Safety, effectiveness and predictors for early reoperation in therapeutic and prophylactic vertebroplasty: short-term results of a prospective case series of patients with osteoporotic vertebral fractures

Abstract Introduction Vertebroplasty (VP) is a cost-efficient alternative to kyphoplasty; however, regarding safety and vertebral body (VB) height restoration, it is considered inferior. We assessed the safety and efficacy of VP in alleviating pain, improving quality of life (QoL) and restoring alignment. Methods In a prospective monocenter case series from May 2007 until July 2008, there were 1,408 vertebroplasties performed during 319 interventions in 306 patients with traumatic, lytic and osteoporotic fractures. The 249 interventions in 233 patients performed because of osteoporotic vertebral fractures were analyzed regarding demographics, treatment and radiographic details, pain alleviation (VAS), QoL improvement (NASS and EQ-5D), complications and predictors for new fractures requiring a reoperation. Results The osteoporotic patient sample consisted of 76.7% (179) females with a median age of 80 years. A total of 54 males had a median age of 77 years. On average, there were 1.8 VBs fractured and 5 VBs treated. The preoperative pain was assessed by the visual analog scale (VAS) and decreased from 54.9 to 40.4 pts after 2 months and 31.2 pts after 6 months. Accordingly, the QoL on the EQ-5D measure (−0.6 to 1) improved from 0.35 pts before surgery to 0.56 pts after 2 and to 0.68 pts after 6 months. The preoperative Beck Index (anterior height/posterior height) improved from a mean of 0.64 preoperative to 0.76 postoperative, remained stable at 2 months and slightly deteriorated to 0.72 at 6 months postoperatively. There were cement leakages in 26% of the fractured VBs and in 1.4% of the prophylactically cemented VBs; there were symptoms in 4.3%, and most of them were temporary hypotension and one pulmonary cement embolism that remained asymptomatic. The univariate regression model revealed a tendency for a reduced risk for new or refractures on radiographs (OR = 2.61, 95% CI 0.92–7.38, p = 0.12) and reoperations (OR = 2.9, 95% CI 0.94–8.949, p = 0.1) when prophylactic augmentation was performed. The final multivariate regression model revealed male patients to have an about three times higher refracture risk (radiographic) (OR = 2.78, p = 0.02) at 6 months after surgery. Patients with a lumbar index fracture had an about three to five times higher refracture/reoperation risk than patients with a thoracic (OR = 0.33/0.35, p = 0.009/0.01) or thoracolumbar (OR = 0.32/0.22, p = 0.099/0.01) index fracture. Conclusion If routinely used, VP is a safe and efficacious treatment option for osteoporotic vertebral fractures with regard to pain relief and improvement of the QoL. Even segmental realignment can be partially achieved with proper patient positioning. Certain patient or fracture characteristics increase the risk for early radiographic refractures or new fractures, or a reoperation; a consequent prophylactic augmentation showed protective tendencies, but the study was underpowered for a final conclusion.

Treatment with denosumab reduces the incidence of new vertebral and hip fractures in postmenopausal women at high risk

The FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months) trial showed denosumab significantly reduced the risk of fractures in postmenopausal women with osteoporosis.

Percutaneous cement augmentation techniques for osteoporotic spinal fractures

Minimally invasive vertebral augmentation-based techniques have been used for the treatment of spinal fractures (osteoporotic and malignant) for approximately 25 years. In this review, we try to give an overview of the current spectrum of percutaneous augmentation techniques, safety aspects and indications. Crucial factors for success are careful patient selection, proper technique and choice of the ideal cement augmentation option. Most compression fractures present a favourable natural course, with reduction of pain and regainment of mobility after a few days to several weeks, whereas other patients experience a progressive collapse and persisting pain. In this situation, percutaneous cement augmentation is an effective treatment option with regards to pain and disability reduction, improvement of quality of life and ambulatory and pulmonary function.

