Courtney C. Kennedy

Relation between fractures and mortality: results from the Canadian Multicentre Osteoporosis Study

Background: Fractures have largely been assessed by their impact on quality of life or health care costs. We conducted this study to evaluate the relation between fractures and mortality. Methods: A total of 7753 randomly selected people (2187 men and 5566 women) aged 50 years and older from across Canada participated in a 5-year observational cohort study. Incident fractures were identified on the basis of validated self-report and were classified by type (vertebral, pelvic, forearm or wrist, rib, hip and “other”). We subdivided fracture groups by the year in which the fracture occurred during follow-up; those occurring in the fourth and fifth years were grouped together. We examined the relation between the time of the incident fracture and death. Results: Compared with participants who had no fracture during follow-up, those who had a vertebral fracture in the second year were at increased risk of death (adjusted hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.1–6.6); also at risk were those who had a hip fracture during the first year (adjusted HR 3.2, 95% CI 1.4–7.4). Among women, the risk of death was increased for those with a vertebral fracture during the first year (adjusted HR 3.7, 95% CI 1.1–12.8) or the second year of follow-up (adjusted HR 3.2, 95% CI 1.2–8.1). The risk of death was also increased among women with hip fracture during the first year of follow-up (adjusted HR 3.0, 95% CI 1.0–8.7). Interpretation: Vertebral and hip fractures are associated with an increased risk of death. Interventions that reduce the incidence of these fractures need to be implemented to improve survival.

The impact of incident fractures on health-related quality of life: 5 years of data from the Canadian Multicentre Osteoporosis Study

Background Vertebral fractures in patients with cystic fibrosis (CF) may contribute to an accelerated decline in lung function and can be a contraindication to lung transplantation. In this study, we examined longitudinal change in bone mineral density (BMD) and the prevalence of vertebral fractures in adult CF patients, without lung-transplant, attending a Canadian specialty clinic. Methods Retrospective chart review of all patients attending an Adult Cystic Fibrosis Clinic at Hamilton Health Sciences in Hamilton, Canada. Forty-nine of 56 adults met inclusion criteria. Chest radiographs were graded by consensus approach using Genant’s semi-quantitative method to identify and grade fractured vertebrae. Dual x-ray absorptiometry (DXA) scans were also reviewed. Results The mean age of the cohort was 25.2 years (SD 9.4), 43% were male. The mean body mass index (BMI) was 19.8 (2.8) for males and 21.7 (5.1) for females. At baseline, the rate of at least one vertebral fracture was 16.3%; rising to 21.3% (prevalent and incident) after a 3-year follow-up. The mean BMD T-or Z-scores at baseline were −0.80 (SD 1.1) at the lumbar spine, −0.57 (SD 0.97) at the proximal femur, and −0.71 (SD 1.1) at the whole body. Over approximately 4-years, the mean percent change in BMD was −1.93% at the proximal femur and −0.73% at the lumbar spine. Conclusion Approximately one in five CF patients demonstrated at least one or more vertebral fractures. Moderate declines in BMD were observed. Given the high rate of vertebral fractures noted in this cohort of adult CF patients, and the negative impact they have on compromised lung functioning, regular screening for vertebral fractures should be considered on routine chest radiographs.

Patient adherence to osteoporosis medications: problems, consequences and management strategies.

Adherence to osteoporosis medications is relatively poor. Approximately 20–30% of patients taking daily or weekly treatments may suspend their treatment within 6 to 12 months of initiating therapy. Patients with poor adherence increase their risk of osteoporotic fractures and hospitalisation. The majority of patients who discontinue therapy appear to do so because of drug-induced adverse effects. Fear of adverse effects or other health risks is another commonly cited reason for discontinuing therapy. Factors associated with medication adherence include fractures, regular exercise, female sex, fewer non-osteoporosis medications and co-morbidities, early menopause, willingness to take medications, awareness of osteoporosis status based on a diagnostic test, anti-inflammatory therapy and corticosteroid therapy. Factors associated with non-adherence include adverse effects, pain and being unsure about bone mineral density (BMD) test results. Bisphosphonates, a common class of drugs for treating osteoporosis, have specific administration requirements (e.g. fasting, remaining upright and not ingesting other medications concomitantly). Patient surveys indicate that 12–18% of patients report non-compliance with at least one administration rule. Strategies to increase adherence include reducing administration frequency to weekly or monthly, monitoring patients with bone markers and BMD testing, providing adequate instructions, practitioner feedback and support, and educational materials and sessions. Future studies are needed regarding strategies to increase adherence to osteoporosis medications.

