Risk Of Subsequent Vertebral Fractures Research Articles

Treatment Persistence and Medication Switch Associated With Subsequent Fractures After Osteoporotic Fractures.

Despite prevalent anti-osteoporosis medication (AOM) switching in real-world osteoporosis management, few studies have evaluated the impact of persistent AOM treatment, allowing for AOM switching, on the risk of subsequent fracture. We examined the association between persistence in AOM and subsequent fractures, allowing for medication switching among patients with osteoporotic fractures. This retrospective cohort study used Taiwan National Health Insurance claims data to select patients who initiated AOM between 2013 and 2016. Treatment persistence was defined as use of any AOM on a given day of interest with a 45-day grace period. Medication switch was allowed for persistence if remaining on treatment. AOMs with long-lasting inhibition of bone resorption (zoledronate and denosumab) were categorized as high-potency; others as low-potency. Multivariate Cox models were used to evaluate risk of subsequent fractures ≥3 months after initiating AOM. A total of 119 473 patients were included (mean [SD] follow-up 46.4 [15.6] months), and 26.8% switched from the index AOM. Within 1 year, 52% remained persistent with AOM. Compared to patients with persistent AOM, those not persistent had higher risk of subsequent hip (adjusted hazard ratio [aHR] = 1.31; 95% CI, 1.21-1.42), vertebral (aHR = 1.17; 95% CI, 1.13-1.22), and radius fractures (aHR = 1.16; 95% CI, 1.08-1.25). Patients with persistent AOM who switched from high- to low-potency AOM had higher risk of subsequent vertebral fractures than those with persistent AOM and no potency switch (aHR = 1.28; 95% CI, 1.02-1.60). Patients with non-persistent AOM had higher risk of subsequent fractures than persistent users when allowing AOM switch. Switching AOM potency may influence the risk of subsequent vertebral fractures and warrants further investigation.

Biomechanical CT-computed bone strength predicts the risk of subsequent vertebral fracture.

Following primary fractures and percutaneous kyphoplasty (PKP), patients have a high risk of incurring a subsequent vertebral fracture (SVF). Given that SVF is a consequence of mechanical deterioration of the vertebra, we sought to examine whether vertebral strength derived from QCT-based finite element analysis (i.e., BCT) can predict the risk of SVF. Sixty-six patients who underwent PKP were categorized into two groups: control or non-SVF group (age: 70±7years; n=40) and SVF group (age: 69±8years; n=26). BCT was performed on L4 or L3 vertebrae to noninvasively measure vertebral strength. Vertebral strength was also estimated based upon the geometry and material properties of the vertebra. Additionally, trabecular volumetric bone mineral density (vBMD) and L1 Hounsfield unit (HU) were measured. t-Test, χ2 test or Mann Whitney U test were used to compare differences in these parameters between the two groups. The predictive abilities of BCT strength and other measured parameters were evaluated using the receiver operating characteristic (ROC) analysis. Results showed no significant difference in either vBMD or L1 HU between the control and SVF groups (p>0.05), whereas BCT-computed and estimated vertebral strength values were significantly reduced by 33% and 24% for the SVF group relative to the non-SVF group, respectively. ROC curve indicated that BCT strength had the largest area under the curve, compared to other parameters. These results suggest that BCT-computed vertebral strength may serve as a surrogate for assessing risk of SVF.

Computed tomography-based paravertebral muscle density predicts subsequent vertebral fracture risks independently of bone mineral density in postmenopausal women following percutaneous vertebral augmentation.