Extracortical plate fixation with new plate inserts and cerclage wires for the treatment of periprosthetic hip fractures

PURPOSE Fixation of periprosthetic hip fractures with intracortical anchorage might not be feasible in cases with bulky implants and/or poor bone stock. METHODS Rotational stability of new plate inserts with extracortical anchorage for cerclage fixation was measured and compared to the stability found using a standard technique in a biomechanical setup using a torsion testing machine. In a synthetic PUR bone model, transverse fractures were fixed distally using screws and proximally by wire cerclages attached to the plates using "new" (extracortical anchorage) or "standard" (intracortical anchorage) plate inserts. Time to fracture consolidation and complications were assessed in a consecutive series of 18 patients (18 female; mean age 81 years, range 55-92) with periprosthetic hip fractures (ten type B1, eight type C-Vancouver) treated with the new device between July 2003 and July 2010. RESULTS The "new" device showed a higher rotational stability than the "standard" technique (p < 0.001). Fractures showed radiographic consolidation after 14 ± 5 weeks (mean ± SD) postoperatively in patients. Revision surgery was necessary in four patients, unrelated to the new technique. CONCLUSION In periprosthetic hip fractures in which fixation with intracortical anchorage using conventional means might be difficult due to bulky revision stems and/or poor bone stock, the new device may be an addition to the range of existing implants.

Comparative trends in hospitalizations for osteoporotic fractures and other frequent diseases between 2000 and 2008

In Switzerland, the number, incidence, and cost of acute hospitalizations for major osteoporotic fractures (MOF) and major cardiovascular events (MCE) increased in both women and men between 2000 and 2008, although the mean length of stay (LOS) was significantly reduced. Similar trend patterns were observed for hip fractures and strokes (decrease) and nonhip fractures and acute myocardial infarctions (increase).

Epidemiology and direct medical costs of osteoporotic fractures in men and women in Switzerland

The aim of this study was to estimate the hospitalization incidence and the total number of hospital days related to all fractures and osteoporotic fractures in the year 2000 in Switzerland and to compare these with data from other frequent disorders in men and women. The official administrative and medical statistics database of the Swiss Federal Office of Statistics (SFOS) from the year 2000 was used. It covered 81.2% of all registered patient admissions and was considered to be representative of the entire population. We included the ICD-10 codes of 84 diagnoses that were compatible with an underlying osteoporosis and applied the best matching age-specific osteoporosis attribution rates published for the ICD-9 diagnosis codes to the individual ICD-10 codes. To preserve comparability with previously published data from 1992, we grouped the data related to the ICD-10 fracture codes into seven diagnosis pools (fractures of the axial skeleton, fractures of the proximal upper limbs, fractures of the distal upper limbs, fractures of the proximal lower limbs, fractures of the distal lower limbs, multiple fractures, and osteoporosis) and analyzed them separately for women and men by age group. Incidences of hospitalization due to fractures were calculated, and the direct medical costs related to hospitalization were estimated. In addition, we compared the results with those from chronic pulmonary obstructive disease (COPD), stroke, acute myocardial infarction, heart failure, diabetes and breast carcinoma from the same database. In Switzerland during 2000, 62,535 hospitalizations for fractures (35,586 women and 26,949 men) were registered. Fifty-one percent of all fractures in women and 24% in men were considered as osteoporotic. The overall incidences of hospitalization due to fractures were 969 and 768 per 100,000 in women and men, respectively. The hospitalization incidences for fractures of the proximal lower limbs and the axial skeleton increased exponentially after the age of 65 years. The direct medical cost of hospitalization of patients with osteoporosis and/or related fractures was 357 million CHF. Hip fractures accounted for approximately half of these costs in women and men. Among other common diseases in women and men, osteoporosis ranked number 1 in women and number 2 (behind COPD) in men. When compared with data from 1992, the average length of stay had shortened by 8.4 days for women and 4.7 days for men, leading to a decrease of almost 40% in direct medical costs related to acute hospitalizations. This apparent decrease in cost might result from a shift into the ambulatory cost segment, for which the assessment and management tools need to be developed. We conclude that, in 2000, osteoporosis continued to be a heavy burden on the Swiss healthcare system. Lack of awareness of the disease and its consequences prevents widespread use of drugs with anti-fracture efficacy. This limits their potential to reduce costs.

