Previous fracture and subsequent fracture risk: a meta-analysis to update FRAX.

A large international meta-analysis using primary data from 64 cohorts has quantified the increased risk of fracture associated with a previous history of fracture for future use in FRAX. INTRODUCTION: The aim of this study was to quantify the fracture risk associated with a prior fracture on an international basis and to explore the relationship of this risk with age, sex, time since baseline and bone mineral density (BMD). METHODS: We studied 665,971 men and 1,438,535 women from 64 cohorts in 32 countries followed for a total of 19.5 million person-years. The effect of a prior history of fracture on the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture, and hip fracture alone was examined using an extended Poisson model in each cohort. Covariates examined were age, sex, BMD, and duration of follow-up. The results of the different studies were merged by using the weighted ß-coefficients. RESULTS: A previous fracture history, compared with individuals without a prior fracture, was associated with a significantly increased risk of any clinical fracture (hazard ratio, HR = 1.88; 95% CI = 1.72-2.07). The risk ratio was similar for the outcome of osteoporotic fracture (HR = 1.87; 95% CI = 1.69-2.07), major osteoporotic fracture (HR = 1.83; 95% CI = 1.63-2.06), or for hip fracture (HR = 1.82; 95% CI = 1.62-2.06). There was no significant difference in risk ratio between men and women. Subsequent fracture risk was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any clinical fracture (14%), osteoporotic fracture (17%), and for hip fracture (33%). The risk ratio for all fracture outcomes related to prior fracture decreased significantly with adjustment for age and time since baseline examination. CONCLUSION: A previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by BMD. The effect is similar in men and women. Its quantitation on an international basis permits the more accurate use of this risk factor in case finding strategies.

Update of the fracture risk prediction tool FRAX: a systematic review of potential cohorts and analysis plan.

We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. INTRODUCTION: The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors. METHODS: A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible. RESULTS: Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed. CONCLUSIONS: These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).

Osteoporosis case ascertainment strategies in European and Asian countries: a comparative review.

While many clinical guidelines recommend screening for osteoporosis for early detection and treatment, there is great diversity in the case-finding strategies globally. We sought to compare case-finding strategies, focusing on the approaches used in European and Asian countries. This article provides an overview of the current case-finding strategies in the UK, Germany (including Austria and German-speaking regions of Switzerland), China, Japan, and Korea. We conducted a review of current treatment guidelines in each country and included expert opinions from key opinion leaders. Most countries define osteoporosis among patients with a radiographically identified fracture of the hip or the vertebrae. However, for other types of fractures, or in the absence of a fracture, varying combinations of risk-factor assessment and areal bone mineral density (aBMD) assessed by dual X-ray absorptiometry are used to define osteoporosis cases. A T-score ≤ - 2.5 is accepted to identify osteoporosis in the absence of a fracture; however, not all countries accept DXA alone as the sole criteria. Additionally, the critera for requiring clinical risk factors in addition to aBMD differ across countries. In most Asian countries, aBMD scanning is only provided beyond a particular age threshold. However, all guidelines recommend fracture risk assessment in younger ages if risk factors are present. Our review identified that strategies for case-finding differ regionally, particularly among patients without a fracture. More homogenized ways of identifying osteoporosis cases are needed, in both the Eastern and the Western countries, to improve osteoporosis case-finding before a fracture occurs.Case-finding in osteoporosis is essential to initiate treatment and minimize fracture risk. We identified differences in case-finding strategies between Eastern and Western countries. In the absence of a diagnosed fracture, varying combinations of risk factors and bone density measurements are used. Standardized case-finding strategies may help improve treatment rates.

Perspectives on the non-invasive evaluation of femoral strength in the assessment of hip fracture risk.

