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Osteoporosis Canada Winter 2008 • vol. 12 no. 1 Ostéoporose Canada osteoporosis update a practical guide for Canadian physicians Vertebral fractures Guidelines promote improved diagnosis and reporting Renal safety of bisphosphonates Teriparatide (PTH) for severe osteoporosis Drug coverage in your province ��� �� ���� �� �� �� �� � ������ �������� �� Resources & announcements Page 12 �� Canadian Publications Mail Sales Product Agreement No. 40063504 questions & answers �� �� � �� �� NEW! IN POSTMENOPAUSAL OSTEOPOROSIS ACTONEL 75 mg To help fit her lifestyle, ACTONEL 75 mg provides a new dosing option: two consecutive days per month.2 ACTONEL helps you watch her back 1,2 And her hip/pelvis, clavicle, humerus, leg and wrist * 1,2 † * Composite score for nonvertebral fractures. † Vertebral fractures: ACTONEL 5 mg 2.4% vs. placebo 6.4%; p<0.001, 0-1 year. Nonvertebral fractures: ACTONEL 5 mg 5.2% vs. placebo 8.4%; p=0.02, 0-3 years. ACTONEL is indicated for the treatment and prevention of osteoporosis in postmenopausal women. ACTONEL 75 mg two consecutive days per month is indicated for the treatment of osteoporosis in postmenopausal women. ACTONEL is contraindicated in patients with known hypersensitivity to any component of the prescribed product. ACTONEL is contraindicated in patients with hypocalcemia. These and other disturbances of bone and mineral metabolism should be effectively treated before starting ACTONEL. Adequate intake of calcium and vitamin D is important. ACTONEL is not recommended for use in patients with severe renal impairment (creatinine clearance <30 mL/min). Since some bisphosphonates have been associated with upper gastrointestinal disorders, careful attention should be paid to the ACTONEL dosage and administration instructions especially in patients with a history of esophageal disorders. ACTONEL should be taken on an empty stomach at least 30 minutes before the first food, drink (other than plain water) and/or medication of the day, while in an upright position with sufficient plain water (≥120 mL). Patients should also not lie down for at least 30 minutes after taking ACTONEL. In postmarketing reporting, osteonecrosis of the jaw has been reported in patients treated with bisphosphonates. Clinical judgement, based on individual risk assessment, should guide the management of patients undergoing dental procedures. Musculoskeletal pain, rarely severe, has been reported as a common adverse event in patients who received ACTONEL for all indications. In clinical trials, the overall incidence of adverse events with ACTONEL 5 mg daily was comparable to placebo. The most commonly reported adverse events were (placebo vs. ACTONEL 5 mg) abdominal pain (3.3% vs. 4.1%), dyspepsia (4.8% vs. 5.2%) and nausea (5.0% vs. 4.8%). The overall safety and tolerability profile of ACTONEL 35 mg Once-a-Week is similar to that of ACTONEL 5 mg daily. The overall safety profile, including the incidence and pattern of upper gastrointestinal events of ACTONEL 75 mg on two consecutive days per month, is similar to that of ACTONEL 5 mg daily. Vomiting was reported in more ACTONEL 75 mg-treated patients than 5 mg daily (1.1% vs. 1.0%, respectively).2 Please refer to accompanying Prescribing Information for full dosing instructions and other important information. Product Monograph available on request. Manufactured and Distributed by: Procter & Gamble Pharmaceuticals Canada, Inc., Toronto, Ontario M5W 1C5 Marketed with: sanofi-aventis Canada Inc. Laval, Quebec H7L 4A8 Copyright © 2008 Procter & Gamble Pharmaceuticals Canada, Inc. All rights reserved. M77004-AAU7 CDN.RIS.08.01.01E editorial osteoporosis comment update Improved patient care: the common goal Osteoporosis Update is published by OSTEOPOROSIS CANADA 1090 Don Mills Road, Suite 301 Toronto, Ontario, M3C 3R6 Tel: (416) 696-2663 • Fax: (416) 696-2673 Toll Free: 1-800-463-6842 M I Julie M. Foley, President & CEO Dawn Barbieri, Director, Clinical Programs Parkhurst 400 McGill Street, 3rd Floor Montréal, Québec, H2Y 2G1 Mairi MacKinnon, Managing Editor Tel: (514) 397-8833 • Fax: (514) 397-0228 email: [email protected] Susan Usher, Corporate Editorial Director Pierre Marc Pelletier, Senior Art Director Chris A. Cant, Graphic Designer Louis-Georges Ste-Marie, MD, CPSQ is an endocrinologist and Director of the Metabolic Bone Diseases Laboratory at the Centre de recherche du Centre hospitalier de l’Université de Montréal, Hôpital Saint-Luc. He is Associate Professor of Medicine at l’Université de Montréal. editorial board Angela M. Cheung, MD, PhD, FRCPC University of Toronto Sidney Feldman, MD, FCFP University of Toronto David A. Hanley, MD, FRCPC University of Calgary Anthony B. Hodsman, MB, BS, FRCPC University of Western Ontario Stephanie Kaiser, MD, FRCPC Dalhousie University Gregory Kline, MD, FRCPC University of Calgary Heather McDonald-Blumer, MD, FRCPC University of Toronto Suzanne Morin, MD, FRCPC McGill University Robert Sabbah, MD, FRCSC Université de Montréal Kerry Siminoski, MD, FRCPC University of Alberta Louis-Georges Ste-Marie, MD, CPSQ Université de Montréal © 2008 Osteoporosis Canada No articles may be reprinted without permission. Views expressed by the authors are not necessarily endorsed by Osteoporosis Canada. Osteoporosis Update is made possible with the assistance of unrestricted educational grants from the following sponsors: ore than 65% of vertebral fractures