The risk of subsequent vertebral fractures (SVF) after the primary vertebral fracture cannot be explained by lower bone mineral density (BMD) alone. Computed tomography (CT) measurements of paravertebral muscle density (PMD) are recognized radiographic markers used to predict physical function, fragile fractures. This study aims to investigate the relationship between PMD and the risk of SVF in cohorts of postmenopausal women, and to determine if combining both PMD and BMD measures derived from CT can improve the accuracy of predicting SVF. This study enrolled 305 postmenopausal women between the ages of 50 and 88 for 3years of follow-up studies. Trabecular attenuation (Hounsfield units, HU) was measured at L1 level and muscle attenuation of paravertebral muscle at L3 level on preoperative lumbar CT scans to determine the L1 BMD and L3 PMD. Kaplan-Meier analysis was applied to evaluate SVF-free survival. The hazard ratios (HRs) of PMD for SVF events were estimated with the Cox proportional hazards model. The predictive values of L1 BMD and L3 PMD for SVF were quantified using the Receiver-Operating Characteristic (ROC) curve. During the 3years of follow-up studies, 88 patients (28.9%) suffered an SVF. ROC curve analysis demonstrated that an L3 PMD threshold of 32 HU had a sensitivity of 89.8% and a specificity of 62% for the prediction of SVF. Kaplan-Meier analysis showed that L3 PMD ≤ 32 HU was significantly associated with lower SVF-free survival (p < 0.001; log-rank test). After adjusting for age, BMI, diabetes, postoperative osteoporosis treatment, handgrip strength, L1 BMD, multivariate analyses also indicated a persistent modest effect of L3 PMD on SVF-free survival. The area under the ROC curve of L3 PMD and L1 BMD, combined to predict the risk of SVF, was 0.790, which was significantly higher than the value for L1 BMD alone (0.735). L3 PMD and L1 BMD significantly improved the accuracy of SVF risk prediction compared with L1 BMD alone, which was confirmed by reclassification improvement measures. The inclusion of handgrip strength and postoperative osteoporosis treatment in the model further improved SVF prediction accuracy, and PMD remained significant in the model. Decreased L3 PMD is an independent risk predictor of SVF. Combined CT-based L1 BMD and L3 PMD can significantly improve the accuracy of predicting the risk of SVF in postmenopausal women who have suffered prior osteoporotic vertebral fractures.

Change in vertebral strength and bone mineral density in men and women over the year post-hip fracture: a subgroup analysis.

Compare changes over the first year post-hip fracture in vertebral bone mineral density (BMD) and compressive strength, measured from quantitative computed tomography (QCT) scans of the spine (T12-L1), between women and men. QCT scans were performed on 37 participants (21 men and 16 women) at 2 and 12 months post-hip fracture as part of an ancillary observational study of hip fracture recovery in older community-dwelling men and women. Vertebral BMD and compressive strength were calculated using VirtuOst® (O.N. Diagnostics, Berkeley, CA). Unpaired t-tests were used to compare men and women with respect to baseline demographics, measurements of BMD and bone strength for the whole vertebra and the cortical and trabecular compartments, and any changes in these parameters between months 2 and 12. At 2 months post-fracture, there were no significant sex differences in any measurements of vertebral strength or BMD. Between months 2 and 12, vertebral strength decreased significantly in women (- 3.8%, p < 0.05) but not in men (- 2.3%, p < 0.20), vertebral trabecular BMD decreased similarly in both sexes (- 5.7% women; - 6.0% men), but cortical BMD did not change for either sex. Despite the small sample size, these findings suggest that appreciable loss of vertebral trabecular bone can occur for both sexes in the year following hip fracture, which may increase the risk of subsequent vertebral fracture, particularly for women.

Risk factors for subsequent vertebral fracture after acute osteoporotic vertebral fractures.

To investigate the incidence and characteristics of subsequent vertebral fracture after osteoporotic vertebral fractures (OVFs) and identify risk factors for subsequent vertebral fractures. This post-hoc analysis from a prospective randomized multicenter trial included 225 patients with a 48-week follow-up period. Differences between the subsequent and non-subsequent fracture groups were analyzed. Of the 225 patients, 15 (6.7%) had a subsequent fracture during the 48-week follow-up. The annual incidence of subsequent vertebral fracture after fresh OVFs in women aged 65-85years was 68.8 per 1000 person-years. Most patients (73.3%) experienced subsequent vertebral fractures within 6months. At 48weeks, European Quality of Life-5 Dimensions, the Japanese Orthopedic Association Back Pain Evaluation Questionnaire pain-related disorder, walking ability, social life function, and lumbar function scores were significantly lower, while the visual analog scale (VAS) for low back pain was higher in patients with subsequent fracture. Cox proportional hazards analysis showed that a VAS score ≥ 70 at 0weeks was an independent predictor of subsequent vertebral fracture. After adjustment for history of previous fracture, there was a ~ 67% reduction in the risk of subsequent vertebral fracture at the rigid-brace treatment. Women with a fresh OVF were at higher risk for subsequent vertebral fracture within the next year. Severe low back pain and use of soft braces were associated with higher risk of subsequent vertebral fractures. Therefore, when treating patients after OVFs with these risk factors, more attention may be needed for the occurrence of subsequent vertebral fractures. III.

