Russel Burge

Tibia shaft fractures: costly burden of nonunions

BackgroundTibia shaft fractures (TSF) are common for men and women and cause substantial morbidity, healthcare use, and costs. The impact of nonunions on healthcare use and costs is poorly described. Our goal was to investigate patient characteristics and healthcare use and costs associated with TSF in patients with and without nonunion.MethodsWe retrospectively analyzed medical claims in large U.S. managed care claims databases (Thomson Reuters MarketScan®, 16 million lives). We studied patients ≥ 18 years old with a TSF diagnosis (ICD-9 codes: 823.20, 823.22, 823.30, 823.32) in 2006 with continuous pharmaceutical and medical benefit enrollment 1 year prior and 2 years post-fracture. Nonunion was defined by ICD-9 code 733.82 (after the TSF date).ResultsAmong the 853 patients with TSF, 99 (12%) had nonunion. Patients with nonunion had more comorbidities (30 vs. 21, pre-fracture) and were more likely to have their TSF open (87% vs. 70%) than those without nonunion. Patients with nonunion were more likely to have additional fractures during the 2-year follow-up (of lower limb [88.9% vs. 69.5%, P < 0.001], spine or trunk [16.2% vs. 7.2%, P = 0.002], and skull [5.1% vs. 1.3%, P = 0.008]) than those without nonunion. Nonunion patients were more likely to use various types of surgical care, inpatient care (tibia and non-tibia related: 65% vs. 40%, P < 0.001) and outpatient physical therapy (tibia-related: 60% vs. 42%, P < 0.001) than those without nonunion. All categories of care (except emergency room costs) were more expensive in nonunion patients than in those without nonunion: median total care cost

Does Teriparatide Improve Femoral Neck Fracture Healing: Results From A Randomized Placebo-controlled Trial.

25,556 vs.

Lifestyle-Related Metabolic Disorders, Osteoporosis, and Fracture Risk in Asia: A Systematic Review

11,686, P < 0.001. Nonunion patients were much more likely to be prescribed pain medications (99% vs. 92%, P = 0.009), especially strong opioids (90% vs. 76.4%, P = 0.002) and had longer length of opioid therapy (5.4 months vs. 2.8 months, P < 0.001) than patients without nonunion. Tibia fracture patterns in men differed from those in women.ConclusionsNonunions in TSF’s are associated with substantial healthcare resource use, common use of strong opioids, and high per-patient costs. Open fractures are associated with higher likelihood of nonunion than closed ones. Effective screening of nonunion risk may decrease this morbidity and subsequent healthcare resource use and costs.

Systematic review of raloxifene in postmenopausal Japanese women with osteoporosis or low bone mass (osteopenia)

AbstractBackground There is a medical need for therapies that improve hip fracture healing. Teriparatide (Forteo®/ Forsteo®, recombinant human parathyroid hormone) is a bone anabolic drug that is approved for treatment of osteoporosis and glucocorticoid-induced osteoporosis in men and postmenopausal women at high fracture risk. Preclinical and preliminary clinical data also suggest that teriparatide may enhance bone healing.Questions/purposesWe wished to test the hypotheses that treatment with teriparatide versus placebo would improve femoral neck fracture healing after internal fixation as measured by (1) frequency of revision surgery, (2) radiographic fracture healing, and (3) other outcomes including pain control, gait speed, and safety.MethodsWe initiated two separate, but identically designed, clinical trials to meet FDA requirements to provide substantial evidence to support approval of a new indication. The two prospective, randomized double-blind, placebo-controlled Phase III studies were designed to evaluate the effect of subcutaneous teriparatide (20 μg/day) for 6 months versus placebo on fracture healing at 24 months. The trials were conducted concurrently with a planned enrollment of 1220 patients per trial. However, enrollment was stopped owing to very slow patient accrual, and an a priori decision was made to pool the results of those studies for statistical analyses before study completion; pooling was specified in both protocols. Randomization was stratified by fixation (sliding hip screw or multiple cancellous screws) and fracture type (displaced or nondisplaced). An independent Central Adjudication Committee reviewed revision surgical procedures and radiographs. A total of 159 patients were randomized in the two trials (81 placebo, 78 teriparatide). The combined program had very low power to detect the originally expected treatment effect but had approximately 80% power to detect a larger difference of 12% between treatment groups for risk of revision surgery.ResultsThe proportion of patients undergoing revision surgery at 12 months was 14% (11 of 81) in the placebo group versus 17% (13 of 78) in the teriparatide group. Central Adjudication Committee review excluded two of these patients treated with placebo from the primary analysis. After exclusions, the proportion of patients who did not undergo revision surgery at 12 months (primary endpoint) was not different between the study and placebo groups, at 88% in the placebo group (90% CI, 0.79–0.93) versus 84% in the teriparatide group (90% CI, 0.75–0.90; p = 0.743). There also were no differences between groups in the proportion of patients achieving radiographic fracture healing at 12 months (75% [61 of 81] placebo versus 73% [57 of 78] teriparatide; odds ratio, 0.89; 90% CI, 0.46–1.72; p = 0.692) or in measures of pain control (such as pain during ambulation, 92% [55 of 62] placebo versus 91% [52 of 57] teriparatide; odds ratio, 0.91; 90% CI, 0.25–3.37; p = 0.681). The frequency of patients reporting adverse events was 49% [40 of 81] in the placebo group versus 45% [35 of 78] in the teriparatide group (p = 0.634) during the 6-month treatment period.ConclusionsThe small sample size limited this study’s power to detect potential differences, and the results are exploratory. With the patients available, teriparatide did not decrease the risk of revision surgery, improve radiographic signs of fracture healing, or decrease pain compared with the placebo. The adverse event data observed were consistent with the teriparatide safety profile. Functional and health outcome data from the studies may help improve our understanding of patients recovering from femoral neck fractures. Further large controlled studies are required to determine the effect of teriparatide on fracture healing.Level of EvidenceLevel II, prospective study.

