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

Abstract

Summary

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.

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Letter to the Editor about the article “A systematic review and meta-analysis of the effect of bisphosphonate drug holidays on bone mineral density and osteoporotic fracture risk”

FGF 23 and trabecular microarchitecture

FGF23 and bone microarchitecture

Revisit three “I” model: a novel five “I” model of fracture liaison service

Influence of fall environment and fall direction on risk of injury among pre-frail and frail adults Abstract Summary In this prospective study, half of all falls resulted in injury. Pre-frail adults sustained more injuries, while more frail adults had injuries requiring hospitalization or fractures. Pre-frail adults fell more often when in movement compared with frail adults who fell more often when standing and in indoor public spaces. Purpose To assess prospectively how fall environment and direction are related to injury among pre-frail and frail adults. Methods We included 200 community-dwelling adults with a prior fall (pre-frail, mean age 77 years) and 173 adults with acute hip fracture (frail, mean age 84 years; 77% community-dwelling). Falls were prospectively recorded using standardized protocols in monthly intervals, including date, time, fall direction and environment, and injury. We used logistic regression to assess the odds of injury adjusting for age, body mass index (BMI), and gender. Results We recorded 513 falls and 331 fall-related injuries (64.5%) among the 373 participants. While the fall rate was similar between groups, pre-frail adults had more injuries (71% among pre-frail vs. 56% among frail, p = 0.0004) but a lower incidence of major injuries (9% among pre-frail vs. 27% among frail, p = 0.003). Pre-frail adults fell more often while in movement (84% among pre-frail vs. 55% among frail, p < 0.0001), and frail adults fell more often while standing (26% vs. 15% respectively, p = 0.01). The odds of injury among frail adults was increased 3.3-fold when falling sideways (OR = 3.29, 95% CI = 1.68–6.45) and 2.4-fold when falling in an indoor public space (OR = 2.35, 95% CI = 1.00–5.53), and was reduced when falling at home (OR = 0.55, 95% CI = 0.31–0.98). The odds of injury among pre-frail adults was not influenced by environment and was 53% lower when falling backwards (OR = 0.47, 95% CI = 0.26–0.82). Conclusion While pre-frail adults sustain more fall-related injuries, frail adults were more likely to sustain major injuries, especially when falling sideways or outside their home.

Fracture prediction from self-reported falls in routine clinical practice: a registry-based cohort study Abstract Summary A simple question construct regarding number of falls in the previous year, ascertained by a single question, was strongly associated with incident fractures in routine clinical practice using a population-based dual-energy X-ray absorptiometry (DXA) registry. Introduction There is conflicting evidence from research cohorts that falls independently increase fracture risk. We examined the independent effects of falls on subsequent fractures in a large clinical registry of bone mineral density (BMD) results for the Province of Manitoba, Canada that has been systematically collecting self-reported falls information since September 1, 2012. Methods The study population consisted of 24,943 women and men aged 40 years and older (mean age 65.5 ± 10.2 years) with fracture probability assessment (FRAX), self-reported falls for the previous year (categorized as none, 1, 2, or > 3) and fracture outcomes. Adjusted hazard ratios (HR) with 95 confidence intervals (CI) for time to fracture were estimated using Cox proportional hazards models. Results During mean observation time of 2.7 ± 1.0 years, 863 (3.5%) sustained one or more major osteoporotic fractures (MOF), 212 (0.8%) sustained a hip fracture, and 1210 (4.9%) sustained any incident fracture. Compared with no falls in the previous year (referent), there was a gradient of increasing risk for fracture with increasing number of falls (all P < 0.001). Results showed minimal attenuation with covariate adjustment. When adjusted for baseline fracture probability (FRAX score with BMD) the HR for MOF increased from 1.49 (95% CI 1.25–1.78) for one fall to 1.74 (1.33–2.27) for two falls to 2.62 (2.06–3.34) for ≥ 3 falls. HRs were similar for any incident fracture and slightly greater for prediction of hip fracture, reaching 3.41 (95% CI 2.19–5.31) for ≥ 3 previous falls. Conclusions Self-report number of falls in the previous year is strongly associated with incident fracture risk in the routine clinical practice setting, and this risk is independent of age, sex, BMD, and baseline fracture probability. Moreover, there is dose–response with multiple falls (up to a maximum of 3) conferring greater risk than a single fall.