Vertebroplasty Increases the Incidence Of New Vertebral Compression Fractures Compared To Conservative Management

Abstract Background Vertebral osteoporotic fractures are a major cause of morbidity and disability among the elderly population.This study sought to compare the incidence of new vertebral fractures in patients treated by vertebroplasty with that of those managed conservatively, while also assessing the potential risk factors contributing to the occurrence of these fractures. Materials and Methods The details of a total of 121 eligible subjects with radiologically proven osteoporotic vertebral fractures were retrieved from our archive between January 2010 and September 2019 and divided, based on the treatment method, into percutaneous vertebroplasty (PVP) (n = 60) and nonsurgical treatment (n = 61). The included subjects’ clinical data, demographic profiles, and imaging findings on plain radiography, CT, and MRI scans performed at baseline and within 24 months following treatment were reviewed and documented. Results The difference in the incidence of new fractures was statistically significant (p = 0.001), with rates of 70% (n = 32) in the vertebroplasty group and 30% (n = 14) in the conservatively treated cases reported at a median follow-up time point of approximately 4 months. The presence of liver disease (p = 0.037), a history of transplantation (p = 0.003), the use of steroids (p = 0.023), a low-bone mineral density (BMD) score (p = 0.023), and a higher number of fractures on baseline imaging (p = 0.013) were associated with a greater risk of subsequent vertebral fractures. Conclusions The incidence of acute fractures after PVP is higher than that among patients treated conservatively. Decision-making regarding the adoption of this intervention should take into consideration the risk factors leading to a greater risk of subsequent vertebral fractures, such as a higher number of fractures at baseline imaging, low-BMD score, patient comorbidities, and steroid use.

Region-dependent bone loss in the lumbar spine following femoral fracture in mice.

We previously showed that after femur fracture, mice lose bone at distant skeletal sites, including the lumbar vertebrae. This bone loss may increase the risk of subsequent vertebral fractures, particularly if bone is lost from high-strain bone regions, which are most commonly found adjacent to the superior and inferior endplates of the vertebral body. To determine regional bone loss from the lumbar spine following femur fracture, we evaluated the cranial, center, and caudal portions of the L5 vertebral bodies of Young (3month-old) and Middle-Aged (12month-old) female C57BL/6 mice two weeks after a transverse femur fractures compared to Young and Middle-Aged uninjured control mice. We hypothesized that greater bone loss would be observed in the cranial and caudal regions than in the center region in both Young and Middle-Aged mice. Trabecular and cortical bone microstructure were evaluated using micro-computed tomography, and osteoclast number and eroded surface were evaluated histologically. In Young Mice, fracture led to decreased trabecular and cortical bone microstructure primarily in the cranial and caudal regions, but not the center region, while Middle-Aged mice demonstrated decreases in trabecular bone in all regions, but did not exhibit any changes in cortical bone microstructure after fracture. No significant differences in osteoclast number or eroded surface were observed at this time point. These data suggest that bone loss following fracture in Young Mice is concentrated in areas that contain a large amount of high-strain tissue, whereas bone loss in Middle-Aged mice is less region-dependent and is restricted to the trabecular bone compartment. These results illustrate how systemic bone loss after fracture could lead to decreases in vertebral strength, and how distinct regional patterns and age-dependent differences in bone loss may differentially affect vertebral fracture risk.

Association between handgrip strength and subsequent vertebral-fracture risk following percutaneous vertebral augmentation.

