bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone Mineral Density and Fracture Among Prevalent Kidney Stone Cases in the Third National Health and Nutrition Examination Survey
Authors: Lauderdale Diane S. , Thisted Ronald A. , Wen Ming , Favus Murray J. 
Published: April 2006

Abstract
Concern that people who form kidney stones may have reduced bone mineral density (BMD) and increased fracture risk has motivated clinical and population-based studies, but findings are inconsistent. In this cross-sectional study, we use the Third National Health and Nutrition Examination Survey (NHANES III) to determine whether a history of kidney stones (n = 793) is associated with lower femoral neck BMD and whether the association is similar for men and women. We further ask whether dietary calcium modifies the association between kidney stone history and BMD and whether there is an association between kidney stone history and prevalent spine or wrist fracture. We find that men with kidney stone history have lower femoral neck BMD than men without kidney stone history after adjusting for age, body mass index (BMI), race/ethnicity, and other potential confounders. The effect of kidney stone history on BMD is weaker for women. Men with kidney stone history also are more likely to report prevalent wrist and spine fractures. Dietary calcium, represented by usual milk consumption, is associated positively with BMD for both men and women and modifies the effect of kidney stone history on BMD for men. For men who form kidney stones, milk consumption is associated more strongly with femoral neck BMD than for men without such a history. The effect modification is such that the difference in BMD between men with and without kidney stone history is observed only at lower levels of milk consumption.
Regional and Hormone-Dependent Effects of Apolipoprotein E Genotype on Changes in Bone Mineral in Perimenopausal Women
Authors: Gerdes Lars Ulrik , Vestergaard Peter , Hermann Anne Pernille , Mosekilde Leif 
Published: April 2006

Abstract
We studied 479 perimenopausal Danish women aged 45–58 years to examine differences between APOE genotypes with respect to (1) baseline total body bone mineral density (BMD) and densities measured in five different regions (ultradistal forearm, proximal forearm, lumbar spine, femoral neck, and total hip region); (2) serum levels of alkaline phosphatase, bone isoenzyme alkaline phosphatase, osteocalcin, parathyroid hormone (PTH), 25-hydroxyvitamin D, and urine hydroxyproline/creatinine excretion ratio; and (3) changes in bone mineral during 5 years of follow-up. Baseline BMDs were identical, whereas serum levels of alkaline phosphatase and its bone isoenzyme were higher in women with APOE 2–2 and APOE 2–3 than in women with APOE 3–3 and APOE 3–4 and lower in women with APOE 4–4. Among women not receiving hormonal-replacement therapy (HRT; n = 262), those with APOE 2–2 and APOE 2–3 had 30–40% lower rates of femoral neck and total hip bone mineral loss than women with APOE 3–3 and APOE 3–4, whereas the rates of mineral loss in other skeletal regions did not differ between these APOE genotypes. Women with APOE 4–4 appeared to have lower rates of bone mineral loss in all regions. Women treated with hormones throughout the follow-up period (n = 113) gained bone mineral, and women with APOE 3–4 and APOE 4–4 gained relatively more mineral than other women. A comparison of untreated and treated women with APOE 2–3, APOE 3–3, and APOE 3–4 suggests a possible modification of the effect of APOE genotype by HRT. In conclusion, the common APOE polymorphism has a complex effect on bone metabolism in perimenopausal Danish women including possible modification by hormone use: (1) among women not receiving HRT, those with APOE2 have lower bone mineral losses in the femoral neck and hip region than other women, and (2) among women receiving HRT, those with APOE4 gain more bone mineral than other women.
Perspective: Postmenopausal Osteoporosis as a Failure of Bone's Adaptation to Functional Loading: A Hypothesis
Authors: Lanyon Lance , Skerry Tim 
Published: April 2006

Abstract
There is substantial evidence that bones' ability to withstand functional loading without damage depends on the processes of bone modeling and remodeling, which are responsible for establishing and maintaining bone architecture, being influenced by a feedback mechanism related to the control of functional strains. It is probably useful to consider the diminished ability to maintain bone strength in postmenopausal osteoporosis as a failure of this mechanism. Acceptance of this approach would not only increase understanding of the etiology of postmenopausal osteoporosis but also significantly influence the ways in which it is investigated and treated. This would not mean that the many other factors affecting bone mass and bone cell activity will be ignored, but rather these factors will be put in perspective. Research to prevent or treat osteoporosis could be directed usefully to understanding how osteoblasts, lining cells, and osteocytes respond to mechanically derived information and how these responses are converted into stimuli controlling structurally appropriate modeling and remodeling. Evidence suggesting that early strain-related responses of bone cells in males and females involve the estrogen receptor (ER) could explain decreased effectiveness of this pathway when ER levels are low.
Chromosome 13 Locus, Pbd2, Regulates Bone Density in Mice
Authors: Shimizu Motoyuki , Higuchi Keiichi , Kasai Soichiro , Tsuboyama Tadao , Matsushita Mutsumi , Mori Masayuki , Shimizu Yasuhiko , Nakamura Takashi , Hosokawa Masanori 
Published: April 2006

