Patho-2-Osteoporosis Flashcards
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
Examples of anabolic agents
PTH
Example of dual agents
Strontium ralenate
What is the requirement to be included to OP management regimen?
Tx needs to demonstrate:
- increase in bone density
- reduction in # sites
MOA of bisphosphates
Encourage osteoclast to undergo apoptosis
MOA of denosumab
inhibits maturation of osteoclast by binding to & inhibiting RANKL
Function of RANKL
promotes maturation of osteoclasts
Effectiveness of Oestrogen
Risk of breast cancer significant so not advised for OP treatment any more
SERM
Selective Estrogen Receptor Modulator
MOA of SERM
Acts on estrogen receptors in bone and not in breast tissue
MOA of calcitrol
- Regulates calcium homeostasis and bone metabolism
- Promotes bone mineralisation
MOA of parathyroid hormone
increases serum calcium –> increases bone resorption
MOA of Strontium Ralenate
- Increases bone formation and decreases bone remodelling.
- Induces pre-osteoblasts & osteoblast differentiation
- inhibits osteoclast differentiation
Choice of Rx for Post-menopausal women
- Bisphosphates and denosumab
- 2nd line: Strontium
Choice of Rx for Male OP
- Bisphosphates
- 2nd line: Strontium
Choice of Rx for Corticosteroid induced OP
Bisphosphates
Choice of Rx for prevention of fracture
Bisphosphates and denosumab
How is Osteoporosis diagnosed?
- When a fracture occurs after fall down stairs
- When the patient has a family history of osteoporosis
- When Bone density is below -3.0
- When a facture occurs after minimal trauma
- If Vitamin D is low
- When Bone density is below -3.0
Treatment of established osteoporosis
- Requires Hydrotherapy to improve bone density
- Needs Medicare approval
- Calcium supplement is adequate
- Anabolic Agents are always needed to build bone is osteoporosis
- Antiresorptiveagents are first line therapy
- Antiresorptiveagents are first line therapy
