bluuebunny/crossref_metadata_2025_split huggingface dataset:
PTH-related protein is released into the mother's bloodstream during lactation: Evidence for beneficial effects on maternal calcium-phosphate metabolism
Authors: Lippuner Kurt , Zehnder Hans-Jakob , Casez Jean-Paul , Takkinen Ritva , Jaeger Philippe 
Published: February 2010

AbstractRecent studies have indicated that parathyroid hormone-related protein (PTHrP) may have important actions in lactation, affecting the mammary gland, and also calcium metabolism in the newborn and the mother. However, there are as yet no longitudinal studies to support the notion of an endocrine role of this peptide during nursing. We studied a group of 12 nursing mothers, mean age 32 years, after they had been nursing for an average of 7 weeks (B) and also 4 months after stopping nursing (A). It was assumed that changes occurring between A and B correspond to the effect of lactation. Blood was assayed for prolactin (PRL), PTHrP (two-site immunoradio-metric assay with sheep antibody against PTHrP(1-40), and goat antibody against PTHrP(60-72), detection limit 0.3 pmol/1), intact PTH (iPTH), ionized calcium (Ca2+), 25-hydroxyvitamin D3 (25(OH)D3) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), alkaline phosphatase (alkP), as well as for creatinine (Cr), protein, phosphorus (P), and total calcium (Ca). Fasting 2-h urine samples were analyzed for Ca excretion (CaE) and renal phosphate threshold (TmP/GFR). PRL was significantly higher during lactation than after weaning (39 ± 10 vs. 13 ± 9 μg/l; p = 0.018) and so was PTHrP (2.8 ± 0.35 vs. 0.52 ± 0.04 pmol/l; p = 0.002), values during lactation being above the normal limit (1.3 pmol/l) in all 12 mothers. There was a significant correlation between PRL and PTHrP during lactation (r = 0.8, p = 0.002). Whole blood Ca2+ did not significantly change from A (1.20 ± 0.02 mmol/l) to B (1.22 ± 0.02, mmol/l), whereas total Ca corrected for protein (2.18 ± 0.02 mmol/l) or uncorrected (2.18 ± 0.02 mmol/l) significantly rose during lactation (2.31 ± 0.02 mmol/l, p = 0.003 and 2.37 ± 0.03 mmol/l, p = 0.002, respectively). Conversely, iPTH decreased during lactation (3.47 ± 0.38 vs. 2.11 ± 0.35 pmol/l, A vs. B, p = 0.02). Serum-levels of 25(OH)D3 and 1,25(OH)2D3 did not significantly change from A to B (23 ± 2.3 vs. 24 ± 1.9 ng/ml and 29.5 ± 6.0 vs. 21.9 ± 1.8 pg/ml, respectively). Both TmP/GFR and P were higher during lactation than after weaning (1.15 ± 0.03 vs. 0.86 ± 0.05 mmol/l GF, p = 0.003 and 1.25 ± 0.03 vs. 0.96 ± 0.05 mmol/l, p = 0.002, respectively) as was alkP (74.0 ± 7.1 vs. 52.6 ± 6.9 U/l, p = 0.003). CaE did not differ between A and B (0.015 ± 0.003 vs. 0.017 ± 0.003 mmol/l GF, A vs. B, NS). We conclude that lactation is accompanied by an increase in serum PRL. This is associated with a release of PTHrP into the maternal blood circulation. A rise in total plasma Ca ensues, probably in part by increased bone turnover as suggested by the elevation of alkP. PTH secretion falls, with a subsequent rise of TmP/GFR and plasma P despite high plasma levels of PTHrP.
Stimulation of neonatal mouse calvarial bone resorption by the glucocorticoids hydrocortisone and dexamethasone
Authors: Conaway Herschel H. , Grigorie Daniel , Dr. Lerner Ulf H. 
Published: February 2010

