bluuebunny/crossref_metadata_2025_split huggingface dataset:
Osteoblastic Proliferation in Bone Biopsies from Patients with End-Stage Chronic Renal Failure
Authors: Dr. Serrano Sergio , Mariñoso Maria L. , Torres Armando , Lorenzo Victor , Keysers Ursula , Lloreta Jose , Nacher Montserrat , Garcia Carmen , Ballester Jorge , Diez Adolfo , Aubia Jaume 
Published: April 2006

Abstract
Osteoblasts have traditionally been considered to be terminally differentiated cells and therefore unable to divide. Data in recent years, however, indicate that cellular differentiation does not usually preclude preservation of proliferative ability and that most differentiated cells are able to divide under adequate stimuli. The aim of this study was to assess whether cubic osteoblasts undergo proliferation during the formation phase of the remodeling cycle under a stimulus that increased bone turnover. For that purpose, the osteoblastic proliferation index (OPI) was analyzed by DNA image cytometry in transiliac bone biopsies from 33 patients with chronic renal failure (23 men, 10 women; mean age 50.4 ± 15.1 years) who have been classified into low (n = 13), normal (n = 15), and high (n = 15) bone turnover according to activation frequency (Ac.f). OPI was significantly higher (p &lt; 0.002) in the high bone turnover group (13.90 ± 4.72%) compared with the low (2.38 ± 4.13%) and normal turnover groups (2.84 ± 4.04%). There was a positive correlation between OPI and the following histomorphometric parameters: bone formation rate, surface referent (r = 0.76, p = 0.00001), activation frequency (r = 0.73, p = 0.00001), mineral apposition rate (r = 0.73, p = 0.00001), bone formation rate, volume referent (r = 0.71, p = 0.00001), and mineralizing surface (r = 0.62, p = 0.0001). This study shows that a rise in bone turnover is associated with a marked increase of bone-forming cell proliferation in patients with end-stage chronic renal failure. From this finding, it may be concluded that cubic osteoblasts do not behave as “terminally differentiated” cells in vivo, because a high proportion of them are still able to divide.
Determinants of Radial Bone Density as Measured by PQCT in Pre- and Postmenopausal Women: The Role of Bone Size
Authors: Wapniarz Monika , Lehmann Reiner , Reincke Martin , Schönau Eberhard , Klein Klaus , Allolio Bruno 
Published: April 2006

Abstract
The aim of the present study was to examine the influence of anthropometric, hormonal, and geometric factors on the variability of radial bone mineral density (BMD) in women. In 583 healthy pre- and postmenopausal females (aged 40–60 years) radial total (BD) and trabecular BMD (TBD) was measured by peripheral quantitative computerized tomography at the nondominant distal forearm. In addition, 29 women who had suffered a Colles' fracture after minor trauma were also evaluated. There was no age-dependent change in radial BD and TBD before menopause. We found a negative correlation between BMD and age and years since menopause (YSM) in postmenopausal women (BD = 422.73 − 2.342 age − 6.308YSM; r = 0.36, p = 0.0001, n = 128). The variation of YSM, body mass index (BMI), and age accounted for 20% of the variability of BD in postmenopausal women. In contrast, in premenopausal women, only 3% of the variability could be explained by anthropometric variables. Bone mineral content (BMC) and bone area, but not BMD at the distal radius, were significantly correlated to grip strength (r = 0.25, p = 0.006 for BMC, r = 0.26, p = 0.003 for area). The cross-sectional bone area of the CT slice showed a significant increase with aging (y = 263.02 + 1.25x; r = 0.14, p = 0.0009). There was a strong negative correlation between bone area and BD and TBD (y = 516.04 − 0.668x; r = −0.57, p &lt; 0.0001 for BD). If BMD is normalized for BA, variation is reduced by 32% (for BD) and 10% (for TBD), respectively. Women with Colles' fracture had a significantly lower TBD normalized for BA (fracture group [−0.71 ± 0.88] vs. normals [0.03 ± 0.99]; p = 0.00009). Our results show that YSM and BMI are predictors of postmenopausal BMD. However, radial BMD is influenced strongly by geometric variables such as cross-sectional bone area.
Prostaglandin E2 (PGE2) and Risedronate Was Superior to PGE2 Alone in Maintaining Newly Added Bone in the Cortical Bone Site After Withdrawal in Older Intact Rats
Authors: Ma Yan Fei , Lin Bai Yun , Jee Webster S. S. , Lin Chao Hua , Chen Yong Yong , Ke Hua Zhu , Li Xiao Jian 
Published: April 2006

