Vertebroplasty and kyphoplasty: a systematic review of 69 clinical studies

STUDY DESIGN: Systematic literature review. OBJECTIVE: To evaluate the safety and efficacy of vertebroplasty and kyphoplasty using the data presented in published clinical studies, with respect to patient pain relief, restoration of mobility and vertebral body height, complication rate, and incidence of new adjacent vertebral fractures. SUMMARY OF BACKGROUND DATA: Vertebroplasty and kyphoplasty have been gaining popularity for treating vertebral fractures. Current reviews provide an overview of the procedures but are not comprehensive and tend to rely heavily on personal experience. This article aimed to compile all available data and evaluate the clinical outcome of the 2 procedures. METHODS: This is a systematic review of all the available data presented in peer-reviewed published clinical trials. The methodological quality of included studies was evaluated, and data were collected targeting specific standard measurements. Where possible, a quantitative aggregation of the data was performed. RESULTS: A large proportion of subjects had some pain relief, including 87% with vertebroplasty and 92% with kyphoplasty. Vertebral height restoration was possible using kyphoplasty (average 6.6 degrees ) and for a subset of patients using vertebroplasty (average 6.6 degrees ). Cement leaks occurred for 41% and 9% of treated vertebrae for vertebroplasty and kyphoplasty, respectively. New fractures of adjacent vertebrae occurred for both procedures at rates that are higher than the general osteoporotic population but approximately equivalent to the general osteoporotic population that had a previous vertebral fracture. CONCLUSIONS: The problem with stating definitely that vertebroplasty and kyphoplasty are safe and effective procedures is the lack of comparative, blinded, randomized clinical trials. Standardized evaluative methods should be adopted.

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.

Scaling relations between trabecular bone volume fraction and microstructure at different skeletal sites

In this study, we investigated the scaling relations between trabecular bone volume fraction (BV/TV) and parameters of the trabecular microstructure at different skeletal sites. Cylindrical bone samples with a diameter of 8mm were harvested from different skeletal sites of 154 human donors in vitro: 87 from the distal radius, 59/69 from the thoracic/lumbar spine, 51 from the femoral neck, and 83 from the greater trochanter. μCT images were obtained with an isotropic spatial resolution of 26μm. BV/TV and trabecular microstructure parameters (TbN, TbTh, TbSp, scaling indices (< > and σ of α and αz), and Minkowski Functionals (Surface, Curvature, Euler)) were computed for each sample. The regression coefficient β was determined for each skeletal site as the slope of a linear fit in the double-logarithmic representations of the correlations of BV/TV versus the respective microstructure parameter. Statistically significant correlation coefficients ranging from r=0.36 to r=0.97 were observed for BV/TV versus microstructure parameters, except for Curvature and Euler. The regression coefficients β were 0.19 to 0.23 (TbN), 0.21 to 0.30 (TbTh), −0.28 to −0.24 (TbSp), 0.58 to 0.71 (Surface) and 0.12 to 0.16 (<α>), 0.07 to 0.11 (<αz>), −0.44 to −0.30 (σ(α)), and −0.39 to −0.14 (σ(αz)) at the different skeletal sites. The 95% confidence intervals of β overlapped for almost all microstructure parameters at the different skeletal sites. The scaling relations were independent of vertebral fracture status and similar for subjects aged 60–69, 70–79, and >79years. In conclusion, the bone volume fraction–microstructure scaling relations showed a rather universal character.

Increased vertebral morphometric fracture in patients with postsurgical hypoparathyroidism despite normal bone mineral density

