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Biomedical subjects

L Palermo

Publications and source records attributed to L Palermo.

33 records · Page 2Linked to original sources

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↗

Comparison of methods for defining prevalent vertebral deformities: the Study of Osteoporotic Fractures.

Women with vertebral deformities caused by osteoporosis have more back pain and disability and are at higher risk for subsequent vertebral deformities than women without deformities. Despite the importance of vertebral deformities, there has been a great deal of controversy about how to identify or define them. In order to compare methods for defining vertebral deformities, we studied spinal radiographs from women in the Study of Osteoporotic Fractures (SOF), a cohort study of 9704 non-black women over age 65 recruited from population-based listings in four clinical centers. Using radiographs obtained at the baseline exam, we compared five methods for defining vertebral deformities: one based on a semiquantitative reading by a radiologist and four using vertebral morphometry. The semiquantitative method was compared with the other methods in a random sample of 503 films, while the morphometric methods were compared with each other in a larger sample of 9575 films. We tested a system of "triage" in which only those films with evidence of deformity were assessed by morphometry. We compared the relationship between deformity, defined by each method, and a variety of clinical criteria including bone mineral density at the lumbar spine, height loss since age 25, back pain, and incidence of subsequent deformity. Semiquantitative reading and three of the four morphometry-based methods provided similar relationships to clinical criteria. The fourth morphometry method (based on ratios of each vertebral height to the corresponding height at T4) produced significantly weaker relationships for several of the clinical validation criteria. Triage of radiographs rarely resulted in missed deformities and did not reduce the performance of any of the methods. We conclude that use of any of the similar methods, with or without triage, provides a valid approach to defining vertebral deformities.

Aged↗

Body composition and bone mineral density in premenopausal and early perimenopausal women.

Body composition appears to be an important determinant of bone mineral density (BMD). BMD at the femoral neck, lumbar spine, and whole-body and the whole-body soft-tissue composition were measured cross-sectionally in 334 healthy premenopausal and early perimenopausal women, aged 44-50 years, using a Hologic QDR densitometer. Correlations between lean mass and BMD at the hip, spine, and whole-body were greater (r = 0.40, r = 0.44, and r = 0.45, respectively, p < 0.0001) than those for fat mass (r = 0.19, r = 0.16, and r = 0.16, respectively, p < 0.01). There was a significant linear trend in femoral BMD from the lowest to highest category of lean mass (0.75 +/- 0.10 g/cm2, 0.80 +/- 0.10 g/cm2, and 0.86 +/- 0.09 g/cm2, p < 0.0001). Similar trends were demonstrated for spinal and whole-body density. For categories of fat mass, there was a significant linear trend at the hip (0.78 +/- 0.10 g/cm2, 0.79 +/- 0.10 g/cm2, and 0.83 +/- 0.10 g/cm2, p = 0.0106), but not at the spine or whole body. There was a 5.00% (3.62, 6.38; 95% confidence limits) difference in hip BMD per unit (standard deviation) of lean mass, while only a 0.73% (-0.66, 2.11) difference in hiP BMD per unit (SD) of fat mass. Differences in BMD were examined by categories of lean and fat mass (low, medium, high) for a total of nine possible combinations of lean and fat measures. BMD at the hip, spine, and whole-body were significantly higher in those with high lean mass than in those with low lean mass, irrespective of fat mass. Women with high lean/low fat had similar hip, spinal, and whole-body BMD as those with high lean/high fat, despite their significantly lower body weight (62.5 +/- 3.3 kg vs 85.7 +/- 5.4 kg, respectively, p < 0.0001). In premenopausal and early perimenopausal women, body weight alone may not be associated with increased bone mass unless a significant proportion of that weight is comprised of lean mass. The stronger association between lean mass and BMD than that for fat mass may be attributed to differences in determinants of lean mass, such as exercise, lifestyle factors, estrogen levels, or a combination of these factors.

Adult↗

Hip and calcaneal bone loss increase with advancing age: longitudinal results from the study of osteoporotic fractures.

It is uncertain whether or how rapidly elderly women continue to lose bone with advancing age. To determine rates of change in bone mass at the hip and at the calcaneus in elderly women and to compare these rates of change among estrogen users and nonusers, we prospectively measured rates of change in bone mineral density (BMD) at the total hip and its four subregions (mean +/- SD, 3.55 +/- 0.29 years between examinations) and at the calcaneus (mean +/- SD, 5.69 +/- 0.33 years between examinations) in 5689 community-dwelling white women aged 65 years or older at the baseline examination. The rate of decline in total hip BMD steadily increased from 2.5 mg/cm 2/year (95% confidence interval 2.0 to 2.9) in women 67-69 years old to 10.4 mg/cm 2/year in those aged 85 or older (95% confidence interval 8.4 to 12.4). The rate of bone loss also increased with aging at all subregions of the hip and at the calcaneus. The average loss of bone from the total hip is sufficient to increase the risk of hip fracture by 21% per 5 years in women aged 80 years or older. Compared with nonusers, current estrogen users had a 33% lower age-adjusted mean rate of loss at the total hip (2.9 vs 4.3 mg/cm 2/year, p < or = 0.0001) and a 35% lower age-adjusted mean rate of loss at the calcaneus (3.9 vs 6.0 mg/cm 2/year, p < or = 0.0001). The rate of bone loss in the hip and calcaneus steadily increases with advancing age in older women. Estrogen therapy may significantly decrease this loss. Efforts to understand and prevent bone loss should include elderly women.

