bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Functional Block of TNF but Not of IL-6 Prevents Bone Loss in Ovariectomized Mice
Authors: Kimble Robert B. , Bain Steve , Pacifici Roberto 
Published: April 2006

Abstract
Considerable evidence supports the hypothesis that estrogen prevents bone loss by blocking the bone marrow cell production of pro-osteoclastogenic cytokines. However, controversy remains on the role of candidate factors, such as tumor necrosis factor (TNF) and interleukin-6 (IL-6). To investigate the contribution of these cytokines to the pathogenesis of ovariectomy (OVX)-induced bone loss, OVX mice were treated with either TNF binding protein (TNFbp), an inhibitor of TNF, the anti–(IL-6) antibody (Ab) 20F3, or estrogen for the first 2 weeks after surgery. OVX caused a rapid decrease in trabecular bone volume (TBV) and an increase in in vivo bone resorption, as assessed by bone histomorphometry. Treatment with TNFbp completely prevented bone loss and the increase in both osteoclast formation and bone resorption induced by OVX, but had no effects in sham-operated controls. In contrast, treatment with anti–IL-6 antibody failed to prevent bone loss, and the increase in bone resorption and osteoclastogenesis induced by OVX. These data demonstrate that in nongenetically manipulated mice, the estrogen-regulated cytokine that plays a central role in the mechanism by which estrogen deficiency causes bone loss is not IL-6, but rather TNF.
Attitudes and Beliefs of Family Physicians and Gynecologists in Relation to the Prevention and Treatment of Osteoporosis
Authors: Suarez-Almazor Maria , Homik Joanne E. , Messina Daniel , Davis Paul 
Published: April 2006

Abstract
The objective of this study was to evaluate the attitudes and beliefs of primary care physicians (PCPs) and obstetricians/gynecologists (O&Gs) in relation to the prevention and treatment of osteoporosis (OP) in postmenopausal women. A survey was mailed to a random sample of PCPs and to all O&Gs registered in the province of Alberta (Canada). The survey evaluated their practice patterns using closed-ended questions, Likert scaled items, and two case studies. Cases 1 and 2 were 52-year-old and 62-year-old healthy postmenopausal women, respectively, with no known risks for OP. Neither had received hormone replacement therapy (HRT). One hundred fifty-seven PCPs and 57 O&Gs participated in the study. Thirty-eight percent of the PCPs and 32% of the O&Gs stated that they never requested bone mineral density measurements (BMDm) in early postmenopausal women. Most would request BMDm only in the presence of risk factors. The most important criteria to request BMDm were chronic glucocorticoid use and recent fractures. For case 1, 7% of the PCPs and 11% of the O&Gs would request BMDm; 76% of the PCPs and 80% of the O&Gs would recommend HRT. For case 2, 29% of the PCPs and 47% of the O&Gs would request BMDm (p = 0.01); 43% of the PCPs and 49% of the O&Gs would prescribe HRT. In general, O&Gs were more inclined to intervene in relation to BMDm and HRT. O&Gs were also more likely to be influenced by clinical trials than PCPs (p &lt; 0.001). Our findings show variations in the patterns of practice of physicians in relation to the prevention of OP. In general, use of densitometry appears to be low. The results of the case studies suggest that individual physician perceptions may be more influential than patient characteristics when requesting BMDm and prescribing HRT, particularly in older postmenopausal women. This group of healthy older women have approximately equal odds of being offered versus not being offered BMDm and HRT according to the physician they consult.
Site of Osteodensitometry in Perimenopausal Women: Correlation and Limits of Agreement Between Anatomic Regions
Authors: Abrahamsen B. , Hansen T. B. , Jensen L. Bjørn , Hermann A. P. , Eiken P. 
Published: April 2006

