Quantitative ultrasound of the heel and fracture risk assessment: an updated meta-analysis.

Meta-analysis of prospective studies shows that quantitative ultrasound of the heel using validated devices predicts risk of different types of fracture with similar performance across different devices and in elderly men and women. These predictions are independent of the risk estimates from hip DXA measures.Introduction Clinical utilisation of heel quantitative ultrasound (QUS) depends on its power to predict clinical fractures. This is particularly important in settings that have no access to DXA-derived bone density measurements. We aimed to assess the predictive power of heel QUS for fractures using a meta-analysis approach.Methods We conducted an inverse variance random effects meta-analysis of prospective studies with heel QUS measures at baseline and fracture outcomes in their follow-up. Relative risks (RR) per standard deviation (SD) of different QUS parameters (broadband ultrasound attenuation [BUA], speed of sound [SOS], stiffness index [SI], and quantitative ultrasound index [QUI]) for various fracture outcomes (hip, vertebral, any clinical, any osteoporotic and major osteoporotic fractures) were reported based on study questions.Results Twenty-one studies including 55,164 women and 13,742 men were included in the meta-analysis with a total follow-up of 279,124 person-years. All four QUS parameters were associated with risk of different fracture. For instance, RR of hip fracture for 1 SD decrease of BUA was 1.69 (95% CI 1.43-2.00), SOS was 1.96 (95% CI 1.64-2.34), SI was 2.26 (95%CI 1.71-2.99) and QUI was 1.99 (95% CI 1.49-2.67). There was marked heterogeneity among studies on hip and any clinical fractures but no evidence of publication bias amongst them. Validated devices from different manufacturers predicted fracture risks with similar performance (meta-regression p values > 0.05 for difference of devices). QUS measures predicted fracture with a similar performance in men and women. Meta-analysis of studies with QUS measures adjusted for hip BMD showed a significant and independent association with fracture risk (RR/SD for BUA = 1.34 [95%CI 1.22-1.49]).Conclusions This study confirms that heel QUS, using validated devices, predicts risk of different fracture outcomes in elderly men and women. Further research is needed for more widespread utilisation of the heel QUS in clinical settings across the world.

Trabecular Bone Score Helps Classifying Women At Riskof Fracture Prospectively In The Ofely Study

Objectives: Trabecular Bone Score (TBS, Med-Imaps, France) is an index of bone microarchitecture calculated from antero-posterior spine DXA scan and reported to be associated with fracture in prior case-control studies and in a large prospective study with the Prodigy DXA device. Our aim was to assess the ability of TBS to predict incident fracture and improve the classification of fracture prospectively in the OFELY study.Materials/Methods: TBS was assessed in 564 postmenopausal women (66±8 years old) from the OFELY cohort, who had a spine DXA scan (QDR 4500A, Hologic, USA) between year 2000 and 2001. During a mean follow up of 7.8±1.3 years, 94 women sustained a fragility fracture.Results: At the time of baseline DXA scan, women with incident fracture were significantly older (70±9 vs. 65± 8 years), had a lower spine BMD (T-score: −1.9±1.2 vs. −1.3±1.3, p<0.001) and spine TBS (−3.1%, p<0.001) than women without incident fracture. After adjustment for age, BMI and the presence of prevalent fracture, the magnitude of fracture prediction was similar for spine BMD (OR=1.42 [1.11;1.82] per SD decrease [95% CI]) and TBS (OR=1.34 [1.04;1.74]) but the combination of TBS and spine BMD did not improve fracture prediction. Spine BMD and TBS were both correlated with age (respectively r=−0.17 and −0.49, p<0.001) and correlated together with 39% of TBS explained by spine BMD (r=0.63, p<0.001). When using the WHO classification, 38% of the fractures occurred in osteoporotic (fracture rate=29%), 47% in osteopenic (fracture rate=16%) and 15% in women with T-score >−1 (fracture rate=9%). By classifying our population in tertiles of TBS, we found that 47% of the fractures occurred in the lowest tertile of TBS (fracture rate=23%) and 39% of the fracture that occurred in osteopenic women were in the lowest tertile of TBS.Conclusions: Spine BMD and TBS predicted fractures equally well. The addition of TBS to spine BMD added only limited information on fracture risk prediction in our cohort when considering the all range of BMD. Nevertheless combining the osteopenic T-score and the lowest TBS helped defining a subset of osteopenic women at higher risk of fracture.Disclosure of Interest: None declared.

