Endocrine and Metabolic Bone Disorders Flashcards
What does bone store?
Stores >95% of body’s Ca2+
What makes up bone?
- Organic components - OSTEOID (unmineralised bone)
o 35% bone mass
o Type 1 collagen fibres (95%)
- Inorganic mineral component
o 65% bone mass
o Calcium hydroxyapatite crystals - fill space betw. collagen fibres
Main 2 types of bone cells?
o Osteoblasts - bone FORMATION
o Osteoclasts - bone RESORPTION
How do osteoblasts work?
Bone FORMATION
Synthesise OSTEOID
Participate in mineralisation/calcification of osteoid
How od osteoclasts work?
Bone RESORPTION
Release lysosomal enzymes - breaks down bone
How do osteoclasts differentiate?
From OSTEOBLASTS!
- RANKL expressed on osteoblast membrane
- RANK-R binds to RANKL
- Stimulates osteoblast formation & activity
How is bone remodelling controlled?
Osteoblasts!
Express receptors for:
o PTH
o calcitriol
SO regulate balance between bone formation & resoprtion
Describe brief structure of bone
Cortical bone - HARD
Trabecular bone - SPONGY
Both formed in a lamellar pattern
o collagen fibrils laid in alternating
o mechanically strong
Woven bone?
DISORGANISED collagen fibrils
WEAKER!!
Definition of VitD deficiency?
Inadequate mineralisation of newly formed bone matrix (osteoid)
Affect of VitD deficiency on children?
RICKETS!
affects cartilage of epiphysial growth plates & bone (still growing!)
o skeletal abnormalities and pain
o growth retardation
o increased fracture risk
Affect of VitD deficiency on adults?
OSTEOMALACIA!
AFTER epiphyseal closure so just affects bone
o skeletal pain
o increased fracture risk
o proximal myopathy
2 things typical to bone when VitD deficient?
- Looser zones - normal stresses on abnormal bone cause insufficiency fractures
- Waddling gait
Explain renal failure and bone disease
Normally 3o hyperparathyroidism!
o PTH is HIGH
o Ca2+ is also HIGH
o Parathyroid becomes autonomous
Leads to DECREASED calcitriol o so LESS PO4 excreted o leads to higher serum PO4 o PO4 hence binds to Ca2+ in the blood o leads to extra-skeletal deposits = VASCULAR CALCIFICATION
Also due to the HYPOcalcaemic nature
o leads to DECREASED bone mineralisation
= OSTEITIS FIBROSA CYSTICA
Osteitis fibrosa cystica?
Hyperparathyroid bone disease - RARE
o XS osteoCLASTIC bone resorption
o 2o to high PTH
o ‘Brown tumours’ - radiolucent bone lesion
Treatment of osteitis fibrosa cystica?
- Hyperphosphataemia
o low PO4 diet
o phosphate binders - reduce GI phosphate absorption - Alphacalidol
o calcitriol analogue - Parathyroidectomy (in 3o hyperparathyroi)
o indicated for hypercalacaemia
AND/OR
o hyperparathyroid bone disease
Define osteoporosis
Loss of bony TRABECULAE
Reduced BONE MASS
WEAKER bone
All of this predisposes to fracture after minimal trauma
When do you diagnose osteoporosis?
BMD <2.5 SDs BELOW average value for young healthy adults
How can osteoporosis be measured?
DEXA - dual energy X-ray Absorpitometry
o femoral neck
o lumbar spine
Mineral (Ca2+) content of bone measured
o the more mineral = grater bone density (BM)
Difference between Osteoporsis vs. Osteomalacia?
BOTH predispose to fracture!
Osteomalacia
o VitD DEFICIENCY (adults) = inadequate mineralisation of bone
o Serum biochemistry = ABNORMAL
- LOW calciferol
- LOW/N Ca2+
- HIGH PTH (2o hyperparathyroid)
Osteoporosis
o Bone RESORPTION»_space; bone formation
o DECREASED bone mass
o Diagnosis via. DEXA Scan
o Serum biochemistry = NORMAL
Pre-disposing conditions for osteoporosis?
- Postmenopausal oestrogen deficiency
o leads to loss of bone matrix
o subsequent increased risk of fracture - Age-related deficiency in bone homeostasis
o e.g. osteoblast senescence - Hypogonadism in young people
- Endocrine conditions
o Cushing’s
o Hyperthyroidism
o 1o hyperparathyroidism - Iatrogenic
o prolonged use of glucocotricoids
o Heparin
4 treatment options for osteoporosis?
- Oestrogen/SERMs
- Bisphosphonates
- Denosumab
- Teriparatide
Evaluate use of Oestrogen (HRT) for treatment in Osteoporosis
Anti-resorptive effects on the skeleton = prevents bone loss
Women w intact uterus need PG - to prevent endometrial hyperplasia/cancer
Use limited largely due to concerns of:
o increased breast Ca risk
o VTE
Evaluate use of SERMs (HRT) for treatment in Osteoporosis
Tissue-selective ER antagonist
e.g. Tamoxifen
o antagonises ER in breast
BUT
o oestrogenic activity in bone
o oestrogenic effects on endometrium persist
Tissue-selective ER agonist
e.g. Raloxifene
o oestrogenic activity in bone
o anti-oestrogenic activity on breast & uterus
BUT
o still have VTE and stroke risks
