bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monoclonal antibodies with selective reactivity against osteoblasts and osteocytes in human bone
Authors: Walsh Susan , Dodds Robert A. , James Ian E. , Bradbeer Jeremy N. , Gowen Maxine 
Published: February 2010

Abstract
Monoclonal antibodies (MAb) may provide valuable tools for studying osteoblast differentiation. We therefore raised a panel of MAb reactive with cells of this phenotype using 1,25(OH)2D3-treated human trabecular osteoblast-like cells (HOBS) as the immunogen. Immunohistochemical studies on various tissues, including undecalcified cryostat sections of fetal and adult human bone, identified 11 bone cell-reactive MAb. Of these, 2 demonstrated particularly selective reactivities against osteocytes (OB/M) and osteoblasts (OB/L). These reactivities were also seen in developing bone from rat, rabbit, and marmoset. OB/L and OB/M demonstrated limited reactivity against a small number of human tissues from the extensive panel of substrates tested. Both MAb exhibited reactivity against discrete populations of cells in the large and small intestine. In addition, OB/L reacted with cells in the basal epidermis of skin and OB/M with cells in blood vessel walls. Both antibodies demonstrated reactivity against a variety of cultured osteoblast-like cell lines and other cultured cell types. These MAb may therefore provide a valuable means of studying osteoblast ontogeny.
Glucocorticoid regulation of calcitonin receptor in mouse osteoclast-like multinucleated cells
Authors: Wada Seiki , Akatsu Takuhiko , Tamura Tatsuya , Takahashi Naoyuki , Suda Tatsuo , Nagata Naokazu 
Published: February 2010

Abstract
Abundant multinucleated cells (MNCs) are formed in cocultures of mouse osteoblastic cells and marrow cells in the presence of 1α, 25-dihydroxyvitamin D3 [1α, 25(OH)2D3], and these cells have the properties of osteoclasts (OCs). In this study using the mammalian OCs, we tried to clarify the role of glucocorticoids (GCs) in calcitonin receptors (CTR) and CT-responsive cAMP production in OCs. Dexamethasone (DEX) dose and time dependently enhanced the specific binding of [125I]salmon calcitonin (sCT). When the MNCs were preincubated with DEX for 24 h, the effect was evident at 10−9 M and the maximum effect was obtained at 10−7 M. The effect developed over 12–48 h at doses of 10−9 and 10−6 M DEX. The numbers of CTR-positive mononuclear cells and MNCs were not altered by the DEX treatment. Prednisolone and triamcinolone reproduced the DEX effect, but 17 β-estradiol, progesterone, testosterone, aldosterone, and 1α, 25(OH)2D3 did not. RU486, a GC receptor antagonist, attenuated the effect of DEX to enhance the specific binding of [125I]sCT. From a Scatchard plot analysis, DEX enhanced CTR number (212 ± 64%) with a minimal change in the affinity to sCT. Autoradiographic studies using [125I]sCT showed that DEX enhanced the density of the grains on the tartrate-resistant acid phosphatase (TRAP)-positive MNCs and mononuclear cells, but not on other types of cells. DEX preincubation also enhanced sCT-stimulated but not prostaglandin E2- or forskolin-stimulated cAMP production. Inhibition of enhancement was possible with cycloheximide, indicating this effect was mediated through de novo protein synthesis. The present study showed that GCs play an important role in the regulation of CT effect through the upregulation of CTR on OCs, and this effect would explain, at least partly, a potentiation by GCs of hypocalcemic action of CT in hypercalcemic patients.
Interactions of growth hormone and parathyroid hormone in renal phosphate, calcium, and calcitriol metabolism and bone remodeling in postmenopausal women
Authors: Lieberman Steven A. , Holloway Leah , Marcus Robert , Hoffman Andrew R. 
Published: February 2010