Abstract
Because the bone mineral density (BMD) in different anatomic regions is heterogenous the number of women who fulfill the World Health Organization definition of osteopenia or osteoporosis increases with the number of regions examined. The purpose of this study was to investigate the agreement between measurements of the spine, femur, forearm, and whole body following menopause. Two thousand and five healthy, perimenopausal women, mean age 50.6 years, were studied using Hologic QDR-1000/W and QDR-2000 densitometers. Though the BMD of different anatomic regions were correlated (r = 0.40–0.77, p &lt; 0.01), the variability in each patient regarding T and Z scores between regions was considerable. For example, despite a high correlation (r = 0.67, p &lt; 0.01) and no systematic difference between the T scores for total femoral and lumbar BMD, the limits of agreement (mean difference ± 2 SD) for the comparison were −1.89 to 1.87. Femoral neck T scores were 0.5 SD lower than those of the other regions, confirming reports that the young adult reference for this measurement is disproportionally high. The prevalence of osteoporosis was 1.2% when femur total BMD was considered alone and 5.9% when lumbar and ultradistal forearm results were included. However, as many as 7.9% showed osteoporosis of the femoral neck when the Hologic T score was used, compared with 0.7% using National Health and Nutrition Examination Survey (NHANES) values. The choice of anatomic region and availability of appropriate young adult reference data has considerable impact on the apparent prevalence of osteoporosis. Given the heterogeneity between regions, a combination of spinal and femoral densitometry should be used in diagnosing osteoporosis, though this increases the prevalence of osteoporosis by 50% or more in perimenopausal women.
Hip Fracture Prediction in Elderly Men and Women: Validation in the Rotterdam Study
Authors: De Laet Chris E. D. H. , Van Hout Ben A. , Burger Huibert , Weel Angelique E. A. M. , Hofman Albert , Pols Huibert A. P. 
Published: April 2006

Abstract
The aim of our study was to validate a hip fracture risk function, composed of age and femoral neck bone mineral density (BMD). This estimate of the 1-year cumulative risk was previously developed on the basis of Dutch hip fracture incidence data and BMD in men and women. A cohort of 7046 persons (2778 men) aged 55 years and over was followed for an average of 3.8 years. The 1-year hip fracture risk estimate was calculated for each participant according to the risk function and categorized as low (&lt;0.1%), moderate (0.1 to &lt;1%), or high (≥1%). Observed first hip fracture incidence was then analyzed for each of these risk categories by age and gender. Additionally, we calculated the relative risk per standard deviation (SD) decrease in femoral neck BMD in this population. At baseline, 2360 individuals were categorized as low risk, 2567 as moderate risk, and 378 as high risk. During follow-up, 110 first hip fractures were observed corresponding to an incidence rate of 4.1/1000 person-years (pyrs) (95% confidence interval 3.4–5.0). The observed incidence rate in the low risk group was 0.2/1000 pyrs (0.1–0.9), 2.7/1000 pyrs (1.8–3.9) in the moderate risk group, and 18.4/1000 pyrs (12.4–27.2) in the high risk group. Below the age of 70 years, incidence was low in all categories, and very few individuals were considered at high risk. Above the age of 70 years, the observed incidence was high in the high risk group, while in the low and moderate risk groups, the incidence remained low even over 80 years of age. In women, the age-adjusted relative risk for hip fractures was 2.5 per SD decrease in femoral neck BMD (1.8–3.6), while in men this relative risk was 3.0 per SD (1.7–5.4). In conclusion, we observed a similar relation of hip fracture with femoral neck BMD in men and women and were able to predict accurately hip fracture rates over a period of almost 4 years.
Pre- and Postmenopausal Women Have Different Bone Mineral Density Responses to the Same High-Impact Exercise
Authors: Dr. Bassey E. J. , Rothwell M. C. , Littlewood J. J. , Pye D. W. 
Published: April 2006

Abstract
The effects of a vertical jumping exercise regime on bone mineral density (BMD) have been assessed using randomized controlled trials in both pre- and postmenopausal women, the latter stratified for hormone replacement therapy (HRT). Women were screened for contraindications or medication likely to influence bone. The premenopausal women were at least 12 months postpartum and not lactating; the postmenopausal women had been stable on, or off, HRT for the previous 12 months and throughout the study. BMD was measured blind using dual-energy X-ray absorptiometry at the spine (L2–L4) and the proximal femur. The exercise consisted of 50 vertical jumps on 6 days/week of mean height 8.5 cm, which produced mean ground reactions of 3.0 times body weight in the young women and 4.0 times in the older women. In the premenopausal women, the exercise resulted in a significant increase of 2.8% in femoral BMD after 5 months (p &lt; 0.001, n = 31). This change was significantly greater (p &lt; 0.05) than that found in the control group (n = 26). In the postmenopausal women, there was no significant difference between the exercise and control groups after 12 months (total n = 123) nor after 18 months (total n = 38). HRT status did not affect this outcome, at least up to 12 months. It appears that premenopausal women respond positively to this brief high-impact exercise but postmenopausal women do not.
Moderate Exercise During Growth in Prepubertal Boys: Changes in Bone Mass, Size, Volumetric Density, and Bone Strength: A Controlled Prospective Study
Authors: Bradney M. , Pearce G. , Naughton G. , Sullivan C. , Bass S. , Beck T. , Carlson J. , Seeman E. 
Published: April 2006

