bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct Effect of Acute Metabolic and Respiratory Acidosis on Parathyroid Hormone Secretion in the Dog
Authors: Lopez Ignacio , Aguilera‐Tejero Escolastico , Felsenfeld Arnold J. , Estepa Jose Carlos , Rodriguez Mariano 
Published: April 2006

AbstractBecause both metabolic (Met Acid) and respiratory acidosis (Resp Acid) have diverse effects on mineral metabolism, it has been difficult to establish whether acidosis directly affects parathyroid hormone (PTH) secretion. Our goal was to determine whether acute Met Acid and Resp Acid directly affected PTH secretion. Three groups of dogs were studied: control, acute Met Acid induced by HCl infusion, and acute Resp Acid induced by hypoventilation. EDTA was infused to prevent acidosis‐induced increases in ionized calcium, but more EDTA was needed in Met Acid than in Resp Acid. The PTH response to EDTA‐induced hypocalcemia was evaluated also. Magnesium needed to be infused in groups receiving EDTA to prevent hypomagnesemia. The half‐life of intact PTH (iPTH) was determined during hypocalcemia when PTH was measured after parathyroidectomy. During normocalcemia, PTH values were greater (p < 0.05) in Met Acid (92 ± 19 pg/ml) and Resp Acid (77 ± 22 pg/ml) than in controls (27 ± 5 pg/ml); the respective pH values were 7.23 ± 0.01, 7.24 ± 0.01, and 7.39 ± 0.02. The maximal PTH response to hypocalcemia was greater (p < 0.05) in Met Acid (443 ± 54 pg/ml) than in Resp Acid (267 ± 37 pg/ml) and controls (262 ± 48 pg/ml). The half‐life of PTH was greater (p < 0.05) in Met Acid than in controls, but the PTH secretion rate also was greater (p < 0.05) in Met Acid than in the other two groups. In conclusion, (1) both acute Met Acid and Resp Acid increase PTH secretion when the ionized calcium concentration is normal; (2) acute Met Acid may increase the bone efflux of calcium more than Resp Acid; (3) acute Met Acid acts as a secretogogue for PTH secretion because it enhances the maximal PTH response to hypocalcemia.
Tryptophan Missense Mutation in the Ligand‐Binding Domain of the Vitamin D Receptor Causes Severe Resistance to 1,25‐Dihydroxyvitamin D
Authors: Nguyen T. M. , Adiceam P. , Kottler M. L. , Guillozo H. , Rizk‐Rabin M. , Brouillard F. , Lagier P. , Palix C. , Garnier J. M. , Garabedian M. 
Published: April 2006

AbstractIn this study, two related young children, brother and sister, exhibited severe vitamin D‐resistant rickets without alopecia. Sequence analysis of the total vitamin D receptor (VDR) cDNA from skin fibroblasts revealed a substitution of the unique tryptophan of the VDR by arginine at amino acid 286 (W286R). Cultured skin fibroblasts of the two patients expressed normal‐size VDR protein (immunocytochemistry and Western blotting) and normal length VDR mRNA (Northern blotting). But, these fibroblasts, as well as COS‐7 cells transfected with the W286R mutant, failed to bind 3H 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3]. The tryptophan substitution did not affect VDR trafficking toward the nucleus but abolished the 24‐hydroxylase gene response to 1,25(OH)2D3, even at 10−6 M concentrations. In conclusion, this case report of a new family with hereditary vitamin D‐ resistant rickets (HVDRR) emphasizes the crucial role of the VDR tryptophan for ligand binding and for transactivation of 1,25(OH)2D3 target genes. It clearly shows the clinical significance of this VDR amino acid for calcium homeostasis and bone mineralization. This observation suggests further that the presence of a stable VDR‐bound ligand may not be obligatory for normal hair follicle development.
Biglycan Deficiency Interferes With Ovariectomy-Induced Bone Loss
Authors: Nielsen Karina L , Allen Matthew R , Bloomfield Susan A , Andersen Thomas L , Chen Xiao-Dong , Poulsen Hans S , Young Marian F , Heegaard Anne-Marie 
Published: April 2006