Abstract
The mechanisms underlying the effects of recombinant human growth hormone (rhGH) on vitamin D, mineral, and bone metabolism are not known. We examined whether these effects are mediated by parathyroid hormone (PTH) by measuring renal phosphorus (P) and calcium (Ca) handling, serum calcitriol, and markers of bone turnover for 24 h before and 72 h after an infusion of hPTH(1–34) in eight healthy postmenopausal women at baseline and following short-term (1 week) and sustained (5 weeks) rhGH treatment. On short-term rhGH, serum phosphorus and basal TmP/GFR were unaffected, but the fall in TmP/GFR after hPTH infusion was exaggerated (integrated response: −99.2 ± 22.3 versus −144.1 ± 15.0 minute-mg/dl, P = 0.0021). Basal calcitriol levels rose from 115 ± 17 to 163 ± 16 pM (P = 0.0002), but the increase in calcitriol following hPTH infusion was unaffected by short-term rhGH. The basal Ca excretion index (CEI) rose from 0.054 ± 0.005 to 0.073 ± 0.007 mM (P = 0.0095), but markers of bone turnover were unaffected. With sustained rhGH treatment, serum P (1.47 ± 0.05 mM), basal TmP/GFR (4.29 ± 0.24 mg/dl), and basal CEI (0.067 ± 0.005 mM) were elevated compared with control values, and the PTH-induced lowering of TmP/GFR was again enhanced (- 158.7 ± 22.8 minute-mg/dl, P = 0.0021). Basal calcitriol concentrations returned to control levels (108 ± 10 pM), but the calcitriol response to hPTH remained unchanged. Markers of bone remodeling were elevated with sustained rhGH treatment. Neither short-term nor sustained rhGH affected plasma ionized Ca, serum PTH levels, or the magnitude of the acute hydroxyproline, calcitriol, or cAMP responses to hPTH. We conclude that GH has PTH-independent effects on renal phosphate handling and 1α-hydroxylase activity, exerting its effects at a postreceptor step beyond adenylate cyclase activation.
Reduced bone mineral density in men with a previous femur fracture
Authors: Kannus Pekka , Järvinen Markku , Sievänen Harri , Järvinen Tero A. H. , Oja Pekka , Vuori Ilkka 
Published: February 2010

Abstract
This study determined the areal bone mineral density (BMD) from the lumbar spine (L2–4), right distal radius and ulna, and the femoral neck, trochanter area of the femur, distal femur, patella, proximal tibia, and calcaneus of both extremities in 29 men who had a femur shaft fracture 10 years earlier. For evaluation of the patients' BMDs in the spine and distal forearm, 29 age-, weight-, and height-matched normal men were also measured. Compared with normal men (mean ± SD = 1.123 ± 0.153), the spinal BMDs of the patients were significantly (p = 0.0054) lower (1.018 ± 0.119, −9.3%). Distal radius and distal ulna showed no significant group differences. In patients, the mean BMD of the injured extremity (compared with the uninjured side) was significantly lower in the distal femur (-6.8%; p = 0.0000), patella (-5.4%; p = 0.0000), proximal tibia (-4.7%; p = 0.0000), and calcaneus (-2.2%; p = 0.0259). In the proximal femur, this value was at the same level (femoral neck 1.3%, NS) or higher (trochanter area 6.3%, p = 0.0002) than that in the uninjured extremity. The relative BMDs of the injured extremity did not associate with the fracture type, fracture location, age, muscle strength, follow-up time, or non-weight-bearing time but showed significant (r = 0.33–0.64) positive correlation with low pain assessment and high functional scores of the injured extremity. The relative BMDs were especially strongly associated with the four-step functional classification of the International Knee Documentation Committee: the higher the functional class of the injured extremity, the less bone loss caused by the injury (p = 0.0001–0.0328). In conclusion, the femur shaft fracture results in permanently reduced bone density in the lumbar spine and lower parts of the injured extremity. The proximal femur is not affected. The observed decrease (9% in spine and 5–7% in the knee region of the injured limb) is clinically important with respect to age-related bone loss of 1% per year after the age of peak bone mass. Additional follow-up is needed to determine any increased risk of osteoporotic fractures in spine and injured extremity. Recovery of normal limb function seems to be crucial for good bony recovery.
Age-associated changes in ultrasound measurements of the calcaneus in men and women: The rotterdam study
Authors: van Daele P.L.A. , Burger H. , Algra D. , Hofman A. , Grobbee D.E. , Birkenhäger J.C. , Pols H.A.P. 
Published: February 2010

