Colin Robertson, Smile A While: Dentistry, History, Theater and Golf.

Many commentators argue that, until the 1980s, Brisbane and Queensland were cultural backwaters within the Australian context. However, with the hosting of the highly successful XII Commonwealth Games (1982) and World Expo 88 (1988) and with the development of the Queensland Cultural (1976-) and South Bank (1974-) Precincts, Brisbane and Queensland cast aside perennial apologism to acquire prominence, maturity, and self-respect. Within these national, state, and municipal settings, the theme, timing, and venue for the 24th Australian Dental Congress (1985) involved risk. Enter a Brisbane dental practitioner, Colin Robertson: a theater critic and a scriptwriter, who possessed competitive and entrepreneurial streaks, a vivid imagination, a steely resolve, and a love of golf. Robertson became an erudite, incisive, and prolific commentator, who penned much of the historical musical Smile A While (aka Smile Awhile) for the abovementioned congress. He contributed to an outstanding Dental Health Week (1980), served on the Australian Dental Association Queensland Branch Council (1981), its Fluoridation Committee (1973) and chaired both its Oral Health Education Committee (1981) and the Congressional Entertainment Division within the Congress Organizing Committee (1982-1985). Accordingly, the authors use historical methods to expose and explore a scarcely acknowledged narrative within dental history in Queensland.

Christensen House: A Case Study for Inclusive Decision-making within Professional Associations.

Accounts of dental history in Queensland are few and almost invariably authored by those who either held or hold power. The focus is 'who, what, when' rather than 'why and how'. House-related developments as a case study provide an opportunity to assess aspects of the Australian Dental Association Queensland Branch's (ADAQ) model of administration in the early 1970s. The authors use literature review and historical methods. The ADAQ's articles of association, codes of conduct and memoranda centralized Brisbane-based authority and elite leadership into its management. The ADAQ council's decision to build Christensen House in Brisbane, prompted by the posthumous benevolence of George Christensen, was informed, logical, measured and appeared timely. The advocates for the house were innovative, optimistic, resolute, and well-intentioned, with their design and selected location of the building being appropriate. However, the decision occurred at a time of latent discontent within the membership, many of whom did not support the project financially. Distance in Queensland dictates that provincial members either accept or tolerate Brisbane-based centralized authority within ADAQ administration. Nonetheless, when it comes to policy warranting membership subscription, the Christensen House experience demonstrates that the modus operandi of the ADAQ council should be, as far as possible, inclusive, and representative.

Incremental costs of fragility fractures: a population-based matched -cohort study from Ontario, Canada.

Using a matched cohort design, the 1-year excess cost of incident fragility fractures at any site was $26,341 per patient, with 43% of total excess costs attributed to hospitalization. The high economic burden of fractures in Ontario underscores the urgency of closing the secondary fracture prevention gap. INTRODUCTION: This retrospective real-world observational study was conducted to document the incremental costs associated with fragility fractures in Ontario, Canada. METHODS: Patients aged >65 years with an index fragility fracture occurring between January 2011 and March 2015 were identified from administrative databases and matched 1:1 to a cohort of similar patients without a fracture. Healthcare resource utilization data were extracted from healthcare records and associated costs were calculated on a per-patient level and for the province of Ontario. Costs were presented as 2017 Canadian dollars. RESULTS: The eligible cohort included 115,776 patients with a fragility fracture. Of these, 101,773 patients were successfully matched 1:1 to a non-fracture cohort. Overall, hip fractures (n = 31,613) were the most common, whereas femur fractures (n = 3002) were the least common type. Hospitalization and continuing care/home care/long-term care accounted for more than 60% of 1-year direct costs, whereas 5% was attributed to medication costs. First-year costs per patient in the fracture cohort were approximately threefold higher versus the non-fracture cohort (mean $37,362 versus $11,020, respectively). The incremental first-year direct healthcare costs of fragility fractures for the province of Ontario were calculated at $724 million per year. CONCLUSIONS: Fragility fractures were associated with a threefold increase in overall mean healthcare costs per patient compared to patients without fractures. With an aging population, there is an urgent need for improved prevention strategies for patients at high-risk of fracture to decrease the economic burden of fragility fractures on the Canadian healthcare system.

Simulated effects of early menopausal bone mineral density preservation on long-term fracture risk: a feasibility study.

