bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Effects of Withdrawal of Bisphosphonate Incadronate Disodium (YM175) on Bone Mineral Density, Mass, Structure, and Turnover in the Lumbar Vertebrae of Ovariectomized Rats
Authors: Tamura Yasuki , Miyakoshi Naohisa , Itoi Eiji , Abe Toshiki , Kudo Takuya , Tsuchida Tsunehisa , Kasukawa Yuji , Sato Kozo 
Published: April 2006

Abstract
This study was designed to evaluate the long-term effects of incadronate disodium (YM175) after its withdrawal on cancellous bone mass in ovariectomized (OVX) rats. Thirteen-week-old female SD rats were randomized into four groups: sham-operated, OVX, low-YM, and high-YM (0.01 mg/kg or 0.1 mg/kg subcutaneously [sc], three times a week after OVX) groups. After 4 weeks of treatment with vehicle or YM175, rats from each group were killed at time points of 0 (baseline), 3, 6, 9, and 12 months after withdrawal of the agent. Bone mineral density (BMD) of the lumbar vertebrae was measured by dual-energy X-ray absorptiometry (DXA). Bone volume (BV/TV), trabecular number and trabecular separation (Tb.N and Tb.Sp), eroded surface (ES/BS), osteoclast number and osteoclast surface (N.Oc/BS and Oc.S/BS), osteoid surface (OS/BS), and bone formation rate (BFR/BS) were measured as histomorphometric parameters of the fifth lumbar vertebra. BMD, BV/TV, Tb.N, and Tb.Sp in YM175-treated groups were maintained at the same level as in the sham group until 12 months after withdrawal in the high-YM group and until 3 months after withdrawal in the low-YM group. YM175 decreased both bone formative and resorptive parameters in histomorphometry. Serum bone-specific alkaline phosphatase (ALP) and urinary deoxypyridinoline at both doses of YM175 also showed a suppressive effect of this agent on bone turnover. These results indicate that YM175, after withdrawal, still maintains bone volume dose dependently by depressing bone resorption and formation in OVX rats. Intermittent YM175 treatment with a long interval may be sufficient to maintain the bone volume and structure in OVX rats.
Effect of Pamidronate in Preventing Local Bone Loss After Total Hip Arthroplasty: A Randomized, Double-Blind, Controlled Trial
Authors: Wilkinson J. Mark , Stockley Ian , Peel Nicola F. A. , Hamer Andrew J. , Elson Reginald A. , Barrington N. Anne , Eastell Richard 
Published: April 2006

Abstract
Acute periprosthetic bone loss occurs after total hip arthroplasty. Bone loss undermines the support of the implant and may contribute to prosthetic failure. At present, there is no established prophylaxis for this process. We studied the effect of a single-dose infusion of 90 mg of pamidronate on early periprosthetic bone mineral density (BMD), biochemical markers of bone turnover, radiological, and clinical outcome in a 26-week, prospective, randomized, double-blinded study of 47 men and women undergoing total hip arthroplasty. Pamidronate therapy led to a significant reduction in bone loss compared with placebo for both the proximal femur and the pelvis (repeated measures analysis of variance [ANOVA]); p = 0.001 and p = 0.01, respectively). Pamidronate therapy was associated with suppression of all biochemical markers of bone turnover compared with placebo (repeated measures ANOVA; p &lt; 0.05 for all comparisons), with the exception of urinary free deoxypyridinoline. Pamidronate did not interfere with the clinical improvement in symptoms after total hip arthroplasty, or radiological outcome, and was not associated with an increase in adverse events. This study provides clinical data on the efficacy and safety of bisphosphonates for the prevention of bone loss after total hip arthroplasty and supports the establishment of larger-scale clinical trials to determine the long-term clinical efficacy of this intervention using implant failure as the primary endpoint.
Moderate Alcohol Consumption Suppresses Bone Turnover in Adult Female Rats
Authors: Turner R. T. , Kidder L. S. , Kennedy A. , Evans G. L. , Sibonga J. D. 
Published: April 2006

Abstract
Chronic alcohol abuse is a major risk factor for osteoporosis but the effects of moderate drinking on bone metabolism are largely uninvestigated. Here, we studied the long-term dose-response (0, 3, 6, 13, and 35% caloric intake) effects of alcohol on cancellous bone in the proximal tibia of 8-month-old female rats. After 4 months of treatment, all alcohol-consuming groups of rats had decreased bone turnover. The inhibitory effects of alcohol on bone formation were dose dependent. A reduction in osteoclast number occurred at the lowest level of consumption but there were no further reductions with higher levels of consumption. An imbalance between bone formation and bone resorption at higher levels of consumption of alcohol resulted in trabecular thinning. Our observations in rats raise the concern that moderate consumption of alcoholic beverages in humans may reduce bone turnover and potentially have detrimental effects on the skeleton.
Changes in Bone Density During Childhood and Adolescence: An Approach Based on Bone's Biological Organization
Authors: Rauch Frank , Schoenau Eckhard 
Published: April 2006