Abstract
Bone density is inherited as a complex polygenic trait. Previously, we identified two quantitative trait loci (QTLs) specifying the peak relative bone mass (bone mass corrected by bone size) on chromosomes (Chrs) 11 and 13 by interval mapping in two mouse strains: SAMP2 and SAMP6. The latter strain is an established murine model of senile osteoporosis and exhibits a significantly lower peak relative bone mass than SAMP2 mice. In this study, we report the effects of the Chr 13 QTL on peak bone density (Pbd2). First, we constructed a congenic strain P6.P2-Pbd2b, which carried a single genomic interval from the Chr 13 of SAMP2 on an SAMP6-derived osteoporotic background, to dissect this polygenic trait into single gene factors. This congenic strain had a higher bone density than the background strain using three measurement methods with different principles for bone density. Next, we measured the peak relative bone mass of the AKR/J strain and the 13 senescence-accelerated mouse (SAM) strains, which are considered to be a series of recombinant-like inbred (RI) strains derived from the AKR/J strain and other unspecified strains. We then determined the microsatellite marker haplotypes of these strains around the Pbd2 locus, in which three strains with a high relative bone mass shared the same haplotype over the 26-centimorgan (cM) region. In the Pbd2 locus, a high relative bone mass was associated with alleles of the unknown strain, whereas a low relative bone mass was associated with the alleles from the AKR/J strain. These results confirmed the existence of a Pbd2 locus regulating bone density in the SAM strains.
The Frequency of Common Progenitors for Adipocytes and Osteoblasts and of Committed and Restricted Adipocyte and Osteoblast Progenitors in Fetal Rat Calvaria Cell Populations
Authors: Bellows C. G. , Heersche J. N. M. 
Published: April 2006

Abstract
In fetal rat calvaria (RC) cell populations, adipocyte differentiation is stimulated by both dexamethasone (Dex) and 1,25 dihydroxyvitamin D3 [1,25(OH)2D3], whereas osteoblast differentiation is stimulated by Dex but inhibited by 1,25(OH)2D3. We examined whether the osteoblastic and adipocytic colonies were derived from a common progenitor, from committed and restricted adipocyte and osteoblast progenitors, or from both and whether the adipocyte progenitors stimulated by 1,25(OH)2D3 constitute a population of progenitors that is different from that stimulated by Dex. RC cells were isolated by sequential enzyme digestion yielding five populations designated I-V. In population I the effect of Dex on adipocyte formation was greater than that of 1,25(OH)2D3, whereas the effect of 1,25(OH)2D3 was greater than that of Dex in populations III-V. We next applied replica plating techniques to further investigate the response characteristics of individual osteoprogenitors and adipocyte progenitors by looking at the fate of duplicate colonies derived from the same progenitor under different culture conditions. RC cells were plated at 1000–1500 cells/100 mm culture dish and a 17-μm mesh polyester membrane overlaid onto master dishes on day 4 or day 5 and removed on day 11 or day 12. Then, replicas and master dishes were cultured separately in medium containing either Dex, 1,25(OH)2D3, or Dex plus 1,25(OH)2D3 for a further 17–21 days and then fixed and stained with both Sudan IV and the von Kossa technique. Nine hundred twenty-seven matched colonies present on both master dishes and replica membranes were screened and colonies were classified as either adipocytic, osteoblastic (bone or osteoid), or fibroblastic. Results show convincingly that most of the osteoprogenitors present in fetal RC cells are committed and restricted to the osteoblastic cell lineage (95.29%); that the 1,25(OH)2D3-responsive adipocyte progenitors are different from the Dex-responsive adipocyte progenitors, but both are restricted to form adipocytes and finally; and that a common osteoblast/adipocyte progenitor is present in a low frequency (4.71% of osteoprogenitors).
Early Detection of Bone Metastases in a Murine Model Using Fluorescent Human Breast Cancer Cells: Application to the Use of the Bisphosphonate Zoledronic Acid in the Treatment of Osteolytic Lesions
Authors: Peyruchaud Olivier , Winding Bent , Pécheur Isabelle , Serre Claire-Marie , Delmas Pierre , Clézardin Philippe 
Published: April 2006