go undetected. Physician awareness of the importance of these fractures, which are associated with a major risk for future fractures and a significant predictor of morbidity and mortality, is crucial. Given the increasing evidence of this care gap, Osteoporosis Canada and the Canadian Association of Radiologists published a set of recommendations to promote and facilitate the diagnosis and reporting of vertebral fractures. In the feature article on page 4 of this issue, we present a summary of the document’s key points to guide clinicians and healthcare providers involved in the care of individuals with osteoporosis. On page 6, experts from the Scientific Advisory Council (SAC) Drs. Anthony Hodsman and Sophie Jamal answer timely questions on the effect of long-term bisphosphonate therapy on the kidneys and the use of the bone-building agent teriparatide (PTH [Forteo®]) for severe osteoporosis. Next, a special section on provincial formularies (page 7) provides physicians across the country useful information on which osteoporosis drugs are available through benefit programs in their region. Finally, on page 9, we wish to congratulate the 2007 winner of the Lindy Fraser Memorial Award, Dr. Anthony Hodsman, for his outstanding contribution to osteoporosis research and education over the years. Dr. Hodsman had a leadership role as Chair of the SAC from 2003 to June 2006, and has published extensively in the basic science and clinical fields, as well as on the application of clinical practice guidelines in osteoporosis. We also take the opportunity to highlight some of the important Canadian studies presented in September 2007 at the American Society for Bone and Mineral Research (ASBMR) Annual Meeting. The contribution of Canada’s researchers at this meeting was substantial. While we are unable to mention all of them here, we laud all their efforts, which are so vital to the goal of improving treatment and care for the 1.4 million Canadians with osteoporosis. We hope you will find this issue informative and useful in your daily practice. The SAC welcomes your feedback — please send any questions or comments to [email protected]. Eli Lilly Canada Inc. P&G Pharmaceuticals and sanofi aventis The financial support received from sponsors does not constitute an endorsement by OsteopoRosis Canada of any of the sponsors’ products or services. OST1201 ISSN 1480–3119 Canadian Publications Mail Sales Product Agreement No. 40063504 Return undeliverable Canadian addresses to: Circulation, 400 McGill Street, 3rd Floor Montréal, Québec, H2Y 2G1 [ Bisphosphonate and calcium concerns In our next issue, the SAC will address recent reports on the use of oral bisphosphonates and risk of aseptic osteonecrosis, as well as a possible risk of cardiovascular events in older women who take calcium. Meanwhile, physicians are advised to consult www.osteoporosis.ca for updated information. osteoporosis update Winter 2008 3 f eatu re Vertebral fracture diagnosis Recommendations to help reduce future risk VI ertebral fractures, the most common type of osteoporotic fractures, are a major risk factor for future fractures and a significant predictor of morbidity and mortality. While early detection can lead to further investigation and appropriate therapy that helps cut the risk of future fractures, increasing evidence shows that these important clinical markers of osteoporosis are both underdiagnosed and inadequately followed up. The Scientific Advisory Council of Osteoporosis Canada, together with the Canadian Association of Radiologists, created a multidisciplinary working group to address this care gap. Their recently published recommendations (Lentle BC, Brown JP, Khan A et al. Recognizing and reporting vertebral fractures: reducing the risk of future osteoporotic fractures. CARJ 2007;58:27-36) stress the need for physician awareness of the importance of vertebral fracture diagnosis in assessing future osteoporotic fracture risk. While not advocating widespread radio- Key messages • Radiologists should identify and report vertebral fractures incidental to radiologic exams done for other reasons. • The Genant semiquantitative method (measuring loss of vertebral endplate parallelism, cortical interruptions, and changes in the anterior, midbody and posterior heights of vertebral bodies) is most effective for assessing vertebral fracture from lateral spine or chest radiographs; Grade II and III fractures should receive the most emphasis. • When spine radiographs are performed, anteroposterior exams may assist in the initial evaluation. • Follow-up may only require single lateral views of the thoracic and lumbar spine, including T4 to L4 vertebrae. • Dual-energy x-ray absorptiometry (DXA) exams that include lateral spinal morphological assessments (VFA) may contribute to fracture recognition. • All physicians should be educated on the clinical significance of vertebral fracture recognition as a potential indicator of future risk of osteoporotic fracture, with its associated morbidity and mortality. 