Prevention of early menopausal bone loss may reduce the future burden of osteoporosis. In this modelling exercise, an osteoporosis prevention strategy involving 5-year infusions of zoledronic acid, beginning early in menopause, reduced long-term fracture risk and the proportion of aging women with femoral neck densitometric osteoporosis. This strategy warrants further evaluation. INTRODUCTION: Preventing early menopausal bone loss may substantially reduce the future burden of osteoporosis. We modelled the effects of infrequent zoledronic acid infusions on long-term fracture risk. METHODS: Data from the Canadian Multicentre Osteoporosis Study (CaMos) were used to determine the expected natural history of femoral neck areal bone mineral density (BMD) and fracture risk (using FRAX®) from ages 50-80 for women with no antiresorptive drug exposures. We modelled the effects of three infusions of zoledronic acid (at ages 50, 55, 60) on long-term fracture risk, assuming this intervention would preserve BMD until age 65 years, followed by losses mirroring early menopausal BMD loss. RESULTS: At age 65, untreated women and zoledronic acid recipients had expected mean (SD) femoral neck T-scores of - 1.5(1.0) and - 0.8(1.0), 10-year major osteoporotic fracture (MOF) risks of 9.8%(5.0) and 8.0%(3.7) and hip fracture risks of 1.7%(2.4) and 0.8%(1.2), respectively. At age 80, untreated women and zoledronic acid recipients had expected femoral neck T-scores of - 1.9(0.9) and - 1.4(0.9), MOF risks of 17.9%(8.2) and 14.9%(6.4) and hip fracture risks of 6.3%(6.2) and 4.4%(4.5), respectively. The expected proportion of women with femoral neck T-score ≤ - 2.5 was 14.9% for untreated women and 3.8% for zoledronic acid recipients at age 65, increasing to 28.1% and 12.0%, respectively, at age 80. Numbers-needed-to-treat to prevent one case of densitometric osteoporosis were 9 at age 65 and 5 at age 80. CONCLUSION: Infrequent infusions of zoledronic acid, initiated early in menopause, are expected to reduce long-term fracture risk and result in a substantial reduction in the proportion of women with densitometric osteoporosis after age 65.

A scorecard for osteoporosis in Canada and seven Canadian provinces.

The scorecard evaluates the burden and management of osteoporosis in Canada and how care pathways differ across Canadian provinces. The results showed there are inequities in patients' access to diagnosis, treatment, and post-fracture care programs in Canada. Interventions are needed to close the osteoporosis treatment gap and minimize these inequities. INTRODUCTION: The purpose of this study was to develop a visual scorecard that assesses the burden of osteoporosis and its management within Canada and seven Canadian provinces. METHODS: We adapted the Scorecard for Osteoporosis in Europe (SCOPE) to score osteoporosis indicators for Canada and seven provinces (British Columbia, Alberta, Saskatchewan, Ontario, Quebec, New Brunswick, and Newfoundland). We obtained data from a comprehensive literature review and interviews with osteoporosis experts. We scored 20 elements across four domains: burden of disease, policy framework, service provision, and service uptake. Each element was scored as red, yellow, or green, indicating high, intermediate, or low risk, respectively. Elements with insufficient data were scored black. RESULTS: Canada performed well on several elements of osteoporosis care, including high uptake of risk assessment algorithms and minimal wait times for hip fracture surgery. However, there were no established fracture registries, and reporting on individuals with high fracture risk who remain untreated was limited. Furthermore, osteoporosis was not an official health priority in most provinces. Government-backed action plans and other osteoporosis initiatives were primarily confined to Ontario and Alberta. Several provinces (Saskatchewan, New Brunswick, Newfoundland) did not have any registered fracture liaison service (FLS) programs. Access to diagnosis and treatment was also inconsistent and reimbursement policies did not align with clinical guidelines. CONCLUSION: Government-backed action plans are needed to address provincial inequities in patients' access to diagnosis, treatment, and FLS programs in Canada. Further characterization of the treatment gap and the establishment of fracture registries are critical next steps in providing high-quality osteoporosis care.

James Meyrick Croker: A Model for Professional Behavior.

