bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term effects of a treatment course with oral alendronate of postmenopausal osteoporosis
Authors: Rossini M. , Gatti D. , Zamberlan N. , Braga V. , Dorizzi R. , Adami S. 
Published: February 2010

Abstract
Several bisphosphonates are under investigation for the treatment and prevention of postmenopausal osteoporosis. Alendronate, one of these compounds, has been shown to inhibit bone turnover and induce substantial increases in bone mass, but little is known about the duration of its effects. This is considered important, keeping in mind the long half-life of bisphosphonate in bone. In this double-blind controlled study, two groups of 15 postmenopausal women with spinal bone mineral density (BMD) &gt; 2 SD below adult mean peak without vertebral fractures were randomized to receive either alendronate, 20 mg/day, or placebo for 6 months. The treatment course with alendronate significantly suppressed all indices of bone turnover (hydrox-yproline, collagen crosslinks, and alkaline phosphatase activity) within 3 months, and a further slight decrease was observed in the subsequent 3 months. After treatment withdrawal, all indices of bone turnover slowly increased, and they attained the pretreatment values within 6–9 months. Lumbar spine BMD rose by 3.7% (± 1.7 SD) after 6 months of alendronate therapy but did not change 6 and 12 months after treatment withdrawal (4.6 ± 2.8 and 4.7 ± 2.6% versus baseline, respectively). In control patients a slow decrease in lumbar spine BMD was observed, but this was significant only at month 18 of the study. Femoral BMD did not significantly change in the alendronate group, but it slowly decreased in the control group at all sites of evaluation. The fractional loss became statistically significant versus both baseline and the active group by the end of the study only at the level of the femoral neck. These results may imply that the positive bone balance induced by alendronate is sustained long after stopping therapy, despite the reestablishment of pretreatment bone turnover.
Effect of administration and subsequent cessation of buserelin on cancellous bone of female rats
Authors: Dr. Tobias J.H. , Chambers T.J. , Gallagher A. 
Published: February 2010

Abstract
Although hormone replacement therapy is effective in preventing postmenopausal bone loss, it fails to cause a return of bone mass to normal in patients with established osteoporosis. Similarly, in the ovariectomized rat, estrogen administration protects the skeleton from bone loss but fails to reverse this once it has occurred. However, physiologically produced sex steroids may, in contrast to conventional methods of sex steroid administration, be capable of restoring bone mass in osteopenic states. To investigate this question, we analyzed the effect of treatment with the LHRH agonist buserelin for varying durations, and subsequent cessation thereof, on histomorphometric indices of rat cancellous bone. Female rats 13 weeks old were given daily SC injections of vehicle or buserelin as follows: vehicle days 1-90; vehicle days 1-150; vehicle days 1-60, buserelin days 61-90; vehicle days 1-60, buserelin days 61-90, vehicle days 91-150; vehicle days 1-30, buserelin days 31-90; vehicle days 1-30, buserelin days 31-90, vehicle days 91-150; buserelin days 1-90; buserelin days 1-90, vehicle days 91-150. At the end of the treatment period, animals were killed, tibiae removed, and histomorphometric indices assessed at the secondary spongiosa of the proximal metaphysis. Analysis of vaginal smears confirmed that buserelin rapidly suppressed ovulation, which quickly returned once treatment was stopped. We found that administration of buserelin for 30, 60, or 90 days reduced cancellous bone volume because of a reduction in both the number and thickness of trabeculae. The bone loss was at least partly a result of increased bone resorption, because buserelin significantly increased osteoclast surface and number. After cessation of buserelin administration, trabecular number remained unchanged but trabecular thickness increased in all groups, returning to that of vehicle-treated animals. We conclude that buserelin reduces cancellous bone volume in female rats by decreasing trabecular number and thickness and that the latter, but not the former, is restored to normal by the return of ovulation on stopping treatment.
Pharmacokinetics of clodronate in renal failure
Authors: Saha H. , Castren-Kortekangas P. , Ojanen S. , Juhakoski A. , Tuominen J. , Tokola O. , Pasternack A. 
Published: February 2010