Quality of anticoagulation and use of warfarin-interacting medications in long-term care: A chart review

BackgroundMaintenance of therapeutic International Normalized Ratio (INR) in the community is generally poor. The supervised environment in long-term care facilities may represent a more ideal setting for warfarin therapy since laboratory monitoring, compliance, dose adjustment, and interacting medications can all be monitored and controlled. The objectives of this study were to determine how effectively warfarin was administered to a cohort of residents in long-term care facilities, to identify the proportion of residents prescribed warfarin-interacting drugs and to ascertain factors associated with poor INR control.MethodsA chart review of 105 residents receiving warfarin therapy in five long-term care facilities in Hamilton, Ontario was performed. Data were collected on INR levels, warfarin prescribing and monitoring practices, and use of interacting medications.ResultsOver a 12 month period (28,555 resident-days, 78.2 resident years) 3065 INR values were available. Residents were within, below and above the therapeutic range 54%, 35% and 11% of the time, respectively. Seventy-nine percent of residents were prescribed at least one warfarin-interacting medication during the period in review. Residents receiving interacting medications spent less time in the therapeutic range (53.0% vs. 58.2%, OR = 0.93, 95% confidence interval 0.88 to 0.97, P = 0.002). Adequacy of anticoagulation varied significantly between physicians (time in therapeutic range 45.9 to 63.9%).ConclusionIn this group of long-term care residents, warfarin control was suboptimal. Both prescriber and co-prescription of interacting medications were associated with poorer INR control. Future studies should seek strategies to improve prescriber skill and decrease use of interacting medications.

Alendronate once weekly for the prevention and treatment of bone loss in Canadian adult cystic fibrosis patients (CFOS trial).

BACKGROUND Patients with cystic fibrosis (CF) are at risk for early bone loss, and demonstrate increased risks for vertebral fractures and kyphosis. A multicenter, randomized, controlled trial was conducted to assess the efficacy, tolerability, and safety of therapy with oral alendronate (FOSAMAX; Merck; Whitehouse Station, NJ) in adults with CF and low bone mass. METHODS Participants received placebo or alendronate, 70 mg once weekly, for 12 months. All participants received 800 IU of vitamin D and 1,000 mg of calcium daily. Adults with confirmed CF with a bone mineral density (BMD) T score of < - 1.0 were eligible for inclusion. Participants who had undergone organ transplantation or had other reported contraindications were excluded from the study. The primary outcome measure was the mean (+/- SD) percentage change in lumbar spine BMD after 12 months. Secondary measures included the percentage change in total hip BMD, the number of new vertebral fractures (grade 1 or 2), and changes in quality of life. RESULTS A total of 56 participants were enrolled in the study (mean age, 29.1 +/- 8.78 years; 61% male). The absolute percentage changes in lumbar spine and total hip BMDs at follow-up were significantly higher in the alendronate therapy group (5.20 +/- 3.67% and 2.14 +/- 3.32%, respectively) than those in the control group (- 0.08 +/- 3.93% and - 1.3 +/- 2.70%, respectively; p < 0.001). At follow-up, two participants (both in the control group) had a new vertebral fracture (not significant), and there were no differences in quality of life or the number of adverse events (including serious and GI-related events). CONCLUSION Alendronate therapy was well tolerated and produced a significantly greater increase in BMD over 12 months compared with placebo.

