bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loading-related increases in prostaglandin production in cores of adult canine cancellous bone in vitro: A role for prostacyclin in adaptive bone remodeling?
Authors: Rawlinson Simon C.F. , El-Haj Alicia J. , Minter Sarah L. , Tavares Ignatius A. , Bennett Alan , Dr. Lanyon Lance E. 
Published: February 2010

Abstract
Cyclic mechanical loading sufficient to engender strains of physiologic magnitude applied to recently excised canine cancellous bone cores in vitro increased the release of prostaglandin E (PGE) and prostacyclin (PGI2, measured as its breakdown product 6-keto-PGF1α), during a 15 minute loading period in which PG levels were measured in perfusing medium at 5 minute intervals. Peak production occurred in the 0–5 minute sample. Mean levels preload compared to during load were PGE, 2.66 and 3.67 ng/ml (p &lt; 0.002); and 6-keto-PGF1α, 543 and 868 pg/ml (p &lt; 0.007). The elevated levels then declined to preload levels during the loading period. However, the 5–10 minute but not the 10–15 minute samples still contained levels greater than preload values. A second 15 minute period of load, 1 h following the end of the first, produced smaller increases in the levels of release that were statistically significant only for the first 0–5 minute sample during load (preload compared to load mean values, PGE, 1.09–1.66 ng/ml, p &lt; 0.02; 6-keto-PGF1α, 401–558 pg/ml, p &lt; 0.04). Immunolocalization revealed PGE and 6-keto-PGF1α in lining cells and 6-keto-PGF1α but not PGE in osteocytes. Addition to the medium of 1 μM PGE2, approximating the concentration produced by loading, had no significant effect on the specific activity of the extractable RNA fraction labeled with [3H]uridine, whereas 1 μM PGI2 produced an increase similar to that seen previously with loading. These results suggest that both PGE and PGI2 may be involved in loading-related adaptive bone modeling and remodeling. The presence of the PGI2 breakdown product in osteocytes and the RNA response to PGI2 suggest that this prostanoid may be an early factor in the cascade of events between strain in the bone matrix and subsequent osteoregulatory responses performed by bone cell populations.
Bone morphogenetic proteins (BMP-2 and BMP-3) promote growth and expression of the differentiated phenotype of rabbit chondrocytes and osteoblastic MC3T3-E1 cells in vitro
Authors: Hiraki Yuji , Inoue Hiroyuki , Shigeno Chohei , Sanma Yuji , Bentz Hanne , Rosen David M. , Asada Akira , Suzuki Fujio 
Published: February 2010

Abstract
We studied the effects of highly purified bone morphogenetic protein 2 and 3 (BMP-2 and −3) on growth plate chondrocytes and osteoblastic cells in vitro and compared to TGF-β. A mixture of BMP-2 and 3 (BMPs) strongly stimulated DNA synthesis of chondrocytes in the presence of fibroblast growth factor (FGF). BMPs induced rapid maturation of chondrocytes at a growing stage: BMPs transformed the cells into rounded cells and induced marked accumulation of cartilage matrix; TGF-β slightly reduced matrix accumulation and changed cell morphology into spindle-like in the presence of FGF. Moreover, exposure of chondrocytes to BMPs resulted in a dramatic increase of the putative ˜80 kD PTH receptors expressed on the cell surface. In multilayered chondrocytes at the calcifying stage, BMPs stimulated alkaline phosphatase (ALPase) activity but TGF-β inhibited it. In osteoblastic MC3T3-E1 cells, BMPs were found to be the most potent stimulator of ALPase activity thus far described: ALPase in the cells treated with ˜100 ng/ml of BMPs reached 5- to 20-fold over the basal, whereas TGF-β inhibited expression of ALPase activity in these cells. The stimulatory action of BMPs overrode the inhibition of ALPase activity by TGF-β when the cells were incubated with TGF-β and BMPs. BMPs also upregulated expression of the ˜80 kD PTH receptor on the cells. These results suggest that BMPs have unique biologic activities in vitro that lead to growth and phenotypic expression of cells playing a critical role in endochondral bone formation.
Journal of Bone and Mineral Research
Authors: Marx Stephen J. 
Published: February 2010