AbstractThe pharmacokinetic parameters describing the fate of one intravenous clodronate (disodium dichloromethane diphosphonate) dose was studied in 24 normal subjects and in 24 patients with different degrees of renal insufficiency. The aim of the study was to derive data for adjustment of dosage in relation to renal function. Disodium clodronate in serum and urine samples was analyzed by capillary gas chromatography with mass-selective detection. The renal clearance (CLR) of clodronate was highly dependent on renal function and declined successively with declining glomerular filtration rate (GFR). Plasma clearance (CLP) declined, too, but to a lesser degree than CLR. The impairment of renal function resulted in decreased cumulative urinary elimination of clodronate and increased total areas under the serum concentration-time curve (AUC0-∞). Hence, as the renal elimination of clodronate diminishes with decreasing GFR, there is a related retention of the substance. As a result of the present study, the following dosages are recommended: creatinine clearance (CLCr) from 50 to 80 ml/minute, 75-100% of normal dose; CLCr 12-50 ml/minute, 50-75% of normal dose; and ClCr &lt; 12 ml/minute, 50% of normal dose. The results must be interpreted with caution in patients with malignancy and severe skeletal disease, in whom the nonrenal clearance may vary markedly.
Preliminary in situ identification of estrogen target cells in bone
Authors: Dr. Braidman Isobel P. , Davenport Lisa K. , Carter Howard D. , Selby Peter L. , Mawer Barbara E. , Freemont Anthony J. 
Published: February 2010

Abstract
Although estrogens profoundly influence skeletal growth and maturation, their mechanism of action is still unclear. To identify their target cells in bone, estrogen receptors were located by immunofluorescence using the H222 monoclonal antibody in cryosections (both undecalcified and briefly decalcified) of hyperplastic mandibular condyle (persistent asymmetric mandibular growth) from a 14-year-old girl and radius and ulna from an 18-month-old female pig (epiphyseal fusion) and from a 3-month-old guinea pig (epiphyses open). Bone was removed from the animals at the peak of estrus. The most striking feature in all three species was the high proportion (approximately 50%) of receptor positive osteocytes. Although all sections contained active bone-forming surfaces, we were unable to identify clearly osteoblasts or lining cells that were estrogen receptor positive. In pig bone only, distinctive groups of receptor positive chondrocytes, with a pericellular localization of collagen type 1, were detected above the growth plate but below secondary centers of ossification. This observation suggests that osteocytes are major skeletal estrogen target cells and may be involved in coordinating the response of surface bone cells to the hormone, and further that chondrocytes may be involved in estrogen-induced epiphyseal growth plate fusion.
Effects of tiludronate on bone loss in paraplegic patients
Authors: Dr. Chappard D. , Minaire P. , Privat C. , Berard E. , Mendoza-Sarmiento J. , Tournebise H. , Basle Mf , Audran M. , Rebel A. , Picot C. , Gaud C. 
Published: February 2010

Abstract
Immobilization secondary to spinal cord injury is associated with a marked and rapid atrophy of trabecular bone (disuse osteoporosis). This is due to an early increase of osteoclastic bone resorption associated with a pronounced decreased osteoblastic bone formation. Bisphosphonates are antiosteoclastic compounds and they have been effective in preventing disuse osteoporosis. However, some of them also depress osteoblastic activity and may impair the mineralization process. Tiludronate was shown effective in reducing bone resorption in several metabolic bone diseases without inducing mineralization defects. Twenty paraplegic patients (6 females and 14 males) were randomly assigned to three groups: 6 patients entered the placebo group; 7 patients received tiludronate 200 mg/day; and 7 received 400 mg/day. Histomorphometric analysis was performed on transiliac bone biopsies before and after 3 months treatment An insignificant decrease of bone volume was observed in the placebo group and the 200 mg group. In patients receiving 400 mg/day, a slight increase was noted. Osteoid parameters changed nonsignificantly in three groups although the 400 mg group exhibited a slight tendency to decrease osteoid volume and thickness. Eroded surfaces increased in all groups. The number of osteoclasts (identified histochemically by TRAP staining) increased in the placebo group but decreased in groups receiving tiludronate. Tiludronate appears effective in reducing bone resorption without impairing bone formation in a manner that preserved bone mass and bone cell coupling.
Biosynthesis of bone sialoprotein by a human osteoclast-like cell line (FLG 29.1)
Authors: Masi Laura , Brandi Maria Luisa , Robey Pamela Gehron , Crescioli Clara , Calvo Juan Carlos , Bernabei Pietro , Kerr Janet M. , DR. Yanagishita Masaki 
Published: February 2010