4 osteoporosis update Winter 2008 graphic screening (due to reasons of cost and radiation exposure), the document concludes that it is to patients’ benefit that radiologists report all vertebral fractures seen on chest or other radiographs, regardless of the initial purpose of the examination, and, where appropriate, make recommendations for further evaluation. The recommendations, reached by consensus, were reviewed and endorsed by the following organizations: • Canadian Association of Nuclear Medicine • Canadian Association of Radiologists • Canadian Orthopaedic Association • Canadian Panel of the International Society for Clinical Densitometry • Osteoporosis Canada • Society of Obstetricians and Gynaecologists of Canada The full text, as well as a Powerpoint slide presentation, are available at www.osteoporosis.ca, in the Health Professionals section. This article presents a brief summary. Impact of vertebral fractures Both clinical and occult vertebral fractures are associated with significant health consequences. Clinical fractures, detected when patients present with back pain, account for approximately one-third of osteoporotic vertebral fractures. The rest are occult fractures; they do not cause severe pain and consequently go undiagnosed in routine medical evaluations that do not include x-rays. Vertebral fractures can lead to deterioration of physical function and decreased ability to perform activities of daily living. Effects include: • chronic back pain • reduced range of motion • slower gait • impaired pulmonary function • higher likelihood of disability • loss of independence • social isolation • lower quality of life Vertebral deformities are associated with a marked increase in the risk of additional fractures, including hip fractures, and also with higher short- and mid-term mortality rates. Five-year mortality rates following ver tebral fractures are comparable to those following hip fracture. Since physicians and healthcare providers involved in the care of these patients may not always appreciate the future implications of vertebral fractures, increased awareness is crucial. Underreporting of vertebral fractures: clinical implications More than 65% of spinal fractures go undetected. To compound this problem, studies reveal that radiology reports often neglect to mention fractures evident on chest or other radiographs done for other reasons. In one study of 934 women aged 60 years or over who had chest x-rays, 132 of the women were diagnosed with one or more spinal fractures using Genant’s semiquantitative criteria (the most widely used criteria for defining vertebral fracture), but only 65 cases (49%) were reported. Further, the diagnosis was entered in the medical record of only 23 (17%) of the patients, and only 25 of these women with fractures (19%) received osteoporosis treatment. A similar Canadian study of emergency department radiographs looked at a population comprised of 47% women, mean age 75 years, 46% of whom were admitted to hospital. According to the reviewing radiologist, the prevalence of moderate to severe vertebral fractures (Genant Grades II and III) was 22%; only 55% of these were mentioned in the official radiology reports. In an analysis of data from the IMPACT (Improving the Measurements of Persistence on Actonel Treatment) trial, Delmas et al identified underdiagnosis of vertebral fractures as a worldwide problem. False-negative rates of fracture reporting in women aged 65–80 years ranged from 29.5% to 46.2% in various countries, while the false-positive rate, at 5%, was not a significant issue. For clinicians, including radiologists, these data present a considerable opportunity for better patient management through prevention of the disease and disability associated with fractures. It is clearly to patients’ benefit that radiologists report vertebral fractures detected on chest or other radiographs, no matter how incidental to the primary reason for the examination. Bone mineral density (BMD) testing should be considered if a fracture is found. Precise indication by the radiologist of the grade of fracture and vertebrae involved will be useful to the clinician. Radiographic techniques To date, vertebral radiographs provide the best simple method for assessing the presence of vertebral fractures. In the absence of localized pain, no adequate alternative exists to indicate the need for more sophisticated examinations such as computed tomography (CT) or magnetic resonance imaging (MRI) of the spine. It is to patients’ benefit that radiologists report all vertebral fractures seen on chest or other radiographs, regardless of the initial purpose of the examination, and, where appropriate, make recommendations for further evaluation For the initial assessment of spinal osteoporotic fractures, both the anteroposterior and lateral projections of the thoracic and lumbar spines are advised. For follow-up, only lateral radiographs are required as these are the most effective in detecting osteoporotic fractures. Tools to measure bone quality could improve fracture risk assessment and follow-up. At present, osteoporosis is diagnosed based on BMD measurements or the existence of a low-trauma fracture, the history of which provides the simplest measure of bone quality. As appreciation of the importance of diagnosing asymptomatic fractures grows, makers of some central x-ray-based densitometers are adding software to image relevant spinal segments (lateral imaging, T4 to L4). Vertebral fracture assessment (VFA, also described by various manufacturers as instant vertebral assessment, lateral vertebral assessment and dual-energy vertebral assessment) provides lower-resolution images that are not subject to projection distortion. While this technology is promising, further research is needed before VFA is adopted for widespread clinical use. (For more information on