Abstract
The objects of this study were (1) to determine the effects of risedronate (Ris) and prostaglandin E2 (PGE2) alone and in combination, on tibial diaphyses of older intact female rats; and (2) to observe the fate of any extra bone if formed after withdrawal of the treatment. Nine-month-old female Sprague-Dawley rats were treated with 6 mg of PGE2/kg/day, 1 or 5 μg of Ris/kg twice a week, or 6 mg of PGE2/kg/day plus 1 or 5 μg of Ris/kg twice a week for the first 60 days and followed by vehicle injections for another 60 days. Cross-sections of double fluorescent labeled, undecalcified tibial diaphyses proximal to the tibiofibular junction were processed for histomorphometry. We found that: (1) neither the 1 μg nor the 5 μg of Ris treatment in the 60-day on/60-day off group showed any histomorphometric differences from age-related controls; (2) while the 60 days of PGE2 treatment added extra cortical bone (6%) on the tibial shaft (due to stimulation of periosteal, endocortical, and marrow trabecular bone formation), the new endocortical and most of the new marrow trabecular bone were lost when treatment was withdrawn; however, the new periosteal bone remained; (3) PGE2 with Ris added the same amount of new bone to tibial diaphysis as did PGE2 alone and upon withdrawal, new marrow trabecular bone was lost but new periosteal and endocortical bones were preserved in PGE2 + 1 μg of Ris on/off group. In contrast, all the new bone was maintained in the PGE2 + 5 μg of Ris on/off group; (4) PGE2 + Ris cotreatment failed to block the increase in cortical bone porosity induced by PGE2; and (5) in the PGE2 alone and PGE2 + 1 μg of Ris on/off groups bone turnover was higher than that in the PGE2 + 5 μg of Ris on/off group. These results indicate that on/off treatment with PGE2 and Ris is superior to PGE2 alone in that it forms the same amount of new bone during treatment, but preserves more cortical bone during withdrawal. Depression of bone resorption and turnover were the tissue mechanisms responsible for this protection.
Phenotypic Heterogeneity of Osteoblast-like MC3T3-E1 Cells: Changes of Bradykinin-Induced Prostaglandin E2 Production During Osteoblast Maturation
Authors: Dr. Leis Hans J. , Hulla Wolfgang , Gruber Reinhard , Huber Evelyn , Zach Doris , Gleispach Helmut , Windischhofer Werner 
Published: April 2006

Abstract
We have examined clonal murine calvarial MC3T3-E1 cells obtained from different sources to compare their osteoblastic features (alkaline phosphatase [ALP], cyclic adenosine monophosphate [cAMP] response to parathyroid hormone, prostaglandin E2 (PGE2) and PGE1, bradykinin-induced production of PGE2). It was found that the sublines investigated showed large variation of the above-mentioned parameters, which may be attributed to distinct differentiated stages of osteoblast development. Increase of ALP activity was paralleled by an increase in cAMP accumulation in response to the above-mentioned agents. The most striking difference was observed with bradykinin-induced production of PGE2. Early stage cells (low ALP) produced high levels of PGE2, whereas cells with high ALP activity showed no bradykinin stimulation at all. This was consistent with the results of specific binding of3H-bradykinin to its receptor and also correlated well with the bradykinin-induced signal transduction sequence (inositol triphosphate liberation and elevation of intracellular calcium levels). This was confirmed by Northern blot analysis of bradykinin receptor mRNA expression. These results indicate that the widely used osteoblast-like cell line MC3T3-E1 is synonymous for multiple sublines, representing different stages of osteoblast development. These sublines were most likely emerging from the early stage cell line due to the applied culture conditions. Moreover, distinct biochemical features are displayed in correlation to the differentiation stage, thus providing a useful model to study the molecular mechanism of osteoblast maturation.
Episodic Secretion of Parathyroid Hormone in Postmenopausal Women: Assessment by Deconvolution Analysis and Approximate Entropy
Authors: Dr. Samuels M. H. , Veldhuis J. D. , Kramer P. , Urban R. J. , Bauer R. , Mundy G. R. 
Published: April 2006

