Osteoporosis Update: Treatments and Controversies

Transcription

1 Osteoporosis Update: Treatments and Controversies Sabrina Gill MD MPH FRCPC Clinical Professor, UBC St. Paul s Hospital Images provided by D. Dempster, PhD, Helen Hayes Hospital, NY Honoraium for CME and Consulting fees from: Disclosure Lilly, Amgen, Novartis, Merck, Sanofi-Aventis, Novo Nordisk, Glaxo- Smithe-Kline 1

2 Learning Objectives At the end of this educational program, participants will be better able to: Undertake a systematic evaluation of patients at risk for osteoporosis and stratify them according to the new Osteoporosis Canada guidelines Apply evidence-based approaches to managing osteoporosis and preventing/reducing risk of fractures Understand the risks, benefits and controversies related to pharmacotherapy for patients at moderate and high risk of fracture Who suffers from the burden of osteoporosis? 2

3 Prevalence of Vertebral Deformity* The Canadian Multicentre Osteoporosis Study (CaMos) Deformity; % Men Women Age; years *In this study, spinal morphometry of the initial radiographs was performed to determine the prevalence of vertebral deformity (fracture). Jackson SA et al. Osteoporosis Int 2000; 11: Osteoporosis fracture incidence vs. incidence of other diseases in women 2,000,000 Annual incidence of common diseases 1,500,000 1,000, , ,456,000 * 223,000 hip 327,000 wrist 415,000 other sites 103,000 pelvic 389,000 vertebral Osteoporotic fractures 345,000 Heart attack 373,000 Stroke 269,730 Breast cancer *Annual fracture incidence, women ages 50+. Annual estimate new and recurrent myocardial infarction in women ages 35+. Annual estimate new and recurrent stroke in women all ages new cases in situ and invasive breast cancer, all ages. Burge R, et al. J Bone Miner Res. 2007;22: Jemal A, et al. CA Cancer J Clin. 2005;55; Rosamond W, et al. Circulation. 2007;115;e69-e171. 3

4 What are the consequences of fragility fractures? Fragility Fracture A fracture that occurs spontaneously or following a minor trauma such as: Fall from standing height or less 1,2 Excluding craniofacial, hand, ankle and foot fractures Fall from sitting position Fall from supine position (bed or reclining deck chair <1 meter high) Fall after having missed 1 to 3 steps in a staircase After a movement outside of the typical plane of motion or coughing Currently, low BMD is the primary trigger for initiation of therapy 2-6 Most fragility fractures occur in those with a BMD in the non-osteoporotic range (T-score higher than -2.5) 7 Over-reliance on BMD can lead to a missed opportunity to prevent future fractures. 7,8 BMD = bone mineral density 1. Kanis JA et al. Osteoporosis Int 2001; 12: Bessette L et al. Osteoporosis Int 2008; 19: Papaionannou A et al. BMC Muskuloskelet Disor 2004; 6: Elliot-Gibson V et al. Osteoporosis Int 2004; 15: Papaioannou A et al. Osteoporosis Int 2008; 19: Cranney A et al. Osteoporosis Int 2009; 20: Cranney A et al. CMAJ 2007; 177: Langsetmo L et al. J Bone Miner Res 2009; 24:

5 Fracture Is a Predictor of Future Fractures Risk of experiencing another fracture in the year following a hip fracture*: 5%-10% 1,2 Risk of experiencing another vertebral fracture in the year following a vertebral fracture (in postmenopausal women): 20% 3 Prevalent vertebral fractures also predict hip fracture* 4,5 40% of Canadians who experience a fracture have a history of prior fracture 6 *In men and women 1. Papaioannou A et al. JOGC 2000; 22: Colon-Emeric C et al. Osteoporosis Int 2003; 14: Lindsay R et al. JAMA 2001; 285: Ismail AA et al. Osteoporos Int 2001; 12: Melton, LJ 3 rd et al. Osteoporosis Int 1999; 10: Hajcsar EE et al. CMAJ 2000; 163: How do I assess patients for osteoporosis and fracture risk? 5

