In Vivo Efficacy of Measles Virus Fusion Protein-Derived Peptides Is Modulated by the Properties of Self-Assembly and Membrane Residence.

Measles virus (MV) infection is undergoing resurgence and remains one of the leading causes of death among young children worldwide despite the availability of an effective measles vaccine. MV infects its target cells by coordinated action of the MV hemagglutinin (H) and fusion (F) envelope glycoproteins; upon receptor engagement by H, the prefusion F undergoes a structural transition, extending and inserting into the target cell membrane and then refolding into a postfusion structure that fuses the viral and cell membranes. By interfering with this structural transition of F, peptides derived from the heptad repeat (HR) regions of F can inhibit MV infection at the entry stage. In previous work, we have generated potent MV fusion inhibitors by dimerizing the F-derived peptides and conjugating them to cholesterol. We have shown that prophylactic intranasal administration of our lead fusion inhibitor efficiently protects from MV infection in vivo We show here that peptides tagged with lipophilic moieties self-assemble into nanoparticles until they reach the target cells, where they are integrated into cell membranes. The self-assembly feature enhances biodistribution and the half-life of the peptides, while integration into the target cell membrane increases fusion inhibitor potency. These factors together modulate in vivo efficacy. The results suggest a new framework for developing effective fusion inhibitory peptides. IMPORTANCE: Measles virus (MV) infection causes an acute illness that may be associated with infection of the central nervous system (CNS) and severe neurological disease. No specific treatment is available. We have shown that fusion-inhibitory peptides delivered intranasally provide effective prophylaxis against MV infection. We show here that specific biophysical properties regulate the in vivo efficacy of MV F-derived peptides.

Congenital prosopagnosia in a child: Neuropsychological assessment, eye movement recordings and training.

Here we report the assessment and treatment of a 6-year-old boy (L.G.) who was referred to us for congenital prosopagnosia (CP). We investigated his performance using a test battery and eye movement recordings pre- and post-training. L.G. showed deficits in recognising relatives and learning new faces, and misrecognition of unfamiliar people. Eye movement recordings showed that L.G. focused on the lower part of stimuli in naming tasks based on familiar or unfamiliar incomplete or complete faces. The training focused on improving his ability to explore internal features of faces, to discriminate specific facial features of familiar and unfamiliar faces, and to provide his family with strategies to use in the future. At the end of the training programme L.G. no longer failed to recognise close and distant relatives and classmates and did not falsely recognise unknown people.

Peculiar body representation alterations in hemineglect: a case report.

We report the case of FP affected by personal and extrapersonal neglect and a body representation deficit characterized by delusional ideas. When FP performed the human figure, he placed body parts to the left, despite his extrapersonal neglect. Differently, when he performed the car figure, he placed all parts to the right, in line with his deficit. Comparing FP with a small patient group with the same clinical features without delusional ideas about body emerged that he was the only one to suffer from a specific body representation deficit characterized by a lack of body ownership sense.

What analytic method should clinicians use to derive spine T-scores and predict incident fractures in men? Results from the MrOS study.

UNLABELLED: In this study, the area under the curve was highest when using the lowest vertebral body T-score to diagnose osteoporosis. In men for whom hip imaging is not possible, the lowest vertebral body T-score improves the ability to diagnose osteoporosis in men who are likely to have an incident fragility fracture. INTRODUCTION: Spine T-scores have limited ability to predict fragility fracture. We hypothesized that using lowest vertebral body T-score to diagnose osteoporosis would better predict fracture. METHODS: Among men enrolled in the Osteoporotic Fractures in Men Study, we identified cases with incident clinical fracture (n = 484) and controls without fracture (n = 1,516). We analyzed the lumbar spine bone mineral density (BMD) in cases and controls (n = 2,000) to record the L1-L4 (referent), the lowest vertebral body, and International Society for Clinical Densitometry (ISCD)-determined T-scores using a male normative database and the L1-L4 T-score using a female normative database. We compared the ability of method to diagnose osteoporosis and, therefore, to predict incident clinical fragility fracture, using area under the receiver operator curves (AUCs) and the net reclassification index (NCI) as measures of diagnostic accuracy. ISCD-determined T-scores were determined in only 60 % of participants (n = 1,205). RESULTS: Among 1,205 men, the AUC to predict incident clinical fracture was 0.546 for L1-L4 male, 0.542 for the L1-L4 female, 0.585 for lowest vertebral body, and 0.559 for ISCD-determined T-score. The lowest vertebral body AUC was the only method significantly different from the referent method (p = 0.002). Likewise, a diagnosis of osteoporosis based on the lowest vertebral body T-score demonstrated a significantly better net reclassification index (NRI) than the referent method (net NRI +0.077, p = 0.005). By contrast, the net NRI for other methods of analysis did not differ from the referent method. CONCLUSION: Our study suggests that in men, the lowest vertebral body T-score is an acceptable method by which to estimate fracture risk.