Abstract
Primary hyperparathyroidism is caused by defects in the parathyroid gland. Investigations have implicated three interesting genes whose mutation can cause primary hyperparathyroidism. Familial hypocalciuric hypercalcemia is believed to be an atypical form of primary hyperparathyroidism with an inherited defect in calcium recognition expressed not only in all parathyroid chief cells (thus a polyclonal defect) but in some renal tubular cells as well. In typical primary hyperparathyroidism a monoclonal parathyroid tumor is usually the central cause. Either of two apparently different genes on the long arm of chromosome 11 has been implicated in development of a parathyroid tumor clone. One gene (D11S287) was shown to have undergone a rearrangement with the parathyroid hormone gene on the short arm of the same chromosome (pericentro-meric inversion) in a small fraction of tumors; the D11S287 locus may encode a growth stimulator. Another gene, the locus for familial multiple endocrine neoplasia type 1 (FMEN1), is likely to encode a growth inhibitor. Inactivation of this gene or another nearby gene by somatic mutation has been indirectly implicated in one-quarter of sporadic parathyroid adenomas and in more than half of parathyroid tumors in FMEN1. In conclusion, studies have suggested three different mechanisms for parathyroid gland dysfunction in primary hyperparathyroidism: (1) a defect in calcium recognition, (2) a monoclonal tumor from overexpression of a growth stimulator, or (3) a monoclonal tumor from inactivation of a growth inhibitor.
Journal of Bone and Mineral Research
Authors: Lafferty Frederic W. 
Published: February 2010

Abstract
The differential diagnosis of hypercalcemia has expanded to over 25 separate disease states, with primary hyperparathyroidism and malignancy accounting for 80–90% of all hypercalcemic patients. Primary hyperparathyroidism comprises the majority of hypercalcemic patients among the ambulatory population, but malignancy accounts for up to 65% of such patients in the hospital. Factors favoring primary hyperparathyroidism include a family history of hyperparathyroidism or multiple endocrine neoplasia, a history of childhood radiation to the head and neck, the postmenopausal state, a history of renal calculi or peptic ulcer, hypertension, the induction of hypercalcemia by thiazides, or an asymptomatic patient with a prolonged, stable mild hypercalcemia. The usefulness of the serum calcium, parathyroid hormone, chloride, phosphorus, serum 25-OHD, and l,25-(OH)2D, and urinary calcium in the differential diagnosis of hypercalcemia is discussed. The pitfalls of an excessive reliance on the serum PTH in diagnosing hyperparathyroidism are stressed. The discriminant values of the serum calcium, chloride, phosphorus, and parathyroid hormone are explored, with the serum parathyroid hormone, chloride, and calcium proving most useful in separating primary hyperparathyroidism from other forms of hypercalcemia. Multivariate discriminant analysis using the serum calcium, phosphorus, and chloride and the hematocrit achieves an accuracy of 95–98% and is the most economical method of identifying hyperparathyroidism. The addition of the amino-terminal or intact PTH assay increases the accuracy to 99% and is essential in the presence of renal insufficiency.
Journal of Bone and Mineral Research
Authors: Ott Susan M. 
Published: February 2010

Abstract
Bone disease is one of the most important clinical manifestations of primary hyperparathyroidism. Recent studies have shown that the loss of bone in “modern” hyperparathyroidism is not homogeneous throughout the skeleton. Whereas measurements of the spine and the trabecular portion of iliac crest are normal or even slightly increased, the wrist and the cortical bone of the iliac crest are significantly lower than expected. Thus, knowledge of the percentage of trabecular bone at each measurement site is important. These include distal radius, 80%; midradius, 5%; vertebrae, 19–25%; vertebral body, 33–42%; and femoral neck, 43%. Knowledge of the precision and its relationship to ranges and rates of change of bone mass are essential. For an individual, the bone mass should change by 2.8 times the precision before one can determine with 90% confidence that the change was real, not due to measurement error. Noninvasive methods of measuring bone mass that are commercially available include single- and dual-photon absorptiometry, quantitative computed tomography, and dual-energy x-ray absorptiometry. The precision of these techniques varies, with the best values reported using dual-energy x-ray absorptiometry. Research should be done to describe more completely the patterns of bone loss in this disease, including longitudinal studies on rates of loss at different skeletal sites. Studies that relate the bone mass at a particular site to fractures must be done in populations with hyperparathyroidism to see if the risk of fracture is similar to the risk in normal or osteoporotic individuals.
Journal of Bone and Mineral Research
Authors: Mitlak Bruce H. , Daly Margaret , Potts John T. , Schoenfeld David , Neer Robert M. 
Published: February 2010

