Purpose

To compare the efficacy and safety of balloon kyphoplasty (BKP) to non-surgical management (NSM) over 24 months in patients with acute painful fractures by clinical outcomes and vertebral body kyphosis correction and surgical parameters.

Balloon kyphoplasty (BKP) is a minimally invasive treatment for vertebral fractures (VCF) aiming to correct deformity using balloon tamps and bone cement to stabilize the body. Patients with 1 - 3 non-traumatic acute VCF were enrolled within three months of diagnosis and randomly assigned to receive either BKP (N=149) or nonsurgical care (N=151). Follow-up was 2 years.

The mean SF-36 physical component summary (PCS) score improved 5.1 points (95%CI, 2.8-7.4; p<0.0001) more in the kyphoplasty than the nonsurgical group at one month, the primary endpoint of the study.

Kyphoplasty improved the PCS score by an average of 3.0 points (95%CI, 1.6-5.4; p=0.002) during the two-year follow-up. There was a significant interaction between treatment and follow-up time (p=0.003), indicating that the treatment effect over the year is not uniform across follow-up; a result from early improvement that persists in the kyphoplasty group whereas the nonsurgical group shows more incremental improvement over time.

Overall, patients assigned to kyphoplasty also had statistically significant improvements over the two years compared to the control group in global quality of life (EQ-5D), pain relief (VAS), back disability (RMDQ) and days of limited activity (within a two-week period).

There was no statistical significant difference between groups in the number of patients with adverse events or new VCF's over 24 months.

Compared to the control, BKP improved quality of life and reduced back pain and disability and did not increase adverse events including the risk of new vertebral fractures over 2 years.

Background

Vertebral body compression fractures (VCFs) impair quality of life (QOL) and increase patient morbidity and mortality. The international, multicentre, randomised, controlled Fracture Reduction Evaluation (FREE) trial was initiated to compare effectiveness and safety of Balloon kyphoplasty (BKP) to non-surgical management (NSM) for the treatment of acute painful VCFs. We describe the primary endpoint of the ongoing 2-year study.

Fracture prevention has so far been studied in patients included on the basis of low bone density, and not after a fracture. In this study the inclusion criteria was a new hip fracture irrespective of bone density. An international, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial (HORIZON-RFT) studied whether the bisphosphonate, zoledronic acid (ZOL) 5 mg, reduced subsequent clinical fractures in men and women ≥50 yrs after a hip fracture.

Methods: Patients with hip fracture were included. They received daily vitamin D3 and calcium supplements. Of 2127 randomized, 2111 were treated with once-yearly IV infusions of ZOL 5 mg (n=1054) or placebo (PBO; n=1057) and followed until 211 experienced new clinical fractures (the primary efficacy endpoint).

Results: Baseline characteristics were similar. Median age was 76 yrs (range, 50–98); 76% were women. Clinical fractures occurred in 92 ZOL and 139 PBO patients. 2-year cumulative event rates were 8.59% and 13.88%, respectively (Kaplan-Meier); relative risk reduction was 35% (HR=0.65; 95% CI: 0.50–0.84; P=.0012). ZOL reduced risk for clinical vertebral and nonvertebral fractures vs. PBO by 46% (HR=0.54; 95% CI: 0.32–0.92; P=.0210) and 27% (HR=0.73; 95% CI: 0.55–0.98; P=.0338), respectively. ZOL reduced risk of hip fractures by 30% vs. PBO (HR=0.70; 95% CI: 0.41–1.19; P=NS). AEs and SAEs were comparable between groups. There were no significant differences in cardiovascular parameters or long-term renal function. No cases of ONJ were reported. Death occurred in 9.58% of ZOL patients vs 13.34% PBO, a 28% lower mortality risk (HR=0.72; 95% CI: 0.56–0.93, P=.0117).

Conclusions: Subjects with a new hip fracture treated with annual IV ZOL infusions experienced significantly fewer clinical fractures vs. placebo. ZOL was well tolerated with a favorable safety profile. This is the first trial demonstrating a mortality benefit for an antiresorptive agent.

Purpose: Balloon kyphoplasty (BKP) is a minimally invasive treatment for acute vertebral compression fractures (VCF) that aims both to correct associated vertebral deformity (reduce) and stabilize the fracture by injecting bone cement. We performed the first multicenter randomized trial to assess the effect of BKP.

Method: Patients with 1–3 non-traumatic vertebral compression fractures diagnosed within 3 months were randomly assigned to receive either BKP (N=149) or usual nonsurgical care (NSC) (N=151). Measurements of quality of life, back pain and function, days of disability and bed rest were assessed at baseline, 1, 3, 6 and 12 months.

