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Summary: In this population-based study, we compared incident fracture rates in long-term care (LTC) versus community seniors between 2002 and 2012. Hip fracture rates declined more rapidly in LTC than in the community. An excess burden of fractures occurred in LTC for hip, pelvis, and humerus fractures in men and hip fractures only in women., Introduction: This study compares trends in incident fracture rates between long-term care (LTC) and community-dwelling seniors ≥65 years, 2002-2012., Methods: This is a population-based cohort study using administrative data. Measurements were age/sex-adjusted incident fracture rates and rate ratios (RR) and annual percent change (APC)., Results: Over 11 years, hip fracture rates had a marked decline occurring more rapidly in LTC (APC, -3.49 (95% confidence interval (CI), -3.97, -3.01)) compared with the community (APC, -2.93 (95% CI, -3.28, -2.57); p < 0.05 for difference in slopes). Humerus and wrist fracture rates decreased; however, an opposite trend occurred for pelvis and spine fractures with rates increasing over time in both cohorts (all APCs, p < 0.05). In 2012, incident hip fracture rates were higher in LTC than the community (RRs: women, 1.55 (95% CI, 1.45, 1.67); men, 2.18 (95% CI, 1.93, 2.47)). Higher rates of pelvis (RR, 1.48 (95% CI, 1.22, 1.80)) and humerus (RR, 1.40 (95% CI, 1.07, 1.84)) fractures were observed in LTC men, not women. In women, wrist (RR, 0.76 (95% CI, 0.71, 0.81)) and spine (RR, 0.52 (95% CI, 0.45, 0.61)) fracture rates were lower in LTC than the community; in men, spine (RR, 0.75 (95% CI, 0.57, 0.98) but not wrist fracture (RR, 0.91 (95% CI, 0.67, 1.23)) rates were significantly lower in LTC than the community., Conclusion: Previous studies in the community have shown declining hip fracture rates over time, also demonstrated in our study but at a more rapid rate in LTC. Rates of humerus and wrist fractures also declined. An excess burden of fractures in LTC occurred for hip fractures in women and for hip, pelvis, and humerus fractures in men., Competing Interests: Conflicts of interests Alexandra Papaioannou received grants/funds from Amgen, Eli Lilly, and Merck, a honoraria from Amgen and Eli Lilly, participated in a speaker forum for Amgen and Eli Lilly, and was a consultant for Amgen and Eli Lilly. Jonathan D. Adachi received grants/funds from Actavis, Amgen, Eli Lilly, Merck, and Novartis, a honoraria from Amgen, Eli Lilly, Merck, and Novartis, participated in a speaker forum for Amgen, Eli Lilly, Merck, and Novartis, acted as a consultant for Amgen, Eli Lilly, Merck, and Novartis, and is a board member for the International Osteoporosis Foundation. Courtney Kennedy, George Ioannidis, Cathy Cameron, Ruth Croxford, Sara Mursleen, and Susan Jaglal have no conflicts of interest to declare.

