Endo 13 - Endocrine and Metabolic Bone disorders Flashcards
In primary HPT, there is high Ca and high PTH. Why?
No negative feedback (i.e. autonomous PTH secretion despite hypercalcaemia)
Removal of adenoma is how it is treated
Describe how secondary HPT may arise
- Low Ca (often due to Vit D deficiency)
- PTH increases - to try to normalise serum Ca
- Secondary HPT - marked by:
High PTH, low/normal Ca
What are the biochemical findings in Vit D deficiency
- Low plasma 25(OH)D3
- Low plasma Ca (may be normal if secondary hyperparathyroidism developed)
- Low plasma phosphate
- High pTH
How is vitamin D deficiency treated
Normal renal function:
1. Give 25-hydroxy vitamin D - will be converted into active Vit D via 1a hydroxylase in kidney.
e.g. Ergocalciferol, cholecalciferol
If renal failure:
1. Give alfacalcidol - 1ahydroxycholecalciferol
When can Vit D excess occur as a result of?
- Excessive treatment with active Vit D metabolites e.g. Alfacalcidol
- Granulomatous diseases - e.g. sarcoidosis, leprosy and TB all have macrophages that produce 1a hydrolyase
What can Vit D excess/intoxication lead to
- Hypercalcaemia
2. Hypercalcuria
How are osteoclast precursors stimulated to become activated osteoclasts
Osteoclast precursor must bind to RANKL - stimulates differentiation and fusion (RANKL expressed by osteoblasts/stromal cell)
Osteoblasts contain receptors for?
- PTH
2. Calcitriol (active Vit D)
Cortical (hard) and trabecular (soft) bone are both formed in what pattern?
Lamellar pattern - collagen fibrils (type 1) laid in alternating orientations - mechanically strong
What are the effects of Vit D deficiency on bone
Causes inadequate mineralisation of newly formed bone matrix (osteoid)
Children - rickets.
- Cartilage of epiphyseal growth plates and bone
- Skeletal abnormalities, pain, increased fracture risk, growth retardation
Adults - osteomalacia
- Occurs after epiphyseal closure
- Skeletal pain, increased fracture risk, proximal myopathy
Normal stresses on abnormal bone can cause insufficiency fractures. What are these known as?
Loosers zones
Waddling gait is typical
Tertiary HPT may occur when?
Chronic Kidney disease - low plasma Ca constantly
PT glands constantly producing PTH so they get revved up and start to hypertrophy
How can impaired renal function contribute to bone disease
Decreased renal function causes both less active Vit D and also impaired phosphate excretion
Decreased Vit D –> less Ca absorption —> hypocalcaemia –> Less bone mineralisation —> Osteitis fibrosa cystica
Decreased phosphate excretion —> increased plasma phosphate (causes vascular calcification too) —> hypocalcaemia —> increased PTH —-> increased bone resorption —–> osteitis fibrosa cystica
What are brown tumours
Radiolucent bone lesions - often as a result of osteitis fibrosa cystica (HPT bone disease)
How is osteitis fibrosa cystica treated
- Low phosphate diet and phosphate binders (reduce GI phosphate absorption) - to treat hyperphosphataemia
- Alphacalcidol - calcitriol analogues
- Parathyroidectomy in tertiary HPT
Osteoporosis is a reduction in bone mass, weaker bone that is predisposed to fracture after minimal trauma. What type of bone is lost
Loss of bony trabeculae
How is osteoporosis defined and diagnosed
<2.5 SD below avg value for young healthy adults on BMD
Where is a DEXA scan usually used to measure BMD
Femoral neck and lumbar spine
Distinguish between osteoporosis and osteomalacia
Both predispose to fracture
Osteomalacia = ABNORMAL serum biochemistry - it is how it is diagnosed (low 25-Vit-D, low/N calcium, high PTH)
Osteomalacia is caused by Vit D deficiency causing inadequately mineralised bone
Osteoporosis = Decreased bone mass, diagnosis via DEXA scan. NORMAL serum biochemistry. Bone resorption exceeds formation
What are the predisposing conditions for osteoporosis
- Postmenopausal oestrogen deficiency
- Age related deficiency in bone homeostasis - e.g. osteoblast senescence
- Hypogonadism
- Endocrine conditions (e.g. Cushings, hyperthyroidism, primary HPT)
- Iatrogenic - e.g. prolonged use of glucocorticoids, heparin
What are the treatments for osteoporosis
- Oestrogen
- Bisphosphates
- Denosumab
- Teriparatide
Describe the use of oestrogen (HRT) to treat osteoporosis
Has anti-resorptive effects on bone - less bone loss
BUT women with intact uterus need to be given progestogen to prevent endometrial hyperplasia/cancer
Limited use due to:
Increased risk of breast cancer and venous thromboembolism
Describe the use of bisphosphonates to treat osteoporosis (main treatment - firstline)
They bind avidly to hydroxyapatite crystals - which are ingested by osteoclasts - impairs ability of osteoclasts to reabsorb bone
Decrease osteoclast progenitor development and recruitment
Promote osteoclast apoptosis
Net result = reduced bone turnover
What are the medical uses of bisphosphonates
- Osteoporosis
- Malignancy
- Pagets disease
- Severe hypercalcaemic emergency