6 Clinical Paradigm Shift 2002 WHO BMD From BMD to determining 10-year absolute risk 2005 Osteoporosis Canada, CAR, and SOGC 10-year absolute fracture risk WHO: World Health Organization CAR: Canadian Association of Radiologists SOGC: Society of Obstetricians and Gynae. of Canada 2010 Osteoporosis Canada Guidelines Updated 10-year absolute fracture risk 1. Brown JP, Josse RG. CMAJ. 2002;167(10 Suppl):S1-S Siminoski K, et al. Can Assoc Radiol 2005;56: SOGC Committee. J Obstet Gynaecol Can. 2009;31(Suppl 1):S1-S Papaioannou A, et al CMAJ Understanding Fragility Fracture: Key to Appropriate Patient Management BMD vs. Osteoporotic Fracture Rates/Number Fracture rate per 1000 person-years >1.0 BMD distribution Fracture Rate No of Fractures 60% of women with fragility fractures have 30 non-osteoporotic bone mineral density (T-score >-2.5) 1.0 to to to to to to 2.0 BMD T-scores 2.0 to to to 3.5 < No of Fractures Adapted from Siris ES, et al: JAMA 2001; 286:

7 Risk of fracture increases with age despite BMD Fracture Risk (% per 10 Years) Age BMD T-score For a given BMD, risk increases with age in women Kanis JA, et al, Osteoporos Int. 2001;12: Adapted from Hui SL et al. J Clin Invest. 1988;81: Who needs to be screened? 7

8 What are the Canadian guidelines for identifying fracture risk? Absolute Fracture Risk Tools Fracture risk assessment under the FRAX/CAROC system is based upon the femoral neck T-score only Calculate risk for treatment-naïve patients only Cannot be used to monitor response to therapy Using CAROC or FRAX in a patient on therapy only reflects theoretical risk of a hypothetical patient who is treatment-naïve and does not reflect the risk reduction associated with therapy CAROC = Canadian Association of Radiologists and Osteoporosis Canada Osteoporosis Canada. Assessment of 10-Year Fracture Risk Women and Men. Available at: Accessed; March 21, World Health Organization Collaborating Centre for Metabolic Bone Diseases. FRAX: WHO Fracture Risk Assessment Tool. Available at: Accessed: March 21,

9 How do we assess 10-year fracture risk? In Canada: CAROC: updated tool of the Canadian Association of Radiologists and Osteoporosis Canada Stratifies women and men over age 50 into 3 zones of risk for major osteoporotic fracture within 10 years: Low (<10%) Medium (10-20%) High (>20%) Initial risk category obtained from age, sex and T-score for the femoral neck Preferred national risk assessment at the present time for the purposes of BMD reporting FRAX: Fracture risk assessment tool of the WHO, specific for Canada Uses sex, age, BMI, prior fracture, parental hip fracture, prolonged glucocorticoid use, RA (or secondary causes of osteoporosis), current smoking, alcohol intake ( 3 units daily) and BMD of femoral neck (optional) BMI = body mass index; RA = rheumatoid arthritis Osteoporosis Canada. Assessment of 10-Year Fracture Risk Women and Men. Available at: Accessed; March 21, World Health Organization Collaborating Centre for Metabolic Bone Diseases. FRAX: WHO Fracture Risk Assessment Tool. Available at: Accessed: March 21, CAROC basal risk by 1 category if fragility # age >40 or recent prolonged systemic glucocorticoid use basal risk by 2 categories if both of these modifiers are present Papaioannou et al CPG for the Diagnosis and Management of Osteoporosis in Canada. Osteoporosis Canada. 9