Unlabelled: We created a 30-item Frailty Index in the Canadian Multicentre Osteoporosis Study. A Frailty Index is a sensitive measure that can quantify fracture risk according to degree of frailty. Our results indicated that at any age, frailty was an important independent risk factor for fracture over 10 years., Introduction: In later life, frailty has been linked to fractures. It is likely that the antecedents of fracture are seen across the life course, in ways not entirely captured by traditional osteoporosis risk factors. Using data collected from the prospective, population-based Canadian Multicentre Osteoporosis Study (CaMos), we created the 30-item CaMos Frailty Index and examined whether it was associated with incident fractures over 10 years., Methods: All CaMos participants aged 25 years and older (n = 9,423) were included in the analysis. To examine the relationship between baseline Frailty Index scores and incident fractures, a competing risk proportional sub-distribution hazards model was used with death considered a competing risk. Analyses were adjusted for age, sex, body mass index, education level, femoral neck T-score, and antiresorptive therapy., Results: At baseline, the mean age was 62.1 years [standard deviation (SD) 13.4], and 69.4 % were women. The mean Frailty Index score was 0.13 (SD 0.11), ranging from 0 to 0.66. For every 0.10 increase in Frailty Index scores (approximately one SD), the hazard ratio was 1.25 (p < 0.001) for all fractures, 1.18 (p = 0.043) for hip fractures, and 1.30 (p ≤ 0.001) for clinical vertebral fractures., Conclusion: The CaMos Frailty Index quantified fracture risk according to degree of frailty. Irrespective of age and bone mineral density, the Frailty Index was associated with hip, vertebral, and all-type clinical fractures. Predicting late onset illnesses may have to consider overall health status and not just traditional risk factors., Competing Interests: Kenneth Rockwood discloses that the Dalhousie University Industry-Liaison Office is reviewing the commercialization potential of one version of the Frailty Index (not the one used here) based on a Comprehensive Geriatric Assessment. Dr. Alexandra Papaioannou has received grants and research support from Amgen, Eli Lilly, Merck Canada Inc., Warner Chilcott and consults for Amgen, Eli Lilly. Dr. Jonathan Adachi consults for and has received lecture fees from Amgen, Eli Lilly, Merck, Novartis, Warner Chilcott. Courtney C. Kennedy, George Ioannidis, Lehana Thabane, Susan Kirkland, and Laura E. Pickard declare no conflict of interest.

Unlabelled: SAUMMARY: Using a Markov state-transition model, we estimated fractures averted with risedronate using two different types of clinical efficacy data. Summary data, as opposed to individual patient data (IPD), underestimated the number of fractures averted when applied in a specified high risk population. The choice of clinical efficacy data is an important consideration in health economic models evaluating osteoporosis therapies., Introduction: This paper contrasts fracture reduction estimates for risedronate utilizing efficacy data from two approaches to meta-analysis: summary data versus individual patient data. We also examined differences in fracture reduction explained by varied cohort selection, especially the inclusion of low- versus high-risk populations., Methods: Using a Markov state-transition model, we compared fractures averted over 3 years in a hypothetical cohort by inputting fracture risk reduction estimates (risedronate versus placebo) from two data sources (summary data versus IPD). The cohort consisted of 100,000 Canadian women, age > or =65 years with osteoporosis (WHO criteria T-score < or = -2.5) and prevalent morphometric vertebral fracture., Results: Non-vertebral fractures averted with risedronate were: 3,571 and 6,584 per 100,000 women for summary data and IPD, respectively. For vertebral fractures, the numbers were 8,552 and 10,127. When IPD versus summary data was used, an additional 3,013 more non-vertebral fractures and 1,575 vertebral fractures were averted., Discussion: Relative risk estimates from IPD analyses were the best choice for modelling fracture outcomes when applied in a specified high-risk population. In addition to superior statistical methodology, they utilized RCT cohorts that are more representative of higher risk patients requiring treatment (osteoporotic women > or =65 years with a prevalent vertebral fracture)., Competing Interests: Jonathan D. Adachi is a consultant for Amgen; Astra Zeneca, Eli Lilly; GlaxoSmithKline; Merck Frosst; Novartis; Proctor & Gamble; Roche; sanofi-aventis; Servier; and Wyeth (clinical trials: Eli Lilly; GlaxoSmithKline; Merck; Novartis; Pfizer; Proctor & Gamble; sanofi-aventis; Servier; and Wyeth). Alexandra Papaioannou is a consultant and adviser for Amgen, Eli Lilly, Merck Frosst, Novartis, Proctor & Gamble, sanofi-aventis, and Servier (clinical trials: Amgen, Eli Lilly, Merck, Novartis, Proctor & Gamble, and sanofi-aventis). William D. Leslie received speaker fees, research honoraria, and unrestricted research grants from Merck Frosst Canada Ltd; research honoraria and unrestricted educational grants from The Alliance for Better Bone Health: sanofi-aventis and Procter & Gamble Pharmaceuticals Canada, Inc.; unrestricted research grants from Novartis Pharmaceuticals Canada, Inc.; unrestricted educational grants from Genzyme Canada. Valery Walker is a paid consultant for Alliance for Better Bone Health, Procter & Gamble Pharmaceuticals Canada, and sanofi-aventis Canada Inc. Courtney C. Kennedy and George Ioannidis have no disclosures.