Postmenopausal women treated with combination parathyroid hormone (1-84) and ibandronate demonstrate different microstructural changes at the radius vs. tibia: the PTH and Ibandronate Combination Study (PICS).

SUMMARY: In postmenopausal women receiving combination parathyroid hormone (PTH) (1-84) therapy and ibandronate, we evaluated bone microarchitecture and biomechanics using high-resolution peripheral quantitative computed tomography (HR-pQCT). Cortical and trabecular changes were different at the nonweight-bearing radius vs. the weight-bearing tibia, with more favorable overall changes at the tibia. INTRODUCTION: PTH therapy and bisphosphonates decrease fracture risk in postmenopausal osteoporosis, but their effects on bone microstructure and strength have not been fully characterized, particularly during combination therapy. PTH increases trabecular bone mineral density (BMD) substantially but may decrease cortical BMD, possibly by stimulating intracortical remodeling. We evaluated bone microarchitecture and biomechanics with HR-pQCT at the radius (a nonweight-bearing site) and tibia (weight bearing) in women receiving combination PTH(1-84) and ibandronate. METHODS: Postmenopausal women with low bone mass (n = 43) were treated with 6 months of PTH(1-84) (100 µg/day), either as one 6- or two 3-month courses, in combination with ibandronate (150 mg/month) over 2 years. HR-pQCT was performed before and after therapy. RESULTS: Because changes in HR-pQCT parameters did not differ between treatment arms, groups were pooled into one cohort for analysis. Trabecular BMD increased at both radius and tibia (p < 0.01 for each). Cortical thickness and BMD decreased at the radius (p < 0.01), consistent with changes in dual-energy X-ray absorptiometry, while these parameters did not change at the tibia (p ≤ 0.02 for difference between radius and tibia). In contrast, cortical porosity increased at the tibia (p < 0.01) but not radius. Stiffness and failure load decreased at the radius (p < 0.0001) but did not change at the tibia. CONCLUSIONS: Cortical and trabecular changes in response to the PTH/ibandronate treatment combinations utilized in this study were different at the nonweight-bearing radius vs. the weight-bearing tibia, with more favorable overall changes at the tibia. Our findings support the possibility that weight bearing may optimize the effects of osteoporosis therapy.

The Walking Corsi Test (WalCT): standardization of the topographical memory test in an Italian population.

Selective visuo-spatial memory deficits can seriously affect many aspects of daily life; for example, an individual may not remember where he put an object or which path he took to reach his destination. In general, visuo-spatial memory is assessed through pen-and-paper tests that mainly assess memory components in peripersonal space. Recent studies (Piccardi et al. in Exp Brain Res 206:171-177, 2010; Piccardi et al. in Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 18:362-384, 2011) have shown that brain-damaged patients selectively fail on navigation memory tasks but not on other tests of visuo-spatial memory ability. These findings underline the need for a standardized test that measures memory in navigation separately from other types of visuo-spatial memory. Here, we report the validation of the Walking Corsi Test (WalCT: Piccardi et al. in Neurosci Lett 432:127-131, 2008) on 289 individuals aged 15-86 years. The WalCT is a new instrument that assesses topographical memory in real environments and reproduces on a large-scale version the Corsi Block-Tapping Test (CBT: Corsi in Unpublished doctoral dissertation, McGill University, Montreal, 1972). The WalCT has been used in clinical practice and has proven sensitive in detecting navigational memory deficits even in individuals who have no other memory impairments (Piccardi et al. in Exp Brain Res 206:171-177, 2010; Piccardi et al. in Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 18:362-384, 2011; Bianchini et al. in Neuropsychologia 48:1563-1573, 2010 ).

