Fracture definitions in observational osteoporosis drug effects studies that leverage healthcare administrative (claims) data: a scoping review.

Healthcare administrative (claims) data are commonly utilized to estimate drug effects. We identified considerable heterogeneity in fracture outcome definitions in a scoping review of 57 studies that estimated osteoporosis drug effects on fracture risk. Better understanding of the impact of different fracture definitions on study results is needed. PURPOSE: Healthcare administrative (claims) data are frequently used to estimate the real-world effects of drugs. Fracture incidence is a common outcome of osteoporosis drug studies. We aimed to describe how fractures are defined in studies that use claims data. METHODS: We searched MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCO), and gray literature for studies published in English between 2000 and 2020 that estimated fracture effectiveness (hip, humerus, radius/ulna, vertebra) or safety (atypical fracture of the femur, AFF) of osteoporosis drugs using claims data in Canada and the USA. Literature searches, screening and data abstraction were completed independently by two reviewers. RESULTS: We identified 57 eligible studies (52 effectiveness, 3 safety, 2 both). Hip fracture was the most common fracture site studied (93%), followed by humerus (66%), radius/ulna (59%), vertebra (61%), and AFF (9%). Half (n = 29) of the studies did not indicate specific data sources, codes, or cite a validation paper. Of the papers with sufficient detail, heterogeneity in fracture definitions was common. The most common definition within each fracture site was used by less than half of the studies that examined effectiveness (12 definitions in 29 hip fracture papers, 8 definitions in 17 humerus papers, 8 definitions in 13 radius/ulna papers, 9 definitions in 15 vertebra papers), and 3 definitions among 4 AFF papers. CONCLUSION: There is ambiguity and heterogeneity in fracture outcome definitions in studies that leverage claims data. Better transparency in outcome reporting is needed. Future exploration of how fracture definitions impact study results is warranted.

Over half of seniors who start oral bisphosphonate therapy are exposed for 3 or more years: novel rolling window approach and patterns of use.

Most adherence studies only consider treatment following a first prescription. Using an extended follow-up, we found that 60% of seniors starting oral bisphosphonate therapy were exposed for ≥ 3 years (48% for ≥ 5 years). Studies are needed to examine the benefits and harms of continuing bisphosphonate therapy beyond 3 years. INTRODUCTION: The purpose of this study was to identify and describe patterns of long-term oral bisphosphonate use among seniors using a novel methodological approach that considers extended follow-up. METHODS: Among Ontarians aged 66 years or older, we identified subjects with a first dispensing of alendronate or risedronate between November 2000 and December 2016. We followed them until death or December 2019 to identify patients with ≥ 3 years of bisphosphonate use, defined as a proportion of days covered ≥ 80%, using 3-year rolling windows. We calculated the proportion of patients with long-term therapy (≥ 3 years of use) using Kaplan-Meier estimates. We described patterns of long-term use and compared patient characteristics between patients with and without long-term therapy. RESULTS: We identified 260,784 eligible seniors initiating bisphosphonate therapy. Of these, 60% continued therapy ≥ 3 years (77% women), and 48% continued ≥ 5 years. Characteristics did not meaningfully differ between patients with or without long-term therapy. The median length of long-term therapy was 7.0 (IQR 5.1) years for women and 6.1 (IQR 4.3) years for men. Only 20% experienced a treatment gap before long-term therapy, yet 50% experienced a treatment gap of ≥ 120 days after a median 5.3 years of therapy. Eighty-one percent who returned to therapy following a treatment gap re-initiated an oral bisphosphonate, with 18% switching to denosumab. CONCLUSIONS: Among seniors initiating oral bisphosphonates, we found that 60% receive at least 3 years of therapy when using an extended follow-up. Studies are needed to examine the benefits and harms of continuing bisphosphonate therapy beyond 3 years.

Denosumab utilization among older adults in Ontario: patient characteristics, persistence with therapy, and return to therapy after an extended gap.

