Educational Content Developed by ASBMR and the Faculty

Educational Content Developed by ASBMR and the Faculty Listed Below Stuart L. Silverman, MD, FACP, FACR (Chair) Medical Director Cedars-Sinai Bone Center of Excellence Los Angeles, California Michael Mc. Clung, MD, FACP, FACE Director Oregon Osteoporosis Center Portland, Oregon Cheryl L. Lambing, MD, FAAFP Clinical Professor University of California, Los Angeles, California Ethel S. Siris, MD Madeline C. Stabile Professor of Clinical Medicine Columbia University New York, New York E. Michael Lewiecki, MD, FACP, FACE Clinical Assistant Professor of Medicine University of New Mexico School of Medicine Albuquerque, New Mexico Nelson B. Watts, MD, FACP, MACE Director Mercy Health Osteoporosis and Bone Health Services Cincinnati, Ohio

Osteoporosis Education for the PCP? Osteoporosis is under-recognized Fractures are not recognized as sentinel events PCPs are critical for screening, diagnosis, and treatment Osteoporosis is under-treated ASBMR and The France Foundation Curriculum for PCPs AAFP chapter meetings www. osteocme. org

Learning Objectives • Improve the ability to assess risk factors for osteoporosis and apply evidence-based screening recommendations to these at-risk patients within one’s practice • Develop strategies to improve the treatment of patients with osteoporosis • Utilize the tools and other information provided within this initiative, including patient education tools and systemsbased approaches to facilitate improving the assessment and care being provided to patients with osteoporosis

Postmenopausal Osteoporosis in the Primary Care Setting • • What is osteoporosis? Why you should care? Whom to test and how? Whom to treat and how?

Definition of Osteoporosis • A skeletal disorder characterized by – Compromised bone strength predisposing to – An increased risk of fracture Normal Bone • Bone strength reflects the integration of two main features: – Bone density – Bone quality Osteoporotic Bone 2000 NIH Consensus Development Conference

Osteoporosis Is a Serious Public Health Problem • Affects 10 million Americans (80% women) • 2 million fractures yearly • Direct cost $17 billion Distribution of Fractures

Osteoporosis in Perspective 60 48 M Americans with Risk Factors, in Millions 50 40 34 M 36 M Low Bone Mass Uncontrolled HT 30 20 10 0 Uncontrolled LDL

Osteoporosis in Perspective Lifetime risk at age 50 Women 60% 50% Men 40% 30% 25% 20% 12% 10% 0% 20% 17% 15% Fracture Breast Cancer 10% 5% 0% Fracture Prostate Cancer

Identified Treatment Gap NCQA HEDIS Measure % Compliance* Beta-blocker persistence after a heart attack 81. 3% Breast cancer screening 70. 5% Colorectal cancer screening 62. 4% Osteoporosis management after a fracture 22. 8% *2011 HMO Rates NCQA State of Healthcare 2012 - HMO Statistics (Commercial or Medicare data from 2011). http: //www. ncqa. org/Portals/0/State%20 of%20 Health%20 Care/2012/SOHC%20 Report%20 Web. pdf. Accessed February 2013.

National Osteoporosis Foundation 2013 Guidelines Major clinical recommendations • Universal (risk, diet, vitamin D, exercise, smoking, monitoring) • Diagnosis (BMD, vertebral imaging, causes of secondary osteoporosis) • Monitoring (BMD) • Treatment (initiation criteria, options, duration) http: //www. nof. org/hcp/practice/tools. Accessed March 2013.

Who Should Have a Bone Density Test? AAFP 1 and NOF 2 Women age 65 and older and men age 70 and older Younger postmenopausal women and men ages 50– 69 with clinical risk factors Adults who have a fracture after age 50 Adults with a condition (e. g. , rheumatoid arthritis) or taking a medication (e. g. , glucocorticoids) associated with low bone mass or bone loss 1. Sweet MG, et al. Am Fam Physician. 2009; 79(3): 193 -200. 2. National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. www. nof. org. Accessed February 2013.

Reimbursement for DXA Final Rule Since 2006, Medicare covers bone densitometry for five indications 1. Estrogen-deficient women at clinical risk for osteoporosis 2. Patients with vertebral abnormalities 3. Patients receiving long-term glucocorticoids (prednisone ≥ 5 mg/d or equivalent for 3+ months) 4. Patients with primary hyperparathyroidism 5. Patients being monitored to assess the response to an approved drug Federal Register. 2006; 71(231): 67783 -67784.

