302 osteoporosis pathophysiology Flashcards
What is a fragility fracture?
A fracture by falling from standing or less or a spontaneous fracture not caused by malignancy
Why do people get fragility fractures?
Because the exposure to trauma exceeds the mechanical strength of the bone due to:
-Reduced bone mineral density
-Altered bone architecture
–mutations in type 1 collagen
–Altered hydroxyapatite crystal structure
–Advanced glycation end products in diabetes
How is bone mineral density measured?
Through bone densitometry (DXA)
How is altered bone architecture measured?
Through a trabecular bone score (DXA)
or high resolution quantitative CT (pQCT)
What is skin autofluorescence associated with?
Low bone mineral density in T2 diabetes
What is microindentation used for?
For measuring the hardness of a material on a microscopic scale
Which factors can be improved by an individual to reduce fragility fractures?
-Reduce falls risk factors
-Improve coordination
-Improve muscle strength
What is fluoride treatment used for?
Used to make bones and teeth stronger
What is Etidronate used for?
It’s used to treat Piaget’s disease by preventing heterotopic ossification (bones develop in soft tissues)
Describe the bone re-modelling cycle
- Quiescence
- Resorption
- Reversal
- Formation
What is the function of the RANK ligand in bone resorption?
The signalling regulates osteoclast formation, activation and survival in normal bone modelling and remodelling and in a variety of pathologic conditions characterized by increased bone turnover
The RANKL joins with an osteoclast precursor to create a mature osteoclast
What is the function of OPG?
OPG protects bone from excessive resorption by binding to RANKL and preventing it from binding to RANK
What is Denosumab?
A full human monoclonal antibody that binds to the RANK ligand (inhibits human RANK)
This reduced the risk of fractures
How is Denosumab administered?
A subcutaneous injection every 6 months
-Long half-life
How is Denosumab cleared in the body?
Cleared by the Reticuloendothelial system
No renal excretion
What is Scerosteosis?
A syndrome characterized clinically by variable syndactyly and progressive skeletal overgrowth (particularly of the skull), resulting in distinctive facial features (mandibular overgrowth, frontal bossing, midfacial hypoplasia), cranial nerve entrapment
Caused by a SOST gene mutation
What is the effect of Sclerostin antagonising Wnt signalling?
The SOST gene in Osteocytes produces Sclerostin which inhibits the WnT signalling system which reduces osteoblast activity
Which drug inhibits Sclerostin?
Romosozumab
It’s a antisclerostin antibody
What is the function of Grancalcin?
It’s secreted by senescent immune cells to promote skeletal aging
It represses osteogenesis and promotes adipogenesis
Genetic depletion of Gca in neutrophils and macrophages slows skeletal aging
What is Grancalcin neutralising antibody treatment used for?
To improve skeletal health during aging
