bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary Protein Intake and Risk of Osteoporotic Hip Fracture in Elderly Residents of Utah
Authors: Wengreen Heidi J , Munger Ronald G , West Nancy A , Cutler D Richard , Corcoran Christopher D , Zhang Jianjun , Sassano Nancy E 
Published: April 2006

Abstract
The role of protein intake in osteoporosis is unclear. In a case-control study in Utah (n = 2501), increasing level of protein intake was associated with a decreased risk of hip fracture in men and women 50–69 years of age but not in those 70–89 years of age. Protein intake may be important for optimal bone health.
Introduction: Protein is an important component of bone, but the role of dietary protein intake in osteoporosis and fracture risk remains controversial.
Material and Methods: The role of dietary protein intake in osteoporotic hip fracture was evaluated in a statewide case-control study in Utah. Patients, 50–89 years of age, with hip fracture (cases) were ascertained through surveillance of 18 Utah hospitals during 1997–2001. Age- and gender-matched controls were randomly selected. Participants were interviewed in their place of residence, and diet was assessed using a picture-sort food frequency questionnaire previously reported to give a useful measure of usual dietary intake in the elderly Utah population. The association between protein intake and risk of hip fracture was examined across quartiles of protein intake and stratified by age group for 1167 cases (831 women, 336 men) and 1334 controls (885 women, 449 men).
Results: In logistic regression analyses that controlled for gender, body mass index, smoking status, alcohol use, calcium, vitamin D, potassium, physical activity, and estrogen use in women, the odds ratios (OR) of hip fracture decreased across increasing quartiles of total protein intake for participants 50–69 years of age (OR: 1.0 [reference]; 0.51 [95% CI: 0.30–0.87]; 0.53 [0.31–0.89]; 0.35 [0.21–0.59]; p &lt; 0.001). No similar associations were observed among participants 70–89 years of age. Results from analyses stratified by low and high calcium and potassium intake did not differ appreciably from the results presented above.
Conclusion: Higher total protein intake was associated with a reduced risk of hip fracture in men and women 50–69 years of age but not in men and women 70–89 years of age. The association between dietary protein intake and risk of hip fracture may be modified by age. Our study supports the hypothesis that adequate dietary protein is important for optimal bone health in the elderly 50–69 years of age.
Loss of Chaotic Trabecular Structure in OPG-Deficient Juvenile Paget's Disease Patients Indicates a Chaogenic Role for OPG in Nonlinear Pattern Formation of Trabecular Bone
Authors: Salmon Phil 
Published: April 2006

Abstract
The RANK-RANKL-OPG system of osteoclast regulation may play a key role in determining chaotic structure in trabecular bone. Iliac trabecular bone from juvenile Paget's disease patients deficient in functional OPG shows parallel, anisotropic structure instead of normal chaotic structure. Evidence from experimental systems suggests that RANK-RANKL-OPG controls key nonlinear “chaogenic” parameters, such as friction, forcing frequency, feedback, and boundary forcing.
The RANK-RANKL-osteoprotegerin (OPG) system of osteoclast regulation may play a key role in determining chaotic structure in trabecular bone. Iliac trabecular bone from juvenile Paget's disease (JPD) patients deficient in functional OPG shows parallel, anisotropic structure instead of normal chaotic structure. Evidence from experimental systems suggests that RANK-RANKL-OPG controls key nonlinear “chaogenic” parameters, such as friction, forcing frequency, feedback, and boundary forcing. The Belousov-Zhabotinsky reaction-diffusion system, the catalytic oxidation of CO on platinum surfaces, and thermal diffusion in liquid helium allow visualization of nonlinear emergent patterns such as labyrinthine structures, turbulence, and cellular structures, all of which bear some resemblance to trabecular bone. In JPD, the gene for OPG (TNFRSF11B) is subject to an inactivating mutation, leading to increased resorption and accelerated remodeling. Histomorphometric images of iliac crest trabecular bone from teenagers suffering from JPD show a highly unusual array of parallel, regular trabecular plates, instead of the typical chaotic, fractal patterns of normal trabecular bone. Loss of OPG function is associated with a change from chaotic to regular structure, suggesting that the RANK-RANKL-OPG system is controlling key nonlinear “chaogenic” parameters. Looking at trabecular bone from the perspective of nonlinear pattern formation may help understand other phenomena, such as the marked dependence of trabecular bone's architectural and mechanical quality on remodeling rate independent of the trabecular bone mass.
The Chloride Channel Inhibitor NS3736 Prevents Bone Resorption in Ovariectomized Rats Without Changing Bone Formation
Authors: Schaller Sophie , Henriksen Kim , Sveigaard Christina , Heegaard Anne-Marie , Hélix Nathalie , Stahlhut Martin , Ovejero Maria C , Johansen Jens V , Solberg Helene , Andersen Thomas L , Hougaard Dorit , Berryman Mark , Shiødt Christine B , Sørensen Bjørn H , Lichtenberg Jens , Christophersen Palle , Foged Niels T , Delaissé Jean-Marie , Engsig Michael T , Karsdal Morten A 
Published: April 2006