Abstract
A very common metastatic site for human breast cancer is bone. The traditional bone metastasis model requires human MDA-MB-231 breast carcinoma cell inoculation into the left heart ventricle of nude mice. MDA-MB-231 cells usually develop osteolytic lesions 3–4 weeks after intracardiac inoculation in these animals. Here, we report a new approach to study the formation of bone metastasis in animals using breast carcinoma cells expressing the bioluminescent jellyfish protein (green fluorescent protein [GFP]). We first established a subclone of MDA-MB-231 cells by repeated in vivo passages in bone using the heart injection model. On stable transfection of this subclone with an expression vector for GFP and subsequent inoculation of GFP-expressing tumor cells (B02/GFP.2) in the mouse tail vein, B02/GFP.2 cells displayed a unique predilection for dissemination to bone. Externally fluorescence imaging of live animals allowed the detection of fluorescent bone metastases approximately 1 week before the occurrence of radiologically distinctive osteolytic lesions. The number, size, and intensity of fluorescent bone metastases increased progressively with time and was indicative of breast cancer cell progression within bone. Histological examination of fluorescent long bones from B02/GFP.2-bearing mice revealed the occurrence of profound bone destruction. Treatment of B02/GFP.2-bearing mice with the bisphosphonate zoledronic acid markedly inhibited the progression of established osteolytic lesions and the expansion of breast cancer cells within bone. Overall, this new bone metastasis model of breast cancer combining both fluorescence imaging and radiography should provide an invaluable tool to study the effectiveness of pharmaceutical agents that could suppress cancer colonization in bone.
A Role for G Protein-Coupled Lysophospholipid Receptors in Sphingolipid-Induced Ca2+ Signaling in MC3T3-E1 Osteoblastic Cells
Authors: Lyons Jeremy M. , Karin Norman J. 
Published: April 2006

Abstract
Sphingolipids have been proposed to modulate cell function by acting as intracellular second messengers and through binding to plasma membrane receptors. Exposure of MC3T3-E1 osteoblastic cells to sphingosine (SPH), sphingosine-1-phosphate (SPP), or sphingosylphosphorylcholine (SPC) led to the release of Ca2+ from the endoplasmic reticulum (ER) and acute elevations in cytosolic-free Ca2+ ([Ca2+]i). Desensitization studies suggest that SPP and SPC bind plasma membrane endothelial differentiation gene (Edg) receptors for lysophosphatidic acid (LPA). Consistent with the coupling of Edg receptors to G proteins, SPP- and SPC-induced Ca2+ signaling was inhibited by pretreatment of the cells with pertussis toxin (PTx). Of the Edg receptors known to bind SPH derivatives in other cell types, MC3T3-E1 cells were found to express transcripts encoding Edg-1 and Edg-5 but not Edg-3, Edg-6, or Edg-8. In contrast to SPP and SPC, the ability of SPH to elicit [Ca2+]i elevations was affected neither by prior exposure of cells to LPA nor by PTx treatment. However, LPA-induced Ca2+ signaling was blocked in MC3T3-E1 cells previously exposed to SPH. Elevations in [Ca2+]i were not evoked by SPP or SPC in cells treated with 2-aminoethoxydiphenylborate (2-APB), an inhibitor of inositol 1,4,5-trisphosphate (IP3)-gated Ca2+ channels in the ER. No effect of 2-APB was observed on SPH- or LPA-induced [Ca2+]i elevations. The data support a model in which SPP and SPC bind Edg-1 and/or Edg-5 receptors in osteoblasts leading to the release of Ca2+ from the ER through IP3-gated channels.
Extracellular Signal-Regulated Kinases and Calcium Channels Are Involved in the Proliferative Effect of Bisphosphonates on Osteoblastic Cells In Vitro
Authors: Mathov Irina , Plotkin Lilian I. , Sgarlata Cecilia L. , Leoni Juliana , Bellido Teresita 
Published: April 2006