Six years of denosumab treatment in postmenopausal women with osteoporosis: results from the first three years of the freedom extension

Background/Purpose: Denosumab (DMAb) is an approved therapy for the treatment of postmenopausal women with osteoporosis at increased risk for fracture. A favorable risk/benefit profile was demonstrated in the pivotal, 3-year FREEDOM trial (Cummings et al NEJM 2009). The open-label, active-treatment FREEDOM Extension study is investigating the efficacy and safety of DMAb for up to 10 years. The Extension trial enrolled women who had received DMAb or placebo in FREEDOM and provides an opportunity to evaluate the long-term efficacy and safety of continuous DMAb treatment (long-term group), and to replicate the DMAb findings observed in FREEDOM (cross-over group). Here, we report the results from the first 3 years of the Extension, representing up to 6 continuous years of DMAb exposure.Methods: During the Extension, each woman is scheduled to receive 60 mg DMAb every 6 months and supplemental calcium and vitamin D daily. For the analyses reported here, women from the FREEDOM DMAb group received 3 more years of DMAb for a total of 6 years of exposure (long-term group) and women from the FREEDOM placebo group received 3 years of DMAb exposure (cross-over group).Results: Of the 5928 women eligible for the Extension, 4550 (77%) enrolled (N_2343 long-term; N_2207 cross-over). In the long-term group, further significant mean increases in bone mineral density (BMD) occurred 4044 for cumulative 6-year gains of 15.2% at the lumbar spine and 7.5% at the total hip (Figure). During the first 3 years of DMAb treatment during the Extension, the cross-over group had significant mean gains in BMD at the lumbar spine (9.4%) and total hip (4.8%), similar to those observed in the long-term DMAb group during the first 3 years of FREEDOM (lumbar spine, 10.1%; total hip, 5.7%). Serum CTX was rapidly and similarly reduced after the 1st (cross-over) or 7th (long-term) DMAb dose with the characteristic attenuation observed at the end of the dosing period. In the cross-over group, yearly incidences of new vertebral and nonvertebral fractures were lower than in the FREEDOM placebo group. Fracture incidence remained low in the long-term group. Incidences of adverse events (AEs) and serious AEs did not increase over time with DMAb treatment. There were 2 subjects with AEs adjudicated to ONJ in the cross-over group and 2 in the long-term group. Both cases in the cross-over group healed completely and without further complications; 1 of these subjects continues to receive DMAb. Both women in the long-term group continue to be followed. No atypical femur fractures have been observed to date. Figure. Percent changes in bone mineral density during FREEDOM and the Extension Conclusion: DMAb treatment for 6 continuous years (long-term group) remained well tolerated, maintained reduced bone turnover, and continued to significantly increase BMD. Fracture incidence remained low. DMAb treatment for 3 years in the cross-over group reproduced the original observations in FREEDOM.

An unusual natural history of a L5-S1 spondylolisthesis presenting with a sacral insufficiency fracture.

Sacral insufficiency fractures have been described in association with conditions leading to osteoporosis. No association with spondylolisthesis has been described to date. A 60-year-old patient with known lumbosacral isthmic spondylolisthesis presented with exacerbation of symptoms initially thought to be linked to her known spinal pathology. Plain radiography, computer tomography, MRI and bone scan confirmed the presence of a recent sacral insufficiency fracture with anterior angulation. Conservative treatment resulted in improvement of symptoms after 6 months. Care should be taken when considering older patients for more aggressive treatment if they present with exacerbation of back pain and sciatica in the presence of a pre-existing spondylolisthesis. A suspicion of insufficiency fracture should be raised if risk factors exist and further investigations ordered in particular if plain radiography is normal. Lumbosacral fusion might be inappropriate in this setting.

Energy balance in elderly patients after surgery for a femoral neck fracture.

