bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estrogen receptors and human bone cells: Immunocytochemical studies
Authors: Colston Kay W. , King R.J.B. , Hayward J. , Fraser D.I. , Horton M.A. , Stevenson J.C. , Arnett T.R. 
Published: February 2010

Abstract
In this immunocytochemical study we have probed a number of human bone cell types and bone preparations for the presence of the estrogen receptor (ER) with two distinct monoclonal antibodies. Using a well-validated antibody (H222) that recognizes human ER and standard peroxidase-antiperoxidase methodology, we were unable to demonstrate nuclear staining for ER in cultured primary or transformed human bone-derived cells or in fetal bone sections. Attempts to visualize ER in osteosarcoma cell lines (TE85C and HTB96) using a silver enhancement procedure were also unsuccessful. Additionally, we failed to detect immunocytochemical staining for the progesterone receptor (using monoclonal antibody mPR1) in control or estrogen-treated human bone cell cultures. Estrogen and progesterone receptor staining was readily detectable in MCF7 human breast cancer cells. In contrast, with a monoclonal antibody that recognizes a 29 kDa cytoplasmic component (p29) closely related to human ER, we observed specific staining in all the osteoblastlike cells studied. Cytoplasmic staining for this p29 antigen was most intense in primary cultures of human bone-derived cells. It is possible that the relatively abundant but as yet undefined p29 antigen may act as a sensitive marker for the presence of ER in cells at levels below the detection limit of the anti-ER monoclonal antibody. If so, our results are consistent with the presence of ER in osteoblastlike cells at very low concentrations.
Biomechanical properties of the proximal femur determined in vitro by single-energy quantitative computed tomography
Authors: Esses Steven I. , Lotz Jeffrey C. , Hayes Wilson C. 
Published: February 2010

Abstract
To assess the use of quantitative computed tomography as an in vivo predictor of fracture in the osteoporotic hip, we examined the in vitro relationship between single-energy quantitative computed tomography data, calibrated for scanner drift, and the mechanical properties of trabecular bone from the proximal femur. For 49 samples, the apparent density and ultimate strength were measured and their functional relationship to the computed tomography data determined. Apparent density demonstrated a moderate linear correlation to the computed tomography numbers (R2 = 0.60), and the ultimate strength was related through a power law (R2 = 0.83). In addition, for 8 intact femora, average computed tomographic data from the sub-capital region were moderately correlated to the ultimate fracture load applied under controlled in vitro conditions (R2 = 0.64). The average fracture energy for these femora was 43 J, a value more than an order of magnitude less than the energy available in a fall from standing height, suggesting that fall mechanics are a more important determinant of fracture risk than has been previously thought. The relationship between the energy absorbed to failure and the computed tomography data was best described by a power law (R2 = 0.90). Based on these results, it appears that quantitative computed tomography provides a potentially useful approach for the direct estimate of that component of fracture risk that can be attributed to a reduction in bone strength.
High extracellular calcium increases the production of a parathyroid hormone-like activity by cultured leydig tumor cells associated with humoral hypercalcemia
Authors: Dr. Rizzoli R. , Bonjour J.-P. 
Published: February 2010

Abstract
Cultured Leydig tumor cells produce a parathyroid hormone (PTH)-like activity, but little is known about the regulation of the release of this factor. In the present work, we investigated the influence of the extracellular calcium concentration on the production of adenylate cyclase-stimulating activity, as evaluated in the osteoblast-like PTH-responsive cell line UMR 106. Medium conditioned in the presence of 0.4 mM or 3 mM Ca elicited a 5.8 ± 0.4-fold and 10.3 ± 0.9-fold increase over basal of cAMP production, respectively (p &lt; 0.001, n = 11 experiments). This effect, which was selective for PTH-like activity, was detectable after 2 h of incubation and maximal at 6–14 h. It was abolished by the protein synthesis inhibitor cycloheximide, but not by actinomycin D or cordycepin, suggesting a post-transcriptional site of action. Thus, the production of a tumoral circulating factor implicated in the pathogenesis of humoral malignant hypercalcemia may be influenced in a positive way by an increase in extracellular calcium concentration.
Central osteosclerosis with ectodermal dysplasia: Clinical, laboratory, radiologic, and histopathologic characterization with review of the literature
Authors: Civitelli Roberto , McAlister William H. , Teitelbaum Steven L. , Dr. Whyte Michael P. 
Published: February 2010