The rationale that underpins volunteering has long fascinated behavioral scientists. James Meyrick Croker's personal life, professional career and community engagement conform to the classic twentieth century model for professional behavior. Accordingly, the authors use historical methods of investigation to evaluate the influences on and the legacies from a remarkable contribution to the professions and the community. The narrative demonstrates elements of altruism, collaboration, conviction, compassion, drive, entrepreneurialism, familial and grammar school influence, leadership, pragmatism and vision. Croker's professional and community service was multi-organizational. Concurrent demands on his time warranted discipline, energy and expertise. For the behavioral scientist, achievement, affiliation, nature and nurture appear relevant to the outcome. Available archives provide no evidence of ego-driven motivation. Leadership style was transformational not transactional. Major legacies to the national and state Australian Dental Associations are ADAQ Christensen House (1972-1980), the eventual financial stability for the Australian Dental Association Queensland Branch, formal dental assistant training, policies of the Australian and Queensland Councils of Professions, a notable Goddard Oration and the successful 24th Australian Dental Congress.

A single dose of zoledronate preserves bone mineral density for up to 2 years after a second course of romosozumab.

This phase 2 study evaluated the efficacy and safety of transitioning to zoledronate following romosozumab treatment in postmenopausal women with low bone mass. A single dose of 5 mg zoledronate generally maintained the robust BMD gains accrued with romosozumab treatment and was well tolerated. INTRODUCTION: Follow-on therapy with an antiresorptive agent is necessary to maintain the skeletal benefits of romosozumab therapy. We evaluated the use of zoledronate following romosozumab treatment. METHODS: This phase 2, dose-finding study enrolled postmenopausal women with low bone mineral density (BMD). Subjects who received various romosozumab doses or placebo from months 0-24 were rerandomized to denosumab (60 mg SC Q6M) or placebo for 12 months, followed by open-label romosozumab (210 mg QM) for 12 months. At month 48, subjects who had received active treatment for 48 months were assigned to no further active treatment and all other subjects were assigned to zoledronate 5 mg IV. Efficacy (BMD, P1NP, and ß-CTX) and safety were evaluated for 24 months, up to month 72. RESULTS: A total of 141 subjects entered the month 48-72 period, with 51 in the no further active treatment group and 90 in the zoledronate group. In subjects receiving no further active treatment, lumbar spine (LS) BMD decreased by 10.8% from months 48-72 but remained 4.2% above the original baseline. In subjects receiving zoledronate, LS BMD was maintained (percentage changes: - 0.8% from months 48-72; 12.8% from months 0-72). Similar patterns were observed for proximal femur BMD in both groups. With no further active treatment, P1NP and ß-CTX decreased but remained above baseline at month 72. Following zoledronate, P1NP and ß-CTX levels initially decreased but approached baseline by month 72. No new safety signals were observed. CONCLUSION: A zoledronate follow-on regimen can maintain robust BMD gains achieved with romosozumab treatment.

Efficacy and safety of denosumab vs. bisphosphonates in postmenopausal women previously treated with oral bisphosphonates.

Transitioning postmenopausal women with osteoporosis from a bisphosphonate to denosumab appears to be safe and more effective at improving BMD than continuing treatment with a bisphosphonate. INTRODUCTION: We conducted a patient-level pooled analysis of four studies to estimate the efficacy and safety of transitioning to denosumab vs. continuing bisphosphonate treatment in postmenopausal women who previously received oral bisphosphonates. METHODS: Patients received 60 mg denosumab once every 6 months or a bisphosphonate (oral alendronate, risedronate, ibandronate, or intravenous zoledronic acid). Endpoints were change from baseline in lumbar spine, total hip, femoral neck, and 1/3 radius BMD at month 12, change from baseline in serum CTX-1 and P1NP, and incidence of adverse events. RESULTS: A total of 2850 randomized patients (1424 bisphosphonate:1426 denosumab) were included in the analysis. Percentage change in BMD was significantly greater (p < 0.001) for denosumab vs. bisphosphonate at each skeletal site; differences in BMD changes ranged from 0.6 to 2.0%. Percentage decrease in serum CTX-1 and P1NP was significantly greater (p < 0.0001) for denosumab vs. bisphosphonate at months 1, 6, and 12; in the denosumab group only, percentage change in serum CTX-1 at month 1 was significantly correlated with percentage change in lumbar spine and total hip BMD at month 12. The incidences of adverse events were similar between treatment groups. Three patients (one bisphosphonate and two denosumab) had atypical femoral fractures, all from the denosumab vs. zoledronic acid study. CONCLUSION: Postmenopausal women can safely transition from a bisphosphonate to denosumab, which is more effective at improving BMD than continuing with a bisphosphonate. CLINICAL TRIALS REGISTRATION: NCT00377819, NCT00919711, NCT00936897, NCT01732770.