Abstract
Biglycan is a matrix proteoglycan with a possible role in bone turnover. In a 4-week study with sham-operated or OVX biglycan-deficient or wildtype mice, we show that biglycan-deficient mice are resistant to OVX-induced trabecular bone loss and that there is a gender difference in the response to biglycan deficiency.
Introduction: Biglycan (bgn) is a small extracellular matrix proteoglycan enriched in skeletal tissues, and biglycan-deficient male mice have decreased trabecular bone mass and bone strength. The purpose of this study was to investigate the bone phenotype of the biglycan-deficient female mice and to investigate the effect of estrogen depletion by ovariectomy (OVX).
Materials and Methods: OVX or sham operations were performed on 21-week-old mice that were divided into four groups: wt sham (n = 7), wt OVX (n = 9), bgn-deficient sham (n = 10) and bgn-deficient OVX (n = 10). The mice were killed 4 weeks after surgery. Bone mass and bone turnover were analyzed by peripheral quantitative computed tomography (pQCT), biochemical markers, and histomorphometry.
Results and Conclusions: In contrast to the male mice, there were only few effects of bgn deficiency on bone metabolism in female mice, showing a clear gender difference. However, when stressed by OVX, the female bgn knockout (KO) mice were resistant to the OVX-induced trabecular bone loss. The wt mice showed a decrease in trabecular bone mineral density by pQCT measurements, a decrease in trabecular bone volume (BV/TV), and an increase in mineral apposition rate. In contrast, no significant changes were detected in bgn KO mice after OVX. In addition, analysis of the bone resorption marker deoxypyridinoline showed no significant increase in the bgn KO OVX mice compared with bgn KO sham mice. Measurements of serum osteoprotegerin (OPG) and RANKL revealed increased levels of OPG and decreased levels of RANKL in the bgn KO mice compared with wt mice. In conclusion, the bgn deficiency protects against increased trabecular bone turnover and bone loss in response to estrogen depletion, supporting the concept that bgn has dual roles in bone, where it may modulate both formation and resorption ultimately influencing the bone turnover process.
Shock Wave Application Enhances Pertussis Toxin Protein-Sensitive Bone Formation of Segmental Femoral Defect in Rats
Authors: Chen Yeung-Jen , Kuo Yur-Ren , Yang Kuender D , Wang Ching-Jen , Huang Hue-Chen , Wang Feng-Sheng 
Published: April 2006

Abstract
Extracorporeal shock waves (ESWs) elicit a dose-dependent effect on the healing of segmental femoral defects in rats. After ESW treatment, the segmental defect underwent progressive mesenchymal aggregation, endochondral ossification, and hard callus formation. Along with the intensive bone formation, there was a persistent increase in TGF-β1 and BMP-2 expression. Pretreatment with pertussis toxin reduced ESW-promoted callus formation and gap healing, which presumably suggests that Gi proteins mediate osteogenic signaling.
Introduction: Extracorporeal shock waves (ESWs) have previously been used to promote bone repair. In our previous report, we found that ESWs promoted osteogenic differentiation of mesenchymal cells through membrane perturbation and activation of Ras protein. In this report, we show that ESWs elicit a dose-dependent effect on the healing of segmental defects and that Gi proteins play an important role in mediating ESW stimulation.
Materials and Methods: Rats with segmental femoral defects were subjected to ESW treatment at different energy flux densities (EFD) and impulses. Bone mass (mineral density and calcium content), osteogenic activities (bone alkaline phosphatase activity and osteocalcin content), and immunohistochemistry were assessed.
Results: An optimal ESW energy (500 impulses at 0.16 mJ/mm2 EFD) stimulated complete bone healing without complications. ESW-augmented healing was characterized by significant increases (p &lt; 0.01) in callus size, bone mineral density, and bone tissue formation. With exposure to ESW, alkaline phosphatase activity and osteocalcin production in calluses were found to be significantly enhanced (p &lt; 0.05). After ESW treatment, the histological changes we noted included progressive mesenchymal aggregation, endochondral ossification, and hard callus formation. Intensive bone formation was associated with a persistent increase in transforming growth factor-beta 1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2) expression, suggesting both growth factors were active in ESW-promoted bone formation. We also found that pertussis toxin, an inhibitor of membrane-bound Gi proteins, significantly reduced (p &lt; 0.01) ESW promotion of callus formation and fracture healing.
Conclusion: ESW treatments enhanced bone formation and the healing of segmental femoral defects in rats. It also seems likely that TGF-β1 and BMP-2 are important osteogenic factors for ESW promotion of fracture healing, presumably through Gi protein-mediated osteogenic signaling.
Bone Histomorphometric Changes After Liver Transplantation for Chronic Cholestatic Liver Disease
Authors: Guichelaar Maureen MJ , Malinchoc Michael , Sibonga Jean D , Clarke Bart L , Hay J Eileen 
Published: April 2006