Results: The primary outcome measure, the difference between groups in change from baseline scores in the physical component summary of the SF-36 questionnaire, improved 3.5 points (95% CI, 1.6 to 5.4; p=0.0004) more in the BKP group when averaged across 12 months of follow-up. Compared with the NSC group, those assigned to BKP also had greater improvement in quality of life and back function throughout 12 months of follow-up as measured by the EuroQol and Roland-Morris scales; a difference of 0.14 points (95% CI, 0.05 to 0.23; p=0.0023) more and 3.2 points (95% CI, 1.7 to 3.8; p< 0.0001) and reported fewer days of limited activity in the previous 2 weeks due to back pain (2.5 fewer days; 95% CI, 1.2 to 3.8; p=0.0001). New radiographically detected vertebral fractures occurred in 41.8% of subjects in the kyphoplasty and 37.8% in the nonsurgical group (4% difference; 95% CI −7.5 to 15.6; p=0.5).

Conclusion: Compared to nonsurgical treatment, balloon kyphoplasty improved multiple measurements of quality of life, back pain and disability that last at least one year after the procedure. No difference is seen between groups in radiographically detected VCF’s (Clinicaltrials.gov number, NCT00211211).

Background: Balloon kyphoplasty is a minimally invasive treatment for acute vertebral fractures that aims to reduce and correct vertebral deformity by inserting expandable balloon tamps and then stabilize the body by filling it with bone cement. The effect of balloon kyphoplasty on quality of life has not been tested in a randomized trial.

Methods: Patients with up to 3 non-traumatic acute vertebral compression fractures were enrolled within 3 months of diagnosis and randomly assigned to receive either balloon kyphoplasty (N=149) or usual nonsurgical care (N=151). Measurements of quality of life, back pain and function, and days of disability and bed rest and spine radiographs were assessed through 12 months of follow-up.

Results: Compared with those assigned to nonsurgical care, participants assigned to balloon kyphoplasty had 5.2 points (95% CI, 2.9 to 7.4; p< 0.0001) greater improvement in the physical component of the SF-36 quality of life questionnaire at one month and 1.5 points (95% CI, − 0.8 to 3.8; p=0.2) at twelve months. Those in the balloon kyphoplasty group also had greater improvement in quality of life by the EuroQol questionnaire at one (0.18 points; 95% CI, 0.08 to 0.28; p=0.0003) and twelve months (0.12 points; 95% CI, 0.01 to 0.22; p=0.025) and improved disability by the Roland-Morris scale at one month (4.0 points; 95% CI, 2.6 to 5.5; p< 0.0001) and twelve months (2.6 points; 95% CI, 1.0 to 4.1; p=0.0012). Balloon kyphoplasty patients had less back pain on a 0 to 10-point numeric rating scale at seven days (2.2 points; 95% CI, 1.6 to 2.8; p< 0.0001) and twelve months (0.9 points; 95% CI, 0.3 to 1.5; p=0.0034) and reported fewer days of limited activity at one month (2.9 days per 2 weeks; 95% CI, 1.3 to 4.6; p=0.0004) and twelve months (1.6; 95% CI, − 0.1 to 3.3; p=0.068). Fewer patients assigned to balloon kyphoplasty took pain medications or used walking aids during follow-up. There was no significant difference in the number of patients with adverse events or serious adverse events in the kyphoplasty and nonsurgical groups. New radiographically detected vertebral fractures occurred in 41.8% of subjects in the balloon kyphoplasty and 37.8% in the nonsurgical group (4% difference; 95% CI − 7.5 to 15.6; p=0.5) and were not statistically different.

Conclusion: Compared to nonsurgical treatment, balloon kyphoplasty safely improved quality of life and reduced back pain, disability and the use of pain medications and walking aids. Significant improvements in multiple measurements of quality of life, pain and disability continue for at least 1 year. Balloon kyphoplasty did not increase adverse events including the risk of vertebral fractures (Clinicaltrials.gov number, NCT00211211).

Objectives: A recent meta-analysis (JAMA. 2005;293:2257–2264) reported that supplementation with oral vitamin D 700–800 IU/day reduces the risk of hip or any nonvertebral fracture in elderly individuals by approximately 25%. However, this metaanalysis was unable to define the role of additional calcium supplementation. The aim of the current study was to assess the need for calcium supplementation in individuals receiving vitamin D for the prevention of hip and nonvertebral fractures.

