bluuebunny/crossref_metadata_2025_split huggingface dataset:
Femoral Neck Structure in Adult Female Athletes Subjected to Different Loading Modalities
Authors: Nikander Riku , Sievänen Harri , Heinonen Ari , Kannus Pekka 
Published: April 2006

Abstract
Loading modality is a strong external determinant of structure and concomitant strength of the femoral neck. Particularly effective seem to be loadings, which arise from high impacts or impacts from atypical loading directions.
Introduction: Physical loading plays an important role, not only in the process of bone modeling and remodeling, but also in shaping a mechanically appropriate bone structure. This study aimed at testing the hypothesis that the type of loading partly determines the femoral neck structure.
Materials and Methods: A total of 255 premenopausal female athletes representing volleyball, hurdling, squash-playing, soccer, speed skating, step aerobics, weight-lifting, orienteering, cross-country skiing, cycling, and swimming and their 30 nonathletic counterparts were measured with DXA. Besides the conventional areal BMD (aBMD) of the femoral neck, the hip structure analysis (HSA) was used to estimate the cross-sectional area (CSA), subperiosteal width (W), and section modulus (Z, an index of bone strength) at the narrowest section of the femoral neck. Also, training history, muscle strength, and calcium intake were assessed. The above-mentioned sports were classified according to the type of loading they apparently produce at the hip region; that is, high-impact loading (volleyball, hurdling), odd-impact loading (squash-playing, soccer, speed-skating, step aerobics), high-magnitude loading (weightlifting), low-impact loading (orienteering, cross-country skiing), and nonimpact loading (swimming, cycling).
Results: High-impact and odd-impact loading sports were associated with the highest age-, weight-, and height-adjusted aBMD (23% and 29% higher values compared to nonathletic referents), CSA (22% and 27%), and Z (22% and 26%). In contrast, repetitive, nonimpact loading sports were not associated with any clear benefit in any bone value compared with the referents. The W at the narrowest femoral neck section was similar in all groups. Body height and weight accounted virtually for one-half of the variation in Z, whereas the type of loading predicted 13% of the total variation of this variable—clearly more than the 2% attributable to isometric leg extension strength. Both high-impact and odd-impact loading modalities were associated with a large benefit in Z, corresponding to &gt;1 SD in the reference group, whereas repetitive, low-impact loading showed a benefit that was only one-half of that. Surprisingly, high-magnitude loading (weightlifting) was not associated with a statistically significant increase in Z.
Conclusion: We conclude that mechanical loading and its modality are strong external determinants of structure and concomitant strength of the femoral neck. Particularly effective seem to be loadings, which arise from high impacts or impacts from atypical loading directions.
Mechanism and Function of High Vitamin D Receptor Levels in Genetic Hypercalciuric Stone-Forming Rats
Authors: Karnauskas Alexander J , van Leeuwen Johannes PTM , van den Bemd Gert-Jan CM , Kathpalia Paru P , DeLuca Hector F , Bushinsky David A , Favus Murray J 
Published: April 2006

Abstract
The functional status and mechanism of increased VDR in GHS rats were investigated. Basal VDR and calbindins were increased in GHS rats. 1,25(OH)2D3 increased VDR and calbindins in controls but not GHS rats. VDR half-life was prolonged in GHS rats. This study supports the mechanism and functional status of elevated VDR in GHS rats.
Introduction: Genetic hypercalciuric stone-forming (GHS) rats form calcium kidney stones from hypercalciuria arising from increased intestinal calcium absorption and bone resorption and decreased renal calcium reabsorption. Normal serum 1,25-dihydroxyvitamin D3 ‘1,25(OH)2D3’ levels and increased vitamin D receptor (VDR) protein suggest that high rates of expression of vitamin D-responsive genes may mediate the hypercalciuria. The mechanism of elevated VDR and state of receptor function are not known.
Materials and Methods: GHS and non-stone-forming control (NC) male rats (mean, 249 g), fed a normal calcium diet, were injected intraperitoneally with 1,25(OH)2D3 (30 ng/100 g BW) or vehicle 24 h before cycloheximide (6 mg/100 g, IP) and were killed 0–8 h afterward. Duodenal VDR was measured by ELISA and Western blot, and duodenal and kidney calbindins (9 and 28 kDa) were measured by Western blots.
Results and Conclusions: Duodenal VDR protein by Western blot was increased 2-fold in GHS versus NC rats (633 ± 62 versus 388 ± 48 fmol/mg protein, n = 4, p &lt; 0.02), and 1,25(OH)2D3 increased VDR and calbindins (9 and 28 kDa) further in NC but not GHS rats. Duodenal VDR half-life was prolonged in GHS rats (2.59 ± 0.2 versus 1.81 ± 0.2 h, p &lt; 0.001). 1,25(OH)2D3 prolonged duodenal VDR half-life in NC rats to that of untreated GHS rats (2.59 ± 0.2 versus 2.83 ± 0.3 h, not significant). This study supports the hypothesis that prolongation of VDR half-life increases VDR tissue levels and mediates increased VDR-regulated genes that result in hypercalciuria through actions on vitamin D-regulated calcium transport in intestine, bone, and kidney.
Effects of Low-Dose Prednisone on Bone Metabolism
Authors: Ton Francine N , Gunawardene Samantha C , Lee Hang , Neer Robert M 
Published: April 2006