Abstract
In healthy young subjects, parathyroid hormone (PTH) is secreted presumptively in a dual fashion, with low amplitude pulses apparently superimposed on tonic secretion. In contrast, PTH secretion has not been as well characterized in postmenopausal women, and relationships among bone density, estrogen status, and PTH release have not been explored. It is possible that a pulsatile pattern of PTH secretion is important for bone remodeling, since exogenous PTH administered in a pulsatile manner stimulates bone formation. To assess the importance of pulsatile PTH secretion as a determinant of bone mass, we measured PTH in blood sampled every 2 minutes for 6 h in four groups of older women: (1) high bone density receiving estrogen (n = 6), (2) high bone density not receiving estrogen (n = 5), (3) low bone density receiving estrogen (n = 6), and (4) low bone density not receiving estrogen (n = 8). The plasma PTH release profiles were subjected to deconvolution analysis, which resolves measured hormone concentrations into secretion and clearance components, and to an approximate entropy (ApEn) estimate, which provides an ensemble measure of the serial regularity or orderliness of the release process. In postmenopausal subjects, PTH was secreted in a fashion similar to that observed in young adults, with significant tonic secretion and PTH pulse occurrences averaging every 18–19 minutes. Pulsatile PTH secretion accounted for approximately 25% of the total secreted PTH. There were no differences in the amplitude or frequency of pulsatile PTH secretory parameters or in ApEn values among the four groups or compared with young controls. We conclude that in postmenopausal women, PTH secretory patterns and temporal organization are similar to those in healthy young subjects and are not altered in states of low bone density or estrogen deficiency. This suggests that abnormalities in orderly pulsatile PTH secretion are unlikely to play a major role in established postmenopausal osteoporosis.
A New Trabecular Region of Interest for Femoral Dual X-Ray Absorptiometry: Short-Term Precision, Age-Related Bone Loss, and Fracture Discrimination Compared with Current Femoral Regions of Interest
Authors: Takada Masahiko , Grampp Stephan , Ouyang Xiaolong , Engelke Klaus , Genant Harry K. 
Published: April 2006

Abstract
We defined a new region of interest (ROI) for femoral Ward's triangle, centered on the femoral neck axis including comparatively trabecular-rich bone. Forty-seven premenopausal, 39 healthy postmenopausal, and 35 osteoporotic postmenopausal women with vertebral fractures were evaluated comparing the new with the standard femoral ROIs, using a Hologic QDR-2000. Additionally, spinal dual X-ray absorptiometry (DXA) was performed. The short-term precision error of the new ROI expressed as the root mean square of the coefficient of variations was 1.34% for premenopausal women, 1.69% for healthy postmenopausal women, and 2.46% for osteoporotic postmenopausal women. Bone mineral density (BMD) values of the new ROI correlated highly with those of the standard femoral ROIs (r = 0.91 − 0.96) and the spinal BMD (r = 0.74). Age-related bone loss of the new ROI was 0.75% per year (r = 0.66) in healthy women, which was approximately 1.5 times higher than the bone loss of the standard femoral ROIs, except for Ward's triangle. Regarding the intergroup discrimination, the t-value of the new ROI was similar to the t-value of Ward's triangle, and the intergroup percent decrements in BMD of the new ROI approximated those of Ward's triangle. For discriminating women with vertebral fractures, the new ROI demonstrated odds ratios of 1.6 similar to most ROIs but lower than that of the trochanteric region. The new, substantially trabecular ROI appears to be an alternative to the Ward's ROI traditionally used in femoral DXA having improved short-term precision and comparable sensitivity.
Synovial Fluids from Patients with Osteoarthritis and Rheumatoid Arthritis Contain High Levels of Parathyroid Hormone–Related Peptide
Authors: Kohno Hiroaki , Shigeno Chohei , Kasai Ryuichi , Akiyama Haruhiko , Iida Hirokazu , Tsuboyama Tadao , Sato Kanji , Konishi Junji , Nakamura Takashi 
Published: April 2006

