bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crush fracture syndrome in senile osteoporosis: A nutritional consequence?
Authors: Prof. Dr. Rico H. , Revilla M. , Villa L. F. , Hernandez E. R. , Fernandez J. P. 
Published: February 2010

Abstract
Osteoporosis is a very important age-related health problem. The body's composition changes with age, and these changes are a true reflection of aging and of the individuals's nutritional status. Mineral content changes have been reported in vertebral osteoporosis. Interestingly, enough, there have not been reports on concomitant water, fat, and fat-free mass changes associated with this condition. In this report, changes in the latter parameters are compared between patients with osteoporosis and controls. The four components (water, mineral, fat, and fat-free mass) were found significantly reduced (p &lt; 0.001) in osteoporosis. Serum albumin and protein mass were also reduced (p &lt; 0.001).
An assay system utilizing devitalized bone for assessment of differentiation of osteoclast progenitors
Authors: Amano Shigeru , Hanazawa Shigemasa , Kawata Yasuhiro , Ohta Kazuzo , Kitami Hidekazu , Kitano Shigeo 
Published: February 2010

Abstract
The present study provides a novel assay system to examine the differentiation of osteoclast progenitors on devitalized bone slices. We used the population of bone cells liberated enzymatically from 14-day-old mouse embryonal calvariae as a source of osteoclast progenitors. The analysis of differentiation of osteoclast progenitors into preosteoclasts and mature osteoclasts was assessed in terms of the formation of TRAP-positive cells and pits or resorption lacunae, respectively, on devitalized bone slices. Osteoclasts having bone-resorbing activity appeared when the calvarial cell population was cultured in the presence of 1α,25-(OH)2D3 on devitalized bone slices. The resorbing activity increased in a 1α,25-(OH)2D3 dose-related manner. However, calcitonin, a potent inhibitor of differentiation and activation of osteoclast lineage cells, reduced the area of the resorption lacunae in a dose-dependent fashion. The bone-resorbing cells on the bone slices expressed an obvious ruffled border and clear zone, structures specific to mature osteoclasts. These results suggest that osteoclast progenitors in the mouse calvarial population examined differentiated into mature osteoclasts in the presence of 1α,25-(OH)2D3 on devitalized bone slices. Further, using this assay system we assessed the effect of some other osteotropic factors on the differentiation of osteoclast progenitors to mature osteoclasts. IL-1, IL-6, and PTH increased the formation of TRAP-positive cells and pits and the area of resorption lacunae in a dose-dependent fashion. However, prostaglandin E2 was unable to induce the formation of resorption lacunae, although a significant appearance of TRAP-positive cells was observed at a concentration of 200 ng/ml. In contrast, the stimulating effect of these osteotropic factors on the formation of resorption lacunae was inhibited significantly by indomethacin treatment (200 ng/ml). This novel assay system is thus useful for study of the differentiation of osteoclast progenitors to preosteoclasts and mature osteoclasts on devitalized bone slices and also for assessment of the effect of cytokines and hormones on the differentiation of osteoclast progenitors.
Influence of prostaglandins on DNA and matrix synthesis in growth plate chondrocytes
Authors: O'Keefe Regis J. , Crabb Ian D. , Puzas J. Edward , Rosier Randy N. 
Published: February 2010