Abstract
IBIDS is a syndrome characterized by ichthyosis, brittle hair, impaired intelligence, decreased fertility, and short stature, but unassociated with skeletal lesions. This condition is considered a form of trichothiodys-trophy because hair from several cases has been found to have a low sulfur content. We describe a 9-year and 10-month-old white boy whose clinical features resemble the IBIDS syndrome (ichthyosis, brittle hair, cataracts, and short stature), but who also has marked axial osteosclerosis and peripheral osteopenia. No abnormalities of mineral homeostasis were noted. Histopathologic assessment of nondecalcified bone specimens excluded osteopetrosis, but suggested slow skeletal remodeling. When subjected to polarized light microscopy, his hair exhibited the band-like pattern of birefringence described in trichothiodystrophy. Literature review disclosed 8 patients, 2 of whom had been diagnosed as trichothiodystrophy, with like clinical features including osteosclerosis. These skeletal abnormalities together with clinical features of the IBIDS/trichiodystrophy syndrome, we believe, reflect the prototype of a disorder that seems best described as central osteosclerosis with ectodermal dysplasia.
Mild versus definite osteoporosis: Comparison of bone densitometry techniques using different statistical models
Authors: Heuck Andreas F. , Block Jon , Glueer Claus-Christian , Steiger Peter , Dr. Genant Harry K. 
Published: February 2010

Abstract
The purpose of this investigation was to determine the ability of three bone densitometry techniques to discriminate subjects with mild vertebral deformities from those with definite compression fractures. We determined bone mineral density (BMD) in 68 postmenopausal women by quantitative computed tomography (QCT) and dual-photon absorptiometry (DPA) of the spine, as well as single-photon absorptiometry (SPA) of the radius. Forty four individuals were classified as having mild deformities of the spine and 24 were considered to have definite vertebral compressions. Several statistical approaches were used to compare these subgroups and to estimate the relative risk of vertebral fracture. Included among these were percent decrements and z-scores, ROC curves, odds ratio estimations, and logistic regression analysis. Individuals with definite vertebral fractures had lower bone mineral density at all sites, but measurement of radial compact bone by SPA failed to reach significance. Using ROC analysis to distinguish mild deformities from true compressions, we found that measurement of spinal trabecular bone by QCT to be the most sensitive discriminator; although measurement of spinal integral bone by DPA also gave satisfactory discrimination, whereas assessment of radial compact bone did not adequately differentiate patients with mild deformities from those with definite compressions. Likewise, we found determination of spinal trabecular bone to be the most robust predictor of relative risk of definite fracture using either odds ratios or logistic regression analysis. Measurement of BMD in the peripheral cortical skeleton offered no predictive power for true vertebral fracture. We concluded that direct assessment of the spine, particularly of the trabecular portion, offered the strongest discrimination and relative risk prediction for definite osteoporotic fractures compared with milder forms of this condition.
Aminohydroxypropylidene bisphosphonate (APD) treatment for tumor-associated hypercalcemia: A randomized comparison between a 3-day treatment and single 24-hour infusions
Authors: Body J. J. , Magritte A. , Seraj F. , Sculier J. P. , Borkowski A. 
Published: February 2010

