Osteo

Question 1

How is the diagnosis of osteoporosis different from historically

Answer 1

used to be after a fracture but now we can measure BMD

Question 2

How do you Measure the central skeleton

what is measured

Answer 2

DXA

Spine, proximal femur, whole skeleto

Question 3

how to you measure the peripheral skeleton

Answer 3

QUS (quantitative ultrasound) – Peripheral x-ray methods (forearm, calcaneal), radiographic absorptiometry, radiogrammetry, – Quantitative computerized tomography (QCT

Question 4

why would someone be meausred more than once

Answer 4

To identify individuals with continued BMD loss, despite appropriate osteoporosis treatment

Question 5

Continued BMD loss exceeding the Least significant change may reflect:

Answer 5

Poor adherence to therapy – Failure to respond to therapy – Previously unrecognized secondary causes of osteoporosi

Question 6

Most anti-osteoporosis therapies do what to BMD

Answer 6

do not cause large BMD increases2 – Stable BMD is consistent with successful treatment

Question 7

what frequency of BMD should be followed

Answer 7

Usually repeated every 1 – 3 years, with a decrease in testing once therapy is shown to be effective • In those at low risk without additional risk factors for rapid BMD loss, a longer testing interval (5 – 10 years) may be sufficient

Question 8

When should the helthy population go for BMD testing

Answer 8

All women and men age > 65

Question 9

IF THE POPULATION HAS CLINICAL RISK FRACTURES, WHEN SHOULD THEY GO FOR BMD TESTING

Answer 9

Postmenopausal women, and men aged 50 – 64 with clinical risk factors for fracture: – Fragility fracture after age 40 – Prolonged glucocorticoid use† – Other high-risk medication use* – Parental hip fracture – Vertebral fracture or osteopenia identified on X-ray – Current smoking – High alcohol intake – Low body weight (< 60 kg) or major weight loss (>10% of weight at age 25) – Rheumatoid arthritis – Other disorders strongly associated with osteoporosis (TYPE 1 DIABETES, CUSHINGS DISEASE, MALABSORPTION…)

Question 10

Indications for BMD Testing for Individuals Under Age 50 Year

Answer 10

Fragility fracture • Prolonged use of glucocorticoids* • Use of other high-risk medications† • Hypogonadism or premature menopause • Malabsorption syndrome • Primary hyperparathyroidism • Other disorders strongly associated with rapid bone loss and/or fractur

Question 11

T VERSUS Z SCORES

Answer 11

T (only for a specific population)-score is the number of standard deviations that BMD is above or below the mean normal peak BMD for young white women (NHANES III for hip measurements)

• Z-score is the number of standard deviations that BMD is above or below the mean normal BMD for sex, age, and (if references are available) race/ethnicity

Question 12

can osteo be diagnoses with BMD alone for those under 50

Answer 12

no

Question 13

what is BMD reporting based upon

Answer 13

based upon lowest value for lumbar spine (minimum two vertebral levels), total hip, and femoral neck – If either the lumbar spine or hip is invalid, then the forearm should be scanned and the distal one-third region reported

Question 14

What is FRAX and CAROC.

what is it based upon (what measurement)

which organisation are they from

Answer 14

its a way of assessing the risk of a fracture occuring.

choice based on personal preference and convenience

based on femoral neck t-scores only

CAROC: Joint initiative of the Canadian Association of Radiologists and Osteoporosis Canada1 – FRAX: Fracture Risk Assessment Tool developed by the World Health Organization2

Question 15

10-year Risk Assessment: CAROC

Answer 15

Semiquantitative method for estimating 10-year absolute risk of a major osteoporotic fracture* in postmenopausal women and men over age 50 – Stratified into three zones (Low: < 10%, moderate, high: > 20%) • Basal risk category is obtained from age, sex, and T-score at the femoral neck

USES GRAF

Question 16

What factors increase the CAROC basal risk by one catagory ( for example from low to moderate)

Answer 16

Fragility fracture after age 40*1,2 – Recent prolonged systemic glucocorticoid use**

Question 17

Risk Assessment Using FRAX- what factors are considered

Answer 17

Uses age, sex, BMD, and clinical risk factors to calculate 10-year fracture risk* – BMD must be femoral neck – FRAX also computes 10-year probability of hip fracture alone • This system has been validated for use in Canada1 • There is an online FRAX calculator with detailed instructions at: www.shef.ac.uk/FRAX

Question 18

FRAX Clinical Risk Factors

Answer 18

Parental hip fracture • Prior fracture • Glucocorticoid use • Current smoking • High alcohol intake • Rheumatoid arthritis