Abstract
Bone densitometry has great potential to improve our understanding of bone development. However, densitometric data in children rarely are interpreted in light of the biological processes they reflect. To strengthen the link between bone densitometry and the physiology of bone development, we review the literature on physiological mechanisms and structural changes determining bone mineral density (BMD). BMD (defined as mass of mineral per unit volume) is analyzed in three levels: in bone material (BMDmaterial), in a bone's trabecular and cortical tissue compartments (BMDcompartment), and in the entire bone (BMDtotal). BMDmaterial of the femoral midshaft cortex decreases after birth to a nadir in the first year of life and thereafter increases. In iliac trabecular bone, BMDmaterial also increases from infancy to adulthood, reflecting the decrease in bone turnover. BMDmaterial cannot be determined with current noninvasive techniques because of insufficient spatial resolution. BMDcompartment of the femoral midshaft cortex decreases in the first months after birth followed by a rapid increase during the next 2 years and slower changes thereafter, reflecting changes in both relative bone volume and BMDmaterial. Trabecular BMDcompartment increases in vertebral bodies but not at the distal radius. Quantitative computed tomography (QCT) allows for the determination of both trabecular and cortical BMDcompartment, whereas projectional techniques such as dual-energy X-ray absorptiometry (DXA) can be used only to assess cortical BMDcompartment of long bone diaphyses. BMDtotal of long bones decreases by about 30% in the first months after birth, reflecting a redistribution of bone tissue from the endocortical to the periosteal surface. In children of school age and in adolescents, changes in BMDtotal are site-specific. There is a marked rise in BMDtotal at locations where relative cortical area increases (metacarpal bones, phalanges, and forearm), but little change at the femoral neck and midshaft. BMDtotal can be measured by QCT at any site of the skeleton, regardless of bone shape. DXA allows the estimation of BMDtotal at skeletal sites, which have an approximately circular cross-section. The system presented here may help to interpret densitometric results in growing subjects on a physiological basis.
Low-Intensity Pulsed Ultrasound Accelerates Rat Femoral Fracture Healing by Acting on the Various Cellular Reactions in the Fracture Callus
Authors: Azuma Yoshiaki , Ito Masaya , Harada Yoshifumi , Takagi Hideko , Ohta Tomohiro , Jingushi Seiya 
Published: April 2006

Abstract
Low-intensity pulsed ultrasound (LIPUS) has been shown to accelerate fracture healing in both animal models and clinical trials, but the mechanism of action remains unclear. In fracture healing, various consecutive cellular reactions occurred until repair. We investigated whether the advanced effects of LIPUS depended on the duration and timing of LIPUS treatment in a rat closed femoral fracture model to determine the target of LIPUS in the healing process. Sixty-nine Long-Evans male rats that have bilateral closed femoral fractures were used. The right femur was exposed to LIPUS (30 mW/cm2 spatial and temporal average [SATA], for 20 minutes/day), and the left femur was used as a control. Rats were divided into four groups according to timing and duration of treatment (Ph-1, days 1–8; Ph-2, days 9–16; Ph-3, days 17–24; throughout [T], days 1–24 after the fracture). Animals were killed on day 25. After radiographs and microfocus X-ray computed tomography (μCT) tomograms were taken, the hard callus area (HCA), bone mineral content (BMC) at the fracture site, and mechanical torsion properties were measured, and histological analysis was conducted. Interestingly, the maximum torque of the LIPUS-treated femur was significantly greater than that of the controls in all groups without any changes in HCA and BMC. The multiviewing of three-dimensional (3D) μCT reconstructions and histology supported our findings that the partial LIPUS treatment time was able to accelerate healing, but longer treatment was more effective. These results suggest that LIPUS acts on some cellular reactions involved in each phase of the healing process such as inflammatory reaction, angiogenesis, chondrogenesis, intramembranous ossification, endochondral ossification, and bone remodeling.
Fractal Analysis of Radiographic Trabecular Bone Texture and Bone Mineral Density: Two Complementary Parameters Related to Osteoporotic Fractures
Authors: Benhamou C. L. , Poupon S. , Lespessailles E. , Loiseau S. , Jennane R. , Siroux V. , Ohley W. , Pothuaud L. 
Published: April 2006