We reviewed the experimental and clinical evidence that hip bone strength estimated by BMD and/or finite element analysis (FEA) reflects the actual strength of the proximal femur and is associated with hip fracture risk and its changes upon treatment. INTRODUCTION: The risk of hip fractures increases exponentially with age due to a progressive loss of bone mass, deterioration of bone structure, and increased incidence of falls. Areal bone mineral density (aBMD), measured by dual-energy X-ray absorptiometry (DXA), is the most used surrogate marker of bone strength. However, age-related declines in bone strength exceed those of aBMD, and the majority of fractures occur in those who are not identified as osteoporotic by BMD testing. With hip fracture incidence increasing worldwide, the development of accurate methods to estimate bone strength in vivo would be very useful to predict the risk of hip fracture and to monitor the effects of osteoporosis therapies. METHODS: We reviewed experimental and clinical evidence regarding the association between aBMD and/orCT-finite element analysis (FEA) estimated femoral strength and hip fracture risk as well as their changes with treatment. RESULTS: Femoral aBMD and bone strength estimates by CT-FEA explain a large proportion of femoral strength ex vivo and predict hip fracture risk in vivo. Changes in femoral aBMD are strongly associated with anti-fracture efficacy of osteoporosis treatments, though comparable data for FEA are currently not available. CONCLUSIONS: Hip aBMD and estimated femoral strength are good predictors of fracture risk and could potentially be used as surrogate endpoints for fracture in clinical trials. Further improvements of FEA may be achieved by incorporating trabecular orientations, enhanced cortical modeling, effects of aging on bone tissue ductility, and multiple sideway fall loading conditions.

Effectiveness of a two-step population-based osteoporosis screening program using FRAX: the randomized Risk-stratified Osteoporosis Strategy Evaluation (ROSE) study.

The Risk-stratified Osteoporosis Strategy Evaluation (ROSE) study investigated the effectiveness of a two-step screening program for osteoporosis in women. We found no overall reduction in fractures from systematic screening compared to the current case-finding strategy. The group of moderate- to high-risk women, who accepted the invitation to DXA, seemed to benefit from the program. INTRODUCTION: The purpose of the ROSE study was to investigate the effectiveness of a two-step population-based osteoporosis screening program using the Fracture Risk Assessment Tool (FRAX) derived from a self-administered questionnaire to select women for DXA scan. After the scanning, standard osteoporosis management according to Danish national guidelines was followed. METHODS: Participants were randomized to either screening or control group, and randomization was stratified according to age and area of residence. Inclusion took place from February 2010 to November 2011. Participants received a self-administered questionnaire, and women in the screening group with a FRAX score ≥ 15% (major osteoporotic fractures) were invited to a DXA scan. Primary outcome was incident clinical fractures. Intention-to-treat analysis and two per-protocol analyses were performed. RESULTS: A total of 3416 fractures were observed during a median follow-up of 5 years. No significant differences were found in the intention-to-treat analyses with 34,229 women included aged 65-80 years. The per-protocol analyses showed a risk reduction in the group that underwent DXA scanning compared to women in the control group with a FRAX ≥ 15%, in regard to major osteoporotic fractures, hip fractures, and all fractures. The risk reduction was most pronounced for hip fractures (adjusted SHR 0.741, p = 0.007). CONCLUSIONS: Compared to an office-based case-finding strategy, the two-step systematic screening strategy had no overall effect on fracture incidence. The two-step strategy seemed, however, to be beneficial in the group of women who were identified by FRAX as moderate- or high-risk patients and complied with DXA.

Non-participation in systematic screening for osteoporosis-the ROSE trial.

Population-based screening for osteoporosis is still controversial and has not been implemented. Non-participation in systematic screening was evaluated in 34,229 women age 65-81 years. Although participation rate was high, non-participation was associated with comorbidity, aging other risk factors for fractures, and markers of low social status, e.g., low income, pension, and living alone. A range of strategies is needed to increase participation, including development of targeted information and further research to better understand the barriers and enablers in screening for osteoporosis. INTRODUCTION: Participation is crucial to the success of a screening program. The objective of this study was to analyze non-participation in Risk-stratified Osteoporosis Strategy Evaluation, a two-step population-based screening program for osteoporosis. METHODS: Thirty-four thousand two hundred twenty-nine women aged 65 to 81 years were randomly selected from the background population and randomized to either a screening group (intervention) or a control group. All women received a self-administered questionnaire designed to allow calculation of future risk of fracture based on FRAX. In the intervention group, women with an estimated high risk of future fracture were invited to DXA scanning. Information on individual socioeconomic status and comorbidity was obtained from national registers. RESULTS: A completed questionnaire was returned by 20,905 (61%) women. Non-completion was associated with older age, living alone, lower education, lower income, and higher comorbidity. In the intervention group, ticking "not interested in DXA" in the questionnaire was associated with older age, living alone, and low self-perceived fracture risk. Women with previous fracture or history of parental hip fracture were more likely to accept screening by DXA. Dropping out when offered DXA, was associated with older age, current smoking, higher alcohol consumption, and physical impairment. CONCLUSIONS: Barriers to population-based screening for osteoporosis appear to be both psychosocial and physical in nature. Women who decline are older, have lower self-perceived fracture risk, and more often live alone compared to women who accept the program. Dropping out after primary acceptance is associated not only with aging and physical impairment but also with current smoking and alcohol consumption. Measures to increase program participation could include targeted information and reducing physical barriers for attending screening procedures.