Predictors of new and severe vertebral fractures: results from the HORIZON Pivotal Fracture Trial.

UNLABELLED: We examined prevalent and recent vertebral fractures in 1 year as predictors of new vertebral fractures over subsequent 2 years using data from RCT placebo patients. We found that prevalent and recent vertebral fractures strongly and independently predicted subsequent vertebral fractures including those which were severe. INTRODUCTION: While several studies have shown that prevalent vertebral fractures (pVFx) increase the risk of new vertebral fractures (VFx), the impact of recent vertebral fractures on future fractures is less studied. METHODS: Data from the placebo arm of the HORIZON Pivotal Fracture Trial, an international trial of zoledronic acid in postmenopausal, osteoporotic women between 65 and 85 years, were used. We included the subset of 2677 women with annual spinal radiographs to study the impact of vertebral fractures in year 1 (Y1 VF) on those occurring in years 2 and 3 using morphometric and semiquantitative (SQ) criteria. In addition, a subset of severe VFx was defined using SQ criteria. Logistic regression examined the impact of pVFx and Y1 VF on all incident VFx and on severe incident VFx. RESULTS: Two hundred fourty-five (9.1%) women sustained a new VFx in years 2-3. VFx risk in years 2-3 was 3.9% in those without pVFx or VFy1 and 29.8% in those with both risk factors. Both pVF and VFy1 remained independent predictors for future VF when they were both entered into a logistic regression model (odds ratio (OR) = 3.3; 95% confidence interval (CI), 2.3-4.7; OR = 3.7, 95% CI, 2.3, 5.8, respectively). ORs were similar after adjustment. Of the total number of women, 4.1% had severe VFx. PVFx and Y1 VF were also significant predictors of severe VFx; however, Y1 VF appeared more strongly predictive of severe VFx. CONCLUSIONS: Prevalent and incident vertebral fractures are highly predictive of subsequent new and severe vertebral fractures. Women with both of these risk factors are likely to benefit from anti-osteoporosis treatment.

The prevalence of radiographic vertebral fractures in Mexican men.

SUMMARY: The prevalence of radiographically ascertained vertebral fractures in a random sample of 413 in Mexican men is 9.7% (95% CI 6.85-12.55). Increase of vertebral fracture rises with age from 2.0% in the youngest group (50-59 years) to 21.4% in the oldest group (80 years and over). INTRODUCTION: This is the first population-based study of vertebral fractures in Mexican men using a standardized methodology reported in other studies. METHODS: The presence of radiographic vertebral fractures increases with age. This same pattern was found in Mexican women with steady age increments, but the higher prevalence of fractures in women starts at age 70, whereas in men, the higher prevalence starts a decade later (80 years and over). RESULTS: The standardized prevalence per 1,000 men 50 years and over in the Mexican population for the year 2005 is 65.8 (95% CI 29.9-105.5), and it is 68.6 (95% CI 32.2-108.7) in the US population for the year 2000.

Vitamin D insufficiency does not affect response of bone mineral density to alendronate.

SUMMARY: We investigated whether osteoporosis therapy with alendronate in postmenopausal patients is equally effective in patients who are vitamin D insufficient as in those who are vitamin D sufficient. We found that vitamin D insufficiency is common among patients with low bone density but that vitamin D insufficiency did not impair response to alendronate. INTRODUCTION: Treatment of vitamin D deficiency leads to significant improvements in bone mineral density (BMD); however, whether insufficiency affects BMD's response to bisphosphonate therapy is unknown. METHODS: To determine whether vitamin D insufficiency at initiation of alendronate therapy for low BMD affects treatment efficacy, we used data from 1,000 postmenopausal women randomly selected from the vertebral fracture arm (n = 2,027) of the placebo-controlled Fracture Intervention Trial of alendronate. Participants were randomly assigned to placebo (50%) or alendronate therapy and most (83%) to calcium (500 mg/day) and cholecalciferol (250 IU/day). We measured serum 25-hydroxy vitamin D (25OHD) at enrollment, then categorized baseline vitamin D status according to 25OHD concentration (10 but 30 ng/ml = sufficient) and used linear regression to compare the effects of alendronate treatment among these categories. RESULTS AND CONCLUSION: At baseline, participants were vitamin D sufficient (14%), insufficient (83%), and deficient (2%). We found that BMD response to therapy at total hip or spine did not vary by vitamin D status at baseline (p for heterogeneity = 0.6). We determined that vitamin D insufficiency is common among participants with low BMD. However, vitamin D status at initiation of therapy does not affect BMD's response to alendronate, when it is coadministered with cholecalciferol and calcium.

