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Biomedical subjects

L Palermo

Publications and source records attributed to L Palermo.

At least 19 recordsLinked to original sources

Digital X-ray radiogrammetry predicts hip, wrist and vertebral fracture risk in elderly women: a prospective analysis from the study of osteoporotic fractures.

Digital X-ray radiogrammetry (DXR) is a technique that uses automated image analysis of standard hand radiographs to estimate bone mineral density (DXR-BMD). Previous studies have shown that DXR-BMD measurements have high precision, are strongly correlated with forearm BMD and are lower in individuals with prevalent fractures. To determine whether DXR-BMD measurements predict wrist, hip and vertebral fracture risk we conducted a case-cohort study within a prospective study of 9704 community-dwelling elderly women (the Study of Osteoporotic Fractures). We compared DXR-BMD, and BMD of the radius (proximal and distal), calcaneus, femoral neck and posteroanterior lumbar spine in women who subsequently suffered a wrist (n = 192), hip (n = 195), or vertebral fracture (n = 193) with randomly selected controls from the same cohort (n = 392-398). DXR-BMD was estimated from hand radiographs acquired at the baseline visit. The radiographs were digitized and the Pronosco X-posure System was used to compute DXR-BMD from the second through fourth metacarpals. Wrist fractures were confirmed by radiographic reports and hip fractures were confirmed by radiographs. Vertebral fractures were defined using morphometric analysis of lateral spine radiographs acquired at baseline and an average of 3.7 years later. Age-adjusted odds ratio (OR, vertebral fracture) or relative hazard (RH, wrist and hip fracture) for a 1 SD decrease in BMD were computed. All BMD measurements were similar for prediction of wrist (RH = 1.5-2.1) and vertebral fracture (OR = 1.8-2.5). Femoral neck BMD best predicted hip fracture (RH = 3.0), while the relative hazards for all other BMD measurements were similar (RH = 1.5-1.9). These prospective data indicate that DXR-BMD performs as well as other peripheral BMD measurements for prediction of wrist, hip and vertebral fractures. Therefore, DXR-BMD may be useful for prediction of fracture risk in clinical settings where hip BMD is not available.

Absorptiometry, Photon↗

Quantitative ultrasound and mortality: a prospective study.

Previous studies suggest that low bone mineral density (BMD) is associated with increased mortality, but the relationship between quantitative ultrasound (QUS) and mortality is unknown. We studied 5816 women over age 70 years enrolled in the Study of Osteoporotic Fractures. QUS of the calcaneus, and BMD of the calcaneus and hip, were measured at baseline, and women were contacted every 4 months to determine vital status. All reported deaths were confirmed by review of the death certificate or hospital records, and classified by ICD-9 code. During 5.0 years of follow-up, 677 women died. Women in the lowest quintile of QUS had the highest mortality during follow-up. After adjustment for age, grip strength, weight, height, health status, estrogen use, smoking, physical activity, and history of hypertension, diabetes, cardiovascular disease, cancer and stroke, each 1 SD reduction in broadband ultrasonic attenuation (BUA) was associated with a 16% increase in mortality (RH = 1.16; 95% CI: 1.07, 1.26). Mortality from cardiovascular disease, cancer and other causes were all increased among women with low QUS, but the association with cancer deaths was not statistically significant after multiple adjustments (RH = 1.09; CI: 0.93, 1.27). Low BMD was also associated with an increased risk of total and cause-specific mortality, but we found little evidence that BUA and BMD were independent predictors of mortality. Results were similar among women who did not fracture during follow-up. In this large population-based study of older women, low QUS is associated with both total and cause-specific mortality. This relationship was independent of other factors associated with mortality, such as age and health status, and suggests QUS and BMD may reflect some aspect of aging not captured by these traditional factors.

Absorptiometry, Photon↗

An assessment tool for predicting fracture risk in postmenopausal women.