Longitudinal analysis of vertebral fracture and BMD in a Canadian cohort of adult cystic fibrosis patients

BackgroundVertebral fractures in patients with cystic fibrosis (CF) may contribute to an accelerated decline in lung function and can be a contraindication to lung transplantation. In this study, we examined longitudinal change in bone mineral density (BMD) and the prevalence of vertebral fractures in adult CF patients, without lung-transplant, attending a Canadian specialty clinic.MethodsRetrospective chart review of all patients attending an Adult Cystic Fibrosis Clinic at Hamilton Health Sciences in Hamilton, Canada. Forty-nine of 56 adults met inclusion criteria. Chest radiographs were graded by consensus approach using Genants semi-quantitative method to identify and grade fractured vertebrae. Dual x-ray absorptiometry (DXA) scans were also reviewed.ResultsThe mean age of the cohort was 25.2 years (SD 9.4), 43% were male. The mean body mass index (BMI) was 19.8 (2.8) for males and 21.7 (5.1) for females. At baseline, the rate of at least one vertebral fracture was 16.3%; rising to 21.3% (prevalent and incident) after a 3-year follow-up. The mean BMD T-or Z-scores at baseline were -0.80 (SD 1.1) at the lumbar spine, -0.57 (SD 0.97) at the proximal femur, and -0.71 (SD 1.1) at the whole body. Over approximately 4-years, the mean percent change in BMD was -1.93% at the proximal femur and -0.73% at the lumbar spine.ConclusionApproximately one in five CF patients demonstrated at least one or more vertebral fractures. Moderate declines in BMD were observed. Given the high rate of vertebral fractures noted in this cohort of adult CF patients, and the negative impact they have on compromised lung functioning, regular screening for vertebral fractures should be considered on routine chest radiographs.

Comparison between frailty index of deficit accumulation and phenotypic model to predict risk of falls: data from the global longitudinal study of osteoporosis in women (GLOW) Hamilton cohort.

Objectives To compare the predictive accuracy of the frailty index (FI) of deficit accumulation and the phenotypic frailty (PF) model in predicting risks of future falls, fractures and death in women aged ≥55 years. Methods Based on the data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) 3-year Hamilton cohort (n = 3,985), we compared the predictive accuracy of the FI and PF in risks of falls, fractures and death using three strategies: (1) investigated the relationship with adverse health outcomes by increasing per one-fifth (i.e., 20%) of the FI and PF; (2) trichotomized the FI based on the overlap in the density distribution of the FI by the three groups (robust, pre-frail and frail) which were defined by the PF; (3) categorized the women according to a predicted probability function of falls during the third year of follow-up predicted by the FI. Logistic regression models were used for falls and death, while survival analyses were conducted for fractures. Results The FI and PF agreed with each other at a good level of consensus (correlation coefficients ≥ 0.56) in all the three strategies. Both the FI and PF approaches predicted adverse health outcomes significantly. The FI quantified the risks of future falls, fractures and death more precisely than the PF. Both the FI and PF discriminated risks of adverse outcomes in multivariable models with acceptable and comparable area under the curve (AUCs) for falls (AUCs ≥ 0.68) and death (AUCs ≥ 0.79), and c-indices for fractures (c-indices ≥ 0.69) respectively. Conclusions The FI is comparable with the PF in predicting risks of adverse health outcomes. These findings may indicate the flexibility in the choice of frailty model for the elderly in the population-based settings.

Prevalence of Osteoporosis in Osteoarthritic Patients Undergoing Total Hip or Total Knee Arthroplasty

OBJECTIVE To determine the prevalence of osteoporosis in osteoarthritic patients undergoing total hip or total knee arthroplasty. DESIGN Cross-sectional study. SETTING The Specialized Outpatient Rehabilitation Services (SORS) Pre-surgical Arthroplasty Service located at the Chedoke Hospital, Hamilton Health Sciences, Hamilton, ON, Canada. PARTICIPANTS SORS outpatients (N=364), from the period of March 2006 to March 2007. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Prevalence of osteoporosis was determined by review of a self-reported survey, and defined by (1) self-reported diagnosis of osteoporosis, (2) history of fragility fracture (defined by a bone fracture occurring as a result of a fall from standing height or less after the age of 50), or (3) current treatment for osteoporosis using bisphosphonates. RESULTS Of the study cohort, 26% were classified as having osteoporosis, according to our criteria. Of the patients with self-reported osteoporosis or a history of fragility fractures, only 37% and 17% reported current treatment with bisphosphonates, respectively. CONCLUSIONS Osteoporosis is common in the osteoarthritic arthroplasty population, with a prevalence at least equal to that in the general population. Due to the self-reported nature of the study, the prevalence of osteoporosis in this population is likely significantly higher. Results from this study indicate need for further research, specifically in formal assessment for osteoporosis in patients undergoing a joint replacement.

