Osteoporosis: Review of the Clinical Practice Guidelines Ambulatory Internal Medicine Group Practice Seminar Series October 2007 Lianne Tile MD MEd FRCPC

References Consensus Statement from the Osteoporosis Society of Canada (OSC) – CMAJ 2002Consensus Statement from the Osteoporosis Society of Canada (OSC) – CMAJ 2002Consensus Statement from the Osteoporosis Society of Canada (OSC) – CMAJ 2002Consensus Statement from the Osteoporosis Society of Canada (OSC) – CMAJ 2002 Canadian Task Force on Preventive Health Care – CMAJ 2004Canadian Task Force on Preventive Health Care – CMAJ 2004Canadian Task Force on Preventive Health Care – CMAJ 2004Canadian Task Force on Preventive Health Care – CMAJ 2004 Parathyroid hormone for the treatment of osteoporosis: a systematic review – CMAJ 2006Parathyroid hormone for the treatment of osteoporosis: a systematic review – CMAJ 2006Parathyroid hormone for the treatment of osteoporosis: a systematic review – CMAJ 2006Parathyroid hormone for the treatment of osteoporosis: a systematic review – CMAJ 2006

Objectives At the end of this presentation you will:At the end of this presentation you will: –Know the definition of osteoporosis –Understand the recommendations for screening –Have an approach to initial evaluation –Be familiar with nonpharmacological and pharmacological options for prevention and treatment

Case A 70 year old woman is seen in clinic for follow-up of refractory hypertensionA 70 year old woman is seen in clinic for follow-up of refractory hypertension She wonders whether she has osteoporosisShe wonders whether she has osteoporosis How do you make the diagnosis of osteoporosis?How do you make the diagnosis of osteoporosis? Who should be screened for osteoporosis?Who should be screened for osteoporosis?

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 - Definition A systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue with resultant increase in fragility and risk of fractureA systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue with resultant increase in fragility and risk of fracture Bone strength depends on bone density and bone qualityBone strength depends on bone density and bone quality

WHO Definition of Osteoporosis Based on bone mineral density measured by DEXA (hip and lumbar spine are preferred sites)Based on bone mineral density measured by DEXA (hip and lumbar spine are preferred sites) T-score is the number of standard deviations above or below the BMD for young adults of the same gender and raceT-score is the number of standard deviations above or below the BMD for young adults of the same gender and race –Normal BMD: T-score above –1.0 –Osteopenia: T-score between –2.5 and –1.0 –Osteoporosis: T-score below –2.5 –Severe osteoporosis: T-score below –2.5 with a fragility fracture –Note: WHO definitions apply to postmenopausal women Z-score is age matchedZ-score is age matched

but…what really matters is osteoporotic fractures Four key risk factors: 1. 1.Advancing age 2. 2.Prior fragility fracture (after age 40) 3. 3.Family history of osteoporotic fracture 4. 4.Low bone mineral density (BMD)

Why is a history of fracture so 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 testing? Each guideline is slightly differentEach guideline is slightly different All recommend testing ifAll recommend testing if –Age > 65 –Fragility fracture –Long-term (> 3 months) steroid use Osteoporosis Society of Canada recommends screening in those over 50 with 1 major or 2 minor risk factors (see next slide)Osteoporosis Society of Canada recommends screening in those over 50 with 1 major or 2 minor risk factors (see next slide)

OSC Guideline, 2002 Major and Minor Risk Factors MajorMinor Age > 65 Rheumatoid arthritis Vertebral compression fracture History of hyperthyroidism Fragility fracture after age 40 Anticonvulsant therapy Family history of osteoporsis/ # Low dietary calcium intake Steroids > 3 months Smoking Malabsorption Excess caffeine intake Primary hyperparathyroidism Weight < 57 kg Propensity to fall Weight loss > 10% Osteopenia on x-ray Chronic heparin therapy Hypogonadism Early menopause (< age 45)

Rational Clinical Exam: Does this woman have osteoporosis? Greatest positive likelihood ratios with:Greatest positive likelihood ratios with: –Weight <51kg –Tooth count <20 –Rib-pelvis distance <2 finger breadths –Wall-occiput distance >0 cm –Self reported humped back JAMA 2004; 292:

Case - Continued You review the major and minor risk factors for osteoporosis, and determine that your patient has low dietary calcium intake and a family history of a hip fracture in her motherYou review the major and minor risk factors for osteoporosis, and determine that your patient has low dietary calcium intake and a family history of a hip fracture in her mother She is also concerned her back in humpedShe 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 - continued What is the diagnosis?What is the diagnosis? What additional investigations should be done at this time?What additional investigations should be done at this time? Should your patient be treated for osteoporosis, if so, how?Should your patient be treated for osteoporosis, if so, how? What if she was 10 years younger? Taking corticosteroids?What if she was 10 years younger? Taking corticosteroids?