Abstract
Cross-sectional studies of elite athletes suggest that growth is an opportune time for exercise to increase areal bone mineral density (BMD). However, as the exercise undertaken by athletes is beyond the reach of most individuals, these studies provide little basis for making recommendations regarding the role of exercise in musculoskeletal health in the community. To determine whether moderate exercise increases bone mass, size, areal, and volumetric BMD, two socioeconomically equivalent schools were randomly allocated to be the source of an exercise group or controls. Twenty boys (mean age 10.4 years, range 8.4–11.8) allocated to 8 months of 30-minute sessions of weight-bearing physical education lessons three times weekly were compared with 20 controls matched for age, standing and sitting height, weight, and baseline areal BMD. Areal BMD, measured using dual-energy X-ray absorptiometry, increased in both groups at all sites, except at the head and arms. The increase in areal BMD in the exercise group was twice that in controls; lumbar spine (0.61 ± 0.11 vs. 0.26 ± 0.09%/month), legs (0.76 ± 0.07 vs. 0.34 ± 0.08%/month), and total body (0.32 ± 0.04 vs. 0.17 ± 0.06%/month) (all p &lt; 0.05). In the exercise group, femoral midshaft cortical thickness increased by 0.97 ± 0.32%/month due to a 0.93 ± 0.33%/month decrease in endocortical (medullary) diameter (both p &lt; 0.05). There was no periosteal expansion so that volumetric BMD increased by 1.14 ± 0.33%/month, (p &lt; 0.05). Cortical thickness and volumetric BMD did not change in controls. Femoral midshaft section modulus increased by 2.34 ± 2.35 cm3 in the exercise group, and 3.04 ± 1.14 cm3 in controls (p &lt; 0.05). The growing skeleton is sensitive to exercise. Moderate and readily accessible weight-bearing exercise undertaken before puberty may increase femoral volumetric BMD by increasing cortical thickness. Although endocortical apposition may be a less effective means of increasing bone strength than periosteal apposition, both mechanisms will result in higher cortical thickness that is likely to offset bone fragility conferred by menopause-related and age-related endocortical bone resorption.
Genetic and Environmental Contributions to the Association Between Quantitative Ultrasound and Bone Mineral Density Measurements: A Twin Study
Authors: Howard Gabrielle M. , Nguyen Tuan V. , Harris Mark , Kelly Paul J. , Eisman John A. 
Published: April 2006

Abstract
This study was designed to assess the relative contributions of genetic and environmental factors to the variation and covariation of quantitative ultrasound (QUS) measurements and their relationships to bone mineral density (BMD). Forty-nine monozygotic (MZ) and 44 dizygotic (DZ) female twins between 20 and 83 years of age (53 ± 13 years, mean ± SD) were studied. Digital (phalangeal) QUS (speed of sound [SOS]) and calcaneal QUS (broadband ultrasound attenuation [BUA] and velocity of sound [VOS]) were measured using a DBM Sonic 1200 ultrasound densitometer and a CUBA ultrasound densitometer, respectively. Femoral neck (FN), lumbar spine (LS), and total body (TB) BMD were measured using dual-energy X-ray absorptiometry. Familial resemblance and hence heritability (proportion of variance of a trait attributable to genetic factors) were assessed by analysis of variance, univariate, and multivariate model-fitting genetic analyses. In both QUS and BMD parameters, MZ twins were more alike than DZ pairs. Estimates of heritability for age- and weight-adjusted BUA, VOS, and SOS were 0.74, 0.55, and 0.82, respectively. Corresponding indices of heritability for LS, FN, and TB BMD were 0.79, 0.77, and 0.82, respectively. In cross-sectional analysis, both BUA and SOS, but not VOS, were independently associated with BMD measurements. However, analysis based on intrapair differences suggested that only BUA was related to BMD. Bivariate genetic analysis indicated that the genetic correlations between BUA and BMD ranged between 0.43 and 0.51 (p &lt; 0.001), whereas the environmental correlations ranged between 0.20 and 0.28 (p &lt; 0.01). While the genetic correlations within QUS and BMD measurements were significant, factor analysis indicates that common genes affect BMD at different sites. Also, individual QUS measurements appear to be influenced by some common sets of genes rather than by environmental factors. Significant environmental correlations were only found for BMD measurements and ranged between 0.50 and 0.65 (p &lt; 0.001). These data suggest that QUS and BMD measurements are highly heritable traits. While it appears that there is a common set of genes influencing both QUS and BMD measurements, specific genes yet to be identified appear to have greater effects than that of shared genes in each trait.
The Material Basis for Reduced Mechanical Properties in oim Mice Bones
Authors: Camacho Nancy P. , Hou Lindy , Toledano Talya R. , Ilg W. Alex , Brayton Cory F. , Raggio Cathleen L. , Root Leon , Boskey Adele L. 
Published: April 2006

