bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics of an ovariectomized osteopenic rat model
Authors: Yamazaki Iwao , Yamaguchi Hikoharu 
Published: February 2010

Abstract
Although osteoporosis induced by ovariectomy (Ovx) in the rat has been widely used as a model for postmenopausal osteoporosis in humans, the findings of different investigators are not always consistent. This might be mainly due to differences in the age of the animals at Ovx, time after Ovx, and the variables measured. Therefore, in the present study, Ovx was performed at 4, 10, or 52 weeks and bone changes were observed in rats for 6 months. The effects of Ovx on body weight, femoral length, and femoral volume were marked in rats operated on at the age of 4 weeks, slight in rats operated on at the age of 52 weeks, and intermediate in rats operated on at the age of 10 weeks. A reduction in the ratio of cortical thickness to bone width at the midshaft of the femur was observed only in rats ovariectomized at 52 weeks of age. The specific gravity of the femur and the density of the metaphysis of the femur decreased after Ovx in all rats. The ratio of ash weight to dry weight of the femur, a measure of the normal calcification of bone, was unchanged shortly after Ovx but gradually decreased in all rats.
Purification and characterization of human bone tartrate-resistant acid phosphatase
Authors: Allen Susan H. , Nuttleman Peter R. , Ketcham Catherine M. , Roberts R. Michael 
Published: February 2010

Abstract
Tartrate-resistant acid phosphatase (TRAP) is a histochemical marker for osteoclasts, the multinucleated bone resorbing cell. This type 5 acid phosphatase has been purified 500-fold from human bone by three chromatographic steps: cation exchange, gel filtration, and HPLC cation exchange. Like most other TRAPs isolated, it is a basic glycoprotein of a molecular weight about 33,000. Its pH optimum, Km, and Vmax for p-nitrophenyl phosphate are 5.7, 0.8 mM, and 12 units/mg, respectively. Human bone TRAP hydrolyzes aryl phosphates, nucleoside di- and triphosphates, pyrophosphate, and phosphoproteins. It is activated by mild reducing agents but inhibited by molybdate, fluoride, arsenate, phosphate, and dithionite. Its activity is not inhibited by tartrate, a feature that distinguishes it from other acid phosphatases. Sodium etridonate, the bisphosphonate used clinically to reduce bone resorption, is a relatively poor inhibitor of bone TRAP. Human bone TRAP is immunologically related to the porcine uterine secretory TRAP, uteroferrin. Monospecific rabbit antibodies to the bone TRAP have been immunopurified by using affinity chromatography with uteroferrin immobilized on Sepharose and can be used to detect low amounts of the enzyme in a simple dot-blot assay.
Parathyroid function in paget's disease of bone
Authors: Siris Ethel S. , Clemens Thomas P. , McMahon Don , Gordon Arline , Jacobs Thomas P. , Canfield Robert E. 
Published: February 2010

Abstract
In order to determine the prevalence of secondary hyperparathyroidism in patients with Paget's disease of bone, we measured serum parathyroid hormone levels (N-terminal assay) in 39 patients with a wide range of pagetic activity. All patients had normal serum calcium levels. A total of 30 patients were either untreated or had received no treatment for 6 months or longer when studied; the other 9 were receiving either salmon calcitonin (3) or EHDP (6). The results showed that in 7 of the 39 patients (18%) parathyroid hormone levels were increased above normal. These were among the most severely affected cases, as manifested by the degree of elevation of three pagetic biochemical indices: serum alkaline phosphatase, plasma bone Gla protein, and 24 h urinary hydroxyproline-creatinine ratios. Levels of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 were normal.
We examined the relationships between parathyroid hormone and each of the three pagetic indices as well as serum calcium for the entire group of 39 patients. Parathyroid hormone values did not correlate with serum calcium measurements (r = −0.241, p = NS) but did correlate significantly with serum alkaline phosphatase (r = 0.496, p &lt; 0.001), plasma bone Gla protein (r = 0.537, p &lt; 0.001), and urinary hydroxy-proline (r = 0.450, p &lt; 0.011). We conclude that relative or absolute increases in parathyroid hormone may occur in moderately active Paget's disease, possibly in the setting of greater calcium demands during periods of increased pagetic new bone formation. This may be of pathophysiologic importance, since higher concentrations of parathyroid hormone may drive responsive pagetic osteoclasts to levels of bone-resorbing activity that exceed their intrinsically augmented states, contributing to the metabolic expression of the Paget's disease.
Effects of oral contraceptive and estrogen administration on plasma calcitonin in pre- and postmenopausal women
Authors: Hurley Daniel L. , Tiegs Robert D. , Barta Joyce , Laakso Karen , Dr. Heath Hunter 
Published: February 2010