Remaining lifetime and absolute 10-year probabilities of osteoporotic fracture in Swiss men and women

SUMMARY: Remaining lifetime and absolute 10-year probabilities for osteoporotic fractures were determined by gender, age, and BMD values. Remaining lifetime probability at age 50 years was 20.2% in men and 51.3% in women and increased with advancing age and decreasing BMD. The study validates the elements required to populate a Swiss-specific FRAX model. INTRODUCTION: Switzerland belongs to high-risk countries for osteoporosis. Based on demographic projections, burden will still increase. We assessed remaining lifetime and absolute 10-year probabilities for osteoporotic fractures by gender, age and BMD in order to populate FRAX algorithm for Switzerland. METHODS: Osteoporotic fracture incidence was determined from national epidemiological data for hospitalised fractured patients from the Swiss Federal Office of Statistics in 2000 and results of a prospective Swiss cohort with almost 5,000 fractured patients in 2006. Validated BMD-associated fracture risk was used together with national death incidence and risk tables to determine remaining lifetime and absolute 10-year fracture probabilities for hip and major osteoporotic (hip, spine, distal radius, proximal humerus) fractures. RESULTS: Major osteoporotic fractures incidence was 773 and 2,078 per 100,000 men and women aged 50 and older. Corresponding remaining lifetime probabilities at age 50 were 20.2% and 51.3%. Hospitalisation for clinical spine, distal radius, and proximal humerus fractures reached 25%, 30% and 50%, respectively. Absolute 10-year probability of osteoporotic fracture increased with advancing age and decreasing BMD and was higher in women than in men. CONCLUSION: This study validates the elements required to populate a Swiss-specific FRAX model, a country at highest risk for osteoporotic fractures.

[Epidemiology and burden of osteoporosis in Switzerland]

With increasing life expectancy and a growing proportion of elderly in the Swiss population, the burden of osteoporosis increases continuously. Every other woman and every fifth man aged 50 years or older will suffer an osteoportic fracture during her or his remaining lifetime. While the absolute number of hospitalizations for hip fractures has stabilized between year 2000 and 2007, the total number of hospitalizations for osteoporotic fractures has increased to 16'200 (+ 16 %) and 5'600 (+ 20 %) in women and men, respectively. Thus, osteoporosis continues belonging to those chronic diseases imposing the highest economic burden to the Swiss healthcare system, trend increasing. In addition, the risk of subsequent fractures as well as the adjusted mortality risk increases significantly after a first osteoporotic fracture. Should appropriate measures not be implemented in the near future, so will osteoporosis become one of the key challenges for the Swiss healthcare system within the coming years.

Long-term reaction to bone cement in osteoporotic bone: new bone formation in vertebral bodies after vertebroplasty

Elderly patients frequently suffer from osteoporotic vertebral fractures resulting in the need of vertebroplasty or kyphoplasty. Nevertheless, no data are available about the long-term consequences of cement injection into osteoporotic bone. Therefore, the aim of the present study was to evaluate the long-term tissue reaction on bone cement injected to osteoporotic bone during vertebroplasty. The thoracic spine of an 80-year-old female was explanted 3.5 years after vertebroplasty with polymethylmethacrylate. The treatment had been performed due to painful osteoporotic compression fractures. Individual vertebral bodies were cut in axial or sagittal sections after embedding. The sections were analysed using contact radiography and staining with toluidine blue. Furthermore, selected samples were evaluated with scanning electron microscopy and micro-compted tomography (in-plane resolution 6 microm). Large amounts of newly formed callus surrounding the injected polymethylmethacrylate were detected with all imaging techniques. The callus formation almost completely filled the spaces between the vertebral endplate, the cancellous bone, and the injected polymethylmethacrylate. In trabecular bone microfractures and osteoclast lacuna were bridged or filled with newly formed bone. Nevertheless, the majority of the callus formation was found in the immediate vicinity of the polymethylmethacrylate without any obvious relationship to trabecular fractures. The results indicate for the first time that, contrary to established knowledge, even in osteoporosis the formation of large amounts of new bone is possible.