Osteoporosis and treatments in Japan: management for preventing subsequent fractures

BACKGROUND The prevalence of both lifestyle-related metabolic disorders and osteoporosis is increasing in Asia. OBJECTIVES To conduct a systematic review of the published literature to identify studies examining disorders of glucose and lipid metabolism (type 2 diabetes, hyperglycemia, hypercholesterolemia, hyperlipidemia, dyslipidemia, metabolic syndrome [MetS], and atherosclerosis) as risk factors for osteoporosis and fracture in Asian populations. Studies examining the relationship between metabolic disorders and bone mineral density (BMD) were also included. METHODS EMBASE (including MEDLINE) and the Cochrane Library were searched. Studies conducted only within Asia, which reported multivariate analysis with a sample size of 200 or more subjects, were included. RESULTS A total of 32 studies were included. All six studies examining diabetes and fracture found that subjects with diabetes had a significantly higher risk of fracture than did subjects without diabetes (risk estimate range 1.26-4.73). Two studies found that subjects with atherosclerosis had a significantly higher risk of fracture (risk estimate range 1.10-2.52). Studies consistently reported that MetS is likely associated with osteoporosis or decreased BMD in men but not women. No consistent association was found for diabetes and BMD, with studies reporting contrasting results. There was limited evidence investigating lipid metabolism and hyperglycemia and risk of fracture or bone loss in Asian populations. CONCLUSIONS These findings suggest that diabetes is a risk factor for fracture in Asian populations. MetS may be associated with bone loss in Asian men and atherosclerosis associated with increased fractures; however, caution is needed interpreting these findings given limitations in study design.

Retrospective database study to assess the economic impact of hip fracture in the United Kingdom.

Purpose To systematically review the literature describing the efficacy, effectiveness, and safety of raloxifene for postmenopausal Japanese women with osteoporosis or low bone mass (osteopenia). Materials and methods Medline via PubMed and Embase was systematically searched using prespecified terms. Retrieved publications were screened and included if they described randomized controlled trials or observational studies of postmenopausal Japanese women with osteoporosis or osteopenia treated with raloxifene and reported one or more outcome measures (change in bone mineral density [BMD]; fracture incidence; change in bone-turnover markers, hip structural geometry, or blood–lipid profile; occurrence of adverse events; and change in quality of life or pain). Excluded publications were case studies, editorials, letters to the editor, narrative reviews, or publications from non-peer-reviewed journals; multidrug, multicountry, or multidisease studies with no drug-, country-, or disease-level analysis; or studies of participants on dialysis. Results Of the 292 publications retrieved, 15 publications (seven randomized controlled trials, eight observational studies) were included for review. Overall findings were statistically significant increases in BMD of the lumbar spine (nine publications), but not the hip region (eight publications), a low incidence of vertebral fracture (three publications), decreases in markers of bone turnover (eleven publications), improved hip structural geometry (two publications), improved blood–lipid profiles (five publications), a low incidence of hot flushes, leg cramps, venous thromboembolism, and stroke (12 publications), and improved quality of life and pain relief (one publication). Conclusion Findings support raloxifene for reducing vertebral fracture risk by improving BMD and reducing bone turnover in postmenopausal Japanese women with osteoporosis or osteopenia. Careful consideration of fracture risk and the risk–benefit profile of antiosteoporosis medications is required when managing patients with osteoporosis.

Adherence and Persistence with Once-Daily Teriparatide in Japan: A Retrospective, Prescription Database, Cohort Study

Prevalent fractures are major contributors to an increased risk of subsequent fractures, particularly in people with osteoporosis. While many studies have been conducted to assess the incidence of fracture in Japanese people with osteoporosis, far fewer have been conducted to assess the risk of subsequent fractures. This article reviews the morbidity, mortality, and risk of fracture in patients who are at high risk of subsequent fracture in Japan and the current treatment options available for these patients. Osteoporotic fractures in Japan are associated with high morbidity and mortality that result in significant financial and social costs. The rise in the proportion of elderly women in the Japanese population is contributing to a greater proportion of people with osteoporotic fractures and the high cost of osteoporosis. Although hip fractures have a significant effect on costs, a greater proportion of the Japanese population experience vertebral fractures. An increase in the incidence of vertebral fractures is concerning because preexisting vertebral fractures in older patients are associated with an increased risk of subsequent fractures. Hence, there is a clear rationale for pharmacological treatment of patients with prevalent vertebral fractures, or for those who are hospitalized or undergo surgery for osteoporotic fractures. Several pharmacological therapies are now available in Japan for the treatment of patients with osteoporosis. Understanding the consequences of subsequent fractures and the treatment options available for patients at high risk of subsequent fractures may contribute to clinical decision-making and improved outcomes for patients with osteoporosis.