Abstract
Chloride channel activity is essential for osteoclast function. Consequently, inhibition of the osteoclastic chloride channel should prevent bone resorption. Accordingly, we tested a chloride channel inhibitor on bone turnover and found that it inhibits bone resorption without affecting bone formation. This study indicates that chloride channel inhibitors are highly promising for treatment of osteoporosis.
Introduction: The chloride channel inhibitor, NS3736, blocked osteoclastic acidification and resorption in vitro with an IC50 value of 30 μM. When tested in the rat ovariectomy model for osteoporosis, daily treatment with 30 mg/kg orally protected bone strength and BMD by ∼50% 6 weeks after surgery. Most interestingly, bone formation assessed by osteocalcin, mineral apposition rate, and mineralized surface index was not inhibited.
Materials and Methods: Analysis of chloride channels in human osteoclasts revealed that ClC-7 and CLIC1 were highly expressed. Furthermore, by electrophysiology, we detected a volume-activated anion channel on human osteoclasts. Screening 50 different human tissues showed a broad expression for CLIC1 and a restricted immunoreactivity for ClC-7, appearing mainly in osteoclasts, ovaries, appendix, and Purkinje cells. This highly selective distribution predicts that inhibition of ClC-7 should specifically target osteoclasts in vivo. We suggest that NS3736 is inhibiting ClC-7, leading to a bone-specific effect in vivo.
Results and Conclusion: In conclusion, we show for the first time that chloride channel inhibitors can be used for prevention of ovariectomy-induced bone loss without impeding bone formation. We speculate that the coupling of bone resorption to bone formation is linked to the acidification of the resorption lacunae, thereby enabling compounds that directly interfere with this process to be able to positive uncouple this process resulting in a net bone gain.
Nongenomic Androgen Activation of Phosphatidylinositol 3-Kinase/Akt Signaling Pathway in MC3T3-E1 Osteoblasts
Authors: Kang Hong-Yo , Cho Chung-Lung , Huang Kai-Lieh , Wang Jyh-Chwan , Hu Yueh-Chiang , Lin Hui-Kuan , Chang Chawnshang , Huang Ko-En 
Published: April 2006

Abstract
Androgens have important effects on the bone metabolism. However, the effect and mechanism of androgen action on the osteoblasts remains unknown. Here we showed that androgens increase phosphorylation and nuclear translocation of Akt. siRNA-AR prevented androgen-induced Akt activation in MC3T3-E1 cells. This suggests that nongenomic androgen activation of Akt is mediated by androgen receptor in osteoblasts.
Introduction: Androgens have important effects on the human skeleton in both males and females. However, the mechanism of androgen action on bone metabolism remains unknown. The aims of this study were to determine the effect and mechanism of androgen action on the osteoblast cells.
Materials and Methods: Here we showed that 5α-dihydrotestosterone (DHT) accelerates cell growth of the MC3T3-E1 cell line in a time- and dose-dependent manner. The specific phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor LY294002 and kinase-deficient Akt mutant can repress the androgen effect on MC3T3-E1 cells. Western blot analysis showed that DHT, 17β-estradiol, and testosterone (T) induce a rapid and transient phosphorylation of Akt in MC3T3-E1 cells. This activation reached to a plateau after 15 minutes and gradually diminished after 60 minutes of DHT treatment.
Results: Fluorescence microscopy showed a distinct increase in immunostaining intensity in the nuclear interior after androgen treatment but no change in the subcellular distribution of Akt when the cells were pretreated with hydroxyflutamide (HF) or LY294002. In addition, small interfering RNA against androgen receptor (siRNA-AR) prevented DHT-induced Akt phosphorylation and cell growth.
Conclusion: These findings represents the first physiological finding to indicate how steroid hormones such as androgens can mediate the nuclear localization of Akt/PKB in osteoblasts that has previously mainly been linked to growth factor-induced events occurring at the plasma membrane level.
Prevention of Bone Loss in Paraplegics Over 2 Years With Alendronate
Authors: Zehnder Yvonne , Risi Simone , Michel Dieter , Knecht Hans , Perrelet Romain , Kraenzlin Marius , Zäch Guido A , Lippuner Kurt 
Published: April 2006