Methods: MEDLINE (search terms: ‘vitamin D’ AND ‘hip fracture’), bibliographies of articles retrieved, and the authors’ reference files were used to identify randomized controlled trials (RCTs) of oral vitamin D supplementation with or without calcium supplementation vs placebo/no treatment in postmenopausal women and/or older men (over 50 years) specifically reporting hip fracture risk. Data extraction was independent by

Results: All pooled analyses are based on random-effects models. Based on 4 RCTs (9083 subjects), the pooled relative risk (RR) of hip fracture for vitamin D supplementation alone was 1.10 (95% confidence intervals [CI], 0.89 to 1.36). No between-trial heterogeneity was observed. For the 5 RCTs (9227 subjects) of vitamin D supplementation with calcium supplementation, the pooled RR for hip fracture was 0.79 (95% CI, 0.64 to 0.97). There was no heterogeneity between trials. The RRs for all nonvertebral fracture were 0.98 (0.83 to 0.16) for vitamin D alone and 0.84 (0.73 to 0.96) for vitamin D with calcium, with moderate heterogeneity between trials. In an adjusted indirect comparison of the summary RRs from the 2 meta-analyses, the RR for hip fracture for vitamin D with calcium vs vitamin D alone was 0.72 (95% CI, 0.53 to 0.96) and the RR for all non-vertebral fractures was 0.77 (95% CI, 0.60 to 0.99).

Conclusions: Oral vitamin D supplementation appears to reduce the risk of hip and any nonvertebral fractures only when calcium supplementation is added. Our findings suggest that to optimize clinical efficacy, vitamin D supplementation should be complemented with calcium supplements.

Objectives: To determine the magnitude and duration of excess mortality after hip fracture among postmenopausal women.

Methods: We conducted a systematic review and meta-analysis of the literature to estimate the pooled relative risk of death after hip fracture by time since fracture. We selected only controlled studies that reported data on postmenaupausal women aged 50 years or older, carried out a life-table analysis, and displayed the survival curves of the hip-fracture group and an ageand sex-matched control group. Using random-effects models we calculated the pooled relative risk of death with 95% confidence intervals (95%CI) by time since fracture.

Results: Twenty-three studies contributed to this meta-analysis. The pooled relative risk of dying within three, six, twelve, and twenty-four months following hip fracture was 5.06 (95%CI: 4.31, 5.93), 3.92 (95%CI: 3.11, 4.94), 2.71 (95%CI: 2.33, 3.14), and 2.02 (95%CI: 1.83, 2.23), respectively. Thereafter, excess mortality remained relatively constant. The relative risk of mortality at five years, ten years, and fifteen years post-fracture was 1.44 (95%CI: 1.29, 1.62), 1.40 (95%CI: 1.35, 1.45), and 1.36 (95%CI, 1.31, 1.41), respectively.

Conclusions: Excess mortality among postmenopausal women having suffered a hip fracture was most apparent immediately after the event, declined steeply during the first years post-fracture, but did not return to that of age- and sex-matched controls, even at the longest duration of follow-up. The impact of a hip fracture on excess mortality among postmenopausal women continued for up to 15 years.

Purpose: We conducted a prospective study among elderly women with a first hip fracture to document survival and functional outcome, and to determine whether outcomes differ by fracture type.

Methods: The design was a one-year prospective cohort study in the context of standard day-to-day clinical practice. The main outcome measures were survival and functional outcome, both at hospital discharge and one year later. Functional outcome was assessed using the Rapid Disability Rating Scale version-2.

Results: Of the 170 women originally enrolled, 86 (51%) had an intertrochanteric and 84 (49%) a femoral neck fracture. There were no significant differences between the two groups with respect to median age (80 and 78 years, respectively), type and number of comorbidities, and prefracture residence at the time of injury. At hospital discharge, intertrochanteric hip-fracture patients had a higher mortality (relative risk [RR] 9.8; 95% confidence interval [CI]: 1.3 to 74.6; p=0.006) and were functionally more impaired (0.4 units difference in ability to walk independently; p=0.005). One year later, mortality was still significantly higher after intertrochanteric fracture (RR 2.5; 95% CI: 1.3 to 5.1; p=0.008), but functional outcome among surviving patients was similar in both groups. During the one-year period after hospital discharge, a significant functional recovery was observed regardless of fracture type (improvement by 3.9 units [p=0.003] and by 2.6 units [p=0.015] in patients with intertrochanteric and femoral neck fractures, respectively). In both groups, this recovery was reflected in a significant improvement in walking ability (p< 0.001 and p=0.006, respectively) and mobility (p=0.004 and p< 0.001, respectively).