The role of patient-mode high-resolution peripheral quantitative computed tomography indices in the prediction of failure strength of the elderly women's thoracic vertebral body.

UNLABELLED: The correlations between the failure load of 20 T12 vertebral bodies, their patient-mode high-resolution peripheral quantitative computed tomography (HR-pQCT) indices, and the L1 areal bone mineral density (aBMD) were investigated. For the prediction of the T12 vertebral failure load, the T12 HR-pQCT microarchitectural parameters added significant information to that of L1 aBMD and to that of cortical BMD, but not to that of T12 vertebral BMD and not to that of T12 trabecular BMD. INTRODUCTION: HR-pQCT is a new in vivo imaging technique for assessing the three-dimensional microarchitecture of cortical and trabecular bone at the distal radius and tibia. But little is known about this technique in the direct measurement of vertebral body. METHODS: Twenty female donors with the mean age of 80.1 (7.6) years were included in the study. Dual X-ray absorptiometry of the lumbar spine and femur was performed. The spinal specimens (T11/T12/L1) were dissected, scanned using HR-pQCT scanner, and mechanically tested under 4° wedge compression. The L1 aBMD, T12 patient-mode HR-pQCT indices, and T12 vertebral failure loads were analyzed. RESULTS: For the prediction of vertebral failure load, the inclusion of BV/TV into L1 aBMD was the best model (R (2) = 0.52), Tb.N and Tb.Sp added significant information to the L1 aBMD and to the cortical BMD, but none of the vertebral microarchitectural parameters yielded additional significant information to the trabecular BMD (or BV/TV) and to the vertebral BMD. CONCLUSION: Vertebral microarchitectural parameters obtained from the patient-mode HR-pQCT analysis provide significant information on bone strength complementary to that of aBMD and to that of cortical BMD, but not to that of vertebral BMD and not to that of trabecular BMD.

Self-perceived facture risk: factors underlying women's perception of risk for osteoporotic fractures: the Risk-Stratified Osteoporosis Strategy Evaluation study (ROSE).

SUMMARY: This Danish cross-sectional study (n=20,905) showed that women aged 65-81 years generally underestimated fracture risk compared to absolute risk estimated by the FRAX® algorithm. Significant association was found between risk factors (e.g., previous fracture, parental hip fracture, and self-rated heath) and self-perceived fracture risk. Although women recognized the importance of some fracture risk factors, a number of significant risk factors appeared to be less well known. INTRODUCTION: The aim of this study is to investigate women's self-perceived fracture risk and potential factors associated with this and to compare self-perceived risk with absolute fracture risk estimated by FRAX® in women aged 65-80 years. METHODS: Data from 20,905 questionnaires from the ROSE study were analyzed. The questionnaire included 25 items on osteoporosis, risk factors for fractures, and self-perceived risk of fractures and enabled calculation of absolute fracture risk by FRAX®. Data were analyzed using bivariate tests and regression models. RESULTS: Women generally underestimated their fracture risk compared to absolute risk estimated by FRAX®. Women with risk factors for facture estimated their fracture risk significantly higher than their peers. No correlation between self-perceived risk and absolute risk was found. The ordered logistic regression model showed a significant association between high self-perceived fracture risk and previous fragility fracture, parental hip fracture, falls, self-rated heath, conditions related to secondary osteoporosis, and inability to do housework. CONCLUSIONS: These women aged 65-81 years underestimated their risk of fracture. However, they did seem to have an understanding of the importance of some risk factors such as previous fractures, parental hip fracture and falls. Risk communication is a key element in fracture prevention and should have greater focus on less well-known risk factors. Furthermore, it is important to acknowledge that risk perception is not based solely on potential risk factors but is also affected by experiences from everyday life to personal history.

A low-radiation exposure protocol for 3D QCT of the spine.