radiographic techniques, see the full CARJ document.) Tools to bridge the care gap A care gap exists in the identification, reporting and follow-up of vertebral fractures. Physician awareness of the importance of vertebral fracture diagnosis in assessing future risk is key. Chest radiographs are a valuable casefinding tool for assessing vertebral fractures. Radiologists should recognize the need for reporting fractures seen on these or other radiographs. Where appropriate, the report should include recommendations for further evaluation (e.g. thoracic and lumbar spine radiographs and DXA testing) to promote further action on the part of the clinician. ● Possible wording for reporting vertebral fractures Incidental note is made of fractures in the thoracic spine involving Tx, Tx’ and Tx”. If these are low-trauma fractures, this finding strongly suggests that the patient has osteoporosis and is very likely to sustain further fractures in the next year. Further investigation and follow-up is strongly recommended. osteoporosis update Winter 2008 5 qu estions & answers q. Can long-term bisphosphonate treatment for osteoporosis be harmful to the kidneys? Which patients are at risk, and what can be done to minimize the risk? Dr. Anthony Hodsman responds: Nephrotoxicity following intravenous (IV) bisphosphonates has been reported with both pamidronate and zoledronic acid in cancer patients, mostly in cases of multiple myeloma. The complication is uncommon, but appears to be related to high doses infused over relatively short time periods (< 2 hours for pamidronate and < 15 minutes for zoledronic acid). To my knowledge, direct nephrotoxicity has not been reported following the use of oral or IV bisphosphonates in doses recommended or approved for osteoporosis. While a 25% dose reduction for zoledronic acid as used in cancer patients is advised (from 4 mg to 3 mg for glomerular filtration rates [eGFR] < 40 ml/min), no such reduction has been recommended for the unit dose (5 mg) of once-yearly zoledronic acid for treating osteoporosis. Protocol amendments were introduced during the Phase III Oncology trials of IV zoledronic acid based on impaired renal function, but none were in place during the pivotal Phase III HORIZON trial in osteoporosis patients. Renal function was carefully monitored in subgroups, and no differences in either efficacy outcome or renal function were found between the treated and placebo groups. However, the Phase III clinical trials for all bisphosphonates used as osteoporosis therapy excluded patients with chronic kidney disease (creatinine clearance rate [eGFR] < 35 ml/min). There is therefore little data about fracture prevention efficacy and long-term adverse effects in these individuals. Bisphosphonate labelling warns against using these drugs when the eGFR is < 35 ml/min. Retrospective analysis of the Fracture Intervention Trials (FIT) and pooled data from 9 risedronate studies revealed that approximately 10% of subjects had severe renal impairment (eGFR < 30–45 ml/min), and up to 45% had moderate renal impairment (eGFR 30–60 ml/min). In the post-hoc analyses, both alendronate and risedronate increased bone mineral density (BMD) and prevented vertebral fractures regardless of the degree of renal impairment, compared with placebo. There were no apparent differences in adverse event rates between subjects with normal or reduced renal function with either oral bisphosphonate. While small increments Dr. Anthony Hodsman founded the London Regional Osteoporosis Program, and is currently Professor in the Department of Medicine at the University of Western Ontario, in London. Dr. Sophie Jamal is Medical Director and Director of Research of the Osteoporosis Program at Women’s College Hospital, and Assistant Professor in the Division of Endocrinology and Metabolism at the University of Toronto. 6 osteoporosis update Winter 2008 in serum creatinine were observed during the 3-year FIT study, these were similar both in individuals with and without reduced renal function at the outset, as well as in groups taking placebo and active drug. It is important to remember that the clinical syndrome of renal osteodystrophy (uremic bone disease associated with progressive 2° hyperparathyroidism and phosphorus retention) becomes manifest at eGFR < 30 ml/min. Vitamin D deficiency becomes more frequent as general health and nutrition deteriorate with advancing kidney failure. Moreover, the diagnostic value of bone densitometry is invalid in such patients, since bone mineralization is impaired by both the presence of hyperparathyroid bone disease and osteomalacia, thus apparently lowering the reported T-score. The management of patients with apparent osteoporotic fractures — with advanced chronic renal failure and/or on renal replacement therapy — is a grey zone. While bisphosphonate therapy is tempting, in the absence of any alternative treatment, physicians should use these drugs in the knowledge that there is no proof of efficacy in this patient group, either in improving BMD or preventing fractures. To my knowledge, direct nephrotoxicity has not been reported following the use of oral or IV bisphosphonates in doses recommended or approved for osteoporosis The kidneys excrete approximately 50% of an administered bisphosphonate dose. The remainder is bound to bone, where it exerts its selective action on osteoclasts. While it would be reasonable to assume that a 50% dose reduction should