Abstract
Prednisone 5 mg/day suppresses multiple indices of bone formation in a randomized placebo-controlled trial in healthy postmenopausal females. This suggests that even low doses of prednisone may reduce bone repair or renewal and may have adverse effects on bone mass and/or bone strength.
Introduction: High doses of chronic glucocorticoids are known to have adverse effects on bone, and measures to prevent bone loss are well established for doses &gt;7.5 mg daily, because these doses can cause premature or exaggerated osteoporosis. However, it is unclear if chronic prednisone doses of 5 mg daily have the same effects on bone. There are no established recommendations for preventing glucocorticoid-induced osteoporosis in people taking prednisone 5 mg daily, a dose used frequently in medical practice to treat diseases of the lungs, joints, skin, muscles, eyes, nerves, etc. Our primary objective was to test whether prednisone 5 mg daily affects serum and urine indices of bone metabolism in healthy postmenopausal women. Our secondary objectives were to determine if prednisone 5 mg affected systolic or diastolic blood pressure or causes side effects.
Materials and Methods: A double-blinded randomized placebo-controlled 8-week trial in 50 healthy postmenopausal women was conducted at the Massachusetts General Hospital Outpatient General Clinical Research Center. Patients were randomly assigned to prednisone 5 mg daily or matching placebo for 6 weeks, followed by a 2-week recovery phase. Markers of bone formation and resorption were determined at weeks 0, 2, 4, 6, and 8. Indices of osteoblast activity included serum propeptide of type I N-terminal procollagen (PINP), propeptide of type I C-terminal procollagen (PICP), osteocalcin, and bone-specific alkaline phosphatase (BSALP). Indices of osteoclast activity included urine and serum type I collagen N-telopeptide (NTX) and free urinary deoxypyridinoline (DPD).
Results and Conclusions: Prednisone rapidly and significantly decreased serum PINP (p &lt; 0.01), PICP (p &lt; 0.01), and osteocalcin (p &lt; 0.01) and free urinary deoxypyridinoline (p = 0.017). These changes were largely reversed during the recovery period. Side effects were indistinguishable in the two groups. Neither systolic nor diastolic blood pressure changed significantly throughout the study between the two groups. In conclusion, low-dose prednisone significantly decreases indices of bone formation and may decrease indices of bone resorption in postmenopausal women. Further studies are needed to assess the effects of low-dose prednisone on BMD and fracture risk.
Initial Years of Recreational Artistic Gymnastics Training Improves Lumbar Spine Bone Mineral Accrual in 4- to 8-Year-Old Females
Authors: Laing Emma M , Wilson Alissa R , Modlesky Christopher M , O'Connor Patrick J , Hall Daniel B , Lewis Richard D 
Published: April 2006

