Lecture 27 - Bones in Rheumatoid Arthritis Flashcards
Osteopenia
Decrease in bone mass and mineral density
Not as severe as osteoporosis
Most debilitating bone problem in RA
Focal bone erosion
Patterns of bone loss in RA
1)
2)
3)
1) Juxta-articular/peri-articular osteopenia
2) Focal bone erosion
3) Systemic osteoporosis
Juxta-articular or peri-articular osteopenia
1)
2)
1) Occurs early in RA
2) Occurs in cancellous or trabecular bone near affected joint
Focal bone erosion
1)
2)
1) Occurs within cortical bone, at affected joint
2) Normally begins at the join between cartilage and bone
Systemic osteoporosis in RA
1)
2)
1) Present in many patients
2) Thinning of trabecular/cancellous bone and cortical bone at sites remote from affected joint (EG: hip, vertebrae)
How were osteoclasts first identified as causative agents of RA bone loss?
In situ hybridisation
Staining with RNA probe for bone-degrading enzymes
Sources of RANKL in synovial joints
1)
2)
3)
1) Osteoblast-lineage cells
2) T cells
3) Synovial fibroblasts
RANKL/OPG ratio at pannus/bone junction in RA
RANKL outweighs OPG
Leads to net bone loss
Bone phenotype of RANKL KO mice?
Osteopetrotic
Effect of inducing RA in RANKL KO mice
Mice are protected from bone loss, as there are no osteoclasts
Still significant inflammation
Effect of OPG.Fc treatment 1) 2) 3) 4)
1) Reduces osteoclast numbers in inflammed joint
2) Focal bone erosion
3) Systemic bone loss in animal models
4) No effect on synovial inflammation
OPG.Fc
Osteoprotegerin -immunoglobulin segment complex
A RANKL inhibitor
Function of osteoclasts in RA
Osteoclasts are the only cell responsible for bone loss in RA
Do focal bone lesions recover with treatment?
No
Continued erosion can be controlled, but erosive lesions often persist