Abstract
Intravenous aminohydroxypropylidene bisphosphonate (APD) normalizes serum calcium in most hypercalcemic cancer patients, however the optimal therapeutic scheme has not been established. We compared in a randomized prospective trial the efficacy and the tolerance of APD given as a 3-day treatment of daily 2-h infusions of 0.5 mg/kg·d in 250 ml of saline (group A) with single 24-h infusions of 1.5 mg/kg (group B) or of 0.5 mg/kg in 1 liter of saline (group C). Thirty-three cancer patients remaining hypercalcemic after a 48-h rehydration period were included and monitored daily until normocalcemia or treatment failure was documented. Serum calcium became normal in all but 1 patient (in group C) but remained normal for only 1 or 2 days in 4 other patients (1 in A, 1 in B, 2 in C). The decline in total or ionized serum calcium was slightly less marked in group C than in the two other groups, but the differences were not significant. The fall of fasting urinary calcium excretion was however significantly less rapid in group C (p &lt; 0.05 from day 1 to day 4). Serum concentrations of iPTH and 1,25-dihydroxyvitamin D [1,25-(OH)2D] increased significantly in the three groups. Serum magnesium concentrations fell slightly from 1.41 ± 0.05 to 1.28 ± 0.04 mEq/liter (p &lt; 0.001) after rehydration but returned to normal after APD administration (day 5, 1.52 ± 0.04 mEq/liter, p &lt; 0.001 versus day 0). On the other hand, APD induced a fall in serum phosphate levels, from 2.9 ± 0.1 to 2.3 ± 0.1 mg/dl on day 4 (p &lt; 0.001), without any significant change in TmP/GFR. Treatment was very well tolerated; we only observed 3 cases of drug-induced fever, 1 in each group. Based on this and other dose-response trials, we recommend a total dosage of 1.0 to 1.5 mg of APD/kg body weight for the therapy of tumor-associated hypercalcemia; this treatment can be safely and efficiently given as a single 24 h infusion or as daily 2 h infusions for 3 days.
The synthetic human parathyroid hormone-related protein is inhibited by a parathyroid hormone antagonist in rats in vivo
Authors: Horiuchi Noboru , Hongo Takashi , Clemens Thomas L. 
Published: February 2010

Abstract
The structure of a novel protein, parathyroid hormone-related protein (PTHrP), secreted by human tumors associated with hypercalcemia has recently been determined. Administration of a synthetic fragment of this protein in vivo reproduces features of the clinical paraneoplastic syndrome of humoral hypercalcemia of malignancy and produces biologic responses closely similar to those obtained with parathyroid hormone (PTH). A PTH antagonist designed to reversibly occupy PTH receptors inhibited major actions of the tumor peptide in vivo, including phosphaturia, urinary cAMP excretion, and increased serum ionized calcium. These studies indicate that PTHrP and PTH mediate their bioactivities through shared receptors in vivo and establish a potential specific mechanism-based approach utilizing PTH antagonists for the therapy of tumor-associated hypercalcemia.
1,25-dihydroxyvitamin D3 metabolism in a human osteosarcoma cell line and human bone cells
Authors: Miller Barbara E. , Chin David P. , Jones Glenville 
Published: February 2010

Abstract
The metabolism of 1,25-dihydroxy vitamin D3 [l,25-(OH)2D3] by a human osteoblastic sarcoma cell line, U-2 OS, and by primary cultures of human bone-derived cells was examined at physiologic (5 x 10−11 M) and pharmacologic (3.5 x 10−7 M) substrate concentrations. For metabolite identification purposes, cells nearing confluency were incubated for 18 h with 3.5 x 10−7 M l,25-(OH)2D3 in serum-free medium. The putative vitamin D metabolites produced during this incubation were isolated from a total lipid extract of cells and medium. Identification of the metabolites was achieved by comigration with authentic standards on three high-performance liquid chromatography systems, UV spectral analysis, mass spe trometry, and chemical modification by sodium borohydride and sodium metaperiodate. The identified metabolites produced from l,25-(OH)2D3 by the human osteosarcoma cells include 1,24,25-trihydroxyvitamin D3; 24-oxo-l,25-dihy-droxyvitamin D3; 24-oxo-l,23,25-trihydroxyvitamin D3; and 24,25,26,27-tetranor-l,23-dihydroxyvitamin D3. Evidence is presented that (1) l,25-(OH)2D3 metabolism occurs constitutively in U-2 OS osteosarcoma cells at a physiologic substrate concentration (5 x 11−11 M), (2) the pathway can be further induced by pharmacologic 1,25-(OH)2D3 concentrations (10−7 M), and (3) this pathway is present in primary cultures of normal human bone-derived cells.
A short course of recombinant human growth hormone treatment stimulates osteoblasts and activates bone remodeling in normal human volunteers
Authors: Dr. Brixen Kim , Nielsen Henning K. , Mosekilde Leif , Flyvbjerg Allan 
Published: February 2010