Abstract
Trabecular bone microarchitecture and bone mineral density (BMD) are two main factors related to osteoporotic fractures. Currently, however, microarchitecture is not evaluated. We have developed and validated a trabecular bone texture analysis from radiographic images. The objective was to determine if the fractal analysis of texture was able to distinguish osteoporotic fracture groups from control groups, either in vertebrae, hip, or wrist fractures, and to determine if this indicator and BMD were independent and complementary. In this cross-sectional unicenter case-control population study in postmenopausal women, 107 fracture cases were enrolled and age-matched with 197 control cases. This population comprised 40 vertebral fractures (with 70 controls), 30 hip fractures (55 controls), and 37 wrist fractures (62 controls). Hip and lumbar spine BMD were measured by double-energy X-ray absorptiometry. Fractal analysis of texture was performed on calcaneus radiographs and the result was expressed as the H parameter (H = 2-fractal dimension). The H parameter showed a lower value (0.679 ± 0.053 SD) in fracture cases versus control cases (0.696 ± 0.030; p = 0.007), the statistical significance persisting after adjustment for age and for lumbar spine (LS) or hip BMD. This result was confirmed in vertebral fractures (p = 0.0001) and hip fractures (p = 0.003) but not wrist fractures (p = 0.07). We determined the threshold between high and low H values and then the odds ratios (OR) of fracture for low H for BMD ≤ −2.5 SD in T score and for the combinations of both parameters. The OR of fracture for low H was 1.6 (95% CI, 1.1–2.6). For LS BMD ≤ −2.5 SD the OR of 6.1 (3.4–10.8) shifted to 9.0 (4.0–20.4) when we added low H and for hip BMD it shifted from 5.6 (3.3–9.4) to 8.1 (4.0–16.8). In vertebral, hip, and wrist fracture cases the results were also significant. These data have shown that the fractal analysis of texture on calcaneus radiographs can distinguish osteoporotic fracture groups from control groups. This analysis and BMD provide independent and complementary information. These data suggest that we can improve the fracture risk evaluation by adding information related to microarchitecture, derived from analysis of conventional radiographic images.
Mechanical Strain Effect on Bone-Resorbing Activity and Messenger RNA Expressions of Marker Enzymes in Isolated Osteoclast Culture
Authors: Kurata Kosaku , Uemura Toshimasa , Nemoto Atsuko , Tateishi Tetsuya , Murakami Teruo , Higaki Hidehiko , Miura Hiromasa , Iwamoto Yukihide 
Published: April 2006

Abstract
Adaptive modeling and remodeling are controlled by the activities of osteoblasts and osteoclasts, which are capable of sensing their mechanical environments and regulating deposition or resorption of bone matrix. The effects of mechanical stimuli on isolated osteoclasts have been scarcely examined because it has proven to be difficult to prepare a number of pure osteoclasts and to cultivate them on mineralized substratum during mechanical stimulation. Recently, we developed an apparatus for applying mechanical stretching to the ivory slice/plastic plate component on which cells could be cultured. The loading frequency, strain rate, and generated strain over an ivory surface could be controlled by a personal computer. Using this apparatus, we examined the role of mechanical stretching on the bone-resorbing activity of the osteoclasts. Mature and highly enriched osteoclasts were cultured for 2, 12, and 24 h on the ivory/plate component while being subjected to intermittent tensile strain. The stretched osteoclasts showed enhanced messenger RNA (mRNA) expression levels of osteoclast marker enzymes, tartrate-resistant acid phosphatase (TRAP), and cathepsin K and increases of resorbed-pit formation, suggesting that the mechanical stretching up-regulated the bone-resorbing activity of the osteoclasts. A stretch-activated cation (SA-cat) channel blocker significantly inhibited the increases of the mRNA level and pit formation after 24 h of stretching. This study suggested the possibility that the mature osteoclasts responded to mechanical stretching through a mechanism involving a SA-cat channel in the absence of mesenchymal cells and, as a result, up-regulated their bone-resorbing activity.
Study of the Maturation of the Organic (Type I Collagen) and Mineral (Nonstoichiometric Apatite) Constituents of a Calcified Tissue (Dentin) as a Function of Location: A Fourier Transform Infrared Microspectroscopic Investigation
Authors: Magne David , Weiss Pierre , Bouler Jean-Michel , Laboux Olivier , Daculsi Guy 
Published: April 2006

