bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of Calcium Intake and Physical Activity With Bone Density and Size in Premenopausal and Postmenopausal Women: A Peripheral Quantitative Computed Tomography Study
Authors: Uusi-Rasi Kirsti , Sievänen Harri , Pasanen Matti , Oja Pekka , Vuori Ilkka 
Published: April 2006

Abstract
The purpose of this cross-sectional study was to examine the impact of long-term physical activity (PA) and calcium intake on non-weight-bearing radius and weight-bearing tibia. Altogether, 218 healthy, nonsmoking women, [92 premenopausal women, mean age, 32.6 years (SD, 2.2 years), and 126 postmenopausal women, mean age, 67.3 years (SD, 2.0 years)] participated. The subjects were divided according to their habitual levels of physical activity (PA+ or PA−) and calcium intake (Ca+ or Ca−). The distal end and shaft regions of the radius and tibia were evaluated with peripheral quantitative tomography (pQCT). For the shaft regions, bone mineral content (BMC), cortical cross-sectional area (CoA), cortical density (CoD), and bone strength index, that is, 1-11.9% of the density-weighted section modulus (BSI) were determined. For the distal ends, BMC, total cross-sectional area (ToA), trabecular density (TrD), and BSI were determined. The BMC at the distal radius in the young PA+ group was 6.6% (95% CI, 1-to 11.9%) lower than that of the PA− group. A similar nonsignificant trend was found for the radial shaft. The radial shaft showed a mechanically more competent structure among the older subjects with a BSI 8.5% (95% CI, 1.8-15.6%) higher in the older PA+ group than in the older PA− group. The associations between calcium intake and the radial bone characteristics were systematically positive in both age groups. PA seemed to benefit the distal tibia. In the younger age group the TrD was 6.9% (95% CI, 1.8-12.4%) higher in the PA+ group, and in the elderly the BMC was 5% (95% CI, 0.3-9.9%) higher in the PA+ group than in the PA− group. Note that in the younger age group the ToA was 5.1% (95% CI, 0-9.1%) smaller in the PA+ group than in the PA− group, and in the older age group the ToA was 4.2% (95% CI, −0.3-8.9%) greater in the PA+ group than in the PA− group. The association of PA and bone characteristics at the tibial shaft was positive in both age groups (statistically significant for the older subjects). The tibial shaft BSI of the older PA+ group was 8.6% (95% CI, 2.6-14.9%) better than that of the old PA− group. There was no association between calcium intake and the tibial bone characteristics in either age group. In conclusion, high calcium intake was positively associated with a mechanically competent structure in the radius among both younger and older women, whereas the influence of PA did not become apparent until older ages. PA seemed to benefit particularly the weight-bearing tibia, whereas calcium intake was not associated with the tibia.
Human Osteoblasts' Proliferative Responses to Strain and 17β-Estradiol Are Mediated by the Estrogen Receptor and the Receptor for Insulin-Like Growth Factor I
Authors: Cheng Ming Zhao , Rawlinson Simon C. F. , Pitsillides Andrew A. , Zaman Gul , Mohan Subburaman , Baylink David J. , Lanyon Lance E. 
Published: April 2006

Abstract
The mechanism by which mechanical strain and estrogen stimulate bone cell proliferation was investigated using monolayer cultures of human osteoblastic TE85 cells and female human primary (first-passage) osteoblasts (fHOBs). Both cell types showed small but statistically significant dose-dependent increases in [3H]thymidine incorporation in response to 17β-estradiol and to a single 10-minute period of uniaxial cyclic strain (1 Hz). In both cell types, the peak response to 17β-estradiol occurred at 10−8-10−7 M and the peak response to strain occurred at 3500 microstrain (μϵ). Both strain-related and 17β-estradiol-related increases in [3H]thymidine incorporation were abolished by the estrogen receptor (ER) modulator ICI 182,780 (10−8 M). Tamoxifen (10−9-10−8 M) increased [3H]thymidine incorporation in both cell types but had no effect on their response to strain. In TE85 cells, tamoxifen reduced the increase in [3H]thymidine incorporation associated with 17β-estradiol to that of tamoxifen alone but had no such effect in fHOBs. In TE85 cells, strain increased medium concentrations of insulin-like growth factor (IGF) II but not IGF-I, whereas 17β-estradiol increased medium concentrations of IGF-I but not IGF-II. Neutralizing monoclonal antibody (MNAb) to IGF-I (3 μg/ml) blocked the effects of 17β-estradiol and exogenous truncated IGF-I (tIGF-I; 50 ng/ml) but not those of strain or tIGF-II (50 ng/ml). Neutralizing antibody to IGF-II (3 μg/ml) blocked the effects of strain and tIGF-II but not those of 17β-estradiol or tIGF-I. MAb αIR-3 (100 ng/ml) to the IGF-I receptor blocked the effects on [3H]thymidine incorporation of strain, tIGF-II, 17β-estradiol, and tIGF-I. HOBs and TE85 cells, act similarly to rat primary osteoblasts and ROS 17/2.8 cells in their dose-related proliferative responses to strain and 17β-estradiol, both of which can be blocked by the ER modulator ICI 182,780. In TE85 cells (as in rat primaries and ROS 17/2.8 cells), the response to 17β-estradiol is mediated by IGF-I, and the response to strain is mediated by IGF-II. Human cells differ from rat cells in that tamoxifen does not block their response to strain and reduces the response to 17β-estradiol in TE85s but not primaries. In both human cell types (unlike rat cells) the effects of strain and IGF-II as well as estradiol and IGF-I can be blocked at the IGF-I receptor.
Possible Involvement of IκB Kinase 2 and MKK7 in Osteoclastogenesis Induced by Receptor Activator of Nuclear Factor κB Ligand
Authors: Yamamoto Aiichiro , Miyazaki Tsuyoshi , Kadono Yuho , Takayanagi Hiroshi , Miura Toshiki , Nishina Hiroshi , Katada Toshiaki , Wakabayashi Kenji , Oda Hiromi , Nakamura Kozo , Tanaka Sakae 
Published: April 2006