Long-term denosumab treatment restores cortical bone loss and reduces fracture risk at the forearm and humerus: analyses from the FREEDOM Extension cross-over group.

Upper limb fractures (including wrist, forearm, and humerus) represent a significant burden among postmenopausal women with osteoporosis. Up to 7 years of treatment with denosumab resulted in an increase in bone mineral density and decrease in fractures in upper limb sites. INTRODUCTION: Upper limb (wrist, forearm, and humerus) fractures are a significant burden in osteoporosis, associated with significant morbidity and mortality. Denosumab, a monoclonal antibody against RANK ligand, increases bone mineral density (BMD) and decreases vertebral, nonvertebral, and hip fractures. Here, we evaluated the long-term effect of denosumab treatment on upper limb fracture risk and BMD. METHODS: In the FREEDOM trial, subjects were randomized 1:1 to receive every-6-month denosumab 60 mg or placebo subcutaneously for 3 years, after which all subjects could receive denosumab for up to 7 years (Extension). Among placebo subjects who completed FREEDOM and enrolled in the Extension, wrist, forearm, humerus, and upper limb fracture rates and rate ratios between different time periods (FREEDOM years 1-3, Extension years 1-3, and Extension years 4-7) were computed. BMD at the ultradistal radius, 1/3 radius, and total radius was analyzed in a subset of subjects in a BMD substudy. RESULTS: This analysis included 2207 subjects (116 in the BMD substudy). Fracture rates decreased over the 7-year Extension; fracture rate ratios between Extension years 4-7 (denosumab) and FREEDOM years 1-3 (placebo) reduced significantly for the wrist (0.57), forearm (0.57), humerus (0.42), and upper limb (0.52; p < 0.05 for all). Percentage increase in BMD from Extension baseline at the ultradistal radius, 1/3 radius, and total radius was significant by Extension year 7 (p < 0.05 for all). CONCLUSIONS: Long-term treatment with denosumab decreases upper limb fracture risk and increases forearm BMD, suggesting beneficial effects on both cortical and trabecular bone accruing over time.

Relationship Between Bone Mineral Density T-Score and Nonvertebral Fracture Risk Over 10 Years of Denosumab Treatment.

Although treat-to-target strategies are being discussed in osteoporosis, there is little evidence of what the target should be to reduce fracture risk maximally. We investigated the relationship between total hip BMD T-score and the incidence of nonvertebral fracture in women who received up to 10 years of continued denosumab therapy in the FREEDOM (3 years) study and its long-term Extension (up to 7 years) study. We report the percentages of women who achieved a range of T-scores at the total hip or femoral neck over 10 years of denosumab treatment (1343 women completed 10 years of treatment). The incidence of nonvertebral fractures was lower with higher total hip T-score. This relationship plateaued at a T-score between -2.0 and -1.5 and was independent of age and prevalent vertebral fractures, similar to observations in treatment-naïve subjects. Reaching a specific T-score during denosumab treatment was dependent on the baseline T-score, with higher T-scores at baseline more likely to result in higher T-scores at each time point during the study. Our findings highlight the importance of follow-up BMD measurements in patients receiving denosumab therapy because BMD remains a robust indicator of fracture risk. These data support the notion of a specific T-score threshold as a practical target for therapy in osteoporosis. © 2019 The Authors Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).

Performance of predictive tools to identify individuals at risk of non-traumatic fracture: a systematic review, meta-analysis, and meta-regression.