Abstract
Fourier transform infrared microspectroscopy (FTIRM) was used to investigate the organic and mineral phases of a calcified tissue (dentin) as a function of its location from predentin toward enamel. Thin dentin slices (decalcified or not) were fixed in formaldehyde and embedded in glycolmethylmethacrylate (GMA). Fixation did not denature collagen, and GMA did not interact with organic or mineral constituents of dentin. The ν1ν3 PO4 domain was studied in particular in order to estimate mineral maturity and amide I, II, A, and B to obtain data on protein conformation. The results showed that dentin apatite became increasingly mature (stoichiometric) from the mineralization front toward the enamel, especially through loss of HPO42− groups and vacancies. Moreover, collagen fibrils became less and less hydrated, suggesting that intrafibrillar mineralization partially dehydrated the collagen. Combined study of the organic and mineral fractions of calcified tissues may help clarify their relationships in physiological and pathological tissues.
Pubertal Maturation Characteristics and the Rate of Bone Mass Development Longitudinally Toward Menarche
Authors: Van Coeverden Silvia C. C. M. , De Ridder Christine M. , Roos Jan C. , Van'T Hof Martin A. , Netelenbos J. Coen , Delemarre-Van De Waal Henriette A. 
Published: April 2006

Abstract
To assess risks for osteoporosis and to compare bone mass in different groups of healthy children or children with diseases, it is important to have knowledge of their sexual maturation status during puberty. The aim of our study was to evaluate bone mass formation longitudinally in relation to pubertal maturation characteristics in healthy white girls. We investigated the bone mineral content (BMC) and the bone mineral density (BMD) at different skeletal sites in 151 girls with increasing pubertal stages in relation with their chronological age and with an early or late onset of puberty or menarche and with a slow or fast maturation. Bone mass was measured at the onset of puberty, during puberty, and at menarche. We conclude the following: (1) from midpuberty to menarche, the increase in bone mass formation is highest at all skeletal sites in white girls; (2) early mature girls at the onset of puberty have slightly but definitely lower bone masses at all skeletal sites and at all pubertal stages than late mature girls, whereas the average bone mass formation from the onset of puberty to menarche is similar in both groups; (3) girls with a slow rate of pubertal maturation have lower bone mass values 2 years after the onset of puberty, but at menarche bone mass is similar compared with fast maturers; and (4) it cannot be confirmed that there is an effect of menarcheal age on bone mass values at menarche.
Inhaled Corticosteroids Reduce Bone Mineral Density in Early Postmenopausal but Not Premenopausal Asthmatic Women
Authors: Fujita K. , Kasayama S. , Hashimoto J. , Nagasaka Y. , Nakano N. , Morimoto Y. , Barnes P. J. , Miyatake A. 
Published: April 2006

Abstract
Inhaled corticosteroids are widely used in the treatment of bronchial asthma, but it is still uncertain whether long-term use of the inhaled corticosteroids affects bone metabolism in asthmatic patients. In this study, we examined the effect of inhaled beclomethasone dipropionate (BDP) on bone mineral density (BMD) and biochemical markers of bone metabolism in pre- and early postmenopausal asthmatic women. Thirty-six (17 premenopausal and 19 early postmenopausal) asthmatic women and 45 healthy control (24 premenopausal and 21 early postmenopausal) women were investigated. All the asthmatic patients were treated with BDP (542 ± 298 μg/day; 100–1200 μg/day) without any systemic administration of corticosteroids for at least 1 year. In premenopausal women, BMD as well as the biochemical markers of bone metabolism did not differ between control subjects and BDP-treated asthmatic patients. By contrast, in early postmenopausal women, BMD was significantly lower in BDP-treated asthmatic patients than in control subjects. In these early postmenopausal women, serum intact osteocalcin concentration was lower in the BDP-treated asthmatic patients than in the control subjects whereas urinary free pyridinoline (F-PYD) and free deoxypyridinoline (F-DPD) concentrations did not differ between the groups. Thus, early postmenopausal, but not premenopausal, asthmatic patients who were treated with inhaled BDP had reduced BMD, which was associated with a decreased level of the bone formation marker. Ovarian hormones may be protective against the adverse effect of inhaled BDP on bone metabolism in the premenopausal patients.
Naphthol-ASBI Phosphate as a Preferred Substrate for Tartrate-Resistant Acid Phosphatase Isoform 5b
Authors: Janckila Anthony J. , Takahashi Karen , Sun Susan Z. , Yam Lung T. 
Published: April 2006

