bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ethnic differences in regional bone density, hip axis length, and lifestyle variables among healthy black and white men
Authors: Nelson D.A. , Jacobsen G. , Barondess D.A. , Parfitt A.M. 
Published: February 2010

Abstract
There are few published data on bone mass, measured by dual-energy X-ray absorptiometry (DXA), in healthy white or black men. Similarly, a recently described predictor of hip fracture among white women, hip axis length (HAL), has not been studied in men. We recruited 160 white and 34 black men, aged 23–80 years, and screened for diseases and drug exposures that adversely affect skeletal health. We measured bone mineral density (BMD) in the lumbar spine, femoral neck, and radial shaft by DXA; height and weight; skin color by reflectometry; and hip axis length both directly from DXA output and using automated software in a subsample. We also obtained historical data on education, smoking, exercise, and fractures. There were no significant black/white differences in mean weight, height, body mass index (BMI), or HAL. The black men had higher BMDs than did the white men at every site (5% for the radius, 10% for the lumbar spine, and 20% for the femoral neck). Skin pigmentation and BMD were not significantly correlated in either group (p &gt; 0.38). Among the white men, smoking was associated with lower lumbar BMD, but there was no significant relationship between BMD and exercise frequency in either group. There was no significant ethnic difference in fracture experience. We conclude that: (1) the higher BMD in black men than in white men is not due to greater body size, (2) the lower hip fracture risk reported for black men than for white men is not due to a difference in hip axis length; (3) skin color is not related to BMD in either sex.
Carboxy-terminal propeptide of human type I collagen and pyridinium cross-links as markers of bone growth in infants 1 to 18 months of age
Authors: Lieuw-A-Fa Mariska , Sierra Rosa I. , Dr. Specker Bonny L. 
Published: February 2010

Abstract
Serum carboxy-terminal propeptide of human type I collagen (PICP) concentrations, as a marker for bone formation, and urinary pyridinium (Pyd) cross-link concentrations, as a marker of bone resorption, were determined in 66 healthy infants aged 1–18 months who are being studied longitudinally. We hypothesized that there would be a positive correlation of growth velocity, increase in bone area, and bone mass accretion rates with PICP and Pyd cross-link concentrations. Since osteocalcin is currently used as a marker of bone formation, serum osteocalcin concentrations were also measured. Mean serum PICP and urinary Pyd cross-link concentrations were significantly greater than adult concentrations. Future growth velocity, increase in bone area, and bone mass accretion rates were not associated with PICP, Pyd cross-link, or osteocalcin concentrations. Growth velocity during the 3 months preceding sample collection correlated with serum PICP, Pyd/kg, and osteocalcin concentrations (r = 0.474, p &lt; 0.001; r = 0.379, p &lt; 0.001; and r = 0.516, p &lt; 0.001, respectively). Previous increase in bone area correlated with serum PICP concentrations (r = 0.359, p = 0.01). The relationship between the infant's previous bone mass accretion rate and PICP was of borderline significance (r = 0.281, p = 0.055). In summary, normative data for PICP, Pyd cross-link concentrations, and parameters of bone growth are provided for infants 1–18 months of age and indicate that these markers reflect past and current bone metabolism and may be helpful in monitoring bone disorders in infants.
Effects of methotrexate on human osteoblasts in vitro: Modulation by 1,25-dihydroxyvitamin D3
Authors: Dr. Scheven Ben A.A. , van der Veen Maaike J. , Damen Cora A. , Lafeber Floris P.J.G. , van Rijn Herman J.M. , Bijlsma Johannes W.J. , Duursma Sumen A. 
Published: February 2010