Abstract
Gymnasts' bone mineral characteristics are generally not known before starting their sport. Prepubertal females who enrolled in beginning artistic gymnastics (n = 65) had lower bone mineral than controls (n = 78). However, 2 years of gymnastics participation versus no participation led to a significantly greater accrual of forearm bone area and lumbar spine areal BMD.
Introduction: The skeletal response to exercise in children compared with adults is heightened because of the high bone turnover rate and the ability of bone to change its size and shape. Whereas child gymnasts generally have greater rates of bone mineral accrual compared with nongymnasts, it is unknown if some of these skeletal advantages are present before the onset of training or are caused entirely by training.
Materials and Methods: Changes in bone area (BA; cm2), BMC (g), and areal BMD (aBMD; g/cm2) over 24 months were examined in prepubertal females, 4–8 years of age, who selected to perform recreational gymnastics (GYM; n = 65), nongymnastic activities, or no organized activity (CON; n = 78). Participants had essentially no lifetime history of organized athletic participation (&lt;12 weeks). Pubertal maturation was assessed annually by a physician. Total body, lumbar spine, total proximal femur, and forearm BA, BMC, and aBMD were measured every 6 months using DXA (Hologic QDR-1000W). Independent samples t-tests determined baseline group differences. Nonlinear mixed effects models were used to model 24-month changes in bone data. In subset analyses, high-level gymnasts advancing to competition (HLG; n = 9) were compared with low-level nonadvancing gymnasts (LLG; n = 56).
Results: At baseline, GYM were shorter, lighter, and had lower BA, BMC, and aBMD compared with CON (p &lt; 0.05), whereas HLG did not differ significantly in these measurements compared with LLG (p &gt; 0.05). Controlling for differences in race, baseline measures of body mass, height, and calcium intake, and change in breast development beyond stage II at 24 months, GYM had greater long-term (asymptotic) mean responses for total body aBMD and forearm BMC (p &lt; 0.04) and greater rates of increase in the mean responses of lumbar spine aBMD and forearm BA compared with CON over 24 months. Over time, forearm BA increased to a greater extent in HLG compared with LLG (p &lt; 0.01).
Conclusions: Females participating in recreational gymnastics initiated during childhood have enhanced bone mineral gains at the total body, lumbar spine, and forearm over 24 months. Higher-level training promotes additional gains in forearm BA.
Nonreplication in Genetic Studies of Complex Diseases—Lessons Learned From Studies of Osteoporosis and Tentative Remedies
Authors: Shen Hui , Liu Yongjun , Liu Pengyuan , Recker Robert R , Deng Hong-Wen 
Published: April 2006

Abstract
Inconsistent results have accumulated in genetic studies of complex diseases/traits over the past decade. Using osteoporosis as an example, we address major potential factors for the nonreplication results and propose some potential remedies.
Over the past decade, numerous linkage and association studies have been performed to search for genes predisposing to complex human diseases. However, relatively little success has been achieved, and inconsistent results have accumulated. We argue that those nonreplication results are not unexpected, given the complicated nature of complex diseases and a number of confounding factors. In this article, based on our experience in genetic studies of osteoporosis, we discuss major potential factors for the inconsistent results and propose some potential remedies. We believe that one of the main reasons for this lack of reproducibility is overinterpretation of nominally significant results from studies with insufficient statistical power. We indicate that the power of a study is not only influenced by the sample size, but also by genetic heterogeneity, the extent and degree of linkage disequilibrium (LD) between the markers tested and the causal variants, and the allele frequency differences between them. We also discuss the effects of other confounding factors, including population stratification, phenotype difference, genotype and phenotype quality control, multiple testing, and genuine biological differences. In addition, we note that with low statistical power, even a “replicated” finding is still likely to be a false positive. We believe that with rigorous control of study design and interpretation of different outcomes, inconsistency will be largely reduced, and the chances of successfully revealing genetic components of complex diseases will be greatly improved.
Fracture Risk With Multiple Myeloma: A Population-Based Study
Authors: Melton L Joseph , Kyle Robert A , Achenbach Sara J , Oberg Ann L , Rajkumar S Vincent 
Published: April 2006