Abstract
Thirty-three patients with cholestatic liver disease underwent histomorphometric assessment of paired bone biopsy specimens at time of orthotopic liver transplantation (OLT) and 4 months thereafter. At 4 months after OLT, bone metabolism improved, with bone formation increasing to normal and no change in bone resorption. Early post-transplant bone loss may be attributed to an additional insult to bone formation early after transplantation.
Introduction: Patients with advanced liver disease, especially chronic cholestasis, often have osteopenia, which worsens early after orthotopic liver transplantation (OLT) before starting to recover. The changes in bone metabolism leading to this rapid loss of bone after OLT, and to its recovery, are poorly defined.
Materials and Methods: In thirty-three patients with advanced chronic cholestatic liver disease, tetracycline-labeled bone biopsy specimens were analyzed prospectively at time of OLT and at 4 months after OLT, as part of a randomized trial to study the efficacy of calcitonin on post-transplant bone loss. Hierarchical cluster analysis of histomorphometric parameters was performed in an attempt to establish the functional grouping of individual histomorphometric parameters before and after OLT.
Results and Conclusions: Results showed that from the time of OLT to 4 months after OLT, bone mineral density of the lumbar spine and histomorphometric parameters of bone volume decreased, consistent with early post-transplant bone loss. Histomorphometric resorption parameters were increased before OLT, with no change after OLT. Histomorphometric formation parameters increased from low values before OLT to normal values at 4 months after OLT, with the exception of mean wall thickness values, which further decreased after OLT, suggesting an additional insult to bone formation during the study period. Histomorphometric changes after OLT were similar in female and male patients, pre- and postmenopausal women, and in patients treated and not treated with calcitonin. Hierarchical cluster analysis suggested that before OLT, bone resorption was functioning independently of bone formation, but that by 4 months after OLT, their coupled relationship had improved. Therefore, despite post-transplant bone loss, by 4 months after OLT, bone metabolism had improved, with increased bone formation and more coupled bone balance, as suggested by hierarchical cluster analysis.
Interrelationships Between Structural Parameters of Cancellous Bone Reveal Accelerated Structural Change at Low Bone Volume
Authors: Parkinson Ian H , Fazzalari Nicola L 
Published: April 2006

Abstract
This study shows that change to cancellous bone structure is bone volume-dependent in a nonlinear manner. At low bone volume (&lt;15%), trabecular thickness and trabecular separation change at a much greater rate than at higher bone volume. This suggests that the structural integrity of the cancellous bone may become rapidly compromised when bone volume falls below a critical value.
Introduction: While bone mass is the major determinant of bone strength, this mass-based paradigm does not fully account for the contribution of the bone microstructure to mechanical efficiency. Geometric models of cancellous bone structure have been formulated based on stylized representations of the trabecular elements, where the relationships between bone volume and bone surface of cancellous bone are complex and reflect the modulating effect on the cancellous bone structure of bone remodeling at the trabecular surfaces. Using the plate model of cancellous bone structure, the interrelationships between parameters of cancellous bone structure have been studied.
Materials and Methods: Two hundred eighty histological sections of human cancellous bone from eight skeletal sites were analyzed. The structural parameters of cancellous bone (BV/TV, BS/TV, BS/BV, Tb.Th, Tb.Sp, Tb.N, and TBPf) were obtained.
Results and Conclusions: This study shows that change to cancellous bone structure is bone volume-dependent in a nonlinear manner. At low bone volume (&lt;15%), structural parameters of cancellous bone, such as trabecular thickness and trabecular separation, change at a much greater rate than at higher bone volume. This suggests that the structural integrity of the cancellous bone may become rapidly compromised when bone volume falls below a critical value. These data describe the complex relationships between bone mass and structure in cancellous bone that are often overlooked in the mass-based paradigm of bone strength. Histomorphometric descriptors of cancellous bone structure highlight the potential for accelerated deterioration of the structure with low bone volume, which leads to increased risk of fracture. From a clinical viewpoint, estimation of an individual's fracture risk is constrained to noninvasive techniques, which only provide bone mineral density or bone mineral content. Therefore, there is a need to better correlate measurement of bone mass with measurements of structural parameters.
A Prospective Study of Risedronate on Regional Bone Metabolism and Blood Flow at the Lumbar Spine Measured by18F-Fluoride Positron Emission Tomography
Authors: Frost Michelle L , Cook Gary JR , Blake Glen M , Marsden Paul K , Benatar Nigel A , Fogelman Ignac 
Published: April 2006