Abstract
This study was designed to investigate whether methotrexate (MTX), used in the treatment of rheumatoid arthritis (RA), affects proliferation and differentiation of human osteoblasts in culture. The effects of MTX were assessed by analyzing markers of proliferation and differentiation of human trabecular bone–derived osteoblast-like cells cultured in the presence or absence of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3). Treatment of the osteoblastic cells with MTX resulted in a strong dose-dependent inhibition of cell proliferation with half maximal response at a dose of 30 nM. MTX did not interfere with cellular alkaline phosphatase (AP) activity, the number of cells expressing cytochemical AP, or basal osteocalcin production. Addition of 1,25(OH)2D3 to the cultures caused an enhanced AP expression and osteocalcin production coinciding with a decreased osteoblast proliferation. Coincubation of 1,25(OH)2D3 with MTX in doses ≥100 nM further inhibited osteoblast growth and induced a significant stimulation of AP expression and activity, and production of osteocalcin above the values reached in the 1,25(OH)2D3 cultures. In conclusion, MTX proved to be a potent inhibitor of osteoblast proliferation but did not affect basal osteoblastic phenotypic expression. In the presence of the osteoblast differentiation-promotor, 1,25(OH)2D3, MTX further inhibited cell growth which was associated with enhanced AP activity and osteocalcin production. Thus, MTX may have profound effects on bone metabolism and remodeling by interfering with bone cell turnover.
A comparison of the effects of parathyroid hormone and parathyroid hormone-related protein on osteocalcin in the rat
Authors: Gundberg Caren M. , Fawzi Mervat I. , Clough Mary E. , Calvo Mona S. 
Published: February 2010

Abstract
We compared the effects of parathyroid hormone (PTH1–34) and parathyroid hormone-related protein (PTHrpl–34) on osteocalcin release in the isolated rat hindlimb and in intact and thyroparathyroidectomized (TPTX) rats. PTH1–34 suppressed osteocalcin release from perfused rat hindquarters, while PTHrp1–34 had no effect on osteocalcin release, despite comparable stimulation of cAMP production. Similarly, serum osteocalcin declined in the intact and TPTX animals by 5 h after a single dose of PTH1–34, while there was no response to PTHrpl–34. Chronic administration of PTH1–34 or PTHrpl–34 produced comparable hypercalcemia and hypophosphatemia in sham-operated and TPTX animals. Chronic PTH1–34 administration produced significant increases in serum osteocalcin both in the sham-operated rats and in the TPTX animals. However, in animals chronically treated with PTHrp1–34, there was no change at any time point in osteocalcin in either sham-operated or TPTX rats. These differences could be inherent or merely due to potency differences between the two peptides.
Serum pyridinoline as a specific marker of collagen breakdown and bone metabolism in hemodialysis patients
Authors: Ureńa Pablo , Ferreira Aníbal , Kung Viola T. , Morieux Caroline , Simon Pierre , Ang Kim S. , Souberbielle Jean Claude , Segre Gino V. , Drüeke Tilman B. , de Vernejoul Marie Christine 
Published: February 2010

AbstractType I collagen represents more than 90% of bone matrix. Quantitative analysis of collagen cross‐link molecules such as pyridinoline (PYD) provides valuable information on bone resorption rate. We have studied 37 hemodialysis patients who underwent a systematic transiliac bone biopsy for histomorphometry study. Eighteen of them had tetracycline double labeling, allowing to determine dynamic, in addition to static bone parameters. Measurement of serum‐free PYD was performed using a new competitive enzyme immunoassay. Serum PYD values were compared with those of three other serum markers of bone metabolism, namely intact PTH (iPTH), bone‐specific alkaline phosphatase (bAP), and osteocalcin, for the correlations with bone histomorphometric parameters. Serum PYD levels (mean ± SD) were significantly higher in dialysis patients than in normal individuals, 90.6 ± 99.6 nM versus 1.9 ± 0.4 nM, respectively. Patients with high turnover bone disease had significantly higher serum PYD levels than patients with normal or low bone turnover, 108.8 ± 108.0 nM versus 34.1 ± 12.8 nM, respectively. Serum PYD levels were positively correlated with bone resorption parameters including osteoclast surface (r = 0.59, p < 0.0001) and osteoclast number/mm2 (r = 0.61, p < 0.0001), and also with bone formation parameters, osteoblast surface (r = 0.43, p < 0.008), double‐labeled surface (r = 0.81, p < 0.001), and BFR (r = 0.91, p < 0.0001). The BFR was better correlated with serum PYD levels than with either serum iPTH or osteocalcin concentrations. However, correlation with serum bAP was comparable. Serum cross‐linked type I carboxy‐terminal telopeptide (ICTP) and type I carboxy‐terminal extension peptide (PICP) levels were also significantly increased in both groups of dialysis patients but they did not correlate with any of the bone turnover parameters. In conclusion, PYD, which is a specific serum marker of collagen breakdown, provides valuable information on bone turnover in hemodialysis patients.
Extra cancellous bone induced by combined prostaglandin E2 and risedronate administration is maintained after their withdrawal in older female rats
Authors: Dr. Jee Webster S. S. , Lin Bai Yun , Ma Yan Fei , Ke Hua Zhu 
Published: February 2010