The prevalence of radiographic vertebral fractures in Latin American countries: the Latin American Vertebral Osteoporosis Study (LAVOS).

UNLABELLED: In the first population-based study of vertebral fractures in Latin America, we found a 11.18 (95% CI 9.23-13.4) prevalence of radiographically ascertained vertebral fractures in a random sample of 1,922 women from cities within five different countries. These figures are similar to findings from studies in Beijing, China, some regions of Europe, and slightly lower than those found in the USA using the same standardized methodology. INTRODUCTION: We report the first study of radiographic vertebral fractures in Latin America. METHODS: An age-stratified random sample of 1,922 women aged 50 years and older from Argentina, Brazil, Colombia, Mexico, and Puerto Rico were included. In all cases a standardized questionnaire and lateral X-rays of the lumbar and thoracic spine were obtained after informed consent. RESULTS: A standardized prevalence of 11.18 (95% CI 9.23-13.4) was found. The prevalence was similar in all five countries, increasing from 6.9% (95% CI 4.6-9.1) in women aged 50-59 years to 27.8% (95% CI 23.1-32.4) in those 80 years and older (p for trend < 0.001). Among different risk factors, self-reported height loss OR = 1.63 (95% CI: 1.18-2.25), and previous history of fracture OR = 1.52 (95% CI: 1.14-2.03) were significantly (p < 0.003 and p < 0.04 respectably) associated with the presence of radiographic vertebral fractures in the multivariate analysis. In the bivariate analyses HRT was associated with a 35% lower risk OR = 0.65 (95% CI: 0.46-0.93) and physical activity with a 27% lower risk of having a vertebral fracture OR = 0.73 (95% CI: 0.55-0.98), but were not statistically significant in multivariate analyses CONCLUSION: We conclude that radiographically ascertained vertebral fractures are common in Latin America. Health authorities in the region should be aware and consider implementing measures to prevent vertebral fractures.

Evidence of taxonomy for Developmental Topographical Disorientation: Developmental Landmark Agnosia Case 1.

We report Developmental Landmark Agnosia (DLA) in a 6-year-old boy (L.G.) who was referred to us for congenital prosopagnosia (see Pizzamiglio et al., 2017 , in which both testing and rehabilitation of Congenital Prosopagnosia are reported). We investigated his performance using a neuropsychological battery and eye movement recordings. The assessment showed the presence of deficits in recognizing familiar places (along with Congenital Prosopagnosia), but not common objects. Eye movement recordings confirmed his problems in recognizing familiar landmarks and misrecognition of unfamiliar places. L.G. is the first evidence of a DLA, suggesting identification of taxonomy of navigational disorders in Developmental Topographical Disorientation is possible, as in the Acquired Topographical Disorientation.

Short-term changes in bone turnover markers and bone mineral density response to parathyroid hormone in postmenopausal women with osteoporosis.

CONTEXT: Treatment of osteoporotic women with PTH increases biochemical markers of bone turnover, increases axial bone mineral density (BMD), and reduces fracture risk. OBJECTIVE: Our objective was to determine the relationship between levels of baseline turnover before PTH therapy and short-term changes in turnover during PTH therapy and subsequent changes in areal and volumetric BMD. DESIGN AND SETTING: We conducted a randomized, placebo-controlled trial at four academic centers. PATIENTS: Patients included 238 postmenopausal women with low hip or spine BMD. INTERVENTION: Subjects were randomized to sc PTH (1-84), 100 mug/d (119 women), for 1 yr. MAIN OUTCOME MEASURE: Bone turnover markers were measured in fasting blood samples collected before therapy and after 1 and 3 months. Areal and volumetric BMD at the spine and hip were assessed by dual-energy x-ray absorptiometry and quantitative computed tomography (QCT) after 1 yr of therapy. RESULTS: Among women treated with PTH alone, the relationships between baseline turnover and 1-yr changes in dual-energy x-ray absorptiometry and QCT BMD were inconsistent. Greater 1- and 3-month increases in turnover, particularly the formation marker N-propeptide of type I collagen, were associated with greater increases in areal BMD. When volumetric hip and spine BMD were assessed by QCT, greater short-term increases in turnover were even more positively associated with 1-yr increases in BMD. Each sd increase in the 3-month change of N-propeptide of type I collagen was associated with an a 21% greater increase in QCT spine trabecular BMD. CONCLUSIONS: Greater short-term changes in turnover with PTH therapy are associated with greater 1-yr increases in spine and hip BMD among postmenopausal osteoporotic women.

