302 osteoporosis pathophysiology

Question 1

What is a fragility fracture?

Answer 1

A fracture by falling from standing or less or a spontaneous fracture not caused by malignancy

Question 2

Why do people get fragility fractures?

Answer 2

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

Question 3

How is bone mineral density measured?

Answer 3

Through bone densitometry (DXA)

Question 4

How is altered bone architecture measured?

Answer 4

Through a trabecular bone score (DXA)

or high resolution quantitative CT (pQCT)

Question 5

What is skin autofluorescence associated with?

Answer 5

Low bone mineral density in T2 diabetes

Question 6

What is microindentation used for?

Answer 6

For measuring the hardness of a material on a microscopic scale

Question 7

Which factors can be improved by an individual to reduce fragility fractures?

Answer 7

-Reduce falls risk factors
-Improve coordination
-Improve muscle strength

Question 8

What is fluoride treatment used for?

Answer 8

Used to make bones and teeth stronger

Question 9

What is Etidronate used for?

Answer 9

It’s used to treat Piaget’s disease by preventing heterotopic ossification (bones develop in soft tissues)

Question 10

Describe the bone re-modelling cycle

Answer 10

1. Quiescence
2. Resorption
3. Reversal
4. Formation

Question 11

What is the function of the RANK ligand in bone resorption?

Answer 11

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

Question 12

What is the function of OPG?

Answer 12

OPG protects bone from excessive resorption by binding to RANKL and preventing it from binding to RANK

Question 13

What is Denosumab?

Answer 13

A full human monoclonal antibody that binds to the RANK ligand (inhibits human RANK)

This reduced the risk of fractures

Question 14

How is Denosumab administered?

Answer 14

A subcutaneous injection every 6 months
-Long half-life

Question 15

How is Denosumab cleared in the body?

Answer 15

Cleared by the Reticuloendothelial system

No renal excretion

Question 16

What is Scerosteosis?

Answer 16

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

Question 17

What is the effect of Sclerostin antagonising Wnt signalling?

Answer 17

The SOST gene in Osteocytes produces Sclerostin which inhibits the WnT signalling system which reduces osteoblast activity

Question 18

Which drug inhibits Sclerostin?

Answer 18

Romosozumab

It’s a antisclerostin antibody

Question 19

What is the function of Grancalcin?

Answer 19

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

Question 20

What is Grancalcin neutralising antibody treatment used for?

Answer 20

To improve skeletal health during aging