be employed when treating patients with advanced renal failure, the available oral bisphosphonates in Canada have been used at higher than the approved dose (for extended periods), without apparent adverse effects. Unfortunately, there is no information about the safety of conventional doses in advanced renal failure, or comparative efficacy when using a 50% dose reduction (either reducing the unit dose or extending the dosing interval). The best advice I can give in this circumstance is to refer the patient to a physician with experience in using bisphosphonates in the setting of advanced renal failure. Unfortunately, such specialists are few and far between. References Miller PD, Roux C, Boonen C et al. Safety and efficacy of risedronate in patients with age-related reduced renal function as estimated by the Cockroft-Gault method: a pooled analysis of nine clinical trials. J Bone Mineral Res 2005;20:2105-15. Jamal S, Bauer DC, Ensrud KE et al. Alendronate treatment in women with normal to severely impaired renal function: an analysis of the fracture intervention trial. J Bone Mineral Res 2007;22:503-8. q. When should I consider teriparatide (Forteo®) as first-line therapy for my postmenopausal patient with very low BMD? Is it better to try other osteoporosis therapies first? What should I advise patients taking Forteo about calcium and vitamin D? Dr. Sophie Jamal explains: Teriparatide is the only anabolic agent available for treating osteoporosis. Ana bolics increase bone formation, activation frequency and bone turnover, and induce microarchitectural changes to create a new bone structure. The Canadian product monograph for teriparatide suggests that is appropriate for postmenopausal women with severe osteoporosis who are at high risk of fracture or who have failed, or are intolerant to, other therapies. These broad recommendations are sometimes curbed by cost concerns. For example, the drug is not covered by Ontario Drug Benefits and costs about $15,000 for the 18-month treatment course. Practically speaking, teriparatide is usually prescribed for patients who have had a low-trauma fracture while adherent with a second-generation bisphosphonate, with no clinical or laboratory evidence of secondary osteoporosis. To date, there are no compelling data to suggest that prior use of osteoporosis therapies influences the efficacy p rovincial of teriparatide on fracture reduction. Regardless of whether teriparatide is prescribed following, or as a firstline agent prior to additional antiresorptive therapy, once the course is completed patients should receive maintenance antiresorptive treatment (Black DM et al. NEJM 2005;353:555-65). Administration of teriparatide is associated with transient increases in serum calcium about 4 to 6 hours after dosing, but sustained hypercalcemia is unusual. A large randomized trial of teriparatide for postmenopausal women with osteoporosis in which all patients received calcium (1000 mg) and vitamin D (400–1200 IU) reported that mild hypercalcemia (serum calcium > 2.6 mmol/L) based on samples obtained approximately a month after treatment was observed in 2% of women on placebo and 11% of women receiving 20 mcg of teriparatide (Neer RM et al. NEJM 2001;344:1434-41). In the majority of cases, reducing calcium intake corrected the hypercalcemia. It is also important to note that women who did not have hypercalcemia in the first 6 months of treatment seldom had it later. Based on this data, it seems reasonable to advise patients to continue taking the recommended amounts of calcium and vitamin D. Fasting serum calcium, measured 24 hours after the last teriparatide dose, should be monitored periodically at least for the first 6 months of therapy and if elevated, patients should stop or reduce their calcium supplements. ● f ormularies Osteoporosis drug coverage in Canada P I rovinces are responsible for deciding which medications (approved by Health Canada) to include in their drug benefit plans. Provinces provide selective drug coverage for eligible groups, including individuals over 65 years of age and those on social assistance and disability. Provincial formularies list which drugs are available, either as general or restricted benefits: • General benefits (open listing) require no special criteria or paperwork. • Restricted benefits require that individuals meet certain clinical criteria. In general, the physician must submit a special form along with the patient’s prescription. Certain osteoporosis medications (e.g. etidronate [Didrocal®] and hormone [estrogen] replacement therapy) are listed as general benefits in most provincial formularies. The table on page 8 outlines the status of the newer therapies on provincial formularies across the country. In general, where generic versions of a drug are available, these will be substituted and the lesser cost reimbursed. Patients who choose to stay on the brand version instead of accepting the generic must pay the difference. The whole cost may be covered if the physician specifies the brand version only, but in this case the prescription must be accompanied by a completed special authorization request form. ● Continued on page 8 osteoporosis update Winter 2008 7 Formulary listings for osteoporosis drugs This chart reflects listings for use in osteoporosis patients. Listings of these drugs may differ for other conditions. Coverage is under constant review and is subject to change. Selective estrogen