Abstract
The effect of risedronate on bone metabolism at the lumbar spine was assessed in 18 women who had a18F-fluoride PET scan at baseline and after 6 months of therapy. The net plasma clearance of fluoride to bone mineral reflecting osteoblastic activity decreased significantly after therapy.
Introduction: Quantitative radionuclide studies of bone reflect bone blood flow and regional osteoblastic activity, and the latter should change after treatment with a bisphosphonate, although this has not been previously demonstrated. The aim of this study was to examine regional18F-fluoride kinetics in the lumbar spine measured by18F-fluoride positron emission tomography (PET) before and after treatment with risedronate.
Materials and Methods: Eighteen women, with a mean age of 67.0 years and a T-score of less than −2 at the spine or hip, had a dynamic PET scan of the lumbar spine after the injection of 90 MBq18F-fluoride ion at baseline and 6 months after commencing risedronate therapy. The arterial plasma input function was derived using aorta arterial activity from the PET image. Time-activity curves were measured by placing regions of interest over the lumbar vertebrae. A three-compartmental model was used to calculate bone blood flow (K1) and the net plasma clearance of tracer to bone mineral (Ki). Rate constants k2, k3, and k4, which describe transport between plasma, the extracellular fluid (ECF) compartment, and the bone mineral compartment, respectively, were also measured.
Results: Mean vertebral Ki decreased significantly by 18.4% from baseline (3.32 × 10−2 ml/min/ml) to 6 months post-treatment (2.71 × 10−2 ml/min/ml; p = 0.04). This decrease was similar in magnitude to the decrease observed for bone-specific alkaline phosphatase, a marker of bone formation. There was no significant difference in K1 from baseline (1.49 × 10−1 ml/min/ml) to 6 months after treatment (1.38 × 10−1 ml/min/ml; p &gt; 0.05). There was a significant increase in k2, reflecting the reverse transport of fluoride from the extravascular tissue compartment to plasma, after 6 months of treatment (2.90 × 10−1/min versus 4.43 × 10−1/min; p = 0.01). No significant changes were seen for k3 or k4. There was a significant decrease from baseline in the fraction of tracer in the extravascular tissue space that underwent specific binding to the bone matrix (k3/[k2 + k3]), decreasing by 18.1% (p = 0.02).
Conclusion: K i, the net plasma clearance to bone mineral reflecting regional osteoblastic activity, displayed a significant decrease after 6 months of antiresorptive therapy. This is the first study to show a direct metabolic effect of antiresorptive therapy on skeletal kinetics at the clinically important site of the lumbar spine. The use of18F-fluoride PET may provide a useful noninvasive tool to assess novel treatments currently being developed for osteoporosis.
Gender Differences in Mortality After Hip Fracture: The Role of Infection
Authors: Wehren Lois E , Hawkes William G , Orwig Denise L , Hebel J Richard , Zimmerman Sheryl I , Magaziner Jay 
Published: April 2006