There is no consensus on which tool is the most accurate to assess fracture risk. The results of this systematic review suggest that QFracture, Fracture Risk Assessment Tool (FRAX) with BMD, and Garvan with BMD are the tools with the best discriminative ability. More studies assessing the comparative performance of current tools are needed. INTRODUCTION: Many tools exist to assess fracture risk. This review aims to determine which tools have the best predictive accuracy to identify individuals at high risk of non-traumatic fracture. METHODS: Studies assessing the accuracy of tools for prediction of fracture were searched in MEDLINE, EMBASE, Evidence-Based Medicine Reviews, and Global Health. Studies were eligible if discrimination was assessed in a population independent of the derivation cohort. Meta-analyses and meta-regressions were performed on areas under the ROC curve (AUCs). Gender, mean age, age range, and study quality were used as adjustment variables. RESULTS: We identified 53 validation studies assessing the discriminative ability of 14 tools. Given the small number of studies on some tools, only FRAX, Garvan, and QFracture were compared using meta-regression models. In the unadjusted analyses, QFracture had the best discriminative ability to predict hip fracture (AUC = 0.88). In the adjusted analysis, FRAX with BMD (AUC = 0.81) and Garvan with BMD (AUC = 0.79) had the highest AUCs. For prediction of major osteoporotic fracture, QFracture had the best discriminative ability (AUC = 0.77). For prediction of osteoporotic or any fracture, FRAX with BMD and Garvan with BMD had higher discriminative ability than their versions without BMD (FRAX: AUC = 0.72 vs 0.69, Garvan: AUC = 0.72 vs 0.65). A significant amount of heterogeneity was present in the analyses. CONCLUSIONS: QFracture, FRAX with BMD, and Garvan with BMD have the highest discriminative performance for predicting fracture. Additional studies in which the performance of current tools is assessed in the same individuals may be performed to confirm this conclusion.

Persistence at 24 months with denosumab among postmenopausal women with osteoporosis: results of a prospective cohort study.

Persistence with prescribed medications for chronic diseases is important; however, persistence with osteoporosis treatments is historically poor. In this prospective cohort study of postmenopausal women treated for osteoporosis in real-world clinical practice settings in the USA and Canada, 24-month persistence with denosumab was 58%. PURPOSE: Patients who persist with their prescribed osteoporosis treatment have increased bone mineral density (BMD) and reduced risk of fracture. Twelve-month persistence with denosumab in routine clinical practice is as high as 95%, but there are limited data on longer-term persistence with denosumab in this setting. METHODS: This single-arm, prospective, cohort study evaluated 24-month persistence with denosumab administered every 6 months in postmenopausal women receiving treatment for osteoporosis in real-world clinical practice in the USA and Canada. Endpoints and analyses included the percentage of patients who persist with denosumab at 24 months (greater than or equal to four injections with a gap between injections of no more than 6 months plus 8 weeks), the total number of injections received by each patient, changes in BMD in persistent patients, and the incidence of serious adverse events (SAEs) and fractures. RESULTS: Among 935 enrolled patients, 24-month persistence was 58% (50% in US patients and 75% in Canadian patients). A majority of patients received at least four injections over the observation period (62% of US patients and 81% of Canadian patients). Among patients who were persistent at 24 months and who had a baseline, 12-month, and 24-month DXA scan, mean BMD increased from baseline to 24 months by 7.8% at the lumbar spine and 2.1% at the femoral neck. SAEs and fractures were reported for 122 (13.0%) patients and 54 (5.8%) patients, respectively. CONCLUSIONS: Persistence with denosumab for 24 months yields improvement in BMD among postmenopausal women with osteoporosis treated in routine clinical practice in the USA and Canada.

Atypical femur fractures: a survey of current practices in orthopedic surgery.

The results of a self-administered online survey demonstrate that orthopedic surgeons' management practices for AFF are variable. These data will inform the development of clinical practice guidelines. INTRODUCTION: We aimed to determine current AFF treatment practices of orthopedic surgeons to inform clinical practice guideline development. METHODS: A self-administered online survey was developed and sequentially posted on the Orthopaedic Trauma Association (OTA) website from July to August 2015 and the Canadian Orthopaedic Association (COA) website from December 2015 to January 2016. Level of confidence in diagnosis and treatment as well as treatment preferences between respondents who self-identified as trauma surgeons vs. non-trauma surgeons were compared. RESULTS: A total of 172 completed surveys were obtained (OTA, N = 100, 58%; COA, N = 72, 8%). Seventy-eight percent of respondents had treated ≥1 AFF in the previous 6 months. Seventy-six percent reported feeling extremely or very confident in diagnosing AFF (trauma 84% vs. non-trauma surgeons 70%, p = 0.04), and 63% reported feeling extremely or very confident in treating AFF (trauma 82%, non-trauma surgeons 50%, p < 0.01). Preferred management for complete and symptomatic incomplete AFFs was surgical fixation with a cephalomedullary nail (CMN) by 88 and 79%, respectively, while close follow-up was preferred for asymptomatic incomplete AFFs in 72% of respondents. Trauma surgeons used the CMN more frequently than non-trauma surgeons (90 vs. 76% p = 0.03). In patients with bilateral AFFs, with one side surgically treated, 56% were extremely likely to surgically treat the contralateral side, if symptomatic. Most felt guidelines (81%) and educational resources (73%) would be valuable. CONCLUSIONS: Current orthopedic treatment practices for AFFs are variable. The results of this survey will inform the development of practice guidelines and educational resources.