We studied 46,797 older adults who initiated denosumab in Ontario, Canada. Patient characteristics remained relatively stable over time and aligned with public reimbursement restrictions. Almost half of patients persisted with therapy for at least 3 years. Fifty-nine percent of patients who discontinued denosumab returned to treatment within 3.6 years. INTRODUCTION: The purpose of this study was to describe the characteristics of patients who initiated denosumab and estimate persistence with therapy. METHODS: We identified older adults (aged ≥ 66 years) in Ontario who initiated denosumab between 2012/02 and 2015/03 and followed them to 2016/03. Patient characteristics were summarized using medical and pharmacy claims in the year before starting denosumab and osteoporosis drug use considered since 1996/10. Persistence with denosumab and return after discontinuation (> 90-day gap) were estimated using Kaplan-Meier curves. Analyses were stratified by community and long-term care (LTC) residence. RESULTS: We identified 46,797 patients (monthly mean = 1263, SD = 187); 97% female, 13% LTC. Community-dwelling patients had a higher prevalence of bone mineral density testing (62% vs. 5%), yet were younger (mean age 78.5 vs. 86.6 years) and had lower prevalence of hip fractures (3% vs. 10%) compared to LTC patients. Eighty-two percent of patients had used osteoporosis medications in the past; 99% of whom took an oral bisphosphonate. Persistence was similar between community-dwelling and LTC patients: 59% persisted ≥ 2 years, 48% ≥ 3 years, and 38% ≥ 4 years, yet a larger proportion of LTC patients returned to denosumab after discontinuation (76% vs. 57%). CONCLUSIONS: Denosumab utilization is increasing at a steady rate in Ontario. However, persistence remains a concern given the highly reversible pharmacokinetic profile of denosumab that results in a rapid increased fracture risk following discontinuation. Over 80% of patients had a history of oral bisphosphonate therapy, which may persist in bone despite discontinuing denosumab. Consequently, better understanding of denosumab safety and effectiveness among real-world users is important.

Time trends in oral bisphosphonate initiation in Ontario, Canada over 20 years reflect drug policy and healthcare delivery changes.

Characteristics of patients starting oral bisphosphonate therapy changed over time, reflecting trends in osteoporosis management (e.g., new drugs to market), and general healthcare delivery (e.g., benzodiazepine use declined, statin use increased). When designing studies that examine osteoporosis drug effects, potential time-related biases must be considered. INTRODUCTION: To describe the type of oral bisphosphonate initiated and characteristics of patients starting oral bisphosphonate therapy over time. METHODS: We identified community-dwelling older adults (ages ≥ 66 years) initiating oral bisphosphonate therapy from April 1996 to March 2016 (1996 to 2015 fiscal years) using healthcare administrative data in Ontario. Patients with conditions other than osteoporosis that may impact bisphosphonate prescribing were excluded. The bisphosphonate initiated and patient characteristics were summarized by fiscal year and stratified by sex. RESULTS: We identified 560,817 eligible patients (81% women). Most patients initiated cyclical etidronate from 1996 until 2005, and then weekly regimens became dominant. In 2008, risedronate became the main oral bisphosphonate (46% risedronate, 43% alendronate, 11% etidronate); with its use increasing after availability of monthly and delayed-release risedronate formulations. In 2015, 71% of patients started risedronate, 28% started alendronate, and less than 2% started etidronate. Characteristics of patients changed over time, reflecting changes in osteoporosis management and general healthcare delivery. Over time, a larger proportion of men (9% to 28%) and patients with diabetes (women 10% to 17%, men 14% to 22%) initiated therapy; benzodiazepine (women 22% to 13%, men 20% to 10%) and estrogen-based hormone replacement therapy (12% to 15% of women 1996-2002 to 3% since 2008) decreased, while statin use increased (women 15% to 39%, men 14% to 52%). CONCLUSIONS: The characteristics of patients starting oral bisphosphonate therapy have changed over time. Consideration must be given to these time trends when designing studies that examine osteoporosis drug effects.

Five-year refracture rates of a province-wide fracture liaison service.

We examined the 5-year refracture rate of 6543 patients and found an overall rate of 9.7%. Adjusted analysis showed that presenting with multiple fractures was an indicator of a higher refracture risk; while presenting with an ankle fracture was associated with a lower refracture risk. INTRODUCTION: To examine refractures among patients screened in a province-wide fracture liaison service (FLS). METHODS: We assessed the 5-year refracture rate of fragility fracture patients aged 50+ who were screened at 37 FLS fracture clinics in Ontario, Canada. Refracture was defined as a new hip, pelvis, spine, distal radius, or proximal humerus fracture. Kaplan-Meier curves and Cox proportional hazards model adjusting for age, sex, and index fracture type were used to examine refracture rates. RESULTS: The 5-year refracture rate of 6543 patients was 9.7%. Those presenting with multiple fractures at baseline (i.e., two or more fractures occurring simultaneously) had the highest refracture rate of 19.6%. As compared to the 50-65 age group, refracture risk increased monotonically with age group (66-70 years: HR = 1.3, CI 95%, 1.0-1.7; 71-80 years: HR = 1.7, CI 1.4-2.1; 81+ years: HR = 3.0, CI 2.4-3.7). Relative to distal radius, presenting with multiple fractures at screening was associated with a higher risk of refracture (HR = 2.3 CI 1.6-3.1), while presenting with an ankle fracture was associated with a lower risk of refracture (HR = 0.7 CI 0.6-0.9). Sex was not a statistically significant predictor of refracture risk in this cohort (HR = 1.2, CI 1.0-1.5). CONCLUSIONS: One in ten patients in our cohort refractured within 5 years after baseline. Presenting with multiple fractures was an indicator of a higher refracture risk, while presenting with an ankle fracture was associated with a lower refracture risk. A more targeted FLS approach may be appropriate for patients at a higher refracture risk.