WHO Criteria for Postmenopausal Osteoporosis The T-score compares an individual’s BMD with the mean value for young adults and expresses the difference as a standard deviation score. Category T-score Normal -1. 0 and above Low bone mass (osteopenia) Between -1. 0 to -2. 5 Osteoporosis -2. 5 and below

Whom to Treat: NOF Guidelines 2013 Women ≥ 65 and men ≥ 70 (younger with risk factors) DXA test T-score ≤ -2. 5 in the lumbar spine, total hip, or femoral neck or Hip or spine fracture (clinical or radiographic) YES Candidate for TREATMENT YES http: //www. nof. org/hcp/practice/tools. Accessed March 2013. T-score between -1. 0 and -2. 5 and increased fracture risk FRAX 10 -y fracture risk ≥ 3% for hip fracture or ≥ 20% for major osteoporotic fractures

Web Version 3. 4

Clinical Benefits of FRAX Derives 10 -year probability of clinical event from measurable parameters Internationally recognized and validated Based on data from multiple cohorts Easily accessible on the Internet or DXA software Helps identify patients who need treatment

Limitations of FRAX Not valid to monitor patients on treatment Only femoral neck BMD is considered Risk is “yes/no” – there is no consideration of “dose” (e. g. , fractures, glucocorticoids, smoking, alcohol) Not all risk factors are included Clinical judgment is required Do patients with high FRAX scores benefit from medication? (Unknown) Watts NB, et al. J Bone Miner Res 2009; 24: 975 -979.

Patient Care Goals • Identify patients at risk of fractures • Reduce incidence of fractures • Maintain quality of life – Activity – Independence – Health

Universal Recommendations for Bone Health • Counsel on the risk of fractures • Eat a diet rich in fruits and vegetables (supplemented if necessary) to a total calcium intake of – 1000 mg per day for men 50 -70 – 1200 mg per day for women ≥ 51 – 1200 mg per day for men ≥ 71 • Vitamin D intake should be 800 -1000 IU per day, supplemented if necessary (age ≥ 50) • Regular weight-bearing and muscle-strengthening exercise • Fall prevention evaluation and training http: //www. nof. org/hcp/practice/tools. Accessed March 2013.

FDA-approved Medications Osteoporosis Drug Estrogen Postmenopausal Prevent Treat Male Prevent Treat Calcitonin* (Miacalcin®, Fortical®) Raloxifene (Evista®) Ibandronate (Boniva®) Alendronate (Fosamax®) Risedronate (Actonel®, Atelvia®) Risedronate (Atelvia®) Zoledronate (Reclast®) Glucocorticoid -induced Denosumab (Prolia™) Teriparatide (Forteo®)

Evidence for Fracture Reduction Drug Vertebral Nonvertebral Fracture Hip Fracture Calcitonin Raloxifene Ibandronate Alendronate Risedronate Zoledronic acid Denosumab Teriparatide Adapted from Murad MH, et al. J Clin Endocrinol Metab. 2012; 97(6): 1871 -1880.

Clinical Benefit of Bisphonates • Relative risk reduction for fractures • Postmenopausal women with osteoporosis • 3 years bisphonate treatment Vertebrae Khosla S, et al. J Clin Endocrinol Metab. 2012; 97(7): 2272 -2282. Hip

Bisphonates Side Effects/Safety Concerns Oral formulations may cause esophageal irritation Can cause acute phase response (IV and high-dose oral) Contraindicated in patients with hypocalcemia Limited to patients with good kidney function (GFR > 30 or 35 m. L/min) • Musculoskeletal pain? • Osteonecrosis of the jaw? • Atypical femur fractures? • •

How Long Should Bisphonate Treatment Last? • Bisphonates have a long residence time in bone – Does long-term treatment create safety concerns that limit the duration of treatment? – Given the long retention in bone, with release and possibly recycling of drug, does cumulative exposure lead to a reservoir in bone, so that after therapy is stopped, sufficient drug will be released to exert a continuing benefit? Porras AG, et al. Clin Pharmacokinet. 1999; 36(5): 315 -328. Watts NB, et al. J Clin Endocrinol Metab. 2010; 95(4): 1555 -1565.

Long-term Experience with Alendronate Fit Long-term Extension (FLEX) Study • 5 -year extension to 5 year alendronate trial • Alendronate patients re-randomized – Continue alendronate (n = 662) – Switch to placebo (n = 437) • Results – Clinical vertebral fractures were reduced by 55% overall in continuation group – Nonvertebral fractures were reduced by 50% in continuing women with T-scores -2. 5 or below at the start of FLEX Schwartz AV, et al. J Bone Miner Res. 2010; 25: 976 -982.

Clinical Vertebral Fractures in the FLEX Study Cumulative Incidence of Fractures (%) 6 5. 3% ALN 5 years Placebo 5 years Alendronate 10 years 5 4 RR 55% P = 0. 013 3 2. 4% 2 1 0 0 1 2 3 4 5 417 650 414 646 Years Since FIT ALN/PLB 437 ALN/ALN 662 428 659 Black DM, et al. JAMA. 2006; 296: 2927 -2938. 429 657 421 654

How Long to Treat with Bisphonates? • 5– 10 years appears to be safe for most patients • Assess for risk: Lower Risk Higher Risk Drug Holiday After 3 -5 years Drug Holiday After 10 years Watts NB and Diab D. J Clin Endocrinol Metab. 2010; 95(4): 1555 -1565.