SUMMARY: Cadaver and phantom measurements and simulations confirmed that radiation exposure in 3D QCT of the spine can be reduced if 80 kV instead of 120 kV protocols are used; 120 mAs and slice thicknesses of 1-1.3 mm should be usable but obese patient will require higher milliampere-second settings. PURPOSE: To develop a low-radiation exposure CT acquisition protocol for 3D QCT of the thoracolumbar spine. METHODS: Twenty-six cadavers were scanned with a standard protocol of 120 kV, 100 mAs and with a low-dose protocol using 90 kV, 150 mAs. The scan range included the vertebrae T6 to L4. Each vertebra was segmented and the integral volume and BMD of the total vertebral body were determined. Effective dose values were estimated. The impact of milliampere-second reduction on image quality was simulated by adding noise. RESULTS: One hundred ninety-six vertebrae were analyzed. Integral volume as well as integral BMD correlated significantly (p < 0.001) between standard and low-dose protocols (volume, r (2) = 0.991, residual root mean square (RMS) error, 0.77 cm(3); BMD, r (2) = 0.985, RMS error, 4.21 mg/cm(3)). The slope significantly differed from 1 for integral BMD but not for volume hinting at residual field inhomogeneity differences between the two voltage settings that could be corrected by cross-calibration. Compared to the standard protocol, effective dose was reduced by over 50 % in the low-dose protocol. Adding noise in the 90 kV images to simulate a reduction from 150 to 100 mAs did not affect the results for integral volume or BMD. CONCLUSIONS: For 3D QCT of the spine, depending on scanner type, 80 or 90 kV instead of 120 kV protocols may be considered as an important option to reduce radiation exposure; 120 mAs and slice thicknesses of 1-1.5 mm are usable if segmentation is robust to noise. In obese patients, higher milliampere-second settings will be required.

TBS result is not affected by lumbar spine osteoarthritis.

UNLABELLED: The effect of lumbar osteoarthritis on bone density and trabecular bone score (TBS) was evaluated cross-sectionally and prospectively in postmenopausal women. Lumbar spine osteoarthritis was graded according to Kellgren and Lawrence grades. Lumbar osteoarthritis was found to increase lumbar spine bone density, but not TBS. INTRODUCTION: Lumbar osteoarthritis overestimates lumbar bone density (areal bone mineral density (aBMD)). A new texture parameter, the TBS, has been proposed. Calculation of aBMD uses grey level value, while TBS uses grey level variation. Therefore, our hypothesis was that TBS is not influenced by lumbar spine osteoarthritis. METHODS: Menopausal women participating in osteoporosis and ultrasound (OPUS) study were included. They had an aBMD measurement of the spine and hip at baseline and 6-year visit. TBS was calculated on lumbar spine dual-energy X-ray absorptiometry (DXA) scans in an automated manner. The presence of lumbar osteoarthritis was evaluated on baseline radiographs using Kellgren and Lawrence (K&L) classification. Grades range from 0 to 4. In our study, osteoarthritis was defined by at least K&L grade 2. RESULTS: This study included 1,254 menopausal women (66.7 ± 7.1 years). Among them, 727 attended the 6-year follow-up visit. Patients with lumbar osteoarthritis had an aBMD higher than those without lumbar osteoarthritis at the lumbar spine, but not at the hip. However, the aBMD significantly increased in all sites with the grade of K&L. In contrast, spine TBS was not different between patients with and without lumbar osteoarthritis (p = 0.70), and it was not correlated with K&L grade. Spine TBS and aBMD at all sites were negatively correlated with age (p < 0.0001). Body mass index was correlated positively with aBMD and negatively with spine TBS (p < 0.0001). The 6-year change of aBMD was significant in the hip and nonsignificant in the lumbar spine. That of TBS was significant, with a 3.3 % decrease (p < 0.0001), independent of K&L grade (p = 0.28). CONCLUSION: In postmenopausal women, lumbar osteoarthritis leads to an increase in lumbar spine aBMD. In contrast, spine TBS is not affected by lumbar osteoarthritis.

Impact of femoral neck and lumbar spine BMD discordances on FRAX probabilities in women: a meta-analysis of international cohorts.