AbstractIn vitro stimulation of bone resorption was observed with the glucocorticoids hydrocortisone and dexamethasone. Dosage-dependent release of 45Ca from neonatal mouse calvarial bones was found for both steroids, with half-maximal responses for hydrocortisone and dexamethasone of 0.3 and 0.08 μM, respectively. Significant release of stable calcium (Ca2+), inorganic phosphate (Pi), and the lysosomal enzyme β-N-acetylglucosaminidase was noted following treatment of mouse calvariae with either 1 μM hydrocortisone or 1 μM dexamethasone. Additionally, both 1 μM hydrocortisone and 1 μM dexamethasone elicited release of 3H from calvarial bones prelabeled with [3H]proline. The stimulation of bone resorption by the glucocorticoids, as assessed by 45Ca release, was sustained over 120 h of culture. Inhibition of 45Ca release from calvariae treated with either 1 μM hydrocortisone or 0.1 μM dexamethasone was observed with 0.01-30 nM salmon calcitonin (sCT), 0.1 mM acetazolamide, and 0.1 mM of the bisphosphonate AHPrBP. Inhibition of glucocorticoid-induced bone resorption by sCT occurred without “escape from calcitonin-induced inhibition.” The 45Ca release stimulated by 1 μM hydrocortisone and 0.1 μM dexamethasone was also inhibited by 10 μM progesterone in a competitive manner and by 1 μM of the antiglucocorticoid RU38486, both of which are modulators of glucocorticoid binding. Prostaglandin E2 (PGE2) formation by 10 nM parathyroid hormone (PTH) in neonatal mouse calvarial bones was inhibited by both 1 μM hydrocortisone and 1 μM dexamethasone, but neither compound altered basal PGE2 formation. Exposure of calvarial bones to the mitotic inhibitors hydroxyurea and mitomycin C inhibited 45Ca release stimulated by 1 μM hydrocortisone and 1 μM dexamethasone. In contrast, addition of 1 ng/ml of recombinant murine granulocyte macrophage colony stimulating factor (rmGM-CSF) had no effect on 45Ca release elicited by the glucocorticoids. These results suggest that hydrocortisone and dexamethasone stimulate osteoclastic resorption in neonatal mouse calvariae by a receptor-mediated mechanism that is dependent on cellular replication.
Creatine kinase brain isoenzyme (BB-CK) presence in serum distinguishes osteopetroses among the sclerosing bone disorders
Authors: Whyte Michael P. , Chines Arkadi , Silva David P. , Landt Yvonne , Ladenson Jack H. 
Published: February 2010

Abstract
Creatine kinase (CK) isoenzyme BB-CK is predominantly found in brain and is not normally detected in the blood. A few recent reports, however, have described BB-CK in serum from several patients with osteopetrosis (OP). To evaluate the presence and specificity of BB-CK in serum in the osteopetroses among disorders that increase skeletal mass, we quantitated total CK activity and CK isoenzymes in 15 patients representing the five major clinical forms of OP (2 infantile, 3 intermediate, 7 adult [2 type I, 5 type II], and 3 carbonic anhydrase II [CA II] deficiency cases) and in 22 patients representing 14 other types of sclerosing bone disease. All OP patients (except the two adult type I subjects) had BB-CK readily detected in their serum. Conversely, only 1 of the 22 patients with other sclerosing bone disorders had detectable BB-CK in serum (1 of 3 patients with fibrodysplasia [myositis] ossificans progressiva who had barely measurable activity). In three OP patients (one of two with the infantile form and two of five with adult, type II disease), BB-CK values were sufficiently high that serum total CK activity was elevated. In a newborn with malignant OP, both cord blood plasma and peripheral blood serum had substantial amounts of BB-CK. In three subjects (with adult type II OP), who were restudied 2-6 years later, BB-CK was still elevated in their blood. BB-CK in serum appears to distinguish the osteopetroses among the sclerosing bone disorders. Absence of serum BB-CK in adult type I disease suggests that this condition may not be a genuine form of OP. Assay of BB-CK in fetal blood could be studied as a means for prenatal diagnosis of malignant OP. Why the osteoclast failure that characterizes all true forms of OP is associated with BB-CK in the circulation is a new question for skeletal biologists.
Human osteoclastoma-derived stromal cells: Correlation of the ability to form mineralized nodules in vitro with formation of bone in vivo
Authors: James Ian E. , Dodds Robert A. , Olivera Diane L. , Nuttall Mark E. , Gowen Maxine 
Published: February 2010