Abstract
Prostaglandins are locally produced in a number of tissues in response to a variety of stimuli, including local growth factors and systemic hormones. The present investigation characterizes prostaglandin effects on growth plate chondrocytes. Since cyclic adenosine monophosphate (cAMP) may act as a prostaglandin-stimulated second messenger, the effects of prostaglandins A1, D2, E1, E2, F2α, and I2 (10−10-10−6 M) on cAMP levels and thymidine incorporation were evaluated. The stimulation of cAMP and thymidine incorporation by the various prostaglandin metabolites were dose dependent and highly correlated (r = 0.99, p &lt; 0.001). The magnitude of the effect varied but was maximal at 10−6 M for each of the prostaglandins. Prostaglandins of the E series (E1 and E2) were the most potent, causing significant effects at 10−10 M and with maximal 12- and 13-fold increases in DNA synthesis after a 24 h exposure. Prostaglandins D2 and A1 maximally stimulated thymidine incorporation by 4.7- and 3.1-fold but caused significant increases only at 10−8 M. Prostaglandins F2α and I2 were the least stimulatory, producing small but significant increases in thymidine incorporation at 10−6 M (30 and 100% stimulations). A causal relationship between cAMP and thymidine incorporation was further verified by the ability of dibutyryl-cAMP to increase DNA synthesis. Long-term chondrocyte cultures treated continuously with PGE2 demonstrated an increase in cell number, confirming the proliferative effect. Indomethacin did not alter the potent dose-dependent stimulations of chondrocyte DNA synthesis by TGF-β1, basic FGF, or PTH, indicating that these known mitogens act independently of prostaglandin metabolism. PGE2 was further examined for its effects of matrix synthesis. PGE2 inhibited collagen synthesis with a maximal 42% decrease but did not alter noncollagen protein synthesis. In contrast, PGE2 maximally increased sulfate incorporation by 35% and caused a small dose-dependent inhibition in alkaline phosphatase activity. Thus, prostaglandins alter DNA and matrix synthesis in growth plate chondrocytes and may have an important role in chondrocyte metabolism in the growth plate, fracture callus, and other areas of endochondral ossification.
Contribution of vertebral deformities to chronic back pain and disability
Authors: Ettinger Bruce , Black Dennis M. , Nevitt Michael C. , Rundle Amy Chen , Cauley Jane A. , Cummings Steven R. , Genant Harry K. 
Published: February 2010

Abstract
Among 2992 white women aged 65–70 years recruited from population-based listings, we measured radiographic vertebral dimensions of T5–L4 and calculated ratios of heights: anterior/posterior, mid/posterior, and posterior/posterior of either adjacent vertebra. The degree of deformity for each vertebra was analyzed in terms of the number of standard deviations (SD) that ratio differed from the mean ratio calculated for the same vertebral level in this population. We correlated the severity of each woman's worst vertebral deformity with back pain, back disability in six activities of daily living, and height loss since age 25. Only 39.4% of the cohort had no vertebral deformity; 10.2% had a deformity ≥ 4 SD. Vertebral deformities &lt; 4 SD below the mean were not associated with increased back pain, disability, or loss of height. In contrast, women whose deformity was ≥ 4 SD had a 1.9 (95% CI, 1.5–2.4) times higher risk of moderate to severe back pain and a 2.6 (95% CI, 1.7–3.9) times higher risk of disability involving the back; they were also 2.5 (95% CI, 2.0–3.2) times more likely to have lost ≥ 4 cm in height. All three types of vertebral deformity (wedge, end plate, and crush) were equally associated with these outcomes. Multiple deformities &lt; 4 SD did not increase the likelihood of these three outcomes, but multiple deformities &gt;≥ 4 SD tended to be associated with increased back pain, disability, and height loss. This large cross-sectional study suggests that vertebral deformities cause substantial pain, disability, or loss of height only if vertebral height ratios fall 4 SD below the normal mean. Much back pain could not be attributed to vertebral deformities, suggesting other causes.
Intermittent administration of bovine PTH-(1–34) increases serum 1,25-dihydroxyvitamin D concentrations and spinal bone density in senile (23 month) rats
Authors: Mitlak Bruce H. , Williams Daniel C. , Bryant Henry U. , Paul Donald C. , Neer Robert M. 
Published: February 2010

