2010 Guidelines Case Study #4: Mr. JM 2010 Guidelines

2010 Guidelines2010 Guidelines

Case Study #4:Case Study #4:Mr. JMMr. JM

2010 Guidelines


Case PresentationCase Presentation

• 64-year-old retired firefighter– Retired nine years ago; now doing contract

carpentry

• Presents for physical examination, complaining his back has been “worse than usual” the past three weeks

• On no medications• Prior smoker (45 pack/year history)

– Quit smoking one year ago


Physical ExaminationPhysical Examination

• Height: 180 cm (5'11")– Patient recalls being 185.5 cm (6'1")

• Weight: 80 kg (up 5 kg from one year ago)• Body mass index (BMI): 24.7 kg/m2

– Changes in height and weight can be signs of vertebral fractures

– Other indicators of vertebral fracture in physical examination: Rib-pelvis distance and occiput-wall distance


Risk Factor AssessmentRisk Factor Assessment

• Family history: none significant• No history of systemic glucocorticoids or

androgen-deprivation therapy• No history of secondary causes of osteoporosis• Historical height loss• No previous trauma• Alcohol use: approximately two drinks per week

Click here for a discussion of factors known to increase fracture risk in men.


Why is Osteoporosis Underappreciated Why is Osteoporosis Underappreciated in Men?in Men?

• Men have higher peak bone mass• Slower rate of bone loss• Shorter life expectancy• Greater periosteal bone formation (greater

cross-sectional bone diameter and a biomechanical advantage since larger bones have less fracture risk)

Khan AA, et al. CMAJ 2007;176(3):345-348.


QuestionQuestion

• What tests would you consider ordering?


Mr. JM: Diagnostic Testing Mr. JM: Diagnostic Testing

• Screening for osteoporosis with dual energy X-ray absorptiometry (DXA) is indicated, based on 2010 guideline criteria– T-score -1.9 at femoral neck

• Lateral thoraco-lumbar spine X-ray is ordered to rule out vertebral compression deformities– The radiologist makes note of two vertebrae being

wedge shaped and just meeting the criteria for vertebral compression fracture


QuestionQuestion

• Given the presence of vertebral fractures, is further risk assessment necessary before initiating pharmacologic therapy?


Considerations for TherapyConsiderations for Therapy

• The guidelines do recommend that diagnosis and treatment decisions should be based on a validated 10-year risk-assessment tool (i.e., CAROC or FRAX)– FRAX predicts 12% risk (moderate)1

• However, the presence of multiple vertebral fractures in this case place Mr. JM at high risk– In fact, 10-year assessment tools underestimate

risk in patients with vertebral fractures

1. Leslie WD, Lix LM, et al. Osteoporos Int 2010. In press.


QuestionQuestion

• How would you proceed with therapy for Mr. JM?


Treatment ConsiderationsTreatment Considerations

• Bloodwork to rule out secondary causes of osteoporosis

• Assume vitamin D level is low and start supplementation (with calcium)

• According to the 2010 OC guidelines– Pharmacotherapy is indicated for a high-risk patient

(see integrated management model)– Testosterone therapy is not recommended


Mr. JM: ConclusionsMr. JM: Conclusions

• Mr. JM is high risk because of his vertebral fractures

• In this case, 10-year assessment tools underestimate risk

• Patients at high risk benefit from pharmacologic therapy– Recommended agents for first-line use in men are

alendronate, risedronate, or zoledronic acid


Case 4 Case 4 – – Mr. JM

Back-up MaterialBack-up MaterialAdditional slides that can be accessed from hyperlinks on case slides


Importance of WeightImportance of Weight

• In men > 50 years and postmenopausal women, the following are associated with low bone mineral density (BMD) and fractures– Low body weight (< 60 kg)– Major weight loss (> 10%

of weight at age 25)

1. Papaioannou A, et al. Osteoporos Int 2009; 20(5):703-715.2. Waugh EJ, et al. Osteoporos Int 2009; 20:1-21.

3. Cummings SR,et al. N Engl J Med 1995; 332(12):767-773.4. Papaioannou A, et al. Osteoporos Int 2005; 16(5):568-578.

5. Kanis J, et al. Osteoporos Int 1999; 9:45-54.6. Morin S, et al. Osteoporos Int 2009; 20(3):363-70.Return to case


Importance of Height LossImportance of Height Loss

• Increased risk of vertebral fracture– Historical height loss (> 6 cm)1,2

– Measured height loss (> 2 cm)3-5

• Significant height loss should be investigated by a lateral thoracic and lumbar spineX-ray

