Two-year results of a randomized placebo-controlled trial of vertebroplasty for acute osteoporotic vertebral fractures

We previously reported the results of a randomized controlled trial that found no benefit of vertebroplasty over a sham procedure for acute osteoporotic vertebral fractures up to 6 months. We report here the 12-month and 24-month clinical outcomes of this trial. Eligible participants (n = 78) were randomly assigned to receive either vertebroplasty (n = 38) or a sham procedure (n = 40). Randomization was stratified by treatment center, sex, and symptom duration (<6 weeks or ≥6 weeks). Participants, investigators (except the treating radiologists), and outcome assessors were blinded to group assignments. Enrolment occurred between April 2004 and October 2008 with follow-up completed October 2010. The primary outcome was overall pain measured on a scale of 0 (no pain) to 10 (maximal imaginable pain). Secondary outcomes included pain at rest and at night, disability, quality of life, perceived recovery, and adverse events, including incident clinically apparent vertebral fractures. At 12 and 24 months, complete data were available for 67 (86%) and 57 (73%) participants, respectively. At 12 months participants in the active group improved by 2.4 ± 2.7 (mean ± SD) units in overall pain compared with 1.9 ± 2.8 units in the sham group, adjusted between-group mean difference (MD) 0.3 (95% confidence interval [CI], –0.9 to 1.5), whereas at 24 months participants in the active group had improved by 3.0 ± 3.1 units compared with 1.9 ± 3.0 units in the sham group, MD 1.1 (95% CI, –0.3 to 2.4). No significant between-group differences were observed for any of the secondary efficacy outcomes at 12 or 24 months. There were no between-group differences in incident clinical vertebral fractures up to 24 months (active: n = 14, sham: n = 13), although the study had inadequate power for this outcome. These results provide further evidence that the use of this treatment in routine care is unsupported.

Sex- and age-specific associations between income and incident major osteoporotic fractures in Canadian men and women: a population-based analysis

We investigated sex- and age-specific associations between income and fractures at the hip, humerus, spine, and forearm in adults aged ≥50 years. Compared to men with the highest income, men with the lowest income had an increased fracture risk at all skeletal sites. These associations were attenuated in women.

The social gradient of fractures at any skeletal site in men and women: data from the Geelong Osteoporosis Study Fracture Grid.

Age-specific and age-standardized associations between socioeconomic status (SES) and fractures in adults showed a social gradient of fracture, irrespective of fracture site. Compared to the highest SES, males in the lowest SES group had a sixfold increased odds for any fracture, whilst females had a twofold increased odds.

Changes in quality of life associated with fragility fractures: Australian arm of the International Cost and Utility Related to Osteoporotic Fractures Study (AusICUROS).

We investigated change in health-related quality of life due to fracture in Australian adults aged over 50 years. Fractures reduce quality of life with the loss sustained at least over 12 months. At a population level, the loss was equivalent to 65 days in full health per fracture.

Interobserver Variability in the Treatment of Little Finger Metacarpal Neck Fractures

Purpose To address the null hypothesis that surgeons shown radiographs of little finger metacarpal neck fractures with measured fracture angulation would recommend surgery as often as surgeons shown unmarked radiographs. Methods Members of the Science of Variation Group, an international collaboration of fully trained orthopedic and trauma surgeons, were asked to review 20 little finger metacarpal neck fracture cases, which included a vignette and 3 high-quality radiographs. Members were then randomized to review radiographs with or without measured fracture angulation on the lateral view and select operative or nonoperative management. Results Surgeons shown radiographs with measured angulation were more likely to recommend surgery, and there was less variability among these surgeons, particularly for fractures with less angular deformity. Conclusions Measured fracture angulation has a small but significant influence on treatment recommendations for little finger metacarpal neck fractures.