There are occasional marked discordances in BMD T-scores at the lumbar spine (LS) and femoral neck (FN). We investigated whether such discordances could contribute independently to fracture prediction using FRAX. We studied 21,158 women, average age 63 years, from 10 prospective cohorts with baseline FRAX variables as well as FN and LS BMD. Incident fractures were collected by self-report and/or radiographic reports. Extended Poisson regression examined the relationship between differences in LS and FN T-scores (ΔLS-FN) and fracture risk, adjusted for age, time since baseline and other factors including FRAX 10-year probability for major osteoporotic fracture calculated using FN BMD. To examine the effect of an adjustment for ΔLS-FN on reclassification, women were separated into risk categories by their FRAX major fracture probability. High risk was classified using two approaches: being above the National Osteoporosis Guideline Group intervention threshold or, separately, being in the highest third of each cohort. The absolute ΔLS-FN was greater than 2 SD for 2.5% of women and between 1 and 2 SD for 21%. ΔLS-FN was associated with a significant risk of fracture adjusted for baseline FRAX (HR per SD change = 1.09; 95% CI = 1.04-1.15). In reclassification analyses, only 2.3-3.2% of the women moved to a higher or lower risk category when using FRAX with ΔLS-FN compared with FN-derived FRAX alone. Adjustment of estimated fracture risk for a large LS/FN discrepancy (>2SD) impacts to a large extent on only a relatively small number of individuals. More moderate (1-2SD) discordances in FN and LS T-scores have a small impact on FRAX probabilities. This might still improve clinical decision-making, particularly in women with probabilities close to an intervention threshold.

Effect of weight loss and regain on adipose tissue distribution, composition of lean mass and resting energy expenditure in young overweight and obese adults.

BACKGROUND: Although weight cycling is frequent in obese patients, the adverse consequences on body composition and an increased propensity to weight gain remain controversial. OBJECTIVE: We investigated the effect of intentional weight loss and spontaneous regain on fat distribution, the composition of lean mass and resting energy expenditure (REE). DESIGN: Weight regainers (≥ 30% of loss, n=27) and weight-stable subjects (within <± 20% of weight change, n=20) were selected from 103 overweight and obese subjects (body mass index 28-43 kg m(-2), 24-45 years) who passed a 13-week low-calorie diet intervention. REE and body composition (by densitometry and whole-body magnetic resonance imaging) were examined at baseline, after weight loss and at 6 months of follow-up. RESULTS: Mean weight loss was -12.3 ± 3.3 kg in weight-stable subjects and -9.0 ± 4.3 kg in weight regainers (P<0.01). Weight regain was incomplete, accounting for 83 and 42% of weight loss in women and men. Regain in total fat and different adipose tissue depots was in proportion to weight regain except for a higher regain in adipose tissue of the extremities in women and a lower regain in extremity and visceral adipose tissue in men. In both genders, regain in skeletal muscle of the trunk lagged behind skeletal muscle regain at the extremities. In contrast to weight-stable subjects, weight regainers showed a reduced REE adjusted for changes in organ and tissue masses after weight loss (P<0.001). CONCLUSION: Weight regain did not adversely affect body fat distribution. Weight loss-associated adaptations in REE may impair weight loss and contribute to weight regain.

Cancer-associated bone disease.

Bone is commonly affected in cancer. Cancer-induced bone disease results from the primary disease, or from therapies against the primary condition, causing bone fragility. Bone-modifying agents, such as bisphosphonates and denosumab, are efficacious in preventing and delaying cancer-related bone disease. With evidence-based care pathways, guidelines assist physicians in clinical decision-making. Of the 57 million deaths in 2008 worldwide, almost two thirds were due to non-communicable diseases, led by cardiovascular diseases and cancers. Bone is a commonly affected organ in cancer, and although the incidence of metastatic bone disease is not well defined, it is estimated that around half of patients who die from cancer in the USA each year have bone involvement. Furthermore, cancer-induced bone disease can result from the primary disease itself, either due to circulating bone resorbing substances or metastatic bone disease, such as commonly occurs with breast, lung and prostate cancer, or from therapies administered to treat the primary condition thus causing bone loss and fractures. Treatment-induced osteoporosis may occur in the setting of glucocorticoid therapy or oestrogen deprivation therapy, chemotherapy-induced ovarian failure and androgen deprivation therapy. Tumour skeletal-related events include pathologic fractures, spinal cord compression, surgery and radiotherapy to bone and may or may not include hypercalcaemia of malignancy while skeletal complication refers to pain and other symptoms. Some evidence demonstrates the efficacy of various interventions including bone-modifying agents, such as bisphosphonates and denosumab, in preventing or delaying cancer-related bone disease. The latter includes treatment of patients with metastatic skeletal lesions in general, adjuvant treatment of breast and prostate cancer in particular, and the prevention of cancer-associated bone disease. This has led to the development of guidelines by several societies and working groups to assist physicians in clinical decision making, providing them with evidence-based care pathways to prevent skeletal-related events and bone loss. The goal of this paper is to put forth an IOF position paper addressing bone diseases and cancer and summarizing the position papers of other organizations.

