2010 Guidelines Case Study #3: Mrs. SP 2010 Guidelines.

2010 Guidelines2010 Guidelines

Case Study #3:Case Study #3:Mrs. SPMrs. SP

2010 Guidelines


Case PresentationCase Presentation

• 73-year-old woman presenting for a physical examination

• History of low-trauma Colles' fracture (11 years ago)

• BMD from three years ago– Spine -3.6; Hip -2.0

• No prescription medications– Takes a multivitamin daily plus a calcium tablet

• Looks and feels healthy and well


Physical ExaminationPhysical Examination

• Weight: 55 kg (121 lbs.)• Height: 157 cm (5’2”)• Body Mass Index (BMI): 22.3 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


QuestionQuestion

• Should Mrs. SP be treated with pharmacologic

therapy for osteoporosis?


InvestigationsInvestigations

• Mrs. SP should have her 10-year risk of fracture assessed– Prior DXA done, in accordance with Osteoporosis

Canada guideline indications for use– CAROC and FRAX are the risk assessment tools

validated for use in Canada

• She has been taking multivitamin with vitamin D and calcium (800 IU and 500 mg)– Consider assessing serum 25-OH-D


Calculating AbsoluteCalculating Absolute10-year Fracture Risk: FRAX Tool10-year Fracture Risk: FRAX Tool

Mrs. SP is at moderate risk of fractures using the FRAX model

Click here tosee herCAROCassessment


Treatment ConsiderationsTreatment Considerations

• Counselling should be provided on benefits of vitamin D and calcium, as well as nonpharmacologic interventions (e.g., exercise)

• The 2010 Osteoporosis Canada guidelines algorithm recommends assessment of additional risk factors among moderate-risk patients


QuestionQuestion

• What additional risk factors may aid in decision-making for Mrs. SP?


Assessment of Other Risk FactorsAssessment of Other Risk Factors

• Low spine T-score (-3.6):– Lumbar spine BMD is not considered

in the initial risk assessment for either CAROC or FRAX, and fracture risk is slightly underestimated when the lumbar spine T-score is much lower than the hip T-score1

– A lumbar spine T-score much lower than femoral neck T-score is one of the factors warranting consideration of pharmacologic therapy in those at moderate risk1

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


Communicating the Benefits, Risks, Communicating the Benefits, Risks, and Harms of Therapyand Harms of Therapy

• There are several agents with level 1 evidence for fracture prevention in menopausal women

• Counsel patients about these benefits as well as potential adverse events

• Osteoporosis treatment is indefinite; counsel on importance of adherence


QuestionQuestion

• How should you approach monitoring for a patient like Mrs. SP?


Considerations for MonitoringConsiderations for Monitoring

• Rationale for monitoring: To identify individuals with continued bone mineral density (BMD) loss, despite appropriate osteoporosis treatment

• Aspects of monitoring– Serial BMD measurements– Assessment of adherence


Mrs. SP: Follow-up (What if...?)Mrs. SP: Follow-up (What if...?)

• Mrs. SP presents to your office two years after

being on therapy for follow-up of a vertebral compression fracture diagnosis made in the emergency room a short while ago– She assures you she is always adherent to therapy

• Is this considered a treatment failure?– Consider referral to specialist


Mrs. SP: ConclusionsMrs. SP: Conclusions

• Diagnosis and treatment decisions should start with the 10-year assessment of risk using a validated tool– Mrs. SP is moderate risk using FRAX (10-year risk: 15%)

– Additional clinical risk factors should be considered when

making a treatment decisions

• For monitoring, repeat BMD every one to three years, with a decrease in testing once therapy is shown to be effective


Case C Case C – – Mrs. SP

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 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 DistancesRib-Pelvis and Occiput-to-Wall Distances

4 cm

3 FBs

8 cm

12 cm

2 FBs

Height loss3 cm

8 cm

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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


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.


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

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 -3.8 below -3.8

55 above -2.5 -2.5 to -3.8 below -3.8

60 above -2.3 -2.3 to -3.7 below -3.7

65 above -1.9 -1.9 to -3.5 below -3.5

70 above -1.7 -1.7 to -3.2 below -3.2

75 above -1.2 -1.2 to -2.9 below -2.9

80 above -0.5 -0.5 to -2.6 below -2.6

85 above +0.1 +0.1 to -2.2 below -2.2

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


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

* 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

Return to case1. 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.


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: Online CalculatorFRAX Tool: Online 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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Age Low Risk Moderate Risk High Risk

50 above -2.5 -2.5 to -3.8 below -3.8

55 above -2.5 -2.5 to -3.8 below -3.8

60 above -2.3 -2.3 to -3.7 below -3.7

65 above -1.9 -1.9 to -3.5 below -3.5

70 above -1.7 -1.7 to -3.2 below -3.2

75 above -1.2 -1.2 to -2.9 below -2.9

80 above -0.5 -0.5 to -2.6 below -2.6

85 above +0.1 +0.1 to -2.2 below -2.2

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


Summary Statement for Other Summary Statement for Other Nonpharmacologic TherapiesNonpharmacologic Therapies

Statement Strength

Exercises for individuals with osteoporosis should include weight bearing, balance, and strengthening exercises

Level 2

Exercise-focused interventions improve balance and reduce falls in community-dwelling older people

Level 2

Hip protectors may reduce the risk of hip fractures in long-term care residents, however compliance with their use may pose a challenge for the older adult

Level 2

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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


Integrated Approach, ContinuedIntegrated Approach, Continued

Assessment of fracture risk


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…

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

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Factors that Warrant Consideration for Factors that Warrant Consideration for Pharmacological Therapy in Moderate Risk PatientsPharmacological Therapy in Moderate Risk Patients