The aim of this study was to investigate the association between handgrip strength (HGS) and the risk of subsequent vertebral fracture (SVF) after percutaneous vertebral augmentation (PVA). A total of 340 patients aged over 50years with osteoporotic vertebral fracture were enrolled in this 3-year follow-up investigation. HGS was measured with a hand-held dynamometer before PVA. Female patients and male patients were grouped using the HGS threshold recommended by the Asian Working Group for Sarcopenia (AWGS). Kaplan-Meier analysis was used to evaluate SVF-free survival. The hazard ratios (HRs) of HGS for SVF events were estimated with the Cox proportional hazards model. During the follow-up period, a total of 93 patients (27.4%) experienced SVF. Kaplan-Meier analysis showed that the HGS of female patients < 18.0kg and male patients < 28kg was significantly associated with lower SVF-free survival (female patients: p < 0.001, male patients: p = 0.038; log-rank test). Among women, each 1-kg increase in HGS was associated with a 9% lower risk of SVF (HR 0.91, p = 0.035) after adjustment for potential risk factors. Among men, although the associations between low HGS and increased risk of SVF were significant in the crude model (HR 0.79, p < 0.001), this significance disappeared after adjustment for bone mineral density of the femoral neck. Low HGS was significantly associated with lower SVF-free survival among elderly patients who underwent single-level PVA for osteoporotic vertebral fracture.

Vertebral fracture in elderly female patients after posterior fusion with pedicle screw fixation for degenerative lumbar pathology: a retrospective cohort study

BackgroundThere have been only a few reports of subsequent postoperative vertebral fracture following posterior spinal instrumentation fusion, especially in elderly female patients. This study attempted to evaluate the long-term prevalence of subsequent postoperative vertebral fracture in female patients aged 70 years and older who underwent spine decompression and fusion surgery with pedicle screw fixation.MethodsWe retrospectively reviewed prospectively collected data from 125 patients who met our inclusion and exclusion criteria. Patients were divided into 2 groups according to age: patients aged 70 years and older (Group A) and patients aged under 70 years of age (Group B). We evaluated incidence of subsequent postoperative vertebral fractures, type and timing of vertebral fractures, preoperative bone mineral density (BMD), preoperative diagnosis, surgical procedure, number of levels fused, extension of fusion to the lumbosacral junction, and presence of a transverse fixator.ResultsBaseline characteristics excluding patients’ age were not statistically different between the two groups. Preoperative BMD of Group A was an average 81.7% of the young adult mean (YAM) value and that of Group B was an average 85.1% YAM value. Subsequent postoperative vertebral fractures occurred in 22 (41.5%) of 53 in Group A. On the other hand, fracture occurred in 17 (23.6%) of 72 in Group B. There were significant differences between the groups (p = 0.02). The odds ratio for subsequent vertebral fracture was 2.4 (95% confidence interval: 1.1–5.2) in favor of Group A. Survival analysis showed that the rate of subsequent vertebral fracture was significantly higher in Group A (log-rank test, P = 0.007).ConclusionsThe incidence of subsequent vertebral fracture in patients aged 70 years and older was significantly higher than in patients aged under 70 years of age. In the case of pedicle screw fixation in elderly female patients, it is necessary to note the high risk of subsequent vertebral fracture despite short or non-rigid fusion. Vertebral fracture after posterior fusion surgery even for degenerative lumbar pathology could occur in more than one-third of female patients aged 70 years and older.

Which is the best treatment of osteoporotic vertebral compression fractures: balloon kyphoplasty, percutaneous vertebroplasty, or non-surgical treatment? A Bayesian network meta-analysis

