Bone Pathologies Flashcards
What are the THREE broad reasons for Rickets/ osteomalacia?
- Vitamin D deficiency
- Resistance to Vitamin D effects
- Phosphate pahtologies
What separates the diagnosis of rickets and osteomalacia?
Rickets the bone plates have not fused, where as in osteomalacia they have.
i.e rickets effects children and osteomalacia effects adults.
What may be seen on x-rays that looks like fractures but isn’t on patients with Osteomalacia?
Where are these commonly seen?
Looser Zones - areas of poor crystallization of the bone, looking like fractures
- scapula
- Pelvis
- Ribs
- Femur
What are the typical symptoms of Osteomalacia?
- Bone pain
- Muscle pain - thighs and shoulder usually
- Weakness - without atrophy
- Gait changes
What would you expect in blood serums to find for osteomalacia?
- High PTH
- Low - normal - calcium
- Low - normal - phosphate
- Low - normal - Alkaline phosphatase
What is VDDR 1A rickets?
Vitamin D Dependent Resistant/ Rickets
- where 25(OH)D cannot be converted to 1,25 (OH)D
**Mutation in 25 - hyroxyvitamin D - 1 - Alpha hydroxylase
VDDR 1B?
Mutation in 25 hyroxylase.
Pre-vitamin 3 never gets converted to 25(OH)D
Why might there be abnormally low levels of phosphate causing Rickets?
Mutation in FGF -23 resulting in increased excretion of phosphate
What are the primary blood markers for bone formation?
- Serum Pro-collagen Type 1 - N - Terminal Pro peptide: PINP
- Total Alkaline Phosphatase levels
What are the primary blood markers for bone resorption?
Serum Collagen Type - 1 linked Telopeptide - CTx
What are the stages of Vitamin D synthesis?
> 7 - dehydrocholesterol
> Cholecaliferol (Pre-vitamin D)
> 25 dihydroxycholecaliferol
> 1,25 dihydroxycholecaliferol (Calitriol)
In x-linked hypophosphatamia, what is the gene mutated and what is the result?
PHREX gene
increased expression of FGF-23
What is oestogensis imperfecta?
Due to multiple genetic defects there is abnormal production of type I collagen.
What genes are usually implicated in Osteogensis imperfecta and what mutations are involved?
COL1A1
COL1A2
Promoter region mutation - fails to initiate
Stop Condon Mutation - poor mRNA formation
mRNA mutations - mRNA is too fragile and breaks
In mild oestogenesis imperfecta, what is primary problem?
Not enough Alpha 1 pre-collagen made - resulting in a LACK of type I collagen
What is the mechanisms behind serve osteogenesis imperfecta?
Glyscine is not at every 3rd amino acid base. - helical structure unable to fold.
- extra time in R.E.R
results in over glycosalation of it and other proteins. putting excessive stress on the cell.
- cell may then enter apoptosis.
What are the treatments for osteoporosis?
- Lifestyle changes:
- increased intake of Calcium
- increased exercise
- minimising fall risks
- reduce smoking
- reduce alcohol - Anti-absorption drugs
- bisphosphantes
- Selective Oestorgen Receptor modulators - Anabolic stimulation of bone growth
- PTH - Teriparatide
What is the experimental drug for achondroplasia? What is its function?
Vosoritide
Degrades FGF-3
With regard to indirect fracture healing, what are the stages and times associated?
- Fracture Haematoma and inflammation - 6-8 hours
- Fibrocartilage - soft callus. Lasts up to ~ 3 weeks. chondrocytes make fibrocartilage.
- fibroblasts and progenitor cells invade into the procallus - Hard callus formation. Lasts up to ~ 3-4 months. Osteoblasts lay down woven bone
- Osteoclasts remodel the bone into compact or trabecular bone
Where in the renal system is calcium re-absorption controlled by PTH?
Thick ascending loop of Henle and the distal convoluted tubule
Define indirect fracture healing
Formation of bone via tissue differentiation until normal skeletal continuity is restored
Define direct fracture healing
This is a intervention, usually surgical. The bone heals through direct contact without the formation of callus.
What are some of the risk factors that can affect fracture healing?
Anatomical
- blood supply - surgical neck of humorous
Patient factors:
- obesity
- diabetic
- malnutrition
- anaemic
- smoking
- age
Medication:
- steroids
- NSAIDs
- Bisphosphanates
What is VDDR2b
Normal expression of 1, 25 D(OH) D. But other molecules are released which inhibit it.