Due to the magnitude of the morbidity and mortality associated with untreated osteoporosis, it is essential that high-risk individuals be identified so that they can receive appropriate evaluation and treatment. The objective of this investigation was to develop a simple clinical assessment tool based on a small number of risk factors that could be used by women or their clinicians to assess their risk of fractures. Using data from the Study of Osteoporotic Fractures (SOF), a total of 7782 women age 65 years and older with bone mineral density (BMD) measurements and baseline risk factors were included in the analysis. A model with and without BMD T-scores was developed by identifying variables that could be easily assessed in either clinical practice or by self-administration. The assessment tool, called the FRACTURE Index, is comprised of a set of seven variables that include age; BMD T-score, fracture after age 50 years, maternal hip fracture after age 50, weight less than or equal to 125 pounds (57 kg), smoking status, and use of arms to stand up from a chair. The FRACTURE Index was shown to be predictive of hip fracture, as well as vertebral and nonvertebral fractures. In addition, this index was validated using the EPIDOS fracture study. The FRACTURE Index can be used either with or without BMD testing by older postmenopausal women or their clinicians to assess the 5-year risk of hip and other osteoporotic fractures, and could be useful in helping to determine the need for further evaluation and treatment of these women.

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Bone marrow angiogenesis and plasma cell angiogenic and invasive potential in patients with active multiple myeloma.

Factor VIII-related antigen-positive microvessel areas were measured by both immunohistochemistry and computerized image analysis in patients with active multiple myeloma (MM), nonactive MM and monoclonal gammopathies of undetermined significance (MGUS). A 5- to 6-fold larger area was found in patients with active MM compared to the other two groups. The conditioned medium (CM) of their bone marrow plasma cells stimulated endothelial cell proliferation and chemotaxis, monocyte chemotaxis and angiogenesis in vivo [chick embryo chorioallantoic membrane (CAM) system] more strongly and frequently than the CM of patients with nonactive MM and MGUS. An immunoassay of plasma cell lysates gave significantly higher levels of fibroblast growth factor-2 (FGF-2) in patients with active MM than in the other two groups, and a neutralizing anti-FGF-2 antibody inhibited by 54-68% the biological activity exerted by the CM in vitro and in the CAM. In situ hybridization of bone marrow plasma cells and gelatin zymography of CM showed that patients with active MM express higher levels of matrix metalloproteinase-2 (MMP-2) mRNA and protein than those with nonactive MM and MGUS, whereas MMP-9 expression and secretion overlapped in all groups. Overall data suggest that patients with active MM represent the vascular phase of plasma cell tumors that is triggered by bone marrow plasma cells, at least partly, through FGF-2 and MMP-2. Both angiogenesis and MMP-2 secretion can account for intramedullary and extramedullary spreading of plasma cells during the active MM.

Bone Marrow↗

A normative reference database study for Pronosco X-posure System.

Cortical width from radiographs has been used for more than 40 yr as a means of estimating bone strength. In the last 5-10 yr, increased availability of computers and the development of automated algorithms for image assessment have led to an increased interest in radiogrammetry. In this study, we examined a new radiogrammetry device, the Pronosco X-posure System, which estimates bone mineral density (BMD) from forearm/hand radiographs. We obtained hand and forearm radiographs and performed dual X-ray absorptiometry (DXA) at the wrist and hip on 832 women ages 20-79 at four clinical centers across the United States. We then used the X-posure System to estimate BMD (DXR-BMD). The goal of the study was to establish reference ranges for the method and to compare the measurement to DXA measurements of BMD at the wrist and hip. Using statistical models, we estimated that the peak value for DXR-BMD occurred at age 38 (mean = 0.598 g/cm2, standard deviation = 0.034 g/cm2). The correlation between DXR-BMD and DXA was 0.90 at the wrist and 0.61 at the hip. The relationship of DXR-BMD to reported history of fracture was of similar magnitude to that for DXA at the wrist and hip. The strong correlation of DXR-BMD from the X-posure System with DXA at the wrist from the Hologic machine suggests that the X-posure System may be an alternative to DXA at the wrist for the assessment of osteoporosis.

Absorptiometry, Photon↗

Monitoring osteoporosis therapy with bone densitometry: misleading changes and regression to the mean. Fracture Intervention Trial Research Group.

