Biochemical Disorders of Bone Flashcards
Osteoporosis is a ______________ defect of bone
Quantitative
How is osteoporosis defined?
- Reduced bone mineral density
- Increased bone porosity
(i.e. the bone is of normal quality, there is just less of it)
Osteoporosis can lead to what?
Fragility of bone and increased fracture risk
What is the term given to the intermediate stage on the progression to osteoporosis?
Osteopenia
(bone mineral density is lower than normal but not enough to be classified as osteoporosis)
Loss of bone mineral density is a ___________ process which generally begins to occur after the age of __
Normal
30
Which sex is affected more by osteoporosis and why?
Females
There is an increased osteoclastic response after the menopause as oestrogen is reduced and no longer provides a protective effect
How many types of primary osteoporosis exist?
2
What is type 1 osteoporosis?
Post-menopausal osteoporosis
Why does post-menopausal osteoporosis occur?
There is an increased osteoclastic response due to reduced oestrogen which usually counteracts this response
What are the risk factors for type 1 osteoporosis?
- Early menopause
- Genetics
- Alcohol abuse
- White caucasian
- Smoking
- Lack of exercise
- Poor diet
Which type of fractures are associated with type 1 osteoporosis?
- Colles’ fractures
- Vertebral insufficiency fractures
What is a Colles’ fracture?
A fracture involving the distal radius, where the fractures bone is bent backwards
This is associated with causing carpa tunnel syndrome by compressing the tunnel
What is type 2 osteoporosis?
Osteoporosis of old age
What are the risk factors for type 2 osteoporosis?
- Female gender
- Genetics
- White caucasians
- Smoking
- Alcohol abuse
- Lack of exercise
- Poor diet
- Chronic disease
- Reduced sunlight exposure (low vitamin D)
Which type of fractures are most common in type 2 osteoporosis?
- Femoral neck fractures
- Vertebral fractures
Osteoporosis can occur secondary to which other conditions?
- Corticosteroid use
- Alcohol abuse
- Malnutrition
- Chronic disease (CKD, malignancy, RA)
- Endocrine disorders (Cushing’s, hyperthyroidism, hyperparathyroidism)
How is osteoporosis diagnosed?
DEXA bone scan
Serum calcium and phosphate are __________ in osteoporosis
Normal
What are the aims of treatments for osteoporosis?
To reduce disease progression
What are the possible pharmacological treatments for osteoporosis?
- Calcium supplements
- Vitamin D supplements
- Bisphosphonates
- Desunomab
- Strontium
- Zoledronic acid
- Intranasal calcitonin
- Raloxifene
- Hormone replacement therapy
Give three examples of bisphosphonates and what is the purpose of this drug class in relation to osetoporosis?
- Alendronate
- Risedronate
- Etidronate
They aim to reduce osteoclast activity
What does Desunomab do?
It is a monoclonal antibody which reduces osteoclast activtity
What does strontium do?
Increases osteoblastic replication and reduces osteoclastic activity
What is zoledronic acid and what is its function?
A once yearly IV bisphosphonate
Why is intranasal calcitonin unlikely to be used over other treatments for osteoporosis?
It shows no benefit over other treatments
It carries a small risk of breast and endometrial cancer as well as DVT
What is Raloxifene?
An oestrogen receptor modulator
(risk of DVT)
What are the best osteoporosis medications taking into account price, efficacy and side effects?
Oral bisphosphonates
Osteomalacia is a ___________ defect of bone
Qualitative
What is osteomalacia?
An abnormal softening of bone due to deficient mineralisation of osteoid
This occurs due to low levels of calcium and phosphorus in the body
What is Ricket’s disease?
Osteomalacia in children
What are the principal causes of osteomalacia and Rickets disease?
- Insufficient calcium (lack of intestinal uptake, low dietary intake, malnutrition)
- Deficiency or resistance to vitamin D (e.g. malabsorption, lack of sunlight exposure)
- Phosphate deficiency (due to increased renal losses, re-feeding syndrome, alcohol abuse, malabsorption, renal tubular acidosis)
- Long term anti-convulsant use
- Chronic kidney disease (reduced phosphate resorption, failure of activation of vitamin D)
- Inherited disease
What do patients with osteomalacia complain of?
- Bone pain (pelvis, spine and femur)
- Deformities from soft bones
- Pathological fractures
- Symptoms of hypocalcaemia
What are the symptoms of hypocalcaemia?