Abstract
To assess the effects of long-term treatment of bone loss with alendronate in a group of paraplegic men, 55 patients were evaluated in a prospective randomized controlled open label study that was 2 years in duration comparing alendronate and calcium with calcium alone. Bone loss was stopped at all cortical and trabecular infralesional sites (distal tibial epiphysis, tibial diaphysis, total hip) with alendronate 10 mg daily.
Introduction: Bone loss after spinal cord injury (SCI) leads to increased fracture risk in the lower limbs of paraplegics. The aim of this study was to document long-term treatment of bone loss with alendronate in a group of paraplegic men with complete motor lesion after SCI.
Materials and Methods: Sixty-five men with complete motor post-traumatic medullary lesion between T1 and L3 with total motor and sensory loss (Frankel classification, stage A) or with total motor and partial sensory loss (Frankel classification, stage B) after SCI were included in this prospective randomized controlled open label study that was 2 years in duration. The patients were randomized to either the treatment group with alendronate 10 mg daily and elemental calcium 500 mg daily or to the control group with elemental calcium 500 mg daily alone. The primary endpoint was defined as the effect over 24 months of alendronate and calcium compared with calcium alone on the BMD values at the distal tibial epiphysis (as a surrogate for trabecular bone in the paralyzed zone). The secondary endpoints were changes in BMD at supra- and infralesional sites of measurement. Biochemical markers of bone turnover were assessed.
Results: Fifty-five subjects, 0.1-29.5 years post-SCI, completed the study over 24 months. BMD at the distal tibial epiphysis significantly decreased from baseline in the calcium group (−10.8 ± 2.7% at 24 months, p &lt; 0.001), whereas it remained stable in the alendronate plus calcium group (−2.0 ± 2.9% at 24 months, p = not significant versus baseline), leading to a significant intergroup difference over time (p = 0.017). At the tibial diaphysis, similar significant results were observed. At the ultradistal radius and the radial shaft, BMD did not change significantly from baseline in either treatment group. At the total hip, BMD decreased significantly in the calcium group (−4.1 ± 1.6%, p = 0.038) but remained stable in the alendronate plus calcium group (+0.43 ± 1.2%), with a significant intergroup difference (p = 0.037). At the lumbar spine, BMD increased significantly (p &lt; 0.0001) from baseline in both groups. Biochemical markers of bone resorption were significantly decreased with alendronate versus baseline and control. Alendronate and calcium were generally safe and well tolerated.
Conclusions: In paraplegic men, SCI bone loss was stopped at all measured cortical and trabecular infralesional sites over 24 months with alendronate 10 mg daily.
Loss of Regularity in the Curvature of the Thoracolumbar Spine: A Measure of Structural Failure
Authors: Zebaze Roger MD , Maalouf Ghassan , Maalouf Naim , Seeman Ego 
Published: April 2006

