OSTEOPOROSIS Flashcards
For every 1SD below normal T score (T score below -1), , relative risk of fracture is increased by…
1.5-1.5 fold
Normal BMD
Over T score -1
osteopenia definition
-1 to -2.5 T score
osteoporosis
less than -2.5 T score
Severe osteoporosis
below -2.5 T score and at least one fracture
When to use Z score
when below -2 may be useful in identifying those with accelerated cause of bone loss
When to use FRAX and when to use Garvan institute
Frax is a tool only valid in over 40s. Garvan better if older as includes recent falls in data. Recommend treatment if 10 year risk of hip fracture over 3 percent and 10 year risk of any fracture over 14%- but PBS reimbursement not based on this yet
Physically, what is the glucocorticoid effect on bones
Loss of both horizontal and vertical trabeculae there for tend to fracture at relatively higher BMD. Glucocort and below -1.5 get bisphos on PBS
What is the evidence for calcium and vitamin D in reducing fractures
RECORD trial- no effect- but poor compliance in this trial
Associated with- reduced bone loss at hip and spine
In trials with greater compliance, reduction in any fracture, osteoporotic fracture (33%)
Need higher doses in fat people as fat soluble
Most benefit is for people with lower baseline vitamin D
Effects of calcium on MI
insufficient evidence to support this finding- analysed trials were not designed to assess impact of calcium on CV risk. Data conflicting.
Numerous large studies- no increase in CV event risk
Food best source calcium, supplement only if cannot be achieved
Elderly and others with impaired renal function who take supplements may be at higher risk of CVD
Lower doses calcium (500-600mg) likely to be as effective
Side effects of raloxifene
Hot flushes, leg cramps. Only spinal fracture risk reduction
Should you delay administration of a bisphosphonate in the acute post fracture period?
Better to delay ZA administration 2 weeks post fracture
No evidence of impaired healing, actually strengthen callus formation
Is strontium ranelate associated with ONJ?
No
What can happen when you take bisphosphonates for more than 7 years?
Femural stress fractures Ask for thigh or groin pain Plain films may show periostial elevation - bone scan sees hot spots. Stop treatments. 1 in 1000 to 10000 on treatment
Criteria for teriparatide on PBS?
T score below -3 and 2 minimal trauma fractures and intolerant to bisphosphonates or one fracture has happened after at least 12 months on a bisphosphonate
Black box warning on teriparatide why?
In a rat strain prone to cancer long term teriparatide caused osteogenic sarcoma
2 cases in half a million people
Strontium ranelate effect on MI?
Increase risk of MI but not mortality - in postmenopausal women over age 75
Rate of ONJ in malignancy and osteoporosis
malig: 0.8-12%
osteoporosis: 1 in 1000 to 1 in 10000
** new name is antiresorptive associated ONJ, as denosumab also does this
RISK FACTORS for ONJ
malignancy smoking age over 65 use of bisphosphonates more than 2 years denture wearing diabetes invasive procedures like tooth extractions periodontitis
What are the best markers of new bone formation?
bone specific ALP
P1NP
(also osteocalcin)
What are the best markers of bone destruction?
C-telopeptide cross links (serum)
N-telopeptide cross links (uriNe)
How do you best characterise bone loss in men vs women with age?
At menopause there is an ACCELERATED PHASE OF TRABECULAR BONE LOSS which is from trabecular perforation and loss of connectivity.
This is followed by a slower phase that occurs in both med and women - affects CORTICAL SITES. Reduced osteoblast numbers, number of trabeculae. DECREASED WALL WIDTH is the most consistent finding in men and women with osteoporosis who are older.
Bone loss in older men is associated with trabecular thinning rather than perforation.
Oestrogen deficiency leads to cortical bone loss.
Explain the system with RANK, RANKL, OPG, and denosumab.
Normally, RANKL on osteoblasts binds to RANK on pre-osteoclasts, which triggers maturation and bone resorption. Osteoblasts secrete OPG, which binds to their own RANKL to prevent this from happening.
Denosumab is a monoclonal against RANKL, mimicking the OPG effect.
Mechanism of action of bisphosphonates
Inhibit enzyme farnesyl pyrophosphate synthase in osteoCLASTS which is involved in cholesterol synthesis . Intermediate metabolites of the pathway are needed for cell membrane ruffled border. Loss ruffled border means cannot absorb so eventually apoptose.
