Non-fractured Women Research Articles

Denosumab improves trabecular bone score in relationship with decrease in fracture risk of women exposed to aromatase inhibitors.

Trabecular bone score (TBS) is a gray-level textural metric that has shown to correlate with risk of fractures in several forms of osteoporosis. The value of TBS in predicting fractures and the effects of bone-active drugs on TBS in aromatase inhibitors (AIs)-induced osteoporosis are still largely unknown. The primary objective of this retrospective study was to assess the effects of denosumab and bisphosphonates (BPs) on TBS and vertebral fractures (VFs) in women exposed to AIs. 241 consecutive women (median age 58years) with early breast cancer undergoing treatment with AIs were evaluated for TBS, bone mineral density (BMD) and morphometric VFs at baseline and after 18-24months of follow-up. During the study period, 139 women (57.7%) received denosumab 60mg every 6months, 53 (22.0%) BPs, whereas 49 women (20.3%) were not treated with bone-active drugs. Denosumab significantly increased TBS values (from 1.270 to 1.323; P < 0.001) accompanied by a significant decrease in risk of VFs (odds ratio 0.282; P = 0.021). During treatment with BPs, TBS did not significantly change (P = 0.849) and incidence of VFs was not significantly different from women untreated with bone-active drugs (P = 0.427). In the whole population, women with incident VFs showed higher decrease in TBS vs. non-fractured women (P = 0.003), without significant differences in changes of BMD at any skeletal site. TBS variation predicts fracture risk in AIs treated women. Denosumab is effective to induce early increase of TBS and reduction in risk of VFs.

Bone Texture Assessment on Lateral VFAs Using the Texture Research Investigational Platform (TRIP) and its Fracture Discrimination Ability

Texture Research Imaging Platform applies trabecular bone score (TBS) measurement principles to images acquired with multiple modalities to assess bone texture at various skeletal sites. This study aimed to assess the bone texture score in dual-energy X-ray absorptiometry-acquired lateral vertebral fracture assessment (VFA) images (BTSVFA), evaluate its reproducibility, and vertebral fracture discrimination ability. Subjects included 178 VF cases and 178 non-VF controls, 136 women and 42 men in each group, age 55–92 years, from two research centers. Cases and controls were matched for age (±5 years), body mass index (±5 kg/m2) and TBS. All participants underwent dual-energy X-ray absorptiometry TBS assessment from standard posterior-anterior lumbar spine scans and BTSVFA assessment. VF presence was determined using VFA images applying the Genant's method. BTSVFA was lower among fractured women compared to non-fractured (0.626 ± 0.109 vs 0.675 ± 0.099, p < 0.01), but not among men. In a binary logistic regression adjusted for study center and sex, for each SD lower BTSVFA, there was a 40% increase (OR 1.40, 95% CI (1.13–1.74)) in the risk of having a prevalent VF; area under the curve (95% CI) 0.616 (0.557–0.675). Inter-assessor and inter-centers ICCs for BTSVFA measurements were very good; 0.96 (0.64–0.99) and 0.98 (0.95–0.99), respectively. The BTSVFA precision (coefficient of variation) was 2.42%. This feasibility study demonstrates the potential to assess trabecular bone texture in lateral VFA images with good reproducibility. BTSVFA can discriminate between fractured and non-fractured women independent of their age, body mass index and TBS. In conclusion, BTSVFA, a potential trabecular texture assessment that excludes the posterior elements, may have value in fracture prediction or as a novel approach to be further investigated in spine surgery planning.

Gait analysis of patients with distal radius fracture by using a novel laser Timed Up-and-Go system

BackgroundPostmenopausal women are at risk of fall and fracture with the physical decline. Distal radius fracture (DRF) is considered as the primary fragility fracture, and women with this fracture showed poor results in the usual Timed Up-and-Go (TUG) test, indicating a decline in balance and physical ability. The detailed physical characteristics of female DRF patients have not been extensively examined. Research questionIs the novel laser TUG system able to detect and analyze the detailed gait characteristics in patients with DRF whose physical ability has tended to decline? MethodsIn this cross-sectional case control study, the gait characteristics of 32 female patients with DRF who had undergone surgery were evaluated at 2 weeks postoperatively with a laser TUG system to analyze the detailed leg motion during normal TUG test. Forty-three age- and sex-matched non-fractured women were evaluated by the laser TUG system as controls. Lifestyle and present illness were corrected at the time of TUG measurement. Detailed data during laser TUG in both groups were compared statistically, and odds ratio and thread shod of the fracture was elucidated through a logistic regression analysis. ResultsDRF patients showed slower speed and had to do more steps to complete the TUG test. Furthermore, asymmetric trajectory and significantly further distance from the marker were observed. Thirteen steps to complete the TUG test was the thread shod of DRF. SignificanceDetailed gait characteristics of patients with DRF were detected by the laser TUG system. The gait decline and abnormality could be one of the reasons of consecutive fragility fracture. To prevent secondary fragility fractures, this system can be useful for screening.

