CORTEXT 1 - Basic Sciences BIOCHEM

Question 1

Define Osteoporosis clinically, and the WHO definition

Answer 1

Quantitive defect of bone - reduced bone density and increased porosity, leading to increased fragility and increased fracture risk

WHO - bone mineral density less than 2.5 standard deviations below the mean peak value of young adults of the same race and sex.

Question 2

What is Osteopenia?

Answer 2

an intermediate stage where bone mineral density is between 1 and 2.5 SD below mean peak.

Question 3

What mechanism causes the physiological loss of bone mineral density?

Answer 3

Gradual slow down in osteoblastic activity (after aged 30)

Question 4

What are the two types of primary osteoporosis?

Answer 4

Type 1 Post Menopausal

Type 2 Osteoporosis of old age with a greater than expected decline

Question 5

What are the risk factors for both types of primary osteoporosis?

Answer 5

Smoking
Alcohol
Poor diet
Lack of Exercise

Type 1 specific - early menopause, familial and environmental factors, white caucasians

Type 2 specific - chronic disease, reduced sunlight exposure.

Question 6

What type of fractures commonly occur in the two different types of osteoporosis?

Answer 6

Type 1 - Colles, Vertebral insufficiency

Type 2 - Femoral neck, Vertebral

Question 7

What conditions may secondary osteoporosis occur following?

Answer 7

Corticosteroid use
Alcohol Abuse
Malnutrition
Chronic disease including CKD, malignancy, RA
Endocrine disorders including Cushing’s, Hyperthyroidism, Hyperparathyroidism

Question 8

How is Osteoporosis Diagnosed?

Answer 8

DEXA scanning to measure bone mineral density, compare with standard peak values

NB - Serum calcium and phosphate are normal

Question 9

What is the treatments for Osteoporosis?

Answer 9

Prevention by building bone density when younger
Calcium and Vit D Supplementation
Biphosphonates (alendronate, risendronate, etidronate) for reducing osteoclastic resorption
Desunomab (monoclonal AB) to reduce osteoclast activity
Strontium (increase osteoblast replication)
Can give Zoledronic Acid once yearly IV biphosphonate, but this is expensive
HRT or Raloxifene can be used is SEs with other medications

NB - treatment aims to slow progression, not build bone mineral density

Question 10

What is Osteomalacia?

Answer 10

Qualitative defect of bone with abnormal softening due to deficiency of mineralisation of osteoid, secondary to inadequate calcium and phosphorus

Rickets = osteomalacia in children, subsequent effects of growing skeleton

Question 11

Causes of Osteomalacia

Answer 11

Insufficient calcium absorption from the intestine due to lack of dietary calcium, or a deficiency/resistance of vitamin D

Phosphate insufficiency due to increase renal losses

Malnutrition 
Malabsorption 
Lack of sunlight 
Hypophosphataemia 
Long term anticonvulsant use 
CKD 
Inherited renal disorders

Question 12

How does Osteomalacia present?

Answer 12

Bone pain (pevis, spine, femora)
Deformities (e.g. rickets)
Easily sustain pathological fractures
Symptoms of hypocalcaemia – paraesthesiae, muscle cramps, irritability, fatigue, seizures, brittle nails

Question 13

What can be seen upon clinical investigation for Osteomalacia?

Answer 13

Radiographs may show peusdofractures (Looser’s zones) of pubic rami, proximal femora, ulna and ribs

Serum biochemistry is abnormal - low calcium, low serum phosphate, high serum alkaline phosphatase

Question 14

Treatment of Osteomalacia?

Answer 14

Vitamin D therapy with calcium and phosphate supplementation

Question 15

What is Hyperparathyroidism?

Answer 15

Overactivity or the parathyroid glands, with high level of PTH

Question 16

What causes the three types of hyperparathyroidism?

Answer 16

Primary - benign adenoma, hyperplasia, malignant neoplasia
Secondary - physiological overproduction due to hypocalcaemia due to vit D deficiency or CKD
Tertiary - chronic secondary + adenoma

Question 17

What are the symptoms of Hyperparathyroidism?

Answer 17

fatigue 
depression 
bone pain 
myalgia 
nausea 
thirst 
polyuria 
renal stones 
osteoporosis

NB - symptoms are of hypercalcaemia due to overproduction of PTH

Question 18

What is Renal Dystrophy?

Answer 18

Bone changes due to CKD

Reduced phosphate excretion and inactive activation of vit D -> secondary hyperparathyroidism -> osteomalacia, sclerosis of bone, calcification of soft tissues

Question 19

What is Paget’s Disease?

Answer 19

Thickened, brittle misshapen bones due to increased osteoclast and osteoblast activity

Question 20

What are causes of Paget’s?

Answer 20

Genetic defects 
Viral infection (paramyxoviruses)

Question 21

What are the most commonly affected areas in Paget’s?

Answer 21

Pelvis 
Femur
Skull 
Tibia 
Ear Ossicles (conductive deafness)

Question 22

How does Paget’s Disease present?

Answer 22

Incidental finding @ XR 
Arthritis 
Pathological fracture 
Deformity 
Pain 
High output cardiac failure

Question 23

Ix findings for Paget’s Disease

Answer 23

Serum alkaline phosphatase raised
Calcium and phosphorus normal

Radiology - enlarged bone, thickened cortices, coarse trabeculae, mixed areas of lysis and sclerosis
Bone scan - marked increase uptake in affected bone

Question 24

Treatment of Paget’s Disease?

Answer 24

Biphosphonates (inhibit osteoclasts)
Calcitonin if lytic disease

Joint replacement may be required
Fractures stabilised with long intramedullary nails/plates