Abstract
Biosynthesis of bone sialoprotein (BSP) by a human osteoclastic cell line (FLG 29.1) during its differentiation induced by phorbol 12-myristate 13-acetate (TPA) was studied using metabolic radiolabeling experiments. The FLG 29.1 cells were metabolically radiolabeled with [3H] glucosamine and [35S] sulfate, and the labeled glycoproteins were analyzed by anion exchange chromatography, sodium dodecyl sulfate—polyacrylamide gel electrophoresis (SDS-PAGE) and immunoprecipitation experiments. One of the major glycoproteins synthesized by the TPA-treated FLG 29.1 cells was sulfated, had an identical electrophoretic mobility to purified BSP, and could be immunoprecipitated with a specific antibody against human BSP (LF 6). Thus, this glycoprotein was tentatively identified as the BSP. Furthermore, mRNA for BSP was also detected in TPA-treated FLG 29.1 cells by RNA-polymerase chain reaction. Most BSP synthesized by FLG 29.1 cells remained cell-associated, and this is in contrast with those synthesized by osteoblasts, where the protein is rapidly released into the extracellular matrix. Immunocytochemistry using an anti-BSP antibody showed a prominent paranuclear (suggestive of Golgi apparatus) localization of BSP in the TPA-treated FLG 29.1 cells after permeabilization, while untreated cells were not significantly immunostained. Localization of BSP at the plasma membrane was also demonstrated in the TPA-treated FLG 29.1 cells by the fluorescence-activated cell sorting analysis. Since TPA has been demonstrated to induce expression of various osteoclastic characteristics in FLG 29.1 cells, induction of BSP expression by TPA suggests that the protein may play a role during the differentiation process of osteoclasts or in functions of differentiated osteoclasts.
Basic fibroblast growth factor regulates IGF-I binding proteins in the clonal osteoblastic cell line MC3T3-E1
Authors: Dr. Hurley Marja M. , Abreu Christine , Hakeda Yoshiyuki 
Published: February 2010

Abstract
In previous studies, we reported that basic fibroblast growth factor (bFGF) regulates insulin-like growth factor messenger RNAs and protein levels in the osteoblastic MC3T3-E1 cells. In the present study, we examined the expression of insulin-like growth factor binding proteins (IGFBPs) in MC3T3-E1 cells and determined whether bFGF altered IGFBP mRNAs and protein levels. Since previous studies suggested that IGFBPs can inhibit DNA synthesis stimulated by IGF-I, we wondered whether the mitogenic effect of bFGF was altered by exogenous IGFBP-3. Confluent MC3T3-E1 cells were serum-deprived for 24 h and then treated with bFGF for 6–24 h. In control cultures, MC3T3-E1 cells expressed the mRNAs for IGF-I, IGF-II, and IGFBP-2, 4, 5, and 6 but not IGFBP-1 or 3. A 24 h treatment with bFGF at 10−8 M decreased IGF-I mRNA by 97%, IGF-II mRNA by 73%, IGFBP-2 by 64%, IGFBP-4 by 73%, IGFBP-5 by 95%, and IGFBP-6 by 65%. The inhibitory effect of bFGF on IGF-I and IGFBP mRNA levels was not altered by aphidicolin, an inhibitor of cell replication. bFGF 10 nM decreased IGF-I levels determined by radioimmunoassay after acidification by 45% and 72% at 24 and 48 h, respectively. Western ligand blot for IGF binding proteins revealed that MC3T3-E1 cells expressed IGFBPs of 24, 30, and 34 kD. Treatment with bFGF 10−8 M decreased the levels of the 24 and 30 kD band at 24 h but increased the 34 kD band. Western immunoblot revealed that the 24 kD protein was IGFBP-4 and the 34 kD band was IGFBP-2. bFGF at 10−9-10−8 M increased thymidine incorporation into DNA (TdR) in a dose-dependent manner. When exogenous IGFBP-3 was added to the cultures there was a significant reduction in DNA synthesis while the mitogenic effect of bFGF was not blocked. In summary, bFGF not only regulates IGF-I mRNA and protein levels but it also regulates the IGF-II mRNA and mRNA and protein levels of the IGFBPs expressed in MC3T3-E1 cells. However, the mitogenic effect of bFGF may be independent of endogenous IGF-I. These results may be important in understanding the role of bFGF in bone cell function.
Ultrasound discriminates patients with hip fracture equally well as dual energy X-ray absorptiometry and independently of bone mineral density
Authors: Schott A.M. , Weill-Engerer S. , Hans D. , Duboeuf F. , Delmas P.D. , Meunier P.J. 
Published: February 2010