Abstract
Broadband ultrasound attenuation (BUA) and speed of sound (SOS) of the os calcis were measured in a sample of 1405 persons (628 men), aged 55–93 years, from the cohort of the Rotterdam Study, a population-based study of diseases in the elderly. We studied the effect of age, body mass index, age at menopause, current use of thiazides, loop diuretics, and estrogens, smoking, and disability on SOS and BUA. Comparisons were made between ultrasound measurements and bone mineral density (BMD) measurements of the lumbar spine and proximal femur using DXA. We found a significant decline with age in SOS and BUA in men (-0.4 and −0.1 %/year, respectively) and women (-1.3 and −0.4%/year, respectively), which persisted after adjustment for body mass index. Age at menopause was not associated with SOS or BUA. Pack-years of smoking was negatively related to SOS in both sexes and to BUA in men. Severe disability was associated with lower SOS and BUA in men, but not in women. Despite the small number of exposed persons, current corticosteroid use was associated with lower BUA in men. The other risk factors examined did not affect the ultrasound measurements. We observed modest correlations between SOS or BUA, on the one hand, and BMD of the lumbar spine, on the other hand (r = 0.32–0.42). Similar correlations were found between ultrasound measurements and BMD measurements of the proximal femur. We conclude that in persons 55 years or over (1) there is a significant age-related decline of BUA and SOS, which is about three times higher in women compared with men, and (2) ultrasound measurements are not able to predict low BMD in hip or spine.
Alendronate increases skeletal mass of growing rats during unloading by inhibiting resorption of calcified cartilage
Authors: Bikle Daniel D. , Morey-Holton Emily R. , Doty Stephen B. , Currier Patricia A. , Tanner Sharon J. , Halloran Bernard P. 
Published: February 2010

Abstract
Loss of bone mass during periods of skeletal unloading remains an important clinical problem. To determine the extent to which resorption contributes to the relative loss of bone during skeletal unloading of the growing rat and to explore potential means of preventing such bone loss, 0.1 mg P/kg alendronate was administered to rats before unloading of the hindquarters. Skeletal unloading markedly reduced the normal increase in tibial mass and calcium content during the 9 day period of observation, primarily by decreasing bone formation, although bone resorption was also modestly stimulated. Alendronate not only prevented the relative loss of skeletal mass during unloading but led to a dramatic increase in calcified tissue in the proximal tibia compared with the vehicle-treated unloaded or normally loaded controls. Bone formation, however, assessed both by tetracycline labeling and by [3H]proline and 45Ca incorporation, was suppressed by alendronate treatment and further decreased by skeletal unloading. Total osteoclast number increased in alendronate-treated animals, but values were similar to those in controls when corrected for the increased bone area. However, the osteoclasts had poorly developed brush borders and appeared not to engage the bone surface when examined at the ultrastructural level. We conclude that alendronate prevents the relative loss of mineralized tissue in growing rats subjected to skeletal unloading, but it does so primarily by inhibiting the resorption of the primary and secondary spongiosa, leading to altered bone modeling in the metaphysis.
Bone mineral density at distal tibia using dual-energy x-ray absorptiometry in normal women and in patients with vertebral osteoporosis or primary hyperparathyroidism
Authors: Casez J.-P. , Troendle A. , Lippuner K. , Jaeger P. 
Published: February 2010

Abstract
To assess the effect of age and disease on mineral distribution at the distal third of the tibia, bone mineral content (BMC) and bone mineral density (BMD) were measured at lumbar spine (spine), femoral neck (neck), and diaphysis (Dia) and distal epiphysis (Epi) of the tibia in 89 healthy control women of different age groups (20-29, n = 12; 30-39, n = 11; 40-44, n = 12; 45-49, n = 12; 50-54, n = 12; 55-59, n = 10; 60-69, n = 11; 70-79, n = 9), in 25 women with untreated vertebral osteoporosis (VOP), and in 19 women with primary hyperparathyroidism (PHPT) using dual-energy x-ray absorptiometry (DXA; Hologic QDR 1000 and standard spine software). A soft tissue simulator was used to compensate for heterogeneity of soft tissue thickness around the leg. Tibia was scanned over a length of 130 mm from the ankle joint, fibula being excluded from analysis. For BMC and BMD, 10 sections 13 mm each were analyzed separately and then pooled to define the epiphysis (Epi 13-52 mm) and diaphysis area (Dia 91-130 mm). Precision after repositioning was 1.9 and 2.1% for Epi and Dia, respectively. In the control group, at any site there was no significant difference between age groups 20-29 and 30-39, which thus were pooled to define the peak bone mass (PBM). Mean decrease in BMD from PBM (mean + SEM) was significant after age 49 at Epi (-11.8 + 12.7%), after age 54 at spine (-14.2 + 5.9%) and neck (-11.2 + 8.6%), and after age 59 at Dia (-10.9 + 6.9%). Epiphysis and diaphysis BMC but not BMD were correlated with body weight (r = 0.22, p &lt; 0.04 for both sites). In patients with PHPT mean tibial BMD expressed as Z scores was significantly lower than in controls, from 39 to 130 mm but was similar to that in controls from 0 to 39 mm as well as at spine and neck. In patients with untreated VOP, mean BMD (Z scores) was lower than in controls at spine and neck as well as tibia from 0 to 52 mm (p &lt; 0.01) but not between 52 and 130 mm. We conclude that DXA measurement at tibia is a suitable tool to assess bone loss and distribution of bone mass between Dia (cortical) and Epi (with a substantial amount of trabecular bone) in a single weight-bearing bone in health and bone diseases.
Osteoporosis in african hemosiderosis: Role of alcohol and iron
Authors: Schnitzler Christine M. , Macphail A. Patrick , Shires Roy , Schnaid Edward , Mesquita Julia M. , Robson Heather J. 
Published: February 2010