Cost-of-illness studies in chronic ulcers: a systematic review.

OBJECTIVE: To systematically review the published academic literature on the cost of chronic ulcers. METHODS: A literature search was conducted in MEDLINE, EMBASE, HealthSTAR, Econlit and CINAHL up to 12 May 2016 to identify potential studies for review. Cost search terms were based on validated algorithms. Clinical search terms were based on recent Cochrane reviews of interventions for chronic ulcers. Titles and abstracts were screened by two reviewers to determine eligibility for full text review. Study characteristics were summarised. The quality of reporting was evaluated using a modified cost-of-illness checklist. Mean costs were adjusted and inflated to 2015 $US and presented for different durations and perspectives. RESULTS: Of 2267 studies identified, 36 were eligible and included in the systematic review. Most studies presented results from the health-care public payer or hospital perspective. Many studies included hospital costs in the analysis and only reported total costs without presenting condition-specific attributable costs. The mean cost of chronic ulcers ranged from $1000 per year for patient out of pocket costs to $30,000 per episode from the health-care public payer perspective. Mean one year cost from a health-care public payer perspective was $44,200 for diabetic foot ulcer (DFU), $15,400 for pressure ulcer (PU) and $11,000 for leg ulcer (LU). CONCLUSIONS: There was large variability in study methods, perspectives, cost components and jurisdictions, making interpretation of costs difficult. Nevertheless, it appears that the cost for the treatment of chronic ulcers is substantial and greater attention needs to be made for preventive measures.

Efficacy of osteoporosis pharmacotherapies in preventing fracture among oral glucocorticoid users: a network meta-analysis.

UNLABELLED: Efficacy of osteoporosis medication is not well-established among patients taking oral glucocorticoids. We assessed the efficacy of approved osteoporosis pharmacotherapies in preventing fracture by combining data from randomized controlled trials. Teriparatide, risedronate, and etidronate were associated with decreased vertebral fracture risk. INTRODUCTION: Several osteoporosis drugs are approved for the prevention and treatment of glucocorticoid (GC)-induced osteoporosis. However, the efficacy of these treatments among oral GC users is still limited. We aimed to examine the comparative efficacy of osteoporosis treatments among oral GC users. METHODS: We updated a systematic review through to March 2015 to identify all double-blinded randomized controlled trials (RCTs) that examined osteoporosis treatment among oral GC users. We used a network meta-analysis with informative priors to derive comparative risk ratios (RRs) and 95 % credible intervals (95 % CrI) for vertebral and non-vertebral fracture and mean differences in lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD). Treatment ranking was estimated using the surface under the cumulative ranking curve (SUCRA) statistic. A meta-regression was completed to assess a subgroup effect between patients with prior GC exposures and GC initiators. RESULTS: We identified 27 eligible RCTs examining nine active comparators. Etidronate (RR, 0.41; 95%CrI = 0.17-0.90), risedronate (RR = 0.30, 95%CrI = 0.14-0.61), and teriparatide (RR = 0.07, 95%CrI = 0.001-0.48) showed greater efficacy than placebo in preventing vertebral fractures; yet, no treatment effects were statistically significant in reducing non-vertebral fractures. Alendronate, risedronate, and etidronate increased LS BMD while alendronate and raloxifene increased FN BMD. In preventing vertebral fractures, teriparatide was ranked as the best treatment (SUCRA: 77 %), followed by risedronate (77 %) and zoledronic acid (76 %). For non-vertebral fractures, teriparatide also had the highest SUCRA (69 %), followed by risedronate (64 %). No subgroup effect was identified with regards to prior GC exposure. CONCLUSIONS: Despite weak trial evidence available for fracture prevention among GC users, we identified several drugs that are likely to prevent osteoporotic fracture. Teriparatide, risedronate, and etidronate were associated with decreased vertebral fracture risk.

Fracture risk in oral glucocorticoid users: a Bayesian meta-regression leveraging control arms of osteoporosis clinical trials.

