Endocrine Bone Disorders Flashcards
What is the most important vitamin D metabolite?
1, 25-dihydroxycholecalciferol (calcitriol)
What is the principle effect of calcitriol?
Increase calcium, magnesium and phosphate absorption in the small intestines
What are the other effects of calcitriol?
Increased reabsorption of calcium and decreased phosphate reabsorption in the kidneys (via FGF23) Stimulates osteoclast formation from precursors Stimulates osteoblasts to make osteoclast-activating factors (OAFs e.g. RANKL)
What does vitamin D deficiency cause? State some symptoms.
Lack of bone mineralisation Softening of bone (can lead to bowing of the legs) Bone deformities Bone pain Severe proximal myopathy
What are the different names for vitamin D deficiency in children and adults?
Children – Rickets Adults – Osteomalacia
State some causes of vitamin D deficiency.
Inadequate dietary intake Lack of sunlight Receptor defects Renal failure Gastrointestinal malabsorptive states
Which step, in vitamin D metabolism, required UV light?
The conversion of 7-dehydrocholesterol in the skin to cholecalciferol (vitamin D3) requires UV light
Describe the two hydroxylation reactions in vitamin D metabolism.
Cholecalciferol is firstly hydroxylated to form 25-hydroxycholecalciferol in the Liver It then goes to the kidneys where it undergoes its next hydroxylation (by 1-hydroxylase) to form 1, 25-dihydroxycholecalciferol (calcitriol)
What can stimulate 1-hydroxylase in the kidneys?
Parathyroid Hormone (PTH)
How can lack of sunlight cause vitamin D deficiency?
It will mean that less 7-dehydrocholesterol is being converted to cholecalciferol
How can liver disease cause vitamin D deficiency?
The liver is where the first hydroxylation takes place and where 25-hydroxycholecalciferol is stored so liver disease can interfere with this step in vitamin D metabolism
How can renal failure cause vitamin D deficiency?
The second hydroxylation step takes place in the kidneys (via 1-alpha-hydroxylase) so renal failure can interfere with 1-alpha-hydroxylase activity
What is usually measured to gage the level of calcitriol? Whatcondition must be fulfilled for this to be a good measure of calcitriol?
25-hydroxycholecalciferol This is only a good measure in the case of normal renal function
Describe how you would diagnose vitamin D deficiency.
Plasma Calcium = LOW Plasma 25-hydroxycholecalciferol = LOW Plasma PTH = HIGH (secondary hyperparathyroidism stimulated by the hypocalcaemia) Plasma Phosphate = LOW Radiological findings e.g. widened osteoid seams
What would you expect the plasma phosphate level to be in someone with renal failure and why?
HIGH – because there is a decrease in plasma excretion via the kidneys
What would you expect the plasma calcium level to be in someone with renal failure and why?
LOW – because they are not producing as much calcitriol (due to renalfailure interfering with 1-alpha hydroxylase) so there is less calcium absorption in the small intestines
What are the consequences of hypocalcaemia caused by renal failure?
There is a decrease in bone mineralisation and an increase in bone resorption (because of an increase in PTH) leading to osteitis fibrosa cystica The imbalance in calcium and phosphate can also lead to the formation of salts that can be deposited in extra-skeletal tissue causing extra-skeletal calcification
What can vitamin D excess lead to?
Hypercalcaemia and hypercalciuria (due to increased intestinal absorption of calcium)
What can vitamin D excess result from?
Excessive treatment with active metabolites of vitamin D, as in patients with chronic renal failure Granulomatous disease – granulomatous tissue has 1-hydroxylase so it can be a source of ectopic calcitriol
What is Paget’s disease?
Very active (increased), localised but disorganised bone metabolism –usually slowly progressive. There is increased bone breakdown and bone formation.
What is Paget’s disease characterised by histologically?
Abnormal, large osteoclasts
State some symptoms of Paget’s disease.
Increased vascularity (warmth over affected bone) Increased osteoblast/osteoclast activity Initially increased osteoclast activity Followed by increased osteoblast activity (leading to thickening of deformed bone) Most commonly affected bones are: pelvis, femur, tibia, skull, and spine Increased incidence of fracture Bone pain
Describe how you would diagnose Paget’s disease.
Plasma calcium = NORMAL Plasma ALP (alkaline phosphatase) = HIGH Radiological findings: Loss of trabecular (spongy) bone Increased bone density Deformity Radioisotope (technetium) scanning can be performed to indicate areas of involvement