Abstract
Osteogenesis imperfecta (OI), a heritable disease caused by molecular defects in type I collagen, is characterized by skeletal deformities and brittle bones. The heterozygous and homozygous oim mice (oim/+ and oim/oim) exhibit mild and severe OI phenotypes, respectively, serving as controlled animal models of this disease. In the current study, bone geometry, mechanics, and material properties of 1-year-old mice were evaluated to determine factors that influence the severity of phenotype in OI. The oim/oim mice exhibited significantly smaller body size, femur length, and moment of area compared with oim/+ and wild-type (+/+) controls. The oim/oim femur mechanical properties of failure torque and stiffness were 40% and 30%, respectively, of the +/+ values, and 53% and 36% of the oim/+ values. Collagen content was reduced by 20% in the oim/oim compared with +/+ bone and tended to be intermediate to these values for the oim/+. Mineral content was not significantly different between the oim/oim and +/+ bones. However, the oim/oim ash content was significantly reduced compared with that of the oim/+. Mineral carbonate content was reduced by 23% in the oim/oim bone compared with controls. Mineral crystallinity was reduced in the oim/oim and oim/+ bone compared with controls. Overall, for the majority of parameters examined (geometrical, mechanical, and material), the oim/+ values were intermediate to those of the oim/oim and +/+, a finding that parallels the phenotypes of the mice. This provides evidence that specific material properties, such as mineral crystallinity and collagen content, are indicative and possibly predictive of bone fragility in this mouse model, and by analogy in human OI.
Novel Serum Markers of Bone Resorption: Clinical Assessment and Comparison with Established Urinary Indices
Authors: Woitge Henning W. , Pecherstorfer Martin , Li Yuming , Keck Andrea-V. , Horn Eva , Ziegler Reinhard , Seibel Markus J. 
Published: April 2006

Abstract
Although urinary measurements of collagen degradation provide valid estimates of bone resorption, their clinical application is hampered by pronounced analytical and biological variability. Therefore, immunoassays for the determination of such parameters in serum have been developed. In this study, we assessed the performance of three new serum markers of bone turnover, i.e., C-terminal and N-terminal telopeptides of type I collagen (S-CTX and S-NTX) and bone sialoprotein. Results were compared with urinary total pyridinoline, total deoxypyridinoline, and urinary C-terminal telopeptides of type I collagen (U-CTX) and urinary N-terminal telopeptides of type I collagen (U-NTX). The study population included healthy men (n = 27), premenopausal (n = 30) and postmenopausal (n = 31) women, patients with hepatic dysfunction (HF, n = 24), renal failure (RF, n = 30), breast cancer without (BC–, n = 24) and with (BC+, n = 30) bone metastases, primary vertebral osteoporosis (OPO, n = 27), primary hyperparathyroidism (PHPT, n = 16), active Paget's disease of bone (n = 18), multiple myeloma (MM, n = 18), and patients with hypercalcemia of malignancy before and after treatment with pamidronate (HOM, n = 28). Changes in urinary and serum markers were similar in most metabolic bone diseases. However, differentiation between healthy controls and OPO, or PHPT, was improved by the serum markers. In MM, all serum and urinary markers were elevated (p &lt; 0.05 vs. controls). In BC+, skeletal involvement was reflected by significant increments in all indices (p &lt; 0.01 vs. BC–), except U-CTX and S-CTX. In HOM, pamidronate-induced changes in biomarkers were most pronounced for U-CTX and S-CTX and S-NTX. HF and RF were associated with elevated levels of all serum markers (p &lt; 0.05 vs. controls). In conclusion, measurements in serum reflect bone resorption to the same extent as the urinary indices. Since serum markers circumvent some of the limitations of urinary measurements, their use potentially improves the assessment of skeletal disorders.
Biochemical Markers of Bone Turnover and Prediction of Hip Bone Loss in Older Women: The Study of Osteoporotic Fractures
Authors: Bauer Douglas C. , Sklarin Peter M. , Stone Katie L. , Black Dennis M. , Nevitt Michael C. , Ensrud Kristine E. , Arnaud Claude D. , Genant Harry K. , Garnero Patrick , Delmas Pierre D. , Lawaetz Henrik , Cummings Steven R. 
Published: April 2006