A randomised controlled trial of low-dose aspirin for the prevention of fractures in healthy older people : protocol for the ASPREE-Fracture substudy

Background Disability, mortality and healthcare burden from fractures in older people is a growing problem worldwide. Observational studies suggest that aspirin may reduce fracture risk. While these studies provide room for optimism, randomised controlled trials are needed. This paper describes the rationale and design of the ASPirin in Reducing Events in the Elderly (ASPREE)-Fracture substudy, which aims to determine whether daily low-dose aspirin decreases fracture risk in healthy older people. Methods ASPREE is a double-blind, randomised, placebo-controlled primary prevention trial designed to assess whether daily active treatment using low-dose aspirin extends the duration of disability-free and dementia-free life in 19 000 healthy older people recruited from Australian and US community settings. This substudy extends the ASPREE trial data collection to determine the effect of daily low-dose aspirin on fracture and fall-related hospital presentation risk in the 16 500 ASPREE participants aged ≥70 years recruited in Australia. The intervention is a once daily dose of enteric-coated aspirin (100 mg) versus a matching placebo, randomised on a 1:1 basis. The primary outcome for this substudy is the occurrence of any fracture-vertebral, hip and non-vert-non-hip-occurring post randomisation. Fall-related hospital presentations are a secondary outcome. Discussion This substudy will determine whether a widely available, simple and inexpensive health intervention-aspirin-reduces the risk of fractures in older Australians. If it is demonstrated to safely reduce the risk of fractures and serious falls, it is possible that aspirin might provide a means of fracture prevention.

Higher dietary calcium intakes are associated with reduced risks of fractures, cardiovascular events, and mortality: a prospective cohort study of older men and women

The aim of this population-based, prospective cohort study was to investigate long-term associations between dietary calcium intake and fractures, non-fatal cardiovascular disease (CVD), and death from all causes. Participants were from the Melbourne Collaborative Cohort Study, which was established in 1990 to 1994. A total of 41,514 men and women (∼99% aged 40 to 69 years at baseline) were followed up for a mean (SD) of 12 (1.5) years. Primary outcome measures were time to death from all causes (n = 2855), CVD-related deaths (n = 557), cerebrovascular disease-related deaths (n = 139), incident non-fatal CVD (n = 1827), incident stroke events (n = 537), and incident fractures (n = 788). A total of 12,097 participants (aged ≥50 years) were eligible for fracture analysis and 34,468 for non-fatal CVD and mortality analyses. Mortality was ascertained by record linkage to registries. Fractures and CVD were ascertained from interview ∼13 years after baseline. Quartiles of baseline energy-adjusted calcium intake from food were estimated using a food-frequency questionnaire. Hazard ratios (HR) and odds ratios (OR) were calculated for quartiles of dietary calcium intake. Highest and lowest quartiles of energy-adjusted dietary calcium intakes represented unadjusted means (SD) of 1348 (316) mg/d and 473 (91) mg/d, respectively. Overall, there were 788 (10.3%) incident fractures, 1827 (9.0%) incident CVD, and 2855 people (8.6%) died. Comparing the highest with the lowest quartile of calcium intake, for all-cause mortality, the HR was 0.86 (95% confidence interval [CI] 0.76-0.98, ptrend  = 0.01); for non-fatal CVD and stroke, the OR was 0.84 (95% CI 0.70-0.99, ptrend  = 0.04) and 0.69 (95% CI 0.51-0.93, ptrend  = 0.02), respectively; and the OR for fracture was 0.70 (95% CI 0.54-0.92, ptrend  = 0.004). In summary, for older men and women, calcium intakes of up to 1348 (316) mg/d from food were associated with decreased risks for fracture, non-fatal CVD, stroke, and all-cause mortality.

New vertebral fractures after vertebroplasty: 2-year results from a randomised controlled trial

Summary: A randomised controlled trial of vertebroplasty (VP) versus placebo assessed the effect of VP on the risk of further vertebral fractures. While no statistically significant between-group differences for new or progressed fracture risk at 12 and 24 months were observed, we observed a consistent trend towards higher risk of any type of fracture in the group undergoing VP. Our analysis was underpowered, and further adequately powered studies are needed to be able to draw firm conclusions about further vertebral risk with vertebroplasty. Purpose: This study seeks to assess the effect of VP on the risk of further radiologically apparent vertebral fracture within two years of the procedure. Methods: We conducted a randomised placebo-controlled trial of VP in people with acute osteoporotic vertebral fracture. Eligible participants were randomly assigned to VP (n = 38) or placebo (n = 40). Cement volume and leakage were recorded for the VP group. Plain thoracolumbar radiographs were taken at baseline, 12 and 24 months. Two independent radiologists assessed these for new and progressed fractures at the same, adjacent and non-adjacent levels. Results: At 12 and 24 months, radiographs were available for 45 (58 %) and 47 (60 %) participants, respectively. There were no between-group differences for new or progressed fractures: 32 and 40 in the VP group after 12 and 24 months compared with 21 and 33 in the placebo group (hazard ratio (HR) 1.80, 95 % confidence interval (CI) 0.82 to 3.94). Similar results were seen when considering only adjacent (HR (95 % CI) 2.30 (0.57 to 9.29)) and non-adjacent (HR (95 % CI) 1.45 (0.55 to 3.81) levels. In all comparisons, there was a consistent trend towards higher risk of any type of fracture in the group undergoing VP. Within the VP group, fracture risk was unrelated to total (HR (95 % CI) 0.91 (0.71 to 1.17)) or relative (HR (95 % CI) 1.31 (0.15 to 11.48)) cement volume or cement leakage (HR (95 % CI) 1.20 (0.63 to 2.31)). Conclusion: For patients undergoing VP, our study did not demonstrate significant increases in subsequent fracture risk beyond that experienced by those with vertebral fractures who did not undergo the procedure. However, because of the non-significant numerical increases observed, studies with adequate power are needed to draw definite conclusions about fracture risk.