BK, PVP, and NST are widely used to treat OVCFs, but preferable treatment is unknown. The aim of the current study was to use a Bayesian network meta-analysis to evaluate the relative benefits and risks of BK, PVP, and NST for patients with OVCFs. PubMed, EMBASE, and the Cochrane Library were screened. Based on the preplanned eligibility criteria, we screened and included randomized controlled trials that compared BK, PVP, and NST in treating patients with OVCFs. The risk of bias for individual studies was appraised. The data were pooled using a Bayesian network meta-analysis and a traditional direct comparison meta-analysis. Of the 1057 relevant studies, 15 were eligible and included. Compared with NST, PVP significantly reduced pain, Oswestry Disability Index (ODI), and Roland-Morris Disability Questionnaire (RMDQ). The comparative efficacy of BK and PVP was similar for pain (mean difference (MD) 0.51, 95% credible interval (CrI) - 0.35 to 1.4), ODI (MD 0.11, 95% CrI - 13 to 13), and RMDQ (MD 1.2, 95% CrI - 2.7 to 5.4). The European Quality of Life-5 Dimensions (EQ-5D) and Physical Component Summary subscales of the Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36 PCS) did not differ significantly. There were also no substantial differences in the risks of subsequent vertebral fractures, adjacent vertebral fractures, and re-fractures at the treated level across all comparators. The results of pairwise meta-analyses were almost consistent with those of network meta-analyses. The treatment ranking indicated that PVP had the highest probability of being the most effective for pain, ODI, RMDQ, and EQ-5D. BK had the highest probability of improving SF-36 PCS and of reducing the risk of subsequent vertebral fractures and re-fractures at the treated level. NST was ranked first in preventing adjacent vertebral fractures. PVP was the most effective method for improving pain, functional status, and quality of life (based on EQ-5D). BK emerged as the best intervention for decreasing the risk of subsequent vertebral fractures and re-fractures at the treated level. NST could be ranked first in reducing adjacent vertebral fractures. The future directions of OVCFs treatment will depend on the outcomes of additional and larger randomized trials in comparing BK with PVP.

The Efficacy and Safety of Vertebral Augmentation: A Second ASBMR Task Force Report

Vertebral augmentation is among the current standards of care to reduce pain in patients with vertebral fractures (VF), yet a lack of consensus regarding efficacy and safety of percutaneous vertebroplasty and kyphoplasty raises questions on what basis clinicians should choose one therapy over another. Given the lack of consensus in the field, the American Society for Bone and Mineral Research (ASBMR) leadership charged this Task Force to address key questions on the efficacy and safety of vertebral augmentation and other nonpharmacological approaches for the treatment of pain after VF. This report details the findings and recommendations of this Task Force. For patients with acutely painful VF, percutaneous vertebroplasty provides no demonstrable clinically significant benefit over placebo. Results did not differ according to duration of pain. There is also insufficient evidence to support kyphoplasty over nonsurgical management, percutaneous vertebroplasty, vertebral body stenting, or KIVA®. There is limited evidence to determine the risk of incident VF or serious adverse effects (AE) related to either percutaneous vertebroplasty or kyphoplasty. No recommendation can be made about harms, but they cannot be excluded. For patients with painful VF, it is unclear whether spinal bracing improves physical function, disability, or quality of life. Exercise may improve mobility and may reduce pain and fear of falling but does not reduce falls or fractures in individuals with VF. General and intervention-specific research recommendations stress the need to reduce study bias and address methodological flaws in study design and data collection. This includes the need for larger sample sizes, inclusion of a placebo control, more data on serious AE, and more research on nonpharmacologic interventions. Routine use of vertebral augmentation is not supported by current evidence. When it is offered, patients should be fully informed about the evidence. Anti-osteoporotic medications reduce the risk of subsequent vertebral fractures by 40-70%. © 2018 American Society for Bone and Mineral Research.

Increased Bone Mineral Density with Monthly Intravenous Ibandronate Contributes to Fracture Risk Reduction in Patients with Primary Osteoporosis: Three-Year Analysis of the MOVER Study

The relationship between gains in bone mineral density (BMD) in the hip and the incidence of vertebral fractures in the MOVER study was examined. Japanese patients from the ibandronate and risedronate treatment groups whose hip BMD had increased during the 3-year treatment period were classified into those with or without vertebral fractures. In both the ibandronate group and the risedronate group, hip BMD gains in the patients who had developed no vertebral fractures during the treatment period were greater than in the patients who developed vertebral fractures. We categorized the gains in hip BMD at 6 months into 3 groups (≤0, >0 to ≤3, and >3 %), and used logistic regression analysis to estimate odds ratios and the probabilities of incidence of vertebral fractures at 12, 24, and 36 months. The current study demonstrated that greater gains in hip BMD during the first 6 months of treatment were associated with a reduction in the risk of subsequent vertebral fractures during the duration of treatment, and suggested that measurement of hip BMD gain at that time could lead to a prediction of the risk of the future vertebral fracture incidence.