Treatment with alendronate prevents fractures in women at highest risk: results from the Fracture Intervention Trial.

BACKGROUND: The efficacy of antiresorptive therapy in preventing fractures in women at highest fracture risk, such as very elderly women or those with severe osteoporosis, is uncertain. PARTICIPANTS AND METHODS: Using data from a double-blind, randomized, placebo-controlled clinical trial that enrolled 2027 postmenopausal women aged 55 to 81 years with low femoral neck bone mineral density (BMD) and existing vertebral fractures, we examined the consistency of the effect of treatment with alendronate sodium in preventing fractures within a priori-specified risk subgroups defined at baseline by age, bone density, number of preexisting vertebral fractures, and history of postmenopausal fracture. The women were randomized to oral administration of alendronate or placebo and followed up for an average of 2.9 years. The initial dose of alendronate sodium was 5 mg/d; the dosage was increased from 5 to 10 mg/d at 24 months. New vertebral fractures, the primary end point of this arm of the trial, were defined by morphometry as a decrease of 20% and at least 4 mm in any vertebral height between baseline and a follow-up radiograph at 36 months. Incident clinical fractures, the secondary end point, included nonspine and clinical (symptomatic) vertebral fractures. All clinical fractures were confirmed with x-ray film reports or, in the case of clinical vertebral fractures, x-ray films. RESULTS: Overall, there was a 47% significant reduction in risk of new vertebral fractures in the alendronate group compared with the placebo group. The reduction in risk of new vertebral fracture was consistent across fracture risk categories including age (relative risk [RR], 0.49 in women < 75 years compared with 0.62 in those > or = 75 years), BMD (RR, 0.54 in women with a femoral neck BMD < 0.59 g/cm2 [median] compared with 0.53 in those with a BMD > or = 0.59 g/cm2), and number of preexisting vertebral fractures (RR, 0.58 in women with 1 vertebral fracture compared with 0.52 in those with > or = 2). The overall significant 28% reduction in risk of incident clinical fractures in the alendronate group compared with the placebo group was also observed within these subgroups. Compared with the number of lower-risk women, a similar or smaller number of high-risk women needed to be treated to prevent 1 fracture. For example, 8 women aged 75 years or older compared with 9 women younger than 75 years, or 4 women with 2 or more existing vertebral fractures compared with 16 women with 1 existing vertebral fracture, needed to be treated with alendronate for 5 years to prevent 1 new vertebral fracture. CONCLUSIONS: Alendronate effectively reduces fracture risk in postmenopausal women with vertebral fractures and low BMD, including those women at highest risk because of advanced age or severe osteoporosis. Since the risk reductions observed with alendronate treatment were consistent within fracture risk categories, more fractures were prevented by treating women at highest risk.

Vertebral fractures and mortality in older women: a prospective study. Study of Osteoporotic Fractures Research Group.