Abstract
Prostaglandin E2 (PGE2) has been recognized for its marked anabolic effect on bone, but the bone gain is lost after the cessation of PGE2 treatment. In previous studies, we were successful in maintaining the new bone by administering a bisphosphonate after the withdrawal of PGE2 treatment. The objective of this study was to determine the fate of the extra bone induced by a combination with PGE2 and risedronate after discontinuing treatment. Ninety-six 9-month-old virgin female Sprague-Dawley rats were treated with 1 or 5 μg of risedronate/ kg/twice weekly, 6 mg of PGE2/kg/day alone or 6 mg of PGE2/kg/day plus 1 or 5 μg of risedronate/kg/twice weekly for 60 days (day 0) and followed by 60 days without treatment (day 60). We have reported the results from the groups treated for 60 days previously. This report is restricted to the histomorphometric findings on the secondary spongiosa of the proximal tibial metaphysis in the groups after withdrawal for 60 days. We found that the only group that maintained the PGE2 induced new bone after withdrawal was the group treated with 6 mg of PGE2/kg/day plus 5 μg of risedronate/kg/twice a week. Withdrawal of this combined treatment depressed bone turnover (bone-based bone formation rate, activation frequency) and bone resorption (percent eroded perimeter). The tissue mechanisms responsible for the protection drew from the previously deposited risedronate.
Nitric oxide: A cytokine-induced regulator of bone resorption
Authors: Ralston Stuart H. , Ho Ling-Pei , Helfrich Miep H. , Grabowski Peter S. , Johnston Peter W. , Benjamin Nigel 
Published: February 2010

Abstract
Nitric oxide (NO) has been reported to inhibit osteoclastic bone resorption, yet potent stimulators of bone resorption, such as interleukin-1 (IL-1) and tumor necrosis factor (TNF), are known to stimulate NO production. This paradox prompted us to reinvestigate the relationship between NO production and bone resorption in mouse calvarial organ cultures. Control cultures and those stimulated with calciotropic hormones and individual cytokines produced little NO, and under these conditions the NO synthase inhibitor, L-NG-monomethyl arginine (LMMA), had no significant effect on bone resorption. Cytokine combinations were much more potent stimulators of NO production than individual cytokines. Dramatic stimulation of NO production and inhibition of bone resorption resulted when gamma-interferon (IFN) was combined with IL-1 or TNF and these effects were reversed by LMMA. IFN had no effect on bone resorption and little effect on NO production when used alone or in combination with calciotropic hormones, however, suggesting that IFN selectively inhibits cytokine-induced bone resorption by generating large amounts of NO. IL-1 and TNF acted together to stimulate NO production but to a lesser degree than when combined with IFN. LMMA inhibited bone resorption induced by IL-1 and TNF, suggesting that lower concentrations of NO stimulate bone resorption. Experiments with the pharmacological NO donor S-nitroso-acetyl-penicillamine (SNAP) supported this view in showing generalized suppression of bone resorption at high SNAP concentrations, but potentiation of IL-1 induced bone resorption at lower SNAP concentrations. We conclude that cytokines are potent inducers of NO in bone and that cytokine-induced NO production has biphasic effects on bone resorption. While the mechanisms of action of NO in bone will require further research, these data raise the possibility that local production of NO may be involved in the regulation of bone remodeling, especially in diseases of cytokine activation such as rheumatoid arthritis.
Normalization of mineral homeostasis after reversal of osteopetrosis
Authors: Nesbitt Teresa , Drezner Marc K. , Marks Sandy C. , Jackson Mary E. , Mackay Carole A. 
Published: February 2010