Background In human malaria, the naturally-acquired immune response can result in either the elimination of the parasite or a persistent response mediated by cytokines that leads to immunopathology. The cytokines are responsible for all the symptoms, pathological alterations and the outcome of the infection depends on the reciprocal regulation of the pro and anti-inflammatory cytokines. IL-10 and IFN-gamma are able to mediate this process and their production can be affected by single nucleotide polymorphisms (SNPs) on gene of these cytokines. In this study, the relationship between cytokine IL-10/IFN-gamma levels, parasitaemia, and their gene polymorphisms was examined and the participation of pro-inflammatory and regulatory balance during a natural immune response in Plasmodium vivax-infected individuals was observed. Methods The serum levels of the cytokines IL-4, IL-12, IFN-gamma and IL-10 from 132 patients were evaluated by indirect enzyme-linked immunosorbent assays (ELISA). The polymorphism at position +874 of the IFN-gamma gene was identified by allele-specific polymerase chain reaction (ASO-PCR) method, and the polymorphism at position -1082 of the IL-10 gene was analysed by PCR-RFLP (PCR-Restriction Fragment Length Polymorphism). Results The levels of a pro- (IFN-gamma) and an anti-inflammatory cytokine (IL-10) were significantly higher in P. vivax-infected individuals as compared to healthy controls. The IFN-gamma levels in primoinfected patients were significantly higher than in patients who had suffered only one and more than one previous episode. The mutant alleles of both IFN-gamma and IL-10 genes were more frequent than the wild allele. In the case of the IFNG+874 polymorphism (IFN-gamma) the frequencies of the mutant (A) and wild (T) alleles were 70.13% and 29.87%, respectively. Similar frequencies were recorded in IL-10-1082, with the mutant (A) allele returning a frequency of 70.78%, and the wild (G) allele a frequency of 29.22%. The frequencies of the alleles associated with reduced production of both IFN-gamma and IL-10 were high, but this effect was only observed in the production of IFN-gamma. Conclusions This study has shown evidence of reciprocal regulation of the levels of IL-10 and IFN-gamma cytokines in P. vivax malaria, which is not altered by the presence of polymorphism in the IL-10 gene.

Bone mineral density (BMD) and vertebral trabecular bone score (TBS) for the identification of elderly women at high risk for fracture: the SEMOF cohort study

PURPOSE To determine the predictive value of the vertebral trabecular bone score (TBS) alone or in addition to bone mineral density (BMD) with regard to fracture risk. METHODS Retrospective analysis of the relative contribution of BMD [measured at the femoral neck (FN), total hip (TH), and lumbar spine (LS)] and TBS with regard to the risk of incident clinical fractures in a representative cohort of elderly post-menopausal women previously participating in the Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture Risk study. RESULTS Complete datasets were available for 556 of 701 women (79 %). Mean age 76.1 years, LS BMD 0.863 g/cm(2), and TBS 1.195. LS BMD and LS TBS were moderately correlated (r (2) = 0.25). After a mean of 2.7 ± 0.8 years of follow-up, the incidence of fragility fractures was 9.4 %. Age- and BMI-adjusted hazard ratios per standard deviation decrease (95 % confidence intervals) were 1.58 (1.16-2.16), 1.77 (1.31-2.39), and 1.59 (1.21-2.09) for LS, FN, and TH BMD, respectively, and 2.01 (1.54-2.63) for TBS. Whereas 58 and 60 % of fragility fractures occurred in women with BMD T score ≤-2.5 and a TBS <1.150, respectively, combining these two thresholds identified 77 % of all women with an osteoporotic fracture. CONCLUSIONS Lumbar spine TBS alone or in combination with BMD predicted incident clinical fracture risk in a representative population-based sample of elderly post-menopausal women.

An experimental and finite element investigation of the biomechanics of vertebral compression fractures