Early changes in biochemical markers of bone formation during teriparatide therapy correlate with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis.

UNLABELLED: Changes of the bone formation marker PINP correlated positively with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis (GIO) who received 18-month treatment with teriparatide, but not with risedronate. These results support the use of PINP as a surrogate marker of bone strength in GIO patients treated with teriparatide. INTRODUCTION: To investigate the correlations between biochemical markers of bone turnover and vertebral strength estimated by finite element analysis (FEA) in men with GIO. METHODS: A total of 92 men with GIO were included in an 18-month, randomized, open-label trial of teriparatide (20 µg/day, n = 45) and risedronate (35 mg/week, n = 47). High-resolution quantitative computed tomography images of the 12th thoracic vertebra obtained at baseline, 6 and 18 months were converted into digital nonlinear FE models and subjected to anterior bending, axial compression and torsion. Stiffness and strength were computed for each model and loading mode. Serum biochemical markers of bone formation (amino-terminal-propeptide of type I collagen [PINP]) and bone resorption (type I collagen cross-linked C-telopeptide degradation fragments [CTx]) were measured at baseline, 3 months, 6 months and 18 months. A mixed-model of repeated measures analysed changes from baseline and between-group differences. Spearman correlations assessed the relationship between changes from baseline of bone markers with FEA variables. RESULTS: PINP and CTx levels increased in the teriparatide group and decreased in the risedronate group. FEA-derived parameters increased in both groups, but were significantly higher at 18 months in the teriparatide group. Significant positive correlations were found between changes from baseline of PINP at 3, 6 and 18 months with changes in FE strength in the teriparatide-treated group, but not in the risedronate group. CONCLUSIONS: Positive correlations between changes in a biochemical marker of bone formation and improvement of biomechanical properties support the use of PINP as a surrogate marker of bone strength in teriparatide-treated GIO patients.

Discrepancies Between Osteoporotic Fracture Evaluations in Men Based on German (DVO) Osteoporosis Guidelines or the FRAX Score.

INTRODUCTION: Established scores estimate 10-year fracture risk in osteoporosis to assist with treatment recommendations. This study compared the risk probabilities of major osteoporotic and hip fractures calculated by the FRAX tool with those of the DVO score, established in German-speaking countries. MATERIAL AND METHODS: This seven-year retrospective study analyzed data of 125 male patients (mean age: 59.2±10.7 years) evaluated for osteoporosis. For the DVO score, the therapy threshold of>30% for vertebral and hip fractures suggested by DVO guidelines was implemented. We calculated fracture risks based on FRAX scores with aBMD and applied a common therapy threshold of≥3% for hip fracture and subsequently determined the "DVO-equivalent risk level" for FRAX-based assessment that would identify as many male patients as identified by the DVO score. RESULTS: Based on DVO score, 60.0% of patients had a 10-year risk of hip and vertebral fractures>30%. The recommendations for individuals based on FRAX scores for hip fracture with aBMD with risk≥3% overlapped with those based on DVO score in 36% of patients. Patients identified for treatment only by DVO score presented a higher percentage of spine fractures (65 vs. 41%). The thresholds for this "DVO-equivalent risk level" for 'FRAX with aBMD' was estimated to be≥6.7% for major osteoporotic fracture and≥2.1% for hip fracture.This study demonstrates that the DVO score was more sensitive than the FRAX score for patients with prevalent spinal fractures. We suggest considering the appropriate score and therapy threshold carefully in the daily care of male patients.

Association between incident and baseline vertebral fractures in European women: vertebral fracture assessment in the Osteoporosis and Ultrasound Study (OPUS).