10 FRAX +/- BMD as a screen Not validated for patients formally or currently on pharmacotherapy, women under the age of 40yo or men under age 50yo Secondary causes include: type 1 diabetes, osteogenesis imperfecta, longstanding hyperthyroidism, hypogonadism, premature menopause, chronic malnutrition, malabsorption or liver disease not included if femoral neck BMD or T- score included No information on spine BMD or other clinical factors With a T-score of -2.6 this patients risk is only 7.8%. What biochemical tests should be ordered in the assessment of osteoporosis? 10

11 Recommended Biochemical Tests for Patients Being Assessed for Osteoporosis Calcium, corrected for albumin CBC Creatinine Alkaline phosphatase Thyroid-stimulating hormone Serum protein electrophoresis (for patients with vertebral fractures) 25(OH)D* In clinical practice, these tests help rule out sec ondary causes of osteoporosis. *Should be measured after 3-4 months of adequate supplementation and should not be repeated if an optimal level (at least 75 nmol/l) is achieved. CBC = complete blood count; 25(OH)D = 25-hydroxy vitamin D Papaioannou A et al. CMAJ 2010; 182: When should treatment for osteoporosis be initiated? 11

12 Encourage bone health for all individuals including: regular active weight bearing exercise, calcium (diet and supplements) 1200 mg daily, vitamin D: IU daily after age 50 ( for those < age 50 at low risk), and fall prevention strategies. Age <50 Age Age 65 Initial BMD testing Low risk 10-year fracture risk <10% Unlikely to benefit from pharmacotherapy Reassess risk in 5 years Fracture risk assessment Moderate risk 10-year fracture risk 10-20% High risk 10-year fracture risk >20%, or Prior fragility fracture of hip, or spine, or More than one fragility fracture Factors that can Lateral change thoracolumbar fracture X-ray (T4-L4) risk or by 1 category: vertebral fracture analysis may aid in decision-making by identifying Glucocorticoid >7.5 vertebral mg, >3 fractures. months Prior fragility fracture Always consider patient preference Repeat BMD testing in 1-3 years and reassess risk Factors that warrant consideration for pharmacological therapy Good evidence of benefit from pharmacotherapy Papaioannou, A et al. CMAJ 2010; 182: To be discussed later in the presentation Who is High Risk Automatically? HIP FRACTURE 1 or more vertebral fractures (prevalent, morphometric or clinical) 2 or more non-vert, non-hip fractures Hip / vertebral fracture High risk (> 20%) > 1 non-vertebral fragility fracture THESE PATIENTS DO NOT REQUIRE A BMD FOR DIAGNOSIS AND TREATMENT OF OSTEOPOROSIS 12

13 Low-Risk Individuals The Role of Non-pharmacological Interventions Advice to Patients about Exercise Remember exercise is important to: Improve overall health, Maintain muscle strength Maintain coordination Prevent falls Evidence best for weight bearing exercise, but other forms are of benefit Encourage programs that they love to do Papaioannou A et al. CMAJ 2010; 182:

14 What is the appropriate amount of calcium and vitamin D supplementation? Current Recommendations for Calcium and Vitamin D Calcium 1200 mg (total) from diet and supplement combined Vitamin D In healthy adults <50 years old: IU (10-25 μg) per day is recommended Serum 25(OH)D should not be measured Adults over 50 years old: IU daily Papaioannou A et al. CMAJ 2010; 182:

15 Consequences of Vitamin D Insufficiency PTH calcium release (i.e., bone resorption) BMD Vitamin D insufficiency: 25(OH)D <75 nmol/l muscle strength balance falls fractures In patients with a history of fractures of falls, 97% had serum 25(OH)D levels below 75 nmol/l in 1 study and 72% had vitamin D levels below 50 nmol/l in another study Dhesi JK et al. Age Aging 2002; 31: Simonelli C et al. J Bone Miner Res 2004; 19(Suppl 1):S433. Moderate Risk 15