Predicting bone strength from CT data: Clinical applications

In this review we summarise over 15 years of research and development around the prediction of whole bones strength from Computed Tomography data, with particular reference to the prediction of the risk of hip fracture in osteoporotic patients. We briefly discuss the theoretical background, and then provide a summary of the laboratory and clinical validation of these modelling technologies. We then discuss the three current clinical applications: in clinical research, in clinical trials, and in clinical practice. On average the strength predicted with finite element models (QCT-FE) based on computed tomography is 7% more accurate that that predicted with areal bone mineral density from Dual X-ray Absorptiometry (DXA-aBMD), the current standard of care, both in term of laboratory validation on cadaver bones and in terms of stratification accuracy on clinical cohorts of fractured and non-fractured women. This improved accuracy makes QCT-FE superior to DXA-aBMD in clinical research and in clinical trials, where the its use can cut in half the number of patients to be enrolled to get the same statistical power. For routine clinical use to decide who to treat with antiresorptive drugs, QCT-FE is more accurate but less cost-effective than DXA-aBMD, at least when the decision is on first line treatment like bisphosphonates. But the ability to predict skeletal strength from medical imaging is now opening a number of other applications, for example in paediatrics and oncology.

THE UTILITY OF TBS-ADJUSTED BMD T-SCORE IN THE DISCRIMINATION OF THE MAJOR OSTEOPOROTIC FRACTURES IN THE POSTMENOPAUSAL WOMEN OF THE ROTTERDAM AND THE OSTEOLAUS STUDIES

Introduction Lumbar spine (LS) trabecular bone score (TBS) can be used to modify the output from FRAX to enhance fracture prediction. Leslie et al. (ASBMR 2017) proposed an alternative approach for using TBS in clinical practice based upon a risk-equivalent offset adjustment to the bone mineral density (BMD) T-score. The aim of this study is to test whether the TBS-adjusted BMD T-score (BMDTBS T-score) outperforms BMD T-score in the detection of major osteoporotic fractures (MOF). Methods Our study included 3,018 postmenopausal women (age 46-99 y) from the OsteoLaus (N=1,314) and the Rotterdam (N=1,704) Studies. All women had DXA scans (Hologic Discovery or GE-Lunar Prodigy) of LS and hip (TH). In total, 413 prevalent MOF were self-reported. BMDTBS T-score of femoral neck (FN), TH or LS were calculated using the formulas provided by Leslie et al..Contingency 2 × 2 tables were divided according to the WHO osteoporosis definition (BMD T-score ≤-2.5, or BMDTBS T-score≤-2.5) and according to the presence of prevalent MOF. Sensitivity and specificity of BMD T-score and BMDTBS T-score were then calculated. Additionally, a t-test was performed to study whether non-fractured women classified as osteoporotic by the BMDTBS T-score but not by the BMD T-score, had a higher FRAX probability for MOF. Results Women who fractured were older, had lower TBS, BMD T-score and BMDTBS T-score in all three regions. The results of the analysis on sensitivity and specificity are shown in Table 1. In general, the BMDTBS T-score showed a higher sensitivity than BMD T-score in MOF detection, whereas BMD T-score was more specific. Nevertheless, the increase in sensitivity of the BMDTBS T-score was superior to the decrease in specificity. The non- fractured women classified as osteoporotic by BMDTBS T-scorebut not by BMD T-score, had a significantly higher FRAX probability (all p Conclusion This study illustrates how the adjustment of BMD by TBS contributes to MOF discrimination by increasing the sensitivity. As BMD has been shown to have low sensitivity, this need in the field might be filled by the information provided by TBS. This approach considers both bone parameters and postulates itself as a helpful strategy to improve patient care in regions where intervention guidelines are based solely on the BMD T-score.

