bluuebunny/crossref_metadata_2025_split huggingface dataset:
Excessive L-thyroxine therapy decreases femoral bone mineral densities in the male rat: Effect of hypogonadism and calcitonin
Authors: Ongphiphadhanakul Boonsong , Alex Sharon , Braverman Lewis E. , Baran Daniel T. 
Published: February 2010

Abstract
Excess thyroid hormone decreases bone mineral density (BMD), a potential problem in managing patients with differentiated thyroid carcinoma and nontoxic goiter who require lifelong TSH-suppressive doses of thyroid hormone. We studied the effect of thyroid hormone excess on vertebral and femoral BMD and the role of hypogonadism in modulating this effect in a rat model. The potential role of calcitonin (CT) in preventing thyroid hormone-associated bone loss was also investigated. A total of 40 male Sprague-Dawley rats were divided into four groups. Groups 1 and 2 were orchidectomized (ORX); groups 3 and 4 were sham operated (SO). Groups 1 and 3 received 20 μg intraperitoneal L-thyroxine (L-T4) per 100 g body weight daily for 3 weeks; groups 2 and 4 received vehicle IP. Another 40 rats were divided into four groups. Groups 1 and 2 received L-T4, and groups 1 and 3 received CT, 2.5 U per 100 g body weight, subcutaneously (SC) daily for 3 weeks. BMD of the L4 and 5 and the right femur were measured by dual-energy x-ray absorptiometry at baseline and at the end of the study. Orchidectomy decreased femoral (P &lt; 0.05) but not lumbar BMD. The administration of excess L-T4 decreased femoral (cortical) BMD in both SO (P &lt; 0.05) and ORX rats (P &lt; 0.05) without affecting lumbar (trabecular) BMD. CT increased lumbar BMD in both vehicle (P &lt; 0.001) and L-T4-treated rats (P &lt; 0.001). However, CT did not affect femoral BMD in vehicle-treated rats and did not prevent the L-T4-induced femoral bone loss. Serum tartrate-resistant acid phosphatase (TRAP) was increased in the L-T4-treated (P &lt; 0.001) and the orchidectomized (P &lt; 0.05) rats. CT had no effect on TRAP activity and did not prevent the L-T4-induced increase in TRAP. Neither excess L-T4 nor orchidectomy affected osteocalcin concentrations. CT decreased serum osteocalcin concentrations, alone (P &lt; 0.05) and in the presence of excess L-T4 (P &lt; 0.05). We conclude that large doses of L-T4 administered to the rat preferentially decrease femoral BMD. Short-term hypogonadism decreases femoral but not lumbar BMD and does not make the lumbar spine more susceptible to the potential thyroid hormone-induced bone loss. CT increases lumbar BMD but does not prevent the thyroid hormone-induced decrease in femoral BMD. This rat model can be utilized to evaluate different therapies to prevent bone loss induced by excess thyroid hormone administration.
Regulation of calcitonin gene expression by hypocalcemia, hypercalcemia, and vitamin D in the rat
Authors: Naveh-Many Tally , Raue Friedhelm , Grauer Andreas , Silver Justin 
Published: February 2010

Abstract
High calcium leads to the secretion of calcitonin, and the administration of 1,25-dihydroxyvitamin D3 leads to a decreased transcription of the calcitonin gene. We now report the effect of chronic hypercalcemia, hypocalcemia, and vitamin D deficiency on calcitonin gene expression in vivo in the rat. Hypercalcemia was created by calcium infusions for 6 h, a high-calcium diet given to weanling rats for 3 weeks, and the transplantation of the Walker carcinosarcoma 256 cell line. Despite serum calcium as high as 22 mg/dl, there was no difference in calcitonin mRNA levels among these rats. The control genes studied, actin and somatostatin, which is specific for C cells in the thyroparathyroid tissue, also did not differ among the different groups of rats. Injected 1,25-(OH)2D3 decreased calcitonin mRNA levels at 6 h, as previously reported. Hypocalcemia, created by feeding diets deficient in calcium and vitamin D to weanling rats for 3 weeks, had no effect on calcitonin mRNA levels, in contrast to the large increases in PTH mRNA levels. These results demonstrate that calcitonin gene expression in vivo in the rat is regulated by administered 1,25-(OH)2D3 but not by changes in serum calcium.
Bone mineral density, muscle strength, and recreational exercise in men
Authors: Snow-Harter Christine , Whalen Robert , Myburgh Kathy , Arnaud Sara , Marcus Robert 
Published: February 2010