Abstract
We examined the effect of intermittent administration of bovine parathyroid hormone (1–34) (bPTH) on spinal bone mineral content (BMC) and bone mineral density (BMD), serum 1,25-dihydroxyvitamin D concentrations, and serum markers of osteoblast function in senile male and female rats (23 and 24 months of age, respectively). Sexually mature young (3 month) male rats were similarly treated for comparison. bPTH administration increased serum osteocalcin concentrations without changing serum inorganic phosphate or calcium concentrations in either group of old animals. In young animals, PTH administration increased the serum calcium and inorganic phosphate concentrations significantly (p &lt; 0.05), although values remained within the normal range. In the vehicle-treated male rats, serum 1,25-dihydroxyvitamin D concentrations were lower in the senile than in the young animals (18 ± 5 versus 47 ± 6 pg/ml, p &lt; 0.05). PTH administration resulted in significantly increased serum 1,25-dihydroxyvitamin D concentrations in the senile and young male animals (both, p &lt; 0.05) and the final mean serum 1,25-dihydroxy vitamin D concentrations were not statistically different (68 ± 9 versus 85 ± 6 pg/ml respectively; p = NS). Serum 1,25-dihydroxyvitamin D concentrations were significantly (p &lt; 0.05) higher in the PTH-treated senile female rats than the sex-matched, vehicle-treated controls. The pretreatment spinal BMC and BMD as assessed by dual-energy x-ray absorptiometry (DEXA) were significantly higher in the senile male animals than in the young animals. Spinal BMC and BMD decreased in the vehicle-treated senile male rats (p &lt; 0.05) over the 3 weeks of the study despite a gain in weight. bPTH administration prevented this fall in spinal BMC and increased spinal BMD (p &lt; 0.05). Spinal BMC and BMD increased significantly (p &lt; 0.05) in the young vehicle-treated rats, and PTH administration caused a further significant increase in both parameters of bone mass. Spinal BMD was significantly (p &lt; 0.05) higher in the PTH-treated senile female rats than in vehicle-treated controls. These findings demonstrate that intermittent PTH administration increases serum 1,25-dihydroxyvitamin D concentrations of senile animals to the levels of PTH-treated, young, sexually mature animals. In addition, PTH administration arrests bone loss and increases spinal BMD of senile rats.
Effect of dietary phosphate deprivation and supplementation of recipient mice on bone formation by transplanted cells from normal and X-linked hypophosphatemic mice
Authors: Ecarot B. , Glorieux F.H. , Desbarats M. , Travers R. , Labelle L. 
Published: February 2010

Abstract
The hypophosphatemic (Hyp) mouse is the murine homolog for human hypophosphatemic vitamin D-resistant rickets. We previously reported that bone cells isolated from normal and Hyp mice produced abnormal bone when transplanted intramuscularly into mutant mice. To assess the role of hypophosphatemia on bone formation in transplants, normal and Hyp mouse periostea were pair transplanted into control or phosphate (P)-supplemented Hyp mice and into control or P-deprived normal mice. The bone nodules formed in transplants after 2 weeks were characterized by measuring the thickness of the surrounding osteoid seams and the relative osteoid volume. P restriction in normal recipient mice impaired bone formation by transplanted normal cells and aggravated the defective bone formation by Hyp cells. The osteoid thickness and volume remained significantly higher in Hyp transplants than in normal cotransplants, however. P supplementation of Hyp recipient mice normalized bone formation by transplanted normal cells but not by Hyp cells. However, a marked decrease in osteoid thickness and volume was observed in Hyp transplants down to values observed in normal recipient mice. These results indicate that hypophosphatemia is not the only cause of abnormal bone formation in the Hyp mouse but that an osteoblast dysfunction contributes to the bone disease. These observations further support the concept that the osteoblast may be an important target for the Hyp mutation.
Effect of transforming growth factor β on parathyroid hormone receptor binding and cAMP formation in rat osteosarcoma cells
Authors: Seitz Patricia K. , Zhu Bao-Ting , Cooper Cary W. 
Published: February 2010