Sex-specific association between obesity and self-reported falls and injuries among community-dwelling Canadians aged 65 years and older.

This study investigated the relationship between body mass index (BMI) and falls among community-dwelling elderly. Results indicate that obesity is associated with increased falls and there appears to be a sex-specific difference with obese men at higher risk of falling. Obesity is identified as a risk factor for falls in men. INTRODUCTION: The prevalence of falls, fall-related injuries, and obesity has increased over the last decade. The objectives of this study were to investigate sex-specific association and dose-response relationship between BMI and falls (and related injuries) among community-dwelling elderly. METHODS: Our study sample consisted of 15,860 adults aged 65 years or older (6399 men and 9461 women) from the 2008-2009 Canadian Community Health Survey-Healthy Aging (CCHS-HA). Falls, fall-related injuries, and BMI measures were self-reported. For both sex, dose-response curves presenting the relationship between BMI, falls, and fall-related injuries were first examined. Thereafter, multivariate logistic regression analyses were also performed to investigate these relationships after adjustment for potentially confounding variables. RESULTS: Of women, 21.7 % reported a fall and 16.9 % of men. The dose-response relationship between BMI and prevalence of falls showed that underweight and obese individuals reported falling more than normal and overweight individuals; this being more apparent in men than women. Finally, the dose relationship between BMI and prevalence of fall-related injuries showed that only obese men seem more likely to have sustained a fall-related injury. Results from the multivariate analysis showed that obesity in men was significantly associated with higher odds of falling odds ratio (OR) 1.33 (1.04-1.70) and was not significantly associated with higher odds of fall-related injuries OR 1.10 (0.66-1.84) over a 12-month period compared to normal weight men. For women, obesity was not significantly associated with higher fall prevalence OR 0.99 (0.79-1.25) and fall-related injuries OR 0.71 (0.51-1.00). CONCLUSION: Obesity is associated with self-reported falls, and there appears to be a sex-specific difference in elderly persons.

Denosumab or Zoledronic Acid in Postmenopausal Women With Osteoporosis Previously Treated With Oral Bisphosphonates.

CONTEXT: Denosumab and zoledronic acid (ZOL) are parenteral treatments for patients with osteoporosis. OBJECTIVE: The objective of the study was to compare the effect of transitioning from oral bisphosphonates to denosumab or ZOL on bone mineral density (BMD) and bone turnover. DESIGN AND SETTING: This was an international, multicenter, randomized, double-blind trial. PARTICIPANTS: A total of 643 postmenopausal women with osteoporosis previously treated with oral bisphosphonates participated in the study. INTERVENTIONS: Subjects were randomized 1:1 to sc denosumab 60 mg every 6 months plus iv placebo once or ZOL 5 mg iv once plus sc placebo every 6 months for 12 months. MAIN OUTCOME MEASURES: Changes in BMD and bone turnover markers were measured. RESULTS: BMD change from baseline at month 12 was significantly greater with denosumab compared with ZOL at the lumbar spine (primary end point; 3.2% vs 1.1%; P < .0001), total hip (1.9% vs 0.6%; P < .0001), femoral neck (1.2% vs -0.1%; P < .0001), and one-third radius (0.6% vs 0.0%; P < .05). The median decrease from baseline was greater with denosumab than ZOL for serum C-telopeptide of type 1 collagen at all time points after day 10 and for serum procollagen type 1 N-terminal propeptide at month 1 and at all time points after month 3 (all P < .05). Median percentage changes from baseline in serum intact PTH were significantly greater at months 3 and 9 with denosumab compared with ZOL (all P < .05). Adverse events were similar between groups. Three events consistent with the definition of atypical femoral fracture were observed (two denosumab and one ZOL). CONCLUSIONS: In postmenopausal women with osteoporosis previously treated with oral bisphosphonates, denosumab was associated with greater BMD increases at all measured skeletal sites and greater inhibition of bone remodeling compared with ZOL.