Fracture risk assessment in postmenopausal women with diabetes: comparison between DeFRA and FRAX tools

This study aimed to compare the performance of Fracture Risk Assessment Tool (FRAX) with that of Derived FRAX (DeFRA) in estimating fracture risk in a cohort of type-2 diabetes mellitus (T2DM) postmenopausal women. One hundred nineteen T2DM postmenopausal women and 118 consecutive healthy postmenopausal women were enrolled. Fracture risk was assessed with FRAX (adjusted or non- for trabecular bone score, TBS) and DeFRA. Bone mineral density (BMD) and TBS were evaluated by dual-energy X-ray absorptiometry (DXA). The outcome was the presence of vertebral/non-vertebral fragility fractures (FFs). T2DM women showed higher spinal BMD T-score (p < .05), but lower TBS (p < .05), than controls. Diabetic patients had higher prevalence of FFs compared to controls (p < .05), but no significant difference were found in the scores of any of the predictor tools. Differently, in the T2DM group, the scores of DeFRA, FRAX and adjusted-FRAX were significantly (p < .01 for all) higher in fractured compared with non-fractured women. DeFRA showed the best discriminative power among all fracture risk predictor tools (area under curves: DeFra: 0.89; adjusted FRAX: 0.80; non-adjusted FRAX: 0.73). In summary, all fracture risk assessment tools appeared to be effective in predicting bone fractures in T2DM postmenopausal women, with DeFRA showing a slightly better diagnostic accuracy.

SAT0468 An Innovative Ultrasound-Based Method for the Estimation of Osteoporotic Fracture Risk

BackgroundOsteoporosis affects about 200 million people in the world and is responsible for 8.9 million fractures each year worldwide. Hip fractures are a major public health burden, from both social...

Rate of Bone Density Change Does Not Enhance Fracture Prediction in Routine Clinical Practice

There is contradictory information on whether the rate of bone mineral density (BMD) loss is an independent risk factor for osteoporotic fractures and whether this should be included in fracture prediction systems. This study was undertaken to better define rate of BMD loss as a contributor to fracture risk in routine clinical practice. We performed a retrospective cohort study using a database of all clinical BMD results for the province of Manitoba, Canada. We included 4498 untreated women age 40 yr and older at the time of a second BMD test performed between April 1996 and March 2009. A total of 146 women with major osteoporotic fracture outcomes after the second BMD test (mean observation, 2.7 yr) and relevant covariates were identified in population-based computerized health databases. Annualized percentage change in total hip BMD was no greater in fracture compared to nonfracture women (-0.4 ± 1.7 vs. -0.5 ± 1.4; P = 0.166). After adjustment for final total hip BMD, other covariates, and medication use, rate of total hip BMD change did not predict major osteoporotic fractures (hazard ratio, 0.95 per sd decrease; 95% confidence interval, 0.81-1.10). Similar results were also seen in analyses based upon change in lumbar spine and femoral neck BMD. We found no evidence that BMD loss, as detected during routine clinical monitoring, was a significant independent risk factor for major osteoporotic fractures.

Vulnerability of healthy vertebrae in patients with and without previous vertebral fracture

Vertebral deformities are associated with a marked increase in morbidity, mortality, and burden in terms of sanitary expenditures. Patients with vertebral fractures have a negative impact in their health, less quality of life, and loss of functional capacity and independence.The purpose of this study was to explore the vulnerability of healthy vertebrae in patients who have sustained already a compression fracture and in patients who do not have prevalent fractures in the thoracic spine; and to explore the association of the deformity in healthy vertebrae with different variables, such as bone mineral density (BMD), body mass index, age, loss of height, presence of clinical kyphosis, history of other osteoporotic fractures, and falls occurring during the last year.Clinical data and complementary studies from 175 postmenopausal outpatients were analyzed. These women (age: 69.7±11.1years) had not received any treatment for osteoporosis. Anteroposterior and lateral radiographs of the thoracic spine and bone densitometry of the hip were obtained; morphometry was performed in 1575 thoracic vertebrae from T4 to T12.The angle of wedging of each vertebral body was calculated using a trigonometric formula. Then, the sum of wedge angles of vertebral bodies (SWA) was determined, and Cobb angle was measured.In patients with vertebral fractures, after excluding the angles of fractured vertebral bodies, the mean wedge angle of the remaining vertebrae (MWAhealthy) was calculated. The same procedure was followed in patients without vertebral fractures. MWAhealthy was considered as an indicator of the structural vulnerability of non-fractured vertebrae.Patients with prevalent fractures had lower BMD, wider Cobb angle, and higher sum of wedge angles than patients without vertebral fractures. The proportion of patients with accentuation of clinical kyphosis was higher in the group with prevalent vertebral fractures. A highly significant difference was found in the MWAhealthy, which was higher in patients with prevalent fractures (4.1±1.3° vs. 3.0±1.1°; p<0.001). Patients showing vertebral fractures had 7.1±4.2cm height loss in average, significantly superior than that found among non-fractured women (3.6±3.2cm; p<0.01).In multivariate analysis, the increase of MWAhealthy was associated with advancing age (p<0.02), lower femoral neck BMD (p<0.005), presence of clinical kyphosis (p<0.01) and vertebral fractures (p<0.02).This study presents evidence that a series of factors independently influence the increase in wedging deformity of vertebral bodies that are not fractured yet. These factors could contribute to an increased vulnerability of the vertebrae, making them more susceptible to fracture.