Abstract
Of 118 consecutive white patients referred for asymptomatic primary hyperparathyroidism, the diagnosis was clinically confirmed in 100, of whom 85 adults had a serum calcium less than 3.0 mM (12 mg/dl) and no skeletal, rheumatic, or significant neuropsychiatric symptoms, azotemia, or other significant illnesses. Among these 85, 68 had both asymptomatic and medically uncomplicated hyperparathyroidism, whereas 17 had historical, radiographic, or ultrasonic evidence of renal stone disease. The 20% with past or present renal calculi concentrated their urine significantly better than the 68 others (p = 0.05), but these two groups were otherwise not distinguished by the tests we performed, so all 85 patients were analyzed together. Systolic and diastolic blood pressures were normal, but premature osteopenia and/or impaired renal function were present in 29–36% of the patients. Micrometer measurements of metacarpal radiographs and 125I photon absorptiometry at the shaft of the radius revealed cortical osteopenia. Osteopenia was equally significant in the distal radius (cortical plus trabecular bone). These quantitative measurements were superior to routine bone radiography, and ROC analysis showed that 125I absorptiometry at either site was superior (p &lt; 0.01) to metacarpal cortex measurements for detecting premature osteopenia, which was present in more than a third of these patients. Creatinine clearances (24 h) and maximum urine concentrating capacity (overnight dehydration plus the synthetic vasopressin analog DDAVP) were each significantly reduced, despite all patients' normal BUN and serum creatinine levels. Sequential performance of a 24 h creatinine clearance and a urine concentration test revealed abnormalities in the renal function of 27 of 74 patients (36%), with a specificity of 95% and a higher sensitivity than either test alone (27–29%). Testing the kidneys' ability to acidify the urine to pH 5.3 or less identified only 1 additional abnormal patient. Silent complications of primary hyperparathyroidism are thus common in “asymptomatic” patients with mild hypercalcemia. Their presence was only weakly correlated with urinary calcium excretion (measured on a low-calcium diet) and serum alkaline phosphatase. From these data, it is not possible to predict whether these complications progress in the absence of treatment or diminish with successful treatment of the primary hyperparathyroidism.
Journal of Bone and Mineral Research
Authors: Clark Orlo H. , Wilkes William , Siperstein Allan E. , Duh Quan-Yang 
Published: February 2010

AbstractSeveral recent articles question whether patients with asymptomatic hyperparathyroidism and minimal hypercalcemia should be treated by parathyroidectomy. We therefore reviewed our experience in 103 consecutive patients with primary hyperparathyroidism who were treated by parathyroidectomy to determine, first, how many of these patients had asymptomatic or symptomatic hyperparathyroidism, and second, did these patients benefit from parathyroidectomy? We also analyzed the safety of parathyroidectomy in 426 consecutive patients, including 79 who required reoperation for hyperparathyroidism, specifically looking for complications and the outcome of these procedures. Our study documents the following: (1) only 2 of 103 (2%) patients referred for parathyroidectomy had “true” asymptomatic hyperparathyroidism; (2) only symptoms of fatigue, bone pain, and weight loss correlated with the degree of hypercalcemia, whereas muscular weakness, psychiatric symptoms, nocturia, polyuria, recent memory loss, constipation, and nephrolithiasis did not; (3) only 1 of 15 patients who were referred as asymptomatic were truly asymptomatic after more thorough questioning, and all 14 improved following parathyroidectomy; (4) 81% of the patients who were referred with symptoms improved following parathyroidectomy; and (5) permanent complications occurred in only 4 patients. All but 1 had reoperations for persistent or recurrent hyperparathyroidism (3 vocal cord paralyses and 1 hypoparathyroidism requiring autotransplantation of cryopreserved parathyroid tissue). There was 1 death of an 84-year-old woman with hypercalcemic crisis. Thus, most patients with hyperparathyroidism are symptomatic and benefit symptomatically and metabolically from parathyroidectomy, which is a safe operation.
Mineral metabolism in infants with malignant osteopetrosis: Heterogeneity in plasma 1,25-dihydroxyvitamin D levels and bone histology
Authors: Cournot Giulia , Trubert-Thil Claire Lise , Petrovic Milka , Boyle Allison , Cormier Catherine , Girault Danielle , Fischer Alain , Garabedian Michèle 
Published: February 2010