Unlabelled: Using prospective data from the Canadian Multicentre Osteoporosis Study (CaMos), we compared health utilities index (HUI) scores after 5 years of follow-up among participants (50 years and older) with and without incident clinical fractures. Incident fractures had a negative impact on HUI scores over time., Introduction: This study examined change in health-related quality of life (HRQL) in those with and without incident clinical fractures as measured by the HUI., Methods: The study cohort was 4,820 women and 1,783 men (50 years and older) from the CaMos. The HUI was administered at baseline and year 5. Participants were sub-divided into incident fracture groups (hip, rib, spine, forearm, pelvis, other) and were compared with those without these fractures. The effects of both time and fracture type on HUI scores were examined in multivariable regression analyses., Results: Men and women with hip fractures, compared to those without, had lower HUI measures that ranged from -0.05 to -0.25. Both women and men with spine fractures had significant deficits on the pain attributes (-0.07 to -0.12). In women, self-care (-0.06), mobility and ambulation (-0.05) were also negatively impacted. Women with rib fractures had deficits similar to women with spine fractures, and these effects persisted over time. In men, rib fractures did not significantly affect HUI scores. Pelvic and forearm fractures did not substantially influence HUI scores., Conclusion: The HUI was a sensitive measure of HRQL change over time. These results will inform economic analyses evaluating osteoporosis therapies., Competing Interests: Alexandra Papaioannou: Consulting Role: Amgen, Eli Lilly, Merck Frosst, Novartis, Proctor & Gamble, sanofi aventis Clinical Trials: Eli Lilly, Merck, Novartis, Proctor & Gamble, sanofi-aventis Jonathan D. Adachi: Consulting Role: Amgen; Astra Zeneca, Eli Lilly; Glaxo-SmithKline; Merck Frosst; Novartis; Proctor & Gamble; Roche; Sanofi Aventis; Servier Clinical Trials: Eli Lilly; GlaxoSmithKline; Merck; Novartis; Pfizer; Proctor & Gamble; sanofi-aventis; Servier; Wyeth-Ayerst Courtney Kennedy: none to declare Andreas Freitag: none to declare John O’Neill: none to declare Margaret Pui: none to declare Colin Webber: none to declare Anjali Pathak: none to declare Suzanne Hansen: none to declare Rosamund Hennessey: none to declare George Ioannidis: none to declare

Summary: In this systematic review, we summarize risk factors for low bone mineral density and bone loss in healthy men age 50 years or older. Consistent risk factors were: age, smoking, low weight, physical/functional limitations, and previous fracture. Data specific to men has clinical and policy implications., Introduction: Osteoporosis is a significant health care problem in men as well as women, yet the majority of evidence on diagnosis and management of osteoporosis is focused on postmenopausal women. The objective of this systematic review is to examine risk factors for low bone mineral density (BMD) and bone loss in healthy men age 50 years or older., Materials and Methods: A systematic search for observational studies was conducted in MEDLINE, Cochrane Database of Systematic Reviews, DARE, CENTRAL, CINAHL and Embase, Health STAR. The three main search concepts were bone density, densitometry, and risk factors. Trained reviewers assessed articles using a priori criteria., Results: Of 642 screened abstracts, 299 articles required a full review, and 25 remained in the final assessment. Consistent risk factors for low BMD/bone loss were: advancing age, smoking, and low weight/weight loss. Although less evidence was available, physical/functional limitations and prevalent fracture (after age 50) were also associated with low BMD/bone loss. The evidence was inconsistent or weak for physical