- Paraesthesiae
- Muscle cramps
- Irritability/anxiety
- Fatigue
- Seizures
- Brittle nails
- Heart failure
As well as true fractures, what may radiographs also show for patients with osetomalacia?
Pseudofractures
(also called Looser zones, or Milkman lines)
They are common in the pubic rami, proximal femur, ulna and rubs
What are Looser zones?
Incomplete stress fractures that transverse midway through bone
They generally occur at right angles to the associated cortex
They are associated most with osteomalacia and Rickets
What is serum bone biochemistry like in osteomalacia or Rickets?
It is abnormal
There is:
- Low calcium
- Low serum phosphate
- High serum alkaline phosphotase (ALP)
What is the treatment for osteomalacia or Rickets?
- Vitamin D therapy
- Calcium supplementation
- Phosphate supplementation
What does hyperparathyroidism involve?
- Overactivity of the parathyroid glands
- Increased parathyroid hormone (PTH)
What causes primary hyperparathyroidism?
- Benign adenoma
- Hyperplasia (of the parathyroid gland)
- Malignant neoplasm (rarely)
What does overproduction of PTH cause?
Hypercalcaemia
What are the associated symptoms of hypercalcaemia?
- Fatigue
- Depression
- Bone pain
- Myalgia
- Nausea
- Thirst
- Polyuria (excess urination)
- Renal stones
- Osteoporosis
What is serum biochemistry like in hyperparathyroidism?
- Serum PTH is elevated
- Serum calcium is high
- Phosphate is normal (or low)
What causes secondary hyperparathyroidism?
A physiological overproduction of PTH as a result of hypocalcaemia
(i.e. the parathyroid glands are trying to correct the low calcium)
What are the two most common causes for hypocalcaemia?
- Vitamin D deficiency
- CKD
In which instance is tertiary hyperparathyroidism seen?
In patients with secondary hyperparathyroidism who develop an adenoma
(i.e. despite the correction of hypocalcaemia being corrected, the tumour maintains the high secretion of PTH)
What can hyperparathyroidism result in?
- Fragility fractures
- Lytic lesions in bone (Brown Tumours, or osteitis fibrosa cystica)
What is the treatment for lytic lesions of bone as a result of hyperparathyroidism?
Potential skeletal stabilisation
What is the treatment of hyperparathyroidism?
- Removal of adenomatous gland
- Treatment of the underlying cause (e.g. vitamin D supplementation)
What is the treatment of very high serum calcium levels?
This is an emergency
- IV fluids
- Bisphosphonates
- Calcitonin
What is renal osteodystrophy?
Typical bone changes which occur due to CKD when the kidneys fail to control calcium and phosphate levels
Reduced phosphate excretion and inactive activation of vitamin D results in what?
Secondary hyperparathyroidism
Leading to osteomalacia, sclerosis of bone, calcification of soft tissues
What is Paget’s disease?
A chronic bone disorder causing thickened, brittle and mishapen bones
Which two things have been implicated in the aetiology for Paget’s disease?
- Viral infection with paramyxoviruses
- Genetic defects
Describe what occurs in Paget’s disease to result in thickened brittle bones?
- Potentially due to an exaggerated vitamin D response, there is increased osteoclastic activity
- In response osteoblasts become more active to compensate
- New bone is formed yet it fails to remodel successfully
- Resulting bone is thicker and more brittle as a result
Paget’s disease commonly affects which bones?
- Pelvis
- Femur
- Skull
- Tibia
- Ear ossicles (results in conductive deafness)
Paget’s disease is often _____________
Asymptomatic
Paget’s disease can cause which other conditions?
- Arthritis (when close to a joint)
- Pathological fractures
- Deformities
- Pain
- High output cardiac failure (increased blood flow through pagetic bone)
What are the blood serum changes in Paget’s disease?
- ALP is raised
- Calcium is normal
- Phosphate is normal
What are the radiological features of Paget’s disease?
- Enlarged bone
- Thickened cortices
- Coarse and thickened trabeculae
- Mixed areas of lysis and sclerosis
What is the treatment for Paget’s disease?
- Bisphosphonates (to inhibit osteoclasts)
- Calcitonin (when there is excessive lytic disease)
- Joint replacement may be required
- Stabilisation of femoral fractures with long intramedullary nails or plates