UNLABELLED: Little data exist on the frequency of fracture among oral glucocorticoid users. We examined the effect of oral glucocorticoids on fracture incidence using data from randomized controlled trials. Patients starting glucocorticoids had a higher probability of fracture and decline in bone mineral density compared to chronic glucocorticoid users. INTRODUCTION: Oral glucocorticoids (GCs) are the leading cause of secondary osteoporosis. However, there have been few studies that quantify the rate of fracture among GC users. We sought to provide a pooled estimate of fracture risk from randomized controlled trials (RCTs) of GC-treated patients. METHODS: We updated a MEDLINE search published by the American College of Rheumatology through to March 2015 and identified RCTs of osteoporosis therapies that reported fracture and bone mineral density (BMD) among oral GC users. We restricted the analysis to placebo or control arms. RCT arms were stratified by GC exposure at enrolment to GC initiators (≤6 months) and chronic GC users (>6 months). Bayesian meta-regression was used to estimate the annual probability of vertebral fracture (primary), non-vertebral fracture and percentage change in lumbar spine and femoral neck BMD. RESULTS: The annual incidence of vertebral and non-vertebral fracture was 5.1 % (95 % CrI = 2.8-8.2) and 2.5 % (95 % CrI = 1.2--4.2) among GC initiators, and 3.2 % (95 % CrI = 1.8-5.0) and 3.0 % (95 % CrI = 0.8-5.9) among chronic GC users. Our meta-regression identified a non-significant effect of group-level variables (mean age, mean BMD, mean GC daily dose, patients with previous vertebral fractures, proportion of women and adjuvant used) on vertebral fracture rate. CONCLUSION: Our study found higher vertebral fracture incidence among GC initiators, yet a relative decline in fracture incidence with longer exposure. Our findings suggest that fracture incidence among oral GC users may be more common than previously estimated. Optimizing GC-induced osteoporosis management during early exposure to GC is essential to prevent fractures.

Glucocorticoid-induced osteoporosis management among seniors, by year, sex, and indication, 1996-2012.

UNLABELLED: We identified that glucocorticoid-induced osteoporosis management (bone mineral density testing or osteoporosis treatment) among seniors improved among men (2 to 23 %) and women (10 to 48 %) between 1996 and 2007, and then remained relatively stable through to 2012. Differences were also noted by indication (from a low of 21 % for respiratory conditions to a high of 41 % for rheumatic conditions). PURPOSE: The aim of our study was to describe the proportion of chronic oral glucocorticoid (GC) users that receive osteoporosis management (bone mineral density test or osteoporosis treatment) by sex and over time. METHODS: We identified community-dwelling older adults initiating chronic oral GC therapy in Ontario using pharmacy data from 1996 to 2012. Chronic GC use was defined as greater than or equal to two oral GC prescriptions dispensed and ≥450 mg prednisone equivalent over a 6-month period. Osteoporosis management within 6 months of starting chronic GC therapy was examined by sex, year, indication for therapy, and osteoporosis management history. Results were summarized using descriptive statistics. RESULTS: We identified 72,099 men and 95,975 women starting chronic oral GC therapy (mean age = 74.9 years, SD = 6.5). Approximately two thirds of patients (65 %) received ≥900 mg within the 6-month chronic use window. GC-induced osteoporosis management increased from 2 to 23 % (men) and 10 to 48 % (women) between 1996 and 2007, and then remained relatively stable through to 2012. A higher proportion of patients with prior osteoporosis management were managed within 6 months (56 % men, 67 % women) of chronic GC use, compared to patients without prior management (12 % men, 23 % women). Patients with rheumatic disease were managed most commonly (41 %), and patients with respiratory conditions were managed least commonly (21 %). CONCLUSIONS: GC-induced osteoporosis management improved significantly over time for both sexes yet remains low. Significant care gaps by sex and between clinical areas represent a missed opportunity for fracture prevention among patients requiring chronic GC therapy.

Uptake and characteristics of zoledronic acid and denosumab patients and physicians in Ontario, Canada: impact of drug formulary access.