Abstract
Muscle strength has been shown to predict bone mineral density (BMD) in women. We examined this relationship in 50 healthy men who ranged in age from 28 to 51 years (average 38.3 years). BMD of the lumbar spine, proximal femur, whole body, and tibia were measured by dual-energy x-ray absorptiometry (Hologic QDR 1000W). Dynamic strength using one repetition maximum was assessed for the biceps, quadriceps, and back extensors and for the hip abductors, adductors, and flexors. Isometric grip strength was measured by dynamometry. Daily walking mileage was assessed by 9 week stepmeter records and kinematic analysis of video filming. Subjects were designated as exercisers and nonexercisers. Exercisers participated in recreational exercise at least two times each week. The results demonstrated that BMD at all sites correlated with back and biceps strength (p &lt; 0.01 to p = 0.0001). Body weight correlated with tibia and whole-body BMD (p &lt; 0.001); age negatively correlated with Ward's triangle BMD (p &lt; 0.01). In stepwise multiple regressions, back strength was the only independent predictor of spine and femoral neck density (R2 = 0.27). Further, back strength was the most robust predictor of BMD at the trochanter, Ward's triangle, whole body, and tibia, although biceps strength, age, body weight, and leg strength contributed significantly to BMD at these skeletal sites, accounting for 35–52% of the variance in BMD. Exercisers and nonexercisers were similar for walking (3.97 versus 3.94 miles/day), age (37.8 versus 38.5 years), and weight (80.0 versus 77.7 kg). However, BMD and muscle strength were significantly greater in exercisers than in nonexercisers. In conclusion, in young to middle-aged men, (1) muscle strength makes important contributions to bone mineral density; (2) strength of back extensors more powerfully predicts BMD than age, body weight, or strength of other muscle groups; and (3) recreational exercise is a better predictor of BMD than habitual daily walking.
Regulation of cytoplasmic calcium concentration in tetracycline-treated osteoclasts
Authors: Donahue Henry J. , Iijima Kazumoto , Goligorsky Michael S. , Rubin Clinton T. , Rifkin Barry R. 
Published: February 2010

Abstract
The ability of low-dose tetracyclines to inhibit collagenase activity and inactivate osteoclasts suggests that these compounds have great potential as a prophylaxis for metabolic bone disease. However, the cellular mechanism by which tetracyclines interact with skeletal tissue is not yet clear. To better understand the effects of tetracyclines on bone metabolism, we examined their effect on osteoclast activity in vitro. Because tetracyclines can enter the cell and bind calcium and have been reported to directly interact with osteoclasts, we postulated that exposure to either of two tetracyclines, minocycline or doxycycline, would alter cytosolic Ca2+ regulation in rat osteoclasts. [Ca2+]i was measured in single rat osteoclasts utilizing fura-2. Addition of extracellular Ca2+ (5 mM CaCl2), a potent osteoclast inhibitor, increased [Ca2+]i in all osteoclasts, but 10−6 M salmon calcitonin (sCT) did so only in a subpopulation of osteoclasts. Neither minocycline nor doxycycline (10 μg/ml) altered steady-state osteoclast [Ca2+]i. Further, neither minocycline nor doxycycline pretreatment affected the sCT-mediated increases in [Ca2+]i. However, tetracycline pretreatment significantly decreased the cytosolic Ca2+ response to extracellular CaCl2. Our results strongly suggest that tetracyclines have a specific effect on extracellular Ca2+-stimulated cytosolic Ca2+ mobilization in osteoclasts, which is not solely dependent on their ability to buffer Ca2+. Furthermore, these results point to the potential use of tetracyclines as probes to study cytosolic Ca2+ regulation. However, that tetracyclines attenuate a signal response associated with decreased osteoclastic resorption suggests that the reported antiresorptive attributes of tetracyclines must be achieved independently of an effect on osteoclastic cytosolic Ca2+.
The effect of transforming growth factor β on the plasminogen activator activity of normal human osteoblast-like cells and a human osteosarcoma cell line MG-63
Authors: Dr. Fawthrop Fiona W. , Oyajobi Babatunde O. , Bunning Rowena A.D. , Russell R. Graham G. 
Published: February 2010