receptor modulators (SERMs) Calcitonin Bisphosphonates* Risedronate Raloxifene (Evista®): Miacalin®: nasal oral 60 mg/d spray 200 IU/d (Actonel®): oral 5 mg/d; 35 mg once a (generics available) week; 75 mg/mo on 2 consecutive days; Actonel + calcium Teriparatide (PTH) Forteo®: subcu taneous injection 20 mcg/d, 18 months maximum Alendronate (Fosamax®): oral 10 mg/d; 70 mg once a week (generics available) Alendronate 70 mg plus vitamin D3 2800 IU weekly (Fosavance®) BC SA NL SA (75 mg NL; Actonel + calcium under review) SA NL NL AB SA NL SA (75 mg, Actonel + calcium NL) SA SA (calcitonin solution regular benefit) NL SK EDS NL EDS (75 mg, Actonel + calcium NL) EDS EDS NL MB EDS (Part 3) NL EDS (Part 3) (75 mg, Actonel + calcium NL) EDS (Part 3) EDS (Part 3) NL ON General benefit General benefit General benefit (75 mg, Actonel + calcium NL) LU Miacalcin NL; (calcitonin solution general benefit) NL QC Open NL Open (75 mg NL) Open Open PE NB SA NL SA (75 mg under review; Actonel + calcium NL) SA SA (calcitonin solution general benefit) NL NS EDS NL EDS (75 mg, Actonel + calcium NL) EDS EDS (calcitonin solution general benefit) NL PEI NL NL NL NL NL NL NL SA NL SA (75 mg, Actonel + calcium NL) SA SA NL YT EDS NL EDS (75 mg, Actonel + calcium NL) EDS NIHB LU NL LU (75 mg, Actonel + calcium NL) LU Province *Note: Zoledronic acid (Aclasta®) 5 mg, a once-yearly bisphosphonate given by 15-minute infusion by a certified medical professional, was approved on October 30, 2007 for the treatment of postmenopausal osteoporosis. While it is currently covered by the majority of provincial drug benefit plans (except BC and NL) for the treatment of Paget’s disease, it is not covered for the treatment of osteoporosis. EDS (calcitonin solution listed) LU NL NL SA: Special authorization NL: Not listed in the formulary (i.e. not a benefit) EDS: Exception drug status PE: Patient of exception, under RAMQ but not Québec Basic Prescription Drug Insurance Plan NIHB: Non-Insured Health Benefits, a federal health benefit plan for First Nations and Inuit people in Canada LU: Limited use Online access to formularies BC: www.healthservices.gov.bc.ca/pharme/formulary/index.html AB: www.ab.bluecross.ca/dbl/idbl_main1.html SK: http://formulary.drugplan.health.gov.sk.ca MB: www.gov.mb.ca/health/mdbif/index.html ON: www.health.gov.on.ca/english/providers/program/drugs/odbf_ eformulary.html QC: www.ramq.gouv.qc.ca/en/regie/lois/liste_med.shtml 8 osteoporosis update Winter 2008 NB: www.gnb.ca/0051/0212/index-e.asp NS: www.gov.ns.ca/health/Pharmacare/formulary.asp PEI: www.gov.pe.ca/infopei/index.php3?number=45156 NL: www.health.gov.nl.ca/health/nlpdp/#Formulary YT: www.hss.gov.yk.ca/publications NIHB: http://www.hlthss.gov.nt.ca/Features/Programs_and_ Services/health_care/pdf/drug_benefit_list.pdf p erspective Lindy Fraser Memorial Award 2007 O I steoporosis Canada is pleased to announce that its Scientific Advisory Council (SAC) has selected Dr. Anthony Hodsman to receive this year’s Lindy Fraser Memorial Award, in recognition of his valuable contribution to osteoporosis research and education. This award was established in 1993 in honour of the founder of the first osteoporosis support group in the world. Dr. Hodsman has provided outstanding leadership both as Chair of the SAC from 2003 to June 2006 and through his significant research over the years, particularly in the area of parathyroid hormone (PTH) as a new approach to osteoporosis therapy. Trained in both endocrinology and nephrology, Dr. Hodsman is currently Professor in the Department of Medicine at the University of Western Ontario. He founded the London Regional Osteoporosis Program in 1981 and acted as Medical Director until 2004. Dr. Hodsman’s research interests lie mainly in the field of metabolic bone disease, renal osteodystrophy and osteoporosis. He has published extensively in the basic science and clinical fields as well as on the application of clinical practice guidelines in osteoporosis. Upon receiving the award, Dr. Hodsman had this advice for new researchers: “First, I’d encourage young researchers to realize that most of what we think we know about the skeleton is not biologically correct. Therefore there are an infinite variety of windmills to go and tilt at, with opportunities to get closer to the truth. However, the real truth won’t be clear until after retirement, so you’ll never run out of things to do. “Second, pick a project that is sufficiently circumscribed so that there is a good chance to become an expert — for that, most people need either a mentor, or very good luck. “Third, demand the time protection to accomplish the goal. It is never worth being successful in a university career at the expense of one’s family, health and friends. It is necessary to visit Peru, or the Himalayas along the way.” Please join Osteoporosis Canada and the SAC in congratulating and thanking Dr. Anthony Hodsman. Canada at ASBMR TI he American Society for Bone and Mineral Research (ASBMR) 29th Annual Meeting was held in Honolulu, Hawaii in September 2007, and featured much important Canadian research. Here are some of the highlights. Long-terms effects of vitamin K The long-term effects and safety of vitamin K, promoted as a supplement for decreasing bone loss in postmenopausal women, are unknown. ECKO (Evaluation of the Clinical Use of Vitamin K Supplementation in Post-Menopausal Women With Osteopenia), a 2-year placebo-controlled double-blind trial, randomized 