BACKGROUND: Osteoporotic fractures, including clinically detected vertebral fractures, are associated with increased mortality. However, only one third of vertebral fractures are diagnosed. It is unknown whether vertebral fractures, whether clinically apparent or not, are associated with greater mortality. OBJECTIVES: To test the hypothesis that women with prevalent vertebral fractures have greater mortality than those without fractures and to describe causes of death associated with vertebral fractures. DESIGN: Prospective cohort study with mean follow-up of 8.3 years. SETTING: Four clinical centers in the United States. PARTICIPANTS: A total of 9575 women aged 65 years or older and enrolled in the Study of Osteoporotic Fractures. MEASUREMENTS: Vertebral fractures by radiographic morphometry; calcaneal bone mineral density; demographic, medical history, and lifestyle variables; blood pressure; and anthropometric measures. In a subset of 606 participants, thoracic curvature was measured during a second clinic visit. MAIN OUTCOME MEASURES: Hazard ratios for mortality and cause-specific mortality. RESULTS: At baseline, 1915 women (20.0%) were diagnosed as having vertebral fractures. Compared with women who did not have a vertebral fracture, women with 1 or more fractures had a 1.23-fold greater age-adjusted mortality rate (95% confidence interval, 1.10-1.37). Mortality rose with greater numbers of vertebral fractures, from 19 per 1000 woman-years in women with no fractures to 44 per 1000 woman-years in those with 5 or more fractures (P for trend, <.001). In particular, vertebral fractures were related to the risk of subsequent cancer (hazard ratio, 1.4;95% confidence interval, 1.1-1.7) and pulmonary death (hazard ratio, 2.1;95% confidence interval, 1.4-3.0). In the subset of women who underwent thoracic curvature measurements, severe kyphosis was also related to pulmonary deaths (hazard ratio, 2.6;95% confidence interval, 1.3-5.1). CONCLUSION: Women with radiographic evidence of vertebral fractures have an increased mortality rate, particularly from pulmonary disease and cancer.

Age effect in generating mental images of buildings but not common objects.

Imagining a familiar environment is different from imagining an environmental map and clinical evidence demonstrated the existence of double dissociations in brain-damaged patients due to the contents of mental images. Here, we assessed a large sample of young and old participants by considering their ability to generate different kinds of mental images, namely, buildings or common objects. As buildings are environmental stimuli that have an important role in human navigation, we expected that elderly participants would have greater difficulty in generating images of buildings than common objects. We found that young and older participants differed in generating both buildings and common objects. For young participants there were no differences between buildings and common objects, but older participants found easier to generate common objects than buildings. Buildings are a special type of visual stimuli because in urban environments they are commonly used as landmarks for navigational purposes. Considering that topographical orientation is one of the abilities mostly affected in normal and pathological aging, the present data throw some light on the impaired processes underlying human navigation.

A new approach to defining normal vertebral dimensions.

We developed a method for estimating the mean and standard deviation of ratios of normal vertebral heights from a sample that includes people with and without vertebral fractures. This method assumes that the measurements in normal vertebrae have a Gaussian distribution and that, for any vertebral level, the prevalence of abnormal measurements is less than 10%. Under these assumptions, normal values for nonfractured vertebrae can be estimated from several statistical properties of Gaussian distributions. We applied these methods to the lateral spinal radiographs of 2992 women aged 65-70 years who were recruited from population-based listings. The estimated means and standard deviations for ratios of dimensions in nonfractured vertebrae were very similar to those based on studies of premenopausal women. Our method may be useful for defining normal values from large populations that include normal and abnormal women, does not require x-rays of normal premenopausal women, avoids the potential biases of defining normality based on qualitative judgment, and can be applied to other types of physical and biochemical measurements.

Simple measurement of femoral geometry predicts hip fracture: the study of osteoporotic fractures.

Based on engineering principles, geometric measurements of femoral size should be related to femoral strength and the risk for hip fracture. To evaluate whether a simple measurement of femoral geometry is associated with hip fracture risk, we obtained dual x-ray absorptiometry scans of the proximal femur on 8074 white women age 67 or older. During an average of 1.6 years of follow-up, 64 participants suffered hip fractures. In all fracture cases and in a random sample of 134 women who did not subsequently suffer a hip fracture, we measured hip axis length (the distance from greater trochanter to inner pelvic brim), neck width, and the neck/shaft angle on the scan printout, with the observer blinded to subsequent fracture status of the participant. Results were analyzed using multiple logistic models, and odds ratios were determined. After adjustment for age, each standard deviation decrease in femoral neck bone mineral density increased hip fracture risk 2.7-fold (95% confidence interval 1.7, 4.3), and each standard deviation increase in hip axis length nearly doubled the risk of hip fracture (odds ratio = 1.8; 95% CI 1.3, 2.5). The relationship between hip axis length and fracture risk persisted even after adjustment for age, femoral neck density, height, and weight. A longer hip axis length was associated with an increased risk of both femoral neck (OR = 1.9; 95% CI 1.3, 3.0) and trochanteric fractures (1.6; 1.0, 2.4). We found no significant association between the neck width (1.1; 0.8, 1.5) or the neck/shaft angle (1.4; 0.9, 2.2) and risk of hip fracture.(ABSTRACT TRUNCATED AT 250 WORDS)

Does estimating volumetric bone density of the femoral neck improve the prediction of hip fracture? A prospective study. Study of Osteoporotic Fractures Research Group.