Effects of anti-osteoporosis medications on radiological and clinical results after acute osteoporotic spinal fractures: a retrospective analysis of prospectively designed study Abstract Summary Effects of anti-osteoporosis medications such as anti-resorptive and anabolic agents on healing of osteoporotic spinal fracture were retrospectively investigated. The use of anabolic agent significantly enhanced fracture healing, reduced progressive collapse, and presented good pain relief. These findings suggest that proper selection of medication could improve initial management of acute osteoporotic spinal fractures (OSFs). Introduction Although anti-osteoporosis medications have beneficial effects on prevention of osteoporotic spinal fractures (OSFs), few studies have compared effects of medications on fracture healing following OSFs. Therefore, the purpose of this study was to elucidate the effects of different anti-osteoporosis medications on radiological and clinical outcomes after acute OSFs. Methods A total of 132 patients diagnosed with acute OSFs were enrolled and allocated into three groups [group I (n = 39, no anti-osteoporosis medication), group II (n = 66, bisphosphonate), and group III (n = 27, parathyroid hormone (PTH)]. Radiological parameters including magnetic resonance (MR) classification, occurrence of intravertebral cleft (IVC), and clinical outcomes such as numerical rating scale (NRS) and Oswestry disability index were assessed. Risk analyses for IVC and progressive collapse were done along the related factors and medication type. Results IVC sign was observed in 30 patients. The rate of IVC sign was lower in group III (7.4%) than that in group I (20.5%) or group II (30.3%), although the difference was not statistically significant. Moreover, the degree of NRS improvement was better in group III than that in group I or group II (5.7 vs. 3.1 vs. 3.5, p < 0.001). On multiple regression analysis, mid-portion type fracture in MR classification was a significant risk factor for progressive OSFs. The use of PTH showed significant lower incidences of occurrence of IVC (odds ratio (OR) = 0.160) and increase in height loss (OR = 0.325). Conclusions Different anti-osteoporosis medications presented different clinical and radiological results after acute OSFs. The use of anabolic agent significantly enhanced fracture healing, reduced progressive collapse, and presented better clinical outcomes. Proper selection of medication might improve initial management of acute OSFs.

FRAX-based intervention and assessment thresholds for osteoporosis in Iran Abstract Summary We compared the utility of the current Iranian guidelines that recommend treatment in women with a T-score ≤ − 2.5 SD with a FRAX-based intervention threshold equivalent to women of average BMI with a prior fragility fracture. Whereas the FRAX-based intervention threshold identified women at high fracture probability, the T-score threshold was less sensitive, and the associated fracture risk decreased markedly with age. Introduction The fracture risk assessment algorithm FRAX® has been recently calibrated for Iran, but guidance is needed on how to apply fracture probabilities to clinical practice. Methods The age-specific ten-year probabilities of a major osteoporotic fracture were calculated in women with average BMI to determine fracture probabilities at two potential intervention thresholds. The first comprised the age-specific fracture probabilities associated with a femoral neck T-score of − 2.5 SD, in line with current guidelines in Iran. The second approach determined age-specific fracture probabilities that were equivalent to a woman with a prior fragility fracture, without BMD. The parsimonious use of BMD was additionally explored by the computation of upper and lower assessment thresholds for BMD testing. Results When a BMD T-score ≤ − 2.5 SD was used as an intervention threshold, FRAX probabilities in women aged 50 years was approximately two-fold higher than in women of the same age but with an average BMD and no risk factors. The relative increase in risk associated with the BMD threshold decreased progressively with age such that, at the age of 80 years or more, a T-score of − 2.5 SD was actually protective. The 10-year probability of a major osteoporotic fracture by age, equivalent to women with a previous fracture rose with age from 4.9% at the age of 50 years to 17%, at the age of 80 years, and identified women at increased risk at all ages. Conclusion Intervention thresholds based on BMD alone do not effectively target women at high fracture risk, particularly in the elderly. In contrast, intervention thresholds based on fracture probabilities equivalent to a “fracture threshold” target women at high fracture risk.