Fractures in women treated with raloxifene or alendronate: a retrospective database analysis.

Abstract Objective: Publications containing recent, real-world data on the economic impact of hip fractures in the UK are lacking. This retrospective electronic medical records database analysis assessed medication and healthcare resource use, direct healthcare costs, and factors predicting increased resource use and costs in adult UK hip fracture patients. Methods: Data were obtained from the Clinical Practice Research Datalink linked to the Hospital Episode Statistics for adult patients hospitalized for their first hip fracture between January 1, 2006 and March 31, 2011 (index event); healthcare costs were calculated from the National Health Service perspective using 2011–2012 cost data. Results: Data from 8028 patients were analyzed. Resource use and costs were statistically significantly higher in the year following fracture (mean total [standard deviation (SD)] cost £7359 [£14,937]) compared with the year before fracture (mean total [SD] cost £3122 [£9435]; p < 0.001), and were similar to the total amount of the index hospitalization (mean total [SD] cost £8330 [£2627]). Multivariate regression analysis (using an estimated generalized linear model) showed that older age, male gender, higher comorbidity, osteoporosis, discharge to another institution compared with home, and pre-index hospitalization and outpatient visits were associated with increased post-index hospitalization healthcare costs (all p < 0.05). Conclusions: Although we did not capture all pre- and post-index costs and healthcare utilization, this study provides important insights regarding the characteristics of patients with hip fracture, and information that will be useful in burden-of-illness and economic analyses.

Rapid improvements in health-related quality of life and itch with ixekizumab treatment in randomized phase 3 trials: results from UNCOVER-2 and UNCOVER-3

Adherence and persistence with osteoporosis treatments are essential for reducing fracture risk. Once-daily teriparatide is available in Japan for treating osteoporosis in patients with a high risk of fracture. The study objective was to describe real-world adherence and persistence with once-daily teriparatide 20 μg during the first year of treatment for patients who started treatment during the first eight months of availability in Japan. This prescription database study involved patients with an index date (first claim) between October 2010 and May 2011, a preindex period ≥6 months, and a postindex period ≥12 months and who were aged >45 years. Adherence (medication possession ratio (MPR)) and persistence (time from the start of treatment to discontinuation; a 60-day gap in supply) were calculated. A total of 287 patients started treatment during the specified time period; 123 (42.9%) were eligible for inclusion. Overall mean (standard deviation) adherence was 0.702 (0.366), with 61.0% of patients having high adherence (MPR > 0.8). The percentage of patients remaining on treatment was 65.9% at 180 days and 61.0% at 365 days. Our findings suggest that real-world adherence and persistence with once-daily teriparatide in Japan are similar to that with once-daily teriparatide in other countries and with other osteoporosis medications.

Association of teriparatide adherence and persistence with clinical and economic outcomes in Medicare Part D recipients: a retrospective cohort study

BackgroundRaloxifene and alendronate are anti-resorptive therapies approved for the prevention and treatment of postmenopausal osteoporosis. Raloxifene is also indicated to reduce the risk of invasive breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high risk of invasive breast cancer. A definitive study comparing the fracture effectiveness and rate of breast cancer for raloxifene and alendronate has not been published. The purpose of this retrospective cohort study was to evaluate fracture and breast cancer rates among patients treated with raloxifene or alendronate.MethodsFemales ≥45 years who initiated raloxifene or alendronate in 1998–2006 Truven Health Analytics MarketScan® Databases, had continuous enrollment 12 months prior to and at least 12 months after the index date, and had a treatment medication possession ratio ≥80% were included in this study. Rates of vertebral and nonvertebral fractures and breast cancer during 1, 3, 5, 6, 7, and 8 years of treatment with raloxifene or alendronate were evaluated. Fracture rates were adjusted for potential treatment bias using inverse probability of treatment weights. Multivariate hazard ratios were estimated for vertebral and nonvertebral fractures.ResultsRaloxifene patients had statistically significantly lower rates of vertebral fractures in 1, 3, 5, and 7 years and for nonvertebral fractures in 1 and 5 years. There were no statistically significant differences in the adjusted fracture rates between raloxifene and alendronate cohorts, except in the 3-year nonvertebral fracture rates where raloxifene was higher. Multivariate hazard ratios of raloxifene versus alendronate cohorts were not significantly different for vertebral and nonvertebral fracture in 1, 3, 5, 6, 7, and 8 years. Unweighted and weighted breast cancer rates were lower among raloxifene recipients.ConclusionsPatients treated with alendronate and raloxifene had similar adjusted fracture rates in up to 8 years of adherent treatment, and raloxifene patients had lower breast cancer rates.