Abstract
Recent studies have revealed the essential role of the receptor activator of nuclear factor κB (NF-κB) ligand (RANKL) in osteoclast differentiation and activation. Adenovirus vector could efficiently transduce genes into RAW264.7 cells, which differentiate into osteoclast-like multinucleated cells in the presence of RANKL. The role of NF-κB and c-jun N-terminal kinase (JNK) activation in RANKL-induced osteoclast differentiation was investigated using an adenovirus vector carrying the dominant negative IκB kinase 2 gene (AxIKK2DN) or dominant negative MKK7 gene (AxMKK7DN). IKK2DN and MKK7DN overexpression in RAW cells specifically suppressed the NF-κB activation and JNK activation in response to RANKL, respectively, without affecting other signaling pathways. Either inhibition of NF-κB or JNK pathways dose-dependently inhibited osteoclast formation induced by RANKL. These results suggest that both NF-κB and JNK activation are independently required for osteoclast differentiation.
Vitamin D Hormone Inhibits Osteoclastogenesis In Vivo by Decreasing the Pool of Osteoclast Precursors in Bone Marrow
Authors: Shibata Takeshi , Shira-Ishi Ayako , Sato Takuya , Masaki Toshimi , Sasaki Aya , Masuda Yoshiko , Hishiya Akinori , Ishikura Nobuyuki , Higashi Sayumi , Uchida Yasuhiro , Saito Moto-O , Ito Masako , Ogata Etsuro , Watanabe Ken , Ikeda Kyoji 
Published: April 2006

Abstract
Previous observations that vitamin D hormone induces the expression of the receptor activator of nuclear factor κB (NF-κB) ligand (RANKL), thereby stimulating osteoclastogenesis in vitro, led to the widespread belief that 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] is a bone-resorbing hormone. Here, we show that alfacalcidol, a prodrug metabolized to 1α,25(OH)2D3, suppresses bone resorption at pharmacologic doses that maintain normocalcemia in an ovariectomized (OVX) mouse model of osteoporosis. Treatment of OVX mice with pharmacologic doses of alfacalcidol does not increase RANKL expression, whereas toxic doses that cause hypercalcemia markedly reduce the expression of RANKL. When bone marrow (BM) cells from OVX mice were cultured with sufficient amounts of macrophage colony-stimulating factor (M-CSF) and RANKL, osteoclastogenic activity was higher than in sham mice. Marrow cultures from alfacalcidol- or estrogen-treated OVX mice showed significantly less osteoclastogenic potential compared with those from vehicle-treated OVX mice, suggesting that the pool of osteoclast progenitors in the marrow of vitamin D-treated mice as well as estrogen-treated mice was decreased. Frequency analysis showed that the number of osteoclast progenitors in bone marrow was increased by OVX and decreased by in vivo treatment with alfacalcidol or estrogen. We conclude that the pharmacologic action of active vitamin D in vivo is to decrease the pool of osteoclast progenitors in BM, thereby inhibiting bone resorption. Because of its unusual activity of maintaining bone formation while suppressing bone resorption, in contrast to estrogens that depress both processes, vitamin D hormone and its bone-selective analogs may be useful for the management of osteoporosis.
Proteolysis Involving Matrix Metalloproteinase 13 (Collagenase-3) Is Required for Chondrocyte Differentiation That Is Associated with Matrix Mineralization
Authors: Wu C. William , Tchetina Elena V. , Mwale Fackson , Hasty Karen , Pidoux Isabelle , Reiner Agnes , Chen Jeffrey , Van Wart Harold E. , Poole A. Robin 
Published: April 2006