1. Siminoski K, et al. Osteoporos Int 2006; 17(2):290-296.2. Briot K, et al. CMAJ 2010; 182(6):558-562.

3. Moayyeri A, et al. J Bone Miner Res 2008; 23:425-432.4. Siminoski K, et al. Osteoporos Int 2005; 16(4):403-410.

5. Kaptoge S, et al. J Bone Miner Res 2004; 19:1982-1993.Return to case


Additional Tests for Clinical Additional Tests for Clinical Identification of Vertebral FractureIdentification of Vertebral Fracture

Test Rationale Method Interpretation

Rib-pelvis distance1

To identify lumbar fractures

Measure the distance between the costal margin and the pelvic rim on the mid-axillary line

< 2 fingerbreadths is associated with vertebral fractures

Occiput-to-wall distance2,3

To help identify thoracic spine fractures

Stand straight with heels and back against the wall

> 5 cm raises suspicion of vertebral fracture

1. Olszynski WP, et al. BMC Musculoskeletal Disorders 2002; 3:22.2. Green AD, et al. JAMA 2004; 292(23):2890-2900.

3. Siminoski K, et al. J Bone Miner Res 2001; 16(Suppl):S274.


Rib-Pelvis and Occiput-to-Wall Rib-Pelvis and Occiput-to-Wall DistancesDistances

4 cm

3 FBs

8 cm

12 cm

2 FBs

Height loss3 cm

8 cm

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Risk Factors with Good Evidence Risk Factors with Good Evidence for Low BMD in menfor Low BMD in men

• Advancing age – Between 50 and 80 years, men have1.5% – 2.5%

decline in hip BMD per year– BMD at lumbral-sacral spine increases with age (falsely

elevated due to osteophyte formation)

• Smoking– Current smokers have greater risk of low BMD at the hip

compared to former smokers.– Highest risk subgroups

• Men > 20 pack years• Current smokers with low body weight (< 75 kgs)

Papaioannou A, et al. Osteoporosis Int 2009;20:507-518.


Risk Factors with Good Evidence Risk Factors with Good Evidence for Low BMD in Menfor Low BMD in Men

• Low weight/weight loss– BMD at the hip increases roughly 3% – 7% for

every 10 kg weight gain– Low baseline weight/BMI predicts subsequent bone

loss at the hip

• Physical functional limitations– Men who can rise from a chair without using arms

have 2% – 4% higher hip BMD than those who cannot

• Prevalent fracture after 50 years of age

Papaioannou A, et al. Osteoporosis Int 2009;20:507-518.Return to case


Indications for BMD TestingIndications for BMD Testing

• All women and men age > 65 • 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

Return to case†At least three months cumulative therapy in the previous year at a prednisone-equivalent dose > 7.5 mg daily;* e.g. aromatase inhibitors, androgen deprivation therapy.


Plain RadiographicPlain RadiographicExaminations of the SpineExaminations of the Spine

Type Use(s)

Plain radiographs, complete

To investigate symptoms such as back pain or after trauma

Plain radiographs, limited

Specifically to look for osteoporotic fracturing

Plain radiographs, incidental

Incidental views of the spine on radiographs undertaken for other purposes (e.g., lateral chest films)


Other RadiographicOther RadiographicExaminations of the SpineExaminations of the Spine

Type Use(s)

Vertebral fracture assessment (VFA), T4 to L4

Incidental to DXA – provides lower-resolution images of the spine, not subject to projection distortion

Computed tomography (CT) of the spine

To clarify subtle or uncertain findings on radiographs

Magnetic resonance imaging (MRI) of the spine

To examine soft tissues or clarify the acuteness of spinal fracturing

Radionuclide bone scanningTo look for disease activity or distributionMay also be helpful in diagnosing such conditions as metastatic disease and acuteness of injury

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10-year Risk Assessment: CAROC10-year Risk Assessment: CAROC

• 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

• Other fractures attributable to osteoporosis are not reflected; total osteoporotic fracture burden is underestimated

Siminoski K, et al. Can Assoc Radiol J 2005; 56(3):178-188.

* Combined risk for fractures of the proximal femur, vertebra [clinical], forearm, and proximal humerus


10-year Risk Assessment for Men 10-year Risk Assessment for Men (CAROC Basal Risk)(CAROC Basal Risk)

Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print].Click here for CAROC risk assessment in table format.


10-year Risk Assessment for Men 10-year Risk Assessment for Men (CAROC Basal Risk)(CAROC Basal Risk)

Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print].Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print].