Abstract
This paper aims to examine the relative contributions made by alcohol and iron overload and hypovitaminosis C to the osteoporosis associated with African hemosiderosis. To characterize this bone disorder, we examined double-tetracycline-labeled iliac crest bone biopsies and serum biochemistry in 53 black male drinkers, 38 with (Fe+) and 15 without (Fe−) iron overload, and in controls. We reasoned that abnormalities found in both patient groups were likely to be caused by alcohol abuse and those found only in the Fe+ group to be caused by iron overload and hypovitaminosis C (iron/C−). The patient groups differed only with respect to greater erosion depth (p &lt; 0.05) and abnormal markers of iron overload in the Fe+ group. Ascorbic acid levels were lower in the Fe+ group than in controls (p &lt; 0.001). Bone volume and trabecular thickness were significantly lower in both patient groups compared with controls and therefore likely caused by alcohol. There were no positive correlations between formation and erosion variables in either patient group, which suggests uncoupling of formation from erosion, possibly as a result of alcohol abuse. Prolonged mineralization lag time associated with thin osteoid seams was found in 32% of patients, affecting both groups. This rules out osteomalacia and suggests osteoblast dysfunction, probably caused by alcohol. The number of iron granules in the marrow correlated with erosion depth (r = 0.373, p &lt; 0.01), trabecular number (r = -0.295, p &lt; 0.05), and trabecular separation (r = 0.347, p &lt; 0.05). Abnormalities in these variables were therefore attributed mainly to iron/C−. Several formation variables were significantly directly correlated with indicators of iron overload, suggesting that iron/C− does not adversely affect bone formation. We conclude that alcohol abuse was predominantly associated with thinning of trabeculae and iron overload and hypovitaminosis C with increased erosion depth and disconnection of the trabecular network. Osteomalacia was not seen.
Trochanteric bone mineral density is associated with type of hip fracture in the elderly
Authors: Greenspan Susan L. , Myers Elizabeth R. , Maitland Lauri A. , Kido Tamiko H. , Krasnow Meryl B. , Hayes Wilson C. 
Published: February 2010

Abstract
Hip fractures can be separated into femoral neck (cervical or intracapsular) or trochanteric (extracapsular). Trochanteric fractures have been associated with up to twice the short-term mortality of cervical fractures in the elderly. Fracture type may be influenced by the fall direction and local differences in proximal femur strength properties. We previously demonstrated that fall characteristics and body habitus, in addition to femoral bone mineral density, play a dominant role in the prediction of hip fracture in elderly fallers. To examine the association of these determinants with hip fracture type, we assessed fall characteristics, body habitus, and site-specific bone mineral density measurements in 112 elderly hip fracture patients (85 women and 27 men, mean age 85 years) 1 week after an acute hip fracture. Trochanteric BMD was 13% lower in women and 11% lower in men for patients with trochanteric fracture than in those with femoral neck fracture (p &lt; 0.01). A stepwise multiple logistic regression indicated that trochanteric BMD (decrease of 1.0 SD, adjusted OR 4.6, 95% CI 2.0-9.5, p &lt; 0.0001) and femoral neck BMD (increase of 1.0 SD, adjusted OR 3.0, 95% CI 1.6-5.9, p = 0.0003) were independently associated with trochanteric fracture. Fall characteristics, body habitus, gender, and age were not associated with hip fracture type. We conclude that a relatively low trochanteric BMD or a high femoral neck BMD was associated with a trochanteric hip fracture and that site-specific trochanteric BMD determinations should be measured when assessing risk of trochanteric hip fractures in the elderly.
Variation in vertebral height ratios in population studies
Authors: O'Neill T.W. , Varlow J. , Felsenberg D. , Johnell O. , Weber K. , Marchant F. , Delmas P.D. , Cooper C. , Kanis J. , Silman A.J. ,   European Vertebral Osteoporosis Study Group
Published: February 2010