A randomized controlled trial of vitamin D dosing strategies after acute hip fracture: No advantage of loading doses over daily supplementation

BackgroundThere remains uncertainty regarding the appropriate therapeutic management of hip fracture patients. The primary aim of our study was to examine whether large loading doses in addition to daily vitamin D offered any advantage over a simple daily low-dose vitamin D regimen for increasing vitamin D levels.MethodsIn this randomized controlled study, patients over age 50 with an acute fragility hip fracture were enrolled from two hospital sites in Ontario, Canada. Participants were randomized to one of three loading dose groups: placebo; 50,000 IU vitamin D2; or 100,000 IU D2. Following a placebo/loading dose, all patients received a daily tablet of 1,000 IU vitamin D3 for 90 days. Serum 25-hydroxy vitamin D (25-OHD) was measured at baseline, discharge from acute care (approximately 4-weeks), and 3-months.ResultsSixty-five patients were enrolled in the study (44% male). An immediate rise in 25-OHD occurred in the 100,000 group, however there were no significant differences in 25-OHD between the placebo, 50,000 and 100,000 loading dose groups after 4-weeks (69.3, 84.5, 75.6 nmol/L, p = 0.15) and 3-months (86.7, 84.2, 73.3 nmol/L, p = 0.09), respectively. At the end of the study, approximately 75% of the placebo and 50,000 groups had reached the target therapeutic range (75 nmol/L), and 44% of the 100,000 group.ConclusionsIn correcting vitamin D insufficiency/deficiency in elderly patients with hip fracture, our findings suggest that starting with a lower daily dose of Vitamin D3 achieved similar results as providing an additional large loading dose of Vitamin D2. At the end of the study, all three groups were equally effective in attaining improvement in 25-OHD levels. Given that a daily dose of 1,000 IU vitamin D3 (with or without a loading dose) resulted in at least 25% of patients having suboptimal vitamin D status, patients with acute hip fracture may benefit from a higher daily dose of vitamin D.Trial registrationClinical Trials # NCT00424619

A team-based approach to warfarin management in long term care: A feasibility study of the MEDeINR electronic decision support system

BackgroundPrevious studies in long-term care (LTC) have demonstrated that warfarin management is suboptimal with preventable adverse events often occurring as a result of poor International Normalized Ratio (INR) control. To assist LTC teams with the challenge of maintaining residents on warfarin in the therapeutic range (INR of 2.0 to 3.0), we developed an electronic decision support system that was based on a validated algorithm for warfarin dosing. We evaluated the MEDeINR system in a pre-post implementation design by examining the impact on INR control, testing frequency, and experiences of staff in using the system.MethodsFor this feasibility study, we piloted the MEDeINR system in six LTC homes in Ontario, Canada. All128 residents (without a prosthetic valve) who were taking warfarin were included. Three-months of INR data prior to MEDeINR was collected via a retrospective chart audit, and three-months of INR data after implementation of MEDeINR was captured in the central computer database. The primary outcomes compared in a pre-post design were time in therapeutic range (TTR) and time in sub/supratherapeutic ranges based on all INR measures for every resident on warfarin. Secondary measures included the number of monthly INR tests/resident and survey/focus-group feedback from the LTC teams.ResultsLTC homes in our study had TTRs that were higher than past reports prior to the intervention. Overall, the TTR increased during the MEDeINR phase (65 to 69%), but was only significantly increased for one home (62% to 71%, p < 0.05). The percentage of time in supratherapeutic decreased from 14% to 11%, p = 0.08); there was little change for the subtherapeutic range (21% to 20%, p = 0.66). Overall, the average number of INR tests/30 days decreased from 4.2 to 3.1 (p < 0.0001) per resident after implementation of MEDeINR. Feedback received from LTC clinicians and staff was that the program decreased the work-load, improved confidence in management and decisions, and was generally easy to use.ConclusionAlthough LTC homes in our sample had TTRs that were relatively high prior to the intervention, the MEDeINR program represented a useful tool to promote optimal TTR, decrease INR venipunctures, streamline processes, and increase nurse and physician confidence around warfarin management. We have demonstrated that MEDeINR was a practical, usable clinical information system that can be incorporated into the LTC environment.