Basic science Flashcards
Which are nitrogen containing bisphosphonates?
N2 - Risedronate (PO) & Zolendronate (IV)
Non-N2 - Alendronate (PO) & Pamidronate (IV)
Changed pyrophosphate from POP to PCP
2 side chains
R1 - bone affinity
R2 - anti-resorption capacity
What is the Heuter-Volkman principle
Increased compression forces across physis leads to decreased longitudinal physeal growth
Delpech principle is that increased tension forces across physis increases longitudinal physeal growth
3 modes of action of bisphosphonates
- Bind HA inhibiting OC resorption
- Interfere with OC metabolism - kerbs cycle
- Induce apoptosis of OC
What is tumoral calcinosis?
Rare condition of calcification of extra-articular soft tissues around joints associated with normal Ca and elevated Phosphate levels
Typically affects hips, shoulders and elbows
Kids and young adults
Causes of osteonecrosis
Idiopathic Corticosteroids Alcohol Trauma Systemic disorders Haemoglobinopathies Storage - gauchers Caisson Radiation
What are the characteristics of and genetics of Leri-Weil dyschondrosteosis?
Short stature and bilateral Madelungs
SHOX gene
Sex linked dominant
On either x or Y chromosomes.
Genetics of Cleidocranial dysplasia
Autosomal dominant defect in CBFA-1
Transcriptional factor activatin osteoblast differentiation
Genetics of Ellis van Creveld
Autosomal recessive EVC gene
Acromesomelic shortening and post axial polydactyly amongst other anomalies
What is caused by mutations of -
a) FGFR-2
b) CBFA-1
c) Gs Alpha protein
d) FBGFR-3
a) Apert’s
b) cleidocranial dysplasia
c) fibrous dysplasia
d) achondroplasia
What diseases are associated with defects in A) elastin B) Fibrillin C) type 1 collagen D) Type 2 collagen
A) SVAS and AD cutis lads
B) marfan
C) OI & ED
D) SED, achondrogenesis, Stickler syndrome
What do Somites develop into and what forms from them?
Mesodermal in origin Form - dermatome - Dermis Myotome - skeletal muscle Sclerotome - axial skeleton Neural crest - PNS Lateral plate mesoderm - dermis Dorsal myotome - dorsal muscles
Action of TGF-Beta and IHH and PTHrP at physis
TGF-B potent inhibitor of maturation, type x collage. Expression and ALP activity.
SMAD-3 increases activity of TGF-B
PTHrP slows maturation of proliferators Chondrocytes.
Indian hedgehog protein stimulates Chondrocytes to produce PTHrP.
Northern, western, southern blot, elisa, flow cytometry
Northern - RNA
Southern - DNA
Western - Proteins
ELISA - protein Ag AB
Flow cytometry - DNA bound protein
General inheritance patterns and exceptions?
Structural - AD
Enzyme - AR
X-linked recessive - DMD / Becker’s and haemophilia
X-linked dominant rare - hypophosphatEmic tickets and Leei-Weill dyschondrosteosis
Prophylaxis for Ho
Indomethacin 25mg TDs 6 weeks
Radiation 800Gy
What is cathepsin K?
Protease activated by protons from osteoclasts Degrades the ECM of bone
What factors act on osteoclasts?
IL-1 IL-6 TNF-A Calcitonin Colchicine Gamma interferon
No receptors for PTH, Vit-D
What synthesis characterises osteoblasts?
Express ALK Ph
Synthesis collagen 1
Receptors for PTH, Vit-D
What happens with low calcium?
PTH secreted.
Converts 25-Vit D to active 1,25
Both act in osteoblasts
OB regulates and increases OCl activity
Increases
Bone resorption
GIT absorption
Renal absorption.
What is secreted when Ca high?
Calcitonin
Decreases bone resorption
What are the different forms of Vit-D?
D3 - skin. Cholecalciferol
D2 - git. Ergo calciferol
25-hydroxycholecalciferol in liver
1,25 in kidney
Active vitamin D acts on gut, kidney and on osteoblasts
How does oestrogen affect bone?
Acts on osteoblasts - increase collagen synthesis and ALP activity
Acts on osteoclasts to inhibit function
Risk factors for osteoporosis
Non-modifiable
Caucasian, fair hair, scoliosis, OI, early menopause, slender
Modifiable
Inactivity, malnutrition, etoh, smoking, chronic steroids, medications- thyroid, diuretics, phenytoin
Causes of osteoporosis
Primary - idiopathic Secondary - Thyroid disease Hyperparathyroidism Hypothalamic hypogonadism DM HIV Steroids MM Immobilisation
Lab findings in transient OP
ESR ELEVATED
ALP not.
Hot bone scan and MRI
What are the two types of bone formation and where do you find them?
Intramembranous - Flat bones (pelvis, clavicle), primary bone healing (absolute stability), distraction osteogenesis, blastem bone (amputation)
Cleidocranial dysplasia - defect in IM Ossif. Mutation of CBFA1 (Runx2) on Chrom 6
Enchondral (form with a cartilagenous anlage)-
Long bone formation embryonic and physeal growth, secondary bone healing (relative stability)
Type x collagen, Sox-9 affecting collagen II, IV, XI and aggrecan.
PTHrP - delays Chondrocyte differentiation in hypertrophic zone
