Osteoporosis: Review of the Osteoporosis: Review of the Clinical Practice Guidelines Clinical Practice Guidelines

Ambulatory Internal Medicine Group Ambulatory Internal Medicine Group Practice Seminar SeriesPractice Seminar Series

October 2007October 2007

Lianne Tile MD MEd FRCPCLianne Tile MD MEd FRCPC

ReferencesReferences

• Consensus Statement from the OsteoporoConsensus Statement from the Osteoporosis Society of Canada (OSC) – CMAJ 200sis Society of Canada (OSC) – CMAJ 20022

• Canadian Task Force on Preventive HealCanadian Task Force on Preventive Health Care – CMAJ 2004th Care – CMAJ 2004

• Parathyroid hormone for the treatment oParathyroid hormone for the treatment of osteoporosis: a systematic review – CMf osteoporosis: a systematic review – CMAJ 2006AJ 2006

ObjectivesObjectives

• At the end of this presentation you will:At the end of this presentation you will:– Know the definition of osteoporosisKnow the definition of osteoporosis– Understand the recommendations for screening Understand the recommendations for screening – Have an approach to initial evaluationHave an approach to initial evaluation– Be familiar with nonpharmacological and Be familiar with nonpharmacological and

pharmacological options for prevention and pharmacological options for prevention and treatmenttreatment

Case Case

• A 70 year old woman is seen in clinic for A 70 year old woman is seen in clinic for follow-up of refractory hypertensionfollow-up of refractory hypertension

• She wonders whether she has osteoporosisShe wonders whether she has osteoporosis

• How do you make the diagnosis of How do you make the diagnosis of osteoporosis?osteoporosis?

• Who should be screened for osteoporosis?Who should be screened for osteoporosis?

Background Background

• 1 in 4 Canadian women • 1 in 8 Canadian men have osteoporosis

• A 50-year-old Caucasian woman has lifetime fragility fracture risk of at least 40%

• Prevalence of vertebral fractures is >25% for Canadian women/men > age 50

  

Osteoporosis - DefinitionOsteoporosis - Definition• A systemic skeletal disease characterized by A systemic skeletal disease characterized by

low bone mass and micro-architectural low bone mass and micro-architectural deterioration of bone tissue with resultant deterioration of bone tissue with resultant increase in fragility and risk of increase in fragility and risk of fracturefracture

• Bone strength depends on bone Bone strength depends on bone densitydensity and and bone bone qualityquality

WHO Definition of OsteoporosisWHO Definition of Osteoporosis• Based on bone mineral density measured by DEXA (hip and Based on bone mineral density measured by DEXA (hip and

lumbar spine are preferred sites)lumbar spine are preferred sites)• T-scoreT-score is the number of standard deviations above or below is the number of standard deviations above or below

the BMD for young adults of the same gender and racethe BMD for young adults of the same gender and race– Normal BMD: T-score above –1.0Normal BMD: T-score above –1.0– Osteopenia: T-score between –2.5 and –1.0Osteopenia: T-score between –2.5 and –1.0– Osteoporosis: T-score below –2.5Osteoporosis: T-score below –2.5– Severe osteoporosis: T-score below –2.5 with a fragility Severe osteoporosis: T-score below –2.5 with a fragility

fracture fracture – Note: WHO definitions apply to postmenopausal womenNote: WHO definitions apply to postmenopausal women

• Z-scoreZ-score is age matched is age matched

but…what really matters is but…what really matters is osteoporotic fracturesosteoporotic fractures

Four key risk factors:

1. Advancing age

2. Prior fragility fracture (after age 40)

3. Family history of osteoporotic fracture

4. Low bone mineral density (BMD)

Why is a history of fracture so Why is a history of fracture so important?important?

• ↑ risk of future fragility fractures (x1.5–9.5)

• risk of future fractures depends on – number of prior fractures – site of initial fracture – Age– Fall risk

Who should undergo BMD Who should undergo BMD testing?testing?