Abstract
Transforming growth β (TGF-β) has been proposed to have a role in bone remodeling by affecting the differentiation and activity of osteoblasts and osteoclasts and by inhibiting the production of proteinases, such as plasminogen activators (PAs). Studies on PAs have largely been based on data from nonhuman and fetal cell lines, however. The purpose of this study was to investigate the effect of TGF-β on the PA activity of normal human osteoblast-like cells and to compare this with its action on the human osteosarcoma cell line MG-63. The action of interleukin-1β (IL-1β) was also assessed because it has been shown to increase PA activity in other connective tissue cell types. Normal osteoblast-like cells had low to undetectable basal urokinase (uPA) and tissue plasminogen activator (tPA) activity, which was significantly stimulated by TGF-β1. This action was shown to be dependent on transcription and new protein synthesis. TGY-β2 had a similar action. IL-1β did not stimulate PA activity. In contrast, the MG-63 cell line had high basal tPA and uPA activities. TGF-β1 decreased basal PA activity, the effect being most marked for uPA activity. IL-1β stimulated uPA and tPA activity. TGF-β1 inhibited IL-1β-stimulated uPA activity, but the effect on tPA was more variable. This study has shown that TGF-β has opposite effects on the PA activity of the two osteoblast-like cell types studied. Care must therefore be used before extrapolating data from one cell type to another. It is suggested that under certain circumstances TGF-β may be involved in bone resorption by modulating PA activity.
Bone mass measurement by DXA: Influence of analysis procedures and interunit variation
Authors: Trevisan Carlo , Gandolini Giorgio G. , Sibilla Paolo , Penotti Mauro , Caraceni Maria Pia , Ortolani Sergio 
Published: February 2010

Abstract
Interunit variability among bone densitometers is due to different factors, including different calibration procedures and algorithms and variability in photon source energies and/or intensities. Other factors, such as the choice of scan parameters or the analysis procedures, can also introduce variability. The new generation of dual-energy x-ray absorptiometry (DXA) has partially improved this situation. The aim of this study was to investigate the operator-dependent analysis procedures that can affect scan results and to evaluate the phantom and in vivo interunit variation of some DXA instruments. Four DXA instruments (QDR 1000 and 1000/W, Hologic, Inc.) were used. Potential sources of variability in the analysis procedures of anteroposterior lumbar spine and hip scans were considered: in most cases these procedures significantly influenced scan results. On lumbar spine, an enlargement of the scan window of less than 3 cm was responsible for an average increase in bone mineral density (BMD) of about 3%. On the hip, lowering the scan window by about 1 cm accounted for an increase in the whole-segment BMD of about 4%. After standardization of analysis procedures, interunit and intraunit coefficients of variation and percentage differences among instruments were less than 1% for all the parameters considered (area and bone mineral content and density) with both an anatomic and a geometric phantom, and in nine subjects scanned by two different devices the percentage difference in BMD was greater than 2%. This study shows that present interunit variability allows comparisons among laboratories, but only if highly standardized analysis procedures are used.
Osteoporosis and chronic back pain: A study with single-photon emission computed tomography bone scintigraphy
Authors: Dr. Ryan P.J. , Evans P. , Gibson T. , Fogelman I. 
Published: February 2010

Abstract
A group of 26 patients aged 47–81 years (average 67) with spinal osteoporosis and back pain for more than 6 months were investigated with planar and SPECT bone scintigraphy and anterior and lateral x-rays of the thoracolumbar spine. Abnormal activity on bone scintigraphy was found in all patients, of whom 22 had multiple lesions. A total of 17 (65%) patients had abnormal activity associated with collapsed vertebral bodies, 5 (19%) had degenerative disk disease, and 21 (81%) had facetal joint disease. Of 112 lesions identified by SPECT, 60 (54%) were localized to the apophyseal joints. Facetal lesions were commoner in those patients with more collapsed vertebrae, and 32 facetal lesions (54%) were associated with collapse of the vertebra immediately above or below. Bone scintigraphy findings suggest that in some individuals with osteoporosis and chronic back pain, collapse of the vertebral body or degenerative disk disease are causes of pain. However, the high frequency of increased apophyseal joint activity suggests that the facet joints may also be an important site of origin of pain in these individuals. Bone scintigraphy may identify a subgroup of osteoporotic patients with chronic back pain who would benefit from treatment to the facet joints.
Journal of Bone and Mineral Research
Authors: Shelton Richard M. , El Haj Alicia J. 
Published: February 2010