Osteoporosis is a disease characterized by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Osteoporosis affects over 200 million people worldwide, with an estimated 1.5 million fractures annually in the United States alone, and with attendant costs exceeding $10 billion dollars per annum. Osteoporosis reduces bone density through a series of structural changes to the honeycomb-like trabecular bone structure (micro-structure). The reduced bone density, coupled with the microstructural changes, results in significant loss of bone strength and increased fracture risk. Vertebral compression fractures are the most common type of osteoporotic fracture and are associated with pain, increased thoracic curvature, reduced mobility, and difficulty with self care. Surgical interventions, such as kyphoplasty or vertebroplasty, are used to treat osteoporotic vertebral fractures by restoring vertebral stability and alleviating pain. These minimally invasive procedures involve injecting bone cement into the fractured vertebrae. The techniques are still relatively new and while initial results are promising, with the procedures relieving pain in 70-95% of cases, medium-term investigations are now indicating an increased risk of adjacent level fracture following the procedure. With the aging population, understanding and treatment of osteoporosis is an increasingly important public health issue in developed Western countries. The aim of this study was to investigate the biomechanics of spinal osteoporosis and osteoporotic vertebral compression fractures by developing multi-scale computational, Finite Element (FE) models of both healthy and osteoporotic vertebral bodies. The multi-scale approach included the overall vertebral body anatomy, as well as a detailed representation of the internal trabecular microstructure. This novel, multi-scale approach overcame limitations of previous investigations by allowing simultaneous investigation of the mechanics of the trabecular micro-structure as well as overall vertebral body mechanics. The models were used to simulate the progression of osteoporosis, the effect of different loading conditions on vertebral strength and stiffness, and the effects of vertebroplasty on vertebral and trabecular mechanics. The model development process began with the development of an individual trabecular strut model using 3D beam elements, which was used as the building block for lattice-type, structural trabecular bone models, which were in turn incorporated into the vertebral body models. At each stage of model development, model predictions were compared to analytical solutions and in-vitro data from existing literature. The incremental process provided confidence in the predictions of each model before incorporation into the overall vertebral body model. The trabecular bone model, vertebral body model and vertebroplasty models were validated against in-vitro data from a series of compression tests performed using human cadaveric vertebral bodies. Firstly, trabecular bone samples were acquired and morphological parameters for each sample were measured using high resolution micro-computed tomography (CT). Apparent mechanical properties for each sample were then determined using uni-axial compression tests. Bone tissue properties were inversely determined using voxel-based FE models based on the micro-CT data. Specimen specific trabecular bone models were developed and the predicted apparent stiffness and strength were compared to the experimentally measured apparent stiffness and strength of the corresponding specimen. Following the trabecular specimen tests, a series of 12 whole cadaveric vertebrae were then divided into treated and non-treated groups and vertebroplasty performed on the specimens of the treated group. The vertebrae in both groups underwent clinical-CT scanning and destructive uniaxial compression testing. Specimen specific FE vertebral body models were developed and the predicted mechanical response compared to the experimentally measured responses. The validation process demonstrated that the multi-scale FE models comprising a lattice network of beam elements were able to accurately capture the failure mechanics of trabecular bone; and a trabecular core represented with beam elements enclosed in a layer of shell elements to represent the cortical shell was able to adequately represent the failure mechanics of intact vertebral bodies with varying degrees of osteoporosis. Following model development and validation, the models were used to investigate the effects of progressive osteoporosis on vertebral body mechanics and trabecular bone mechanics. These simulations showed that overall failure of the osteoporotic vertebral body is initiated by failure of the trabecular core, and the failure mechanism of the trabeculae varies with the progression of osteoporosis; from tissue yield in healthy trabecular bone, to failure due to instability (buckling) in osteoporotic bone with its thinner trabecular struts. The mechanical response of the vertebral body under load is highly dependent on the ability of the endplates to deform to transmit the load to the underlying trabecular bone. The ability of the endplate to evenly transfer the load through the core diminishes with osteoporosis. Investigation into the effect of different loading conditions on the vertebral body found that, because the trabecular bone structural changes which occur in osteoporosis result in a structure that is highly aligned with the loading direction, the vertebral body is consequently less able to withstand non-uniform loading states such as occurs in forward flexion. Changes in vertebral body loading due to disc degeneration were simulated, but proved to have little effect on osteoporotic vertebra mechanics. Conversely, differences in vertebral body loading between simulated invivo (uniform endplate pressure) and in-vitro conditions (where the vertebral endplates are rigidly cemented) had a dramatic effect on the predicted vertebral mechanics. This investigation suggested that in-vitro loading using bone cement potting of both endplates has major limitations in its ability to represent vertebral body mechanics in-vivo. And lastly, FE investigation into the biomechanical effect of vertebroplasty was performed. The results of this investigation demonstrated that the effect of vertebroplasty on overall vertebra mechanics is strongly governed by the cement distribution achieved within the trabecular core. In agreement with a recent study, the models predicted that vertebroplasty cement distributions which do not form one continuous mass which contacts both endplates have little effect on vertebral body stiffness or strength. In summary, this work presents the development of a novel, multi-scale Finite Element model of the osteoporotic vertebral body, which provides a powerful new tool for investigating the mechanics of osteoporotic vertebral compression fractures at the trabecular bone micro-structural level, and at the vertebral body level.

Development of a multi-scale finite element model of the osteoporotic lumbar vertebral body for the investigation of apparent level vertebra mechanics and micro-level trabecular mechanics.

Osteoporotic spinal fractures are a major concern in ageing Western societies. This study develops a multi-scale finite element (FE) model of the osteoporotic lumbar vertebral body to study the mechanics of vertebral compression fracture at both the apparent (whole vertebral body) and micro-structural (internal trabecular bone core)levels. Model predictions were verified against experimental data, and found to provide a reasonably good representation of the mechanics of the osteoporotic vertebral body. This novel modelling methodology will allow detailed investigation of how trabecular bone loss in osteoporosis affects vertebral stiffness and strength in the lumbar spine.