Is vertebroplasty a risk factor for subsequent vertebral fracture, meta-analysis of published evidence?

In our paper, we systemically retrieved the eligible study evaluating whether increased incidence of subsequent vertebral fracture is associated with vertebroplasty. Main effect sizes were vertebral fracture rates reported in terms of hazard ratio (HR) for time-to-event data or relative risk (RR) for dichotomous outcome. Our results do not support the hypothesis that vertebroplasty contributes to increased risk of subsequent vertebral fracture, neither adjacent nor total vertebral fracture. Vertebroplasty has been implicated in significant changes in vertebral strength, vertebral shape, and consequently increased risk for subsequent vertebral fracture, especially the adjacent level. Here, we further tested the hypothesis whether new-onset vertebral fracture is a natural result of osteoporosis or consequence of cement augmentation. Relevant literatures were retrieved using PubMed, Web of Knowledge, and Cochrane Central Register of Controlled Trials (CENTRAL), supplemented by a hand-search of the reference lists of selected articles. Eligible studies assessed whether increased morbidity of subsequent vertebral fracture is associated with vertebroplasty. Main effect sizes were vertebral fracture rates reported in terms of hazard ratio (HR) for time-to-event data or relative risk (RR) for dichotomous outcome. Random-effects model was used to account for clinical or methodological heterogeneity across studies. Thirteen studies with a number of 2,551 individuals (1,631 in vertebroplasty group and 920 in control group) were suitable for this meta-analysis. In trials that reported adjacent vertebral fracture as time-to-event data (two trials, n = 328), we found a similar incidence of vertebral fracture in percutaneous vertebroplasty (PVP) group compared to conservative therapy (HR 0.60, 95% confidence interval 0.29 to 1.26; P = 0.18). In trials that reported overall vertebral fracture as time-to-event data (three trials, n = 704), vertebroplasty was associated with a slightly increased but non-significant risk for vertebral fracture (HR 1.14, 95% confidence interval 0.65 to 2.00; P = 0.65). The outcome was further confirmed in the secondary meta-analysis of studies that reported vertebral fracture as dichotomous data. Subgroup analysis according to study design revealed no difference either. Our results do not support the hypothesis that vertebroplasty contributes to increased risk of subsequent vertebral fracture, neither adjacent nor total vertebral fracture. However, adequately designed randomized controlled trials are warranted to confirm the present findings.

Primum Non Nocere

Primum non nocere , or “first do no harm,” is the well-known maxim from the Hippocratic corpus advocating that a physician’s first priority should be to avoid precipitating further injury, or inadvertent worsening of conditions, in patients who are under his or her care. With this founding precept of the health-care tradition in mind, I commend the efforts of Dr. Mandel and his colleagues in bringing to our attention the potential for epidural steroid injections to elevate the risk of vertebral body fracture in elderly individuals. Although this association has been alluded to in previous publications, to the best of my knowledge the study by Mandel et al. is the first scientifically rigorous effort to quantify the fracture risk associated with epidural steroid administration. The study was conducted with use of a propensity-matched cohort with an average age of sixty-six years. Comparison between the patients who received epidural steroid and the controls in the primary analysis revealed that the risk of fracture increased by 21% per episode of steroid administration. Moreover, in the secondary analysis in which the possibility of multiple fractures in a single patient was considered, a significant elevation in the risk of subsequent vertebral fracture following steroid administration was again demonstrated. The identification of this significant association, as well as the quantification of risk inherent with each injection event, represent novel contributions to the literature. It is necessary to appreciate these findings, however, …

Number and severity of prevalent vertebral fractures and the risk of subsequent vertebral fractures in Japanese women with osteoporosis: results from the minodronate trial