Abstract
High levels of immunoreactive and biologically active parathyroid hormone–related peptide (PTHrP) were detected in synovial fluids from patients with osteoarthritis (OA) and rheumatoid arthritis (RA). The levels of PTHrP immunoreactivity in synovial fluids, measured by a two-site immunoradiometric assay (IRMA) which detects hPTHrP(1–72) or longer peptides and a radioimmunoassay (RIA) specific to the carboxy-terminal portion of hPTHrP, were 3.2 ± 0.3 pmol of hPTHrP(1–86)/l and 61 ± 7.0 pmol of hPTHrP(109–141)/l in OA patients (mean ± SE, n = 23), and 4.8 ± 0.8 pmol of hPTHrP(1–86)/l and 164 ± 30 pmol of hPTHrP(109–141)/l in RA patients (n = 26). Synovial fluid PTHrP levels distributed above the normal plasma reference ranges in each assay (0.7–2.6 pmol of hPTHrP(1–86)/l; 16–60.6 pmol of hPTHrP(109–141)/l). After concentration using sequential cation-exchange and reverse-phase chromatography, synovial fluid exhibited the activity that stimulated cyclic adenosine monophosphate (cAMP) accumulation in osteoblastic ROS 17/2.8 cells expressing PTH/PTHrP receptors. The cAMP accumulation activity in synovial fluid was sensitive to coincubation with excess hPTHrP(3–40), a PTH/PTHrP receptor antagonist, and was completely neutralized by preincubation with a monoclonal antibody specific to hPTHrP but not PTH. Immunohistochemical analysis of RA synovium revealed that PTHrP was localized in fibroblast-like cells in the synovial pannus invading articular cartilage. Our data show that PTHrP is produced locally by the diseased synovial tissue and released into synovial fluid at high concentrations, allowing us to hypothesize that PTHrP plays a novel role as a paracrine/autocrine factor in the pathology of OA and RA.
Altered Regulation of Parathyroid Hormone Secretion by Calcium in Pregnant and Lactating Rats
Authors: Schultz Vijitha L. , Boass Agna , Garner Sanford C. , Toverud Svein U. 
Published: April 2006

Abstract
We have previously shown that the serum parathyroid hormone (PTH) concentration in lactating (L) rats is not suppressed by high serum Ca2+ to the same extent as in nonmated (NM) rats. To investigate further Ca2+ regulation of PTH secretion, parathyroid cells from NM rats and rats in late pregnancy and at peak lactation were dispersed and incubated for 2 h in medium containing 0.52–2.05 mM Ca2+. Medium PTH was assayed with a homologous immunoradiometric assay (IRMA). At the two highest Ca2+ levels (1.81 and 2.05 mM), medium PTH was significantly higher (p = 0.031) for cells from L rats than for cells from NM rats. In contrast, significantly less (p &lt; 0.001) PTH was secreted for the L group versus the NM group at medium Ca2+ values of 1.27 and 1.46 mM. Estimated set points for L and NM groups were 1.17 mM and 1.35 mM, respectively, corresponding closely to the prevailing serum Ca2+ for these two groups. Consistent with the present in vitro data, high serum PTH (&gt;40 pg/ml) in L rats occurred only at serum Ca2+ values below 1.27 mM. Elevated serum PTH at lower serum Ca2+ levels was also seen in pregnant rats. Dispersed parathyroid cells from 20− to 21-day pregnant rats secreted significantly more PTH (p = 0.028) than cells from NM rats at all Ca2+ levels tested (1.1–1.6 mM). In conclusion, the relationship between extracellular Ca2+ and PTH secretion is altered in rats during late pregnancy and at peak lactation, perhaps as part of the adaptation to the demands for calcium for pre- and postnatal growth.
Electrophysiological Responses of Human Bone Cells to Mechanical Stimulation: Evidence for Specific Integrin Function in Mechanotransduction
Authors: Salter D. M. , Robb J. E. , Wright M. O. 
Published: April 2006