CONTEXT: The principle of "regression to the mean" predicts that patients with unusual responses to treatment might represent outliers who are likely to have more typical responses if treatment is continued without change. OBJECTIVE: To test whether women who lose bone mineral density (BMD) during the first year of treatment for osteoporosis continue to lose BMD if the same treatment is continued beyond 1 year. DESIGN AND SETTING: Two randomized, double-blind, placebo-controlled trials in 11 US clinical research centers for the Fracture Intervention Trial and 180 centers in the United States and other countries for the Multiple Outcomes of Raloxifene Evaluation Trial. PARTICIPANTS AND INTERVENTIONS: Postmenopausal women with low BMD assigned to treatment with 5 mg/d of alendronate sodium in the Fracture intervention Trial who completed 2 years of BMD monitoring and adhered to study medication (n = 2634), and postmenopausal women with osteoporosis assigned to treatment with 60 or 120 mg/d of raloxifene hydrochloride in the Multiple Outcomes of Raloxifene Evaluation trial who similarly completed 2 years of monitoring while adhering to study medication (n = 3954). MAIN OUTCOME MEASURES: Baseline, 12-, and 24-month hip and spine BMD. RESULTS: Women with the greatest loss of BMD during the first year of treatment were the most likely to gain BMD during continued treatment. Specifically, among women taking alendronate whose hip BMD decreased by more than 4% during the first year, 83% (95% confidence interval [CI], 82%-84%)had increases in hip BMD during the second year, with an overall mean increase of 4.7%. In contrast, those who seemed to gain at least 8% during the first year lost an average of 1% (95% CI, 0.1%-1.9%) during the next year. Similar results were observed among women taking raloxifene for 2 years. CONCLUSIONS: Our data suggest that most women who lose BMD during the first year of treatment with alendronate or raloxifene will gain BMD if the same treatment is continued for a second year. These results illustrate the principle of regression to the mean and suggest that effective treatments for osteoporosis should not be changed because of loss of BMD during the first year of use.

Absorptiometry, Photon↗

Vertebral fracture prevalence among women screened for the Fracture Intervention Trial and a simple clinical tool to screen for undiagnosed vertebral fractures. Fracture Intervention Trial Research Group.

OBJECTIVE: To evaluate the ability of self-reported risk factors to identify postmenopausal women likely to have extant vertebral fractures because approximately two thirds of women with radiographic evidence of vertebral fracture are unaware of the fracture. PATIENTS AND METHODS: Questionnaire and spinal radiographic data were collected from postmenopausal women with a femoral neck bone mineral density T score of -1.6 or lower during screening for the Fracture Intervention Trial. Logistic regression was used to identify risk factors for extant vertebral fractures and to derive a final multivariable model. RESULTS: Almost two thirds of 25,816 women 55 years and older met the bone density criterion, and 21% of those had an extant vertebral fracture. The final model consisted of 5 self-reported items: history of vertebral fracture, history of nonvertebral fracture, age, height loss, and diagnosis of osteoporosis. These were combined to yield a Prevalent Vertebral Fracture Index (PVFI). The prevalence of women with vertebral fracture varied from 3.8% to 62.3% over the range PVFI of 0 to greater than 5. Among the 13,051 women screened with spinal radiographs, a PVFI of 4 or greater identified 65.5% of women with vertebral fractures (sensitivity), with a specificity of 68.6%. Excluding 881 women who reported prior vertebral fractures reduced the sensitivity to 53.6 % and increased the specificity to 70.7% but did not alter the fracture prevalence at PVFI values less than 6. CONCLUSION: In this population, 5 simple questions identified women who were likely to have undiagnosed vertebral fractures. Further research is needed to determine the validity of this index in other populations, including women without low bone mineral density.

Age Distribution↗

Degenerative lumbar listhesis and bone mineral density in elderly women. The study of osteoporotic fractures.

