Endocrine and metabolic bone disorders Flashcards
Differentiate between primary, secondary and tertiary hyperparathyroidism
Primary = PT gland adenoma secreting lots of PTH Secondary = normal physiological response to low Ca++, start of renal failure Tertiary = due to chronic low Ca++, PT glands hypertrophy and then become autonomic
What form of vitamin D is found in the diet?
Ergocalciferol
What foods contain vitamin D?
Oily fish and eggs
Where is vitamin D hydroxylated
- Liver
2. Kidney
What enzyme is responsible for the second hydroxylation of vitamin D?
1-alpha-hydroxylase
Recall the sequential conversions that lead to vitamin D production from sunlight
7-dehydrocholesterol + UVB –> cholecalciferol –> 25-OH-D3 (liver) –> calcitriol (kidney)
Describe the serum calcium, phosphate and PTH and the plasma 25-OH-D3 in primary hyperparathyroidism
Calcium: high
Phosphate: low
PTH: high
25OHD3: low
Describe the serum calcium, phosphate and PTH and the plasma 25-OH-D3 in secondary hyperparathyroidism
Calcium: low
Phosphate: high
PTH: high
25OHD3: low
Describe the serum calcium, phosphate and PTH and the plasma 25-OH-D3 in tertiary hyperparathyroidism
Calcium: high
Phosphate: high
PTH: high
25OHD3: low
What conditions are associated with low vit D?
Children: Rickets
Adults: osteomalacia
Differentiate between osteomalacia and osteoperosis
Osteomalacia = vit D deficiency in adults Osteoperosis = low bone mineral density
How are rickets and osteomalacia different?
Rickets = before epiphysial closure therefore growth retardation + skeletal abnormality as well as pain and proximal myopathy Osteomalacia = after epiphysial closure so no skeletal abnormality but still pain and proximal myopathy
What are the 2 main effects of renal failure that affect calcium level?
- Low calcitrol –> low Ca++ absorption –> hypocalcaemia
2. Low phosphate excretion –> high serum phosphate –> hypocalcaemia
How does hypocalcaemia effect bone and what disease state can chronic hypocalcaemia lead to?
Decreases bone mineral density, can lead to (RARE) osteitis fibrosis cystica
Recall 4 treatments for OFC
- Low phosphate diet
- phosphate-binding drugs
- ACTIVE d3 analogue
- parathyroidectomy
What drugs are given to replace vitamin D in patients with normal renal function?
Ergocalciferol, cholecalciferol (= inactive D3)
What drugs are given to replace vitamin D in patients with renal dysfunction?
1-alpha-hydroxycalciferol (alfacalcidol)
What parameter is used to assess osteoperosis and how is this measured?
Bone mineral density T-score
Measured using DEXA scan (Dual Energy X-ray Absorptiometry)
Why are post-menopausal women particularly at risk of osteoperosis?
Oestrogen deficiency leads to loss of bone matrix
Recall 4 possible endocrine causes of osteoperosis, other than menopause
- Hypogonadism
- Cushing’s
- Hyperthyroidism
- Primary hyperparathyroidism
Recall 2 Iatrogenic causes of osteoperosis
- Prolonged glucocorticoid use
2. heparin use
Recall the 5 possible lines of treeatment for osteoperosis
- Oestrogen
- Selective oestrogen receptor modulators
- Bisphosphonates
- Denosumab
- Teriparatide
Why is oestrogen used to treat osteoperosis?
Reduces bone resorption
What is given in conjunction with oestrogen treatment for osteoperosis, and why?
Progestogen - to prevent endometrial hyperplasia/ cancer
Recall 2 concerns with oestrogen treatment of osteoperosis
- Increased breast cancer risk
2. Increased risk of thromboembolism
What are the 2 types of selective oestrogen receptor moderator drugs? Give an example for each
- Selective ER antagonist eg tamoxifen
2. Selective ER agonist eg raloxifene
Describe the mechanism of action of bisphosphonates in osteoperosis treatment
- BP avidly binds to hydroxyapatite
- Osteoclasts injest hydroxypatite, and BP along with it
- BP promote osteoclast apoptosis
- Net reduced bone turnover
Recall 3 problems with bisphosphonate treatment
- Not absorbed well in the gut
- Often cause oesophagitis
- Can cause osteonecrosis of jaw
What is denosumab?
Human monoclonal Ab
What is the mechanism of action of denosumab?
Binds RANK ligands –> prevents osteoclast activity
What is teriparatide?
recombinant PTH fragment
How is teriparatide administered?
Daily subcut. injection
What is Paget’s disease of the bone?
Accelerated, localised but disorganised bone remodelling
Describe the pathophysiology of paget’s disease of the bone
Osteoclastic overactivity –> compensatory increase in dinovosynthesis of bone = structurally disorganised bone with poor tensile strength
Recall the clinical features of Paget’s disease of the bone
Obvious: Arthritis Fracture Pain Deformity Less obvious: Increased vasculatory --> warmth Deafness Radiculopathy (due to bone involvement)
What is the hallmark biochemical finding in Paget’s disease of the bone?
Really high alkaline phosphatase
Recall the 2 normal treatmnts for Paget’s disease of the bone
Bisphosphonates, analgesia
Recall the effector functions of PTH
Promotes bone resorption to release Ca++
Promotes Ca++ reuptake in kidney
Phosphorylates inactive Vit D in kidney to calcitriol
Decreases renal phosphate resorption
Recall the effector functions of Vit D
Increases GUT RESORPTION of Ca++
Promotes bone resorption to release Ca++ (by increasing oesteoblast RANK-L production)
Promotes Ca++ re-uptake in kidney
Where in the kidney is phosphate resorbed and by what transporter?
PCT
Na+ cotransporter
Recall 2 inhibitors of phosphate resorption in the kidney
PTH
FGF23
What function is shared by PTH and FGF23
Inhibition of Na+/ PO4— cotransporter to promote phosphaturia
Recall an inhibitor of calcitriol
FGF23
Recall how PTH levels are controlled
Ca++ binds parathyroid gland receptors –> negative feedback
Recall a cause of Vit D toxicosis
Granulomatous disease
Recall the Ca++, phosphate, PTH and ALP in Paget’s
Ca++ normal
Phosphate normal
PTH normal
ALP really high