Abstract
Bone cells respond to mechanical stimuli, but the transduction mechanisms responsible are not fully understood. Integrins, a family of heterodimeric transmembrane glycoproteins, which link components of the extracellular matrix with the actin cytoskeleton, have been implicated as mechanoreceptors. We have assessed the roles of integrins in the transduction of cyclical mechanical stimuli to human bone cells (HBCs), which results in changes in membrane potential. HBC showed membrane depolarization following 0.104 Hz mechanical stimulation and membrane hyperpolarization following stimulation at 0.33 Hz. The membrane depolarization response involved tetrodotoxin-sensitive sodium channels and could be inhibited by antibodies against αV, β1, and β5 integrins. In contrast, the hyperpolarization response was inhibited by gadolinium and antibodies to the integrin-associated protein (CD47), α5 and β1 integrin. Both responses could be abrogated by Arg-Gly-Asp (RGD)-containing peptides, inhibition of tyrosine kinase activity, and disruption of the cytoskeleton. These results demonstrate differential electrophysiological responses of HBC to different frequencies of mechanical strain. Furthermore, they suggest that integrins act as HBC mechanoreceptors with distinct signaling pathways being activated by different frequencies of mechanical stimuli.
Differential Effects of Nonsteroidal Anti-Inflammatory Drugs on Constitutive and Inducible Prostaglandin G/H Synthase in Cultured Bone Cells
Authors: Pilbeam Carol C. , Fall Pamela M. , Alander Cynthia B. , Raisz Lawrence G. 
Published: April 2006

Abstract
The production of prostaglandins by osteoblasts is an important mechanism for the regulation of bone turnover. Bone cells contain both inducible and constitutive prostaglandin G/H synthase (PGHS-2 and PGHS-1) and these are differentially regulated. Nonsteroidal anti-inflammatory drugs (NSAIDs), which selectively inhibit one of these enzymes, would be useful in assessing their relative roles in bone metabolism. By Northern analysis, only PGHS-2 is expressed by the immortalized rat osteoblastic cell line, Py1a, while only PGHS-1 is expressed by the rat osteosarcoma cell line, ROS 17/2.8. We tested the relative inhibitory potency (IC50) of seven different NSAIDs on these two cell lines. A recently described selective inhibitor of PGHS-2, NS-398, was approximately 30 times more potent in inhibiting PGHS-2 than PGHS-1, and diclofenac was approximately 10 times more potent. Both had IC50's of approximately 3 nM for PGHS-2 in Py1a cells. Indomethacin, flurbiprofen, naproxen, and piroxicam were relatively nonselective with IC50's ranging from 30 nM to 1 μM, while 6-methoxy-2 naphthyl acetic acid, the active metabolite of nabumetone, was inhibitory only at concentrations greater than 1 μM. These results indicate that the presently available NSAIDs are unlikely to distinguish completely between effects mediated by PGHS-2 or PGHS-1. However, the cell systems employed could provide a model for the analysis of new compounds with greater selective activity.
Effects of a New Positioner on the Precision of Hip Bone Mineral Density Measurements
Authors: Hans D. , Duboeuf F. , Schott A. M. , Horn S. , Avioli L. V. , Drezner M. K. , Meunier P. J. 
Published: April 2006