Abstract
It has been suggested that the stromal element of human osteoclastomas contains osteoblastic cells. In this study, we demonstrate that osteoclast-depleted, passaged stromal cells express alkaline phosphatase and osteocalcin in vitro and form mineralized nodules under appropriate culture conditions. In addition, we describe a model in which severe combined immunodeficient (SCID) mice were used to support the differentiation of these putative human osteoblast progenitors in vivo. Lesions formed from human stromal cells were identified using the OKa blood group antigen and human procollagen type I antibodies. By 21 days, the lesion was a complete bone unit: a fully mineralized cortex, remodeling trabeculae, and a highly cellular marrow space. Stromal cells derived from six out of seven osteoclastomas produced identical lesions. Further studies have demonstrated that the capacity of the osteoclastoma-derived stromal cells to form bone in vivo and in vitro is passage dependent; early passages were osteogenic in both model systems, while later passages were not. In conclusion, we have developed a model in which the osteogenic nature of cells can be confirmed in vivo. Furthermore, human osteoclastoma-derived stromal cells provide a source of these osteogenic cells to study human osteoblast differentiation, both in vivo and in vitro.
Bisphosphonates induce apoptosis in mouse macrophage-like cells in vitro by a nitric oxide-independent mechanism
Authors: Dr. Rogers Michael J. , Chilton Kattya M. , Coxon Fraser P. , Lawry John , Smith M. Olivia , Suri Sunita , Russel R. Graham G. 
Published: February 2010

AbstractBisphosphonates (BPs) are an important class of antiresorptive drugs used in the treatment of bone diseases, including osteoporosis. Although their mechanism of action has not been identified at the molecular level, there is substantial evidence that BPs can have a direct effect on osteoclasts by mechanisms that may lead to osteoclast cell death by apoptosis. BPs can also inhibit proliferation and cause cell death in macrophages in vitro. We have now shown that the toxic effect of BPs on macrophages is also due to the induction of apoptotic, rather than necrotic, cell death. Morphological and biochemical features that are definitive of apoptosis (chromatin condensation, nuclear fragmentation, and endonuclease-mediated internucleosomal cleavage of DNA) could be identified in mouse macrophage-like J774 and RAW264 cells, following treatment with 100 μM Pamidronate, alendronate, and ibandronate for 24 h or more. Clodronate was much less potent, even at 2000 μM, while 2000 μM etidronate did not cause apoptosis. Apoptosis was not due to increased synthesis of nitric oxide and could not be prevented by inhibitors of nitric oxide synthases. Since macrophages, like osteoclasts, are particularly susceptible to BPs, these observations support the recent suggestion that the mechanism by which BPs inhibit bone resorption may involve osteoclast apoptosis. Furthermore, the macrophage-like cell lines used in this study may be a convenient model with which to identify the molecular mechanisms by which BPs promote apoptosis in osteoclasts. Induction of macrophage apoptosis by BPs in vivo may also account, at least in part, for the anti-inflammatory properties of BPs as well as the ability of BPs to cause an acute phase response.
Evaluation of periprosthetic bone using dual-energy X-ray absorptiometry: Precision of the method and effect of operation on bone mineral density
Authors: Kröger Heikki , Miettinen Hannu , Arnala Ilkka , Koski Eila , Rushton Neil , Suomalainen Olavi 
Published: February 2010

Abstract
To assess the perioperative bone loss of femur during total hip arthroplasty (THA), periprosthetic bone mineral density (BMD) of the seven regions of interests (Gruen zones) was determined with dual-energy x-ray absorptiometry (DXA) preoperatively in both proximal femurs and postoperatively in the involved side in 53 patients with degenerative hip osteoarthrosis. The mean (standard deviation, SD) precision error (coefficient of variation percent, CV%) in various regions of interest (ROIs) based on two consecutive measurements (n = 16) were 2.3 (0.8)%, 2.5 (1.5)%, and 2.8 (1.6)% for uncemented stems, cemented stems, and control sides, respectively. Furthermore, the mean variability caused by the rotation of femur was 3.5 (1.4)%. The most significant perioperative bone loss (13.5-19.2%) was found in the calcar area (zone 7) after noncemented THA. Zone 4, representing the bone below the prosthesis, also showed BMD decreases. These decreases suggest perioperative bone loss owing to rasping and reaming the calcar and bone canal. However, after cemented THA, highly significant BMD increases were found in all the lateral zones. The calcar area was the only site where significant perioperative bone loss was detected (12.8%). In conclusion, DXA is a precise method for quantifying bone mass and density changes in the follow-up of THA. However, when interpreting the results, the preoperative BMD, differences between the femurs and the effect of operation on bone mass should be taken into account. We suggest that the best reference for BMD follow-up is the periprosthetic BMD of the involved side measured soon after the THA.
Markers of bone resorption predict hip fracture in elderly women: The EPIDOS prospective study
Authors: Garnero P. , Hausherr E. , Chapuy M.-C. , Marcelli C. , Grandjean H. , Muller C. , Cormier C. , Bréart G. , Meunier P.J. , Dr. Delmas Pierre D. 
Published: February 2010