activity, alcohol consumption, calcium intake, muscle strength, family history of fracture/osteoporosis, and height/height loss., Conclusion: In this systematic review, we identified several risk factors for low BMD/bone loss in men that are measurable in primary practice., Competing Interests: Conflicts of interest Alexandra Papaioannou, MD, FRCPC, MSc Consulting and Advisory Role: Amgen, Eli Lilly, Merck Frosst, Novartis, Proctor & Gamble, Sanofi-aventis, Servier Clinical Trials: Amgen, Eli Lilly, Merck, Novartis, Proctor & Gamble, Sanofi-aventisAnn Cranney, MD, FRCPC, MSc has received honoraria for educational lectures from Merck Frosst, Alliance for Bone Health and Novartis; and consultant fees from Amgen Canada and Research funding from Hofmann La Roche.Jacques P. Brown, MD, FRCPC has received honoraria for lecturing, consultancies, grants and research support for clinical trials: Abbott, Alpharx, Amgen, Arthrolab, Sanofi-aventis Canada, Boehringer Ingelheim/Roche, Bristol-Myers Squibb, Celltech, Eli Lilly Canada, Genizon, Glaxosmithkline, Merck Frosst, Nicox, Novartis, NPS Pharma, Pfizer, Proctor & Gamble, Quintiles, Rhône-Poulenc Rorer, Servier, Wyeth, Zelos.Stephanie M Kaiser, MD, FRCPCAdvisory Boards: Amgen, Eli Lilly, Novartis, Wyeth-Ayerst, ServierSpeaker for: Amgen, Eli Lilly, Novartis, Merck, Procter & Gamble/Sanofi-aventis, AstraZeneca, ServierWilliam D. Leslie, MD, FRCPC, MScSpeaker fees, research honoraria, and unrestricted research grants: Merck Frosst Canada Ltd; research honoraria and unrestricted educational grants from The Alliance for Better Bone Health: Sanofi-aventis and Procter & Gamble Pharmaceuticals Canada, Inc.; unrestricted research grants from Novartis Pharmaceuticals Canada, Inc.; unrestricted educational grants from Genzyme CanadaAliya KhanConsulting Role: Proctor & Gamble, Merck Frosst, NovartisResearch: Proctor & Gamble, Merck Frosst, Servier, Amgen, Eli Lilly Jonathan D. Adachi, MDConsulting Role: Amgen; Astra Zeneca, Eli Lilly; GlaxoSmithKline; Merck Frosst; Novartis; Proctor & Gamble; Roche; Sanofi-aventis; ServierClinical Trials: Eli Lilly; GlaxoSmithKline; Merck; Novartis; Pfizer; Proctor & Gamble; Sanofi-aventis; Servier; Wyeth-AyerstCourtney C. Kennedy, MSc; Gillian Hawker MD, MSc, FRCPC; Anna M. Sawka MD, FRCPC, PhD; Kerry Siminoski, MD, FRCPC; David Webster, MD, FRCP; Jessie McGowan MLIS: No competing interests to declare.

Unlabelled: We examined osteoporosis diagnosis/treatment in 2,187 community dwelling men age 50+. After five years in the study, 90% of men with fragility fractures remained undiagnosed and untreated for osteoporosis. The need to treat fragility fractures is well established in guidelines, and these numbers represent an important care gap., Introduction: Whether physicians in the community are recognizing and appropriately treating osteoporosis and fragility fractures in men remains unknown. We examined the rate of diagnosis and treatment in community dwelling men participating in the Canadian Multicentre Osteoporosis Study (CaMos)., Methods: Between February 1996 and September 2002, 2,187 participants were recruited from nine sites across Canada and prospectively followed. Information on osteoporosis diagnosis, fractures, medications were collected annually by a detailed questionnaire. DXA examination of lumbar spine (L1-4) and hip were conducted at baseline and year five., Results: Diagnosis and treatment in men with clinical fragility fractures was low: at baseline and year five only 2.3% and 10.3% of men with a clinical fracture reported an osteoporosis diagnosis, respectively. At year five, 90% of men with a clinical fragility fracture were untreated. Hip fractures were the most commonly treated (37.5% by year five). A diagnosis of osteoporosis resulted in greater treatment: 67% of participants with diagnosed