bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of immobilization on bone histomorphometry in rats
Authors: Turner Russell T. , Bell Norman H. 
Published: February 2010

Abstract
To determine whether immobilization acts directly on bone by alteration of mechanical loading or systemically, studies of the effects of immobilization were carried out on histomorphometry of diaphyses of tibiae and on subcutaneous implants of demineralized allogenic bone matrix of rats. The right hind leg of growing rats was denervated by severing the tibial nerve. A sham operation on the right hind leg was performed in control animals. Bone formation at the endosteal and periosteal surfaces was significantly lower in tibiae from limbs with severed nerves as compared to tibiae from the intact limbs of nerve-sectioned rats and from both limbs of sham-operated control rats. Bone formation was decreased at both 3 and 7 weeks after immobilization. The decreased formation resulted in significant reductions in cross-sectional area. At 3 weeks post denervation, the periosteal bone formation rate was lower in tibiae of intact limbs from denervated rats as compared to tibiae from intact limbs of sham-operated animals. This finding was attributed to reduced physical activity of the denervated rats. In the implants, nerve section did not alter the amount of implant matrix resorbed, the amount of bone matrix synthesized, or the amount of calcium in the implant. These findings support the hypothesis that inhibition of bone formation at the tibial diaphysis in response to immobilization resulted from altered mechanical loading and not from the production of substances acting systemically. Whereas the mean medullary area of tibiae was not altered by nerve section, it was decreased in tibiae of all groups compared to the values of basal controls, indicating that bone formation was greater than bone resorption. The findings are interpreted to mean that, in the rat, reducing the mechanical loading of an extremity inhibits bone formation at the tibial diaphysis of the affected limb and does not influence bone resorption at that site.
Preferential inhibition of cytokine-stimulated bone resorption by recombinant interferon gamma
Authors: Dr. Gowen Maxine , Nedwin Glenn E. , Mundy Gregory R. 
Published: February 2010

Abstract
It is likely that immune cells in the bone marrow produce factors which are involved in the local control of bone remodeling. Immune cell products such as interleukin-1 and the tumor necrosis factors are potent stimulators of bone resorption in vitro. In this paper, we have studied the effects of recombinant murine interferonγ on bone resorption stimulated by these agents and the systemic calcium-regulating hormones 1,25(OH)2 vitamin D3 and parathyroid hormone. We found that interferon-7 completely abolished bone resorption stimulated by the cytokines interleukin-1, tumor necrosis factor α and tumor necrosis factor ß. In contrast, parathyroid hormone- and 1,25(OH)2 vitamin D3-stimulated bone resorption were not significantly affected by the addition of interferon-γ under the same conditions. Parathyroid hormone-stimulated bone resorption was inhibited slightly when larger concentrations of interferon-γ were used for more prolonged periods. The inhibitory effects on cytokine-stimulated bone resorption occurred at interferon concentrations of 100 U/ml (half-maximal) to 300 U/ml (complete inhibition). This relatively selective inhibition of cytokine-stimulated bone resorption by an immune cell product may have physiological significance in the local control of trabecular bone volume and bone remodeling.
Effect of estrogen/gestagen and 24R,25-dihydroxyvitamin D3 therapy on bone formation in postmenopausal women
Authors: Dr. Thomsen Karsten , Riis Bente , Christiansen Claus 
Published: February 2010

Abstract
The effect of two different estrogen/gestagen regimens and 24R,25-(OH)2-cholecalciferol on bone formation was studied in a randomized trial with 144 healthy postmenopausal women. Urinary excretion (UE) of 99m-technetium-diphosphonate and serum alkaline phosphatase (AP) was determined before and then once a year for 2 years of treatment. Both estimates of bone formation showed highly significant decreases (p &lt; .001) to normal premenopausal levels in women receiving unopposed 17β-estradiol or in a sequential combination with progestagen, whereas unchanged high values were found in the groups receiving 24R,25-(OH)2D3 and placebo. The data show that bone turnover increases in early postmenopausal women concomitantly with the loss of bone mass, and that hormonal substitutional therapy normalizes the total skeletal turnover as well as preventing bone loss.
Regulation by calcium of parathyroid hormone mRNA in cultured parathyroid tissue
Authors: Brookman Jenny J. , Farrow Sheelagh M. , Nicholson Linda , O'riordan Jeffrey L.H. , Dr. Hendy Geoffrey N. 
Published: February 2010