Abstract
Collagenases are involved in cartilage matrix resorption. Using bovine fetal chondrocytes isolated from physeal cartilages and separated into a distinct prehypertrophic subpopulation, we show that in serum-free culture they elaborate an extracellular matrix and differentiate into hypertrophic chondrocytes. This is characterized by expression of type X collagen and the transcription factor Cbfa1 and increased incorporation of45Ca2+ in the extracellular matrix, which is associated with matrix calcification. Collagenase activity, attributable only to matrix metalloproteinase (MMP) 13 (collagenase-3), is up-regulated on differentiation. A nontoxic carboxylate inhibitor of MMP-13 prevents this differentiation; it suppresses expression of type X collagen, Cbfa1, and MMP-13 and inhibits increased calcium incorporation in addition to inhibiting degradation of type II collagen in the extracellular matrix. General synthesis of matrix proteins is unaffected. These results suggest that proteolysis involving MMP-13 is required for chondrocyte differentiation that occurs as part of growth plate development and which is associated with matrix mineralization.
Tests of Linkage and/or Association of Genes for Vitamin D Receptor, Osteocalcin, and Parathyroid Hormone With Bone Mineral Density
Authors: Deng Hong-Wen , Shen Hui , Xu Fu-Hua , Deng Hong-Yi , Conway Theresa , Zhang Hai-Tao , Recker Robert R. 
Published: April 2006

Abstract
Bone mineral density (BMD) is a major determinant of osteoporotic fractures (OFs). The heritability of BMD ranges from 50% to 90% in human populations. Extensive molecular genetic analyses have been performed through traditional linkage or association approaches to test and identify genes or genomic regions underlying BMD variation. The results, particularly those concerning the vitamin D receptor (VDR) gene, have been inconsistent and controversial. In this study, we simultaneously test linkage and/or association of the genes for VDR, osteocalcin (also known as bone Gla protein [BGP]), and parathyroid hormone (PTH) with BMD in 630 subjects from 53 human pedigrees. Each of these pedigrees was ascertained through a proband with an extreme BMD value at the hip or spine (Z score ≤ −1.28). For the raw BMD values, adjusting for significant covariate effects of age, sex, and weight, we performed tests for linkage alone, association alone, and then both linkage and association. For the spine BMD, at the two markers (ApaI and FokI) inside the VDR gene we found evidence for linkage (p &lt; 0.05) and for both linkage and association by the transmission disequilibrium test (TDT; p &lt; 0.05); association was detected (p &lt; 0.07) with regular statistical testing by analyses of variance (ANOVA). In addition, significant results were found for association alone (p &lt; 0.05), linkage alone (p = 0.0005), and for linkage and association (p = 0.0019) for the intragenic marker HindIII of the BGP gene for the hip BMD. Through testing for association, linkage, and linkage and association simultaneously, our data support the VDR gene as a quantitative trait locus (QTL) underlying spine BMD variation and the BGP gene as a QTL underlying hip BMD variation. However, our data do not support the PTH gene as a QTL underlying hip or spine BMD variation. This is the first study in the broad field of bone genetics that tests candidate genes as QTLs for BMD by testing simultaneously for association alone, for linkage alone, and for association and linkage (via the TDT).
Mechanical and Architectural Bone Adaptation in Early Stage Experimental Osteoarthritis
Authors: Boyd Steven K. , Müller Ralph , Dr. Zernicke Ronald F. 
Published: April 2006

