Patho-2-Osteoporosis Flashcards
(42 cards)
Osteoporosis
fragility of bone that causes increase risk of fractures
WHO classification of osteoporosis
BMD T score o f> -2.5
Osteopenia
BMD is lower than normal but enough to be classified as osteoporosis
- bone matrix normally mineralised but there’s less bone
Osteomalacia
insufficient Ca2+ & phosphate to mineralise newly formed osteoid
- bone = softer & liable to bend, deform or fracture
Types of Osteoporosis
- Generalised - primary or secondary (unassociated or associated with other diseases respectively)
- Regional
Generalised Osteoporosis unassociated with other diseases
- post-menopausal
- ageing
Generalised osteoporosis associated with other diseases
Inflammatory arthritis - RA
Environmental:
- calcium deficiency
- alcohol
- drug induced - corticosteroids, heparin
Endocrine causes
- hyper-parathyroidism
- Cushing’s syndrome
- Hyper-thyroidism
- Hypogonadism
- Anorexia nervosa
- Exercise induced amenorrhea
Diagnosis of Osteoporosis
defined in relation to degree to which bone mineral density is reduced
-
T-score (no. of standard deviations from young normal mean)
- useful for dx
-
Z-score (no. of SD from age-matched mean)
- useful to determine if 2ndry cause exists for OP
Osteoporosis = T score below -2.5
BMD sites
Spine (L1-4 or L2-4)
- predicts spine fracture
- trabecular bone
Hip (femoral neck, intertrochanter, trochanteric)
- predictive of # risk hip & spine
- cortical bone
BMD Advantages & Disadvantages
Advantages:
- quick & easy
- minimal radiaiton exposure
- WHO classification based on DEXA
Disadvantages:
- mineral content across specific area not taking depth into consideration
- doesn’t give full assessment of bone strength (microarchitecture, bone turnover)
- vary between instruments
FRAX Tool - WHO Fracture Risk Assessment Tool
determines clinical risk factors & BMD at femoral neck
- algorithm indicates 10yr probabily of #
- computer driven
Normal bone development continues until…
35yrs
After you reach peak bone mass….
bone density starts to decline
Peak bone mass depends on?
- genetic & envrionmental factors
- accrued through intra-uterine growth, childhood, puberty
Describe the bone remodelling process
- Quiescene (lining cells)
- Resorption (osteoclasts)
- resorption cavity
- formation (osteblasts)
- new bone formation
Remodelling in trabecular bone osteoporosis
- resporption cavities more frequent & deeper in osteoporitic bone - perforations occur
- resorption cavities are incompletey replaced by new bone
Remodelling imbalance is due to?
progressive loss of trabecular bone due to increased osteoclastogenesis
Normal Osteoclastogenesis
- RANKL made by osteoblasts binds to RANK on surface of osteoclast precursors & recruits adaptor protein TRAF6 –> NFKB activation & translocation to nucleus
- NFKB increases c-Fos expression which c-Fos interacts with NFATc1 to trigger transcription of osteoclastogenic genes
- OPG inhibits initiation of proces by binding to RANKL
Function of OPG
Inhibits the number of osteoclast by inhibiting differentiation of osteoclast precursors
Effect of Oestrogen on osteoclastogenesis
Anti-resorptive effect by stimulating OPG expression in OB
Osteoblast regulation
- LRP5 = modulator of OB function
- co-receptor series of OB stimulating proteins via Wnt signalling pathway
- Frz & LRP5 bind to Wnt –> activating bone formation
- inhibitory effects of glucocorticosteroids may be via Wnt signalling pathway
Prevention of OP
- calcium intake (800-1200mg/day)
- exercise
- avoid smoking & alcohol
- Vit D intake
Pharmacological Mx of OP
- Anti-resorptives
- Anabolic agents
- Dual agents
Examples of anti-resorptives
- Bisphosphates
- SERMS
- Calcitol
- RANKL inhibitor