A model of osteoporosis impact in Switzerland 2000-2020

The aim of our study was to develop a modeling framework suitable to quantify the incidence, absolute number and economic impact of osteoporosis-attributable hip, vertebral and distal forearm fractures, with a particular focus on change over time, and with application to the situation in Switzerland from 2000 to 2020. A Markov process model was developed and analyzed by Monte Carlo simulation. A demographic scenario provided by the Swiss Federal Statistical Office and various Swiss and international data sources were used as model inputs. Demographic and epidemiologic input parameters were reproduced correctly, confirming the internal validity of the model. The proportion of the Swiss population aged 50 years or over will rise from 33.3% in 2000 to 41.3% in 2020. At the total population level, osteoporosis-attributable incidence will rise from 1.16 to 1.54 per 1,000 person-years in the case of hip fracture, from 3.28 to 4.18 per 1,000 person-years in the case of radiographic vertebral fracture, and from 0.59 to 0.70 per 1,000 person-years in the case of distal forearm fracture. Osteoporosis-attributable hip fracture numbers will rise from 8,375 to 11,353, vertebral fracture numbers will rise from 23,584 to 30,883, and distal forearm fracture numbers will rise from 4,209 to 5,186. Population-level osteoporosis-related direct medical inpatient costs per year will rise from 713.4 million Swiss francs (CHF) to CHF946.2 million. These figures correspond to 1.6% and 2.2% of Swiss health care expenditures in 2000. The modeling framework described can be applied to a wide variety of settings. It can be used to assess the impact of new prevention, diagnostic and treatment strategies. In Switzerland incidences of osteoporotic hip, vertebral and distal forearm fracture will rise by 33%, 27%, and 19%, respectively, between 2000 and 2020, if current prevention and treatment patterns are maintained. Corresponding absolute fracture numbers will rise by 36%, 31%, and 23%. Related direct medical inpatient costs are predicted to increase by 33%; however, this estimate is subject to uncertainty due to limited availability of input data.

Medical treatment of vertebral osteoporosis

Although osteoporosis is a systemic disease, vertebral fractures due to spinal bone loss are a frequent, sometimes early and often neglected complication of the disease, generally associated with considerable disability and pain. As osteoporotic vertebral fractures are an important predictor of future fracture risk, including at the hip, medical management is targeted at reducing fracture risk. A literature search for randomized, double-blind, prospective, controlled clinical studies addressing medical treatment possibilities of vertebral fractures in postmenopausal Caucasian women was performed on the leading medical databases. For each publication, the number of patients with at least one new vertebral fracture and the number of randomized patients by treatment arm was retrieved. The relative risk (RR) and the number needed to treat (NNT, i.e. the number of patients to be treated to avoid one radiological vertebral fracture over the duration of the study), together with the respective 95% confidence intervals (95%CI) were calculated for each study. Treatment of steroid-induced osteoporosis and treatment of osteoporosis in men were reviewed separately, based on the low number of publications available. Forty-five publications matched with the search criteria, allowing for analysis of 15 different substances tested regarding their anti-fracture efficacy at the vertebral level. Bisphosphonates, mainly alendronate and risedronate, were reported to have consistently reduced the risk of a vertebral fracture over up to 50 months of treatment in four (alendronate) and two (risedronate) publications. Raloxifene reduced vertebral fracture risk in one study over 36 months, which was confirmed by 48 months' follow-up data. Parathormone (PTH) showed a drastic reduction in vertebral fracture risk in early studies, while calcitonin may also be a treatment option to reduce fracture risk. For other substances published data are conflicting (calcitriol, fluoride) or insufficient to conclude about efficacy (calcium, clodronate, etidronate, hormone replacement therapy, pamidronate, strontium, tiludronate, vitamin D). The low NNTs for the leading substances (ranges: 15-64 for alendronate, 8-26 for risedronate, 23 for calcitonin and 28-31 for raloxifene) confirm that effective and efficient drug interventions for treatment and prevention of osteoporotic vertebral fractures are available. Bisphosphonates have demonstrated similar efficacy in treatment and prevention of steroid-induced and male osteoporosis as in postmenopausal osteoporosis. The selection of the appropriate drug for treatment of vertebral osteoporosis from among a bisphosphonate (alendronate or risedronate), PTH, calcitonin or raloxifene will mainly depend on the efficacy, tolerability and safety profile, together with the patient's willingness to comply with a long-term treatment. Although reduction of vertebral fracture risk is an important criterion for decision making, drugs with proven additional fracture risk reduction at all clinically relevant sites (especially at the hip) should be the preferred options.

Subclinical thyroid dysfunction and the risk for fractures: a systematic review and meta-analysis.