Abstract
To examine the ability of commercially available biochemical markers of bone formation and resorption to predict hip bone loss, we prospectively obtained serum and timed 2-h urine specimens from 295 women age 67 years or older who were not receiving estrogen replacement therapy. Serum was assayed for two markers of bone formation: osteocalcin (OC) and bone-specific alkaline phosphatase (BALP). Urine specimens were assayed for four markers of bone resorption: N-telopeptides (NTX), free pyridinolines (Pyr), free deoxypyridinoline (Dpyr), and C-telopeptides (CTX). Measurements of hip bone mineral density were made at the time the samples were collected and then repeated an average of 3.8 years later. Higher levels of all four resorption markers were, on average, significantly associated with faster rates of bone loss at the total hip, but not at the femoral neck. Women with OC levels above the median had a significantly faster rate of bone loss than women with levels below the median, but there was no significant association between levels of BALP and hip bone loss. The sensitivity and specificity of higher marker levels for predicting rapid hip bone loss was limited, and there was considerable overlap in bone loss rates between women with high and low marker levels. We conclude that higher levels of urine NTX, CTX, Pyr, Dpyr, and serum OC are associated with faster bone loss at the hip in this population of elderly women not receiving estrogen replacement therapy, but these biochemical markers have limited value for predicting rapid hip bone loss in individuals.
Bone Mineral in Prepubertal Children: Gender and Ethnicity
Authors: Horlick Mary , Thornton John , Wang Jack , Levine Lenore S. , Fedun Barbara , Pierson Richard N. 
Published: April 2006

Abstract
Previous reports of gender and ethnic differences in bone mineral in prepubertal children have been inconsistent due to different methodologies, the problematic nature of bone density by dual-energy X-ray absorptiometry (DXA) calculated as the ratio of bone mineral mass to projected bone area (BA), and the generally small study populations. The aim of this study was to test the hypothesis that gender and ethnic differences in bone mineral by DXA are present in prepubertal children. The subjects were 336 healthy Asian, black, and white prepubertal children (172 females and 164 males). Total body bone mineral content (TBBMC) was adjusted for total body BA (TBBA), age, height, and weight. Adjusted mean TBBMC was greater in males than in females (p = 0.01). The gender difference was independent of ethnicity. Adjusted mean TBBMC was different for black compared with nonblack children (p = 0.001). The ethnic difference was a function of TBBA and weight. This study in a multiethnic population of prepubertal children shows (1) a gender difference in TBBMC and (2) an ethnic difference in TBBMC.
Effects of Loading Frequency on Mechanically Induced Bone Formation
Authors: Hsieh Yeou-Fang , Turner Charles H. 
Published: April 2006

Abstract
The anabolic effect of mechanical loading on bone tissue is modulated by loading frequency. The objective of this study was to characterize the new bone formation on the periosteal and endocortical surfaces of the ulnar diaphysis in adult, female rats in response to controlled dynamic loading and to examine the interactions between strain magnitude, loading frequency, and bone formation rate (BFR/BS) for frequencies ranging from 1 to 10 Hz. Cyclic, compressive loading was applied to the ulnas of 60 adult, female rats divided into 12 loading groups. Loading was applied for 360 cycles/day with peak loads ranging from 4.3 to 18N at frequencies of 1, 5, and 10 Hz. After 2 weeks of loading, bone formation on the periosteal and endocortical surfaces of the ulna was quantified using double-label histomorphometry on transverse sections obtained at the middiaphysis. Periosteal bone formation increased in a dose-response manner with peak load at each of the three loading frequencies tested. Loading frequency significantly affected the x intercepts and slopes of the peak strain versus BFR/BS (p &lt; 0.001) and peak strain versus mineralizing surface (MS/BS; p &lt; 0.001) curves. Periosteal osteogenesis was best predicted by a mathematical model that assumed: (1) bone cells are activated by fluid shear stresses and (2) that stiffness of the bone cells and the extracellular matrix near the cells increases at higher loading frequencies because of viscoelasticity. Consequently, mechanotransduction appears to involve a complex interaction between extracellular fluid forces and cellular mechanics.