To study energy and protein balances in elderly patients after surgery, spontaneous energy and protein intake and resting energy expenditure (REE) were measured in 20 elderly female patients with a femoral neck fracture (mean age 81 +/- 4, SD, range 74-87 years; weight 53 +/- 8, range 42-68 kg) during a 5-6 day period following surgery. REE, measured over 20-40 min by indirect calorimetry using a ventilated canopy, averaged 0.98 +/- 0.15 kcal/min on day 3 and decreased to 0.93 +/- 0.15 kcal/min on day 8-9 postsurgery (p less than 0.02). REE was positively correlated with body weight (r = 0.69, p less than 0.005). Mean REE extrapolated to 24 hr (24-REE) was 1283 +/- 194 kcal/day. Mean daily food energy intake measured over the 5-day follow-up period was 1097 +/- 333 kcal/day and was positively correlated with 24-REE (r = 0.50, p less than 0.05). Daily energy balance was -235 +/- 351 kcal/day on day 3 (p less than 0.01 vs zero) and -13 +/- 392 kcal/day on day 8-9 postsurgery (NS vs zero) with a mean over the study period of -185 +/- 289 kcal/day (p less than 0.01 vs zero). When an extra 100 kcal/day was allowed for the energy cost of physical activity, mean daily energy balance over the 5-day study period was calculated to be -285 +/- 289 kcal/day (p less than 0.01 vs zero). Measurements of total 24-hr urinary nitrogen (N) excretion were obtained in a subgroup of 14 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone mineral density (BMD), micro-architecture estimation (TBS) and vertebral fracture assessment (VFA) extracted from a single DXA device in combination with clinical risk factors improve significantly the identification of women at high risk of fracture

Introduction: Osteoporosis (OP) is a systemic skeletal disease characterized by a low bone mineral density (BMD) and a micro-architectural (MA) deterioration. Clinical risk factors (CRF) are often used as a MA approximation. MA is yet evaluable in daily practice by the Trabecular Bone Score (TBS) measure. TBS is a novel grey-level texture measurement reflecting bone micro-architecture based on the use of experimental variograms of 2D projection images. TBS is very simple to obtain, by reanalyzing a lumbar DXA-scan. TBS has proven to have diagnosis and prognosis value, partially independent of CRF and BMD. The aim of the OsteoLaus cohort is to combine in daily practice the CRF and the information given by DXA (BMD, TBS and vertebral fracture assessment (VFA)) to better identify women at high fracture risk. Method: The OsteoLaus cohort (1400 women 50 to 80 years living in Lausanne, Switzerland) started in 2010. This study is derived from the cohort COLAUS who started in Lausanne in 2003. The main goals of COLAUS is to obtain information on the epidemiology and genetic determinants of cardiovascular risk in 6700 men and women. CRF for OP, bone ultrasound of the heel, lumbar spine and hip BMD, VFA by DXA and MA evaluation by TBS are recorded in OsteoLaus. Preliminary results are reported. Results: We included 631 women: mean age 67.4±6.7 y, BMI 26.1±4.6, mean lumbar spine BMD 0.943±0.168 (T-score -1.4 SD), TBS 1.271±0.103. As expected, correlation between BMD and site matched TBS is low (r2=0.16). Prevalence of VFx grade 2/3, major OP Fx and all OP Fx is 8.4%, 17.0% and 26.0% respectively. Age- and BMI-adjusted ORs (per SD decrease) are 1.8 (1.2- 2.5), 1.6 (1.2-2.1), 1.3 (1.1-1.6) for BMD for the different categories of fractures and 2.0 (1.4-3.0), 1.9 (1.4-2.5), 1.4 (1.1-1.7) for TBS respectively. Only 32 to 37% of women with OP Fx have a BMD < -2.5 SD or a TBS < 1.200. If we combine a BMD < -2.5 SD or a TBS < 1.200, 54 to 60% of women with an osteoporotic Fx are identified. Conclusion: As in the already published studies, these preliminary results confirm the partial independence between BMD and TBS. More importantly, a combination of TBS subsequent to BMD increases significantly the identification of women with prevalent OP Fx which would have been miss-classified by BMD alone. For the first time we are able to have complementary information about fracture (VFA), density (BMD), micro- and macro architecture (TBS & HAS) from a simple, low ionizing radiation and cheap device: DXA. Such complementary information is very useful for the patient in the daily practice and moreover will likely have an impact on cost effectiveness analysis.

Prospective evaluation of risk of vertebral fractures using quantitative ultrasound measurements and bone mineral density in a population-based sample of postmenopausal women: results of the Basel Osteoporosis Study.