STUDY DESIGN: A cross-sectional and prospective study. OBJECTIVES: To investigate the association between lumbar listhesis in elderly white women and bone mineral density at the spine, hip, radius, and calcaneus. SUMMARY OF BACKGROUND DATA: Several types of degenerative spinal changes have been found to be associated with high bone mineral density at the spine and other body sites. METHODS: Lateral radiographs of the lumbar spine for 1400 elderly women enrolled in the Study of Osteoporotic Fractures were digitized. Listhesis (antero and retro) was assessed at L3-L4, L4-L5, and L5-S1. Bone mineral density was measured at the spine, hip, calcaneus, and the distal and proximal radius. RESULTS: After adjusting the data for age and body mass index, retrolisthesis at L3-L4, L4-L5, and L5-S1 was associated with mean spinal bone mineral density levels that were 9% to 13% higher compared with those levels in women with no listhesis (P < 0.0001). In addition, bone mineral density at the hip and appendicular sites increased from 4% to 9%. The mean lumbar spinal bone mineral density of women with anterolisthesis at L3-L4 was 12% higher (P < 0.05) than that of women with no listhesis; it was the same for both groups at L4-L5 and was 7% lower (P < 0.005) at L5-S1. At L5-S1 the bone mineral density level at the hip and appendicular sites was also lower among the women with anterolisthesis at that level. CONCLUSIONS: This study suggests that retrolisthesis, like other spinal degenerative diseases, is associated with increased spinal bone mineral density. Anterolisthesis, however, may involve a different etiology, because its association with bone mineral density varies by spinal level.

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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.

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Association of prevalent vertebral fractures, bone density, and alendronate treatment with incident vertebral fractures: effect of number and spinal location of fractures. The Fracture Intervention Trial Research Group.

Vertebral fractures are the most common osteoporotic fracture and are associated with significant pain and disability. Prior vertebral fracture and low bone mineral density (BMD) are strong predictors of new vertebral fracture. Using data from 6082 women, ages 55-80 years, in the Fracture Intervention Trial (a randomized, placebo-controlled trial of the antiresorptive agent, alendronate), we explored the association of the number of prior vertebral fractures with the risk of new fractures and whether this association is influenced by the spinal location of fractures. The risk of future vertebral fractures increased with the number of prevalent fractures, independently of age and BMD; in the placebo group, more than half of the women with five or more fractures at baseline developed new vertebral fractures, compared to only 3.8% of women without prior vertebral fractures. The magnitude of association with an increased risk of future vertebral fractures was equal for prevalent fractures located in either the "lower" (T12-L4) (relative risk [RR] = 2.9; 95% CI = 1.9, 3.6) or "upper" (T4-10) spine (RR = 2.6; 95% CI = 1.9, 3.6). We found no evidence that the effectiveness of alendronate in reducing the risk of future vertebral fracture was attenuated in women with up to five or more prevalent fractures, or that it varied by the location of prevalent fractures. However, prevalent vertebral fractures in any location were more strongly associated with risk of new fractures in the upper (RR = 5.2; 95% CI = 3.2, 8.3) than in the lower spine (2.3; 1.6, 3.3). In addition, each 1 SD decrease in spinal BMD was associated with a 2.1 (1.7, 2.6) times greater odds of new fracture in the upper spine, compared with 1.5 (1.3, 1.8) for the lower spine. These findings suggest that, in older women, osteoporosis may be a stronger risk factor for new fractures in the upper (vs. lower) thoracolumbar spine, although we found no evidence that the location of prior fractures should influence treatment decisions. Physicians should recognize that prior vertebral fractures are a strong risk factor for future fractures, and consider treating such patients to reduce their risk of subsequent fractures.

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Effect of a lifestyle intervention on bone mineral density in premenopausal women: a randomized trial.

BACKGROUND: The positive association between body weight and bone mineral density (BMD) is well documented; in contrast, the effect of changes in body weight on BMD is not well understood, particularly, in normal-weight populations. OBJECTIVE: We examined the effect of a lifestyle intervention aimed at lowering dietary fat intake and increasing physical activity to produce modest weight loss or prevent weight gain on BMD in a population of 236 healthy, premenopausal women aged 44-50 y. DESIGN: All women were participating in a clinical trial known as The Women's Healthy Lifestyle Project and were randomly assigned to intervention or control groups. Dual-energy X-ray absorptiometry of BMD at the lumbar spine and proximal femur were made before and after 18 mo of participation in the trial. RESULTS: The intervention group (n = 115) experienced a mean (+/-SD) weight loss of 3.2 +/- 4.7 kg over the 18 mo compared with a weight gain of 0.42 +/- 3.6 kg in the control group (n = 121) (P < 0.001). The annualized rate of hip BMD loss was 2-fold higher (P < 0.015) in the intervention group (0.81 +/- 1.3%) than in the control group (0.42 +/- 1.1%); a similar, although nonsignificant pattern was observed for the loss in spine BMD: 0.70 +/- 1.4% and 0.37 +/- 1.5% (P = 0.093) in the intervention and control groups, respectively. Large increases in physical activity attenuated spine BMD loss, but had no significant effect on BMD loss at the hip. CONCLUSIONS: The intervention group, who modified their lifestyle to lose weight, had a higher rate of BMD loss at the hip and lumbar spine than did the weight-stable control group. Recommendations for weight loss must be made with consideration that such an endorsement may result in BMD loss.