UNLABELLED: Vertebral fracture assessment (VFA) with densitometric devices uses less radiation than spinal radiography. We assessed risk of new vertebral fracture (VF) in women with baseline fracture identified on VFA using algorithm-based qualitative diagnosis. Women with VF had significantly greater risk of VF after 6 years compared to those without baseline fracture. INTRODUCTION: Prevalent VFs predict future fracture and are identifiable on vertebral fracture assessment (VFA) using bone densitometry devices. We have previously performed cross-sectional, but not longitudinal, VFA using the algorithm-based qualitative method (ABQ). We aimed to examine the prevalence and incidence of VF and test the association between prevalent and incident VF identified by ABQ VFA. METHODS: We used ABQ to assess vertebral images obtained at baseline and 6 years (Hologic devices) in 674 women at ages 39 to 80 years participating in the Osteoporosis and Ultrasound Study. Criteria for prevalent and incident VF were endplate fracture, with/without cortical fracture. We compared proportions (chi-squared test) and characteristics (two-sample t tests and analysis of variance) of women with and without VF and calculated odds ratios for incident VF in women with prevalent VF (logistic regression). RESULTS: Prevalent VF was identified in one premenopausal woman and 41 postmenopausal women. Incident VF was identified in 18 postmenopausal women. Odds ratios (95% CI) for incident VF in postmenopausal women with prevalent VF were 7.8 (2.8, 22.1) (unadjusted) and 4.3 (1.4, 13.7) (adjusted for age and bone mineral density, BMD). Women with prevalent or incident VF were older (P < 0.01), with lower hip BMD (P < 0.001) compared to women without VF. CONCLUSIONS: Population-based postmenopausal women had relatively low prevalence and incidence of VF analysed with the ABQ method applied to VFA. Women with prevalent fracture had a significantly greater risk of incident VF than women without prevalent fracture.

Prevalence of non-fracture short vertebral height is similar in premenopausal and postmenopausal women: the osteoporosis and ultrasound study.

UNLABELLED: We observed similar prevalence of short vertebral height without endplate depression (SVH) in young women aged 20-39 years and older women aged 55-79 years. There was no association between SVH and low bone density. In older women, therefore, SVH may be largely long standing and not indicative of osteoporotic fracture. INTRODUCTION: Algorithm-based qualitative (ABQ) definition of osteoporotic vertebral fracture (VF) requires evidence of endplate fracture, and there is no minimum threshold for apparent 'reduction' in vertebral height. In older women, SVH without endplate fracture identified on baseline assessment may be long standing and unrelated to VF. If this is so, we would expect to see a similar prevalence of SVH in younger women. We aimed to compare the prevalence of pre- and postmenopausal women with SVH and the characteristics of women with and without SVH. METHODS: We used the ABQ method to classify baseline vertebral images (DXA-based imaging) from 257 premenopausal and 1,361 postmenopausal women participating in the population-based Osteoporosis and Ultrasound Study. Images were classified as follows: normal (no VF, no SVH), SVH (no VF) or VF (with/without SVH in unfractured vertebrae). We compared proportions of women with SVH (chi-squared test) and compared age, height, weight and bone mineral density (BMD) by ABQ classification (two-sample t test/analysis of variance). RESULTS: The prevalence of pre- and postmenopausal women with SVH was 37% and 33%, respectively (P>0.05). Compared to women without SVH, premenopausal women with SVH were older (P<0.001) and heavier (P=0.05), and postmenopausal women with SVH were taller (P<0.05), with higher spine BMD (P<0.01). Postmenopausal women with VF were older (P<0.001) and shorter (P<0.01) with lower BMD (P<0.001) than women without VF. CONCLUSIONS: Short vertebral height without endplate fracture is equally prevalent in pre- and postmenopausal women and not associated with low bone density.

A European multicenter comparison of quantitative ultrasound measurement variables: the OPUS study.

