Osteoporosis: Review of the Clinical Practice Guidelines

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

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

3. Objectives • 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

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

5. 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

6. 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 fracture • Bone strength depends on bone density and bone quality

7. WHO Definition of Osteoporosis • 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 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 matched

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

9. 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

10. Who should undergo BMD testing? • Each guideline is slightly different • All 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)

11. Major and Minor Risk Factors OSC Guideline, 2002

12. Rational Clinical Exam: Does this woman have osteoporosis? • 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; 292:2890-2900

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

15. Case - continued • What is the diagnosis? • What additional investigations should be done at this time? • Should your patient be treated for osteoporosis, if so, how? • What if she was 10 years younger? Taking corticosteroids?

16. This woman has BMD evidence of osteoporosis Further assessment should include: History: Detailed history including diet and lifestyle factors, screen for risk factors and secondary causes of bone loss Past medical history and medications Previous fractures, height loss, kyphosis Fall risk assessment Lab tests for secondary causes of osteoporosis: CBC, ALP, calcium, PO4, creatinine in all TSH, vitamin D, PTH, serum protein electrophoresis, testosterone in selected patients Spine xrays if exam suggests vertebral fractures

17. Physical exam: look for changes in the spine that suggest vertebral fractures A • Height Loss > 6 cm historically or > 2 cm measured prospectively • Wall-Occiput Distance > 0 cm • Rib-Pelvis Distance < 2 finger breadths B C 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

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

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

20. Start with Nutrition and Lifestyle(for everyone!) • Calcium 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 D • Age < 50: 400 I.U./day • Age > 50 or low BMD: 800-1000 I.U./day • Limit caffeine (< 4 cups coffee/day) • Smoking cessation • Weight-bearing exercise 3 times per week

21. 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)

22. Canadian Guidelines Recommend

23. Pharmacological Options • Antiresorptive agents • Bisphosphonates • Selective estrogen receptor modulators • Hormone replacement therapy • Calcitonin • IV Bisphosphonates • Bone formation agents • PTH • Choose based on efficacy, safety, toxicity

24. 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

25. 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

26. 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

27. Hormone Replacement Therapy (HRT) • Good 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 cancer • Although HRT is effective therapy for prevention and treatment of osteoporosis, risks will outweigh benefits for most women

28. Calcitonin • 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

29. Bone Formation Agents • 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

30. New Treatment Options • IV 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 • Vertebroplasty • Injection of bone cement into vertebral fracture for pain relief (done by interventional radiologist) • New therapies on the horizon • Strontium ranelate • RANK ligand inhibitors

31. Back to the Case • You 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 each • She 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’ time