AbstractA group of 16 infants, 2 weeks to 11 months old, with malignant osteopetrosis were investigated to examine their vitamin D metabolism and parathyroid function. Bone biopsies from 6 children were studied by light microscopic histomorphometry and by electron microscopy. Considerable heterogeneity existed among the patients with respect to the parameters reflecting mineral metabolism and with respect to the histological manifestations of the disease. The most constant findings were as follows. Immunoreactive parathyroid hormone (iPTH) was elevated in all children, except in 1 patient who had tubular acidosis, and plasma calcium was low or normal, suggesting skeletal resistance to PTH. Plasma 1,25-dihydroxyvitamin D [1,25-(OH)2D] was not constantly elevated and appeared to depend on plasma phosphorus, as both parameters were negatively correlated (r = 0.704, p &lt; 0.01). Osteoblast activity, as evaluated by circulating alkaline phosphatase and osteocalcin and osteoblast number, measured for 6 children by bone histology, were not increased, despite hyperparathyroidism, suggesting PTH resistance or defective osteoblasts. Osteoclasts could be detected in 5 of the 6 children who had a biopsy. Osteoclast number (5.7–13.3% of bone surface) was normal or mildly increased, and marrow spaces were relatively well developed in 4 patients, whereas 1 child had markedly increased osteoclast number (28.3% of bone surface) and reduced marrow cavities. These 5 children received transplants, and engraftment occurred in all, except in the “hyperosteoclastic” patient. Further studies are necessary to establish the prognostic significance of this histologic feature.
Glucocorticoids decrease vitamin D receptor number and gene expression in human osteosarcoma cells
Authors: Godschalk Michael , Levy James R. , Downs Robert W. 
Published: February 2010

Abstract
The mechanisms by which glucocorticoids (GC) inhibit some actions of vitamin D [1,25-(OH)2D3] are not well understood, but there is growing evidence that GC alter vitamin D receptor (VDR) number. We studied the effects of dexamethasone (DEX) on VDR number and mRNA in the human osteosarcoma cell line, MG-63. The effects of DEX on 1,25-(OH)2D3 binding were examined by incubating confluent cells overnight in media without or with 10−6 M DEX. DEX decreased VDR number (Bmax) by ˜ 70% (110 versus 32 fmol/mg cellular protein, p &lt; 0.001) without significantly changing the apparent affinity (K'D) of 1,25-(OH)2D3 for its receptor (3.8 versus 2.2 x 10−10 M, p &gt; 0.05). Overnight incubation of MG-63 cells with DEX produced a time- and dose-responsive decrease in VDR mRNA compared to untreated controls (p &lt; 0.01). To determine the mechanism of the DEX-mediated decrease in VDR mRNA, the effect of DEX on VDR mRNA stability was studied. We found that the half-life for the VDR mRNA was ˜ 5.7 h and was not significantly changed when the cells were incubated with DEX ( ˜6.3 h). We conclude that DEX decreases both VDR number and mRNA in MG-63 osteosarcoma cells. Since the half-life of VDR mRNA was not significantly modified by dexamethasone, glucocorticoids appear to decrease VDR mRNA by inhibiting VDR gene transcription or by affecting the processing of VDR mRNA.
Dose-related effects of 1,25-dihydroxyvitamin D3 on growth, modeling, and morphology of fetal mouse metatarsals cultured in serum-free medium
Authors: Bagi Cedo M. , Miller Scott C. 
Published: February 2010