UNLABELLED: The addition of Limited Use criteria (less restrictive access) for zoledronic acid resulted in an immediate and significant increase in uptake and resulted in differences in patient/physician characteristics. In comparison, the uptake of denosumab (only listed with Limited Use) was rapid. Thus, formulary access restrictions have significant implications for prescribing. INTRODUCTION: We sought to describe the use of zoledronic acid and denosumab by physicians and patients over time and examine the impact of a 2012 provincial formulary modification that removed the administrative burden on physicians when prescribing zoledronic acid. METHODS: We identified users of zoledronic acid and denosumab using Ontario pharmacy claims data. The number of new patients and physicians was plotted and examined over time. Interrupted time series analysis examined the impact of a formulary modification to zoledronic acid use and prescribing. Descriptive characteristics of patients and prescribers were summarized pre- and post-formulary modification for zoledronic acid and overall for denosumab. RESULTS: We identified 1463 zoledronic acid patients treated by 627 physicians and 16,736 denosumab patients treated by 2904 physicians. In the first 2 months on the market, we identified a rapid uptake of denosumab (>450 physicians and >1200 patients) in contrast to zoledronic acid (<10 physicians and <10 patients). Zoledronic acid use increased significantly in the 2-month post-formulary change, yet no change in denosumab was observed. Prior to the formulary modification, more zoledronic acid patients had a history of osteoporosis therapy (41 vs. 26%) or bone density testing (30 vs. 10%). Compared to zoledronic patients (post-formulary modification), more denosumab patients had prior osteoporosis therapy (55 vs. 26%), yet fewer had a gastrointestinal diagnosis (6 vs. 11%). CONCLUSION: We identified a rapid uptake of denosumab in only 15 months of observation. A provincial formulary modification to zoledronic acid resulted in an increase in utilization and impacted patient characteristics.

Comparative gastrointestinal safety of bisphosphonates in primary osteoporosis: a network meta-analysis.

UNLABELLED: We completed a network meta-analysis of published papers to compare bisphosphonate gastrointestinal safety. We found that zoledronic acid had the highest chance of causing gastrointestinal adverse events. Etidronate had the highest chance of discontinuation due to an adverse event. No difference was found for serious adverse events. INTRODUCTION: Bisphosphonates are first-line treatment for osteoporosis. Gastrointestinal (GI) adverse events (AE) are the primary reason for non-adherence. Little is known about the comparative GI safety of bisphosphonates. PURPOSE: Leverage published clinical trial data to examine the comparative GI safety of bisphosphonates. METHODS: We completed a systematic review of all English-language clinical trials that assessed bisphosphonate safety and/or efficacy in primary osteoporosis through to 2012. Randomized, blinded, and controlled studies were eligible. The primary outcome was any GI-related AE. Subanalyses were completed for upper GI symptoms, serious GI, nausea, esophageal-related events, and discontinuation due to AE. A Bayesian-based network meta-analysis was completed to allow for indirect comparisons. Results were reported as the probability that a specific drug had the highest number of events. RESULTS: We identified 50 studies: 32 alendronate, 12 risedronate, 5 etidronate, and 7 zoledronic acid. Zoledronic acid had the highest probability of having the highest number of any GI AE (91%) and nausea (70%). Etidronate (70%) and zoledronic acid (28%) had the highest probability of having the greatest attrition due to AE. Etidronate had the highest probability (56%) of having the greatest number of upper GI symptoms among oral bisphosphonates. CONCLUSION: Zoledronic acid had the highest probability of causing the greatest number of GI AE, possibly related to nausea. These results question the assumption that annual zoledronic acid will translate into better adherence. Little difference was found between alendronate and risedronate for serious AE. More research into real-world implications of the comparative safety of bisphosphonates is needed.

Direct health-care costs attributed to hip fractures among seniors: a matched cohort study.

SUMMARY: Using a matched cohort design, we estimated the mean direct attributable cost in the first year after hip fracture in Ontario to be $36,929 among women and $39,479 among men. These estimates translate into an annual $282 million in direct attributable health-care costs in Ontario and $1.1 billion in Canada. INTRODUCTION: Osteoporosis is a major public health concern that results in substantial fracture-related morbidity and mortality. It is well established that hip fractures are the most devastating consequence of osteoporosis, yet the health-care costs attributed to hip fractures in Canada have not been thoroughly evaluated. METHODS: We determined the 1- and 2-year direct attributable costs and cost drivers associated with hip fractures among seniors in comparison to a matched non-hip fracture cohort using health-care administrative data from Ontario (2004-2008). Entry into long-term care and deaths attributable to hip fracture were also determined. RESULTS: We successfully matched 22,418 female (mean age = 83.3 years) and 7,611 male (mean age = 81.3 years) hip fracture patients. The mean attributable cost in the first year after fracture was $36,929 (95 % CI $36,380-37,466) among women and $39,479 (95 % CI $38,311-$40,677) among men. These estimates translate into an annual $282 million in direct attributable health-care costs in Ontario and $1.1 billion in Canada. Primary cost drivers were acute and post-acute institutional care. Approximately 24 % of women and 19 % of men living in the community at the time of fracture entered a long-term care facility, and 22 % of women and 33 % of men died within the first year following hip fracture. Attributable costs remained elevated into the second year ($9,017 among women, $10,347 among men) for patients who survived the first year. CONCLUSIONS: We identified significant health-care costs, entry into long-term care, and mortality attributed to hip fractures. Results may inform health economic analyses and policy decision-making in Canada.