Abstract
Estrogen (E) therapy and administration of oral contraceptives (OC) reportedly increase plasma calcitonin (CT) concentrations in women, effects said to mediate in part the beneficial actions of E on bone. To further examine this theory, we tested the effects of three cycles of OC therapy in 12 young women, comparing them to 10 healthy women before and after three normal menstrual cycles. We also determined the effects of 3 months of E therapy (ethinyl estradiol, 20 μg/day, 25 of 30 days) in 14 healthy postmenopausal women, using a crossover design (studied after 3 months with and 3 months without E). We determined CT by radioimmunoassay (antiserum G-1701) in whole plasma (iCT) and silica cartridge extracts of plasma (exCT) after overnight fasting, after calcium (Ca) infusion (2 mg Ca/kg over 5 minutes), and during a normal day at 0800, 1200, 1700, and 2000 h. In no control study was there a significant diurnal change in iCT or exCT, and neither OC nor E therapy altered this. Similarly, OC administration did not affect basal CT levels or the normal iCT and exCT responses to Ca infusion. E therapy induced expected changes in serum Ca, phosphorus, and alkaline phosphatase and urinary Ca and cAMP excretion; basal and diurnal plasma exCT levels were decreased significantly, consonant with the decrement in serum Ca. E did not alter normal iCT and exCT responses to Ca infusion. Thus, administration of either OC or E has no stimulatory effect on CT secretion, which suggests that the beneficial actions of E on bone are not mediated through CT-induced inhibition of bone resorption. Interaction of E with CT action at the cellular level is not excluded by these findings, but there are no data to support such a proposal.
Bone mineral density in women with type II diabetes mellitus
Authors: Weinstock Ruth S. , Goland Robin S. , Shane Elizabeth , Clemens Thomas L. , Lindsay Robert , Dr. Bilezikian John P. 
Published: February 2010

Abstract
Bone mineral density (BMD) was assessed in 28 women with type II diabetes mellitus and compared to 207 age-matched nondiabetic women. Mean BMD, as measured by dual-photon absorptiometry, 1.12 ± 0.3 g/cm2 (±SEM), was similar to the mean BMD of control subjects, 1.06 ± 0.1 g/cm2. Only 1 of the 28 diabetic patients had a BMD less than 0.95 g/cm2 (“fracture threshold”), whereas 25% of the control subjects had a BMD below that level. When diabetic and control subjects were matched for weight as well as age, the data continued to show similar BMD among both groups. Moreover, the disparity between the proportion of weight-matched controls (25%) and diabetic subjects (1 of 28) with a BMD below the fracture threshold persisted. Among the group of 17 diabetic subjects receiving insulin, there was a positive relationship between BMD and insulin dose. There was no significant relationship between BMD, duration of diabetes, or hemoglobin A1c. Thus, women with type II diabetes are not at increased risk for diminished BMD and may be protected against bone loss.
A model system for assessing physicochemical factors affecting calcium absorbability from the intestinal tract
Authors: Dr. Pak Charles Y.C. , Poindexter John , Finlayson Birdwell 
Published: February 2010

Abstract
An in vitro model system was utilized to critically examine physicochemical factors that could play a role in determining the amount of potentially absorbable ionic calcium as well as soluble complexes in the proximal jejunum following ingestion of tricalcium dicitrate, calcium carbonate, or tricalcium diphosphate. The solubility of calcium salts (500 mg calcium each) was tested in 300 ml water containing varying amounts of hydrochloric acid (0, 0.72, 2.4, 7.26, and 24.2 mEq) intended to mimic achlorhydric to peak acid secretory states. Whereas 20% of calcium citrate dissolved in the absence of hydrochloric acid, a negligible amount of calcium carbonate and calcium phosphate underwent dissolution. In solutions containing 0.72–7.26 mEq hydrochloric acid, calcium citrate was more than twofold soluble than calcium carbonate, and calcium phosphate had intermediate solubility. At simulated peak acid secretion, all three salts were completely soluble, or nearly so.
To simulate pancreatic bicarbonate secretion, the filtrates obtained from solubility studies were titrated to pH 5, 6, and 7 with sodium hydroxide. Reprecipitation of calcium citrate and calcium carbonate did not occur. However, substantial calcium phosphate reprecipitation took place especially at high pH and in filtrates derived from high hydrochloric acid content.
In filtrates derived from reprecipitation experiments (at pH 6 and 7), anionic complexation of calcium was calculated in order to estimate the amount of ionic and complexed calcium. Considerable amount of calcium from dissolved calcium citrate was complexed (60–65%), principally as soluble CaCit−, whereas calcium complexation was negligible in the calcium carbonate and calcium phosphate systems.
Regulation of osteosarcoma EGF receptor affinity by phorbol ester and cyclic AMP
Authors: Borst Stephen E. , Catherwood Bayard D. 
Published: February 2010