Abstract
Transforming growth factor β (TGF-β) is now recognized as an important growth regulator and modulator in bone, where it apparently acts in an autocrine or paracrine fashion. In an effort to help elucidate how TGF-β may interact with parathyroid hormone (PTH) to influence bone turnover, we examined the idea that TGF-β might alter the number or affinity of PTH receptors in osteoblastic bone cells, PTH receptor binding was assessed in cultured ROS 17/2.8 cells using [125I]PTHrP-(1–34) as labeled ligand. Specific binding to intact cells was measured in the presence of up to 1 μM unlabeled rPTH-(1–34), and cAMP in cell extracts was determined by RIA. Incubation of ROS cells with 2 ng/ml of TGF-β for the maximally effective time of 3 days increased the number of PTH binding sites (Bmax) by 47 ± 13%, with no change in the Kp (3 nM). TGF-β also increased the intracellular cAMP response to 0.3 nM rPTH-(1–34) (ED50) by 53 ± 22%. Both effects were dose dependent, with 1–4 ng/ml of TGF-β producing maximal effects, and both effects were blocked by the protein synthesis inhibitor cycloheximide (2–5 μM). Since TGF-β induced comparable increases in both PTH binding and cAMP formation, the findings suggest that TGF-β can increase the number of functional PTH receptors in cultured ROS 17/2.8 cells. This effect may reflect an action of TGF-β to slow replication and promote differentiated functions in these cells.
Bone mineral density in elderly men and women: Results from the framingham osteoporosis study
Authors: Hannan Marian T. , Felson David T. , Anderson Jennifer J. 
Published: February 2010

Abstract
Our study investigated bone mineral density of the proximal femur and ultradistal and proximal radius in a population of elderly men and women. The Framingham study started in 1948, following a population-based sample for evaluation of cardiovascular risk factors and events. During the 20th biennial Framingham examination (1988–89) we conducted the Framingham osteoporosis study, measuring bone mineral density in the proximal femur and distal and proximal radius for 1154 study participants. Ages ranged from 68 to 98 years, with a mean age of 76 years. Bone mineral density was measured using Lunar SP2 and DP3 densitometers. This cross-sectional study evaluates mean bone mineral density measurements at each site by 5 year age intervals for men and women, testing for trends in bone density with age. Analyses were repeated adjusting for weight and height. Among the 446 and 708 women, bone mineral density of the femur and bone mineral content of the proximal radius were inversely and significantly related to age in both sexes and were considerably higher in men than women at all sites. The linear decline with age group in our cross-sectional study remained after multivariate adjustment for height and weight. The ultradistal radius showed no significant correlation with age for either sex. There were significant correlations between the bone measurements made at different sites for both men and women (range in r = 0.27–0.89). Cross-sectional curves of bone mineral density with age showed no significant differences in slope between males and females. In this cross-sectional study, we found that increased age was significantly associated with decreased bone mass in a linear and equivalent fashion for both men and women through the elderly years in the proximal femur and proximal radius.
Appendicular bone mineral and a woman's lifetime risk of hip fracture
Authors: Black Dennis M. , Cummings Steven R. , Melton L. Joseph 
Published: February 2010

Abstract
Appendicular bone mass is inversely related to the risk of hip fracture in short-term prospective studies, but hip fractures typically occur about 30 years after menopause. We developed a model that estimates a woman's lifetime risk of hip fracture based on measurement of radial bone mass at age 50 using short-term prospective data relating bone mass to hip fracture, the correlation between bone mass at age 50 and later years, the age-specific incidence of hip fracture and mortality, and prospective data about bone mass and mortality. We estimate that a 50-year-old white woman has a 19% lifetime risk of hip fracture if her radial bone mass is at the 10th percentile for her age and an 11% lifetime risk if her bone mass is at the 90th percentile. Improved measurement techniques that have a higher predictive value for hip fracture in short-term studies could substantially increase this gradient of lifetime risk and therefore be more clinically useful.
Distinct proliferative and differentiated stages of murine MC3T3-E1 cells in culture: An in vitro model of osteoblast development
Authors: Quarles L. Darryl , Yohay Daniel A. , Lever Laura W. , Caton Rashmi , Wenstrup Richard J. 
Published: February 2010