Abstract
Departure from regularity (smoothness) in the curvature of the spine was quantified and correlated with the number of fractures, deficits in height, BMD, and identified women with vertebral fractures.
Introduction: Differences in anterior and posterior vertebral heights (VHs) form the thoracolumbar curvature needed for stability in bipedal gait. Modest differences in VHs within and between adjacent vertebrae allow the spine curve to change its trajectory gently. Large differences in VHs, as occur following a fracture, produce abrupt changes in the direction of the curve, producing a departure from regularity (i.e., irregularity or loss of smoothness).
Materials and Methods: VHs and BMD were measured using DXA in 697 Lebanese women 20-87 years of age. Regularity of the spinal curvature was measured by comparing the ratio of the anterior to the posterior VHs of one vertebra to this ratio of adjacent vertebrae. If these ratios are similar, there is a smooth transition in the trajectory of the spinal curve. Departure from this regularity (smoothness) was measured at each pair of adjacent vertebrae in each individual and expressed as the spinal curvature irregularity index (SCII) for the entire thoracolumbar spine.
Results and Conclusions: In premenopausal women, the mean SCII was 8.5% (range, 4-15%); that is, regularity was 91.5%. Only 0.8% of women had a SCII &gt;17%. In postmenopausal women, the mean SCII was 10% (range, 4-36%) and was correlated with age (r = 0.25), height (r = −0.21), BMD (r = −0.13), and the number of deformities assessed by quantitative vertebral morphometry (QVM; r = 0.31-0.60; all p &lt; 0.001). About 5% of women had an SCII &gt;17%, and this group had 3- to 9-fold more deformities (as defined by QVM) than women with SCII &lt;17%, reduced lumbar spine BMD (−1.01 SD), and 2- to 4-fold greater height deficits (−0.5 SD) than women with deformities (by QVM). The SCII is a robust method of identifying structural failure that is easy to compute and does not require controls.
Risk-Benefit Profile for Raloxifene: 4-Year Data From the Multiple Outcomes of Raloxifene Evaluation (MORE) Randomized Trial
Authors: Barrett-Connor Elizabeth , Cauley Jane A , Kulkarni Pandurang M , Sashegyi Andreas , Cox David A , Geiger Mary Jane 
Published: April 2006

Abstract
Posthoc analysis of the MORE osteoporosis treatment trial assessed risk-benefit profile of raloxifene in 7705 postmenopausal women. A major disease outcomes global index resulted in annual rates of 1.39% and 1.83% in the raloxifene and placebo groups, respectively (HR, 0.75; 95% CI, 0.62-0.92), compatible with a favorable risk-benefit profile for raloxifene for treating postmenopausal osteoporosis.
Introduction: The Women's Health Initiative (WHI) trial reported overall risks that exceeded benefits from use of estrogen-progestin in healthy postmenopausal women. The objective of this posthoc analysis of the Multiple Outcomes of Raloxifene Evaluation (MORE) trial was to assess the safety profile of raloxifene, a selective estrogen receptor modulator indicated for the prevention and treatment of osteoporosis, using the global index method from the WHI trial.
Materials and Methods: A total of 7705 postmenopausal women (mean age, 67 years) were enrolled in the MORE osteoporosis treatment trial and randomly assigned to receive placebo or one of two doses of raloxifene (60 or 120 mg/day) for 4 years. A global index of clinical outcomes, defined as described for the WHI trial (the earliest occurrence of coronary heart disease, stroke, pulmonary embolism, invasive breast cancer, endometrial cancer, colorectal cancer, hip fracture, or death because of other causes) was applied to the MORE trial data. Physicians blinded to treatment assignment adjudicated events. Intention-to-treat survival analysis of time-to-first-event was performed using a proportional hazards model.
Results and Conclusions: The annualized rate of global index events was 1.83% in the placebo group and 1.39% in the combined raloxifene dose groups (hazard ratio [HR], 0.75; 95% CI, 0.62-0.92). Analyzing individual dose groups separately yielded the same results (HR for 60 mg/day, 0.75; 95% CI, 0.60-0.96: HR for 120 mg/day, 0.75; 95% CI, 0.59-0.95). Subgroup analyses showed no significant interactions between age or hysterectomy status and the effect of raloxifene on the global index (interaction p &gt; 0.1), whereas the global index risk reduction seemed to be greater in obese women compared with nonobese women (interaction p = 0.03). The significant 25% reduction in global index is compatible with a favorable risk-benefit safety profile when raloxifene is used for osteoporosis treatment in postmenopausal women. These results require confirmation in ongoing clinical trials.
Effects of Secreted Frizzled-Related Protein 3 on Osteoblasts In Vitro
Authors: Chung Yoon-Sok , Baylink David J , Srivastava Apurva K , Amaar Yousef , Tapia Blanca , Kasukawa Yuji , Mohan Subburaman 
Published: April 2006