Adult↗

Defining incident vertebral deformity: a prospective comparison of several approaches. The Study of Osteoporotic Fractures Research Group.

Vertebral deformities are common and important outcomes in clinical trials and epidemiologic studies of osteoporosis. While several different methods for defining new deformities have been proposed, it is not clear which is best. We used data from serial spine radiographs obtained an average of 3.7 years apart in 7238 women age >/=65 years from the Study of Osteoporotic Fractures to compare several approaches to defining new deformities by morphometry including a fixed percentage reduction in any vertebral height (FIXED%), a change in a summary spinal deformity index, a change in a vertebra from no prevalent deformity at baseline to a deformity at follow-up, as well as several variations of these methods. We compared results of each definition with several clinical correlates, including height loss, back pain, age, baseline bone mineral density, and the presence of a baseline deformity. We also estimated the sample size required for a clinical trial using various cut points. At a given level of incidence, all methods had similar relationships with each of the correlates. Given that similarity, the FIXED% method was simplest and needed no reference data. Using the FIXED% method, a 20-25% vertebral height reduction criterion for deformity maximized the power for a clinical trial. We conclude that all of the morphometric approaches to defining incident deformities have similar relationships to clinical correlates of vertebral deformity, but that use of a fixed percentage reduction in vertebral height is the simplest and most practical. For the FIXED% method, a 20-25% reduction in vertebral height minimizes the sample size required for clinical trials and epidemiologic studies.

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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.

Aged↗

Lumbar olisthesis and lower back symptoms in elderly white women. The Study of Osteoporotic Fractures.

STUDY DESIGN: A Cross-sectional study. OBJECTIVES: To determine the prevalence of lumbar olisthesis among white women aged 65 years and older and its relation to low back pain and back function. BACKGROUND: Degenerative changes in the lumbar spine of elderly individuals may affect spinal stability, causing olisthesis (subluxation) of the lumbar spine. Neither the prevalence of this condition in the United States nor its relation to back symptoms has been studied previously. METHODS: Lateral radiographs of the lumbar spine for 788 women aged 65 years and older who were enrolled in the Study of Osteoporotic Fractures were digitized. Olisthesis (antero- and retro-) was assessed at L3-L4, L4-L5, and L5-S1. Back pain and function also were assessed. RESULTS: When olisthesis was defined as subluxation of 3 mm or more at any of the three levels studied, the overall prevalence of anterolisthesis was 29% and that of retrolisthesis was 14%. In 90% of women with anterolisthesis and 88% of women with retrolisthesis, subluxation occurred at a single vertebral level. The prevalence of anterolisthesis and retrolisthesis did not vary by smoking status, presence of diabetes, or history of oophorectomy. Anterolisthesis was not associated with the presence of back symptoms. Only retrolisthesis at L3-L4 was associated with a statistically significantly increased likelihood of lower back pain, greater severity of back pain, and impairment of back function. CONCLUSIONS: Anterolisthesis of 3 mm or more in the lower lumbar spine is relatively common among elderly women but is not correlated with back problems. Retrolisthesis at L3-L4 is associated with increased back pain and impaired back function.

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Are menopausal symptoms associated with bone mineral density and changes in bone mineral density in premenopausal women?