Abstract
Tartrate-resistant acid phosphatase (TRAP) isoform 5b is a potential serum marker for osteoclastic activity. Biochemical assays for serum TRAP activity with para-nitrophenylphosphate (pNPP) have low specificity for bone because of hydrolysis by unrelated nontype 5 TRAPs of blood cells and by related isoform 5a. Our purpose was to increase the specificity of TRAP assay for osteoclastic activity by using naphthol-ASBI phosphate (N-ASBI-P) as a substrate for serum type 5 TRAP activity and heparin as an inhibitor of isoform 5a. TRAP activity in individual and pooled sera of normal subjects and patients with endstage renal disease (ESRD) and rheumatologic diseases was quantitated using pNPP and N-ASBI-P as substrate at pH 5.5 and 6.1. For some experiments, heparin (23U/ml) was added as a specific inhibitor of isoform 5a activity. Isoforms 5a and 5b were separated from serum pools by cation exchange chromatography and identified by nondenaturing polyacrylamide gel electrophoresis (PAGE). N-ASBI-P was selectively hydrolyzed by TRAP isoform 5b. TRAP assays with pNPP and N-ASBI-P correlated only in ESRD sera, which contained primarily isoform 5b. The two assays did not correlate in normal or rheumatic sera with significant amounts of 5a. Heparin inhibited isoform 5a activity approximately 50% but had little effect on isoform 5b activity. Biochemical assay of serum TRAP activity can be made specific for isoform 5b by using N-ASBI-P and heparin. This method can be adapted to simple microplate biochemical or immunochemical assays. This simplified method for assessment of osteoclastic TRAP 5b activity warrants a detailed investigation in diseases of bone metabolism.
Expression of Osteoprotegerin, Receptor Activator of NF-κB Ligand (Osteoprotegerin Ligand) and Related Proinflammatory Cytokines During Fracture Healing
Authors: Kon Tamiyo , Cho Tae-Joon , Aizawa Toshimi , Yamazaki Masashi , Nooh Nasser , Graves Dana , Gerstenfeld Louis C. , Einhorn Thomas A. 
Published: April 2006

Abstract
Fracture healing is a unique biological process regulated by a complex array of signaling molecules and proinflammatory cytokines. Recent evidence for the role of tumor necrosis family members in the coupling of cellular functions during skeletal homeostasis suggests that they also may be involved in the regulation of skeletal repair. The expression of a number of cytokines and receptors that are of functional importance to bone remodeling (osteoprotegerin [OPG], macrophage colony-stimulating factor [M-CSF], and osteoprotegerin ligand [receptor activator of NF-κB ligand (RANKL)]), as well as inflammation (tumor necrosis factor α [TNF-α] and its receptors, and interleukin-1α [IL-1α] and -β and their receptors) were analyzed over a 28-day period after the generation of simple transverse fractures in mouse tibias. OPG was expressed constitutively in unfractured bones and elevated levels of expression were detected throughout the repair process. It showed two distinct peaks of expression: the first occurring within 24 h after fracture and the second at the time of peak cartilage formation on day 7. In contrast, the expression of RANKL was nearly undetectable in unfractured bones but strongly induced throughout the period of fracture healing. The peak in expression of RANKL did not correlate with that of OPG, because maximal levels of expression were seen on day 3 and day 14, when OPG levels were decreasing. M-CSF expression followed the temporal profile of RANKL but was expressed at relatively high basal levels in unfractured bones. TNF-α, lymphotoxin-β (LT-β), IL-1α, and IL-1β showed peaks in expression within the first 24 h after fracture, depressed levels during the period of cartilage formation, and increased levels of expression on day 21 and day 28 when bone remodeling was initiated. Both TNF-α receptors (p55 and p75) and the IL-1RII receptor showed identical patterns of expression to their ligands, while the IL-1R1 was expressed only during the initial period of inflammation on day 1 and day 3 postfracture. Both TNF-α and IL-1α expression were localized primarily in macrophages and inflammatory cells during the early periods of inflammation and seen in mesenchymal and osteoblastic cells later during healing. TNF-α expression also was detected at very high levels in hypertrophic chondrocytes. These data imply that the expression profiles for OPG, RANKL, and M-CSF are tightly coupled during fracture healing and involved in the regulation of both endochondral resorption and bone remodeling. TNF-α and IL-1 are expressed at both very early and late phases in the repair process, which suggests that these cytokines are important in the initiation of the repair process and play important functional roles in intramembraneous bone formation and trabecular bone remodeling.