AbstractA serum-free, fetal bone organ culture model that permits the simultaneous determination of modeling and growth parameters was used to examine the effects of a near physiologic and a pharmacologic dose of 1,25-dihydroxycholecalciferol [1,25-(OH)bD3]. The fetuses of pregnant mice were removed on day 17 of gestation, and three medial metatarsal rudiments were cleaned and after preculturing were cultured as pairmatched groups for 4 days in MEM supplemented with 0.2% BSA. 1,25-(OH)2D3 was added to the cultures at concentrations of 10−2 or 10−6 M. Cultures treated with the carrier and devitalized bones served as controls. For resorption studies, pregnant mice were given 45Ca on day 17 of pregnancy and fetal metatarsals harvested 24 h later. Resorption was determined by the amount of 45Ca released into the media. DNA synthesis was estimated by determining the incorporation of [3H]thymidine, collagen synthesis by measuring the incorporation of [3H]proline, mineralization by the incorporation of 45Ca, and proteoglycan synthesis by the incorporation of 35S. The amount of radiolabel was detected in media, as well as in noncultured, dead, and cultured rudiments. The total length of the rudiments and length of the calcified diaphyses were measured daily. In addition, rudiments from all experimental groups were prepared for light and electron microscopy. The high dose (10−6 M) of 1,25-(OH)2D3 suppressed total rudiment growth but not the growth of the calcified diaphysis. 1,25-(OH)2D3 also decreased DNA, collagen, and proteoglycan synthesis, reduced calcification, and increased bone resorption in a dose-related manner. There were morphologic and ultrastructural changes in the osseous tissues and cells, particularly with the high dose of vitamin D, that supported the biochemical findings of suppressed activity of the osteogenic and chondrogenic cells. However, the suppression of collagen production and bone cell proliferation observed with the pharmacologic dose of vitamin D may be partially attributable to the decrease in bone mass (from increased resorption), thus resulting in less osseous tissue surface for these events to occur as endochondral osteogenesis progressed. The lower dose of vitamin D, however, had effects on 35S and 45Ca incorporation that could not be attributed to a decreased osseous tissue mass. This study emphasizes the importance of measuring specialized activities of the various cell populations in bone rudiment culture models to more fully understand the changes in tissue metabolism that result in changes in rudiment growth and modeling.
Interaction of androgen and 1,25-dihydroxyvitamin D3: Effects on normal rat bone cells
Authors: Gray Colin , Colston Kay W. , Mackay Alan G. , Taylor M. Louise , Arnett Timothy R. 
Published: February 2010

Abstract
We studied the actions of testosterone (T) and 5α-dihydrotestosterone (DHT) in combination with 1,25-di-hydroxyvitamin D3 [1,25-(OH)2D3] on primary rat bone cells. The actions of androgens were generally anabolic, although response patterns varied considerably between cultures. For example, DHT caused striking dose- and time-dependent increases in [3H]thymidine incorporation into calvarial cells over the range 1–100 nM, with maximal stimulation of 2.5-fold after 9 days in culture. Testosterone (50 nM) also stimulated [3H]-thymidine incorporation into long bone-derived cells. 1,25-(OH)2D3, generally blunted or abolished the proliferative action of androgens but was not itself always inhibitory; in some experiments, stimulation of [3H]-thymidine incorporation occurred. Collagen production, as assessed by [3H]proline incorporation into pepsin-resistant protein secreted by calvarial cells, was also stimulated by DHT. In some cultures, androgen responses were absent, although striking inhibitory responses to 1,25-(OH)2D3 were observed. These results illustrate complex patterns of responses to androgens and 1,25-(OH)2D3 in cells derived from rat bone.
Bone mass and body composition in normal women
Authors: Lindsay Robert , Cosman Felicia , Herrington Brenda S. , Himmelstein Sharon 
Published: February 2010

Abstract
The interrelationships between measurements of bone mass and total-body bone mineral were examined in a cross-sectional study of normal healthy women aged 17–82 years. In addition we evaluated the relationship between measures of body composition, estimated by four independent techniques, and bone mass in the same population. Considering the group as a whole, bone mass at all sites correlated with each other and with total-body bone mineral (TBBM). Cancellous and cortical sites could predict TBBM equally well. As expected, all measurements of bone mass were significantly lower in postmenopausal women in comparison to premenopausal women. Declines in bone mass were only seen in premenopausal women in the femoral neck and Ward's triangle, not in lumbar spine, radius, or skeleton as a whole. In postmenopausal women bone mass correlated negatively with age and years from menopause equally at all sites. TBBM was significantly related to height and weight in both premenopausal and postmenopausal women. In premenopausal and postmenopausal women TBBM also correlated with fat mass, but TBBM was much better correlated with percentage body fat in premenopausal than postmenopausal women. TBBM was a constant proportion of lean body mass in premenopausal women, but the fraction of lean mass occupied by the skeleton declined with age in postmenopausal women. Correction of TBBM for lean mass did not change the relationship between TBBM and percentage fat in premenopausal women but eliminated the relationship in postmenopausal women. Regional measurements, which are at least partially corrected for body size by dividing mass by area, correlated less well with height and weight and with any index of obesity, especially in postmenopausal women.