Abstract
Whether a radiographic and histologic cure of osteopetrosis includes normalization of mineral homeostasis remains unknown. Thus, we explored the extent of defective mineral metabolism in the microphthalmic (mi/mi) mouse before and after cure. Under basal conditions mi mutants exhibit normocalcemia, hypophosphatemia, and elevated renal 25-hydroxyvitamin D-1-hydroxylase activity. However, administration of PTHrP (3 μg/h × 24 h) further stimulated enzyme activity in mi mutants with active disease, to a level no different than that in treated normals. Serum phosphorus levels also declined in mi/mi mice following PTHrP, suggesting a normal renal response to this hormone. In contrast, failure to suppress enzyme function in mi/mi mice following prolonged calcitriol infusion indicates that the observed enhancement of 1,25-dihydroxyvitamin D production occurred secondary to autonomous parathyroid function and/or nonparathyroid hormone-related stimuli. Although an increased fractional excretion and decreased tubular reabsorption of phosphate were demonstrated in mi/mi mice, serum PTH levels were no different in mi mutants compared with normal littermates. Following skeletal cure, the mi/mi mice surprisingly display normal serum phosphorus levels and renal enzyme activity. Moreover, treatment restored normal responsiveness to calcitriol suppression and maintained normal PTHrP responsiveness of enzyme activity. These data indicate that the cure of osteopetrosis in the mi mutant is universal and includes normalization of serum phosphorus and renal 25-hydroxyvitamin D-1-hydroxylase. Furthermore, these data suggest that phosphate depletion of unknown origin is the likely cause of elevated enzyme activity in this murine osteopetrotic mutant.
Degradation of subcutaneous implants of bone particles from normal and warfarin-treated rats
Authors: Serre C. M. , Price P. , Delmas P. D. 
Published: February 2010

Abstract
Osteoclasts are multinucleated cells specific to bone tissue and of hemopoietic origin. They are formed by fusion of mononucleated cells in a manner related to the formation of macrophage polykarions. Subcutaneous implantation of mineralized bone particles induces multinucleated giant cell recruitment. There is controversy, however, about the nature of these cells. Although subcutaneous implantation of bone particles derived from warfarin-treated animals has been applied as an in vivo model to study the role of osteocalcin in bone resorption, the exact nature of multinucleated cells elicited in this model is still unclear. In this paper, subcutaneous implants of bone particles from normal and warfarin-treated rats were implanted in Sprague-Dawley rats. Resorption was assessed in 12 and 16 day implants by chemical analysis (calcium content) and by histomorphometric measurement of the bone particle area and the number of multinucleated and tartrate-resistant acid phosphatase-positive cells. No significant difference in calcium content and bone area were observed, after 12 or after 16 days of implantation, between implants from normal and warfarin-treated rats. The number of tartrate-resistant acid phosphatase-positive cells elicited by bone particles represented less than 25% of the number of multinucleated cells and did not differ between bone particles from normal and warfarin-treated rats. By electron microscopy, a majority of multinucleated cells did not show a ruffled border in contact with bone particles, and their morphological features were suggestive of a foreign body giant cell reaction. In our experience this model appears to elicit only a few osteoclasts among multinucleated macrophagic cells and may not be the most appropriate one for the study of resorption of normal or osteocalcin-depleted bone.
Skeletal unloading induces selective resistance to the anabolic actions of growth hormone on bone
Authors: Halloran Bernard P. , Bikle Daniel D. , Harris Jonathan , Autry Christopher P. , Currier Patricia A. , Tanner Sharon , Patterson-Buckendahl Patricia , Morey-Holton Emily 
Published: February 2010