OBJECTIVE: Prospective studies have shown that quantitative ultrasound (QUS) techniques predict the risk of fracture of the proximal femur with similar standardised risk ratios to dual-energy x-ray absorptiometry (DXA). Few studies have investigated these devices for the prediction of vertebral fractures. The Basel Osteoporosis Study (BOS) is a population-based prospective study to assess the performance of QUS devices and DXA in predicting incident vertebral fractures. METHODS: 432 women aged 60-80 years were followed-up for 3 years. Incident vertebral fractures were assessed radiologically. Bone measurements using DXA (spine and hip) and QUS measurements (calcaneus and proximal phalanges) were performed. Measurements were assessed for their value in predicting incident vertebral fractures using logistic regression. RESULTS: QUS measurements at the calcaneus and DXA measurements discriminated between women with and without incident vertebral fracture, (20% height reduction). The relative risks (RRs) for vertebral fracture, adjusted for age, were 2.3 for the Stiffness Index (SI) and 2.8 for the Quantitative Ultrasound Index (QUI) at the calcaneus and 2.0 for bone mineral density at the lumbar spine. The predictive value (AUC (95% CI)) of QUS measurements at the calcaneus remained highly significant (0.70 for SI, 0.72 for the QUI, and 0.67 for DXA at the lumbar spine) even after adjustment for other confounding variables. CONCLUSIONS: QUS of the calcaneus and bone mineral density measurements were shown to be significant predictors of incident vertebral fracture. The RRs for QUS measurements at the calcaneus are of similar magnitude as for DXA measurements.

What was your fracture risk evaluated by FRAX(®) the day before your osteoporotic fracture?

Osteoporotic fracture (OF) is one of the major causes of morbidity and mortality in industrialized countries. Switzerland is among the countries with the greatest risk. Our aim was (1) to calculate the FRAX(®) in a selected Swiss population the day before the occurrence of an OF and (2) to compare the results with the proposed Swiss FRAX(®) thresholds. The Swiss Association Against Osteoporosis proposed guidelines for the treatment of osteoporosis based on age-dependent thresholds. To identify a population at a very high risk of osteoporotic fracture, we included all consecutive patients in the active OF pathway cohort from the Lausanne University Hospital, Switzerland. FRAX(®) was calculated with the available data the day before the actual OF. People with a FRAX(®) body mass index (BMI) or a FRAX(®) (bone mineral density) BMD lower than the Swiss thresholds were not considered at high risk. Two-hundred thirty-seven patients were included with a mean age of 77.2 years, and 80 % were female. Major types of fracture included hip (58 %) and proximal humerus (25 %) fractures. Mean FRAX(®) BMI values were 28.0, 10.0, 13.0, 26.0, and 37.0 % for age groups 50-59, 60-69, 70-79, and 80-89 years old, respectively. Fifty percent of the population was not considered at high risk by the FRAX(®) BMI. FRAX(®) BMD was available for 95 patients, and 45 % had a T score < -2.5 standard deviation. Only 30 % of patients with a normal or osteopenic BMD were classified at high risk by FRAX(®) BMD. The current proposed Swiss thresholds were not able to classify at high risk in 50 to 70 % of the studied population the day before a major OF.

Multiple non-ossifying fibromas as a cause of pathological femoral fracture in Jaffe-Campanacci syndrome.

BACKGROUND: Jaffe-Campanacci is a rare syndrome characterised by the association of café-au-lait spots, axillary freckles, multiple non-ossifying fibromas of the long bones and jaw, as well as some features of type 1 neurofibromatosis. There are less than 30 reported cases, and a genetic profile has not yet been determined. Furthermore, it has not been clarified whether it is a subtype of type 1 neurofibromatosis or a separate syndrome. The risk of pathological fracture is over 50%, due to substantial cortical thinning of the weight-bearing bones. CASE PRESENTATION: A 17-year-old female patient, known for type 1 neurofibromatosis, presented with a low-energy distal femoral fracture due to disseminated large non-ossifying fibromas. Investigations revealed all of the distinctive signs of Jaffe-Campanacci syndrome. Both her distal femurs and proximal tibias exhibited multiple non-ossifying fibromas. The fracture was treated by open reduction and internal plate fixation. Some of the bony lesions were biopsied to confirm the diagnosis. The fracture healed eventless, as did the lesions biopsied or involved in the fracture. The other ones healed after curettage and bone grafting performed at the time of plate removal. CONCLUSION: Jaffe-Campanacci is a rare syndrome having unclear interactions with type 1 neurofibromatosis, which still needs to be characterised genetically. It is associated with a high risk of pathological fracture, due to the presence of multiple large non-ossifying fibromas of the long bones, with an expected normal healing time. Curettage and bone grafting promote healing of the lesions and should be considered to prevent pathological fracture. We agree with other authors that all patients with newly-diagnosed type 1 neurofibromatosis should undergo an osseous screening to detect disseminated non-ossifying fibromas, and evaluate the inherent risk of pathological fracture.