Age Low Risk Moderate Risk High Risk

50 above -2.5 -2.5 to -3.9 below -3.9

55 above -2.5 -2.5 to -3.9 below -3.9

60 above -2.5 -2.5 to -3.7 below -3.7

65 above -2.4 -2.4 to -3.7 below -3.7

70 above -2.3 -2.3 to -3.7 below -3.7

75 above -2.3 -2.3 to -3.8 below -3.8

80 above -2.1 -2.1 to -3.8 below -3.8

85 above -2.0 -2.0 to -3.8 below -3.8


Risk Assessment with CAROC: Risk Assessment with CAROC: Important Additional Risk FactorsImportant Additional Risk Factors

• Factors that increase CAROC basal risk by one category (i.e., from low to moderate or moderate to high)– Fragility fracture after age 40*1,2

– Recent prolonged systemic glucocorticoid use**2

1. Siminoski K, et al. Can Assoc Radiol J 2005; 56(3):178-188.2. Kanis JA, et al. J Bone Miner Res 2004; 19(6):893-899.Return to case

* Hip fracture, vertebral fracture, or multiple fracture events should be considered high risk** >3 months use in the prior year at a prednisone-equivalent dose ≥ 7.5 mg daily


Risk Assessment Using FRAXRisk Assessment Using FRAX

• 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

1. Leslie WD, et al. Osteoporos Int; In press.

* composite of hip, vertebra, forearm, and humerus


FRAX Tool: On-line CalculatorFRAX Tool: On-line Calculator

www.shef.ac.uk/FRAX.


FRAX Clinical Risk FactorsFRAX Clinical Risk Factors

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

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Recommended Biochemical Tests for Patients Recommended Biochemical Tests for Patients Being Assessed for OsteoporosisBeing Assessed for Osteoporosis

• 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)*

* Should be measured after three to four months of adequate supplementation and should not be repeated if an optimal level ≥ 75 nmol/L is achieved.


Tests for Potential Secondary CausesTests for Potential Secondary Causes

In patients withCondition / Disease

Test

Persistently elevated serum calcium Hyperparathyroidism PTH

Multiple or atypical vertebral fractures Multiple myeloma

Protein electrophoresis

ImmunoelectrophoresisSymptoms/signs of malabsorption or non response to vitamin D therapy

Celiac disease Antibodies associated with gluten enteropathy

Signs and symptoms of androgen deficiency (in men) Hypogonadism

Testosterone (bioavailable or total)

Serum prolactin

History of kidney stones Hypercalciuria 24-hour urine for calcium

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Recommended Vitamin D Recommended Vitamin D SupplementationSupplementation

GroupRecommended

Vitamin D Intake (D3)

Adults < 50 without osteoporosis or conditions affecting vitamin D absorption

400 – 1000 IU daily(10 mcg to 25 mcg

daily)

Adults > 50 or high risk for adverse outcomes from vitamin D insufficiency (e.g., recurrent fractures or osteoporosis and comorbid conditions that affect vitamin D absorption)

800 – 2000 IU daily(20 mcg to 50 mcg

daily)

Hanley DA, et al. CMAJ 2010; 182:E610-E618.


Vitamin D: Optimal LevelsVitamin D: Optimal Levels

• To most consistently improve clinical outcomes such as fracture risk, an optimal serum level of 25-hydroxy vitamin D is probably > 75 nmol/L– For most Canadians,

supplementation is needed to achieve this level



When to Measure Serum 25-OH-DWhen to Measure Serum 25-OH-D

• In situations where deficiency is suspected or where levels would affect response to therapy– Individuals with impaired intestinal absorption– Patients with osteoporosis requiring pharmacotherapy

• Should be checked no sooner than three months after commencing standard-dose supplementation in osteoporosis

• Monitoring of routine supplement use and routine screening of otherwise healthy individuals are not necessary



Recommended Calcium IntakeRecommended Calcium Intake

• From diet and supplementscombined: 1200 mg daily– Several different types of calcium

supplements are available

• Evidence shows a benefit ofcalcium on reduction of fracturerisk1

• Concerns about serious adverse effects with high-dose supplementation2-4

1. Tang BM, et al. Lancet 2007; 370(9588):657-666.2. Bolland MJ, et al. J Clin Endocrinol Metab 2010; 95(3):1174-1181.

3. Bolland MJ, et al. BMJ 2008; 336(7638):262-266.4 Reid IR, et al. Osteoporos Int 2008; 19(8):1119-1123.Return to case


Agents Recommended First-line for Agents Recommended First-line for Fracture Prevention in MenFracture Prevention in Men