Abstract
The purpose of this study was to quantify mechanical and architectural changes to knee joint periarticular subchondral cancellous bone in early stage experimental osteoarthritis (OA). Unilateral anterior cruciate ligament transection (ACLX) was performed on 10 dogs that were assigned randomly to two groups: 3 weeks or 12 weeks post-ACLX. Cylindrical bone cores excised from the medial condyle of the distal femur after death were scanned using high-resolution microcomputed tomography (μCT) and subsequently failed under unconstrained uniaxial compression. The apparent-level elastic modulus was less in the ACLX femur compared with the contralateral control, and the decrease was significant (−45%; p &lt; 0.05) by 12-weeks post-ACLX. A finite element (FE) analysis based on μCT data simulated the uniaxial compression tests on a specimen-by-specimen basis to determine tissue modulus. No change in tissue modulus was detected, and a single tissue modulus of 5100 MPa (95% CI, ±600 MPa) explained the apparent-level modulus changes observed in the disease-related bone adaptation. The three-dimensional (3D) connectivity was evaluated from the original μCT data to quantify architectural alterations in contrast to tissue alterations. Significantly increased connectivity (through plate perforations) occurred as early as 3 weeks post-ACLX and was as high as 127% by 12 weeks post-ACLX in the distal femur. These measured changes indicated that architectural adaptation predominated over tissue modulus changes affecting apparent-level elastic modulus in the early stage of experimental OA and suggests that to maintain normal cancellous bone after a traumatic injury, early intervention should focus on preventing the substantial architectural alterations.
Can Vitamin D Supplementation Reduce the Risk of Fracture in the Elderly? A Randomized Controlled Trial
Authors: Meyer Haakon E. , Smedshaug Guro B. , Kvaavik Elisabeth , Falch Jan A. , Tverdal Aage , Pedersen Jan I. 
Published: April 2006

Abstract
Randomized controlled trials have shown that a combination of vitamin D and calcium can prevent fragility fractures in the elderly. Whether this effect is attributed to the combination of vitamin D and calcium or to one of these nutrients alone is not known. We studied if an intervention with 10 μg of vitamin D3 per day could prevent hip fracture and other osteoporotic fractures in a double-blinded randomized controlled trial. Residents from 51 nursing homes were allocated randomly to receive 5 ml of ordinary cod liver oil (n = 569) or 5 ml of cod liver oil where vitamin D was removed (n = 575). During the study period of 2 years, fractures and deaths were registered, and the principal analysis was performed on the intention-to-treat basis. Biochemical markers were measured at baseline and after 1 year in a subsample. Forty-seven persons in the control group and 50 persons in the vitamin D group suffered a hip fracture. The corresponding figures for all nonvertebral fractures were 76 persons (control group) and 69 persons (vitamin D group). There was no difference in the incidence of hip fracture (p = 0.66, log-rank test), or in the incidence of all nonvertebral fractures (p = 0.60, log-rank test) in the vitamin D group compared with the control group. Compared with the control group, persons in the vitamin D group increased their serum 25-hydroxyvitamin D concentration with 22 nmol/liter (p = 0.001). In conclusion, we found that an intervention with 10 μg of vitamin D3 alone produced no fracture-preventing effect in a nursing home population of frail elderly people.
Gender Differences in the Genetic Factors Responsible for Variation in Bone Density and Ultrasound
Authors: Naganathan Vasi , Macgregor Alex , Snieder Harold , Nguyen Tuan , Spector Tim , Sambrook Philip 
Published: April 2006

Abstract
Although genetic factors are thought to explain a large proportion of the variation in bone density in women, few studies have been conducted in men. Therefore, it is unclear whether the individual differences in bone strength between men and women are a reflection of gender differences in the relative influence of genetic and environmental factors on bone density variance. The aim of this study was to determine if there were gender differences in the genetic components of variance for bone density and ultrasound. In addition, the study aimed to explore the hypothesis that there are unique gender-specific genetic determinants of these traits. Bone mineral density (BMD) of the hip, distal forearm, and lumbar spine were measured by dual-energy X-ray absorptiometry (DXA) as well as quantitative ultrasound (QUS) at the calcaneus in healthy female twin pairs (286 identical [MZ] and 265 nonidentical [DZ]), male twin pairs (72 MZ and 65 DZ), and 82 opposite-sex (OS) pairs aged between 18 and 80 years. For hip BMD, distal forearm, and QUS measurements, the differences between MZ correlations and like-sex DZ correlations were similar for both sexes, suggesting little difference in the component of total variance explained by genetic factors between male and female twin pairs. However, correlations between OS twin pairs were lower than that of like-sex twin pairs, suggesting the possibility of unique gender-specific genetic effects. At the forearm, model fitting suggested a small gender difference in the magnitude of genetic variance as well as the presence of a unique gender-specific genetic variance component. Hip, lumbar spine, and QUS measurements were better explained by models that assumed no gender differences in genetic variance between the sexes, but the study had insufficient power to detect small differences in the genetic components of variance. The results of this study suggest that the proportion of bone strength variance explained by genetic factors is similar for men and women. However, at some regions there is evidence to suggest a gender-specific genetic component to the overall genetic variance.
Retinol Intake and Bone Mineral Density in the Elderly: The Rancho Bernardo Study
Authors: Promislow Joanne H. E. , Goodman-Gruen Deborah , Slymen Donald J. , Barrett-Connor Elizabeth 
Published: April 2006