Abstract
The effects of recombinant human growth hormone (rhGH) on biochemical markers of bone turnover and bone mineral content (BMC) were investigated in 20 normal male volunteers (aged 22-31 years) randomized to treatment for 7 days with either rhGH (0.1 IU/kg subcutaneously twice a day) or placebo. Serum somatomedin C rose during treatment (p &lt; 0.001) but was not significantly different from baseline at day 14. The fasting urinary hydroxyproiine/creatinine (p &lt; 0.001) and calcium/creatinine ratios (p &lt; 0.01) increased during treatment and remained elevated for 4 and 2 weeks, respectively. Serum bone 7-carboxyglutamic acid-containing protein (BGP) increased during treatment (p &lt; 0.001) and remained elevated for 6 months (p &lt; 0.02). Serum bone alkaline phosphatase (B-AP), after an initial fall in the treatment period (p &lt; 0.001), increased slightly in the following months (p &lt; 0.01). In the rhGH group BMC was significantly higher than the prestudy value at day 14 (p &lt; 0.05) but was unaltered at the end of study. The simultaneous increase in markers of bone resorption and formation during rhGH treatment followed by a decline in resorption parameters within a few weeks and the prolonged effect on BGP and B-AP demonstrate that rhGH treatment stimulates osteoblasts and activates bone remodeling.
Prevention of glucocorticoid-induced osteoporosis
Authors: Dr. Reid Ian R. , Schooler Beth A. , Stewart Alistair W. 
Published: February 2010

Abstract
There is increasing evidence that pamidronate and related compounds are effective in the prevention and treatment of osteoporosis. It is therefore of relevance to document the time course and mechanism of bis-phosphonate action in this condition. To this end, the present study describes the biochemical responses to prophylactic treatment with oral pamidronate (APD, 150 mg/day) in 16 glucocorticoid-treated patients and contrasts them with those in 19 steroid-treated control subjects. Measurements were made over a period of 12 months.
The treated patients showed a fall in urine hydroxyproline excretion at 6 weeks associated with a reduction in serum ionized calcium concentration, a rise in serum 1,25-(OH)2D3, and a nonsignificant rise in serum bone gla protein (BGP). In contrast to BGP, serum alkaline phosphatase activity declined at 6 weeks, falling further at 3 months. Between 3 and 12 months, BGP levels paralleled those of alkaline phosphatase and hydroxyproline, all these being significantly below their initial values, and the other parameters returned to baseline. There was a gradual increase in plasma phosphate concentrations in the treated group over the 12 month period.
It is concluded that pamidronate produces an acute and sustained inhibition of bone resorption followed by a more gradual reduction in bone formation. This transient dissociation results in a reduction in serum calcium, leading to a rise in serum 1,25-(OH)2D3, which in turn stimulates BGP production. Thereafter, indices of bone turnover remain subnormal but serum calcium and 1,25-(OH)2D3 return to baseline.
Long-term estrogen replacement therapy in postmenopausal women sustains vertebral bone mineral density
Authors: Moore Marisa , Bracker Mark , Sartoris David , Saltman Paul , Strause Linda 
Published: February 2010

Abstract
The cross-sectional relationship between long-term estrogen use and vertebral (L2-4) bone mineral density (BMD) was determined in 65 postmenopausal white women between 55 and 75 years who were at least 10 years from their menopause. Long-term estrogen users began therapy within 5 years of menopause and continued for a duration of at least 10 years. The mean duration of use was 19.8 years. Controls used estrogen for less than 1 year. There was a significant difference (p &lt; 0.02) in mean spinal BMD between estrogen users (1.219 g/cm2) and controls (1.092 g/cm2). There was no significant difference in age, height, weight, or dietary calcium (Ca) intake between the two groups. The statistical difference in BMD was retained when (1) 23 estrogen users were paired with age-matched controls, (2) only women with a natural menopause or history of bilateral oophorectomy were included, and (3) only women with a natural menopause were compared. A spinal BMD below the estimated fracture threshold of 0.965 g/cm2 was found in 11 of 40 controls and only 2 of 25 estrogen users. Comparison of estrogen users with a natural menopause to those with bilateral oophorectomy revealed no significant difference in BMD. These data confirm the salutary effect of long-term estrogen use in the maintenance of vertebral bone mass in postmenopausal women.
Changes with age in the urinary excretion of lysyl- and hydroxylysylpyridinoline, two new markers of bone collagen turnover
Authors: Beardsworth Lindsay J. , Eyre David R. , Dickson Ian R. 
Published: February 2010