Integrity of the osteocyte bone cell network in osteoporotic fracture: Implications for mechanical load adaptation

The human skeleton has the ability to modify its material composition and structure to accommodate loads through adaptive modelling and remodelling. The osteocyte cell network is now considered to be central to the regulation of skeletal homeostasis; however, very little is known of the integrity of the osteocyte cell network in osteoporotic fragility fracture. This study was designed to characterise osteocyte morphology, the extent of osteocyte cell apoptosis and expression of sclerostin protein (a negative regulator of bone formation) in trabecular bone from the intertrochanteric region of the proximal femur, for postmenopausal women with fragility hip fracture compared to age-matched women who had not sustained fragility fracture. Osteocyte morphology (osteocyte, empty lacunar, and total lacunar densities) and the degree of osteocyte apoptosis (percent caspase-3 positive osteocyte lacunae) were similar between the fracture patients and non-fracture women. The fragility hip fracture patients had a lower proportion of sclerostin-positive osteocyte lacunae in comparison to sclerostin-negative osteocyte lacunae, in contrast to similar percent sclerostin-positive/sclerostin-negative lacunae for non-fracture women. The unexpected finding of decreased sclerostin expression in trabecular bone osteocytes from fracture cases may be indicative of elevated bone turnover and under-mineralisation, characteristic of postmenopausal osteoporosis. Further, altered osteocytic expression of sclerostin may be involved in the mechano-responsiveness of bone. Optimal function of the osteocyte cell network is likely to be a critical determinant of bone strength, acting via mechanical load adaptation, and thus contributing to osteoporotic fracture risk.

A new predictive index for vertebral fractures: The sum of the anterior vertebral body heights

Evaluation of osteoporotic vertebral fracture risk is currently based on measurement of bone mineral density (BMD), but bone strength depends also on bone quality parameters. Aim of this study was to evaluate the validity of a new vertebral morphometric index, the Anterior Vertebral Heights sum (AHs) in discriminating women at high risk of vertebral fracture, comparing its diagnostic accuracy with that of BMD measured at lumbar spine (LS-BMD) and femoral neck (FN-BMD). Materials and methodsA total of 163 Caucasian post-menopausal women (age range 46–74 years, mean age±SD=63.8±7.1 years), who did not present prevalent fractures at baseline evaluation, were observed at longitudinal follow-up. X-ray of the thoracic and lumbar spine, LS-BMD and FN-BMD measurements were obtained in all patients at baseline and repeated at the second follow-up visit 18–24 months later (mean 21±1.7 months). Radiographs of spine were analysed in order to identify vertebral fractures using a visual semiquantitative method (SQ) and vertebral morphometry as well as by calculating the AHs morphometric index. ResultsDuring follow-up, 21/163 patients (12.9%) sustained a new vertebral fracture; 95.2% (20/21) of fractured patients but only 4.9% (7/142) of non-fractured women had reduced AHs values. As regarding BMD, 66.6% (14/21) and 61.9% (13/21) of women with incident fracture were osteoporotic at lumbar spine and femoral neck baseline evaluation , whereas among non-fractured women, 38% (54/142) at LS-BMD and 33.1% (47/142) at FN-BMD were osteoporotic . Analyses of Receiver Operating Characteristic (ROC) curves showed that AHs discriminated vertebral fractures almost perfectly (AUC 0.97; 95% CI 0.95–0.99). On the other hand, the AUC for LS-BMD was only 0.73 (95% CI 0.64–0.81) and for FN-BMD was 0.72 (95%CI 0.63–0.80), showing that the diagnostic accuracy of AHs was significantly higher compared to that of LS-BMD (p<0.001) or FN-BMD (p<0.001). A modified Poisson regression model for binary data was used to assess the independent role of AHs in predicting vertebral fracture. The effect of AHs remained statistically significant (p<0.001) after adjusting by FN-BMD, age, weight and body height. ConclusionsResults of this study indicate the validity of this new morphometric index in evaluating the risk of osteoporotic vertebral fractures thus suggesting that AHs should be considered a valid parameter in clinical practice to assess the need for primary prevention of vertebral fractures.

