Metabolic bone disease Flashcards
1
Q
Where is most of the calcium stored?
A
- 99% of body calcium is in bone and teeth
- Remainin 1% is mainly IC (in SR)
- hormonal control of the tiny EC fraction (<0.1%) is what maintains Ca balance (what we measure)
2
Q
What is calcium needed for?
A
Signalling for NT release and muscle contraction
Bone density
3
Q
How is calcium distributed in plasma?
A
- Half free ions (physiologically active form)
- half protein bound
4
Q
What are osteoblasts?
A
- Differentiate from mesenchymal stem cells
- Bone forming cells - lay down organic bone matrix (osteoid), promote mineralisation of osteoid
- Life cycle determined by control of differentiation and apoptosis
5
Q
What are osteoclasts?
A
- Derived from HSCs
- Resorption of bone - secrete acid to dissolve and release mineral content; enzymes to degrade organic matrix
- Life cycle determined by control of differentiation and apoptosis
6
Q
What are osteocytes?
A
- terminally differentiated, post-mitotic osteoblasts
- Entombed within lacunae in the bone matrix
- Communicate with each other and bone surface via cellular processes (dendrites), which run along canaliculi
- Lacunar-canaliculi network
- may live for decades
7
Q
How is remodelling controlled?
A
- Favouring resorption - bedrest, zero-gravity etc
- Favouring formation - load-bearing exercise
- Osteocytes can detect mechanical stress during load bearing exercise using canaliculi network
- Can adjust secretion of RANKL (differentiation of osteoclasts), osteoprotegerin (blocks RANK), sclerostin (inhibits bone formation - reducing sclerostin = increase osteoblast differentiation)
8
Q
What bone diseases are there?
A
- Osteoporosis - generalised loss of bone density (thin bones)
- osteomalacia - loss of bone mineralisation (soft bones)
- Paget’s disease - imbalance in remodelling cycle in specific localised sites - isolated lesions
9
Q
What hormones act on bone?
A
- PTH
- Vit D
- Calcitonin
10
Q
What is PTH?
A
- Secreted by PT gland.
- Secreted in low Ca2+ conc
- As Ca levels rise, more CaSR are stimulate on the bone PT gland, decreasing PTH secretion
11
Q
What does PTH act on?
A
- kidney - increases calcium reabsorption, decreases phosphate reabsrption
- Bone - increases bone resorption by increasing osteoclast activity
- Also has anabolic effects therapeutically to treat osteoporosis
- Gut - increases calcium absorption via vit D
12
Q
What is Vit D?
A
- Calcitriol (steroid hormone rather than vitamin)
- Synthesised in skin in response to UV
- Activated by 2 metabolic steps - 25 hydroxylation in liver to form calcidiol; 1alpha hydroxylation of calcidiol in kidney to form calcitriol
- Calcitriol increases intestinal absorption of dietary calcium
13
Q
What is calcitonin?
A
- 32 AA peptide
- Secreted by C cells of thyroid
- Secreted in high Calcium conc
- Acts on:
- Kidney - decreases calcium and phosphate reabsorption
- Bone - decreases bone resorption by inhibiting osteoclasts
- Synthetic calcitonin used for Paget’s
14
Q
What are the main causes of hypercalcaemia?
A
- > 2.6mM
Commonest - primary hyperPT
- Malignancy
Less common
- Hyperthyroidism
- Excessive intake of Vit D
15
Q
What are the clinical features of hypercalcaemia?
A
- Renal calcification (kidney stones)
- Abdominal pain, constipation
- Anorexia, nausea, vomiting, depression, fatigue
- Bone pain in malignancy or hyperPT
- Cardiac arrhythmias, cardiac arrest
Bones, stones and psychic moans
16
Q
What is primary hyperparathyroidism?
A
- Usually due to benign adenoma
- Most common in post-menopausal women
- Often detected on screening - many asymptomatic
- ~10% of patients present with clinical evidence of bone disease
- 10-20% with kidney stones
17
Q
What would the blood results be in primary hyperPTism?
A
- Calcum increased
- Phosphate low or normal
- ALP raised in 20% (increased ALP = increased bone turnover)
- Creatinine may be elevated in longstanding disease
- PTH interpreted alongside calcium
18
Q
What malignancies can lead to hypercalcaemia?
A
- PTH-rp - secreted by lung or renal carcinoma (activates PTH receptors)
- Solid tumours with bone metastases
- Haematological malignancy (myeloma) - release cytokines to activate RANK
19
Q
What will PTH levels be like in malignancies?
A
- should be appropriately suppressed as cause of hypercalcaemia is elsewhere
20
Q
What is hypocalcaemia?
A
- Low calcium
- Vit D deficiency (low intake/lack of sun)
- Renal failure - loss of 1alpha hydroxylase -> decreased active Vit D conversion -> decreased Ca -> increased PTH -> no more Ca can be absorbed from gut as no vit D -> bone resorption and damage
- failure of acid-base regulation - decreased H+ excretion -> metabolic acidosis -> bone erosion
- HypoPTH - not common, caused by thyroid surgery or congenital