217 postmenopausal women with osteopenia to receive 5 mg vitamin K1 daily and 223 to placebo. Endpoints included bone mineral density (BMD), bone turnover markers, fractures, long-term side effects and health-related quality of life (HRQOL). The study was extended for earlier participants for up to 4 years. Daily vitamin K supplements for 2 to 4 years did not protect against age-related decline in osteoporosis update Winter 2008 9 BMD in the study population, although it was associated with lower incidences of clinical fractures and cancer. HRQOL was not significantly different between the 2 groups. The team concluded that further studies are needed to confirm the findings. Cheung AM, Tile LE, Lee Y et al. Abstract M399 Case manager interventions A randomized controlled trial by Morrish et al was designed to determine the cost and effectiveness of using case managers to improve inappropriately low osteoporosis diagnosis and treatment rates in patients who have undergone hip fractures. Patients recruited from all hospitals in Capital Health, Edmonton (criteria included age over 50 years, not on active osteoporosis therapy except calcium/vitamin D and not in long-term care) were randomized to intervention by a case manager (n = 110) or usual care (n = 110). Case managers arranged BMD testing, prescribed bisphosphonates and communicated with primary care physicians. At 6 months, patients in the intervention group were more likely to receive appropriate care (prescribed bisphosphonate therapy for T-score < –1.5) than controls (67% vs 26%, adjusted p < 0.001), at a cost of $52 per patient. The researchers concluded that case managers provide a cost-effective way of substantially increasing rates of testing and treatment for osteoporosis in hip fracture patients. Morrish DW, Majumdar SR, Beaupre LA et al. Abstract T329 Alendronate in cystic fibrosis patients In the only Canadian randomized controlled trial of bisphosphonates in adults with cystic fibrosis, Papaioannou et al showed that alendronate was well tolerated and increased BMD significantly over 12 months, compared with placebo. The multicentre trial, which focussed on BMD changes, assigned 56 patients, mean age 29.1, to either placebo or alendronate 70 mg once-weekly for 12 months. Patients received daily calcium and vitamin D supplements. The treatment group had a 4.99% (95% CI: 2.40, 7.59) greater increase in lumbar spine BMD and a 3.50% (95% CI: 1.37, 5.63) greater increase in proximal femur BMD compared with the placebo group (adjusted for age, BMI, baseline BMD, number of baseline vertebral fractures). Papaioannou A, Kennedy CC, Ionnidis G et al. Abstract W360 Adherence improves fracture rates A population-based study by Jaglal et al confirms pre vious reports and should encourage continued efforts to monitor treatment and improve adherence as an effective means to reduce fracture rates. The researchers looked at prescription refill compliance in 74,085 Ontario residents aged 67 and over who started an osteoporosis medication between 2002–2004, after no 10 osteoporosis update Winter 2008 prior bisphosphonate or SERM claim for 2 years. Refill compliance was calculated using the Medication Possession Ratio, defined as the number of days supplied from first to last prescription/length of follow-up (730 days), at cut-offs of 30%, 50%, 67% and 80%. In the period after the initiation of medication, there were 1,751 (2.4%) fractures. Logistic regression analyses were conducted for each refill compliance cut-off (adjusted for age, sex, BMD, other medications, number of physician visits in the 2-year period prior to starting treatment, BMD after initiation of treatment, and Charlson Comorbidity Index). Only 80% and 67% refill compliance were statistically significantly associated with fracture reduction. These data suggest that adherence of at least 67% to 80% is required to effect a measurable reduction in osteoporotic fractures. Jaglal S, Thiruchelvam D, Hawker G. Abstract 1275 Validation of 10-year fracture risk prediction Absolute 10-year fracture risk is the preferred method for fracture risk assessment, but the validity of applying published rates from one population to another is uncertain. In this study that compared predicted and observed fracture risk, Leslie et al concluded that Swedish 10-year fracture risk data (used to predict risk from age-only and age+BMD in Manitoba women age 47.5 years or older at the time of baseline femoral neck BMD) are generally applicable to the Canadian female population referred for BMD testing. Higher observed vs estimated fracture rates for women age 77.5 years or older may be explained by healthy selection bias (elderly women referred for BMD testing have lower mortality than expected, thus more years at risk for fracture). Leslie WD, Tsang JF, Lix LM. Abstract 1078 Nitrates and BMD Using data from the population-based Canadian Multicentre Osteoporosis Study (Camos), researchers demonstrated that nitrate use is associated with increased BMD in men and women aged 50 years and older. BMD was measured in 1,449 men and 2,682 women; of these, 14 men and 35 women reported nitrate use. Nitrate users were significantly older and weighed less than nonusers. Both women and men users had lower annual loss of BMD at all measured sites (hip, femoral neck and lumbar spine) compared to nonusers. These findings are consistent with earlier studies and reinforce the need for a randomized trial to determine the relationship between nitrate use and fracture. Jamal SA, Goltzman D, Hanley DA et al. Abstract 1266 For more information and to view more abstracts, please visit the ABSMR website: www.asbmr.org. Montreal, Québec will host the next annual meeting from September 12–16, 2008. ● It’s the only bone formation agent available in Canada. Will antiresorptive therapy be enough? Is it time to stimulate new bone with FORTEO? FORTEO can stimulate new bone formation. RECOMMEND FORTEO for postmenopausal women with severe osteoporosis. RAPID increase in bone formation markers.