Abstract
To examine if sFRP3s act as decoy receptors for Wnt, we examined the effects of recombinant sFRP3 on mouse osteoblast proliferation and differentiation. We found that sFRP3 unexpectedly increased osteoblast differentiation, suggesting it may act through other mechanisms besides acting as a decoy receptor for Wnt's.
Introduction: Secreted frizzled-related proteins (sFRPs) are a truncated form of frizzled receptor, missing both the transmembrane and cytosolic domains. Because previous studies have shown that sFRPs bind and act as decoy receptors for Wnt proteins that promote osteoblast differentiation, we postulated that sFRP3 acts as an inhibitor of osteoblast differentiation.
Materials and Methods: We examined the effects of mouse recombinant sFRP3 and/or Wnt-3A on cell proliferation and differentiation using MC3T3-E1 mouse osteoblasts and primary cultures of mouse bone marrow stromal cells. We evaluated the effects of sFRP3 on β-catenin levels using Western immunoblot analyses.
Results: We found that sFRP3 suppressed osteoblast cell number in a dose-dependent manner that was the result of a decrease in proliferation and not because of an increase in apoptosis. Surprisingly, sFRP3 increased osteoblast differentiation, which could not be explained based on sFRP3 acting as a decoy receptor for stimulatory Wnt's. Furthermore, sFRP3 did not inhibit Wnt3A-induced increase in alkaline phosphatase (ALP) activity. Wnt3A, but not sFRP3 treatment, increased cellular β-catenin levels, and sFRP3 failed to block Wnt3A-induced increase in cellular β-catenin levels. Treatment with endostatin, an agent known to degrade β-catenin, did not inhibit sFRP3-induced increase in ALP activity. sFRP1, like sFRP3, inhibited proliferation and stimulated ALP activity in MC3T3-E1 mouse osteoblasts.
Conclusions: Based on our findings, we conclude that sFRP3 decreased osteoblast proliferation and unexpectedly increased parameters of osteoblast differentiation. Based on our findings, we propose that sFRP3 may stimulate differentiation through a β-catenin-independent pathway in addition to its previously known function as a decoy receptor for Wnt's.
Different Aspects of Visual Impairment as Risk Factors for Falls and Fractures in Older Men and Women
Authors: de Boer Michiel R , Pluijm Saskia MF , Lips Paul , Moll Annette C , Völker-Dieben Hennie J , Deeg Dorly JH , van Rens Ger HMB 
Published: April 2006

Abstract
Visual impairment has been implicated as a risk factor for falling and fractures, but results of previous studies have been inconsistent. The relationship between several aspects of vision and falling/fractures were examined in a prospective cohort study in 1509 older men and women. The analyses showed that impaired vision is an independent risk factor for both recurrent falling and fractures.
Introduction: Falls and fractures are a major health problem among the elderly. Visual impairment has been implicated as a risk factor for both falls and fractures. However, results from studies are inconsistent. The inconsistency between findings can primarily be attributed to differences in the designs of these studies. Most studies have been cross-sectional or case-control studies, and many have not correctly adjusted for potential confounders. Furthermore, until now, the potential mediating effects of functional limitation, physical performance, and physical activity have not been examined.
Materials and Methods: A total of 1509 people was examined in 1995-1996. Contrast sensitivity was assessed with the VCTS_6000-1 chart for near vision. In addition, self-reported visual impairment was assessed by questions on recognizing faces from a distance of 4 m, reading the small print in the newspaper, and problems with glare. Furthermore, many potential confounders and mediators were assessed. Falls and fractures were assessed prospectively during a 3-year follow-up period. The associations between the vision variables and falls and fractures were examined using Cox proportional hazards analyses.
Results: After adjustment for potential confounders, contrast sensitivity was shown to be associated with recurrent falling (hazard ratio [HR] = 1.5), and the question on recognizing faces was shown to be associated with fractures (HR = 3.1). Furthermore, functional limitations and physical performance were shown to be mediators in the relationship between vision variables and recurrent falling/fractures.
Conclusions: The results indicate that impaired vision is an independent risk factor for falling and fractures, but different aspects of visual functioning may have different relationships to falling and fractures.