Low Estimates of Dietary Acid Load Are Positively Associated with Bone Ultrasound in Women Older Than 75 Years of Age with a Lifetime Fracture

Dietary acid load from Western diets may be a risk factor for osteoporosis. It can be estimated by net endogenous acid production (NEAP). No data currently exists for NEAP estimates and bone indices in the very elderly (i.e. ≥75 y). The aim of this study was to determine the association between NEAP estimates by using the potential renal acid load (PRAL) equation and quantitative bone ultrasound (QUS) measurements at the heel [broadband ultrasound attenuation (BUA)] in Caucasian women. We assessed NEAP and QUS in 401 very elderly Swiss ambulatory women. We evaluated dietary intake and NEAP estimates with a validated FFQ. QUS was measured using Achilles (Lunar). We identified 2 subgroups: 256 women (80.6 y ± 3; BUA, 96.8 dB/MHz) with a fracture history and the remaining 145 (79.9 y SD 2.9; BUA, 101.7 dB/MHz) without. Women who reported having suffered a fracture had lower BUA (P < 0.001) than nonfractured women but did not differ in nutrient intakes and NEAP. Lower NEAP (P = 0.023) and higher potassium intake (P = 0.033) were correlated with higher BUA, which remained significant even after adjustment for age, BMI, and osteoporosis treatment. BUA was positively correlated with calcium (P = 0.016) and BMI (P < 0.001). Women who reported no fractures had no significant correlations between nutrient intake, NEAP, and BUA. Low nutritional acid load was correlated with higher BUA in very elderly women with a fracture history. Although relatively weak compared with age and BMI, this association was significant and may be an important additional risk factor that might be particularly relevant in frail patients with an already high fracture risk.

Quantitative ultrasound technique at the phalanges in discriminating between uremic and osteoporotic patients

This study was conducted to test the ability of quantitative ultrasound technique (QUS) at the phalanges to discriminate between uremic and osteoporotic patients. Three groups of subjects (38 dialytic women, 16 osteoporotic women with vertebral fractures, 19 non-dialytic and non-fractured women) were recruited at the Department of Radiology at “Casa Sollievo della Sofferenza” Hospital, San Giovanni Rotondo, Italy. The groups were matched for age and body mass index (BMI). On all subjects the following measurements were performed: spinal BMD by QCT and by DXA, Femoral BMD by DXA, phalangeal QUS. For QUS measurements, the DBM Sonic (IGEA, Carpi, Italy) was applied to the metaphysis of the proximal phalanges of the last four fingers of the hand. Osteoporotic women with vertebral fractures showed significantly lower values of spinal BMD by QCT and DXA and Ward's Triangle BMD with respect to hemodialytic patients ( p < 0.005). All QUS values, except for BTT and SoS, showed lower values in osteoporotic women with respect to hemodialytic patients ( p < 0.05). Control group showed higher values of AD-SoS, BTT and SoS than hemodialytic patients ( p < 0.005) while the two groups did not differ for BMD values measured with both QCT and DXA. UBPI and FWA data showed a similar behaviour to DXA and QCT results, whereas BTT and SoS showed a completely different behaviour. AD-SoS was the only parameter that could effectively discriminate among the three groups (ANOVA, p < 0.0001). We conclude that phalangeal QUS can discriminate between hemodialysed patients and controls with similar bone mineral density, and can also discriminate between hemodialysed and osteoporotic subjects with vertebral fractures. Different characteristics of ultrasound signal can be ascribed to each bone tissue condition, enabling a clear differentiation of bone tissue changes occurring in menopause, osteoporosis and renal osteodystrophy.