Abstract
We studied the binding and degradation of 125I-labeled epidermal growth factor (EGF) by UMR-106 osteosarcoma cells and the regulation of EGF receptor affinity for EGF by the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and by treatments that raise intracellular levels of cyclic AMP. Cell surface binding of [125I]EGF to A431 cells reached a plateau after a 30 minute incubation at 37°C but was undetectable in UMR-106 cells. Degradation of [125I]EGF proceeded at a 50-fold higher rate in A431 cells on a per cell basis, but receptor-bound [125I]EGF was internalized and degraded at a 3.5-fold higher rate by UMR-106 cells on a per receptor basis. At 4°C, [125I]EGF labeled a single class of surface binding sites in the UMR-106 cell. Treatment with TPA at 37°C reduced subsequent cell surface binding of [125I]EGF at 4°C a maximum of 80% with an IC50 of 1.25 ng/ml. Maximal TPA reduction of [125I]EGF binding was observed within 5–15 minutes and was due to a reduction in the affinity of cell surface receptors of [125I]EGF without a change in receptor density. Pretreatment of the cells for 4 h with 30 μM forskolin, 1 mM isobutylmethylxanthine (IBMX) plus 30 μM forskolin, or 1 mM IBMX plus 100 ng/ml parathyroid hormone (PTH) attenuated the loss in [125I]EGF binding caused by a subsequent dose of 10 ng/ml of TPA by 17% (p &lt; 0.0005), 39% (p &lt; 0.0002), and 35% (p &lt; 0.002), respectively. We concluded that activation of protein kinase C decreases the affinity of UMR-106 EGF receptors and that this action may be opposed by the activation of cyclic AMP-dependent protein kinase.
Models of spinal trabecular bone loss as determined by quantitative computed tomography
Authors: Block Jon E. , Smith Rebecca , Glueer Claus-Christian , Steiger Peter , Ettinger Bruce , Genant Harry K. 
Published: February 2010

Abstract
Noninvasive bone densitometry techniques have significantly improved our understanding of the pattern and magnitude of bone loss over the life span. Quantitative computed tomography (QCT) is capable of selectively measuring highly labile trabecular bone in the central portion of the vertebrae. Trabecular bone mineral density (mg/ml) was determined in 538 healthy women ranging in age from 20 to 80 using GE CT/T scanners at 80 kVp. Various statistical regressions were performed for the entire population to describe the general pattern of bone loss from the spine; a cubic model (r = -0.69, SEE = 26.0 mg/ml) was found to be statistically superior (p &lt; 0.01) to linear, quadratic, or exponential models. An average bone loss was approximated from these regression analyses with a yearly absolute rate of -2.02 ± 0.097 mg/ml per year (p &lt; 0.0001). The average rate of change for premenopausal women was -0.45 mg/ml per year (p &lt; 0.05), for perimenopausal women was -4.39 mg/ml per year (p &lt; 0.0001) and for postmenopausal women was -1.99 mg/ml per year (p &lt; 0.0001). QCT values were also stratified into 5 and 10 year age groups and analyzed seperately for pre- and postmenopausal women. The 5 and 10 year interval stratification revealed no identifiable bone density decrements prior to midlife using analysis of variance statistical methods; significant losses of bone mineral density were noted to correspond with the usual time of menopause and to continue into old age. Various two-phase regressions were employed using age and menstrual status to improve the description of age- and menopause-related bone loss. For all women, a linear-exponential pattern (r = -0.70, SEE = 25.44 mg/ml) with a decrement of 25 mg/ml across the early menopause, appeared most plausible, amounting to an average bone loss of 60% over the life span. We provide normative data here on spinal trabecular bone density appropriate for clinical comparison of female subjects encompassing the adult age range and menopausal status.
Parathyroid hormone-related protein: Immunohistochemical localization in cancers and in normal skin
Authors: Danks J. A. , Ebeling P. R. , Hayman J. , Chou S. T. , Moseley J. M. , Dunlop J. , Kemp B. E. , Martin T. J. 
Published: February 2010