Abstract
Two intermolecular cross-linking amino acids, hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), are promising markers in urine of collagen resorption because their levels in urine should reflect only collagen resorption and, unlike hydroxyproline, should not be influenced by degradation of either newly synthesized collagen molecules or noncollagenous proteins. Changes with age in the urinary excretion of HP and LP were studied in 24 h collections of urine from a group of 22 male and 27 female healthy subjects aged from 2 to 70 years. The pyridinolines were quantitated, utilizing their natural fluorescence, after resolution by reversed-phase HPLC. Levels of both pyridinolines were higher in children than in adults, but in adults no evidence of age or sex variations were observed except in the 20–30 year age group. Mean values of HP/Cr and LP/Cr in 37 adults (21–70 years) were 27.2 ± 1.9 and 8.8 ± 0.8 μol/mol, respectively; in the 12 children (2–15 years) the mean values were 14.4 and 12.4 times higher than the respective adult values. Making certain assumptions, the mean amount of bone resorbed in normal adults was tentatively estimated at 1.9 g per 24 h. The finding that differences between children and adults in these relatively specific markers were greater than with hydroxyproline suggests that hydroxyproline values may considerably underestimate the actual amount of bone turnover occurring in growing children or overestimate the adult turnover rate.
Quantitation of growth factors IGF-I, SGF/IGF-II, and TGF-β in human dentin
Authors: Dr. Finkelman Richard D. , Mohan Subburaman , Jennings John C. , Taylor Arch K. , Jepsen Soren , Baylink David J. 
Published: February 2010

Abstract
Human bone matrix is known to contain a battery of polypeptide growth factors. Since dentin is a mineralized tissue similar to bone in composition and perhaps in formation, human dentin was assayed for the presence of similar growth factors.
Root dentin proteins were extracted by demineralization in 4 M guanidine hydrochloride (Gu) and 30 mM Tris (pH 7.4) containing 20% EDTA and proteinase inhibitors. Gu-EDTA extracts were desalted and used for the following assays: (1) bone cell proliferation in chick calvarial cell mitogenic assay using the incorporation of [3H]thymidine into TCA-insoluble material; (2) osteocalcin by radioimmunoassay (RIA); (3) insulinlike growth factor I (IGF-I) by RIA; (4) skeletal growth factor/insulinlike growth factor II (SGF/IGF-II) by radioreceptor assay; and (5) transforming growth factor beta (TGF-β) by bioassay.
Gu-EDTA extracts stimulated bone cell proliferation. At 10 μg/ml, dentin proteins increased the incorporation of [3H]thymidine by calvarial cells to 320% of that by BSA-treated control cells. Consistent with the presence of mitogenic activity, growth factors were found in dentin in the following concentrations (ng/μg Gu-EDTA protein): (1) IGF-I, 0.06; (2) SGF/IGF-II, 0.52; and (3) TGF-β, 0.017. All three growth factors were present in concentrations lower than that found in human bone. Osteocalcin was detected at a concentration of 3.0 mg/g Gu-EDTA protein, also much lower than that in bone.
Regulation by calcium and 1,25-(OH)2D3 of cell proliferation and function of bovine parathyroid cells in culture
Authors: Ishimi Yoshiko , Russell John , Sherwood Louis M. 
Published: February 2010

Abstract
The effects of high calcium and 1,25-(OH)2D3 on parathyroid cell growth, PTH secretion, and steady-state levels of pre-proPTH mRNA in proliferating bovine parathyroid cells were examined. Cells were established in primary tissue culture and then tested in passages 2 and 5. Cell proliferation was suppressed by 10−9-10−7 M 1,25-(OH)2D3 but not by high calcium (2.5 mM). Cells at passages 2 and 5 were grown to subconfluence and then exposed for 72 h to 2.5 mM calcium or 10 −7 M 1,25-(OH)2D3. Pre-proPTH mRNA was decreased to approximately 50% of control by 2.5 mM calcium compared with 0.3 and 1.0 mM calcium. PTH secretion, as tested by low calcium stimulation for 1 h at the end of 72 h incubation, was inhibited by 50% in cells that had been exposed to high calcium compared with control. Incubation with 10−7 M 1,25-(OH)2D3 caused a decrease in the levels of pre-proPTH mRNA and PTH release to 50% of control at 72 h. These results suggest that cultured bovine parathyroid cells, at least in early passages, have responses to high calcium and l,25-(OH)2D3 similar to those in primary nonproliferating cultures studied earlier and that 1,25-(OH)2D3 inhibits the proliferation of parathyroid cells in a dose-responsive fashion.