Calcium And Phosphate Metabolisms Flashcards
Describe the function of PTH
Prolonged, high levels will promote bone remodelling
Describe the function of FGF23
Decreases phosphate and vitamin D (so Calcium)
- inhibits the formation of active vitamin D3
- will increase phosphate excretion
In response to what is FGF23 secreted?
- High phosphate levels
- Will cause the excretion and so the decrease in phosphate
Describe the function of Vitamin D
- Promotes calcium absorption in the gut
- So deficiency in Vitamin D may cause osteomalacia
Describe what osteoporosis is
Loss of both the cortical and trabecular bone mass - loss of the mineralisation of bone AND loss of the organic bone matrix (collagen)
Name some causes of osteoporosis?
- age (endocrine)
- malignancy
- drug induced
- renal disease
- nutritional
- age
How do we diagnose osteoporosis?
Measure bone mineral density and compare it to cut-off points
- Is done with dual-energy X-ray absorptiometry (DEXA or DXA scan)
- gives a T score and a Z score which are part of a statistical test where if the T score is lower than -2.5 then = diagnosed osteoporosis
What is the T score?
Number of standard deviations below average for young adult at peak bone density
What is osteopenia?
When the T score is between -1 and -2.5 so it is not enough for osteoporosis diagnosis (less than -2.5)
What is the Z score?
Matched to age and/or group
Name some endocrine causes of osteoporosis
- Hypogonadism (especially any cause of oestrogen deficiency but also seen in men due to no conversion of androgen → oestrogen peripherally)
- Exogenous glucocorticoids or also endogenous (think, Cushing’s)
- Hyperparathyroidism (excess resorption)
- Hyperthyroidism
How can we treat osteoporosis?
- Ensure adequate calcium and vitamin D intake, appropriate exercise
- HRT for Postmenopausal women
- Biphosphonates
- PTH analogues
- Denosumab
- Romosozumab
What is romosozumab?
Human monoclonal antibody against sclerostin
What is denosumab?
Human monoclonal antibody against RANK ligand
What do bisphosphonates do?
Inhibits function of osteoclasts
What is osteomalacia?
Loss of bone mineralisation (this is different to osteoporosis as osteoporosis is a loss of bone mineralisation AND the loss of the organic bone matrix)
- so makes bone soft and malleable - known as rickets in children
What is loss of bone mineralisation called in children?
Rickets
What are the symptoms of osteomalacia?
- Diffuse aches
- Chronic fatigue
- Weak bones
What deficiencies cause osteomalacia?
- Deficiency in Ca or Phosphate (or PTH nmy be elevated as well as in osteoporosis)
What is a marker for osteomalacia?
Alkaline phosphatase
What are the causes of osteomalacia?
- Vitamin D deficiency (most common)
- Mutations leading to errors in vitamin D metabolism
- Hypophosphataemia
Name the immediate precursor to active Vitamin D
25 Hydroxy Vitamin D3
What is vitamin D increased by?
- PTH
- Low calcium
- Low phosphate
What is vitamin D decreased by?
- FGF-23
- High calcium
- High phosphate
Name 2 rare mutations that can cause osteomalacia
- 1-alpha hydroxylase mutation
- Vitamin D receptor mutation
How does the alpha hydroxylase mutation work?
no/low conversion of immediate precursor to active vitamin D3 (calcitriol)
How does the Vitamin D receptor mutation work?
No binding of vitamin D3 to its receptor so increased production of vitamin D3
What is type 1 vitamin D dependant rickets caused by?
An alpha hydroxylase mutation
What is type 2 vitamin D dependant rickets caused by?
Vitamin D receptor mutation
What does type 1 vitamin D dependant rickets cause?
Low calcium and phosphate
What does type 2 vitamin D dependant rickets cause?
High calcitrol (vit D) production
What is renal osteodystrophy?
Spectrum of conditions associated with bone lesions in renal failure
What are the lab signs of renal osteodystrophy?
- Low plasma calcium
- PTH rises
- Excess bone resorption
What causes renal osteodystrophy?
- Impaired phosphate excretion
- Impaired vitamin D activation
In renal disease (CKD) describe the levels of Ca, P, Vit D precursor, Vit D and PTH
- low Ca
- high P
- normal 25 OH D3
- low active D3
- very high PTH
What is the most common cause of hypercalcaemia in non-hospitalised patients?
Hyperparathyroidism