The aim was to evaluate the risk of new vertebral fractures with the increasing number and severity of prevalent vertebral fractures in women who received placebo or minodronate in a post hoc analysis of a 2-year randomized, double-blind, placebo-controlled study. The subjects were women aged 55-80years old with 1-5 fragility fractures between the T4 and L4 vertebrae and bone mineral density <80% of the young adult mean. A total of 704 subjects were randomized to take minodronate 1mg (n=359) or placebo (n=345) once a day for 24months. In the placebo group, the risk of incident vertebral fractures during the 2-year observational period was significantly related to the number and severity of prevalent vertebral fractures at baseline. The number of prevalent vertebral fractures was an independent risk factor for incident vertebral fracture in multivariate analysis. The relative risk reductions of vertebral fractures by minodronate treatment were 45.2, 61.1, and 64.2% for patients with 1, 2, and ≥3 prevalent vertebral fractures, respectively, and 87.8, 64.6, and 50.1% for patients with mild, moderate, and severe prevalent vertebral fractures, respectively. In conclusion, the number of prevalent vertebral fractures is an independent risk factor for incident vertebral fracture and minodronate reduces the fracture risk even in patients at a higher risk for fracture.

Commentary: Hypovitaminosis D in patients undergoing kyphoplasty is associated with increased risk of subsequent vertebral fractures

<h3>COMMENTARY ON</h3> Zafeiris CP, Lyritis GP, Papaioannou NA, et al. Hypovitaminosis D as a risk factor of subsequent vertebral fractures after kyphoplasty. Spine J 2012;12:304–12 (<i>in this issue</i>).

Previous fractures at multiple sites increase the risk for subsequent fractures: The global longitudinal study of osteoporosis in women

Previous fractures of the hip, spine, or wrist are well-recognized predictors of future fracture, but the role of other fracture sites is less clear. We sought to assess the relationship between prior fracture at 10 skeletal locations and incident fracture. The Global Longitudinal Study of Osteoporosis in Women (GLOW) is an observational cohort study being conducted in 17 physician practices in 10 countries. Women aged ≥55 years answered questionnaires at baseline and at 1 and/or 2 years (fractures in previous year). Of 60,393 women enrolled, follow-up data were available for 51,762. Of these, 17.6%, 4.0%, and 1.6% had suffered 1, 2, or ≥3 fractures, respectively, since age 45 years. During the first 2 years of follow-up, 3149 women suffered 3683 incident fractures. Compared with women with no previous fractures, women with 1, 2, or ≥3 prior fractures were 1.8-, 3.0-, and 4.8-fold more likely to have any incident fracture; those with ≥3 prior fractures were 9.1-fold more likely to sustain a new vertebral fracture. Nine of 10 prior fracture locations were associated with an incident fracture. The strongest predictors of incident spine and hip fractures were prior spine fracture (hazard ratio [HR] = 7.3) and hip (HR = 3.5). Prior rib fractures were associated with a 2.3-fold risk of subsequent vertebral fracture, and previous upper leg fracture predicted a 2.2-fold increased risk of hip fracture. Women with a history of ankle fracture were at 1.8-fold risk of future fracture of a weight-bearing bone. Our findings suggest that a broad range of prior fracture sites are associated with an increased risk of incident fractures, with important implications for clinical assessments and risk model development.

Balloon kyphoplasty and vertebroplasty in the management of vertebral compression fractures

Vertebral compression fractures (VCFs) are the most prevalent fractures in osteoporotic patients. The classical conservative management of these fractures is through rest, pain medication, bracing and muscle relaxants. The aim of this paper is to review prospective controlled studies comparing the efficacy and safety of minimally invasive techniques for vertebral augmentation, vertebroplasty (VP) and balloon kyphoplasty (BKP), versus non-surgical management (NSM). The Fracture Working Group of the International Osteoporosis Foundation conducted a literature search and developed a review paper on VP and BKP. The results presented for the direct management of osteoporotic VCFs focused on clinical outcomes of these three different procedures, including reduction in pain, improvement of function and mobility, vertebral height restoration and decrease in spinal curvature (kyphosis). Overall, VP and BKP are generally safe procedures that provide quicker pain relief, mobility recovery and in some cases vertebral height restoration than conventional conservative medical treatment, at least in the short term. However, the long-term benefits and safety in terms of risk of subsequent vertebral fractures have not been clearly demonstrated and further prospective randomized studies are needed with standards for reporting. Referral physicians should be aware of VP/BKP and their potential to reduce the health impairment of patients with VCFs. However, VP and BKP are not substitutes for appropriate evaluation and treatment of osteoporosis to reduce the risk of future fractures.