Increased Prevalence of Radiological Spinal Deformities in Active Acromegaly: A Cross-Sectional Study in Postmenopausal Women

This cross-sectional study shows that high numbers of postmenopausal women with acromegaly develop vertebral fractures in relation to the activity of disease. In patients with active acromegaly, vertebral fractures occur even in presence of normal BMD, whereas in patients with controlled acromegaly, vertebral fractures are always accompanied by a pathological BMD. We studied the frequency of radiological vertebral fractures in a cohort of postmenopausal women with active or controlled acromegaly. Thirty-six postmenopausal acromegalic patients (15 with active and 21 with controlled disease) were evaluated for BMD, bone metabolism (serum 25-hydroxyvitamin D, PTH, bone-specific alkaline phosphatase [BSALP], and urinary deoxypyridinoline [Dpd]), and vertebral quantitative morphometry. Thirty-six nonacromegalic postmenopausal women, matched for age, were selected among the patients consulting the Bone Center as a control group for BMD evaluation and vertebral quantitative morphometry. Vertebral fractures were shown in 19 patients (52.8%) and 11 controls (30.6%; chi2: 3.7; p=0.06). Fractured acromegalic women were older and had higher serum IGF-1, Dpd, and BSALP and lower T score and serum vitamin D values compared with nonfractured patients. Moreover, the fractured women had a longer diagnosis and were in the postmenopausal period for a longer period than the nonfractured women. The fracture rate was significantly higher in active than in controlled acromegaly (80% versus 33.3%; chi2: 7.6; p=0.008). The patients with active acromegaly who fractured (12 cases) had significantly higher serum IGF-1 values (356 ng/ml; range: 212-950 versus 120 ng/ml; range: 84-217; p<0.001) and T scores (-1.3 SD, range: -2.9 to +1.3 versus -2.7 SD, range: -3.4 to -1.5, p=0.04) compared with the fractured women whose disease was controlled (7 cases). All fractured women with controlled acromegaly had T scores<-1.0 SD (57.1% of them had osteoporosis, and 42.9% were osteopenic). In contrast, 41.7% of women whose fractures were associated with active disease had a normal T score (>-1.0 SD), whereas osteopenia and osteoporosis were found only in 33.3% and 25.0% of them, respectively. This cross-sectional study shows that high numbers of postmenopausal women with acromegaly develop vertebral fractures in relation to the activity of disease. Furthermore, our study shows that, in patients with active acromegaly, vertebral fractures occur even in the presence of normal BMD, whereas in patients with controlled acromegaly, vertebral fractures are always accompanied by a pathological BMD.

Femoral Neck Bone Loss Predicts Fracture Risk Independent of Baseline BMD

Whereas low BMD is known to be a risk factor for fracture, it is not clear whether loss of BMD is also a risk factor. In elderly women, greater loss of BMD at the femoral neck was associated with increased risk of fracture, independent of baseline BMD and age. Baseline measurement of BMD predicts fracture risk. However, it is not clear whether short-term bone loss is an independent risk factor for fractures. This study was designed to investigate the relationship between changes in BMD and fracture risk in elderly women in the general population. A total of 966 women > or = 60 years of age (mean, 70 +/- 6.7 [SD] years), who had been followed for an average of 10.7 years, were studied. Atraumatic fracture of the proximal femur (hip), symptomatic vertebral fracture, and other major fractures, excluding pathological fractures or those resulting from severe trauma, were recorded and confirmed by radiographs. Femoral neck and lumbar spine BMD was measured by DXA. During the follow-up period, 224 had sustained a fracture (including 43 hip, 71 symptomatic vertebrae, 37 proximal humerus, 46 forearm and wrist, and 27 rib and pelvis fractures). The annual rate of change in BMD in fracture women (-2.1 +/- 4.2%) was significantly higher than that in nonfracture women (-0.8 +/- 2.8%; p = 0.005). In the multivariable Cox's proportional hazards analysis, the following factors were significant predictors of fracture risk: femoral neck bone loss (relative hazard [RH], 1.4; 95% CI, 1.1-1.8 per 5% loss), baseline femoral neck BMD (RH, 2.0; 95% CI, 1.7-2.7 per SD), and advancing age (RH, 1.2; 95% CI, 1.1-1.4). The proportion of fractures attributable to the three factors was 45%. For hip fracture, the attributable risk fraction was approximately 90%. Bone loss at the femoral neck is a predictor of fracture risk in elderly women, independent of baseline BMD and age.