Abstract
An immunoperoxidase method has been developed to detect parathyroid hormone-related protein (PTHrP) in histological specimens of tumors and of normal skin. A rabbit polyclonal antiserum against PTHrP-(1–16) was used that did not cross-react with PTH-(1–34) either under radioimmunoassay conditions or at the high antiserum concentrations used in neutralizing biologic activity. PTHrP antigen was detected in the keratinocyte layer of normal skin and in 100% of 34 samples of squamous cell cancers but in only one of six breast cancers, and none of 15 other adenocarcinomata. It was also detected in four of four samples of renal cortical carcinoma and two of two of melanoma, both of which can be associated with hypercalcemia, and three of three small cell carcinomata of the lung. Immunologic detection of PTHrP could be useful in the diagnosis of tumors of squamous cell origin, particularly in the cytological differentiation of lung cancers, where it may be of value in distinguishing between squamous cell and small cell carcinoma on the one hand and poorly differentiated adenocarcinoma on the other.
Skeletal disease in primary hyperparathyroidism
Authors: Silverberg Shonni J. , Shane Elizabeth , de la Cruz Luz , Dempster David W. , Feldman Frieda , Seldin David , Jacobs Thomas P. , Siris Ethel S. , Cafferty Maureen , Parisien May V. , Lindsay Robert , Clemens Thomas L. , Dr. Bilezikian John P. 
Published: February 2010

Abstract
Most patients with primary hyperparathyroidism in the 1980s do not have evidence of bone disease when they are evaluated by conventional radiography. We sought to determine whether skeletal involvement can be appreciated when more sensitive techniques, such as bone densitometry and bone biopsy, are utilized. We investigated 52 patients with primary hyperparathyroidism. They had mild hypercalcemia, 2.8 ± 0.03 mmol/liter (11.1 ± 0.1 mg/dl), low normal phosphorus, 0.9 ± 0.03 mmol/liter (2.8 ± 0.1 mg/dl), and no symptoms or specific radiological signs of skeletal involvement.
The greatest reduction in bone mineral density was found at the site of predominantly cortical bone, the radius (0.54 ± 0.1 g/cm; 79 ± 2% of expected), whereas the site of predominantly cancellous bone, the lumbar spine (1.07 ± 0.03 g/cm2), was normal (95 ± 3% of expected). The site of mixed composition, the femoral neck (0.78 ± 0.14 g/cm2), gave an intermediate value (89 ± 2% of expected). Preferential involvement of cortical bone with apparent preservation of cancellous bone in primary hyperparathyroidism was confirmed by percutaneous bone biopsy. Over 80% of patients had a mean cortical width below the expected mean, whereas cancellous bone volume in over 80% of patients was above the expected mean. The results indicate that the majority of patients with asymptomatic primary hyperparathyroidism have evidence by bone densitometry and bone biopsy for cortical bone disease. The results also indicate that the mild hyperparathyroid state may be protective of cancellous bone. The therapeutic implications of these observations await further longitudinal experience with this study population.
Normal vertebral dimensions and normal variation in serial measurements of vertebrae
Authors: Davies K. Michael , Recker Robert R. , Heaney Robert P. 
Published: February 2010

Abstract
A total of 568 lateral spine radiographs of 191 generally healthy white perimenopausal women were used to determine the limits of normal for shape and dimensions of the vertebral bodies most often involved in osteoporotic fracture. Anterior and posterior vertebral heights for T7–L4 were used to compute wedge shape, relative posterior height, and relative serial change. Wedge shape was defined as anterior height minus posterior height divided by posterior height. Relative posterior height was defined as the posterior height of a vertebra minus the posterior height of the vertebra superior divided by the posterior height of the vertebra superior.
The degree of normal wedging depended on position: wedge values progressed down the spine, from a mean of −0.106 at T7 to 0.048 at L4. The minimum normal wedge value ranged from −0.209 at T7 to −0.083 at L4.
Radiographs on a cohort of 28 osteoporotic women were evaluated both by ordinary clinical reading of the radiographs and by using the standards developed from the normal subjects. Initial agreement between the two modes of assessment was 85.4%, and in resolving the remaining disagreements the clinician agreed that he had initially misread the films in all but 3.2%. On the basis of this limited experience, we conclude that the use of such objective standards, in a computer-operated algorithm, is more accurate than routine radiographic assessment.
Serial x-rays spanning a 15–20 year period in these women permitted determination of both reproducibility and longitudinal change in vertebral dimensions in the perimenopause. The mean relative serial change was not significantly different from zero for all vertebrae. The normal lower bound for relative change in measured vertebral heights ranged between −10 and −16% anteriorly and −11 and −19% posteriorly.
Normal vertebral dimensions were found to vary from vertebra to vertebra; criteria for deformity should allow for this variation to avoid misdiagnosis.
Ultrastructural localization of tartrate-resistant, purple acid phosphatase in rat osteoclasts by histochemistry and immunocytochemistry
Authors: Clark Samuel A. , Ambrose Wallace W. , Anderson Thomas R. , Terrell Regina S. , Dr. Toverud Svein U. 
Published: February 2010