Abstract
We examine clonal murine calvarial MC3T3-E1 cells to determine if they exhibit a developmental sequence similar to osteoblasts in bone tissue, namely, proliferation of undifferentiated osteoblast precursors followed by postmitotic expression of differentiated osteoblast phenotype. During the initial phase of developmental (days 1–9 of culture), MC3T3-E1 cells actively replicate, as evidenced by the high rates of DNA synthesis and progressive increase in cell number, but maintain a fusiform appearance, fail to express alkaline phosphatase, and do not accumulate mineralized extracellular collagenous matrix, consistent with immature osteoblasts. By day 9 the cultures display cuboidal morphology, attain confluence, and undergo growth arrest. Downregulation of replication is associated with expression of osteoblast functions, including production of alkaline phosphatase, processing of procollagens to collagens, and incremental deposition of a collagenous extracellular matrix. Mineralization of extracellular matrix, which begins approximately 16 days after culture, marks the final phase of osteoblast phenotypic development. Expression of alkaline phosphatase and mineralization is time but not density dependent. Type I collagen synthesis and collagen accumulation are uncoupled in the developing osteoblast. Although collagen synthesis and message expression peaks at day 3 in immature cells, extracellular matrix accumulation is minimal. Instead, matrix accumulates maximally after 7 days of culture as collagen biosynthesis is diminishing. Thus, extracellular matrix formation is a function of mature osteoblasts. Ascorbate and β-glycerol phosphate are both essential for the expression of osteoblast phenotype as assessed by alkaline phosphatase and mineralization of extracellular matrix. Ascorbate does not stimulate type I collagen gene expression in MC3T3-E1 cells, but it is absolutely required for deposition of collagen in the extracellular matrix. Ascorbate also induces alkaline phosphatase activity in mature cells but not in immature cells. β-glycerol phosphate displays synergistic actions with ascorbate to further stimulate collagen accumulation and alkaline phosphatase activity in postmitotic, differentiated osteoblast-like cells. Mineralization of mature cultures requires the presence of β-glycerol phosphate. Thus, MC3T3-E1 cells display a time-dependent and sequential expression of osteoblast characteristics analogous to in vivo bone formation. The developmental sequence associated with MC3T3-E1 differentiation should provide a useful model to study the signals that mediate the switch between proliferation and differentiation in bone cells, as well as provide a renewable culture system to examine the molecular mechanism of osteoblast maturation and the formation of bone-like extracellular matrix.
Maturation-associated changes in the cellular composition of mouse calvariae and in the biochemical characteristics of calvarial cells separated into subclasses on percoll density gradients
Authors: Wong G.L. , Ng M.C. 
Published: February 2010

Abstract
The effects of tissue maturation on the cellular composition and biochemical characteristics of bone were studied in neonatal, young adult, and aging mice. Osteoblast subclasses were isolated on Percoll density gradients. Neonatal calvariae consisted almost exclusively of cells banding at low and intermediate buoyant density. High buoyant density cells constituted 5–10% of total cells at 10 days of age but increased to 50–60% by 5 weeks of age. These latter cells were released late during collagenase digestion. This indicates that they arise from the deeper layer of bone. For this reason, we consider them putative osteocytes. We established that constitutive secretion of IGF-I and TGF-β and activities of cellular alkaline phosphatase paralleled those of the tissue of origin in all cell groups and was highest in cells of intermediate buoyant density. These activities declined rapidly after cessation of growth at 5 weeks of age in both bone and isolated cells. Between 5 and 8 weeks of age, the hormonal response to PTH also declined dramatically. The maximum cAMP induced by PTH declined by about 70% in highly responsive cells of intermediate buoyant density and fell to insignificant levels in cells of high buoyant density. We found that a cyclic AMP response to PTH was positively correlated with stimulated secretion of IGF-I by this hormone in cells from animals of all ages. Despite their inability to respond to PTH with increases in cAMP and IGF-I, adult bone cells of high buoyant density continued to respond to PTH with increases in the secretion of TGF-β. The stimulatory effect of PTH on the secretion of TGF-β could not be mimicked by dibutyryl-cAMP or forskolin in any subclass of osteoblasts, in contrast to IGF-I, which was increased in the presence of these compounds. In summary, we show that PTH increases secretion of TGF-β by bone cells. In addition, separation of bone cells from mature mice on the basis of buoyant density permits separation of specific osteoblastic subclasses whose numbers and biochemistry change with maturity. Furthermore, these data suggest that osteocytic cells (1) accumulate in mature bone, (2) undergo loss of selective PTH responses, including cAMP and IGF-I, and (3) retain cAMP-independent PTH responsiveness as shown by increased secretion of TGF-β.