• Each guideline is slightly differentEach guideline is slightly different• All recommend testing ifAll recommend testing if

– Age > 65Age > 65

– Fragility fractureFragility fracture

– Long-term (> 3 months) steroid useLong-term (> 3 months) steroid use

• Osteoporosis Society of Canada recommends Osteoporosis Society of Canada recommends screening in those over 50 with 1 major or 2 screening in those over 50 with 1 major or 2 minor risk factors (see next slide)minor risk factors (see next slide)

OSC Guideline, 2002OSC Guideline, 2002

Major and Minor Risk FactorsMajor and Minor Risk FactorsMajorMajor MinorMinor

Age > 65Age > 65 Rheumatoid arthritisRheumatoid arthritis

Vertebral compression fracture Vertebral compression fracture History of hyperthyroidismHistory of hyperthyroidism

Fragility fracture after age 40Fragility fracture after age 40 Anticonvulsant therapyAnticonvulsant therapy

Family history of osteoporsis/ #Family history of osteoporsis/ # Low dietary calcium intakeLow dietary calcium intake

Steroids > 3 monthsSteroids > 3 months SmokingSmoking

MalabsorptionMalabsorption Excess caffeine intakeExcess caffeine intake

Primary hyperparathyroidismPrimary hyperparathyroidism Weight < 57 kgWeight < 57 kg

Propensity to fallPropensity to fall Weight loss > 10% Weight loss > 10%

Osteopenia on x-rayOsteopenia on x-ray Chronic heparin therapyChronic heparin therapy

HypogonadismHypogonadism

Early menopause (< age 45)Early menopause (< age 45)

Rational Clinical Exam: Does Rational Clinical Exam: Does this woman have osteoporosis?this woman have osteoporosis?

• Greatest positive likelihood ratios with:Greatest positive likelihood ratios with:– Weight <51kg Weight <51kg – Tooth count <20Tooth count <20– Rib-pelvis distance <2 finger breadthsRib-pelvis distance <2 finger breadths– Wall-occiput distance >0 cmWall-occiput distance >0 cm– Self reported humped backSelf reported humped back

JAMA 2004; 292:2890-JAMA 2004; 292:2890-29002900

Case - ContinuedCase - Continued

• You review the major and minor risk factors You review the major and minor risk factors for osteoporosis, and determine that your for osteoporosis, and determine that your patient has low dietary calcium intake and a patient has low dietary calcium intake and a family history of a hip fracture in her motherfamily history of a hip fracture in her mother

• She is also concerned her back in humped She is also concerned her back in humped • Based on this, you send her for BMD testingBased on this, you send her for BMD testing

Case - continuedCase - continued

• What is the diagnosis?What is the diagnosis?• What additional investigations should be done What additional investigations should be done

at this time?at this time?• Should your patient be treated for osteoporosis, Should your patient be treated for osteoporosis,

if so, how?if so, how?• What if she was 10 years younger? Taking What if she was 10 years younger? Taking

corticosteroids? corticosteroids?

• This woman has BMD evidence of osteoporosisThis woman has BMD evidence of osteoporosis

• Further assessment should include:Further assessment should include:

– History:History:• Detailed history including diet and lifestyle factors, screen for risk factors and secondary Detailed history including diet and lifestyle factors, screen for risk factors and secondary

causes of bone losscauses of bone loss• Past medical history and medicationsPast medical history and medications• Previous fractures, height loss, kyphosisPrevious fractures, height loss, kyphosis• Fall risk assessmentFall risk assessment

– Lab tests for secondary causes of osteoporosis:Lab tests for secondary causes of osteoporosis:• CBC, ALP, calcium, PO4, creatinine in all CBC, ALP, calcium, PO4, creatinine in all • TSH, vitamin D, PTH, serum protein electrophoresis, testosterone in selected patientsTSH, vitamin D, PTH, serum protein electrophoresis, testosterone in selected patients

– Spine xrays if exam suggests vertebral fracturesSpine xrays if exam suggests vertebral fractures

AA

BB

CC

A.A. Height Loss > 6 cm historically or > 2 Height Loss > 6 cm historically or > 2 cm measured prospectivelycm measured prospectively

B.B. Wall-Occiput Distance > 0 cmWall-Occiput Distance > 0 cm

C.C. Rib-Pelvis Distance < 2 finger breadthsRib-Pelvis Distance < 2 finger breadths