Question 19

CAROC AND FRAX ONLY WORK ON WHAT KIND OF PATIENTS, CAN IT MEASURE RESPONSES TO THERAPY

Answer 19

Calculate risk for treatment-naïve patients only • Cannot be used to monitor response to therapy
• Using CAROC or FRAX in a patient on therapy only reflects the theoretical risk of a hypothetical patient who is treatment naïve and does not reflect the risk reduction associated with therapy

Question 20

Bone Turnover Markers (BTMs)

Answer 20

The value of bone turnover markers (BTMs) in estimating future risk of fracture in individual patients needs further research • As a result, BTMs have not yet been integrated in current fracture-risk assessment systems – Bone-specific alkaline phosphatase (BAP) – Urinary collagen type 1 cross-linked C-telopeptide (CTX

Question 21

VFA Recognition and Reportin

Answer 21

VFA is a scanning and software option on bone densitometers • A fracture detected by vertebral fracture assessment (VFA) or radiograph should be considered a prior fracture under the FRAX or CAROC syste

Question 22

1:3 vs 1:5

Answer 22

women vs. men

Question 23

the quick reference quide is intended for

Answer 23

physicians, not specialists

Question 24

Client history, trying to identify risk factors for low BMD, fractures and falls

Answer 24

provides background information
access whether the person is likely to have risk fractures- even answering Yes one
the options are:
prior fragility fracture. parental hip fracture, glucocorticoids use, current smoking (looses weight), high alcohol intake, rheumatoid arthritis, inquire about falls in previous 12 months, inquire about gait and balance

the only 2 that are grade a is prior fragility fractures and previous falls: in randomized control they are more significant

strange that vitamin d and calcium (grade A evidence) questions are not there- but would have to do an interview and take too long

Question 25

physical exam

Answer 25

weightloss
height loss
pysical ability

Question 26

glucocorticoid

Answer 26

adrenal steroids that are hormones that raise blood glucose, the drug name is prednisone
they are anti-inflammatory (take for rheumatoid arthristis)

cause bone loss

the other option is Non-staroidal anti-inflammatory drugs for example aspirin, advil

Question 27

many people who break their hip die within a year- can’t take care of themselves

Answer 27

k

Question 28

what info does a client history or physical examine provide

Answer 28

Client History
Provides background information
Assess whether person likely to have risk for fracture – even answering YES once

Physical Exam 
 Weight loss (weight loss of >10% since age 25 is significant) 

Height loss (measure height, rib to pelvis (less than 2 finger is associated with vertebral fracture) and occiput to wall distance more than 5 cm is suspicious .
- kyphosis)
Physical ability (fall - get up and go test- get up without using arms

radiology reports are often not reported

Question 29

grade a risk factors for low BMD

Answer 29

prior fragility fracture, parental hip fracture, glucocorticoid, smoker, alcohol, rheumatoid, falls)

History of falls in the lastyear is one of the mostsignificant risk factors forpredicting future fall1-6
Dementia and poor physicalfunction have also beenfound to be associated withfalls and fractures in olderadults2,4,5

Question 30

Importance of Height Loss

Answer 30

Increased risk of vertebral fracture
Historical height loss (> 6 cm)1,2
Measured height loss (< 2 cm)3-5
ANUALLY- NEED ACCURATE MEASUREMENT OR 6 CM OVERALL
Significant height loss should be investigated by a lateral thoracic and lumbar spineX-ray
ONCE YOU START TO HUNCH ITS IMPOSSIBLE TO REPAIR THE VERTEBRAES

Question 31

secondary causes of osteo

Answer 31

GI disorders
Genetic disorders
Endocrine disorders
Hypogonadal states
Miscellaneous 
Anything that disrubts your normal hormones , for example cushing disease- increases gluticorticoids

Question 32

what biochemical data should be examined in suspected osteoporosis

Answer 32

Calcium, corrected for albumin 
Complete blood count
Creatinine
Alkaline phosphatase
Thyroid stimulating hormone (TSH)
Serum protein electrophoresis for patients with vertebral fractures
25-hydroxy vitamin D (25-OH-D)*

Question 33

Tests for Potential Secondary Causes

Answer 33

Parathyroid hormone (PTH)
Protein electrophoresis
Antibodies associated with gluten enteropathy
Testosterone (bioavailable or total)
Serum prolactin
24-hour urine for calcium

hyperparathyroidim, multiple myeloma, celiac disease, hypogonadism, hypercalciuria

Question 34

For calcium, ~ DRIs but men at risk 50-70y, OC has

Answer 34

1200 mg Ca.

