Endo 12 - Endocrine Bone Disorders Flashcards
What is the common name given to the most important vitamin D metabolite?
Calcitriol
What is the chemical name of calcitriol?
1, 25-dihydroxycholecalciferol
What is the principle effect of calcitriol?
increases calcium, magnesium and phosphate absorption in the small intestine
What are the other effects of calcitriol?
- increases calcium and phosphate reabsorption from the kidneys
- stimulates osteoclast formation
- stimulates osteoblasts to make osteoclast activating factors
What does Vitamin D deficiency cause?
- lack of bone mineralisation
- softening of bone - bowing of legs
- bone deformities
- bone pain
- severe proximal myopathy
What is vitamin D deficiency called in children?
rickets
What is Vitamin D deficiency called in adults?
Osteomalacia
Name 4 causes of vitamin D deficiency?
- diet
- lack of sunlight
- GI malabsorption
- renal failure
Which step in vitamin D metabolism requires UV light?
conversion of 7-dehydrocholesterol in the skin to form cholecalciferol
How many hydroxylation reactions are there in vitamin D metabolism?
2
Describe the 2 hydroxylation reactions in vitamin d metabolism?
- cholecalciferol hydroxylated to form 25-hydroxycholecalciferol in the liver
- hydroxylated by 1-hydroxylase to form 1,25 dihydroxycholecalciferol (calcitriol)
What can stimulate 1-hydroxylase in the kidneys?
Parathyroid hormone
How can lack of sunlight cause vitamin D deficiency?
will mean less 7-dehydrocholesterol gets converted into cholecalciferol in skin
How can liver disease cause vitamin D deficiency?
liver is where the first hydroxylation takes place
where 25-hydroxycholecalciferol is stored
How can renal failure cause vitamin D deficiency?
where 2nd hydroxylation takes place
What is measured to gage the level of calcitriol?
25-Hydroxycholecalciferol
can only be used if normal renal function
How would you diagnose vitamin d deficiency?
Plasma 25-hydroxycholecalciferol = low plasma calcium = low plasma PTH = high plasma phosphate = low radiology = widened osteoid seams
What would the level of phosphate be in someone with renal failure?
High
What would plasma calcium be in someone with renal failure?
Low - as not producing calcitriol
What is the consequence of hypocalcaemia caused by renal failure?
decrease in bone mineralisation
increase in bone resorption
= osteitis fibrosa cystica
What can vitamin d excess lead to?
Hypercalcaemia and hypercalciuria
What does PTH do to bone?
Breaks it done in order to restore blood calcium level
What can excess vitamin D result from?
excessive treatment
What is Paget’s disease?
Very active, increased localised but disorganised bone metabolism
increased bone breakdown and formation
What is Paget’s disease characterised by?
Abnormal large osteoclasts
State some of the symptoms of Paget’s disease?
- increased warmth over bones increased osteoblast/osteoclast activity - first osteoclast breaks bone down - then osteoblast builds bone back up - pelvis and femur most commonly affected - increased chance of fracture
Describe how you would diagnose Paget’s disease?
plasma calcium - normal
plasma ALP - high
radiology - spongy bone, increased bone density
What are the two components of bone where 95% of body’s calcium is stored?
- Inorganic mineral component - 65%
2. Organic component - 35%
What is the normal plasma calcium range?
2.2-2.6mmol/L
State 2 hormones which increase plasma calcium?
PTH
Calcitriol
Name a hormone that reduces plasma calcium?
Calcitonin
What are the 2 direct effects of PTH?
- Calcium mobilisation from bone
- increased calcium reabsorption in kidneys
What are the 2 direct effects of calcitriol?
- increased calcium absorption in small intestine
- increased mobilisation of calcium in bone
What stimulates PTH release?
hypocalcaemia
State 4 signs of hypocalcaemia?
- parasthesia
- arrhythmias
- convulsions
- tetany
What effect does hypocalcaemia have on excitable tissue?
sensitises excitable tissue
State 2 clinical signs of neuromuscular irritability due to hypocalcaemia?
- Chvostek’s sign - tap facial nerve just below zygomatic arch, twitching = positive response
- Trousseau’s sign = Pump blood pressure cuff for several minutes - +ve = carpopedal spasm
State 4 causes of hypocalcaemia?
- Hypoparathyroidism
- vitamin d deficiency
- pseudohypoparathyroidism
- renal failure - imparied 1 hydroxylase
Describe the effect of hypercalcaemia on neuronal excitability?
reduces neuronal excitability
What are the signs of hypercalcaemia?
- stones, groans and moans
- stones - renal effects - polyuria and thirst
- abdominal moans - anorexia, nausea, constipation
- psychic groans - fatigue, depression, coma
What are the 2 main causes of hypercalcaemia?
- Primary hyperparathyroidism - e.g. adenoma
- Malignancy - bone tumours causing increased bone turnover
How would you differentiate between primary hyperparthyroidism and malignancy?
Primary HPT would have no negative feedback so PTH will be high along with plasma calcium
Malignancy - plasma calcium high but PTH low
Describe the treatment of vitamin D deficiency if normal renal function?
Give 25-hydroxy vitamin D
- patient can convert this to calcitriol using 1-hydroxylase
Name the 2 types of supplements for vitamin D deficiency in normal renal function?
- ergocalciferol
- cholecalciferol
What is the treatment for vitamin D deficiency in patients with renal failure?
Alfacalcidol - 1-hydroxycholecalciferol
What do osteocytes produce?
Type 1 collagen
What is RANK ligand?
osteoclast activating factor
stimulates the maturation of osteoclast from precursors
so more bone resorption
Define osteoporosis
Having a bone mineral density that is 2.5 standard deviations or more below the average for young healthy adults
How is BMD measured?
DEXA scan
State some pre-disposing conditions for osteoporosis?
- post menopausal women
- endocrine disease
- hypogonadism in young people
What are the advantages and disadvantages of estrogen replacement to prevent osteoporosis in post menopausal women?
adv - anti-resorptive effect in bone so prevents bone loss
dis - must be given with progesterone otherwise endometrial carcinoma
also breast cancer
VTE
Name 2 oestrogen receptor modulators and their effects
- Tamoxifen - oestrogenic in bone and anti-oestrogenic in breast and uterus SERM
- Raloxifene - SERM - but causes stroke and VTE
What is the 1st, 2nd and 3rd line treatment for osteoporosis?
- Bisphosphonates
- Denusomab
- Teriparatide
What are bisphosphonates analogues of?
Pyrophosphate
How do bisphosphonates work?
impairs ability of osteoclast to resorp bone
decreases maturation of osteoclasts
promotes osteoclast apoptosis
State some uses of bisphosphonates?
Osteoporosis
malignanacy
paget’s
State some of the unwanted effects of bisphosphonates
oesophagitis
flu like symptoms
What is denusomab?
human monoclonal antibody
binds to RANKL and inhibits osteoclast formation
given every 6-12 months
What is teriparatide?
recombinant PTH
INCREASES BONE RESORPTION and formation