Abstract
We have examined the effect of changes in the concentration of extracellular calcium on parathyroid hormone mRNA in both short-term (hours) and long-term (days) cultures of bovine parathyroid tissue. Using a 32P-labeled PreProPTH cDNA probe, PTH mRNA was measured by gel blot hybridization of total RNA from tissue slices incubated for 4 h in low (0.5 m M) or high (5 m M) calcium concentrations and also by dot blot hybridization of cytoplasmic RNA extracted from aggregates of partially dispersed cells cultured up to 72 h in low (0.4 m M), normal (1 m M), or high (3 m M) calcium concentrations. PTH mRNA was unchanged over 4 h while high calcium had suppressed PTH secretion. However PTH mRNA did respond during long-term culture. By 24 h in high calcium there was a 50% suppression which was maintained for a further 48 h. PTH mRNA in normal calcium remained unchanged over 72 h while in low calcium it had increased slightly by 48 h. In contrast to the effect seen in cultured bovine parathyroid cells, PTH mRNA in human parathyroid adenoma cells cultured for 48 h in high calcium was decreased by only 10%.
Effect of acute increases in bone matrix degradation on circulating levels of bone-gla protein
Authors: Dr. Riggs Lawrence B. , Tsai Kei-Sung , Mann Kenneth G. 
Published: February 2010

Abstract
Serum bone Gla-prolein (BGP), also called osteocalcin, is a specific and sensitive measure of bone turnover in a variety of metabolic bone disorders. Although some BGP diffuses into the circulation after synthesis by osteoblasts, most is incorporated into bone matrix where it remains until bone is resorbed. Thus, serum BGP could reflect bone formation, bone resorption, or a combination of both. The relationship of serum BGP to the components of bone turnover was evaluated in 18 normal women (mean age 48 yr; range 30-70) who received a continuous 24-h intravenous infusion of the 1-34 synthetic fragment of bovine parathyroid hormone. Mean ± SE for urinary hydroxyproline excretion, an index of bone resorption, increased (from 22.7 ± 2.2 to 38.5 ± 3.7 μg/100 ml glomerular filtrate [GF], p &lt; .001), whereas levels of serum alkaline phosphatase, an index of bone formation, were unchanged (from 20 ± 1 to 20 ± 1 U/liter, NS). Despite the increase in bone resorption, levels of serum BGP decreased (from 8.8 ± 0.8 to 6.8 ng/dl, p &lt; .001). The data suggest that circulating levels of BGP are a measure of bone formation but, at least in subjects with normal renal function, not a measure of bone resorption. Presumably BGP in bone matrix is degraded during osteoclastic resorption into fragments that either are not recognized by an antiserum raised against the native molecule or are rapidly cleared from the circulation.
Calcitonin receptor binding as a marker of osteoclast heterogeneity in osteopetrotic rodents
Authors: Rouleau Marie F. , Warshawsky Hershey , Marks Sandy C. , Goltzman David 
Published: February 2010

Abstract
We have employed a radioautographic technique to examine in vivo receptor binding of calcitonin to osteoclasts in four rodent mutants with osteopetrosis. 125I-Labeled calcitonin was injected intravenously alone or with excess unlabeled calcitonin to osteopetrotic (op/op), osteosclerotic (oc/oc), and microphthalmic (mi/mi) mice and to incisor absent (ia/ia) rats. Similar experiments were performed simultaneously in phenotypically normal littermates. Specific binding of calcitonin to receptors on osteoclasts and osteoclast morphology were then examined by light and electron microscope radioautography. Calcitonin binding was increased in mi/mi mice, where osteoclasts were abundant but reduced in size, and was also increased in op/op mice in association with an undulated and redundant osteoclast cell membrane. Binding of the hormone was markedly diminished on osteoclasts of oc/oc mice and ia/ia rats. Thus, in these rodent models of osteopetrosis all of which manifest reduced skeletal remodeling and share a recessive pattern of inheritance, considerable heterogeneity of osteoclast characteristics was demonstrable. Although calcitonin may play no primary pathogenetic role in most forms of this disease, calcitonin receptor binding is a morphological and functional marker of osteoclasts that can be used in assessing the pathophysiology of disorders of bone remodeling.
Attainment of therapeutic fluoride levels in serum without major side effects using a slow-release preparation of sodium fluoride in postmenopausal osteoporosis
Authors: Pak Charles Y.C. , Sakhaee Khashayar , Gallagher Christopher , Parcel Carol , Peterson Roy , Zerwekh Joseph E. , Lemke Martha , Britton Faye , Hsu Ming-Chue , Adams Beverley 
Published: February 2010

