Biochemical Disorders of Bone Flashcards
What is osteoporosis
A quantitative defect of bone, where there is reduced bone density and increased porosity i.e. quality is normal there just isn’t enough of it
WHO definition of osteoporosis
bone mineral density <2.5 standard deviations below the mean peak value of young adults of the same race and sex
WHO definition of osteopenia
An intermediate stage where bone density between 1 - 2.5 standard deviations below mean peak value.
Around what age does loss of mineral bone density start to occur and how does it happen
age 30
gradual decrease in osteoblastic activity
Why do females tend to lose more bone density after the menopause
Increase in osteoclastic bone resorption and loss of the protective effects of oestrogen
Types of primary osteoporosis
- Post-menopausal
2. Osteoporosis of old age with a greater decline in bone density than expected
Risk factors for type 1 osteoporosis
smoking
lack of exercise
poor diet
alcohol abuse
Most common fractures in Type 1 osteoporosis
Colles #
Vertebral insufficiency #
Risk factors for Type 2 osteoporosis
lack of sunlight
chronic disease
inactivity
Most common # in Type 2 osteoporosis
femoral neck #
vertebral #
Conditions causing secondary osteoporosis
Corticosteroid abuse Alcohol abuse Malnutrition Chronic disease (malignancy, CKD, RA) Endocrine disorders (Cushings, hyperthyroidism, hyperparathyroidism)
Dx of osteoporosis
DEXA scanning - provides a measure of bone density to allow comparison to mean values
What is the treatment aim for osteoporosis
Slowing down further loss of bone density - there are no treatments that can increase bone density!
Pharmacological measures to prevent fragility fractures in osteoporosis
Calcium and Vit D supplements - if dietary intake poor
Bisphosphonates (alendronate, risedronate, etidronate)
Desunomab (monoclonal Ab that reduces osteoclast activity)
Strontium (increases osteoblast replication)
Zoledronic acid (once yearly IV bisphosphonate)
Which treatment is not recommended as first line for the prevention of osteoporosis after the menopause?
HRT - increased risk of breast and endometrial Ca and increased risk of DVT.
When can HRT be considered for prevention of osteoporosis?
If side effects with other medications occurs
Which medication is considered first line for Tx of osteoporosis
Oral bisphosphonates
- cheap, effective, low s/e profile
What is osteomalacia
A qualitative effect of bone where it is abnormally soft due to defective mineralisation due to inadequate calcium and phosphorus
What is Rickett’s disease
the same as osteomalacia, but in children
Causes of Osteomalacia
- insufficient calcium absorption in the small intestine (either because there isn’t enough in the diet, or resistance to the action of Vitamin D)
- malnutrition
- lack of sunlight exposure - phosphate deficiency from increased renal losses
- re-feeding syndrome
- alcohol abuse (cause renal tubular acidosis)
- CKD
- long term anticonvulsant use
Presentation of osteomalacia
bone pain
bone deformities
pathological fractures
symptoms of hypocalcaemia (paraesthesia, muscle cramps, irritability, fatigue, seizures, brittle nails)
Bone chemistry in osteoporosis
Normal calcium and phosphate
Bone chemistry in osteomalacia
low calcium
low phosphate
high alk phos
Tx of osteomalacia
Vit D therapy
calcium and phosphate supplements
what is hyperparathyroidism
Overactivity of the parathyroid gland with high levels of parathyroid hormone
Causes of primary hyperparathyroidism
Benign adenoma
Parathyroid hyperplasia
Malignant neoplasia (rare)
Consequences of raised PTH
there will be increased resorption of calcium from bone and raised ca reabsorption from the kidneys - therefore increased serum Ca
symptoms of hypercalcaemia
fatigue depression bone pain myalgia nausea thirst polyuria renal stones osteoporosis
biochemistry in primary hyperparathyroidism
raised PTH
raised Ca
low or normal phosphate
What is secondary hyperparathyroidism
physiological overproduction of PTH in response to a low Ca
Causes of secondary hyperparathyroidism
Vit D deficiency
CKD
What is renal dystrophy
typical bone changes due to CKD
- reduced phosphate excretion and inactivation of Vitamin D, resulting in secondary hyperparathyroidism
How is phosphate excreted from the body
kidneys
What is Paget’s disease of bone
A chronic disorder resulting in thickened, brittle and mis-shapen bones.
Pathophysiology of Paget’s
There is increased osteoclastic activity that results in increased bone turnover. Osteoblasts then become more active to try to compensate. The osteoblasts form new bone but it cannot remodel sufficiently. So it is thicker but still brittle.
Presentation of Paget’s disease
Can be Asymptomatic
Arthritis (if close to the joint)
Pathological fractures
High output cardiac failure - due to increased blood flow through pagetic bone)
Conductive deafness - Pagets can affect the ear ossicles
Biochemistry in Paget’s disease
Raised Alk Phos
Normal calcium
Normal phosphate
Tx of Paget’s
Bisphosphonates (inhibit osteoclasts)
Calcitonin - if excessive lytic disease
Joint replacement
Only biochemical abnormality in Pagets
Raised Alk Phos!!!
Examples of bisphosphonates
alendronic acid
risendronate
zolendronate
most common locations for Paget’s disease
predominately affects central bones
- pelvis
- femur
- skull
- tibia
- ear
How are patients advised to take oral bisphosphonates, and why
take at least 30 minutes before breakfast with plenty of water + sit upright for 30 minutes following
?bisphosphonates cause a variety of oesophageal problems