* REDUCED RISK of fracture has been demonstrated. * Daily administration of FORTEO to postmenopausal women with osteoporosis stimulated bone formation. Peak concentrations of procollagen I carboxy-terminal propeptide (PICP) approximately 41% above baseline were observed after 1 month of treatment, followed by a decline to near-baseline values by 12 months. Serum bone-specific alkaline phosphatase (BSAP) concentration increased by 1 month of treatment and continued to rise more slowly from 6 to 12 months; maximum increases were 45% above baseline. Teriparatide significantly reduced the incidence and severity of back pain. In women with postmenopausal osteoporosis, there was a 26% reduction (p = 0.017) in the spontaneous reports of new or worsened back pain compared to placebo. FORTEO (teriparatide [rDNA origin] injection) is indicated for the treatment of postmenopausal women with severe osteoporosis who are at high risk of fracture or who have failed or are intolerant to previous osteoporosis therapy; and to increase bone mass in men with primary or hypogonadal severe osteoporosis who have failed or are intolerant to previous osteoporosis therapy. The effects of FORTEO on risk for fracture in men have not been demonstrated. severe renal impairment; metabolic bone diseases other than primary osteoporosis (including hyperparathyroidism and Paget’s disease of the bone); unexplained elevations of alkaline phosphatase; prior external beam or implant radiation therapy involving the skeleton; bone metastases or a history of skeletal malignancies. The safety and efficacy of FORTEO (teriparatide [rDNA origin] injection) have not been evaluated beyond 2 years (median 19 months in women and 10 months in men). Consequently, the maximum lifetime exposure to FORTEO for an individual patient is 18 months. FORTEO should not be administered to women who are pregnant or breastfeeding, nor to children or young growing adults. The safety and efficacy of FORTEO have not been studied in pediatric populations. FORTEO is not indicated for use in pediatric patients. Physicians should become familiar with the full content of the Product Monograph prior to prescribing FORTEO (teriparatide [rDNA origin] injection). FORTEO should be prescribed only to patients for whom the potential benefits outweigh the potential risk. In rats, teriparatide caused an increase in the incidence of osteosarcoma that was dose- and treatment duration-dependent at systemic exposures ranging from 3 to 60 times the exposure in humans given a 20 mcg dose. FORTEO should not be prescribed to patients who are at increased baseline risk for osteosarcoma. FORTEO (teriparatide [rDNA origin] injection) is contraindicated in patients with hypersensitivity to teriparatide or any of its excipients; preexisting hypercalcemia; Adverse events considered to be related to FORTEO therapy were nausea, dizziness, and leg cramps. REFERENCE: FORTEO (teriparatide [rDNA origin] injection) Product Monograph. Eli Lilly Canada Inc. June 3, 2004. Patient support available at 1.877.4FORTEO ® Registered trademark owned by Eli Lilly and Company; used under license. © 2007 Eli Lilly Canada Inc. Toronto, Ontario M1N 2E8. www.lilly.ca FTCAD01300807 prescribing summary summaryenclosed on page See prescribing about Osteoporosis Canada Canadian Endocrine Update 2008 Osteoporosis Canada is a national, not-for-profit organization dedicated to educating, empowering and supporting individuals and communities in the prevention and treatment of osteoporosis. The organization, guided by its Scientific Advisory Council (SAC) made up of osteoporosis experts from across the country, works with healthcare professionals to make the latest prevention, diagnostic and treatment options available to Canadians. Save the date for an exciting 3-day symposium presented by McMaster University and the University of Western Ontario, in partnership with the Canadian Society of Endocrinology and Metabolism (CSEM), American Association Of Clinical Endocrinologists (AACE), Osteoporosis Canada (OC), Ontario Association of Medical Radiology Technicians (OAMRT) and International Society of Clinical Densitometry (ISCD). Advances in Endocrinology and Metabolism will feature state of the art lectures on common endocrine disorders, diagnosis and management, and will include an osteoporosis symposium and ISCD course, jointly sponsored by OC, OAMRT and ISCD. Course Directors are Aliya Khan, MD, FRCPC, FACP and Terri L. Paul, MSc, MD, FRCPC. www.osteoporosis.ca May 3 1 – Ju n e 1 , 2 0 0 8 St. Jo s e p h ’s H e a l t h c a re Ham i l t o n , ON For more information and registration details, please visit the Health Professionals section, Calendar of Events page, at www.osteoporosis.ca ISCD Bone Densitometry Courses For information and locations around the world, contact Anabela Gomes at 860-586-7563; [email protected]; www.ISCD.org