Abstract
Periosteal cells grown in macroporous microcarrier bead columns were cyclically loaded with compressive force using a newly developed model. In response to 1/2 h of cyclic compression, RNA synthesis increased significantly by twofold, from 113.4, 19.6 to 260.7 + 363 (p lt; 0.01) after 16 h, whereas DNA synthesis did not increase significantly after 24 h. The microcarrier bead model was calibrated using a linear volume displacement transducer with a range of strain magnitudes applied across the column of 1000–6000 μstrain.
Journal of Bone and Mineral Research
Authors: Lozupone Enrico , Favia Angela , Grimaldi Antonella 
Published: February 2010

Abstract
The structure of metatarsal bones from 18-day-old rats subjected to intermittent mechanical force in organ culture are reported. The application of mechanical force enhances the osteoid thickness and osteoblast number in the periosteum and increases the number of viable osteocytes. These results indicate that (1) the mature bone tissue survives in organ cultures; (2) the mechanical forces better preserve the structure of the osteocytes and stimulate the osteoblasts, and (3) stimulate the osteogenesis.
Journal of Bone and Mineral Research
Authors: Mueller Martina , Schilling Tobias , Minne Helmut W. , Ziegler Reinhard 
Published: February 2010

Abstract
The rate of remodeling in the region of a bone defect exceeds normal tissue activity. It was Frost who described this reaction as the regional acceleratory phenomenon (RAP). We previously showed that restoration of a local bone defect in the rat leads not only to RAP but also leads to a systemic acceleration of osteogenesis (systemic acceleratory phenomenon, SAP) in distant sites of the skeleton. In this study we investigated the impact of immobilization of the defect-bearing extremity on the development of SAP. A hole 1.2 mm in diameter was drilled in the diaphysis of the left tibia of female rats. In the experimental group (n = 15), a knee tenotomy was performed in the defect-bearing left hind leg. We examined both femora, both tibiae, and the fourth lumbar vertebra by computed x-ray densitometry on day 7 postoperatively. Immobilization of the defect-bearing limb led to a decrease in x-ray density not only of the immobilized (p lt; 0.0001) but also of the contralateral tibia (p lt; 0.0001). Both femora (p lt; 0.001) and the fourth lumbar vertebra (p lt; 0.025) of the experimental group also showed a significant decrease in x-ray density. We previously showed that SAP leads to an increase in x-ray density of both femora. This increase is no longer detectable in animals after immobilization of the defect-bearing limb. Thus we conclude that immobilization interferes with SAP. This suggests the possible dependence of SAP on mechanical load. Furthermore, these data suggest a possible impact of local immobilization on the rest of the skeleton.
Journal of Bone and Mineral Research
Authors: Schilling Tobias , Mueller Martina , Minne Helmut W. , Ziegler Reinhard 
Published: February 2010

Abstract
The mineral apposition rate (MAR) is a commonly used parameter for the characterization of bone formation and is often determined to test for experimental effects on cortical bone. We investigated whether there are physiologic variations in rat cortical MAR dependent on the side or site of measurement. In our experiment we used female rats. The animals were sacrificed on day 8, after double-fluorochrome labeling with calcein and tetracycline was performed. The MAR was calculated at 3.6, 5.4, 7.2, 9, and 10.8 mm from the epiphyseal growth plate of the lateral as well as of the medial endosteum of both right and left tibiae. We found a physiologic significant difference in the MAR between the lateral and the medial endosteal sites of the same tibia (p lt; 0.0001), especially near the epiphyseal growth plate. Regarding the same cortical side, there is a significant decrease (p lt; 0.0001) in the endosteal MAR with increasing distance from the epiphyseal growth plate. We conclude that the observed differences in endocortical MAR must be due to specific mechanical challenges. Because these differences are statistically significant, it is necessary to standardize the area of histomorphometric measurement not only with respect to the distance from the epiphyseal growth plate, but also with respect to the cortical side.
Journal of Bone and Mineral Research
Authors: Grigoriev Anatoly I. , Morukov Boris V. , Oganov Victor S. , Rakhmanov Alexander S. , Buravkova Ludmilla B. 
Published: February 2010