• Alendronate• Risedronate • Zoledronic acid

Return to case


Integrated Approach to Management ofIntegrated Approach to Management ofPatients Who Are at Risk for FracturePatients Who Are at Risk for Fracture

Age < 50 yr Age 50-64 yr Age > 65 yr

Encourage basic bone health for all individuals over age 50, including regular active weight-bearing exercise, calcium (diet and supplementation) 1200 mg daily, vitamin D 800-2000 IU (20-50µg) daily and fall-prevention strategies

•Fragility fracture after age 40•Prolonged use of glucocorticoids or other high-risk medications•Parental hip fracture•Vertebral fracture or osteopenia identified on radiography•High alcohol intake or current smoking•Low body weight (< 60 kg) or major weight loss (> 10% of body weight at age 25)•Other disorders strongly associated with

osteoporosis

•Fragility fractures•Use of high-risk

medications•Hypogonadism•Malabsorption syndromes•Chronic inflammatory

conditions•Primary

hyperparathyroidism•Other disorders strongly

associated with rapid bone loss or fractures

•All men and women

Initial BMD Testing


Assessment of fracture risk

Moderate risk(10-year fracture risk 10%-20%)

Low risk(10-year fracture risk < 10%)

Lateral thoracolumbar radiography (T4-L4) or vertebral fracture assessment may aid in decision-making by identifying

vertebral fractures

High risk(10-year fracture risk > 20% or prior fragility fracture of hip or spine or > 1 fragility fracture)

Good evidence of benefit from

pharmacotherapy

Always consider patient

preference

Unlikely to benefit from pharmacotherapy

Reassess in 5 yr

Factors warranting consideration of pharmacologic therapy…

Integrated Approach, ContinuedIntegrated Approach, Continued

Initial BMD Testing







vertebral fractures



pharmacotherapy


preference


Reassess in 5 yr


Initial BMD Testing







vertebral fractures



pharmacotherapy


preference


Reassess in 5 yr


Initial BMD Testing



Lateral thoracolumbar radiography (T4-L4) or vertebral fracture assessment may aid in decision-making by

identifying vertebral fractures

Factors warranting consideration of pharmacologic therapy:•Additional vertebral fracture(s) (by vertebral fracture assessment

or lateral spine radiograph)•Previous wrist fracture in individuals aged > 65 or those with

T-score < -2.5•Lumbar spine T-score much lower than femoral neck T-score•Rapid bone loss•Men undergoing androgen-deprivation therapy for prostate cancer•Women undergoing aromatase inhibitor therapy for breast cancer•Long-term or repeated use of systemic glucocorticoids (oral or

parenteral) not meeting conventional criteria for recent prolonged use•Recurrent falls (> 2 in the past 12 mo)•Other disorders strongly associated with osteoporosis, rapid bone

loss or fractures

Good evidence of benefit

from pharmaco-

therapy

Repeat BMD in 1-3 yr and

reassess risk

Integrated Approach, Integrated Approach, ContinuedContinued



Lateral thoracolumbar radiography (T4-L4) or vertebral fracture assessment may aid in decision-making by identifying vertebral fractures

Factors warranting consideration of pharmacotherapy:•Additional vertebral fracture(s) (by vertebral fracture

assessment or lateral spine radiograph)•Previous wrist fracture in individuals aged > 65 or those

with T-score < -2.5•Lumbar spine T-score much lower than femoral neck T-

score•Rapid bone loss•Men on ADT for prostate cancer•Women on AI for breast cancer•Long-term or repeated use of systemic glucocorticoids

(oral or parenteral) not meeting conventional criteria for recent prolonged use

•Recurrent falls (> 2 in the past 12 mo)•Other disorders strongly associated with osteoporosis,

rapid bone loss or fractures

Good evidence of benefit

from pharmaco-

therapy

Repeat BMD in 1-3 yr and

reassess risk

Integrated Approach, Integrated Approach, ContinuedContinued

Return to case


Testosterone in Men: Summary Testosterone in Men: Summary Statement and Recommendation Statement and Recommendation

Statement Strength

Testosterone maintains BMD in hypogonadal men but has not been shown to reduce the risk of fractures

Level 2

Recommendation Grade

Testosterone is not recommended for the treatment of osteoporosis in men

B

Return to case

Documents

2010 Guidelines Case Study #4: Mr. JM 2010 Guidelines