Abstract
The intracellular localization of the tartrate-resistant purple acid phosphatase in osteoclasts of developing rat bone has been determined immunocytochemically using an antiserum to the purified bone-derived purple acid phosphatase. The localization of the immunoreactivity was compared with the results of enzyme histochemistry using p-nitrophenylphosphate as substrate and 10 mM tartrate. Both methods revealed the presence of the enzyme in numerous vesicles of various sizes up to 2–3 μm in diameter and in granules. There was no immunoreactivity in the Golgi apparatus, and tartrate completely inhibited the histochemical activity of this organelle. No consistent extracellular activity could be detected, nor was any reaction product observed at the ruffled border. The localization of the tartrate-resistant purple acid phosphatase in osteoclasts is consistent with an intracellular function for this enzyme.
G protein-dependent activation of a phosphoinositide-specific phospholipase C in UMR-106 osteosarcoma cell membranes
Authors: Babich Michael , King Kathleen L. , Nissenson Robert A. 
Published: February 2010

AbstractRecent evidence suggests that guanyl nucleotide binding (G) proteins are involved in receptor-mediated bone resorption and in osteoblastic function, but the nature of the G protein coupled to effectors that are involved in these skeletal effects is unknown. The purposes of this study were to determine (1) whether a G protein mediates activation of phosphoinositide-specific phospholipase C in UMR-106 rat osteosarcoma cells, and (2) whether parathyroid hormone (PTH) and a PTH-like protein (PLP) associated with humoral hypercalcemia of malignancy promote GTP-dependent PIP2 hydrolysis. Addition of GTP (10−4 M) or guanosine 5′-0-(3-thiotriphosphate, GTPγS, 10−5 M) to membranes prepared from UMR-106 cells labeled with [3H]myo-inositol increased both [3H]inositol trisphosphate (IP3) and [3H]inositol bisphosphate (IP2) formation. The increases in [3H]IP2 and [3H]IP3 produced by GTP were 8.6- and 4.3-fold, respectively. GTPγS produced a 17.6- and 11.9-fold increase in [3H]IP2 and [3H]IP3, respectively. The stimulatory effects of GTP and GTPγS were dose dependent (GTP ED50 = 3.9 × 10−6 M; GTPγS ED50 = 2.5 × 10−7 M) and progressive over 10 minutes and required the presence of Mg2+. GTP (10−4 M) and GTPγS (10−5 M) decreased membrane [3H]phosphoinositides concomitantly with increased [3H]IP2 and [3H]IP3. The GDP analog guanosine 5′-O-(2-thiodiphosphate, GDPβ) alone did not alter [3H]IP2 or [3H]IP3 production but at 10−4 M blocks the stimulatory effects of GTP and GTPγS. NaF (3 × 10−2 M) produced a 2.8- and 2.0-fold stimulation of [3H]IP2 and [3H]IP3, respectively. In the presence of 10−4 M GTP, bPTH-(1–34) (1 μg/ml) produced an increase in [3H]IP3 and [3H]IP2 of 23.5 + 3.0% (p &lt; 0.001) and 14.1 + 2.5% (p &lt; 0.01) within 2 minutes. hPLP-(1–34)amide (1 μg/ml) produced a 19.8 + 5.3% (p &lt; 0.05) and 13.2 + 4.8% (p &lt; 0.05) increase in [3H]IP3 and [3H]IP2. We conclude that UMR-106 membranes possess a G protein-sensitive phosphoinositide-specific phospholipase C. Conceivably, this signal transduction pathway contributes to the skeletal actions of PTH and PLP.