Abstract
As we enter a phase of space exploration that will involve long-duration flights, there is a need to use ground-based models to study the long-term effects of countermeasures to prevent the loss of bone mineral in microgravity. Mineral balances, hormone levels, and bone density were measured for 360 days in nine bed rest subjects treated with an exercise program used by cosmonauts. Four of these subjects received the bisphosphonate, ethane-1-hydroxy-1-disphosphonate, 900 mg daily, a drug known to inhibit bone resorption. Compared to a 120 day control period, the bisphosphonate combined with exercise reduced negative calcium balances by 50% for the first 120 days, 80% for the second 120 days, and 69% during the third 120 days. Exercise alone had no effect until the second 120 day period, when calcium balance improved 52%. Negative phosphorus balances were not affected by either treatment. Magnesium balances were negative during the first 120 days and returned to nearly normal during the last 240 days in both groups. The combined exercise and bisphosphonate treatment prevented increases in serum ionized calcium and decreases in plasma calcitonin during the first 120 days, as well as trends toward decreases in the mineral density of the femoral neck. These results suggest that bisphosphonates can be efficiently used together with exercise to reduce calcium loss and prevent some of the changes in mineral metabolism during long-term simulated microgravity.
Heritable and life-style determinants of bone mineral density
Authors: Krall Elizabeth A. , Dawson-Hughes Bess 
Published: February 2010

Abstract
Familial resemblance in bone mineral density at five skeletal sites was measured among 160 adult members of 40 families. Each family included a postmenopausal mother, one premenopausal daughter, one son, and the children's father. Similarities in selected life-style factors thought to influence bone density, such as physical activity, smoking, alcohol use, and diet, were also evaluated. Bone density was measured by dual-energy (total body, femoral neck, and lumbar spine) or single-photon (radius and os calcis) absorptiometry. Correlation coefficients between the midparent Z score and offspring Z scores of bone mineral density ranged from 0.22 to 0.52 among daughters and from 0.27 to 0.58 among sons. Adjustment of bone density for age, height, weight, and significant life-style or environmental factors yielded heritability estimates for the five skeletal sites between 0.46 and 0.62. That is, 46–62% of variance in bone density was attributable to heredity. Most estimates derived from the group of daughters were similar to those from the sons. These observations provide support for a significant contribution of heredity to bone density. However, an individual's life-style may account for a potentially large proportion of the nonheritable variance in bone density.
Transient recruitment of osteoclasts and expression of their function in osteopetrotic (op/op) mice by a single injection of macrophage colony-stimulating factor
Authors: Kodama Hiroaki , Yamasaki Akira , Abe Moriaki , Niida Shumpei , Hakeda Yoshiyuki , Kawashima Hiroyuki 
Published: February 2010

Abstract
Severe deficiency of osteoclasts in op/op mice, caused by the absence of functional macrophage colony-stimulating factor (M-CSF), is cured by daily injections of purified recombinant human M-CSF (rhM-CSF). In this study, we found that a single injection of 5 μg rhM-CSF is enough for recruitment of osteoclasts in mutant mice. Osteoclast number increased during the period between 2 and 4 days after the single rhM-CSF injection. When YM175, a new derivative of bisphosphonate, was administered to the mice 4 days after rhM-CSF injection or later, osteoclasts disappeared by 3 days after YM175 administration. However, a significant number of osteoclasts were detected even at 3 days after YM175 administration when YM175 was administered 3 days after rhM-CSF injection or earlier. These results indicate that YM175 is cytotoxic only to functioning osteoclasts and that recruitment of osteoclasts is finished 4 days after a single rhM-CSF injection. The osteoclasts actively resorbed bone trabeculae for a prolonged period, demonstrating that M-CSF is not requisite for the functioning of mature osteoclasts.