BACKGROUND: The relationship between menopausal symptoms and bone mineral density (BMD) was examined in 290 premenopausal women, ages 44-50 years, participating in a randomized clinical trial of a dietary and exercise intervention: The Women's Healthy Lifestyle Project. METHODS: Information on hot flashes (presence, absence), menstrual cycles (irregular, regular) and menstrual flow per period (variable, same) over the past 6 months was collected at entry. Participants reporting at least one menopausal symptom were classified as symptomatic and compared to those having no symptoms. Bone mineral density (BMD) at the lumbar spine (L1-L4), total hip and whole-body were made at baseline and at 30 months using a dual-energy X-ray absorptiometer (Hologic QDR 2000 densitometer). RESULTS: Baseline BMD at the spine, hip and whole-body were significantly reduced in women reporting menopausal symptoms compared to asymptomatic women, after adjustment for age, weight and intervention status (all p < 0.05). Women with irregular menstrual cycles had greater annualized rates of bone loss at the spine and hip than asymptomatic women (spine, -0.77 (1.6)% per year vs. -0.19 (1.0)% per year, p = 0.0043; hip, -0.37 (1.1)% per year vs. -0.04 (1.0)% per year, p = 0.061), after adjustments for age, percent change in weight, intervention status, and baseline BMD. Similar findings were not found for whole-body BMD. CONCLUSIONS: These results suggest that menopausal symptoms are useful for the effective identification of premenopausal women at higher risk of low BMD and perhaps, of osteoporosis.

Absorptiometry, Photon↗

Comparison of semiquantitative visual and quantitative morphometric assessment of prevalent and incident vertebral fractures in osteoporosis The Study of Osteoporotic Fractures Research Group.

The assessment of radiographs for vertebral fractures is important in the clinical evaluation of patients with suspected osteoporosis, in the epidemiological evaluation of elderly populations, and in clinical trials of osteotrophic drugs. The purpose of this study is to compare visual semiquantitative (SQ) approaches and quantitative morphometric approaches for assessing prevalent and incident vertebral fractures in postmenopausal osteoporosis. We analyzed lateral thoracolumbar spine radiographs (baseline and approximately 3.5 year follow-up) of 503 women (age > or = 65) randomly selected from the Study of Osteoporotic Fractures (SOF) population. SQ assessment by an experienced radiologist graded vertebral fractures from 0 (normal) to 3 (severe). Incident fractures by SQ were defined as an increase of > or = 1 grade on follow-up radiographs. Trained research assistants visually triaged women as normal, uncertain, or probably fractured and visually flagged vertebrae with moderate/severe (grade > or = 2) prevalent fractures or with any (grade > or = 1 change) incident fracture. The radiographs were also digitized by research assistants, and quantitative morphometry (QM) was used to classify vertebral deformities at several cut-offs based on standard deviation (SD) reductions in height ratios from normal means, e.g., QM > or = 3 SD. Incident fractures by QM were defined as a decrease in height of more than 15% (QM15) on follow-up radiographs. Finally, a combination of these methods was used to detect moderate/severe prevalent fractures and any grade of incident fractures. In the overall analysis, the prevalence of fractures varied from 14 to 33% and the incidence from 5 to 10% by woman, depending upon the method and cut-off criteria. In the detailed analysis, considering visually triaged uncertain as abnormal, triage by research assistants detected 97.0% (163/168) of women with SQ grade > or = 1 fractures and 100% (70/70) with SQ grade > or = 2 fractures. Visual flagging by research assistants detected 88.5% (108/122) of SQ > or = 2 prevalent fractures (kappa score, kappa = 0.82) and 85.2% (52/61) of SQ incident fractures (kappa = 0.79). QM > or = 3 SD detected 37.9% (141/372) of SQ > or = 1 prevalent fractures (kappa = 0.51) and 79.5% (97/122) of SQ > or = 2 prevalent fractures (kappa = 0.68), plus 18 vertebrae without SQ fractures. QM 15 detected 59% (36/61) of SQ incident fractures (kappa = 0.70), plus five vertebrae without SQ incident fractures. The combination assessment detected 92% (112/122) of SQ > or = 2 prevalent fractures (kappa = 0.76) and 84% (51/61) of SQ incident fractures (kappa = 0.91). The precision errors of QM vertebral height measurements (baseline versus follow-up) ranged from 2.71 to 2.92%. Nevertheless, excluding the 5719 vertebrae that were clearly normal by morphometry, i.e., within 2 SD of the normal means at both baseline and follow-up, two-thirds (358/556) of the remaining vertebrae changed classification by at least 1 SD category. Visual triage and visual flagging by research assistants appear to be highly effective methods for vertebral fracture assessment in osteoporosis, potentially reducing the number of false-positive and false-negative fractures detected by QM, at least relative to SQ by the radiologists. There is higher concordance among the visual approaches studied than between the visual SQ and quantitative morphometric approaches, with QM having limited ability to detect mild fractures but good ability to detect moderate/severe fractures, as classified by SQ. Use of a combination of sensitive qualitative and quantitative criteria, with adjudication by an experienced radiologist, is feasible and draws upon the relative strengths of each of the methods. Quantitative morphometry should not be performed in isolation, particularly when applying highly sensitive morphometric criteria at low threshold levels, without visual assessment to confirm the detected prevalent or incident vertebral defor