The current economic burden of illness of osteoporosis in Canada.

UNLABELLED: We estimate the current burden of illness of osteoporosis in Canada is double ($4.6 billion) our previous estimates ($2.3 billion) due to improved data capture of the multiple encounters and services that accompany a fracture: emergency room, admissions to acute and step-down non-acute institutions, rehabilitation, home-assisted or long-term residency support. INTRODUCTION: We previously estimated the economic burden of illness of osteoporosis-attributable fractures in Canada for the year 2008 to be $2.3 billion in the base case and as much as $3.9 billion. The aim of this study is to update the estimate of the economic burden of illness for osteoporosis-attributable fractures for Canada based on newly available home care and long-term care (LTC) data. METHODS: Multiple national databases were used for the fiscal-year ending March 31, 2011 (FY 2010/2011) for acute institutional care, emergency visits, day surgery, secondary admissions for rehabilitation, and complex continuing care, as well as national dispensing data for osteoporosis medications. Gaps in national data were supplemented by provincial and community survey data. Osteoporosis-attributable fractures for Canadians age 50+ were identified by ICD-10-CA codes. Costs were expressed in 2014 dollars. RESULTS: In FY 2010/2011, the number of osteoporosis-attributable fractures was 131,443 resulting in 64,884 acute care admissions and 983,074 acute hospital days. Acute care costs were $1.5 billion, an 18 % increase since 2008. The cost of LTC was 33.4 times the previous estimate ($31 million versus $1.03 billion) because of improved data capture. The cost for rehabilitation and secondary admissions increased 3.4 fold, while drug costs decreased 19 %. The overall cost of osteoporosis was over $4.6 billion, an increase of 83 % from the 2008 estimate. CONCLUSION: Since the 2008 estimate, new Canadian data on home care and LTC are available which provided a better estimate of the burden of osteoporosis in Canada. This suggests that our previous estimates were seriously underestimated.

Denosumab compared to other treatments to prevent or treat osteoporosis in individuals at risk of fracture: a systematic review and meta-analysis.

UNLABELLED: The aim of this review is to compare the efficacy and safety of denosumab over other treatments for osteoporosis. The results of this study suggest that the safety of denosumab and its efficacy in reducing fractures is not significantly different from bisphosphonates. Denosumab was, however, more effective in increasing bone mineral density. INTRODUCTION: This study was conducted to compare the efficacy and safety of denosumab over other pharmacological treatments for osteoporosis in individuals at risk of fracture. METHODS: Randomised controlled trials comparing denosumab with another pharmacological treatment for osteoporosis were searched in MEDLINE, EMBASE and CENTRAL. Identified articles were screened by two independent reviewers and assessed for inclusion. Data from included studies were extracted and meta-analyses were conducted using random effects models. RESULTS: Nine studies including a total of 4890 postmenopausal women were identified. The follow-up period varied from 12 to 24 months. In all studies except one, the comparator treatment was a bisphosphonate. There was no statistically significant difference between patients receiving denosumab and those receiving a bisphosphonate in terms of fracture risk (RR[95 % CI] = 1.15 [0.84-1.58]), adverse events (RR[95 % CI] = 0.99 [0.96-1.02]) or deaths (OR[95 % CI] = 0.58 [0.12-2.71]). Withdrawals due to adverse events were less frequent in denosumab than in other treatment groups but the difference did not reach statistical significance (OR[95 % CI] = 0.68 [0.45-1.04]). The percent change in bone mineral density at the total hip, lumbar spine, femoral neck and one-third radius was significantly higher in participants who received denosumab (e.g. mean difference [95 % CI] at the total hip: 1.06 [0.86-1.25]). CONCLUSIONS: These results suggest that, after 12 to 24 months, the safety and efficacy of denosumab for reducing fracture risk is not significantly different from bisphosphonates despite higher gains in bone mineral density. In a clinical setting, denosumab may demonstrate greater effectiveness.