Denosumab • Human monoclonal antibody to RANKL • Decreases osteoclast number and function • Reduces risk of spine, hip and nonvertebral fractures • For osteoporosis, SQ dosing every 6 months • No dose adjustment for decreased kidney function • Effect is reversible within 6– 12 months of stopping Cummings SR, et al; FREEDOM Trial. N Engl J Med. 2009; 361(8): 756 -765. Jiang X, et al. Menopause. 2013; 20(2): 117 -119.

Differences Among Antiresorptive Agents “broad spectrum” antifracture efficacy Efficacy (alendronate, risedronate, zoledronate, denosumab) Route of oral (fasting or with food) or parenteral administration Frequency of daily, weekly, monthly, quarterly, twice yearly, administration once yearly Side depends on agent and patient effects/tolerability Non-skeletal effects breast cancer reduction (raloxifene) Cost/insurance generic oral; drugs “administered by health coverage professional” covered by Medicare Part B

Teriparatide • • Recombinant human PTH (rh. PTH [1 -34]) Mechanism of action different from other agents (anabolic) Daily SC injection Indicated for patients at high risk for fracture – Postmenopausal women with osteoporosis – Men with primary or hypogonadal osteoporosis – Men and women with osteoporosis associated with sustained systemic glucocorticoid therapy • Treatment limited to 2 years, follow with antiresorptive agent Forteo PI. http: //www. accessdata. fda. gov/drugsatfda_docs/label/2009/021318 s 012 lbl. pdf. Accessed Feb 2013. Han SL, Wan SL. Int J Clin Pract. 2012; 66: 199 -209.

Monitoring • Monitor with DXA every 1– 2 years – Do not "over-interpret" change – Be happy when BMD is stable OR increasing • Why do some patients lose BMD on treatment? – Adherence – Drug pharmacokinetics – Underlying disorders that need to be addressed • Patients on treatment whose BMD remains low are at high risk of fracture and may benefit from longer treatment

Secondary Fracture Prevention • A fracture is a sentinel event • A fracture in a person over 50 is the most powerful risk factor for a future fracture • Many high risk patients have the fracture successfully treated but do NOT receive subsequent medical assessment and treatment to prevent the next fracture

Where Are We Now? The Good News Improved awareness Excellent diagnostic tools available FRAX is a quantitative risk assessment Safe and effective individualized treatment Better understanding of pathogenesis Federal initiatives to improve care

Where Are We Now? The Bad News Under-recognition of patients at risk for fracture Decreasing access to DXA Poor patient understanding of risk/benefit Increasing patient concerns about side effects Fewer patients on therapy Poor adherence • 30% of patients don’t fill new bisphonate prescriptions • Risk of fracture increased 30– 40% Ross S, et al. Value Health. 2011; 14(4): 571 -581. Reynolds K, et al. Osteoporos Int. 2013 Apr 18. [Epub ahead of print].

Patient Dialog What Can I Do as a PCP? Practical Steps • Risk/benefit communication Decision Aids • Shared decision making • Electronic med records • Checklist for risk • Handouts • Web resources Engage the Care Team • Counseling, follow-up • ID high-risk patients Manage Nonadherence • Identify individual barriers • Address barriers

Fall Prevention Improve lighting Remove loose rugs Add grab bars near bathtubs, toilets and stairways Formal home safety evaluation Physical therapy for core strength and balance Eliminate medications that can affect alertness and balance • Assistive device evaluation and training • • • Sweet MG, et al. Am Fam Physician. 2009; 79(3): 193 -200.

What Can I Do as a PCP? Performance Improvement Activities (PI-CME) ONLINE PERFORMANCE IMPROVEMENT MODULES (PIMs) Stage A: ASSESS • Measure current practice patterns • Show what you are doing compared to quality measures and to your peers Stage B: APPLY • Complete educational activities • Apply new learnings in practice Stage C: • Complete follow-up EVALUATE practice pattern assessments • See how your practice has changed REWARDS TO YOU, THE PHYSICIAN 1. Quality measures are more regularly acknowledged. A PIM will help you stay up to date on the measures 2. Earn MOC (Maintenance of Certification) points MOC is REQUIRED for recertification 3. Practice improvements 4. System improvements for your clinic 5. Better patient outcomes

Performance Improvement CME MOC Part IV Approved American Board of Family Medicine (ABFM) https: //achsos. community 360. net/default. aspx. Accessed April 2013.

Performance Improvement CME MOC Part IV Approved American Board of Internal Medicine (ABIM) www. pi-iq. com/osteoporosis 2

Update on Management of Osteoporosis What is osteoporosis? Decreased bone strength predisposing to an increased risk of fracture Why should you care? Whom to test and how? Common, significant cost, morbidity and mortality DXA for all women by age 65, higher risk women earlier; FRAX is a useful tool Whom to treat and how? Individuals at high risk of fracture; approved agents are safe and effective; treatment decisions must be individualized

Online Tools and Resources • • • www. osteo. CME. org FRAX AAFP guidelines NOF Clinician’s Guide 2013 ACP treatment guidelines 2008 NBHA resource center for Fracture Liaison Services

www. osteo. CME. org