Bisphosphonate prescribing, persistence and cumulative exposure in Ontario, Canada.

UNLABELLED: We studied new users of oral bisphosphonates and found that less than half persisted with therapy for 2 years, and interruptions in use were common. During a median observation period of 4.7 years, 10% of patients filled only a single prescription, 37% switched therapies and median cumulative exposure was 2.2 years. INTRODUCTION: We sought to describe bisphosphonate prescribing, persistence and cumulative exposure among seniors in Ontario, Canada. METHODS: We used Ontario Drug Benefit pharmacy claims to identify residents aged ≥ 66 years who initiated oral bisphosphonate therapy between April 1996 and March 2009. The first date of bisphosphonate dispensing was considered the index date. Persistence with therapy was defined as continuous treatment with no interruption exceeding 60 days. We examined persistence with therapy and the number of extended gaps (>60 days) between prescriptions over time periods ranging from 1 to 9 years. We also identified the proportion of patients filling only a single prescription and switching to a different bisphosphonate, and calculated the median days of exposure irrespective of gaps in therapy. RESULTS: A total of 451,113 eligible new bisphosphonate users were identified: mean age = 75.6 years (SD = 6.9), 84% female, and median follow-up length = 4.7 years. Persistence with therapy declined from 63% at 1 year to 46% at 2 years and 12% at 9 years. Among those with at least 5 years of follow-up (n = 213,029), 61% had one or more extended gaps in bisphosphonate therapy. Overall, 10% of patients filled only a single prescription, 37% switched to a different bisphosphonate and the median exposure was 2.2 years. CONCLUSION: Less than half of patients persisted with bisphosphonate therapy for 2 years and interruptions in therapy were common, with most patients experiencing two or more >60-day gaps in therapy. Interventions are needed to improve persistence with bisphosphonate therapy and reduce the frequency of gaps in treatment.

Impact of a centralized osteoporosis coordinator on post-fracture osteoporosis management: a cluster randomized trial.

UNLABELLED: We conducted a cluster randomized trial evaluating the effect of a centralized coordinator who identifies and follows up with fracture patients and their primary care physicians about osteoporosis. Compared with controls, intervention patients were five times more likely to receive BMD testing and two times more likely to receive appropriate management. INTRODUCTION: To determine if a centralized coordinator who follows up with fracture patients and their primary care physicians by telephone and mail (intervention) will increase the proportion of patients who receive appropriate post-fracture osteoporosis management, compared to simple fall prevention advice (attention control). METHODS: A cluster randomized controlled trial was conducted in small community hospitals in the province of Ontario, Canada. Hospitals that treated between 60 and 340 fracture patients per year were eligible. Patients 40 years and older presenting with a low trauma fracture were identified from Emergency Department records and enrolled in the trial. The primary outcome was 'appropriate' management, defined as a normal bone mineral density (BMD) test or taking osteoporosis medications. RESULTS: Thirty-six hospitals were randomized to either intervention or control and 130 intervention and 137 control subjects completed the study. The mean age of participants was 65 ± 12 years and 69% were female. The intervention increased the proportion of patients who received appropriate management within 6 months of fracture; 45% in the intervention group compared with 26% in the control group (absolute difference of 19%; adjusted OR, 2.3; 95% CI, 1.3-4.1). The proportion who had a BMD test scheduled or performed was much higher with 57% of intervention patients compared with 21% of controls (absolute difference of 36%; adjusted OR, 4.8; 95% CI, 3.0-7.0). CONCLUSIONS: A centralized osteoporosis coordinator is effective in improving the quality of osteoporosis care in smaller communities that do not have on-site coordinators or direct access to osteoporosis specialists.

Osteoporosis medication prescribing in British Columbia and Ontario: impact of public drug coverage.