Abstract
The bioavailability, biochemical effects, and safety of a slow-release preparation of sodium fluoride were examined. In 8 normal volunteers, a single administration of slow-release sodium fluoride (25 mg) caused a slow rise and gradual decline in serum fluoride concentration, thus avoiding sharp peaks produced by a rapid-release preparation. In 37 patients with postmenopausal osteoporosis, serum fluoride concentration was kept within the “therapeutic window” (95-100 ng/ml) during long-term intermittent sodium fluoride (slow-release) therapy (25 mg twice/day, given for 3 months in each 5-month cycle over five cycles). Serum fluoride was also kept within the therapeutic window in 64 patients who took sodium fluoride (slow release) continuously over 12 months. Serum osteocalcin concentration increased progressively during fluoride treatment (correlation coefficient of 0.88, p &lt; .001 for the relationship between serum osteocalcin and duration of therapy). Side effects to slow-release sodium fluoride therapy, assessed in 101 patients at two study sites, were minor and included diarrhea in 2 patients, nausea in 2 patients, abdominal pain and cramping in 2 patients, foot pain in 2 patients, and joint pain in 6 patients. Thus, slow-release sodium fluoride confers desired level of fluoride in serum, while providing safety of usage.
The effect of 1α-hydroxyvitamin D3 on the mineralization defect in disodium etidronate-treated paget's disease — a double-blind randomized clinical study
Authors: Ralston S.H. , Boyce B.F. , Cowan R.A. , Fogelman I. , Smith M.L. , Jenkins A. , Boyle I.T. 
Published: February 2010

Abstract
A double-blind randomized study of 29 patients with symptomatic Paget's disease was conducted comparing the clinical, biochemical, and histomorphometric responses to 3-month treatment with placebo (10 patients), low-dose disodium etidronate (EHDP) (5–7 mg/kg/day) (10 patients), and low-dose EHDP plus 1α-hydroxy-vitamin D3 (1αD3) 0.5 mcg daily (9 patients). In placebo-treated patients no significant changes were observed in symptoms, biochemistry, or bone histomorphometry. Histologically apparent mineralization defects developed after 3 months of therapy in 90% of patients in the EHDP group, compared with 45% of patients in the EHDP/1αD3 group. In 19% of the patients treated with active medication, the mineralization defects in pagetic bone were accompanied by histological evidence of continued osteoclastic resorption. The development of mineralization defects was not related to serum levels of vitamin D metabolites, alkaline phosphatase, or intestinal calcium absorption but did correlate with the occurrence of hyperphosphatemia during treatment, which was most marked in patients treated with EHDP alone. Although mineralization defects were less frequent in the EHDP/1αD3 group, these patients also responded less well symptomatically, thus limiting the potential usefulness of this drug combination in Paget's disease. It is suggested that the diminished response in the EHDP/1αD3 group and the lower frequency of mineralization defects may have been related to an alteration in the intestinal absorption of EHDP by the vitamin D metabolite.
Of patients treated with EHDP alone, 90% had symptomatic and biochemical improvement, suggesting that this agent is generally an effective and safe treatment in Paget's disease. However, in view of the high incidence of mineralization defects, we would continue to advise caution in the use of EHDP where there is significant deformity of, or lytic lesions, in weight-bearing bones.
Changes in the mineral density distribution in human bone with age: Image analysis using backscattered electrons in the SEM
Authors: Reid S.A. , Boyde A. 
Published: February 2010

Abstract
We report a study to test the feasibility of studying mineral density distributions in bone using the backscattered electron signal in scanning electron microscopy. Samples were human sixth ribs ranging in age from 8 weeks to 59 years, embedded in polymethylmethacrylate (PMMA), cut, polished, and carbon coated. The proportions of pixels falling in a uniform set of gray level slices of the BSE signal were determined using a microcomputer-based image analysis system interfaced directly to the SEM. The amount of high-density bone gradually increased with age at the expense of low-density bone, and there was an associated compression of the range of the mineral density distribution. Age-related differences were noted between the density distributions in the outer and inner rib cortices. The distribution in the inner cortex in neonates was influenced by the inclusion of densely mineralized endochondral bone and cartilage trabeculae formed at the growth cartilage zone. In adults it appeared that greater bone turnover occurred in the outer cortex, perhaps reflecting a differential mechanical loading across the rib. The technique enabled rapid, unbiased discrimination between the bone of neonates, children, and adults.
Rapid action of 1,25-dihydroxyvitamin D3 on calcium transport in perfused chick duodenum: Effect of inhibitors
Authors: Nemere Ilka , Dr. Norman Anthony W. 
Published: February 2010