Abstract
Bisphosphonates (BPs) are analogues of pyrophosphate, which are widely used for the treatment of different pathologies associated with imbalances in bone turnover. Recent evidence suggested that cells of the osteoblastic lineage might be targets of the action of BPs. The objective of this work was to determine whether BPs induce proliferation of osteoblasts and whether this action involves activation of the extracellular signal-regulated kinases (ERKs). We have shown that three different BPs (olpadronate, pamidronate, and etidronate) induce proliferation in calvaria-derived osteoblasts and ROS 17/2.8 as measured by cell count and by [3H]thymidine uptake. Osteoblast proliferation induced by all BPs diminished to control levels in the presence of U0126, a specific inhibitor of the upstream kinase MEK 1 responsible for ERK phosphorylation. Consistent with this, BPs induced ERK activation as assessed by in-gel kinase assays. Phosphorylation of ERK1/2 was induced by the BPs olpadronate and pamidronate within 30 s, followed by rapid dephosphorylation, whereas etidronate induced phosphorylation of ERKs only after 90 s of incubation and returned to basal levels within 15–30 minutes. In addition, both BP-induced cell proliferation and ERK phosphorylation were reduced to basal levels in the presence of nifedipine, an L-type voltage-sensitive calcium channel (VSCC) inhibitor. These results show that BP-induced proliferation of osteoblastic cells is mediated by activation of ERKs and suggest that this effect requires influx of Ca2+ from the extracellular space through calcium channels.
In Vitro and In Vivo Analysis of the Immune System of Vitamin D Receptor Knockout Mice
Authors: Mathieu Chantal , Van Etten Evelyne , Gysemans Conny , Decallonne Brigitte , Kato Shigeaki , Laureys Jos , Depovere JOS , Valckx Dirk , Verstuyf Annemieke , Bouillon Roger 
Published: April 2006

Abstract
Immune cells carry receptors for 1,25-dihydroxyvitamin D3 [1,25(OH)2D3; vitamin D receptor (VDR)] and individuals with severe vitamin D deficiency have immune abnormalities. The aim of this study was to investigate the role of vitamin D in the immune system by studying VDR-knockout (VDR-KO) mice. VDR-KO mice had the same metabolic phenotype as rachitic animals with severe hypocalcemia. Leukocytosis, lymphocyte subset composition in different immune organs, and splenocyte proliferation to several stimuli were normal, except for a lower response to anti-CD3 stimulation (simulation index [SI] of 13 ± 4 vs. 24 ± 9 in wild-type mice; p &lt; 0.01). Macrophage chemotaxis was impaired (41 ± 19% vs. 60 ± 18% in wild-type mice; p &lt; 0.01) but phagocytosis and killing were normal. In vivo rejection of allogeneic (31 ± 12 days vs. 45 ± 26 days of survival in wild-type mice, NS) or xenogeneic (10 ± 2 days vs. 16 ± 9 days of survival in wild-type mice, NS) islet grafts was comparable with wild-type mice. Surprisingly, VDR-KO mice were protected from low-dose streptozotocin-induced diabetes mellitus (LDSDM; 5% vs. 65% in wild-type mice; p &lt; 0.001). Correcting hypocalcemia by use of lactose-rich or polyunsaturated fat-rich diets fully restored the immune abnormalities in vitro and the sensitivity to diabetes in vivo. On the other hand, treatment with 1,25(OH)2D3 protected wild-type mice against diabetes but did not protect normocalcemic VDR-KO mice. We conclude that immune defects observed in VDR-KO mice are an indirect consequence of VDR disruption because they can be restored by calcium homeostasis normalization. This study proves that although 1,25(OH)2D3 is a pharmacologic and probably a physiological immunomodulator, its immune function is redundant. Moreover, we confirm the essential role of calcium in the immune system.
Effects of Current and Discontinued Estrogen Replacement Therapy on Hip Structural Geometry: The Study of Osteoporotic Fractures
Authors: Beck Thomas J. , Stone Katie L. , Oreskovic Tammy L. , Hochberg Marc C. , Nevitt Michael C. , Genant Harry K. , Cummings Steven R. 
Published: April 2006

Abstract
It is assumed that estrogen influences bone strength and risk of fractures by affecting bone mineral density (BMD). However, estrogen may influence the mechanical strength of bones by altering the structural geometry in ways that may not be apparent in the density. Repeated dual energy X-ray absorptiometry (DXA) hip scan data were analyzed for bone density and structural geometry in elderly women participating in the Study of Osteoporotic Fractures (SOF). Scans were studied with a hip structural analysis program for the effects of estrogen replacement therapy (ERT) on BMD and structural geometry. Of the 3964 women with ERT-use data, 588 used ERT at both the start and end of the ∼3.5-year study, 1203 had past use which was discontinued by clinic visit 4, and 2163 women had never used ERT. All groups lost BMD at the femoral neck, but the reduced BMD among users of ERT was entirely due to subperiosteal expansion and not bone loss, whereas both bone loss and expansion occurred in past or nonusers. BMD increased 0.8%/year at the femoral shaft among ERT users but decreased 0.8%/year among nonusers. Section moduli increased at both the neck and shaft among ERT users but remained unchanged in past and nonusers. Current, but not past, use of estrogen therapy in elderly women seems to increase mechanical strength of the proximal femur by improving its geometric properties. These effects are not evident from changes in femoral neck BMD.
Alendronate Prevents Further Bone Loss in Renal Transplant Recipients
Authors: Giannini Sandro , D'Angelo Angela , Carraro Gianni , Nobile Martino , Rigotti Paolo , Bonfante Luciana , Marchini Francesco , Zaninotto Martina , Carbonare Luca Dalle , Sartori Leonardo , Crepaldi Gaetano 
Published: April 2006