Humeral fractures in South-Eastern Australia: epidemiology and risk factors

In this study, we report the epidemiology and risk factors for humeral fractures (proximal humerus and shaft) among men and women residing in south-eastern Australia. Incident fractures during 2006 and 2007 were identified using X-ray reports (Geelong Osteoporosis Study Fracture Grid). Risk factors were identified using data from case-control studies conducted as part of the Geelong Osteoporosis Study. Median age of fracture was lower in males than females for proximal humerus (33.0 vs 71.2 years), but not for humeral shaft (8.9 vs 8.5 years). For females, proximal humerus fractures occurred mainly in the 70-79 and 80+ years age groups, whereas humeral shaft fractures followed a U-shaped pattern. Males showed a U-shaped pattern for both proximal humerus and humeral shaft fractures. Overall age-standardised incidence rates for proximal humerus fractures in males and females were 40.6 (95 % CI 32.7, 48.5) and 73.2 (95 % CI 62.2, 84.1) per 100,000 person years, respectively. For humeral shaft fractures, the age-standardised rate was 69.3 (95 % CI 59.0, 79.6) for males and 61.5 (95 % CI 51.9, 71.0) for females. There was an increase in risk of proximal humerus fractures in men with a lower femoral neck BMD, younger age, prior fracture and higher milk consumption. In pre-menopausal women, increased height and falls were both risk factors for proximal humerus fractures. For post-menopausal women, risk factors associated with proximal humerus fractures included a lower non-milk dairy consumption and sustaining a prior fracture. Humeral shaft fractures in both sexes were sustained mainly in childhood, while proximal humerus fractures were sustained in older adulthood. The overall age-standardised rates of proximal humerus fractures were nearly twice as high in females compared to males, whereas the incidence rates of humeral shaft fractures were similar.

The factors influencing the decision making of operative treatment for proximal humeral fractures

Background:
The factors influencing the decision making of operative treatment for fractures of the proximal humerus are debated. We hypothesized that there is no difference in treatment recommendations between surgeons shown radiographs alone and those shown radiographs and patient information. Secondarily, we addressed (1) factors associated with a recommendation for operative treatment, (2) factors associated with recommendation for arthroplasty, (3) concordance with the recommendations of the treating surgeons, and (4) factors affecting the inter-rater reliability of treatment recommendations.
Methods: A total of 238 surgeons of the Science of Variation Group rated 40 radiographs of patients with proximal humerus fractures. Participants were randomized to receive information about the patient and mechanism of injury. The response variables included the choice of treatment (operative vs nonoperative) and the percentage of matches with the actual treatment.
Results: Participants who received patient information recommended operative treatment less than those who received no information. The patient information that had the greatest influence on treatment recommendations included age (55%) and fracture me chanism (32%). The only other factor associated with a recommendation for operative treatment was region of practice. There was no significant difference between participants who were and were not provided with information regarding agreement with the actual treatment (operative vs nonoperative) provided by the treating surgeon.
Conclusion: Patient information - older age in particular - is associated with a higher likelihood of recommending nonoperative treatment than radiographs alone. Clinical information did not improve agreement of the Science of Variation Group with the actual treatment or the generally poor interobserver agreement on treatment recommendations

Patients presenting with fractures are likely to be vitamin D deficient: are we getting enough sun?