Abstract
Retinol is involved in bone remodeling, and excessive intake has been linked to bone demineralization, yet its role in osteoporosis has received little evaluation. We studied the associations of retinol intake with bone mineral density (BMD) and bone maintenance in an ambulatory community-dwelling cohort of 570 women and 388 men, aged 55–92 years at baseline. Regression analyses, adjusted for standard osteoporosis covariates, showed an inverse U-shaped association of retinol, assessed by food-frequency questionnaires in 1988–1992, with baseline BMD, BMD measured 4 years later, and BMD change. Supplemental retinol use, reported by 50% of women and 39% of men, was an effect modifier in women; the associations of log retinol with BMD and BMD change were negative for supplement users and positive for nonusers at the hip, femoral neck, and spine. At the femoral neck, for every unit increase in log retinol intake, supplement users had 0.02 g/cm2 (p = 0.02) lower BMD and 0.23% (p = 0.05) greater annual bone loss, and nonusers had 0.02 g/cm2 (p = 0.04) greater BMD and 0.22% (p = 0.19) greater bone retention. However, among supplement users, retinol from dietary and supplement sources had similar associations with BMD, suggesting total intake is more important than source. In both sexes, increasing retinol became negatively associated with skeletal health at intakes not far beyond the recommended daily allowance (RDA), intakes reached predominately by supplement users. This study suggests there is a delicate balance between ensuring that the elderly consume sufficient vitamin A and simultaneously cautioning against excessive retinol supplementation.
Radioguided Parathyroidectomy via VATS Combined With Intraoperative Parathyroid Hormone Testing: The Surgical Approach of Choice for Patients With Mediastinal Parathyroid Adenomas?
Authors: O'Herrin Jacquelyn K. , Weigel Tracey , Wilson Michael , Chen Herbert 
Published: April 2006

Abstract
Despite the excellent results with bilateral exploration, minimally invasive parathyroidectomy has become the procedure of choice for patients with hyperparathyroidism in which a single parathyroid lesion can be localized preoperatively. In this article, we discuss a patient who presented with primary hyperparathyroidism for the first time and had a Tc-99m sestamibi scan to localize a single parathyroid lesion in the left, anterior mid-mediastinum. We subsequently performed a radioguided parathyroidectomy via video-assisted thoracoscopic surgery (VATS) to resect this parathyroid adenoma and used intraoperative parathyroid hormone (PTH) testing to confirm cure and avoid neck exploration. We concluded that radioguided parathyroidectomy via VATS combined with intraoperative PTH testing is an effective approach for patients with primary hyperparathyroidism and mediastinal parathyroid lesions, and perhaps should be the technique of choice.
Induction of Transcriptional Activity of the Cyclic Adenosine Monophosphate Response Element Binding Protein by Parathyroid Hormone and Epidermal Growth Factor in Osteoblastic Cells
Authors: Swarthout John T. , Tyson Darren R. , Jefcoat Stephen C. , Partridge Nicola C. 
Published: April 2006

Abstract
Previously, we have shown that parathyroid hormone (PTH) transactivation of cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) requires both serine 129 (S129) and serine 133 (S133) in rat osteosarcoma cells UMR 106-01 (UMR) cells. Furthermore, although protein kinase A (PKA) is responsible for phosphorylation at S133, glycogen synthase kinase 3β (GSK-3β) activity is required and may be responsible for phosphorylation of CREB at S129. Here, we show, using the GAL4-CREB reporter system, that epidermal growth factor (EGF) can transactivate CREB in UMR cells in addition to PTH. Additionally, treatment of UMR cells with both PTH and EGF results in greater than additive transactivation of CREB. Furthermore, using mutational analysis we show that S129 and S133 are required for EGF-induced transcriptional activity. EGF activates members of the MAPK family including p38 and extracellular signal—activated kinases (ERKs), and treatment of UMR cells with either the p38 inhibitor (SB203580) or the MEK inhibitor (PD98059) prevents phosphorylation of CREB at S133 by EGF but not by PTH. Treatment of cells with either SB203580 or PD98059 alone or together significantly inhibits transactivation of CREB by EGF but not by PTH, indicating that EGF regulates CREB phosphorylation and transactivation through p38 and ERKs and PTH does not. Finally, the greater than additive transactivation of CREB by PTH and EGF is significantly inhibited by the PKA inhibitor H-89 or by cotreatment with SB203580 and PD98059. Thus, several different signaling pathways in osteoblastic cells can converge on and regulate CREB activity. This suggests, in vivo, that circulating agents such as PTH and EGF are acting in concert to exert their effects.