UNLABELLED: We compared the patterns of osteoporosis medication prescribing between two provinces in Canada with different public drug coverage policies. Oral bisphosphonates were the primary drugs used, yet access to the second-generation oral bisphosphonates (alendronate, risedronate) was limited in one region. Implications of differential access to oral bisphosphonates warrants further study. INTRODUCTION: Approved therapies for treating osteoporosis in Canada include bisphosphonates, calcitonin, denosumab, raloxifene, and teriparatide. However, significant variation in access to these medications through public drug coverage exists across Canada. We sought to compare patterns of osteoporosis medication prescribing between British Columbia (BC) and Ontario. METHODS: Using dispensing data from BC (PharmaNet) and Ontario (Ontario Drug Benefits), we identified all new users of osteoporosis medications aged 66 or more years from 1995/1996 to 2008/2009. We summarized the number of new users by fiscal year, sex, and index drug for each province. BC data were also stratified by whether drugs were dispensed within or outside public PharmaCare. RESULTS: We identified 578,254 (n = 122,653 BC) eligible new users. Overall patterns were similar between provinces: (1) most patients received an oral bisphosphonate (93% in BC and 99% in Ontario); (2) etidronate prescribing declined after 2001/2002, reaching a low of 41% in BC and 10% in Ontario in 2008/2009; and (3) the proportion of males treated increased over time, from 7% in 1996/1997 to 25% in 2008/2009. However, we note major differences within versus outside the BC PharmaCare system. In particular, <2% of drugs dispensed within PharmaCare compared to 79% of drugs dispensed outside PharmaCare were for a second-generation bisphosphonate (alendronate or risedronate). CONCLUSIONS: Oral bisphosphonates are the primary drugs used to treat osteoporosis in Canada. Prescribing practices changed over time as newer medications came to market, yet access to second-generation bisphosphonates through BC PharmaCare was limited. Implications of differential access to oral bisphosphonates warrants further study.

The impact of pharmacist interventions on osteoporosis management: a systematic review.

UNLABELLED: We completed a systematic review of the literature to examine the impact of pharmacist interventions in improving osteoporosis management. Results from randomized controlled trials suggest that pharmacist interventions may improve bone mineral density testing and calcium intake among patients at high risk for osteoporosis. INTRODUCTION: Pharmacists play a key role in many healthcare systems by helping patients manage chronic diseases. We completed a systematic review of the literature to identify randomized controlled trials (RCTs) that have examined the impact of pharmacy interventions in narrowing two gaps in osteoporosis management: identifying at-risk individuals and improving adherence to therapy. METHODS: We searched the electronic databases of EMBASE, HealthStar, International Pharmaceutical Abstracts, MEDLINE, and PubMed from database development to April 2010, examined grey literature, and completed manual searches of reference lists to identify English-language research that examined osteoporosis management interventions within pharmacy practice. Results from RCTs were abstracted and assessed for bias. RESULTS: We identified 25 studies that examined pharmacist interventions in osteoporosis management: 16 cohort, 5 cross-sectional, 1 historical/ecological control, and 3 RCTs. RCT interventions included osteoporosis educational and counseling programs, screening by pharmacists based on risk factor assessment or bone mineral density testing, and physician contact or recommendations for patients to follow-up with a general practitioner. Results from the three RCTs suggest that pharmacist interventions may improve bone mineral density testing (targeted screening) and calcium intake among patients at high risk for osteoporosis. However, two of the three RCTs had high risk of bias, and no study examined the impact of pharmacist intervention on osteoporosis treatment adherence. CONCLUSIONS: Data support the potential role for pharmacists to help reduce gaps in osteoporosis management through improved identification of high-risk patients. More research is needed to examine pharmacist interventions on osteoporosis treatment adherence.

Osteoporosis quality indicators using healthcare utilization data.

SUMMARY: Healthcare utilization data may be used to examine the quality of osteoporosis management by identifying dual-energy X-ray absorptiometry (DXA) testing (sensitivity = 98%, specificity = 93%) and osteoporosis pharmacotherapy (κ = 0.81) with minimal measurement error. INTRODUCTION: In osteoporosis, key quality indicators among older women include risk assessment by DXA and/or pharmacotherapy within 6 months following fracture. METHODS: The purpose of this study was to examine healthcare utilization data for use as quality indicators of osteoporosis management. We linked data from 858 community-dwelling women aged over 65 years who completed a standardized telephone interview about osteoporosis management to their healthcare utilization (medical and pharmacy claims) data. Agreement between self-report of osteoporosis pharmacotherapy and pharmacy claims was examined using kappa statistics. We examined the sensitivity and specificity of medical claims to identify DXA testing as well as the sensitivity and specificity of medical and pharmacy claims to identify those with DXA-documented osteoporosis (T-score ≤ -2.5). RESULTS: Participants were aged 75 (SD = 6) years on average; 96% were Caucasian. Agreement between self-report and claims-based osteoporosis pharmacotherapy was very good (κ = 0.81; 95% CI = 0.76, 0.86). The sensitivity of medical claims to identify DXA testing was 98% (95% CI = 95.9, 99.1), with estimated specificity of 93% (95% CI = 89.8, 95.4). We abstracted DXA results from test reports of 359 women, of whom 114 (32%) were identified with osteoporosis. Medical (osteoporosis diagnosis) and pharmacy (osteoporosis pharmacotherapy) claims within a year after DXA testing had a sensitivity of 80% (95% CI = 71.3, 86.8) and specificity of 72% (95% CI = 66.2, 77.8) to identify DXA-documented osteoporosis. CONCLUSION: Healthcare utilization data may be used to examine the quality of osteoporosis management by identifying DXA testing and osteoporosis pharmacotherapy (care processes) with minimal measurement error. However, medical and pharmacy claims alone do not provide a good means for identifying women with underlying osteoporosis.