Abstract
Increased bone turnover has been suggested as a potential risk factor for osteoporotic fractures. We investigated this hypothesis in a prospective cohort study performed on 7598 healthy women more than 75 years of age. One hundred and twenty-six women (mean years 82.5) who sustained a hip fracture during a mean 22-month follow-up were age-matched with three controls who did not fracture. Baseline samples were collected prior to fracture for the measurement of two markers of bone formation and three urinary markers of bone resorption: type I collagen cross-linked N- (NTX) or C-telopeptide (CTX) and free deoxypyridinoline (free D-Pyr). Elderly women had increased bone formation and resorption compared with healthy premenopausal women. Urinary excretion of CTX and free D-Pyr, but not other markers, was higher in patients with hip fracture than in age-matched controls (p = 0.02 and 0.005, respectively). CTX and free D-Pyr excretion above the upper limit of the premenopausal range was associated with an increased hip fracture risk with an odds ratio (95% confidence interval) of 2.2 (1.3-3.6) and 1.9 (1.1-3.2), respectively, while markers of formation were not. Increased bone resorption predicted hip fracture independently of bone mass, i.e., after adjustment for femoral neck bone mineral density (BMD) and independently of mobility status assessed by the gait speed. Women with both a femoral BMD value of 2.5 SD or more below the mean of young adults and either high CTX or high free D-Pyr levels were at greater risk of hip fracture, with an odds ratio of 4.8 and 4.1, respectively, than those with only low BMD or high bone resorption. Elderly women are characterized by increased bone turnover, and some markers of bone resorption predict the subsequent risk of hip fracture independently of hip BMD. Combining the measurement of BMD and bone resorption may be useful to improve the assessment of the risk of hip fracture in elderly women.
Differences in bone mineral in young Asian and Caucasian Americans may reflect differences in bone size
Authors: Bhudhikanok Grace S. , Wang May-Choo , Eckert Kathyrn , Matkin Chantal , Marcus Robert , Dr. Bachrach Laura K. 
Published: February 2010

Abstract
Bone mineral content (BMC) and areal bone mineral density (BMD) have been reported to be lower in Asian than in Caucasian adults. To determine if racial differences in bone mass are present in younger subjects and whether they reflect differences in estimated volumetric bone density or in bone size, we compared measurements of bone mineral in healthy young Asian- and Caucasian-American males and females. Bone mineral was measured at the lumbar spine (L2-L4), femoral neck (FN), and whole body (WB) by dual-energy X-ray absorptiometry (DXA) in 99 Asians (49 females, 50 males) and 103 Caucasians (54 females, 49 males) ages 9-26 years. Results were expressed as BMC, BMD, and apparent density (BMAD), an estimate of volumetric bone density that reduces the effect of bone size. Subjects were compared on the basis of chronological age as well as by Tanner stage to correct for potential differences in the timing of puberty. Habitual dietary intake and physical activity were also assessed and correlated with bone mineral. The Asian and Caucasian cohorts differed in body size, diet, and physical activity. Asian females were shorter than the Caucasian females at all stages of puberty and weighed less at pre-/early puberty (p &lt; 0.05). Asian males were older than Caucasians at midpuberty (p &lt; 0.01) and weighed less than the Caucasian males at pubertal maturity (p = 0.001). Asian youths also consumed less calcium and reported less weight-bearing activity. Racial differences were most apparent when comparing BMC data. Asian males had greater spine BMC at midpuberty and lower WB BMC at maturity (p &lt; 0.05). Asian females had lower FN BMC through midpuberty and lower WB BMC in pre-/early puberty (p &lt; 0.05). WB BMD and WB BMC/height values were significantly lower in mature Asian versus Caucasian males. No significant racial differences in BMAD were observed. Multivariate regression analysis indicated that the differences in BMD and BMAD between Asian and Caucasian subjects were largely attributable to differences in weight and pubertal stage, and, at the FN, in weight-bearing activity. Further, the explanatory variables were less strongly associated with BMAD than with BMD. In summary, no significant differences in BMD were found between Asian and Caucasian youths through midpuberty; however, WB BMD and WB BMC/height values were lower in Asian males at sexual maturity. We conclude that observed differences in bone mineral between Asians and Caucasians may be partially attributed to the smaller bone size of Asians.
Determinants of premenopausal bone mineral density: The interplay of genetic and lifestyle factors
Authors: Salamone Loran M. , Glynn Nancy W. , Black Dennis M. , Ferrell Robert E. , Palermo Lisa , Epstein Robert S. , Kuller Lewis H. , Cauley Jane A. 
Published: February 2010