Abstract
The aim of this study was to investigate the effects of alendronate, calcitriol, and calcium in bone loss after kidney transplantation. We enrolled 40 patients (27 men and 13 women, aged 44.2 ± 11.6 years) who had received renal allograft at least 6 months before (time since transplant, 61.2 ± 44.6 months). At baseline, parathyroid hormone (PTH) was elevated in 53% of the patients and the Z scores for bone alkaline phosphatase (b-ALP) and urinary type I collagen cross-linked N-telopeptide (u-NTX) were higher than expected (p &lt; 0.001). T scores for the lumbar spine (−2.4 ± 1.0), total femur (−2.0 ± 0.7), and femoral neck (−2.2 ± 0.6) were reduced (p &lt; 0.001). After the first observation, patients were advised to adhere to a diet containing 980 mg of calcium daily and their clinical, biochemical, and densitometric parameters were reassessed 1 year later. During this period, bone density decreased at the spine (−2.6 ± 5.7%; p &lt; 0.01), total femur (−1.4 ± 4.2%; p &lt; 0.05), and femoral neck (−2.0 ± 3.0%; p &lt; 0.001). Then, the patients were randomized into two groups: (1) group A—10 mg/day of alendronate, 0.50 μg/day of calcitriol, and 500 mg/day of calcium carbonate; and (2) group B—0.50 μg/day of calcitriol and 500 mg/day of calcium carbonate. A further metabolic and densitometric reevaluation was performed after the 12-month treatment period. At the randomization time, group A and group B patients did not differ as to the main demographic and clinical variables. After treatment, bone turnover markers showed a nonsignificant fall in group B patients, while both b-ALP and u-NTX decreased significantly in alendronate-treated patients. Bone density of the spine (+5.0 ± 4.4%), femoral neck (+4.5 ± 4.9%), and total femur (+3.9 ± 2.8%) increased significantly only in the alendronate-treated patients. However, no trend toward further bone loss was noticed in calcitriol and calcium only treated subjects. No drug-related major adverse effect was recorded in the two groups. We conclude that renal transplanted patients continue to loose bone even in the long-term after the graft. Alendronate normalizes bone turnover and increases bone density. The association of calcitriol to this therapy seems to be advantageous for better controlling the complex abnormalities of skeletal metabolism encountered in these subjects.
Alendronate Reduces Periprosthetic Bone Loss After Uncemented Primary Total Hip Arthroplasty: A Prospective Randomized Study
Authors: Venesmaa Petri K. , Kröger Heikki P. J. , Miettinen Hannu J. A. , Jurvelin Jukka S. , Suomalainen Olavi T. , Alhava Esko M. 
Published: April 2006

Abstract
Periprosthetic bone loss, especially in the proximal part of the femur, is common after cemented and uncemented total hip arthroplasty (THA). Bone loss can be progressive and, in the extreme, may threaten survival of the prosthesis. To study whether alendronate therapy can reduce bone loss adjacent to prostheses, 13 uncemented primary THA patients were randomized to the study. They received 10 mg alendronate + 500 mg calcium (n = 8) or 500 mg calcium only (n = 5) daily for 6 months follow-up after THA. Periprosthetic bone mineral density (BMD) was measured with dual energy X-ray absorptiometry (DXA). Decreases in periprosthetic BMD in the alendronate-treated group were lower compared with the changes in the calcium-only group in the same regions of interest at the same follow-up time. In the proximal femur, the mean BMD decrease was 17.1% in the calcium-only group, whereas in the alendronate-treated group the decrease was only 0.9% (p = 0.019). The mean periprosthetic BMD change was also significantly different in the total periprosthetic area between the study groups at the end of the follow-up (calcium-only group −9.9% vs. alendronate-treated group −2.6%; p = 0.019). Alendronate therapy led to a significant reduction in periprosthetic bone loss after primary uncemented THA compared with the changes found in patients without therapy. This kind of bone response may improve the support of the prosthesis and may result in better survival of the prosthesis. However, in this study the follow-up time was too short and the study population was too small to make any long-term conclusions as to the prognosis for THA patients treated with alendronate.