UNLABELLED: Quantitative ultrasound (QUS) measurement variables vary between European countries in a different way to hip bone mineral density. Standardization of data can be achieved through statistical approaches to reduce any between-center differences in QUS measurement variables. However, further validation of this method is required before it can be widely applied. INTRODUCTION: European between-center differences in hip bone mineral density (BMD) have been shown to exist; however, little is known about the geographical heterogeneity of QUS measurement variables. We aimed to examine the differences in QUS variables between three different European countries. METHODS: Five calcaneal and phalangeal QUS devices in Sheffield, Aberdeen (UK), Kiel and Berlin (Germany), and three devices in Paris (France) were used to measure QUS variables in younger (n = 463, 20-39 years old) and older (n = 2,399, 55-79 years old) women participating in the European multicenter Osteoporosis and Ultrasound (OPUS) study. Broadband ultrasound attenuation, speed of sound, stiffness index, amplitude-dependent speed of sound, bone transmission time, and ultrasonic bone profiler index data were collected. Between-center differences were examined using ANOVA followed by post hoc Fisher's least significant difference tests, and ANCOVA with linear contrasts. p < 0.05 indicated statistical significance. RESULTS: Between-center differences in nonstandardized QUS measurement variables existed for younger (p = 0.0023 to p < 0.0001) and older women (p < 0.001). Anthropometric characteristics exerted a significant influence on nonstandardized data (p = 0.045 to p < 0.001). However, following statistical standardization, based on height and weight or based on measurements made in young people, geographical heterogeneity in QUS measurement variables was no longer apparent. CONCLUSIONS: QUS measurement variables vary between European countries in a different way to those for hip BMD. Standardization of data can be achieved through statistical approaches to reduce any between-center differences in QUS measurement variables. However, further validation of this method is required before it can be widely applied.

Endogenous estradiol and the risk of incident fracture in postmenopausal women: the OPUS study.

Some, but not all, studies have found that low endogenous estradiol levels in postmenopausal women are predictive of fractures. The aim of this study was to examine the roles of endogenous estradiol (E(2)), sex hormone binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEAS) in the prediction of incident vertebral and nonvertebral fractures. The study subjects were 797 postmenopausal women from the population-based OPUS (Osteoporosis and Ultrasound Study) study. Spine radiographs and dual-energy X-ray absorptiometry scans were obtained for all subjects at baseline and 6-year follow-up. Nonfasting blood samples were taken at baseline for E(2), SHBG, DHEAS, and bone turnover markers. Incident nonvertebral fractures were self-reported and verified; vertebral fractures were diagnosed at a single center from spinal radiographs. Medical and lifestyle data were obtained by questionnaire at each visit. Thirty-nine subjects had an incident vertebral fracture and 119 a nonvertebral fracture. Estradiol in the lowest quartile predicted vertebral fracture independent of confounders including age, body mass index, bone mineral density, bone turnover, fracture history, and use of antiresorptive therapy, with an OR of 2.97 (95 % confidence interval [CI] 1.52-5.82) by logistic regression. A calculated free estradiol index was not a stronger predictor than total E(2). Higher SHBG predicted vertebral fracture independently of age and body mass index, but not independently of E(2), bone mineral density, or prevalent fracture. Low DHEAS did not predict vertebral fracture. Nonvertebral fractures were not predicted by any of E(2), SHBG, or DHEAS, either in univariate or multivariate analyses. These findings suggest that there may be mechanistic differences in the protective effect of E(2) at vertebral compared with nonvertebral sites.

Femur ultrasound (FemUS)--first clinical results on hip fracture discrimination and estimation of femoral BMD.

SUMMARY: A quantitative ultrasound (QUS) device for measurements at the proximal femur was developed and tested in vivo (Femur Ultrasound Scanner, FemUS). Hip fracture discrimination was as good as for DXA, and a high correlation with hip BMD was achieved. Our results show promise for enhanced QUS-based assessment of osteoporosis. INTRODUCTION: Dual X-ray absorptiometry (DXA) at the femur is the best predictor of hip fractures, better than DXA measurements at other sites. Calcaneal quantitative ultrasound (QUS) can be used to estimate the general osteoporotic fracture risk, but no femoral QUS measurement has been introduced yet. We developed a QUS scanner for measurements at the femur (Femur Ultrasound Scanner, FemUS) and tested its in vivo performance. METHODS: Using the FemUS device, we obtained femoral QUS and DXA on 32 women with recent hip fractures and 30 controls. Fracture discrimination and the correlation with femur bone mineral density (BMD) were assessed. RESULTS: Hip fracture discrimination using the FemUS device was at least as good as with hip DXA and calcaneal QUS. Significant correlations with total hip bone mineral density were found with a correlation coefficient R (2) up to 0.72 and a residual error of about one half of a T-score in BMD. CONCLUSIONS: QUS measurements at the proximal femur are feasible and show a good performance for hip fracture discrimination. Given the promising results, this laboratory prototype should be reengineered to a clinical applicable instrument. Our results show promise for further enhancement of QUS-based assessment of osteoporosis.