BACKGROUND: 25-Hydroxyvitamin D serves a crucial role in bone metabolism through its role on osteoclast and osteoblastic function. To assess the implication of vitamin D and its relationship to bone fracture and fracture force, we have examined vitamin D levels in patients requiring inpatient fracture management. METHODS: We performed serological testing of vitamin D levels, calcium, parathyroid hormone and liver function tests on patients admitted to our rural institution in southeastern Australia for inpatient fracture management. All participants completed a questionnaire designed to screen for potential contributing factors to bony fragility. Demographic data were also obtained including age, gender and body mass index. Fracture location and the type of inpatient management as well as the force of injury were included in our analysis. RESULTS: We recruited 100 patients to the study, with a median age of 72 (range 22-98) of whom 66 were women. Most had low-energy fractures (79%), treated by internal fixation (73%) or arthroplasty (9%) with 18 treated non-operatively. The majority of the patients were at best vitamin D insufficient, <75 nmol/L (77%), and 38% were vitamin D deficient (<50 nmol/L). Only 14 patients had a formal diagnosis of osteoporosis at presentation, with 63 patients claiming daily sun exposure in line with recommendations for vitamin D sufficiency. CONCLUSIONS: Our data suggest that the prevalence of vitamin D insufficiency and deficiency is common in patients presenting with fractures in southeastern Australia and is not confined to elderly patients. All patients with fractures should be assessed for vitamin D levels and treated in accordance with vitamin D deficiency guidelines.

Complications associated with operative fixation of acute midshaft clavicle fractures

The aim of this study was to review the complication rate and profile associated with surgical fixation of acute midshaft clavicle fracture in a large cohort of patients treated in a level I trauma centre.Patients and methods: We identified all patients who underwent surgical treatment of acute midshaft clavicle fracture between 2002 and 2010. The study group consisted of 138 fractures (134 patients). There were 107 males (78%) and 31 females (22%) and median age of 35 years (IQR 24-45). The most common mechanism of injury was a road traffic accident (78%). Sixty percent (n = 83) had an injury severity score of ≥ 15 indicating major trauma. The most common fracture type (75%) was simple or wedge comminuted (2B1) according to the Edinburgh classification. The median interval between the injury and operation was 3 days (IQR 1-6). Plate fixation was performed in 110 fractures (80%) and intramedullary fixation was performed in 28 fractures (20%). There were 85 males and 25 females in the plate fixation group with median age of 35 years (IQR: 25-45) There were 22 males and 6 females in intramedullary fixation group with median age of 31 years (IQR 24-42 years). Statistical analysis was performed using Independent sample t-test, Mann-Whitney test, and Chi-square test. Significant P-value was < 0.05.Results: The overall incidence of complication was 14.5% (n = 20). The overall nonunion rate 6%. Post operative wound infection occurred in 3.6% of cases. The incidence of complication associated with plate fixation was 10% (11 of 110 cases) compared to 32% associated with intramedullary fixation (9 of 28 cases) (P = 0.003). Thirty five percent of complications were related to inadequate surgical technique and potentially avoidable. Symptomatic hardware requiring removal occurred in 23% (n = 31) of patients. Symptomatic metalware was more frequent after plate fixation compared to intramedullary fixation (26% vs 7%, P = 0.03).Conclusions: Intramedullary fixation of midshaft clavicle fracture is associated with higher incidence of complications. Plate fixation is associated with a higher rate of symptomatic metalware requiring removal compared to intramedullary fixation. Approximately one in three complications may be avoided by attention to adequate surgical technique.

Interobserver agreement of Neer and AO classifications for proximal humeral fractures

BACKGROUND:The classification of proximal humeral fractures remains challenging. The two main classification systems used, the Neer and the AO classification, have both been shown to have less than ideal interobserver agreement. Agreement in classification is required, however, to guide fracture management.

METHOD:Data from the Victorian Orthopaedic Trauma Outcomes Registry were collected and the X-rays of 104 proximal humeral fractures were reviewed by three orthopaedic consultants. They classified the fractures according to the Neer and AO classifications, as well as their simplified versions. Interobserver agreement was then assessed using kappa statistics.

RESULTS:Interobserver agreement was better overall in the Neer classification, which was moderate (kappa = 0.40-0.58), than the AO classification, which was fair to moderate (kappa = 0.31-0.54). When simplified, the Neer and AO classification interobserver agreement remained similar.

CONCLUSION:The classification of proximal humeral fractures with both the Neer and the AO systems remains difficult with minimal improvements seen when reducing the number of categories in each classification system. From these results, the Neer classification system would appear slightly more useful in clinical practice to guide treatment.