Gender differences in fracture risk and bone mineral density

We have investigated gender-related differences of bone mineral density and fracture threshold in 136 males (age, 60.7±9.3 years) and 337 females (age, 59.7±7.8 years) without evidence of secondary osteoporosis. Women and men were examined for total amount of spine fractures and bone mineral density by quantitative computed tomography (QCT) of three non-fractured vertebral bodies L1–L5. Females with lumbar fractures ( n=96) when compared with non-fracture women ( n=241) were older and had lower bone density at their vertebral sites. Males with vertebral fractures ( n=52) were older and had a significantly reduced bone mineral density of the spine when compared with healthy males ( n=84). When we compared gender-related vertebral fracture rates, we observed a significantly higher prevalence of vertebral fractures in the male population. After matching males and females for age and bone mineral density to exclude an influence of either variable, we compared the prevalence of vertebral fracture risk in both sexes with logistic regression analysis. Data of estimated fracture risk, differed very significantly for sex and bone density at the vertebral site, indicating that men present fracture at a higher bone density level compared with females; in 10% of study population fractures occurred at a QCT level of 105 mg/cm 3 in women and 120 mg/cm 3 in men. The estimated odds ratio for sex of 3.1 (95% CI) means a three-fold increased risk for vertebral fractures compared to males at a given density level. These results underline that a decreased bone mineral density leads to the occurrence of spine fractures in females and males as well.

Trabecular spacing in post-menopausal Australian women with and without vertebral fractures.

Histomorphometric measurements were made from iliac crest biopsies of 32 women with vertebral fractures and 37 women without fracture. All were post-menopausal Australian women who had presented with back pain to a hospital out-patient endocrinology clinic. Bone from the fracture cases was characterised by loss of individual trabecular elements, with the remaining trabeculae being spaced further apart than those in the non-fracture women (p less than 0.0001). This resulted in a significant decrease in trabecular bone volume (p less than 0.01). In addition osteoid surface was reduced (p less than 0.01). Dynamic parameters of bone turnover were not significantly different between the two groups. These data should be useful for the assessment of iliac bone histomorphometry in Australian post-menopausal women suspected of having osteoporosis.

The predictive value of bone loss for fragility fractures in women: A longitudinal study over 15 years

Fifteen years after their forearm bone mineral content was measured, 366 women were measured again with the same single photon technique. 96 of the women had sustained one or more fragility fractures during that period. The initial bone mineral content was less in those women who were to have fractures. The rate of loss over the years did not differ between fracture and non-fracture women--the initial bone mass was the better predictor. Peak bone mass in the women in this study occurred before the age of 40.

Identification of women at risk for developing postmenopausal osteoporosis with vertebral fractures: role of history and single photon absorptiometry

Putative risk factors for the development of postmenopausal osteoporosis (PMO) with vertebral fractures were examined in a retrospective study of 663 postmenopausal white females aged 45–75 years (266 women with non-traumatic vertebral compression fractures (VF+), 134 non-fractured women from a general medicine clinic (controls) and 263 non-fractured women who were evaluated when they presented specifically for osteoporosis screening (VF−)). The VF+ women differed from control women in several respects. The VF+ group reported a higher prevalence of a positive family history of osteoporosis, and a higher prevalence of a history of medical or surgical conditions known to be independently associated with metabolic bone disease, had fewer children, were smaller (weight, height) and were slightly older. The two groups, VF+ and controls, did not differ with respect to cigarette smoking, alcohol consumption, exercise habits, menstrual or menopausal history, dietary intake of milk and cheese or in amount taking calcium supplements during pregnancy. The VF+ group also differed in certain respects from the VF− group. The VF+ group were smaller (weight, height) and were older. The VF+ group had lower cortical bone mass (measured by single photon absorptiometry of the non-dominant forearm) than either the control or VF- groups. The latter two groups did not differ from each other with respect to this measurement. These markers demonstrated limited sensitivity and specificity as estimated from a confirmatory data set, particularly for the historical and anthropometric variables. We conclude that an assessment of the risk of developing PMO with vertebral fractures cannot be based on the putative risk factors as measured in our study, but must be based on measurement of bone mass.