Abstract
Vertebral height ratios are used to define vertebral deformity in clinical and epidemiologic studies of vertebral osteoporosis. However, few data have been obtained on the variation in these ratios in different populations using standard methods. We examined vertebral morphometric measurements obtained in a population survey from three centers: Malmö (Sweden), Montceau-les-Mines (France), and Graz (Austria), to study the influence of sex and the population center on vertebral height ratios. Radiographs were obtained according to a standardized protocol, and morphometric measurements, anterior height Ha, central height Hc, and posterior height Hp, made in Berlin. The height ratios anterior, Ha/Hp, central, Hc/Hp, posterior I, Hp/Hp', and posterior II, Hp/Hp″ (Hp' = posterior height of vertebrae above, Hp″ = posterior height of vertebrae below) were calculated for each vertebra from T4 to L4. The mean and standard deviation of these ratios for each sex and each center were derived using a statistical trimming procedure to normalize the distribution. Threshold values for defining grade 1 and grade 2 deformities, wedge, biconcavity, and compression, were calculated using these parameters. Anterior and central vertebral height ratios were smaller in males than females (p &lt; 0.01). There were significant differences between the three centers (p &lt; 0.01) both in the trimmed mean values for anterior and central vertebral height ratios and in the thresholds derived using standard criteria for defining wedge and biconcavity deformity. The data confirm the impression from single-center studies that vertebral height ratios vary between populations and suggest that reference values for vertebral height ratios should be derived separately for males and females within individual populations whenever possible.
Inhibition of collagen synthesis by prostaglandins in the immortalized rat osteoblastic cell line pyla: Structure-activity relations and signal transduction mechanisms
Authors: Fall Pamela M. , Breault David T. , Raisz Lawrence G. 
Published: February 2010

AbstractWe previously showed that prostaglandin E2 (PGE2) can selectively inhibit collagen synthesis and gene transcription in the immortalized rat osteoblastic clonal cell line Py1a, particularly in the presence of insulin-like growth factor I (IGF-I). In the present study, we examined the structure-activity relations for this effect. PGF2α was approximately 100 times more potent than PGE2. The prostaglandin F receptor (FP) selective agonist, fluprostenol, was the most potent agonist tested, significantly inhibiting incorporation of [3H]proline into both collagen and noncollagen protein at 10−11 M, with more than 90% inhibition of collagen synthesis at 10−8 M. The PGE2 analog, sulprostone, and PGD2 showed activity similar to that of PGE2. PGI2 and its stable analog, carbacyclin, were the least effective. Parathyroid hormone (PTH), forskolin, and isobutylmethylxanthine (IBMX) were ineffective. Phorbol myristate acetate (PMA) inhibited collagen synthesis in a manner similar to that of the prostanoids. The inhibitory effects of PGF2α, fluprostenol, and PMA show a similar time course on α1 (I) procollagen mRNA levels. The inhibition appeared to be caused by a decrease in collagen gene transcription as measured by nuclear run-on analysis. Further evidence for a transcriptional effect was obtained with COLIA1 promoter-CAT reporter constructs, although these showed somewhat smaller effects of prostanoids on CAT activity than on mRNA levels or labeling. Based on these results, we conclude that in the Py1a cell line prostanoids inhibit collagen synthesis by a pathway involving activation of protein kinase C that is not dependent on adenylate cyclase. The structure-activity relations for this response suggest that it is mediated by an FP receptor and is distinctly different from the stimulatory effects on bone resorption and formation.
Activation of the human osteocalcin gene by 24r,25-dihydroxyvitamin d3 occurs through the vitamin d receptor and the vitamin d-responsive element
Authors: Uchida Motoyuki , Ozono Keiichi , Pike Wesley J. 
Published: February 2010

Abstract
1α-25-dihydroxyvitamin D3 [1α,25(OH)2D3], together with vitamin D receptor (VDR), directly activates human osteocalcin (hOC) gene expression through a vitamin D-responsive element (VDRE) located in the promoter of the hOC gene. We investigated the effect of 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] on the regulation of the hOC gene promoter and compared it with that of α,25(OH)2D3. 24R,25(OH)2D3 did not activate the natural promoter in VDR-negative CV-1 cells. 24R,25(OH)2D3, however, induced the activation of this promoter following cotransfection with an hVDR expression vector. In VDR-positive MC3T3-E1 cells, 24R,25(OH)2D3 activated not only the natural hOC promoter but also a chimeric promoter composed of a synthetic hOC VDRE sequence linked to the thymidine kinase promoter. In combination with 1α-25(OH)2D3, 24R,25(OH)2D3 did not exhibit any antagonist activity on the hOC promoter. These results suggest that under conditions of high 24R,25(OH)2D3 levels in vivo, this metabolite of vitamin D3 may activate hOC gene expression through receptor mechanisms identical to that for 1α,25(OH)2D3.