Lumbar spine texture enhances 10-year fracture probability assessment.

We found that lumbar spine texture analysis using trabecular bone score (TBS) is a risk factor for MOF and a risk factor for death in a retrospective cohort study from a large clinical registry for the province of Manitoba, Canada. INTRODUCTION: FRAX® estimates the 10-year probability of major osteoporotic fracture (MOF) using clinical risk factors and femoral neck bone mineral density (BMD). Trabecular bone score (TBS), derived from texture in the spine dual X-ray absorptiometry (DXA) image, is related to bone microarchitecture and fracture risk independently of BMD. Our objective was to determine whether TBS provides information on MOF probability beyond that provided by the FRAX variables. METHODS: We included 33,352 women aged 40-100 years (mean 63 years) with baseline DXA measurements of lumbar spine TBS and femoral neck BMD. The association between TBS, the FRAX variables, and the risk of MOF or death was examined using an extension of the Poisson regression model. RESULTS: During the mean of 4.7 years, 1,754 women died and 1,872 sustained one or more MOF. For each standard deviation reduction in TBS, there was a 36 % increase in MOF risk (HR 1.36, 95 % CI 1.30-1.42, p < 0.001) and a 32 % increase in death (HR 1.32, 95 % CI 1.26-1.39, p < 0.001). When adjusted for significant clinical risk factors and femoral neck BMD, lumbar spine TBS was still a significant predictor of MOF (HR 1.18, 95 % CI 1.12-1.23) and death (HR 1.20, 95 % CI 1.14-1.26). Models for estimating MOF probability, accounting for competing mortality, showed that low TBS (10th percentile) increased risk by 1.5-1.6-fold compared with high TBS (90th percentile) across a broad range of ages and femoral neck T-scores. CONCLUSIONS: Lumbar spine TBS is able to predict incident MOF independent of FRAX clinical risk factors and femoral neck BMD even after accounting for the increased death hazard.

Documentation of fracture severity with the AO classification of pediatric long-bone fractures.

BACKGROUND: The AO comprehensive pediatric longbone fracture classification system describes the localization and morphology of fractures, and considers severity in 3 categories: (1) simple, (2) wedge, and (3) complex. We evaluated the reliability and accuracy of surgeons in using this rating system. MATERIAL AND METHODS: In a first validation phase, 5 experienced pediatric (orthopedic) surgeons reviewed radiographs of 267 prospectively collected pediatric fractures (agreement study A). In a second study (B), 70 surgeons of various levels of experience in 15 clinics classified 275 fractures via internet. Simple fractures comprised about 90%, 99% and 100% of diaphyseal (D), metaphyseal (M), and epiphyseal (E) fractures, respectively. RESULTS: Kappa coefficients for severity coding in D fractures were 0.82 and 0.51 in studies A and B, respectively. The median accuracy of surgeons in classifying simple fractures was above 97% in both studies but was lower, 85% (46-100), for wedge or complex D fractures. INTERPRETATION: While reliability and accuracy estimates were satisfactory as a whole, the ratings of some individual surgeons were inadequate. Our findings suggest that the classification of fracture severity in children should be done in only two categories that distinguish between simple and wedge/complex fractures.

Fracture vertébrate évaluée par ostéodensitométrie. Un nouveau facteur de risque pour la fracture [Vertebral fracture assessed by DXA: a new risk factor for fracture]

At the age of 50, a woman has a lifetime risk of more than 40% to present a vertebral fracture. More than 60% of vertebral fractures remain undiagnosed. As a consequence it is of major importance to develop screening strategies to detect these fractures. Vertebral fracture assessment (VFA) by DXA allows one to detect vertebral fracture from T4 to L4 using DXA devices, while performing also during the same visit the bone mineral density measurement. Such an approach should improve the evaluation of fracture risk and therapeutic indication. Compared to the standard X-ray assessment, VFA highly enables to detect moderate or severe vertebral fractures below T6.