16 According to the 2010 Osteoporosis Canada guidelines, the decision of whether to initiate treatment can be made after: A discussion of benefits and risks with the patient Assessment of patient preferences and health priorities to come up with an individualized intervention threshold Papaioannou A et al. CMAJ 2010; 182: Factors that Warrant Consideration for Pharmacological Therapy in Moderate Risk Patients Previous wrist fracture in those older than age 65 or those with T-score -2.5 Spine T-score much lower than femoral neck T-score Rapid bone loss Men on ADT for prostate cancer Women on aromatase inhibitor therapy for breast cancer Long-term or repeated systemic glucocorticoid use Recurrent falls >2 or more times in the past 12 months Other disorders strongly associated with osteoporosis, rapid bone loss or fractures ADT = androgen deprivation therapy Papaioannou A et al. CMAJ 2010; 182:

17 High Risk Consider: Mechanism of Action Estrogen therapy Selective estrogen receptor modulators Hormones RANKL RANK Bisphosphonates Binds to bone; inhibits osteoclasts Teriparatide PTH analog Denosumab RANK Ligand inhibitor Osteoblast Osteoclast Adapted from Boyle WJ, et al. Nature. 2003;423:337 17

18 What are the recommended treatments? Type of fracture First-Line Therapies with Evidence for Fracture Prevention in Postmenopausal Women* Antiresorptive therapy Bisphosphonates Denosumab Raloxifene Estrogen (hormone Alendronate Risedronate Zoledronic therapy)** acid Bone formation therapy Teriparatide Vertebral Hip Nonvertebral δ δ In clinical trials, non-vertebral fractures are a composite endpoint including hip, femur, pelvis, tibia, humerus, radius and clavicle. * For postmenopausal women, indicates first line therapies and Grade A recommendation. ** For women with menopausal symptoms, hormone therapy (estrogen) can be used as first-line therapy. Papaioannou A et al. CMAJ 2010; 182: RR for Fractures after Treatment with HRT % 22% RR (95% CI) ( ) 0.78 ( ) Vertebral fracture Non-vertebral fracture Includes results from WHI. RR = relative risk; HRT = hormone replacement therapy Hosking DJ et al. QJM 2005; 98:

19 WHI HRT Study: Effect of HRT on Event Rates 60 Risks* Benefits* Neutral Number of cases in 10,000 women per year Additional events Reduced events 6 5 Estrogen + progestin Placebo 0 CHD Stroke Breast cancer VTE Colorectal cancer Hip fracture Endometrial cancer Deaths *Statistically significant based on 95% nominal CI on HRs CHD = coronary heart disease; VTE = venous thromboembolism Adapted from: WHI Investigators. JAMA 2002; 288: Significant symptoms of menopause No NO HT Yes Free of contraindications to HT and no history of CHD, stroke or TIA And No increased risk of Stroke (<10%) Yes No CHD risk over 10yrs Years Since Last Menstrual Period < >10 Very Low risk (<5%) HT OK HT OK NO HT Low risk (5-10%) HT OK HT OK (Transdermal) Moderate Risk (10-20%) HT OK (Transdermal) NO HT NO HT NO HT High risk (>20%) NO HT NO HT NO HT Duration of use dependent on severity of symptoms, patient preference, baseline risk stratification NO HT Manson JE Harrisons Principles

20 Effect of raloxifene in women with or without existing fractures MORE trial: 4 years 30 RR=0.66 (95% CI, ) % Placebo Raloxifene 60 mg/day 10 RR=0.51 (95% CI, ) 5 49% 0 Without prevalent vertebral fractures With prevalent vertebral fractures MORE=Multiple Outcomes of Raloxifene Evaluation Eastell R, et al. J Bone Miner Res 2000 SERMs - Effect of Raloxifene on the Risk of Invasive Breast Cancer RR 0.16* (95% CI = 0.09, 0.30) placebo raloxifene (pooled) RR 1.13 (95% CI = 0.36, 3.66) 0 ER+ Total cases=41 ER- Total cases=13 *p <.001 ER status unknown = 7 MORE trial 4 years Cauley J, et al. Breast Cancer Res Treatment. 2001;65:

21 Bisphosphonates Effect on Fractures Bisphosphonate Vertebral Non-vertebral Hip Etidronate Alendronate Risedronate Zoledronate Papaioannou A et al. CMAJ 2010; 182: Benefits of Alendronate in Postmenopausal Osteoporosis p<0.001 p<0.001 p=0.038 p<0.001 p=0.003 p=0.005 p<0.001 *In postmenopausal women with existing vertebral fracture or without vertebral fracture and T-score <-2.5 (n=3658) FIT = Fracture Intervention Trial Black DM et al. J Clin Endocrinol Metab 2000; 85:

22 Bisphosphonate: Risedronate Radiographic Vertebral Fracture Reduction at 1 Year % of Patients *p<0.05 vs control Control 61%* 65%* 55%* Risedronate 5mg/d VERT-NA VERT-MN HIP GIO Vertebral Efficacy with Risedronate therapy (VERT) 1226 PMW with >2 vertebral fractures 70%* Eastell R et al. Osteoporos Int 2000;11:S208. Zoledronic Acid Reduced 3-Year Risk of Clinical Fracture (Hip, Vertebral and Non-vertebral) % patients with new fracture RRR 40%* (15%-57%) 2.50% (87/3861) Hip fracture Placebo (n=3861) RRR 75% (60%-85%) 2.58% (81/3861) 1.45% (52/3875) 0.57% (20/3875) Clinical vertebral fracture Zoledronic acid 5 mg (n=3875) 10.69% (384/3861) RRR 25% (13%-36%) 7.91% (289/3875) Non-vertebral fracture RRR = relative risk reduction Values above bars are 3-year event rates * p=0.0032; p<0.0001; p= Black DM et al. N Engl J Med 2007; 356:

23 Bisphosphonates and Risks: What are the current controversies? Mild or Unavoidable side effects GI most common 20-30% Take on empty stomach after prolonged fast (>2hr); no food for 30-60min; remain upright due to esophageal irritation/ulceration Acute phase reaction (with IV or monthly po) flu-like sx; usually with first dose Hypocalcemia with IV>PO Ensure adequate calcium and vitamin D replacement 23

24 Potential Adverse Effects of Bisphosphonate Therapy Iritis/Uveitis/conjunctivitis Atrial fibrillation Esophageal cancer Musculoskeletal pain Jaw osteonecrosis Fractures Osteonecrosis of the Jaw With 4mo therapy of clindamycin & chlorhexidine gluconate rinses Exposed neurotic bone in maxillofacial region beyond 6-8 weeks in the absence of previous radiation Pain, swelling, paresthesias, suppuration, soft tissue ulceration, intraor extraoral sinus tracks, loosing of teeth Risk: poor dental hygiene, periodonitis, invasive dental procedures (inc tooth extraction), steroids, malignancy therapy (>90% of cases), smoking, DM 24

25 Recommendations? Regular dental exams and good dental hygeine Inform patients of risk Patients considering dentoalveolar or periodontal surgery should be advised of risks and non-surgical therapy options Do procedures before starting BP if possible Time off BP prior to procedures option but no evidence of improving outcomes Resources: Am Dental Assn; Am Soc Bone Min Res; Am Assn Oral & Maxillofacial surgeons Are Atypical (Subtrochanteric) Fractures Increased With Antiresorptive Therapy? ASBMR Task Force Definition 1 : Major Features* Anywhere along the femur No trauma or minimal trauma Transverse or short oblique configuration Non-comminuted Complete fractures through both cortices (may be associated with a medial spike); incomplete fractures involve only the lateral cortex *All Major features required to define atypical femoral fracture. Image from: Lenart BA, et al. N Engl J Med. 2008;358: Shane E, Burr D, et al. Atypical Subtrochanteric and Diaphyseal Femoral Fractures: Report of a Task Force of the American Society for Bone and Mineral Research. JBMR, 2010; On line Sept 7, DOI /jbmr Lenart BA, et al. N Engl J Med. 2008;358:

26 Are Atypical (Subtrochanteric) Fractures Increased With Antiresorptive Therapy? ASBMR Task Force Definition 1 : Minor Features* Localized periosteal reaction of the lateral cortex (ie beaking) Increase in cortical thickness of the diaphysis Prodromal symptoms Bilateral fractures and symptoms Delayed healing Comorbid conditions Use of pharmaceutical agents (e.g., BPs, GCs, proton pump inhibitors) *None of the Minor Features are required but have been sometimes associated with these fractures. Cortical thickening Image from: Lenart BA, et al. N Engl J Med. 2008;358:1304 Beaking 1. Shane E, Burr D, et al. Atypical Subtrochanteric and Diaphyseal Femoral Fractures: Report of a Task Force of the American Society for Bone and Mineral Research. JBMR, 2010; On line Sept 7, DOI /jbmr Lenart BA, et al. N Engl J Med. 2008;358:1304 Risk vs Benefit? 26

27 Balance of Risk versus Benefit Benefits Vertebral fracture reduction Absolute RR: / patient years Non-vertebral fracture reduction Absolute RR: / patient years Mortality reduction Risks Osteonecrosis of Jaw Absolute RR: 20-28/ patient yrs Prevalence 10-40/ patient yrs Atypical Femoral fracture Incidence / patient years Esophageal cancer Incidence 48/ patient years Denosumab binds RANKL and inhibits osteoclast formation, function, and survival CFU-M Prefusion Osteoclast RANKL RANK Hormones Growth factors Cytokines OPG Denosumab Osteoclast Formation, Function, and Survival Inhibited Osteoblasts In the presence of M-CSF Bone Formation Bone Resorption Inhibited Investigative compound not yet approved by Health Canada. Adapted from Boyle WJ, et al. Nature. 2003;423:

28 Denosumab Reduces Vertebral, Non-vertebral and Hip Fractures in Women with Postmenopausal Osteoporosis Randomized Controlled Trial: FREEDOM 3-Year Pivotal Fracture Trial in Women with Postmenopausal Osteoporosis 15% Denosumb Fracture incidence at Month 36 (%) 10% 5% 0% 7.2% n = (264/3691) RRR 68% 2.3% n = (82/3702) 8.0% n = (84/3875) RRR 20% 6.5% n = (19/3861) 1.2% n = (388/3875) Placebo RRR 40% Vertebral fracture* Non-vertebral fracture Hip fracture 0.7% n = (292/3861) RR=0.32 (95% CI ) p<0.001 vs. placebo *Crude incidence N=7868 PMW Kaplan-Meier estimate of incidence RRR Cummings = relative SR et risk al. reduction N Eng J Med 2009; 361: RR=0.80 (95% CI ) p=0.01 vs. placebo RR=0.60 (95% CI ) p=0.04 vs. placebo Significant Bone Loss with Denosumab Discontinuation Multiple case reports and FREEDOM extension trial analysis 6-8.5% BMD loss at all sites within the first six months Significant increase in bone resorption markers rebound effect? 5/38 (13.15%) patients suffered fragility fracture Vertebral fractures more prevalent Prevalent vertebral fractures before or during treatment period was strongest predictor of new fractures bisphosphonate therapy post discontinuation? Zanchetta et al Osteoporosis Int 2018; Anastasilakis AD et al J Bone Miner Res 2017, Lamy O et al J Clin Endocrinol Metab 2017, Polyzos et al Endocrine 2016; Popp et al OsteoporsInt 2016; Abry-Rozier et a l OsteoprosInt 2016; Anastasilakis et al OsteoporosInt