Development of a bovine collagen-apatitic calcium phosphate cement for potential fracture treatment through vertebroplasty

The aim of this study was to examine the potential of incorporating bovine fibres as a means of reinforcing a typically brittle apatite calcium phosphate cement for vertebroplasty. Type I collagen derived from bovine Achilles tendon was ground cryogenically to produce an average fibre length of 0.96 ± 0.55 mm and manually mixed into the powder phase of an apatite-based cement at 1, 3 or 5 wt.%. Fibre addition of up to 5 wt.% had a significant effect (P = 0.001) on the fracture toughness, which was increased by 172%. Adding =1 wt.% bovine collagen fibres did not compromise the compressive properties significantly, however, a decrease of 39-53% was demonstrated at =3 wt.% fibre loading. Adding bovine collagen to the calcium phosphate cement reduced the initial and final setting times to satisfy the clinical requirements stated for vertebroplasty. The cement viscosity increased in a linear manner (R = 0.975) with increased loading of collagen fibres, such that the injectability was found to be reduced by 83% at 5 wt.% collagen loading. This study suggests for the first time the potential application of a collagen-reinforced calcium phosphate cement as a viable option in the treatment of vertebral fractures, however, issues surrounding efficacious cement delivery need to be addressed. © 2012 Acta Materialia Inc.

Experimental and Computational Approach Investigating Burst Fracture Augmentation Using PMMA and Calcium Phosphate Cements

The aim of the study was to use a computational and experimental approach to evaluate, compare and predict the ability of calcium phosphate (CaP) and poly (methyl methacrylate) (PMMA) augmentation cements to restore mechanical stability to traumatically fractured vertebrae, following a vertebroplasty procedure. Traumatic fractures (n = 17) were generated in a series of porcine vertebrae using a drop-weight method. The fractured vertebrae were imaged using μCT and tested under axial compression. Twelve of the fractured vertebrae were randomly selected to undergo a vertebroplasty procedure using either a PMMA (n = 6) or a CaP cement variation (n = 6). The specimens were imaged using μCT and re-tested. Finite element models of the fractured and augmented vertebrae were generated from the μCT data and used to compare the effect of fracture void fill with augmented specimen stiffness. Significant increases (p <0.05) in failure load were found for both of the augmented specimen groups compared to the fractured group. The experimental and computational results indicated that neither the CaP cement nor PMMA cement could completely restore the vertebral mechanical behavior to the intact level. The effectiveness of the procedure appeared to be more influenced by the volume of fracture filled rather than by the mechanical properties of the cement itself.

Comparison of two osteoporotic fracture management pathways: experience at 1 year

Introduction: Osteoporosis presenting as low-impact fractures to traumatology units is often undiagnosed and under-treated. Results from the Osteocare study in Lausanne (a nurse based intervention, passive pathway) showed that only 19% of patients received management for osteoporosis, and in the literature [1], the rate is between 10-25%. We have evaluated a different management concept, based on the systematic assessment of patients with osteoporotic fractures during and after hospitalization (active pathway). Methods: Inpatients admitted to the Department of Musculoskeletal Medicine for a fragility fracture were identified by a nurse according to a predefined questionnaire and were then clinically evaluated by a doctor. Based on the results, a management plan was proposed to the patients. Patients could choose between follow up either by their GP or by the Centre of Bone Disease of the CHUV. For patients who chose follow-up in our Centre, we assessed their adherence to medical follow-up 1 year inclusion. The results of patients who had been evaluated in our cohort between the 1 November 2008 and the 1 December 2009 were analysed. Results: 573 inpatients received specific management of their osteoporotic fracture over 18 months. The mean age was 77 y (31-99), 81% were women (203 hip fractures, 40 pelvis fractures, 101 arm fractures, 57 vertebral fractures, 63 ankle fractures, and 25 others sites). During the study period, 303 patients received a proposition of a specific treatment. 39 (13%) chose a follow up with the GP, 19 (6%) dead and 245 (81%) preferred a follow up in our Centre. After 1 year, 166 (67%) patients are under follow up in our outpatient clinic. Conclusion: With an active clinical pathway that starts during the hospitalization, consisting on a nursing evaluation followed by a medical consultation by an expert in osteoporosis, the adherence increased from 19% to 67% in terms of follow up. These results lead us to propose a consultation with a doctor experienced in osteoporosis after all osteoporotic fractures.

Bone mineral density measurement and osteoporosis treatment after a fragility fracture in older adults: regional variation and determinants of use in Quebec

Affiliation: Pierre Dagenais : Hôpital Maisonneuve-Rosemont, Faculté de médecine, Université de Montréal