BACKGROUND Data on the association between subclinical thyroid dysfunction and fractures conflict. PURPOSE To assess the risk for hip and nonspine fractures associated with subclinical thyroid dysfunction among prospective cohorts. DATA SOURCES Search of MEDLINE and EMBASE (1946 to 16 March 2014) and reference lists of retrieved articles without language restriction. STUDY SELECTION Two physicians screened and identified prospective cohorts that measured thyroid function and followed participants to assess fracture outcomes. DATA EXTRACTION One reviewer extracted data using a standardized protocol, and another verified data. Both reviewers independently assessed methodological quality of the studies. DATA SYNTHESIS The 7 population-based cohorts of heterogeneous quality included 50,245 participants with 1966 hip and 3281 nonspine fractures. In random-effects models that included the 5 higher-quality studies, the pooled adjusted hazard ratios (HRs) of participants with subclinical hyperthyroidism versus euthyrodism were 1.38 (95% CI, 0.92 to 2.07) for hip fractures and 1.20 (CI, 0.83 to 1.72) for nonspine fractures without statistical heterogeneity (P = 0.82 and 0.52, respectively; I2= 0%). Pooled estimates for the 7 cohorts were 1.26 (CI, 0.96 to 1.65) for hip fractures and 1.16 (CI, 0.95 to 1.42) for nonspine fractures. When thyroxine recipients were excluded, the HRs for participants with subclinical hyperthyroidism were 2.16 (CI, 0.87 to 5.37) for hip fractures and 1.43 (CI, 0.73 to 2.78) for nonspine fractures. For participants with subclinical hypothyroidism, HRs from higher-quality studies were 1.12 (CI, 0.83 to 1.51) for hip fractures and 1.04 (CI, 0.76 to 1.42) for nonspine fractures (P for heterogeneity = 0.69 and 0.88, respectively; I2 = 0%). LIMITATIONS Selective reporting cannot be excluded. Adjustment for potential common confounders varied and was not adequately done across all studies. CONCLUSION Subclinical hyperthyroidism might be associated with an increased risk for hip and nonspine fractures, but additional large, high-quality studies are needed. PRIMARY FUNDING SOURCE Swiss National Science Foundation.

Development of a balanced experimental–computational approach to understanding the mechanics of proximal femur fractures

The majority of people who sustain hip fractures after a fall to the side would not have been identified using current screening techniques such as areal bone mineral density. Identifying them, however, is essential so that appropriate pharmacological or lifestyle interventions can be implemented. A protocol, demonstrated on a single specimen, is introduced, comprising the following components; in vitro biofidelic drop tower testing of a proximal femur; high-speed image analysis through digital image correlation; detailed accounting of the energy present during the drop tower test; organ level finite element simulations of the drop tower test; micro level finite element simulations of critical volumes of interest in the trabecular bone. Fracture in the femoral specimen initiated in the superior part of the neck. Measured fracture load was 3760 N, compared to 4871 N predicted based on the finite element analysis. Digital image correlation showed compressive surface strains as high as 7.1% prior to fracture. Voxel level results were consistent with high-speed video data and helped identify hidden local structural weaknesses. We found using a drop tower test protocol that a femoral neck fracture can be created with a fall velocity and energy representative of a sideways fall from standing. Additionally, we found that the nested explicit finite element method used allowed us to identify local structural weaknesses associated with femur fracture initiation.

The effect of pulsed jet lavage in vertebroplasty on injection forces of PMMA bone cement: an animal study

Percutaneous vertebroplasty, comprising of the injection of polymethylmethacrylate (PMMA) into vertebral bodies, is an efficient procedure to stabilize osteoporotic compression fractures as well as other weakening lesions. Besides fat embolism, cement leakage is considered to be one of the major and most severe complications during percutaneous vertebroplasty. The viscosity of the PMMA during injection plays a key role in this context. It was shown in vitro that the best way to lower the risk of cement leakage is to inject the cement at higher viscosity, which is requires high injection forces. Injection forces can be reduced by applying a newly developed lavage technique as it was shown in vitro using human cadaver vertebrae. The purpose of this study was to prove the in vitro results in an in vivo model. The investigation was incorporated in an animal study that was performed to evaluate the cardiovascular reaction on cement augmentation using the lavage technique. Injection forces were measured with instrumentation for 1 cc syringes, additionally acquiring plunger displacement. Averaged injection forces measured, ranged from 12 to 130 N and from 28 to 140 N for the lavage group and the control group, respectively. Normalized injection forces (by viscosity and injection speed) showed a trend to be lower for the lavage group in comparison to the control group (P = 0.073). In conclusion, the clinical relevance on the investigated lavage technique concerning lowering injection forces was only shown by trend in the performed animal study. However, it might well be that the effect is more pronounced for osteoporotic vertebral bodies.