Abstract
We measured the heels of 43 women who had recently sustained a hip fracture and 86 age matched controls, using an Achilles® ultrasound device. Average BUA, SOS, and Stiffness were significantly lower in fractured patients (p &lt; 0.0001). We also estimated ultrasound parameters for patients as a function of controls and found the mean BUA to be −1.09 SD compared with controls, the mean SOS −0.89 SD, and the mean Stiffness −0.98 SD. Femoral BMD measured at the neck, Ward's triangle, and the trochanter with a DPX Plus® was also significantly lower in fractured patients (p &lt; 0.0001). The increased risk of hip fracture associated with low ultrasound values was estimated with logistic regression analysis for each bone parameter, adjusted for height and weight. The adjusted regression coefficients associated with BUA, SOS, Stiffness, and BMD were all significant (p &lt; 0.0001) demonstrating the influence of all ultrasound and DXA parameters on the risk of hip fracture. After adjusting the logistic regressions for BMD neck, BUA, SOS, and Stiffness were still significant independent predictors of hip fracture. Sensitivity and specificity of all measures were analyzed with the area under the ROC curve which were for BUA, 0.77 ± 0.04; for SOS, 0.75 ± 0.04; for Stiffness, 0.78 ± 0.04; and for BMD, 0.74 ± 0.04. We determined the range for the best compromise between sensitivity and specificity of BUA, 97–98 dB/MHz; SOS, 1482–1487 m/s; Stiffness 59–62% Young Adult; and of BMD, 0.64–0.69 g/cm. The area under the ROC curves of BUA, SOS, Stiffness, and DXA were compared and no statistically significant difference was found. Patients with trochanteric fractures had significantly lower ultrasound parameters than those with cervical fractures (SOS and Stiffness p = 0.001, BUA p = 0.009), whereas no significant difference was found for DXA parameters (BMD neck, BMD Ward, and BMD trochanter p ≥ 0.5). Some previous studies showed a lower bone density in patients with trochanteric fractures and suggested that the two types of fractures might correspond to a different process. Our results suggest that ultrasound is better correlated to the type of fracture than DXA, discriminates subjects with hip fracture equally well as DXA, and does indeed provide an indication of fracture risk independent of BMD.
Rheumatoid arthritis and bone mineral density in elderly women
Authors: Dr. Lane Nancy E. , Pressman Alice R. , Star Vicki L. , Cummings Steven R. , Nevitt Michael C. 
Published: February 2010

Abstract
Previous studies have suggested that women with rheumatoid arthritis (RA) have decreased bone mineral density (BMD) in both the appendicular and axial skeleton. The purpose of this investigation was to determine the association of RA and BMD from a community-based sample of ambulatory Caucasian women age 65 and over. BMD was measured by dual-energy X-ray absorptiometry (DXA) at the hip and lumbar spine and by single photon absorptiometry (SPA) at the distal radius and calcaneus. Study subjects included 120 postmenopausal women with RA who were further classified according to corticosteroid use, i.e., never users, current users, and ex-users, and 7966 age-similar controls. Elderly women with RA had a lower age-adjusted bone density of the distal radius, calcaneus, hip, and lumbar spine. Women with RA who were current users of steroids had the lowest BMD at both appendicular sites and at the hip, but those who never used steroids also had a significantly decreased BMD at all sites. The BMD of women with RA who had never used steroids remained significantly decreased at the distal radius, calcaneus, and hip after adjustment for age, BMD determinants, and functional outcomes of RA Functional outcomes of RA largely accounted for the lower BMD of women who were currently using steroids. Women with RA have lower appendicular and axial bone mass that is not attributable to the use of steroids. Those currently taking steroids have even lower appendicular and axial bone mass that may reflect their poorer functional outcome and is likely to increase the risk of fractures. Prevention of disability and avoidance of long-term steroid use may decrease the risk of fractures in elderly women with RA.
Tissue specificity and mechanism of vitamin D receptor up-regulation during dietary phosphorus restriction in the rat
Authors: Sriussadaporn Sutin , Wong Man-Sau , Pike Wesley J. , Favus Murray J. 
Published: February 2010