osteoporosis were treated with a bisphosphonate and 87% were taking calcium and/or vitamin D (year five)., Conclusions: In this population-based study, both a diagnostic and therapeutic gap existed between knowledge and practice related to fragility fractures and osteoporosis in men aged >or=50 years., Competing Interests: Alexandra Papaioannou, MD, MSc Consulting Role: Amgen, Eli Lilly, Merck Frosst, Novartis, Proctor & Gamble, sanofi aventis Clinical Trials: Eli Lilly, Merck, Novartis, Proctor & Gamble, sanofi-aventis, Wojciech P. Olszynski, MD, PhD Consulting Role: Abbott Laboratories, Merck Frosst, Amgen, Novartis, Aventis, Pfizer, Boehringer Ingelheim, Procter & Gamble, Eli Lilly, Sanofi-Synthelabo, Genzyme, Schering Canada, GlaxoSmithKline, Solvay Pharma, Hoffmann-LaRoche, Wyeth, Janssen-Ortho Inc./Ortho-Biotech STEPHANIE KAISER, MD Consulting Role: Eli Lilly, Proctor & Gamble/Aventis, Merck, Servier, Novartis, Astra Zeneca, Abbott Advisory boards: Eli Lilly, Novartis, Servier David A. Hanley, MD Advisory Boards: Merck, Proctor & Gamble, Eli Lilly, Novartis, NPS Pharmaceuticals, Paladin Clinical Trials: Merck, Proctor & Gamble, Eli Lilly, Novartis, NPS Pharmaceuticals, Pfizer, Amgen, Wyeth-Ayerst, Roche Jonathan D. Adachi, MD Consulting Role: Amgen; Astra Zeneca, Eli Lilly; GlaxoSmithKline; Merck Frosst; Novartis; Proctor & Gamble; Roche; Sanofi Aventis; Servier Clinical Trials: Eli Lilly; GlaxoSmithKline; Merck; Novartis; Pfizer; Proctor & Gamble; sanofi-aventis; Servier; Wyeth-Ayerst David Goltzman, MD Consulting Role: Lilly, Novartis, Merck, sanofi-aventis, Proctor & Gamble, Servier Robert G. Josse, MD Advisory boards, honoraria, research grants: Lilly, Proctor & Gamble/sanofi-aventis, Merck, Novartis, Servier, GlaxoSmithKline, Amgen Jacques P. Brown, MD Consulting Role: Eli Lilly, Novartis, Procter & Gamble, and Sanofi-Aventis Jerilynn C. Prior MD, Courtney C. Kennedy MSc, George Ioannidis MSc, Yongjun Gao MSc, Anna M. Sawka MD, PhD, Nancy Kreiger PhD, Shawn Davison PhD, Laura Pickard MA: No competing interests to declare.

Health-related quality of life (HRQL) is an important consideration in the management of patients with vertebral fractures. The purpose of this study was to examine patient-related factors that contribute to HRQL after vertebral fractures, including co-morbidities, medications, fracture history, family disease history, demographics, exercise, education and living environment. A total of 1,129 post-menopausal women (mean age 67.2, SD 11.9 years) was studied from the Canadian Database of Osteoporosis and Osteopenia (CANDOO). HRQL was measured using the mini-osteoporosis quality of life questionnaire (mini-OQLQ). Separate multivariable linear regression analyses [parameter estimates and corresponding 95% confidence intervals (CI)] were performed for each of the five mini-OQLQ domains: symptoms, physical functioning, emotional functioning, activities of daily living and leisure domains. A strong positive association was found between HRQL and post-secondary education, a family history of osteoporosis, working and thiazide therapy. Exercise improved HRQL; however, several hours a week were required to be meaningful. Living in long-term care had the most marked negative effect on HRQL. Smoking, past surgery of the hip or spine, sedatives, anticonvulsants, atherosclerotic disease and hypertension were also associated with a substantially decreased HRQL across several domains. Calcium channel-blockers, chemotherapy, corticosteroids, diabetes, migraines, the number of non-vertebral fractures and falls had a negative impact on selected domains. We demonstrated that several modifiable factors influence HRQL in patients with vertebral fractures, and physicians should be aware of these and other markers of reduced HRQL to enhance patient care.