inadequate amounts of calcium and phosphorus - deficient mineralization of osteoid - abnormal softening of bone

Question 20

what is ricketts

Answer 20

osteomalacia in children

Question 21

what are the principal causes of osteomalacia?

Answer 21

insufficient Ca absorption from intestine - lack of dietary Calcium 
deficiency of Vitamin D action 
resistance to the action of vitamin D 
phosphate deficiency (increased renal losses)

Question 22

what are specific causes of osteomalacia?

Answer 22

malnutrition (Ca & Vit D)
malabsorption (low Vit D absorption)
lack of sunlight exposure (no activation of Vit D)
hyophosphateamia 
o re-feeding syndrome
o alcohol abuse
 - impairs phosphate absorption
 - malabsorption
 - renal tubular acidosis
long term anticonvulsant use
chronic kidney disease: 
o reduced phosphate resorption
o failure of Vitamin D activation 
inherited renal disorders
o X-linked hypophosphataemia
o vitamin D resistant rickets

Question 23

what are the symptoms of osteomalacia?

Answer 23

Bone pain: pelvis, spine, femur
Deformities from soft bones (rickets)
Pathological fractures
Hypocalcaemia: paraesthesia, muscle cramps, irritability, fatigue, seizure, brittle nails
Radiographs: pseudofractures – Looser’s zones (pubic rami, proximal femur, ulna, ribs)

Question 24

how is osteomalacia diagnosed?

Answer 24

Abnormal serum bone biochemistry
low Calcium
low serum Phosphate
high serum Alkaline Phosphatase

Question 25

how is osteomalacia treated?

Answer 25

vitamin D therapy calcium supplementation phosphate supplementation

Question 26

What is hyperparathyroidism?

Answer 26

``` overactivity of the parathyroid glands high PTH (parathyroidism) ```

Question 27

what are the causes of primary hyperparathyroidism?

Answer 27

benign adenoma hyperplasia malignant neoplasia (rarely)

Question 28

what are the signs/ symptoms caused by overproduction of PTH leading to hypercalcaemia?

Answer 28

``` fatigue depression bone pain myalgia nausea thirst polyuria renal stones osteoporosis ```

Question 29

what are the blood results indicative of hyperparathyroidism?

Answer 29

high serum PTH high calcium normal/ low phosphate

Question 30

what is secondary hyperparathyroidism?

Answer 30

physiological overproduction of PTH secondary to hypopcalcaemia vitamin D deficiency CKD

Question 31

what is tertiary hyperparathyroidism?

Answer 31

chronic secondary hyperparathyroidism (usually chronic kidney disease) adenoma which continues to produce PTH despite biochemical correction

Question 32

what are the symptoms of hyperparathyroism?

Answer 32

fragility fractures lytic lesions in bone = brown tumours/ osteitis fibrosa cystica need skeletal stabilization

Question 33

what is the treatment of hyperparathyroidism?

Answer 33

removal of the adenomatous gland (if applicable) treat underlying cause e.g. vitamin D supplementation very high calcium levels: emergency - IV fluids - bisphosphates - calcitonin

Question 34

why does renal dystrophy cause bone changes?

Answer 34

chronic kidney disease causes typical bone changes because there is reduced phosphate excretion inactivation of vitamin D

Question 35

what are the changes that renal dystrophy can cause?

Answer 35

secondary hyperparathyroidism (subsequent) osteomalacia sclerosis of bone calcification of soft tissues

Question 36

What is Paget's disease?

Answer 36

a chronic disorder which results in thickened, brittle and mis-shapen bones typically 1 or a few bones

Question 37

who gets Paget's disease?

Answer 37

4% of > 55yrs | 10% of > 80s

Question 38

what causes Paget's disease?

Answer 38

viral infection - paramyxoviruses | genetic defects

Question 39

what is the pathophysiology of Paget's disease?

Answer 39

``` increased osteoclast activity (maybe exaggerated response to vit D) increased bone turnover osteoblasts become more active to correct excessive bone resorption new bone fails to remodel sufficiently resulting bone - increased thickness and bone density - brittle - fractures easily ```

Question 40

what are the bones commonly affected by Paget's disease?

Answer 40

``` pelvis femur skull tibia ear ossicles (deafness) ```

Question 41

what are the symptoms of Paget's disease?

Answer 41

can be asymptomatic - incidental Xray finding Arthritis - if close to joint pathologic fractures deformity pain high output cardiac failure (increased blood flow through pagetic bone)

Question 42

How is Paget's disease diagnosed?

Answer 42

``` Serum Alkaline Phosphatase is raised Calcium & Phosphorus normal Radiograph: - affected bone enlarged - thickened cortices - coarse, thickened trabeculae - mixed areas of lysis & sclerosis Bone scans: marked increased uptake in affected bones ```

Question 43

how is Paget's disease treated?

Answer 43

Bisphosphates - inhibit osteoclasts calcitonin - if extensive lytic disease joint replacement may be necessary pathological femoral fractures - stabilized with long intramedullary nails/ plates