Physical exam: look for changes in the spine that suggest vertebral fractures

Rational Clinical Exam: Does This Woman Have Osteoporosis? Amanda D. Green; Cathleen S. Colón-Emeric; Lori Bastian; Matthew T. Drake; Kenneth W. LylesJAMA 2004; 292: 2890-2900

Case - continuedCase - continued

• No prior fractures as an adultNo prior fractures as an adult• History and medications do not suggest a History and medications do not suggest a

secondary cause of bone losssecondary cause of bone loss• Mild thoracic kyphosis on examinationMild thoracic kyphosis on examination• Laboratory investigations reveal a normal Laboratory investigations reveal a normal

CBC, calcium, ALP, creatinine and SPEPCBC, calcium, ALP, creatinine and SPEP• Spinal x-rays (done because of kyphosis) show Spinal x-rays (done because of kyphosis) show

an old T8 compression fracturean old T8 compression fracture

TreatmentTreatment

• Since her T-score is < -2.5 and she has a Since her T-score is < -2.5 and she has a vertebral fracture, you recommend treatment vertebral fracture, you recommend treatment for her osteoporosisfor her osteoporosis

Start with Nutrition and LifestyleStart with Nutrition and Lifestyle(for everyone!)(for everyone!)

• Calcium from diet and/or supplementsCalcium from diet and/or supplements– Age 19-50: 1,000 mg/dayAge 19-50: 1,000 mg/day– Age > 50, steroid use, osteoporosis: 1,500 mg/dayAge > 50, steroid use, osteoporosis: 1,500 mg/day– Note: 1 glass of milk Note: 1 glass of milk ~~ 300 mg calcium 300 mg calcium

• Vitamin D Vitamin D – Age < 50: 400 I.U./dayAge < 50: 400 I.U./day– Age > 50 or low BMD: 800-1000 I.U./day Age > 50 or low BMD: 800-1000 I.U./day

• Limit caffeine (< 4 cups coffee/day)Limit caffeine (< 4 cups coffee/day)• Smoking cessationSmoking cessation• Weight-bearing exercise 3 times per weekWeight-bearing exercise 3 times per week

When should you consider When should you consider pharmacologic therapy?pharmacologic therapy?

• Always look at risk of fractures!

• Four Key Risk Factors are:

• Age (and fall risk)

• Prior fragility fracture (after age 40)

• Family history of osteoporotic fracture

• Low bone mineral density (BMD)

Canadian Guidelines Recommend

Pharmacological OptionsPharmacological Options

• Antiresorptive agentsAntiresorptive agents– BisphosphonatesBisphosphonates– Selective estrogen receptor modulatorsSelective estrogen receptor modulators– Hormone replacement therapyHormone replacement therapy– CalcitoninCalcitonin– IV Bisphosphonates IV Bisphosphonates

• Bone formation agentsBone formation agents– PTHPTH

• Choose based on efficacy, safety, toxicityChoose based on efficacy, safety, toxicity

Alendronate (Fosamax) / Alendronate (Fosamax) / Risedronate (Actonel)Risedronate (Actonel)

– good quality studies show decreases in risk of spine and good quality studies show decreases in risk of spine and nonvertebral fracturesnonvertebral fractures

– Evidence for effectiveness in women and menEvidence for effectiveness in women and men

– Taken weekly, on an empty stomach, 1 hour before Taken weekly, on an empty stomach, 1 hour before eating, must remain uprighteating, must remain upright

– Adverse effects: GERD or esophageal erosions, use Adverse effects: GERD or esophageal erosions, use with caution in renal insufficiency, osteonecrosis of the with caution in renal insufficiency, osteonecrosis of the jaw is a very rare association jaw is a very rare association

– recommended as first line therapy, covered by ODBrecommended as first line therapy, covered by ODB

Etidronate (Didrocal)Etidronate (Didrocal)

– shown to prevent spine but not hip fracturesshown to prevent spine but not hip fractures– taken cyclically: 400 mg/d x 14 days q 3 mo as taken cyclically: 400 mg/d x 14 days q 3 mo as

Didrocal “kit”: 14 tablets of etidronate followed Didrocal “kit”: 14 tablets of etidronate followed by 10 weeks of calcium 500 mgby 10 weeks of calcium 500 mg

– Well toleratedWell tolerated– recommended as second line therapyrecommended as second line therapy