Abstract
Pathologic fractures, especially of the axial skeleton, are extremely common in patients with multiple myeloma and cluster around the time of diagnosis. Osteoporotic fractures seem to be less of a problem in these patients.
Introduction: It is generally believed that fractures are common in patients with multiple myeloma as a result of lytic bone lesions, generalized bone loss, and/or elevated bone turnover from excessive cytokine production, but the actual risk of pathologic versus osteoporotic fractures has not been quantified.
Materials and Methods: In a population-based retrospective cohort study, 165 Olmsted County, MN, residents with myeloma diagnosed from 1945 to 2001 (55% men; mean age, 70.7 ± 11.1 years) were followed for 537 person-years. The relative risk of fractures was assessed by standardized incidence ratios (SIRs), and risk factors were evaluated in proportional hazards models.
Results: Altogether, 134 patients experienced 463 fractures. In the year before diagnosis, 16 times more fractures were observed than expected, mostly pathologic fractures of the vertebrae and ribs. Subsequently, there was a 9-fold increase in fracture risk. However, 69% of these fractures were pathologic, and another 11% were found incidentally on myeloma monitoring. With the latter two groups excluded, subsequent fracture risk was elevated 3-fold, with a 2-fold increase in the risk of an osteoporotic fracture. In multivariate analyses, the predictors of overall fracture risk were oral corticosteroid use and elevated serum calcium levels, whereas pathologic fractures were additionally predicted by use of chemotherapy.
Conclusion: There is a dramatic increase in fractures around the time of diagnosis of myeloma, most of which are pathologic fractures. The most important predictor of overall fracture risk is oral corticosteroid use.
Isolation and Characterization of Piscine Osteonectin and Downregulation of Its Expression by PTH-Related Protein
Authors: Redruello Begoña , Estêvão M Dulce , Rotllant Josep , Guerreiro Pedro M , Anjos Liliana I , Canário Adelino VM , Power Deborah M 
Published: April 2006

Abstract
The skeleton is the main source of osteonectin mRNA in adults of the seawater teleost sea bream Sparus auratus. It is expressed by cells forming the basement membrane of calcifying tissue indicating that, as in mammals, it may play a role in osteoblast differentiation. PTHrP induced downregulation of osteonectin mRNA in vitro in scales, a mineralizing tissue with bone-like metabolism. This indicates a means to redirect calcium to activities such as vitellogenesis when this ion is in high demand.
Introduction: Osteonectin is a unique matricellular calcium-binding glycoprotein and a major noncollagenous constituent of higher eukaryote bone. In terrestrial vertebrates, it has been associated with development, remodeling, cell turnover, and tissue repair, all processes involving substantial changes in extracellular matrix (ECM) structure. In skeleton biology, osteonectin has been described as a positive factor in the mineralization process as well as in osteoblastic cell lineage differentiation and is downregulated by the hypercalcemic hormone PTH. In this study, we report the cloning and characterization of bream S. auratus osteonectin cDNA and its tissue and cellular distribution. Its high expression by fish scales provides a unique in vitro bioassay with which to study regulation of osteonectin gene expression by the recently isolated piscine PTH-related peptide (PTHrP).
Materials and Methods: An intervertebral tissue cDNA library from S. auratus was the source of the full-length cDNA clone for osteonectin. Expression studies were performed by semiquantitative RT-PCR, Northern blot, and in situ hybridization analysis. Moreover, an in vitro bioassay with S. auratus scales was specifically developed for measuring the effect of PTHrP on osteonectin expression.
Results and Conclusions: Phylogenetic analysis showed that S. auratus osteonectin is highly homologous with previously reported osteonectins, supporting the idea of a conserved function for this protein in the ECM. Its expression pattern in adult tissues from S. auratus was markedly biased toward skeletal structures of both dermal or endochondral origin. More specifically, the localization of the osteonectin mRNA in the basement membrane that separates the epithelia from the underlying mineralized connective tissue supports a role for this protein in calcified matrix turnover. Furthermore, the recently identified piscine hypercalcemic factor PTHrP downregulates osteonectin expression in scales, suggesting a catabolic action for this hormone on these structures.
β-Blocker Use, BMD, and Fractures in the Study of Osteoporotic Fractures
Authors: Reid Ian R , Gamble Gregory D , Grey Andrew B , Black Dennis M , Ensrud Kristine E , Browner Warren S , Bauer Douglas C 
Published: April 2006

