Biochemistry Flashcards
what is osteoporosis?
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
what is osteopenia?
one mineral density between 1-2.5 SD below mean peak value
when does physiologyic loss of bone density begin?
starts around 30 - slowdown of osteoblastic activity
menopause effect of bone density
loss of protective effects of oestrogen - increase in osteoclastic bone resorption - loss of bone mineral density
types of primary osteoporosis
post-menopausal osteoporosis
osteoporosis of old age
what is post menopausal osteoporosis?
exacerbated loss of bone in the post-menopausal period
what are the risk factors for post-menopausal osteoporosis?
early menopause environmental factors - white caucasian smoking alcohol abuse lack of exercise poor diet
what is the presentation of post-menopausal osteoporosis?
Colles fracture and vertebral insufficiency
what is osteoporosis of old age?
greater decline in bone density than expected
what are the risk factors for osteoporosis of old age?
greater decline in bone density than expected
what are the risk factors for osteoporosis of old age?
early menopause environmental factors -white Caucasian smoking alcohol abuse lack of exercise poor diet chronic disease inactivity reduced sunlight exposure Vitamin D
causes of secondary osteoporosis
corticosteroid use alcohol abuse malnutrition chronic disease - CKD, malignancy, RA endocrine disorders - Cushing's, hyperthyroidism, hyperparathyroidism
how is osteoporosis diagnosed?
DEXA - measure of bone mineral density
compare DEXA with standard peak values for race, sex and age
Serum Ca and P are normal
How is bone mineral density increased?
no treatment to increase bone mineral density
what is the aim of osteoporosis treatment?
slow any further deterioration and decrease risk of subsequent fracture
what are the pharmacological treatments which help prevent fragility in osteoporosis?
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
how to reduce risk of osteoporosis - build up bone mineral density?
exercise
good diet
healthy levels of sunlight
healthy lifestyle
prevention of osteoporosis after menopause?
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
what is osteomalacia?
a qualitative defect = inadequate amounts of calcium and phosphorus - deficient mineralization of osteoid - abnormal softening of bone
what is ricketts
osteomalacia in children
what are the principal causes of osteomalacia?
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)
what are specific causes of osteomalacia?
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
what are the symptoms of osteomalacia?
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)
how is osteomalacia diagnosed?
Abnormal serum bone biochemistry
low Calcium
low serum Phosphate
high serum Alkaline Phosphatase
how is osteomalacia treated?
vitamin D therapy
calcium supplementation
phosphate supplementation
What is hyperparathyroidism?
overactivity of the parathyroid glands high PTH (parathyroidism)
what are the causes of primary hyperparathyroidism?
benign adenoma
hyperplasia
malignant neoplasia (rarely)
what are the signs/ symptoms caused by overproduction of PTH leading to hypercalcaemia?
fatigue depression bone pain myalgia nausea thirst polyuria renal stones osteoporosis
what are the blood results indicative of hyperparathyroidism?
high serum PTH
high calcium
normal/ low phosphate
what is secondary hyperparathyroidism?
physiological overproduction of PTH secondary to hypopcalcaemia
vitamin D deficiency
CKD
what is tertiary hyperparathyroidism?
chronic secondary hyperparathyroidism (usually chronic kidney disease)
adenoma which continues to produce PTH despite biochemical correction
what are the symptoms of hyperparathyroism?
fragility fractures
lytic lesions in bone = brown tumours/ osteitis fibrosa cystica
need skeletal stabilization
what is the treatment of hyperparathyroidism?
removal of the adenomatous gland (if applicable)
treat underlying cause e.g. vitamin D supplementation
very high calcium levels: emergency
- IV fluids
- bisphosphates
- calcitonin
why does renal dystrophy cause bone changes?
chronic kidney disease causes typical bone changes because there is
reduced phosphate excretion
inactivation of vitamin D
what are the changes that renal dystrophy can cause?
secondary hyperparathyroidism (subsequent)
osteomalacia
sclerosis of bone
calcification of soft tissues
What is Paget’s disease?
a chronic disorder which results in thickened, brittle and mis-shapen bones
typically 1 or a few bones
who gets Paget’s disease?
4% of > 55yrs
10% of > 80s
what causes Paget’s disease?
viral infection - paramyxoviruses
genetic defects
what is the pathophysiology of Paget’s disease?
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
what are the bones commonly affected by Paget’s disease?
pelvis femur skull tibia ear ossicles (deafness)
what are the symptoms of Paget’s disease?
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)
How is Paget’s disease diagnosed?
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
how is Paget’s disease treated?
Bisphosphates - inhibit osteoclasts
calcitonin - if extensive lytic disease
joint replacement may be necessary
pathological femoral fractures - stabilized with long intramedullary nails/ plates