This woman has BMD evidence of osteoporosisThis woman has BMD evidence of osteoporosis Further assessment should include:Further assessment should include: –History: Detailed history including diet and lifestyle factors, screen for risk factors and secondary causes of bone lossDetailed history including diet and lifestyle factors, screen for risk factors and secondary causes 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: CBC, ALP, calcium, PO4, creatinine in allCBC, 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 fractures

A B C A.Height Loss > 6 cm historically or > 2 cm measured prospectively B.Wall-Occiput Distance > 0 cm C.Rib-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. Lyles JAMA 2004; 292:

Case - continued No prior fractures as an adultNo prior fractures as an adult History and medications do not suggest a secondary cause of bone lossHistory and medications do not suggest a secondary cause of bone loss Mild thoracic kyphosis on examinationMild thoracic kyphosis on examination Laboratory investigations reveal a normal CBC, calcium, ALP, creatinine and SPEPLaboratory investigations reveal a normal CBC, calcium, ALP, creatinine and SPEP Spinal x-rays (done because of kyphosis) show an old T8 compression fractureSpinal x-rays (done because of kyphosis) show an old T8 compression fracture

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

Start with Nutrition and Lifestyle (for everyone!) Calcium from diet and/or supplementsCalcium from diet and/or supplements –Age 19-50: 1,000 mg/day –Age > 50, steroid use, osteoporosis: 1,500 mg/day –Note: 1 glass of milk ~ 300 mg calcium Vitamin DVitamin D –Age < 50: 400 I.U./day –Age > 50 or low BMD: 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 pharmacologic therapy? When should you consider 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 Options Antiresorptive agentsAntiresorptive agents –Bisphosphonates –Selective estrogen receptor modulators –Hormone replacement therapy –Calcitonin –IV Bisphosphonates Bone formation agentsBone formation agents –PTH Choose based on efficacy, safety, toxicityChoose based on efficacy, safety, toxicity

Alendronate (Fosamax) / Risedronate (Actonel) –good quality studies show decreases in risk of spine and nonvertebral fractures –Evidence for effectiveness in women and men –Taken weekly, on an empty stomach, 1 hour before eating, must remain upright –Adverse effects: GERD or esophageal erosions, use with caution in renal insufficiency, osteonecrosis of the jaw is a very rare association –recommended as first line therapy, covered by ODB

Etidronate (Didrocal) –shown to prevent spine but not hip fractures –taken cyclically: 400 mg/d x 14 days q 3 mo as Didrocal “kit”: 14 tablets of etidronate followed by 10 weeks of calcium 500 mg –Well tolerated –recommended as second line therapy

SERMs: Raloxifene (Evista) –Estrogen agonist effect on bone, heart; antagonist on breast; neutral on endometrium –Decreases risk of invasive breast cancer, neutral for cardiovascular disease –Studies show decreased risk of vertebral but not hip fractures –Taken daily –Adverse effects include hot flushes, increased risk of thromboembolic disease (similar to HRT) –covered by ODB under limited use criteria

Hormone Replacement Therapy (HRT) Good quality data (Women’s Health Initiative) showing decreased risk of fractures at all sitesGood quality data (Women’s Health Initiative) showing decreased risk of fractures at all sites BUT increased risk of coronary artery disease, stroke, venous thromboembolism and breast cancerBUT increased risk of coronary artery disease, stroke, venous thromboembolism and breast cancer Although HRT is effective therapy for prevention and treatment of osteoporosis, risks will outweigh benefits for most womenAlthough HRT is effective therapy for prevention and treatment of osteoporosis, risks will outweigh benefits for most women

Calcitonin Intranasal calcitonin (Miacalcin)Intranasal calcitonin (Miacalcin) –fair quality data showing decreased risk of fractures –Reduces pain in acute vertebral fractures –well tolerated, safe in renal failure, mild nasal irritation in 30% –recommended as second-line therapy –not covered by ODB

Bone Formation Agents PTH 1-34 (Forteo)PTH 1-34 (Forteo) –Significantly increases bone density, decreases risk of vertebral and nonvertebral fractures –Daily sc injection for 18 months (self administered) –Less effective if given with a bisphosphonate –Tumors seen in animal studies, so PTH is not recommended in high bone turnover states or in cancer patients –Very expensive, not covered

New Treatment Options IV BisphosphonatesIV Bisphosphonates –IV Zoledronic acid 5 mg given once a year reduces fracture risk similar to oral bisphosphonates –There is further evidence that it decreases mortality when given post hip fracture –Not yet approved in Canada for osteoporosis treatment VertebroplastyVertebroplasty –Injection of bone cement into vertebral fracture for pain relief (done by interventional radiologist) New therapies on the horizonNew therapies on the horizon –Strontium ranelate –RANK ligand inhibitors

Back to the Case You recommend calcium 500 mg (elemental) TID, vitamin D 1000 IU daily, and weight bearing exerciseYou recommend calcium 500 mg (elemental) TID, vitamin D 1000 IU daily, and weight bearing exercise You offer treatment with alendronate, risedronate or raloxifene, and discuss the benefits and side effects of eachYou offer treatment with alendronate, risedronate or raloxifene, and discuss the benefits and side effects of each She agrees to start alendronate 70 mg per week and understands how to use it correctlyShe agrees to start alendronate 70 mg per week and 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