Question 35

protein

Answer 35

(.8-1.2 g/kg);

Question 36

caffein

Answer 36

> 4 cups of coffee

Question 37

2 concepts for understanding mechanism of action of drugs for osteo

Answer 37

Anti-resorptive = blocks bone resorption
Action on osteoclasts (either killed prematurely or the number being made is less)
Anabolic = promote bone formation
Action on osteoblasts (only one of theses fo focus on anti-resorption)
1. bone remodelling is a cycle
2. There is interplay between cells

Question 38

OPG =

RANKL

Answer 38

osteoprotegerin

= secreted by osteoblasts to bind to RANK on pre-osteoclasts to promote differentiation. But OPG binds more to RANK than does RANKL

Question 39

On the right is resorption
Osteoblasts (which make bone) secrete RANKL which attach to osteoclast (which breaks down bone)
Bisphophenate
Estrogen is important- after menopause estrogen is decreased and it breaks down bone faster- can give estrogen

The green bubble- its an antibody (ab) competes with osteoblast and binds RANKL

Answer 39

j

Question 40

Mechanism of drug action

Answer 40

Antiresorptives:
Bisphosphonates inhibit osteoclast action
Raloxifene (SERM) is like estrogen; act to reign in factors that stimulate preOC development
Denosumab - is an “antibody” (-ab); acts by binding RANKL which prevents PreOC osteoclast

Bone Forming therapy:
Teriparatide is PTH but when delivered in one large dose, acts to stimulate bone resorption independent of bone remodelling cycle.

Question 41

ANK = receptor activator of nuclear factor kappa-B ligand

Wikipedia -
Precursors to osteoclasts, called pre-osteoclasts, express surface receptors called RANK (receptor activator of nuclear factor-kappa B). RANK is a member of the tumor necrosis factor receptor (TNFR) superfamily. RANK is activated by RANKL (the RANK-Ligand), which exists as cell surface molecules on osteoblasts. Activation of RANK by RANKL promotes the maturation of pre-osteoclasts into osteoclasts. Denosumab inhibits this maturation of osteoclasts by binding to and inhibiting RANKL. This mimics the natural action of osteoprotegerin, an endogenous RANKL inhibitor, that presents with decreasing concentrations (and perhaps decreased avidity) in patients who are suffering from osteoporosis. This protects bone from degradation, and helps to counter the progression of the disease.

Answer 41

s

Question 42

Bone Forming therapy:

Answer 42

Teriparatide is PTH but when delivered in one large dose, acts to stimulate bone resorption independent of bone remodelling cycle.

Question 43

low, moderate and high risk

Answer 43

low: 10-year fracture <10%

moderate risk: 10-year fracture risk 10-20%- good evidence to take drugs

High Risk: 10-year fracture risk >20 - should take drugs

Question 44

Bone turnover biomarkers in serum or urine:

Answer 44

Bone Alkaline Phosphatase
(BAP)

Collagen-propeptide
(P1NP)

Osteocalcin
(OC)

Question 45

Resorption

Answer 45

Tartrate-Resistant Acid Phosphatase 5b
(TRAP-5b)

Pyridinium crosslinks

Crosslinked collagen telopeptides
(CTX, NTX)

Question 46

Factors that Warrant Consideration forPharmacological Therapy in Moderate Risk Patients

Answer 46

Additional vertebral fracture(s) (> 25% height loss with end-plate disruption) identified on VFA or lateral spine X-ray
Previous wrist fracture in individuals > 65 or those with T-score < -2.5
Lumbar spine T-score much lower than femoral neck T-score
Rapid bone loss
Men on androgen deprivation therapy for prostate cancer
Women on aromatase inhibitor therapy for breast cancer
Long-term or repeated systemic glucocorticoid use (oral or parenteral) that does not meet the conventional criteria for recent prolonged systemic glucocorticoid use (i.e., > 3 months cumulative during the preceding year at a prednisone equivalent dose > 7.5 mg daily)
Recurrent falls defined as falling 2 or more times in the past 12 months
Other disorders strongly associated with osteoporosis, rapid bone loss or fractures

Question 47

Speaker notes
A recent case series reported an increased incidence of subtrochanteric fractures associated with long-term use of bisphosphonates.1 The authors identified 15 women with subtrochanteric fractures who had been treated with alendronate. They noted that bisphosphonate use was observed in 37% of all patients presenting with this type of fracture and that in their group of patients these fractures represent only 6% of all hip fractures. Limitations of this report included the small number of women identified with these atypical fractures, the unknown number of patients who sustained these types of fracture who never received alendronate therapy, and the fact that this was not a prospective randomized controlled trial—as such it is not possible to state that alendronate caused the atypical fractures. Further, a recent case-control study reported no increase in the incidence in subtrochanteric fractures among patients taking bisphosphonates compared with controls.2 An increased incidence of subtrochanteric fractures has not been reported with the use of other bisphosphonates. This area is the focus of further research activities.

Answer 47

a