Abstract
Bone mineral density (BMD) is a reflection of both genetic and lifestyle factors. The interplay of genetic (vitamin D receptor [VDR] gene polymorphisms) and lifestyle factors on BMD at the lumbar spine and proximal femur was examined in 470 healthy premenopausal women, aged 44–50 years, using a Hologic QDR 2000 densitometer. The objective of this study was to examine the genetic and lifestyle determinants of premenopausal BMD. Each participant was genotyped for BsmI polymorphism at the VDR gene locus. The presence of a restriction site within VDR, specified as bb (189, 40.2%) (n, %) was associated with reduced spinal BMD, whereas absence of this site in BB (97, 20.6%) conferred greater spinal BMD, as did the genotype Bb (184, 39.1%). Associations between smoking, alcohol use, oral contraceptives, education level, multivitamins, number of children, degree of obesity, body weight, physical activity, dietary calcium intake, and VDR genotype to BMDs were examined. VDR genotype, body weight, degree of obesity, physical activity, and dietary calcium intake were all significant determinants of BMD. The association of VDR genotype with BMD at the femoral neck appeared to be modified by calcium intake (BB and Bb: 0.797 ± 0.11 g/cm2 vs. 0.844 ± 0.11 g/cm2, interaction term, p = 0.06) for low (&lt;1036 mg/day) and high (⩾1036 mg/day; upper quartile) calcium intakes, respectively. A similar trend was demonstrated for physical activity. These findings suggest that prophylactic interventions aimed at achieving and maintaining optimal BMD, such as greater calcium intake or physical activity, may be important in maximizing one's genetic potential for BMD.
Retired elite female ballet dancers and nonathletic controls have similar bone mineral density at weightbearing sites
Authors: Khan Karim M. , Green Robyn M. , Saul Andrew , Bennell Kim L. , Crichton Kenneth J. , Hopper John L. , Wark John D. 
Published: February 2010

Abstract
Elite female ballet dancers exhibit several risk factors for osteoporosis during their performing years. To study the long-term effect of this lifestyle, we compared the bone mineral density (BMD) of 101 retired elite female ballet dancers (mean age 51 years, SD = 14 years) and 101 normal controls, derived from a twin study, matched hierarchically for age, height, weight, and menopausal status. The dancers, who had been retired for a mean of 25.6 years (range 1–53 years) reported a greater prevalence of previous menstrual disturbance, greater lifetime alcohol intake and smoking, and a lower dietary milk intake in adolescence than controls (all p &lt; 0.05). However, current exercise in the dancers was twice that of the controls (p &lt; 0.01). The BMD of retired dancers did not differ from that of the controls at weightbearing sites. The mean ± SE difference in BMD (dancers minus controls) was 0.009 ± 0.013 at the total body, –0.009 ± 0.018 at the total hip, 0.005 ± 0.017 at the femoral neck, 0.014 ± 0.018 at the femoral trochanter, 0.036 ± 0.022 at the femoral intertrochanter and –0.017 ± 0.021 at the lumbar spine. Retired dancers had lower mean (± SE) BMD at the nonweightbearing sites: ultradistal radius (–0.029 ± 0.008) (p &lt; 0.01) and at the midthird radius (–0.019 ± 0.011) (p &lt; 0.05). There was no difference in the proportion in each of the World Health Organization (WHO) categories of osteopenia (t score –1.0 to –2.5) and osteoporosis (t score &lt;–2.5) at any of the measured sites. Regression analysis revealed that menstrual disturbance was negatively associated with BMD at the lumbar spine and the ultradistal radial sites, but not at the weightbearing femoral sites. This sample of retired elite ballet dancers who had multiple historical risk factors does not appear to have an increased risk for future hip or vertebral fracture based on WHO standards.