Abstract
Dietary phosphorus restriction up-regulates intestinal vitamin D receptor (VDR), but the tissue specificity of the up-regulation and the mechanism of receptor accumulation remain unknown. Therefore, the effects of low phosphorus diet (LPD) on VDR content in intestine, kidney, and splenic monocytes/macrophages were examined. Male Sprague-Dawley rats weighing 50–100 g were fed a normal diet (NPD; 0.6% Ca, 0.65% P) as controls followed by an LPD (0.6% Ca, 0.1% P) for 1–10 days (D1-D10). LPD rapidly decreased serum P levels by D1 from 11.11 ± 0.19 mg/dl (mean ± SE) to 4.98 ± 0.37 mg/dl (n = 9). LPD increased total serum Ca from 10.54 ± 0.09 mg/dl to 11.63 ± 0.15, 12.17 ± 0.15, and 12.39 ± 0.18 mg/dl by D1, D2, and D3, respectively, and then remained stable. Serum 1,25-(OH)2D3 rapidly increased from 123 ± 5.4 pg/ml to 304 ± 35 pg/ml by D1, reached a plateau through D5, and then gradually increased to 464.9 ± 27.7 pg/ml by D10. Intestinal VDR quantitated by ligand binding assay increased 3.5-fold from 169.6 ± 13.7 fmol/mg of cytosol protein in rats fed NPD (n = 12) to a peak of 588.3 ± 141.88 fmol/mg of protein by D3 (n = 6; p &lt; 0.001) and then decreased to a plateau level of 2.5-fold greater than NPD (p &lt; 0.05) during D5 to D10. In contrast, LPD did not up-regulate kidney or splenic monocyte/macrophage VDR. Northern blot analysis showed that intestinal VDR mRNA increased 2-fold by D2 (n = 3) of LPD and then gradually decreased to control levels after D5. In contrast, kidney VDR mRNA levels did not change during the first 5 days of P restriction and then subsequently decreased to 50% of NPD controls. The results of these studies indicate that VDR up-regulation during dietary phosphorus restriction is tissue-specific and that the mechanism of the up-regulation is time-dependent. Acutely (D1-D5), phosphorus restriction up-regulates intestinal VDR through increased VDR gene expression, whereas chronic (D5-D10) phosphorus restriction appears to alter VDR metabolism through nongenomic mechanisms that are consistent with prolongation of the half-life of the receptor. The nature of the tissue-specific regulation of VDR during phosphorus restriction remains to be determined.
Quantitative ultrasound and vertebral fracture in postmenopausal women
Authors: Bauer D.C. , Glüer C.C. , Genant H.K. , Stone K. 
Published: February 2010

Abstract
Quantitative ultrasound is a promising technique to evaluate fracture risk. To test the hypothesis that reduction of one ultrasound measurement, broadband ultrasound attenuation (BUA), is associated with an increased risk of vertebral fracture in postmenopausal women, we performed a cross-sectional analysis of 442 women aged 55–80 years enrolling in a clinical trial of alendronate. Prior to randomization, we obtained bone mineral density (BMD) measurements of the hip, spine, and whole body, radiographs of lateral lumbar and thoracic spine, and duplicate measurements of calcaneal BUA with a Walker Sonix UBA575. Vertebral fractures were defined by morphometry and semiquantitative reading by a radiologist. After adjustment for potential confounders, the relative risk of vertebral fracture was 1.8 (95% CI 1.4–2.3) for each standard deviation reduction in BUA; for each standard deviation reduction in BMD, the relative risk was 1.7 (95% CI 1.3–2.1) at the femoral neck, and 2.2 (95% CI 1.7–2.9) at the spine. Adjustment for hip, spine, or whole body BMD did not significantly alter the relation between BUA and vertebral fracture. For example, after adjusting for spine BMD, the relative risk of vertebral fracture was 1.5 (95% CI 1.1–2.0) for each standard deviation reduction in BUA. We conclude that low BUA is associated with the presence of vertebral fractures in postmenopausal women. The relation between BUA and vertebral fracture is similar to that observed for BMD and vertebral fractures. Furthermore, the relation between BUA and vertebral fracture persists after adjustment for BMD. Our findings suggest BUA measures qualities of bone that are in part independent of BMD, and thus may be useful alone or in combination with bone mass measurements in the prediction of vertebral fractures.