Abstract
A role for osteoblastic β-adrenoreceptors in bone regulation is suggested by the finding that β-blockers increase bone mass in mice. We studied the association of β-blocker use with BMD and fractures in the Study of Osteoporotic Fractures. β-blocker use and BMD are unrelated in this cohort, and associations with fracture risk are inconsistent.
Introduction: The central nervous system has been shown to regulate bone mass in mice, possibly by way of the β2-adrenoreceptors on osteoblasts. β-blockers have been shown to increase bone mass in mice. Because these agents are widely used therapeutically, it is possible that they may influence fracture epidemiology in humans, and they are a potential therapy for osteoporosis.
Materials and Methods: We have studied the association of β-blocker use with BMD and fracture rates in the Study of Osteoporotic Fractures. β-blocker use was recorded at the fourth visit, in 8412 women, of whom 1099 were users, and these women were followed for 7 years.
Results: Users had significantly higher weight, more thiazide use, more estrogen use, less glucocorticoid use, more statin use, and more hypertension than nonusers, and they smoked less. Total hip BMD at the fourth visit was higher in the β-blocker users (0.746 versus 0.735 g/cm2, p = 0.02), but adjustment for weight alone, or together with these other variables, eliminated this difference (p = 0.62). There was no effect of β-blocker use on loss of hip BMD over a mean follow-up of 4 years (p = 0.48). Os calcis BMD at visit 4 was also higher in those taking β-blockers (0.385 versus 0.375 g/cm2, p = 0.005), but weight adjustment eliminated this difference (p = 0.14). The frequencies of hip or any fracture (since age 50) were similar in users and nonusers (p = 0.80 and p = 0.51, respectively). Over a mean follow-up of 7 years, there were 2167 total fractures, including 431 at the wrist and 585 at the hip. Among β-blocker users, hazards ratios were 0.92 (0.81, 1.05) for any fracture, 0.74 (0.54, 1.01) for wrist fracture, and 0.76 (0.58, 0.99) for hip fracture. Adjustment for weight and other factors previously shown to influence hip fracture incidence in this cohort made little difference to the outcome. When fracture data were analyzed for nonselective and β1-selective agents separately, trends toward fewer fractures were confined to the users of selective β1-blockers.
Conclusions: β-blocker use and BMD are unrelated in this cohort, and associations with fracture risk are inconsistent. Therefore, a history of use of these drugs is not useful in assessing fracture risk, nor do they have a role in osteoporosis management at this time. The relationship between β-blocker use and hip fracture deserves further study.
β-Arrestin2 Regulates the Differential Response of Cortical and Trabecular Bone to Intermittent PTH in Female Mice
Authors: Bouxsein Mary L , Pierroz Dominique D , Glatt Vaida , Goddard Deborah S , Cavat Fanny , Rizzoli René , Ferrari Serge L 
Published: April 2006

Abstract
Cytoplasmic arrestins regulate PTH signaling in vitro. We show that female β-arrestin2−/− mice have decreased bone mass and altered bone architecture. The effects of intermittent PTH administration on bone microarchitecture differed in β-arrestin2−/− and wildtype mice. These data indicate that arrestin-mediated regulation of intracellular signaling contributes to the differential effects of PTH at endosteal and periosteal bone surfaces.
Introduction: The effects of PTH differ at endosteal and periosteal surfaces, suggesting that PTH activity in these compartments may depend on some yet unidentified mechanism(s) of regulation. The action of PTH in bone is mediated primarily by intracellular cAMP, and the cytoplasmic molecule β-arrestin2 plays a central role in this signaling regulation. Thus, we hypothesized that arrestins would modulate the effects of PTH on bone in vivo.
Materials and Methods: We used pDXA, μCT, histomorphometry, and serum markers of bone turnover to assess the skeletal response to intermittent PTH (0, 20, 40, or 80 μg/kg/day) in adult female mice null for β-arrestin2 (β-arr2−/−) and wildtype (WT) littermates (7-11/group).
Results and Conclusions: β-arr2−/− mice had significantly lower total body BMD, trabecular bone volume fraction (BV/TV), and femoral cross-sectional area compared with WT. In WT females, PTH increased total body BMD, trabecular bone parameters, and cortical thickness, with a trend toward decreased midfemoral medullary area. In β-arr2−/− mice, PTH not only improved total body BMD, trabecular bone architecture, and cortical thickness, but also dose-dependently increased femoral cross-sectional area and medullary area. Histomorphometry showed that PTH-stimulated periosteal bone formation was 2-fold higher in β-arr2−/− compared with WT. Osteocalcin levels were significantly lower in β-arr2−/− mice, but increased dose-dependently with PTH in both β-arr2−/− and WT. In contrast, whereas the resorption marker TRACP5B increased dose-dependently in WT, 20-80 μg/kg/day of PTH was equipotent with regard to stimulation of TRACP5B in β-arr2−/−. In summary, β-arrestin2 plays an important role in bone mass acquisition and remodeling. In estrogen-replete female mice, the ability of intermittent PTH to stimulate periosteal bone apposition and endosteal resorption is inhibited by arrestins. We therefore infer that arrestin-mediated regulation of intracellular signaling contributes to the differential effects of PTH on cancellous and cortical bone.