Adherence to osteoporosis drugs and fracture prevention: no evidence of healthy adherer bias in a frail cohort of seniors.

UNLABELLED: We examined new users of osteoporosis drugs among seniors in Pennsylvania and found no evidence of healthy adherer bias on observed associations between adherence to treatment and non-vertebral fracture risk; we document fracture reduction with better adherence to bisphosphonates, yet no fracture reduction with better adherence to calcitonin or raloxifene. INTRODUCTION: We examined the potential for "healthy adherer bias" when studying the effects of adherence to osteoporosis pharmacotherapy on fracture risk. Based on clinical trial evidence, bisphosphonates, calcitonin, and raloxifene reduce vertebral fracture risk; yet only bisphosphonates are documented to reduce non-vertebral fracture risk. METHODS: This is a cohort study of older women in Pennsylvania who initiated osteoporosis drugs between 1995 and 2005. We included new users of bisphosphonates, calcitonin, and raloxifene. Adherence was categorized based on a measure of compliance as high [proportion of days covered (PDC) ≥ 80%], intermediate (50% < PDC < 80%), or low (PDC ≤ 50%) according to a 180-day ascertainment period. Non-vertebral fracture rates within 365 days after the ascertainment period were compared between adherence categories (reference = low) using Cox proportional hazard models and adjusting for fracture risk factors. Primary and secondary prevention cohorts were examined separately. Adherence to calcitonin and raloxifene were control analyses. RESULTS: We found little difference in fracture rates between levels of adherence to calcitonin, bisphosphonates for primary prevention, or raloxifene for secondary prevention. We document lower fracture rates among high versus low adherent bisphosphonate users for secondary prevention (HR = 0.53, 95%CI = 0.38-0.74) and higher fracture rates among high versus low adherent raloxifene users for primary prevention (HR = 2.01, 95%CI = 1.04-3.87). CONCLUSIONS: We document little evidence of healthy adherer bias when studying the association between better adherence to osteoporosis drugs and fracture risk reduction, with only better adherence to bisphosphonates reducing fracture risk. The higher fracture risk among highly adherent raloxifene users for primary prevention is likely due to residual confounding.

Osteoporosis pharmacotherapy following bone densitometry: importance of patient beliefs and understanding of DXA results.

SUMMARY: Persistence with osteoporosis therapy remains low and identification of factors associated with better persistence is essential in preventing osteoporosis and fractures. In this study, patient understanding of dual energy X-ray absorptiometry (DXA) results and beliefs in effects of treatment were associated with treatment initiation and persistence. INTRODUCTION: The purpose of this study is to examine patient understanding of their DXA results and evaluate factors associated with initiation of and persistence with prescribed medication in first-time users of anti-osteoporotic agents. Self-reported DXA results reflect patient understanding of diagnosis and may influence acceptance of osteoporosis therapy. To improve patient understanding of DXA results, we provided written information to patients and their referring general practitioner (GP), and evaluated factors associated with osteoporosis treatment initiation and 1-year persistence. METHODS: Information on diagnosis was mailed to 1,000 consecutive patients and their GPs after DXA testing. One year after, a questionnaire was mailed to all patients to evaluate self-report of DXA results, drug initiation and 1-year persistence. Quadratic weighted kappa was used to estimate agreement between self-report and actual DXA results. Multivariable logistic regression was used to evaluate predictors of understanding of diagnosis, and correlates of treatment initiation and persistence. RESULTS: A total of 717 patients responded (72%). Overall, only 4% were unaware of DXA results. Agreement between self-reported and actual DXA results was very good (κ = 0.83); younger age and glucocorticoid use were associated with better understanding. Correctly reported DXA results was associated with treatment initiation (OR 4.3, 95% CI 1.2-15.1, p = 0.02), and greater beliefs in drug treatment benefits were associated with treatment initiation (OR 1.4, 95%CI 1.1-1.9, p = 0.006) and persistence with therapy (OR 1.8, 95% CI 1.2-2.7, p = 0.006). CONCLUSION: Our findings suggest that written information provides over 80% of patients with a basic understanding of their DXA results. Communicating results in writing may improve patient understanding thereby also improve osteoporosis management and prevention.