Abstract
In an attempt to reduce patient positioning errors, the authors tested the use of a new hip-specific positioning tool, OsteoDyne's Hip Positioner System (HPS). The HPS is an “A” frame splint designed to abduct both legs approximately 15° to hold them in full extension at the hips and knees and to lock the feet in a neutral position. Seventy volunteer women aged 35–82 years were randomly assigned in two age-matched groups (mean age 56 years). Each group underwent two consecutive femur dual X-ray absorptiometry (DXA) scans with intermediate repositioning using the HPS system and two others utilizing the standard hip positioner provided with Hologic and Lunar scanners. One technician performed all scans using a Hologic QDR 1000-Plus and Lunar DPX-Plus densitometer. One hundred and fifty volunteer women aged 50–84 years (mean age, 64 years) were recruited in a multicenter study for the assessment of precision. Each subject underwent three consecutive femur DXA scans with intermediate repositioning using the HPS system. The coefficient of variation (CV) was significantly improved at the femoral neck by the use of the HPS with 0.7 versus 1.2 with the Hologic densitometer but only moderately altered at other sites. Similar results were found with the Lunar densitometer with improvement of precision at the femoral neck, 0.8 versus 1.8 with a similar trend but no significant difference at the other regions. No statistical difference was noted between the femoral neck BMD measured with the HPS system and with the standard positioners in either group. The mean precision of data obtained on the QDR 1000+ was 0.8% (range 0.1–1.4) for the femoral neck BMD, 1.1% (range 0.1–3.0) for the trochanter BMD, 2.3% (range 0.2–5.2) for Ward's triangle BMD, and 0.8% (range 0.1–1.9) for the total femur BMD. The mean precision of data obtained on the QDR 2000 was 0.7% (range 0.1–2), 1% (range 0.1–4.9), 2.6% (range 0.3–5.7), and 0.7% (range 0.1–1.8), respectively. In conclusion, data obtained with the new OsteoDyne's HPS seem capable of reducing patient positioning errors for the hip measurement. Its use is likely to improve confidence in hip bone mineral density measurements.
Mechanical Stimulation of Tissue Repair in the Hydraulic Bone Chamber
Authors: Guldberg R. E. , Caldwell N. J. , Guo X. E. , Goulet R. W. , Hollister S. J. , Goldstein S. A. 
Published: April 2006

Abstract
A hydraulically activated bone chamber model was utilized to investigate cellular and microstructural mechanisms of mechanical adaptation during bone repair. Woven trabecular bone and fibrotic granulation tissue filled the initially empty chambers by 8 weeks postimplantation into canine tibial and femoral metaphyses. Without mechanical stimulation, active bone remodeling to lamellar trabecular bone and reconstitution of marrow elements were observed between 8 and 24 weeks. In subsequent loading studies, the hydraulic mechanism was activated on one randomly chosen side of 10 dogs following 8 weeks of undisturbed bone repair. The loading treatment applied an intermittent compressive force (18 N, 1.0 Hz, 1800 cycles/day) for durations of a few days up to 12 weeks. Stereological analysis of three-dimensional microcomputed tomography images revealed an increase in trabecular plate thickness and connectivity associated with the loaded repair tissue microstructure relative to unloaded contralateral controls. These microstructural alterations corresponded to an over 600% increase in the apparent modulus of the loaded bone tissue. A significant increase in the percentage of trabecular surfaces lined by osteoblasts immunopositive for type I procollagen after a few days of loading provided further evidence for mechanical stimulation of bone matrix synthesis. The local principal tissue strains associated with these adaptive changes were estimated to range from approximately −2000 to +3000 μstrain using digital image-based finite element methods. This study demonstrates the sensitivity of bone tissue and cells to a controlled in vivo mechanical stimulus and identifies microstructural mechanisms of mechanical adaptation during bone repair. The hydraulic bone chamber is introduced as an efficient experimental model to study the effects of mechanical and biological factors on bone repair and regeneration.