Aged↗

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)

Absorptiometry, Photon↗

Racial differences in hip axis lengths might explain racial differences in rates of hip fracture. Study of Osteoporotic Fractures Research Group.

Compared with white women, Asian women have about a 40%-50% and blacks a 50%-60% lower risk of hip fracture, but the reason for this racial difference is not known. Women with a shorter hip axis have a lower risk of hip fracture. To test the hypothesis that a shorter hip axis length could account for the lower risk of hip fracture among Asian and black women, we measured hip axis length in 135 Caucasian, 74 Asian and 50 black women. The mean hip axis lengths of Asian and black women were significantly shorter (1.2 and 0.7 standard deviations, respectively) than that of the whites (p < 0.0001). We estimate that, compared with white women, Asians would have a 47% lower risk (95% confidence interval: 32%-63%) and blacks would have a 32% (15%-45%) lower risk of hip fracture because of their shorter hip axis. We conclude that a shorter hip axis length might be a major factor accounting for Asian women's lower risk of hip fracture and might contribute to the lower risk in black women.

Aged↗

Kyphosis in older women and its relation to back pain, disability and osteopenia: the study of osteoporotic fractures.

To test the hypothesis that thoracic kyphosis is associated with substantial pain, disability, and height loss, we measured thoracic curvature, using an architect's flexicurve, of 610 women aged 65-91 years who were recruited from population-based listings. We assessed study subjects for back pain, back-related disability, height loss since age 25 years, perceived state of health, and bone mineral density (BMD) at the spine, calcaneus, proximal radius, and distal radius. Compared with the rest of the cohort, the 10% of women with the most severe kyphosis had 7%-17% lower BMD (p < 0.001) and had lost an additional 2.4 cm height (p < 0.001). However, kyphotic women had no greater back pain, disability caused by back problems, or poorer health. This cross-sectional study suggests that kyphosis is associated with decreased BMD and loss of height but does not cause substantial chronic back pain, disability, or poor health in older women.

Aged↗

Bone density at various sites for prediction of hip fractures. The Study of Osteoporotic Fractures Research Group.

Women with low bone density in the radius or calcaneus are at increased risk of hip fracture. To see whether bone density of the hip measured by dual X-ray absorptiometry is a better predictor of hip fracture than measurements of other bones, we assessed bone density at several sites in 8134 women aged 65 years or more. 65 women had hip fractures during a mean follow-up of 1.8 years. Each SD decrease in femoral neck bone density increased the age-adjusted risk of hip fracture 2.6 times (95% CL 1.9, 3.6). Women with bone density in the lowest quartile had an 8.5-fold greater risk of hip fracture than those in the highest quartile. Bone density of the femoral neck was a better predictor than measurements of the spine (p < 0.0001), radius (p < 0.002), and moderately better than the calcaneus (p = 0.10). Low hip bone density is a stronger predictor of hip fracture than bone density at other sites. Efforts to prevent hip fractures should focus on women with low hip bone density.

Absorptiometry, Photon↗

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)

Absorptiometry, Photon↗

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.

Absorptiometry, Photon↗

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.

Aged↗

Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial.

CONTEXT: Alendronate sodium reduces fracture risk in postmenopausal women who have vertebral fractures, but its effects on fracture risk have not been studied for women without vertebral fractures. OBJECTIVE: To test the hypothesis that 4 years of alendronate would decrease the risk of clinical and vertebral fractures in women who have low bone mineral density (BMD) but no vertebral fractures. DESIGN: Randomized, blinded, placebo-controlled trial. SETTING: Eleven community-based clinical research centers. SUBJECTS: Women aged 54 to 81 years with a femoral neck BMD of 0.68 g/cm2 or less (Hologic Inc, Waltham, Mass) but no vertebral fracture; 4432 were randomized to alendronate or placebo and 4272 (96%) completed outcome measurements at the final visit (an average of 4.2 years later). INTERVENTION: All participants reporting calcium intakes of 1000 mg/d or less received a supplement containing 500 mg of calcium and 250 IU of cholecalciferol. Subjects were randomly assigned to either placebo or 5 mg/d of alendronate sodium for 2 years followed by 10 mg/d for the remainder of the trial. MAIN OUTCOME MEASURES: Clinical fractures confirmed by x-ray reports, new vertebral deformities detected by morphometric measurements on radiographs, and BMD measured by dual x-ray absorptiometry. RESULTS: Alendronate increased BMD at all sites studied (P<.001) and reduced clinical fractures from 312 in the placebo group to 272 in the intervention group, but not significantly so (14% reduction; relative hazard [RH], 0.86; 95% confidence interval [CI], 0.73-1.01). Alendronate reduced clinical fractures by 36% in women with baseline osteoporosis at the femoral neck (>2.5 SDs below the normal young adult mean; RH, 0.64; 95% CI, 0.50-0.82; treatment-control difference, 6.5%; number needed to treat [NNT], 15), but there was no significant reduction among those with higher BMD (RH, 1.08; 95% CI, 0.87-1.35). Alendronate decreased the risk of radiographic vertebral fractures by 44% overall (relative risk, 0.56; 95% CI, 0.39-0.80; treatment-control difference, 1.7%; NNT, 60). Alendronate did not increase the risk of gastrointestinal or other adverse effects. CONCLUSIONS: In women with low BMD but without vertebral fractures, 4 years of alendronate safely increased BMD and decreased the risk of first vertebral deformity. Alendronate significantly reduced the risk of clinical fractures among women with osteoporosis but not among women with higher BMD.

Absorptiometry, Photon↗

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.

Administration, Oral↗