Flashcards in MSK L15 Osteoporosis Deck (36):
1
Bone structure:
1. Cortical bone → compact outershel (bone strength)
2. Trabecular bone → network of interconnecting plates →
a. Strength
b. Surface for exchange of calcium
c. Physical template for haemopoiesis
2
Macroarchitecture and bone strength:
1. Bone strength
a. Cross sectional area → large resistance ot bending
b. Cortical thickness
2. Bone shape
a. Hip axis length →
3
Microarchitecture and bone strength
Trabecular bone:
1. Trabecular thickness
2. Trabecular number
3. Trabecular connectivity
Cortical bone
1. Cortical thickness
2. Cortical porosity
4
Connectedness of trabeculae → Eular
Eular Buckling Theory
See image 112 – organisatino of plates important in strength
5
Fibrils →
→ hydroxyapatitie crystals – resistance to compression
6
Organic phase →
type 1 collagen and other non-collagenous proteins e.g. osteocalcin → tensile strength
7
Section 2: Bone remodelling
1. Lifelong process involving discrete sites throughout the while skeleton
2. Each remodelling cycle takes 3-4 months to complete
3. Ensures readily available supply of calcium for calcium homeostasis
4. Maintains bone integrity by replacing sites of fatigue damage
8
Bone Formation
1. Mechanical Loading
2. Androgens
3. Intermittent PTH
4. B-blockers
9
Bone resorption
1. Oestrogen defiency
2. Immobilization
Low Ca
10
Osteoblasts action
→ Pump protons that activated enzymes → TRAP and CATK
11
Osteoclasts Formed from
mononucleur precursors shared with monocytes then a number of factors drive the mononuclear precursors down osteoclast pathway.
12
Osteoclasts Stimulation of formation
Cytokines → RANKL (produced by stromal cells in bone marrow) interact with RANK receptor = stimulation and formation of mature osteoclasts.
13
OPG →
Block RANKL
14
Denosumab →
RANK ligand inhibitor for postmenopausal women = osteoporosis treatment
15
Osteoblasts: Found
Sit on the surface of trabecular bone synthesis
16
Osteoblasts:Mesenchyme precursor →
Produce myoblasts (muscle), adipocytes(fat) chondrocytes(cartilage) and osteoblasts (bone).
17
Osteoblasts: LRP5/Wnt signlaiing pathway
Stimulates osteoblasts formation
18
Osteoblasts: A mutation in LRP5
Constant activation of pathway → excess bone density in hip and spine
19
Osteoblasts: Sclerostin
Secreted by osteocytes, which inhibits bone formation. Strain on bone switches this off.
20
Osteoblasts:Sclerostin defiency
Causes a high bone mass phenotype
• Enlarged mandibles
• Facial nerve palsys due to overgrowth of skull in IAM
21
Sclerostin antibody
Osteoporosis treatment
22
Epi
osteoporosis
More common in women
Fractures most common with age and in hip, vertebrae, colles’ (distal radius)
23
Bone remodelling in osteoporosis
Imbalance – amount of resorption exceeds formation
Oestrogen related
24
Osteoporosis measure in
DXA
25
Peak bone mass
Diet
Exercise
Genes
26
Bone loss
Low calcium/vitamin d
Immobility
Genes
Estrogen defiency
Steroids
27
Vertebral Fracture
1. Kyphoctic deformity
2. Height loss
3. Increased backpain
4. Decreased activity
5. Impaired quality of life
6. Increased mortality
7. Increased risk of vertebral and non-vertebral fractures
28
Bone remodelling and osteoporosis: Trabecular Bone:
1. Increased activation frequency
2. Increased erosion depth
3. Reduced trabecular thickenss
29
Bone remodelling and osteoporosis: Cortical Bone
Structural changes also effect cortical bone, characterised by endosteal expansion, cortical thinning, and an increase in size and number of Haversian canals.
Expansino of endosteal surface, thinning and weakening
30
Treatments:
Anti-resorptive
Mixed action
Anabolic
31
Anti-resorptive
Bisphosphonates → alendronate, risedronate, Ibandronate
Denosumab → RANK ligand inhibitor for postmenopausal women = osteoporosis treatment → more potnet thatn aldrenodate (knocks out osteoclast)
32
Mixed action
Strontium → act as a combination of stimulating osteobalsta and inhibiting osteoclasts
33
Anabolic
PTH → teriparatide (PTH1-34), Preotact (PTH 1-84)
34
Bisphosphonates → Treatment for
1. Osteoporosis
2. Pagets → a particular sites in skeleton get overgrowth of osteoglasts = expansion of bone and bone pain
3. Hypercalcaemia malignancy → secondary depositis in skeleton → stimulatin of osteoclasts, resorption and hypercalcaemia.
35
Bisphosphonates → Chemical structure
Retained in bone as they bind in bone as they bind the crystals
36