Standard projectional bone density of the femoral neck (BMD), defined as bone mineral content divided by the projected area of the neck, predicts hip fractures but may not accurately estimate the true volumetric bone density of the femoral neck. To determine whether an estimate of the volumetric bone density of the neck, "bone mineral apparent density" (BMAD), would be a better predictor of hip fracture, we analyzed dual x-ray absorptiometry scans obtained prospectively from 7963 older white women, of whom 83 suffered a hip fracture during follow-up. Both BMD and BMAD were stronger predictors than bone mineral content (BMC) of the femoral neck. However, BMD and BMAD had very similar predictive values for hip fracture: each standard deviation decrease in either BMD or BMAD of the femoral neck increased the age-adjusted risk of hip fracture 2.6- to 2.7-fold. We conclude that BMD and BMAD of the femoral neck have a similarly strong predictive value for hip fracture.(ABSTRACT TRUNCATED AT 250 WORDS)

Axial and appendicular bone density predict fractures in older women.

To determine whether measurement of hip and spine bone mass by dual-energy x-ray absorptiometry (DEXA) predicts fractures in women and to compare the predictive value of DEXA with that of single-photon absorptiometry (SPA) of appendicular sites, we prospectively studied 8134 nonblack women age 65 years and older who had both DEXA and SPA measurements of bone mass. A total of 208 nonspine fractures, including 37 wrist fractures, occurred during the follow-up period, which averaged 0.7 years. The risk of fracture was inversely related to bone density at all measurement sites. After adjusting for age, the relative risks per decrease of 1 standard deviation in bone density for the occurrence of any fracture was 1.40 for measurement at the proximal femur (95% confidence interval 1.20-1.63) and 1.35 (1.15-1.58) for measurement at the spine. Results were similar for all regions of the proximal femur as well as SPA measurements at the calcaneus, distal radius, and proximal radius. None of these measurements was a significantly better predictor of fractures than the others. Furthermore, measurement of the distal radius was not a better predictor of wrist fracture (relative risk 1.64: 95% CI 1.13-2.37) than other sites, such as the lumbar spine (RR 1.56; CI 1.07-2.26), the femoral neck (RR 1.65; CI 1.12-2.41), or the calcaneus (RR 1.83; CI 1.26-2.64). We conclude that the inverse relationship between bone mass and risk of fracture in older women is similar for absorptiometric measurements made at the hip, spine, and appendicular sites.

Prevalent vertebral deformities predict hip fractures and new vertebral deformities but not wrist fractures. Study of Osteoporotic Fractures Research Group.

Although vertebral deformities are known to predict future vertebral deformities, little is known about their ability to predict other osteoporotic fractures. We examined the association between prevalent vertebral deformities and incident osteoporotic fractures in the Study of Osteoporotic Fractures, a prospective study of 9704 women aged 65 years and older. Prevalent vertebral deformities were determined morphometrically from spinal radiographs at baseline and incident deformities from repeat spinal radiographs after a mean of 3.7 years. Appendicular fractures were collected by postcard every 4 months for a mean of 8.3 years. During follow-up, 389 women with new vertebral deformities, 464 with hip fractures, and 574 with wrist fractures were identified. Prevalent vertebral deformities were associated with a 5-fold increased risk (relative risk 5.4, 95% confidence interval [CI] 4.4, 6.6) of sustaining a further vertebral deformity; the risk increased dramatically with both the number and severity of the prevalent deformities. Similarly, the risks of hip and any nonvertebral fractures were increased with baseline prevalent deformity, with relative risks of 2.8 (95% CI 2.3, 3.4) and 1.9 (95% CI 1.7, 2.1), respectively. Risk increased with number and severity of deformities. These associations remained significant after adjustment for age and calcaneal bone mineral density (BMD). Although there was a small increased risk of wrist fracture, this was not significant after adjusting for age and BMD. In conclusion, the presence of prevalent morphometrically defined vertebral deformities predicts future vertebral and nonvertebral fractures, including hip but not wrist fractures. Spinal radiographs identifying prevalent vertebral deformities may be a useful additional measurement to classify further a woman's risk of future fracture.