Aged↗

Determinants of premenopausal bone mineral density: the interplay of genetic and lifestyle factors.

Bone mineral density (BMD) is a reflection of both genetic and lifestyle factors. The interplay of genetic (vitamin D receptor [VDR] gene polymorphisms) and lifestyle factors on BMD at the lumbar spine and proximal femur was examined in 470 healthy premenopausal women, aged 44-50 years, using a Hologic QDR 2000 densitometer. The objective of this study was to examine the genetic and lifestyle determinants of premenopausal BMD. Each participant was genotyped for BsmI polymorphism at the VDR gene locus. The presence of a restriction site within VDR, specified as bb (189, 40.2%) (n, %) was associated with reduced spinal BMD, whereas absence of this site in BB (97, 20.6%) conferred greater spinal BMD, as did the genotype Bb (184, 39.1%). Associations between smoking, alcohol use, oral contraceptives, education level, multivitamins, number of children, degree of obesity, body weight, physical activity, dietary calcium intake, and VDR genotype to BMDs were examined. VDR genotype, body weight, degree of obesity, physical activity, and dietary calcium intake were all significant determinants of BMD. The association of VDR genotype with BMD at the femoral neck appeared to be modified by calcium intake (BB and Bb: 0.797 +/- 0.11 g/cm2 vs. 0.844 +/- 0.11 g/cm2, interaction term, p = 0.06) for low (< 1036 mg/day) and high (> or = 1036 mg/day; upper quartile) calcium intakes, respectively. A similar trend was demonstrated for physical activity. These findings suggest that prophylactic interventions aimed at achieving and maintaining optimal BMD, such as greater calcium intake or physical activity, may be important in maximizing one's genetic potential for BMD.

Adult↗

The association between vitamin D receptor gene polymorphisms and bone mineral density at the spine, hip and whole-body in premenopausal women.

The genetic influence on bone mineral density (BMD) is thought to be mediated in part by alleles at the vitamin D receptor (VDR) locus. In order to assess the effect of VDR on BMD in premenopausal women, we studied 470 healthy white subjects, aged 44-50 years, participating in the Women's Healthy Lifestyle Project. Each participant was genotyped for the BsmI polymorphism at the VDR gene locus. BMD at the lumbar spine, hip and whole-body, and the whole-body soft tissue composition, were measured cross-sectionally using a Hologic QDR 2000 densitometer. The presence of a polymorphic restriction site at the VDR gene locus was specified as b, whereas absence of this site was B. The frequency distribution of the VDR genotype was: bb, 20.6%; Bb, 39.1%; and BB, 40.2%. Spinal BMD (mean +/- SD) was significantly lower in women with VDR genotype BB (1.038 +/- 0.11 g/cm2) as compared with those with genotype bb (1.069 +/- 0.12 g/cm2, p < 0.05). Trochanter BMD was 2.7% lower in those with genotype BB versus bb (0.685 +/- 0.10 g/cm2 vs 0.708 +/- 0.09 g/cm2). A similar trend was shown at each subregion of the hip, but not at the whole-body. In premenopausal women, allelic status at the VDR locus contributed to variations in spinal and trochanteric BMDs, but the absolute difference in BMDs was small, amounting to 0.26 and 0.23 standard deviations, respectively. It is concluded that in this population of healthy premenopausal women there was a significant association between polymorphisms at the VDR gene locus and both spinal and trochanteric BMDs, yet no association was demonstrated for the whole-body BMD.

Adult↗