Osteoporosis - L6.1

Question 1

What three processes go hand in hand and can either enhance RA progression or prevent RA progression?

Answer 1

Disability, structural damage, and disease activity.

Question 2

RANKL is essential for osteoclast formation, function, and survival. Describe the activity and amount of RANKL in the synovium of patients with:

• active RA
• non-active RA
• healthy control

What does this indicate?

Answer 2

• active RA: high amounts of RANKL
• non-active RA: less RANKL activity than active RA, but still high.
• healthy controls: RANKL activity absent/balanced.

This indicates and confirms the role of RANKL in osteoclast formation, function, and survival and highlights how too much RANKL activity will lead to increased osteoclast formation, function, and survival, ultimately leading to increased bone resorption.

Question 3

• What is the function of denosumab?
• What is the function of anti-sclerostin?

Answer 3

• Denosumab is an anti-resorption medicine that works by blocking RANKL, thereby preventing RANKL from binding to RANK on osteoclasts and preventing bone resorption by osteoclasts.
• Anti-sclerostin: binds to sclerostin, thereby preventing inhibition of Wnt signaling in osteoblasts and preventing inhibition of bone formation.

Question 4

What is seen in postmenopausal women with RA regarding osteoporosis?

Answer 4

That there is a 2-fold increase in osteoporosis in postmenopausal women with RA.

Question 5

Infliximab is a biological that can be used to treat RA. Sum up findings regarding the efficiency of infliximab in the treatment of RA.

Answer 5

• Mixed responses
• Decrease in (markers of) bone degradation
• Changes (i.e. increase) in (markers of) bone formation
• Changes in serum levels of RANKL and OPG (specifically RANKL decreased significantly over a 1 year time period).

Question 6

Name factors that influence bone fragility in RA.

Answer 6

• Serological factors: presence of antibodies to citrullinated protein antigens (ACPAs) (class of autoantibodies highly specific for RA).
• Mechanical factors: lower limbs joint destruction, risk of falls.
• Medications: glucocorticosteroids.
• Clinical risk factors: age, postmenopausal status.
• Systemic inflammation: change in bone remodeling, sarcopenia/rheumatoid cachexia.

Question 7

What is ankylosing spondylitis?

Answer 7

• A chronic and progressive inflammatory disease characterized by inflammatory low back pain and stifness.
• Prevalence between 0.5-0.9%.
• Usually diagnosed at age 30-40 years.
• Associated with genetic marker HLA-B27.