SERMs: Raloxifene (Evista)SERMs: Raloxifene (Evista)– Estrogen agonist effect on bone, heart; Estrogen agonist effect on bone, heart;

antagonist on breast; neutral on endometriumantagonist on breast; neutral on endometrium– Decreases risk of invasive breast cancer, neutral Decreases risk of invasive breast cancer, neutral

for cardiovascular disease for cardiovascular disease – Studies show decreased risk of vertebral but not Studies show decreased risk of vertebral but not

hip fractureship fractures– Taken dailyTaken daily– Adverse effects include hot flushes, increased Adverse effects include hot flushes, increased

risk of thromboembolic disease (similar to HRT)risk of thromboembolic disease (similar to HRT)– covered by ODB under limited use criteriacovered by ODB under limited use criteria

Hormone Replacement Hormone Replacement Therapy (HRT)Therapy (HRT)

• Good quality data (Women’s Health Initiative) Good quality data (Women’s Health Initiative) showing decreased risk of fractures at all sitesshowing decreased risk of fractures at all sites

• BUT increased risk of coronary artery disease, BUT increased risk of coronary artery disease, stroke, venous thromboembolism and breast stroke, venous thromboembolism and breast cancercancer

• Although HRT is effective therapy for prevention Although HRT is effective therapy for prevention and treatment of osteoporosis, risks will outweigh and treatment of osteoporosis, risks will outweigh benefits for most womenbenefits for most women

CalcitoninCalcitonin

• Intranasal calcitonin (Miacalcin)Intranasal calcitonin (Miacalcin)– fair quality data showing decreased risk of fair quality data showing decreased risk of

fracturesfractures– Reduces pain in acute vertebral fracturesReduces pain in acute vertebral fractures– well tolerated, safe in renal failure, mild nasal well tolerated, safe in renal failure, mild nasal

irritation in 30%irritation in 30%– recommended as second-line therapyrecommended as second-line therapy– not covered by ODBnot covered by ODB

Bone Formation AgentsBone Formation Agents

• PTH 1-34 (Forteo)PTH 1-34 (Forteo)– Significantly increases bone density, decreases risk of Significantly increases bone density, decreases risk of

vertebral and nonvertebral fracturesvertebral and nonvertebral fractures

– Daily sc injection for 18 months (self administered)Daily sc injection for 18 months (self administered)

– LessLess effective if given with a bisphosphonate effective if given with a bisphosphonate

– Tumors seen in animal studies, so PTH is not Tumors seen in animal studies, so PTH is not recommended in high bone turnover states or in cancer recommended in high bone turnover states or in cancer patientspatients

– Very expensive, not coveredVery expensive, not covered

New Treatment OptionsNew Treatment Options• IV BisphosphonatesIV Bisphosphonates

– IV Zoledronic acid 5 mg given once a year reduces fracture risk IV Zoledronic acid 5 mg given once a year reduces fracture risk similar to oral bisphosphonatessimilar to oral bisphosphonates

– There is further evidence that it decreases mortality when given There is further evidence that it decreases mortality when given post hip fracturepost hip fracture

– Not yet approved in Canada for osteoporosis treatmentNot yet approved in Canada for osteoporosis treatment

• VertebroplastyVertebroplasty– Injection of bone cement into vertebral fracture for pain relief Injection of bone cement into vertebral fracture for pain relief

(done by interventional radiologist)(done by interventional radiologist)

• New therapies on the horizonNew therapies on the horizon– Strontium ranelateStrontium ranelate– RANK ligand inhibitorsRANK ligand inhibitors

Back to the CaseBack to the Case

• You recommend calcium 500 mg (elemental) TID, You recommend calcium 500 mg (elemental) TID, vitamin D 1000 IU daily, and weight bearing vitamin D 1000 IU daily, and weight bearing exerciseexercise

• You offer treatment with alendronate, risedronate You offer treatment with alendronate, risedronate or raloxifene, and discuss the benefits and side or raloxifene, and discuss the benefits and side effects of eacheffects of each

• She agrees to start alendronate 70 mg per week She agrees to start alendronate 70 mg per week and understands how to use it correctlyand understands how to use it correctly

• You arrange a follow up BMD in 1-2 years’ timeYou arrange a follow up BMD in 1-2 years’ time