Abstract
Transport of 45Ca from the lumen to the venous effluent was studied in duodena of normal, vitamin D3-replete (+D) chicks perfused through the celiac artery with 130 pM 1,25(OH)2D3 or vehicle. Administration of actinomycin D 3 h prior to perfusion did not alter the unstimulated transport rate or diminish the response to exogenous 1,25(OH)2D3: After 40 min exposure to the seco-steroid, 45Ca in the vascular effluent was 140% of control levels. The anti-microfilament agent cytochalasin b and the ionophore monensin, an inhibitor of Golgi function, similarly failed to suppress 1,25(OH)2D3-stimulated calcium transport. In pilot studies, Golgi and basal-lateral membrane fractions were prepared from duodenal epithelium of vitamin D-deficient (-D) chicks treated with vehicle or 650 pmol of 1,25(OH)2D3in vivo 2 h, 10 h, or 15 h before sacrifice, as well as from +D birds. Analyses of Golgi fractions for cathepsin B (CB) activity revealed a biphasic response with time, increasing to 200% of -D levels 2 h after 1,25(OH)2D3 administration and in equivalent preparations from +D birds. Less pronounced increases in acid phosphatase activity were observed in the same membrane fractions. In basal-lateral membranes, enhanced CB activity was detectable 10 h after 1,25(OH)2D3in vivo, rose to 155% of -D levels at 15 h, and to 245% of controls in fractions from +D birds, whereas acid phosphatase was 75%, 81%, and 125% of controls, respectively, at these times. Levels of CB in whole homogenates from which membranes were isolated rose to 200% of controls at 2 h and 10 h after 1,25(OH)2D3, but declined to 112% of controls in +D chicks. Acid phosphatase levels in the same homogenates were lower than or equivalent to control levels. These findings suggested additional perfusion studies in normal birds. Although vascular perfusion with iodoacetate and 1,25(OH)2D3, or leupeptin and 1,25(OH)2D3, failed to inhibit the effect of the vitamin D metabolite, 1,25(OH)2D3-enhanced calcium transport was abolished by addition of 1 mM leupeptin to the lumenal medium, but not by 1 mM pepstatin. The combined data suggest that lysosomes or their hydrolases may be involved in 1,25(OH)2D3-mediated transport of calcium across intestinal epithelial cells.
Microvascular organization at the epiphyseal-metaphyseal junction of growing rats
Authors: Arsenault A. Larry 
Published: February 2010

Abstract
The microarchitecture of the rat metaphyseal nutrient artery, the major blood supply to the calcifying epiphyseal growth plate, was studied by light microscopic serial sections, model reconstruction of serial sections, and scanning electron microscopy of plastic corrosion castings. These techniques illustrate how the metaphyseal artery undergoes extensive arborization and anastomosis upon route through the metaphysis. From this vascular network, closed capillary sprouts abut hypertrophic chondrocytes bordered by scaffolds of mineralized matrix.
Comparison of the effects of auranofin, gold sodium thiomalate, and penicillamine on resorption of cultured fetal rat long bones
Authors: Vargas Socorro J. , Jones Thomas G. , Hurley Marja M. , Raisz Lawrence G. 
Published: February 2010

Abstract
We compared three antirheumatic agents: auranofin (Aur), gold sodium thiomalate (GST), and penicillamine (Pen) for their effect on resorption in control unstimulated cultures of fetal rat long bones and in cultures stimulated by parathyroid hormone (PTH), prostaglandin E2 (PGE2), and murine interleukin-1 (mIL-1). Aur (3 × 10−6M) and GST (10−4M) inhibited PTH-stimulated bone resorption by 39 and 42%, respectively. The same concentrations of Aur and GST inhibited PGE2-stimulated bones by 72 and 44, respectively, and mIL-1-stimulated bones by 74 and 50%, respectively. Pen (10−4M) was not effective against any of the stimulators. Dose-response curves showed that Aur was at least 10 times more potent than GST. Inhibition by Aur was sustained after removal of the drug, while there was full recovery from GST. Aur inhibited 3H-thymidine and 3H-proline incorporation into bones, while GST had no effect. Aur and GST decreased β-glucuronidase activity to undetectable levels at five days of culture. Part of the therapeutic effectiveness of Aur and GST may reside in their ability to inhibit periarticular destruction by inhibiting PGE2- and IL-1-mediated osteoclastic bone resorption.
Evidence that calcium modulates circulating 25-hydroxyvitamin D in man
Authors: Dr. Bell Norman H. , Shaw Sheryl , Turner Russell T. 
Published: February 2010