Prevalent vertebral fractures predict subsequent radiographic vertebral fractures in postmenopausal Korean women receiving antiresorptive agent

The relationship between prevalent vertebral fractures and new vertebral fractures in Korean women has not been previously studied. We found that prevalent vertebral fracture is a strong risk factor for subsequent radiographic vertebral fracture, independent of age and spine bone mineral density (BMD) in postmenopausal Korean women receiving antiresorptive agents. The presence of prevalent vertebral fractures increases the risk of subsequent vertebral fractures. This observational study examined whether prevalent vertebral fractures influenced future incident vertebral fracture in postmenopausal women receiving antiresorptive treatment. Using the medical records, we retrospectively assessed 1,200 postmenopausal women who had visited the osteoporosis clinic. Among them, we selected patients whose BMD was measured at least once a year for 3 years. We excluded patients whose lateral spine X-ray film at baseline or follow-up period was missing, which is the key assessment. In the end, we analyzed 666 postmenopausal women. The mean duration of follow-up period was 3.2 years. The majority of patients (83%) received bisphosphonates or raloxifene during the mean duration of 3.2 years. Fifty-five of the 666 women had new incident radiographic vertebral fractures during the follow-up period. Prevalent vertebral fractures were associated with a five-fold increased risk (odd ratio 5.7, 95% CI 3.09-10.74) of incident vertebral fractures after adjusting for age. These associations remained significant after the adjustment for multiple confounding factors (odd ratio 4.4, 95% CI 1.97-9.75). The risk of incident vertebral fracture increased with the number of prevalent vertebral fractures at baseline: 3.4 (95% CI 1.54-7.70) for those with a single fracture and 7.4 (95% CI 3.10-17.54) for those with two or more after adjustment for age and spine BMD. We confirmed that prevalent vertebral fracture is a strong risk factor for new vertebral fractures, independent of age and spine BMD in postmenopausal Korean women receiving antiresorptive agents.

Efficacy and safety of vertebroplasty for treatment of painful osteoporotic vertebral fractures: a randomised controlled trial [ACTRN012605000079640

BackgroundVertebroplasty is a promising but as yet unproven treatment for painful osteoporotic vertebral fractures. It involves radiographic-guided injection of various types of bone cement directly into the vertebral fracture site. Uncontrolled studies and two controlled quasi-experimental before-after studies comparing volunteers who were offered treatment to those who refused it, have suggested an early benefit including rapid pain relief and improved function. Conversely, several uncontrolled studies and one of the controlled before-after studies have also suggested that vertebroplasty may increase the risk of subsequent vertebral fractures, particularly in vertebrae adjacent to treated levels or if cement leakage into the adjacent disc has occurred. As yet, there are no completed randomised controlled trials of vertebroplasty for osteoporotic vertebral fractures. The aims of this participant and outcome assessor-blinded randomised placebo-controlled trial are to i) determine the short-term efficacy and safety (3 months) of vertebroplasty for alleviating pain and improving function for painful osteoporotic vertebral fractures; and ii) determine its medium to longer-term efficacy and safety, particularly the risk of further fracture over 2 years.DesignA double-blind randomised controlled trial of 200 participants with one or two recent painful osteoporotic vertebral fractures. Participants will be stratified by duration of symptoms (< and ≥ 6 weeks), gender and treating radiologist and randomly allocated to either the treatment or placebo. Outcomes will be assessed at baseline, 1 week, 1, 3, 6, 12 and 24 months. Outcome measures include overall, night and rest pain on 10 cm visual analogue scales, quality of life measured by the Assessment of Quality of Life, Osteoporosis Quality of Life and EQ-5D questionnaires; participant perceived recovery on a 7-point ordinal scale ranging from 'a great deal worse' to 'a great deal better'; disability measured by the Roland-Morris Disability Questionnaire; timed 'Up and Go' test; and adverse effects. The presence of new fractures will be assessed by radiographs of the thoracic and lumbar spine performed at 12 and 24 months.DiscussionThe results of this trial will be of major international importance and findings will be immediately translatable into clinical practice.Trial registrationAustralian Clinical Trial Register # [ACTRN012605000079640]