Endocrine and Metabolic Bone Disorders Flashcards
How is calcium stored?
65% inorganic minerals - calcium hydroxyapatite
35% organic components - type 1 collagn
What do osteoblasts and osteoclasts do?
Osteoblasts - build up bone (synthesise osteoid and mineralise and calcify osteoid) - express receptor for PTH and calcitiol
Osteoclasts - beak down/ reabsorb bone (lysosome enzymes)
What happens during osteoclasts differentiation?
RANKL is expressed on the OSTEOBLAST memberabe
RANK-R on osteoclasts binds to RANKL A-> stimulates osteoclasts formation and activity
Osteoprotegerin (OPG) acts as a competitive inhibitor for RANKL - inhibit it
What are the types of bone?
Cortical (hard) bone - found on outside
Trabecular (spongy) bone - found on inside
*both formed in llamellar pattern - collage fibrils laid down in alternating orientations, mechanically strong
**woven bone - disorganised collagen fibrils - weaker
What are the effects of vitamin D deficiency on bone in adults?
Osteomalacia
- after epiphytes closure, affects bone
- skeletal pain, increased fracture risk, proximal myopathy
What are the effects of vitamin D deficiency on bone in children?
Rickets
- affects cartilage of epiphysial growth pates and bone
- skeletal abnormalities an pain, growth retardation, increased fracture risk
What are ‘looser zones’?
Normal stresses on abnormal bone causing insufficiency fractures
What are the effects of decreased renal function on bone?
- Decreased calcitriol -> decreased Ca2+ absorption -> hypocalcaemia -> decreased bone mineralisation -> osteitis fibrosa cystica
* Hypocalcaemia also leads to increased PTH -> increased bone reabsorption -> osteitis fibrosa cystica - Decreased phosphate excretion -> increased plasma phosphate conc -> hypocalcaemia -> etc.
* increased plasma phosphate conc. -> vascular calcification
What are ‘Brown tumours ’?
Radiolucent bone lesions
Painful and risk of fractures due to bone being so thin
What is the treatment of osteitis fibrosa cystica (hyperparathyroid bone disease)?
Hyperphosphataemis
- low phosphate diet
- phosphate binders - reduce GI phosphate absorption
Alphacalcidol e.g calcitriol analogues
Parathyroidectomy in tertiary hyperparathyroidism
- indicated for hypercalcaemia &/or hyperparathyroid bone disease
What is osteoporosis?
Reduced bone mass and distortion of bone microsarchitecture which predisposes to fracture after minimal trauma
BMD (bone mineral density) < 2.5 SDs or more
*BMD measured by duo energy -ray absorption (DEXA)
What are the risk factors of osteoporosis?
- post-menopausal oestrogndeficiency
- age related deficiency
- hypogoadism in young people
- Endocrine conditions - Cushin’s, hyperthyroidism, primary hyperparathyroidisms
- iatrogenic - prolonged glucocorticoids, heparin
What’s the difference between osteoporosis and osteomalacia?
Both predispose to fracture
Osteomalacia
- vit D deficiency (adults) causing inadequately mineralised bone
- serum biochemistry abnormal ( low 25(OH)vitD, low Ca2+, high PTH - secondary hyperparathyroidism)
Osteoporosis
- bone reabsorption exceeds formation
- decreased bone MASS
- serum biochemistry normal
- diagnosis via DEXA scan
How can oestrogen (HRT) be used to treat osteoporosis?
Treatment of post-menopausal omen with pharalogical doses of oestrogen
- anti -resorptive effects on skeleton
- prevents bone loss
Women with intact uterus need additional progesterone to prevent endometrial hyperplasia/cancer
Use limited largely due to concerns about:
- increased risk of breast cancer
- venous thromboembolism
How can bisphosphonte be used to treat osteoporosis?
Bind avidly to hydroxyapatite and ingested by osteoclasts - impair ability of osteoclasts to reabsorb bone
Decrease osteoclasts progenitor development and recruitment
Promote osteoclasts apoptosis
- net result = reduced bone turnover
Uses:
- osteoporosis (first line treatment)
- malignancy ( associated hypercalcaemia and reduced bone pain from metastises)
- paget’s disease(reduce bony pain)
- severe hypercalcaemia emergency (IV initially - +++ re-hydration first)
Pharmacokinetics:
- Orally active but poorly absorbed - take on empty stomach (milk reduces absorption)
- accumulates at site of bone mineralisation and remains part of the bone until it is reasoned - months/years
Side effects:
oesophagitis - may require switch from oral to IV preparation
Osteoid rosins of the jaw - greatest risk in cancer patients receiving IV bisphosphonates
Atypical fractures - may reflect over-suppression of bone remodelling in prolonged bisphosphonate use
What is denosumab?
Human monoclonal antibody
Binds to RANKL, inhibiting osteoclasts formation and activity
Hence inhibits osteoclasts-mediated bone resorption
6 week SC injections
Very expensive
What is teriparatide?
Recombinant PTH fragment (amino- terminal 234 amino acids of native PTH)
Increases bone formation and bone resorption, but formation outweighs resoprtion
3rd line treatment for osteoporosis
Daily SC injections
Very expensive
What is Paget’s disease?
Accelerated, localised but disorganised bone remodelling
Excessive bone reoption followed by compensatory increase in bone formation -> bone fragility an bone hypertrophy and deformity
- characterised by abnormal, large and numerous osteoclasts
What are the general and clinical features of Paget’s disease?
Features:
- Genetic?
- possible viral origin
- affects men and women equally
- disease not apparent under 50yo
- most patients are asymptotic
- prevalence highest in first world countries
Clinical features:
- skull, thoracolumbar spine, pelvis, femur an Tina most commonly affected
- warmth over affected bone due to increased vascularity
- deafness if choclear bones involved
- radiculophathy due to nerve compression
- fracture
- arthiritis
- pain
- bone deformity
How is Paget’s disease diagnosed?
Normal plasma [Ca2+]
Increased plasma [alkaline]
Plain x-rays = lyric lesions (early), thickened, enlarged, deformed bones (later)
Radionuclide bone scan demonstrates extent of skeletal involvement
What are the treatments for Paget’s disease?
Bisphosphonates (reduce bone pain and disease activity)
Analgesia