Abstract
We previously demonstrated in normal subjects that 1,25-dihydroxyvitamin D3 (1,25(OH)2D) can prevent the increase in serum 25-hydroxyvitamin D (25-OHD) which occurs in response to vitamin D. An investigation was carried out in eight normal subjects, therefore, to determine whether increases in calcium intake would alter the response of serum 25-OHD to challenge with vitamin D. In control studies, vitamin D, 100,000 U/d for 4 d, significantly increased mean serum 25-OHD from 18 ± 3 to 42 ± 5 ng/ml (p &lt; 0.001), an increment of 24 ng/ml (133%). Mean serum calcium, ionized calcium, phosphorus, creatinine, and 1,25(OH)2D did not change. In contrast, the same dose of vitamin D and calcium, 2,000 mg/d for 4 d, administered to the same eight subjects produced an increase in mean serum 25-OHD from 19 ± 3 to 31 ± 4 ng/ml (p &lt; 0.001), an increment of only 12 ng/ml (63%) and significantly less than the control (p &lt; 0.02). Mean serum calcium (8.8 ± 0.1 vs. 9.2 ± 0.1 mg/dl, p &lt; 0.01) and ionized calcium (4.79 ± 0.07 vs. 4.85 ± 0.08 mg/dl, p &lt; 0.05) increased significantly in response to vitamin D and calcium, mean serum phosphorus and creatinine did not change, and mean serum 1,25(OH)2D decreased significantly (37 ± 2 vs. 31 ±4 pg/ml, p &lt; 0.02). In a postcontrol study in six of the normal subjects, vitamin D again significantly increased mean serum 25-OHD from 17 ± 3 to 39 ± 9 ng/ml (p &lt; 0.02), an increment of 22 ng/ml (129%). Urinary calcium increased significantly on each of the four days of the administration of calcium as compared to the control study. The results provide evidence that changes in calcium intake can modulate the metabolism of 25-OHD in man.
Characterization of a human osteoblastic osteosarcoma cell line (SAOS-2) with high bone alkaline phosphatase activity
Authors: Murray Elsa , Provvedini Diego , Curran Deborah , Catherwood Bayard , Sussman Howard , Manolagas Stavros 
Published: February 2010

Abstract
We characterized the alkaline phosphatase activity of the human osteogenic sarcoma cell line, SAOS-2, and studied the regulation of this enzyme and 3',5'-cyclic adenosine monophosphate levels by 1,25-dihydroxyvitamin D3 and triamcinolone acetonide. We report that the basal alkaline phosphatase activity of SAOS-2 cells was 100–1000 times greater than that of other established human osteogenic sarcoma cell lines. The enzymatic activity was thermolabile, could be inhibited by levamisole and L-homoarginine, but not by L-phenylalanine, and was immunoprecipitable with anti-bone/liver/kidney, but not with anti-placental antibody, confirming that it is the tissue-unspecific or bone/liver/kidney isoenzyme. However, in contrast to other established human osteosarcoma cell lines (TE-85, SAOS-1), in which alkaline phosphatase activity is stimulated several-fold by the steroid hormones 1,25-dihydroxyvitamin D3 and hydrocortisone, the alkaline phosphatase activity of SAOS-2 cells was not affected by 1,25-dihydroxyvitamin D3 treatment despite the presence of classical receptors for this hormone. Furthermore, administration of the potent glucocorticoid analogue, triamcinolone acetonide, induced only a modest increase in activity. The SAOS-2 cell line expressed low basal cAMP levels (28 pmol/106 cells) which could be increased 25–40 times by pretreatment with parathyroid hormone. However, unlike other osteoblastic models, in which PTH-induced cAMP stimulation is modulated by 1,25-dihydroxy vitamin D3 and glucocorticoids, neither of these hormones had an effect on the PTH-stimulated cAMP levels in SAOS-2 cells. We conclude that the SAOS-2 cell line is an osteoblastic cell model which expresses high levels of tissue-unspecific alkaline phosphatase activity and exhibits limited responsiveness to two steroid hormones. These cells may prove useful in determining the structure and processing of alkaline phosphatase and in studying other features of the osteoblastic phenotype, such as cAMP production, and their hormonal regulation.