Conclusions: We conclude that intertrochanteric fractures are associated with increased mortality compared to femoral neck fractures. Functional outcome differs according to fracture type at hospital discharge, but these differences do not persist over time. Our data provide evidence that these findings cannot be explained by differences in age or comorbidity. Differences in survival suggest that the two main types of hip fractures should be analyzed separately in clinical and epidemiological studies.

Aims: To explore potential predictors of functional outcome one year after the injury in elderly women who sustained a displaced intracapsular hip fracture and who were treated with internal fixation, hemiarthroplasty, or total hip arthroplasty.

Methods: Eighty-four women aged > 50 years were enrolled on a consecutive basis in this one-year prospective cohort study reflecting standard day-to-day clinical practice. The main outcome measure was the Rapid Disability Rating Scale version-2 applied at hospital discharge and one year later.

Results: The total hip arthroplasty group was younger (p< 0.001) and had a better functional status than the internal fixation or hemiarthroplasty groups (p< 0.001) at hospital discharge. One year later, the best function was still observed in the total arthroplasty group, but the differences were small and failed to achieve the level of statistical significance. During that one-year period, walking ability or mobility did not change significantly after total hip arthroplasty, but a significant proportion of the women developed cognitive impairment, including mental confusion, uncooperativeness, and depression (p< 0.001).

Overall, the most significant predictors of poor functional status one year after fracture were increasing age (p=0.005), living in an institution at time of injury (p=0.034), and poor functional status at discharge (p< 0.001).

Conclusions: In elderly women with a displaced intra-capsular hip fracture, total hip arthroplasty is associated with a functional benefit within the first months after surgery. However, the extent to which this functional benefit is maintained over time, is less clear. Our results support the need for randomised clinical trials among elderly women with a displaced intracapsular hip fracture to quantify the extent to which the early functional benefit of total hip arthroplasty is maintained in the long run or compromised by progressive cognitive impairment and other negative determinants of functional outcome.

Aims: The aim of our study was to compare relative risk of hip fracture after wrist or spine fracture, in both men and women. Methods: We performed a systematic literature review of cohort studies reported since 1982 that included low-trauma wrist or spine fracture as a risk factor for subsequent hip fracture among (white) women and men aged 50 years or older. A fixed effects meta-analysis was used to calculate a common relative risk (RR) with 95% confidence interval (95% CI). Results: Ten cohort studies (six from the U.S.A. and four from Europe) contributed to this meta-analysis. Among postmenopausal women, RRs for future hip fracture after wrist and spine fracture were 1.53 (95% CI 1.34–1.74, p< 0.001) and 2.22 (95% CI 1.95–2.52, p< 0.001), respectively. The RR was significantly higher after spine fracture than after wrist fracture (p< 0.001). Among ageing men, these RRs for future hip fracture were 3.26 (95% CI 2.08–5.11, p< 0.001) and 3.54 (95% CI 2.01–6.23, p< 0.001), respectively. In contrast to the observation in women, this difference was not statistically significant (p=0.82).

The RR was significantly higher in men than in women after wrist fracture (p=0.002), but not after spine fracture (p=0.12). Conclusions: Recent studies have shown consistent and strong prospective associations of hip fracture with previous wrist or spine fracture among postmenopausal women. The findings of our meta-analysis confirm these results and extend them to ageing men. In addition, our results indicate that wrist and spine fractures are equally important risk factors for future hip fracture in ageing men.

Aims:We conducted a prospective study among elderly women with a femoral neck fracture to determine if medical care costs during the one-year period after hospital discharge differ by surgical procedure type. In addition, we analysed potential predictors of costs. Methods: The design was a one-year prospective cohort study assessing day-to-day clinical practice. Eighty-four women were enrolled. Direct costs of care were documented during the oneyear period after hospital discharge and expressed in Euro (€) per hip-fracture patient. Multiple regression analyses were performed to explore potential predictors of costs. Results: Three fracture groups were defined by the type of surgical repair. Total-hiparthroplasty patients were significantly younger than hemiarthroplasty or internal-fixation patients (median age 71, 81, and 80 years, respectively; p = 0.001). Average costs during the one-year follow up period after hospital discharge were lower after total hip arthroplasty (e 9,486) than after hemiarthroplasty (€ 12,146) or internal fixation (€ 15,687), although these trends failed to achieve the level of statistical significance (p = 0.322). A multivariate regression model identified two significant determinants of increased costs: increasing age (p = 0.023) and living in an institution at time of injury (p = 0.004). Conclusions: Direct costs of care during the one-year period after hospital discharge among elderly women with a femoral neck fracture do not depend on the type of surgical procedure. Increasing age and living in an institution at time of injury, on the other hand, are strong predictors of increased costs during the one-year period after hospital discharge.