Abstract
Loss of skeletal weight bearing or physical unloading of bone in the growing animal inhibits bone formation and induces a bone mineral deficit. To determine whether the inhibition of bone formation induced by skeletal unloading in the growing animal is a consequence of diminished sensitivity to growth hormone (GH) we studied the effects of skeletal unloading in young hypophysectomized rats treated with GH (0, 50, 500 μg/100 g body weight/day). Skeletal unloading reduced serum osteocalcin, impaired uptake of 3H-proline into bone, decreased proximal tibial mass, and diminished periosteal bone formation at the tibiofibular junction. When compared with animals receiving excipient alone, GH administration increased bone mass in all animals. The responses in serum osteocalcin, uptake of 3H-proline and 45Ca into the proximal tibia, and proximal tibial mass in non-weight bearing animals were equal to those in weight bearing animals. The responses in trabecular bone volume in the proximal tibia and bone formation at the tibiofibular junction to GH, however, were reduced significantly by skeletal unloading. Bone unloading prevented completely the increase in metaphyseal trabecular bone normally induced by GH and severely dampened the stimulatory effect (158% vs. 313%, p &lt; 0.002) of GH on periosteal bone formation. These results suggest that while GH can stimulate the overall accumulation of bone mineral in both weight bearing and non-weight bearing animals, skeletal unloading selectively impairs the response of trabecular bone and periosteal bone formation to the anabolic actions of GH.
Expression of bone sialoprotein mRNA during bone formation and resorption induced by colchicine in rat tibial bone marrow cavity
Authors: Arai N. , Ohya K. , Kasugai S. , Shimokawa H. , Ohida S. , Ogura H. , Amagasa T. 
Published: February 2010

Abstract
In the rat tibial bone marrow cavity, following colchicine injection, there is a phase of osteogenesis in which bone trabeculae replace the necrotic bone marrow tissues and fill the marrow cavity. The newly formed bone is subsequently resorbed by osteoclasts and normal bone marrow is restored. In this study, we correlated these morphologic events with the pattern of gene expression of bone sialoprotein (BSP), an extracellular matrix protein in mineralized tissues, to elucidate the possible functions of BSP in bone formation and resorption in vivo. The expressions of osteopontin (OPN) and type I collagen were also examined. Northern hybridization of the tibia demonstrated that OPN mRNA was gradually increased and expressed at a maximal level 10 days after colchicine injection (during the bone resorption process), while BSP mRNA expression already reached a maximal level at day 6 (during the initial process of bone formation). Its expression was, thus, quite temporary at the beginning of bone formation and different from that of type I collagen, which was continually elevated from days 6 to 10. In situ hybridization of the newly formed bone induced in the tibia revealed that BSP mRNA was evenly expressed in most osteoblasts and osteocytes, moreover in interconnecting colonies of spindle-shaped cells, possibly preosteoblasts, at day 6. At day 10, however, its expression became restricted to some cells on the bone surfaces, some osteoblasts, and most osteoclasts. These observations suggest that BSP may play an important role mainly in the initiation of bone formation and is also associated with the functions of osteoclast in vivo.
Serum IGF 1 is low and correlated with osteoblastic surface in idiopathic osteoporosis
Authors: Reed Berenice Y. , Zerwekh Joseph E. , Sakhaee Khashayar , Breslau Neil A. , Gottschalk Frank , Pak Charles Y. C. 
Published: February 2010

Abstract
We have previously reported that bone formation is impaired on histomorphometric analysis of bone in patients with idiopathic osteoporosis. In the present study, 30 patients with idiopathic osteoporosis (18 men and 12 women mean age 44 ± 12 years) and spinal and/or appendicular fractures were studied. Compared with control values, bone biopsy analysis demonstrated reduced bone volume (13.0 ± 4.4 vs. 23.2 ± 4.4, p &lt; 0.0001), osteoid volume (0.13 ± 0.13 vs. 0.32 ± 0.19, p = 0.001), osteoid surface (5.9 ± 4.3 vs. 12.1 ± 4.6, p = 0.0004), and diminished double-labeled mineralizing surface (MS/BS 2.0 ± 2.1 vs. 5.1 ± 2.7%, p = 0.0001) in the patients. Since insulin-like growth factor 1 (IGF-1) is one of the major determinants of bone growth and remodeling, we measured the circulating level of this growth factor in these patients. The mean serum IGF-1 concentration was lower in patients as compared with 33 healthy age-matched controls (193 ± 59 SD ng/ml vs. 232 ± 79). A significant difference was noted between the two groups only in subjects younger than 36 years. In patients with idiopathic osteoporosis, regression analysis of serum IGF-1 against the various histological parameters measured from the bone biopsy disclosed significant correlation's between serum IGF-1 and osteoblastic surface (r = 0.429, p = 0.032), mineralizing bone surface with a double label (r = 0.480, p = 0.015), and the bone formation rate (r = 0.457, p = 0.021). These findings suggest that in young eugonadal individuals with idiopathic osteoporosis, reduced IGF-1 concentrations may have an etiological role in the development of this disease.