biochem cortex

Question 1

what is osteoporosis in general terms?

Answer 1

is a quantitative defect of bone characterised by reduced bone mineral density and increased porosity (i.e. the bone is of normal quality, there is just not enough of it). WHO defines osteoporosis as 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

is an intermediate stage where bone mineral density is between 1 to 2.5 standard deviations below mean peak value.

Question 3

what does osteoporosis cause?

Answer 3

leads to fragility of the bone and increased fracture risk with fractures occurring after little or no trauma.

Question 4

is loss of bone mineral density a normal physiological phenomenon ?

Answer 4

yes - usually occurs around the age of 30 due to a very gradual slow down in osteoblastic activity

Question 5

who tends to lose more bone density - males or females and why?

Answer 5

females due to after the menopause there is an increase in osteoclastic bone resorption with the loss of protective effects of oestrogen.

Question 6

there is 2 types of primary osteoporosis - describe type 1 and what are the further risk factors predisposing for type 1

Answer 6

Known as Post‐Menopausal Osteoporosis with an exacerbated loss of bone in the post‐menopausal period.Further risk factors include smoking, alcohol abuse, lack of exercise and poor diet.

Question 7

what type of fractures tend to occur in type 1 osteoporosis ?

Answer 7

colles fractures (a fracture of the radius in the wrist, with a characteristic backward displacement of the hand.) and vertebral insufficiency fractures.

Question 8

what is type 2 osteoporosis ? and what are the risk factors which predispose people to it?

Answer 8

known as Osteoporosis of old age with a greater decline in bone mineral density than expected.Risk factors are similar with the added risks of chronic disease, inactivity and reduced sunlight exposure (Vitamin D).

Question 9

what fractures are commonly seen in type 2 osteoporosis ?

Answer 9

Femoral neck fractures and vertebral fractures predominate in this group

Question 10

what can osteoporosis occur secondary to ?

Answer 10

conditions including corticosteroid use, alcohol abuse, malnutrition, chronic disease (CKD, malignancy, Rheumatoid arthritis) and endocrine disorders (Cushing’s, Hyperthyroidism, Hyperparathyroidism).

Question 11

how is osteoporosis diagnosed ?

Answer 11

DEXA scanning which measures bone mineral density - values are then compared to standard peak values for race and sex

Question 12

Are serum calcium and phosphate levels normal in osteoporosis ?

Answer 12

Yes the are normal

Question 13

what is the aim of treatments in osteoporosis ?

Answer 13

they cannot increase bone mineral density so the aim of them is to slow down the decrease in bone mineral density.

Question 14

Describe the first-line treatment of osteoporosis

Answer 14

• Biposphonates - alendronic acid, risedonate sodium, ibrandronic acid, zoledronic acid
• plus - Calcium and vit D supplementation - ergocalciferol and calcium

Question 15

If side effects occur with the standard treatments used for osteoporosis what could be used ?

Answer 15

HRT could be used but there is an increased risk of cancers and DVT’s. Raloxifene (an oestrogen receptor modulator) could be used as another option but again there is a risk of DVT’s.

Raloxifene or denosumab (HRT)

Question 16

what is osteomalacia ?

Answer 16

It is a defect of bone with abnormal softening of the bone due to deficient mineralization of osteoid (immature bone) secondary to inadequate amounts of calcium and phosphorus.

Question 17

what is ricketts?

Answer 17

it is the same as osteomalacia but occurs in young children and subsequently has effects on the growing skeleton

Question 18

what is the underlying causes of osteomalacia and ricketts?

Answer 18

insufficient calcium absorption from the intestine because of lack of dietary calciumor a deficiency or resistance to the action of vitamin D or phosphate deficiency caused by increased renal losses.

Question 19

what are some of the causes of osteomalacia and ricketts?

Answer 19

malnutrition (Ca & vit D)malabsorption (low vit D absorption)lack of sunlight exposure (no activation vit D)hypophosphateamia (re‐feeding syndrome, alcohol abuse – impairs phosphate absorption, malabsorption, renal tubular acidosis)long term anticonvulsant use and chronic kidney disease (reduced phosphate resorption & failure of activation vitamin D).

Question 20

what are the signs and symptoms of osteomalacia and ricketts?

Answer 20

Patients may complain of bone pain, have deformities from soft bones (particularly rickets), sustain pathological fractures easily and have symptoms of hypocalcaemia (paraesthesiae, muscle cramps, irritability, fatigue, seizures, brittle nails).

Question 21

what may radiographs show for patients with ricketts and osteomalacia ?

Answer 21

pseudofractures (aka Looser’s zones)

Question 22

what is the difference in bone biochemistry when comparing osteoporosis to ricketts and osteomalcia ?

Answer 22

serum bone biochemistry is abnormal with typically a low calcium, low serum phosphate and high serum alkaline phosphatase - for osteomalacia and ricketts wheres its normal for osteoporosis.

Question 23

What is the treatment of osteomalacia and ricketts ?

Answer 23

Treatment involves vitamin D therapy (erogcalciferol or colecalciferol) with calcium and phosphate supplementation.

Question 24

what is hyperparathyroidism?

Answer 24

it is overactivity of the parathyroid gland with high levels of PTH

Question 25

what can hyperparathyroidism cause ?

Answer 25

can result in fragility fractures and can also cause lytic lesions in bone (known as Brown Tumours or osteitis fibrosa cystica) which may need skeletal stabilization.

Question 26

describe renal dystrophy

Answer 26

This describes the typical bone changes due to CKD. Reduced phosphate excretion and inactive activation of vitamin D results in secondary hyperparathyroidism with subsequent osteomalacia, sclerosis of bone and calcification of soft tissues.

Question 27

what is pagets disease ?

Answer 27

A chronic disorder which results in thickened, brittle and mis‐shapen bones.

Question 28

Describe the pathology of pagets disease

Answer 28

* Increased osteoclast activity (possibly due to an exaggerated response to vitamin D) results in increased bone turnover. Osteoblasts become more active to try to correct excessive bone resorption. * The osteoblasts form new bone however the new bone fails to remodel sufficiently and the resulting bone despite its increased thickness and bone density is brittle and can fracture easily.

Question 29

what factors predispose to pagets disease ?

Answer 29

Viral infection (paramyxoviruses) and genetic defects

Question 30

what are the commonly affected areas by pagets disease ?

Answer 30

Bones commonly affected include the pelvis, femur, skull, tibia and sometimes the ear ossicles (resulting in conductive deafness).

Question 31

what are some of the symptoms of pagets disease ?

Answer 31

It can also cause arthritis (if close to the joint), pathologic fractures, deformity, pain and high output cardiac failure (due to increased blood flow through pagetic bone).

Question 32

what are the changes in mineral levels due to pagets disease ?

Answer 32

Serum alkaline phosphatase is raised whilst calcium and phosphorus are usually normal.

Question 33

what are the radiological features of pagets disease ?

Answer 33

demonstrate that the affected bone is enlarged with thickened cortices and coarse, thickened trabeculae with mixed areas of lysis and sclerosis.

Question 34

What is the treatment of pagets disease ?

Answer 34

* 1st line: bisphosphonate * adjunct: calcium and vitamin D supplementation * plus: supportive therapies * 2nd line: calcitonin * adjunct: calcium and vitamin D supplementation * plus: supportive therapies