• 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


Disorders Associated with Osteoporosis Disorders Associated with Osteoporosis and Increased Fracture Riskand Increased Fracture Risk

• Primary hyperparathyroidism• Type I diabetes• Osteogenesis imperfecta• Untreated long-standing hyperthyroidism, hypogonadism, or

premature menopause (< 45 years)• Cushing’s disease• Chronic malnutrition or malabsorption• Chronic liver disease• Chronic obstructive pulmonary disease• Chronic inflammatory conditions (e.g., rheumatoid arthritis

inflammatory bowel disease)

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First Line Therapies with Evidence for Fracture First Line Therapies with Evidence for Fracture Prevention in Postmenopausal Women* Prevention in Postmenopausal Women*

Type of Fracture

Antiresorptive therapyBone

formation therapy

Bisphosphonates

Denosumab RaloxifeneHormone therapy

(Estrogen)**Teriparatide

Alendronate RisedronateZoledronic

acid

Vertebral

Hip - -

Non-vertebral+ -

* For postmenopausal women, indicates first line therapies and Grade A recommendation. For men requiring treatment,alendronate, risedronate, and zoledronic acid can be used as first line therapies for prevention of fractures [Grade D]. + In clinical trials, non-vertebral fractures are a composite endpoint including hip, femur, pelvis, tibia, humerus, radius, and clavicle. ** Hormone therapy (estrogen) can be used as first line therapy in women with menopausal symptoms.

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Adverse Events of Osteoporosis TherapiesAdverse Events of Osteoporosis Therapies

• Consult individual product monographs for adverse event information for approved therapies (click on drug names below to link to online resources)– Bisphosphonates: alendronate, risedronate,

zoledronic acid– Calcitonin– Denosumab– Raloxifene– Teriparatide

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Recommendations forRecommendations forDuration of TherapyDuration of Therapy

Recommendation Grade

Individuals at high risk for fracture should continue osteoporosis therapy without a drug holiday

D

• Evidence supporting recommendations for duration of treatment is limited

• Data for the above recommendation come from the FLEX study (long-term alendronate treatment)1 and the risedronate discontinuation study2

1. Black DM, et al. JAMA 2006; 296(24):2927-2938.2. Watts NB, et al. Osteoporos Int 2008; 19(3):365-372.Return to case


Importance of AdherenceImportance of Adherencein Treatment Successin Treatment Success

• The expectation is that treated patients will experience anti-fracture benefits similar to those reported in clinical trials

• Suboptimal adherence reduces or eliminates anti-fracture benefits1-3

1. Silverman S. et al. Rheum Dis Clin North Am 2006; 32(4):721-731.2. McCombs JS, et al. Maturitas 2004; 48(3):271-287.

3. Gold DT, et al. Curr Osteoporos Rep 2006; 4(1):21-27.


Poor Adherence Leaves Patients At Poor Adherence Leaves Patients At Higher Risk of FractureHigher Risk of Fracture

Siris E, et al. Mayo Clin Proc 2006; 81:1013-22.

50% adherence leaves patients at approximately

the same fracture risk as no therapy

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Types and Rates of NonadherenceTypes and Rates of Nonadherencein Osteoporosis Therapyin Osteoporosis Therapy

• Types of non-adherence1-3

– Frequently missed doses– Failing to take the medication correctly to optimize

absorption and action– Discontinuation of therapy

• Reported one-year adherence rates: 25% – 50%1,3

– Marginally better with less frequent dosing regimens

1. Silverman S. et al. Rheum Dis Clin North Am 2006; 32(4):721-731.2. McCombs JS, et al. Maturitas 2004; 48(3):271-287.

3. Gold DT, et al. Curr Osteoporos Rep 2006; 4(1):21-27.


Approaches for Optimizing AdherenceApproaches for Optimizing Adherence

• Reminders• Patient information• Counselling• Simplification of the dosing regimen• Self-monitoring

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Interpretation ofInterpretation ofSerial BMD MeasurementsSerial BMD Measurements

• Measurement error must be considered when interpreting serial BMD assessments– Each centre should determine its precision error in order to

estimate the least significant change (LSC)1

• Continued BMD loss exceeding the LSC may reflect– Poor adherence to therapy– Failure to respond to therapy– Previously unrecognized secondary causes of osteoporosis

• Most anti-osteoporosis therapies do not cause large BMD increases2

– Stable BMD is consistent with successful treatment

1. Baim S, et al. J Clin Densitom 2005; 8(4):371-378.2. Chen P, et al. J Bone Miner Res 2009; 24(3):495-502.


Recommendations for Frequency of Recommendations for Frequency of BMD TestingBMD Testing

• 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

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When to Refer to Specialist Care: When to Refer to Specialist Care: GeneralGeneral

• Fracture on first-line therapy with optimal adherence

• Significant loss on follow-up BMD on first-line therapy with optimal adherence

• Intolerance of first- and second-line agents


When to Refer to Specialist Care:When to Refer to Specialist Care:Special PopulationsSpecial Populations

• Referrals to physicians with an interest or expertise in osteoporosis– Secondary causes of osteoporosis outside the comfort

zone of the individual primary care physician

– Patients with extremely low BMD

• Referrals to other specialists– Complex individuals with multiple comorbidities, such as

those with frequent falling, Alzheimer’s disease, stroke, and Parkinson’s disease

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2010 Guidelines Case Study #3: Mrs. SP 2010 Guidelines.

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Transcript of 2010 Guidelines Case Study #3: Mrs. SP 2010 Guidelines.