29 Effects of PTH Ct.Th: 0.32 mm CD: 2.9/mm 3 Ct.Th: 0.42 mm CD:4.6/mm 3 Baseline PTH PTH = parathyroid hormone; Ct. Th = cortical thickness Dempster DW et al. J Bone Miner Res 2001; 16: Pharmacological Therapies: rhpth(1-34) on the Risk of New Vertebral Fractures RR 0% 25% 50% 75% 100% rhpth(1-34) = recombinant human parathyroid hormone Neer RM et al. N Engl J Med 2001; 344: Placebo (n=448) RR=0.35 (95% CI )* 65% rhpth 20 (n=444) No. of women who had >1 fracture *p<0.001 vs. placebo % of women 29

30 Pharmacological Therapies: rhpth(1-34) on the Risk of Non-vertebral Fractures *p=0.02 vs. placebo 7 RR=0.47 (95% CI )* % of women % Placebo (n=544) rhpth 20 (n=541) No. of women who had >1 fragility fracture Neer RM et al. N Engl J Med 2001; 344: Bisphosphonates Denosumab Consider: Safety and Tolerability Raloxifene Teriparatide Hypocalcemia* Hypocalcemia* Vasodilation Transient orthostatic hypotension GI symptoms Postmarketing reports of msk pain Infections (serious events 4.1% vs. 3.4% placebo) Dermal events (10.8% vs. 8.2% placebo) VTE ( risk vs. placebo) Lipid and triglyceride monitoring Osteonecrosis of jaw Osteonecrosis of jaw Stroke Renal impairment ** Suppression of bone turnover Atrial fibrillation (2.5% vs. 1.9% placebo) Osteosarcoma (only animal trials, not clinical trials) Urolithiasis 30

31 Issues to consider Whom should be treated to maximize benefit and minimize risk? When do you consider a drug holiday for your patient? What do you do if your patient has been on bisphosphonate therapy for >5yrs? How long should treatment with Bisphosphonates last? Unique to Bisphosphonates in chronic disease of having a cumulative effect and potential residual effect Long-term therapy potentiates risk of rare complications Can we stop denosumab? 31

32 Fracture risk When to consider a drug holiday? Suggested duration of therapy Suggested duration of drug holiday Low No therapy Discontinue if on therapy Mild increase ~3-5yrs Off BP until significant BMD loss or fracture Moderate risk 5-10yrs 2-3yrs or until significant BMD loss or fracture High risk 10yrs 1-2 yrs or until significant BMD loss or fracture Alternate medication (e.g. switch to non-bp treatment) may be given during the holiday from bisphosphonates May consider longer holidays with BPs that bind to bone strongly: Zolendronate3-6yrs; alendronate (3-5yr)) and shorter holidays with less binding abilities (eg 1-2 yrs post Risedronate) Optimize non-pharmacological interventions Data on Denosumab is pending Watts NB & Diab DL. J Clin EndocrinolMet; 2010; Anagnostis P et al (EMAS) Maturitas 2017 Key Messages 32

33 2010 Clinical Practice Guidelines for the Diagnosis and Management of Osteoporosis in Canada Key points: Management of osteoporosis should be guided by an assessment of the patient s absolute risk of osteoporosis-related fractures Fragility fracture increases the risk of further fractures and should be considered in the assessment Lifestyle modifications and pharmacologic therapy should be individualized to enhance adherence to the treatment plan Papaioannou A et al. CMAJ 2010; 182: What is our job as primary care providers? Assess risk Low risk is easy, lifestyle modifications High risk is predictable, needs Rx, counselling about adherence and answer concerns (side effects, AEs) Moderate risk requires thoughtful assessment: What to watch for, how to measure risk assessment, etc. As physicians we need to: Be clear Be proactive Treat aggressively when needed Bottom line: Prevention of fractures, not simple preservation of bone density. AE = adverse effect 33

34 Thank You 34