Abstract
Possible explanations for the observed gender difference in mortality after hip fracture were examined in a cohort of 804 men and women. Mortality during 2 years after fracture was identified from death certificates. Men were twice as likely as women to die, and deaths caused by pneumonia/influenza and septicemia showed the greatest increase.
Introduction: Men are more likely to die after hip fracture than women. Gender differences in predisposing factors and causes of death have not been systematically studied.
Materials and Methods: Participants (173 men and 631 women) in the Baltimore Hip Studies cohort enrolled in 1990 and 1991, at the time of hospitalization for hip fracture, were followed longitudinally for 2 years. Cause-specific mortality 1 and 2 years after hip fracture, identified from death certificates, was compared by gender and to population rates.
Results and Conclusions: Men were twice as likely as women to die during the first and second years after hip fracture (odds ratio [OR], 2.28; 95% CI, 1.47, 3.54 and OR, 2.21; 95% CI, 1.48, 3.31). Prefracture medical comorbidity, type of fracture, type of surgical procedure, and postoperative complications did not explain the observed difference. Greatest increases in mortality, relative to the general population, were seen for septicemia (relative risk [RR], 87.9; 95% CI, 16.5, 175 at 1 year and RR, 32.0; 95% CI, 7.99, 127 at 2 years) and pneumonia (RR, 23.8; 95% CI, 12.8, 44.2 at 1 year and RR, 10.4; 95% CI, 3.35, 32.2 at 2 years). The magnitude of increase in deaths caused by infection was greater for men than for women in both years. Mortality rates for men and women were similar if deaths caused by infection were excluded (3.46 [1.79, 6.67] and 2.47 [1.63, 3.72] at 1 year and 0.96 [0.48, 1.91] and 1.26 [0.80, 1.98] at 2 years). Deaths related to infections (pneumonia, influenza, and septicemia) seem to be largely responsible for the observed gender difference. In conclusion, an increased rate of death from infection and a gender difference in rates persists for at least 2 years after the fracture.
Racial Differences in Bone Mineral Density in Older Men
Authors: George Asha , Tracy J Kathleen , Meyer Walter A , Flores Raymond H , Wilson P David , Hochberg Marc C 
Published: April 2006

Abstract
Studies have examined factors related to BMD in older white, but not black, men. We measured BMD in older white and black men and examined factors related to racial differences in BMD. Black men had significantly higher adjusted BMD at all sites. These results may explain, in part, the lower incidence of fractures in older black men.
Introduction: Several studies have examined factors associated with bone mineral density (BMD)in older men. None, however, have had sufficient numbers of black men to allow for meaningful comparisons by race.
Materials and Methods: A total of 503 white and 191 black men aged 65 and older(75.1 ± 5.8 and 72.2 ± 5.7 years, respectively) were recruited from the Baltimore metropolitan area. All men completed a battery of self-administered questionnaires, underwent a standardized examination, and had BMD measured at the femoral neck, lumbar spine, and total body. Data were analyzed using multiple variable linear regression models, adjusted for potential confounding variables; two-way interactions with main effects were included in models where appropriate.
Results: Black men had significantly higher adjusted BMD at the femoral neck (difference 0.09 [95% CI: 0.07, 0.12] mg/cm2), lumbar spine (0.07 [0.04, 0.10] mg/cm2), and total body (0.06 [0.03, 0.08] mg/cm2) than white men.
Conclusions: Older black men have significantly higher BMD than older white men, even after adjustment for factors associated with BMD. These differences, especially at the femoral neck, may explain the reduced incidence of hip fracture in black compared with white men.
Mechanisms of Tumor Metastasis to the Bone: Challenges and Opportunities
Authors: Reddi A Hari , Roodman David , Freeman Colette , Mohla Suresh 
Published: April 2006

Abstract
In human cancers, bone is a common site for metastasis. It is well known that metastasis is the cause of morbidity and mortality in patients with cancer. Both breast and prostate carcinomas have a propensity to metastasize to bone. In general, metastatic breast cancers result in osteolytic lesions. On the other hand, prostate cancer metastases are osteoblastic and result in osteosclerosis. Thus, bone formation and bone resorption are at the crux of the cancer metastasis problem. For example, in the prostate, there is a vicious cycle of metastasis to bone (Fig. 1). Metastases to bone causes excruciating bone pain, pathological fractures, and eventually death, and therefore is a serious challenge to both bone biologists and cancer cell biologists. The stromal-epithelial interactions in breast and prostate are critical in initiation of carcinogenesis and the progression of the metastatic cascade to bone (Fig. 2). Over a hundred years ago, Stephen Paget enunciated the seed and soil hypothesis in which seeds of metastatic cancer cells of breast preferentially settle in the soil of bone matrix. Thus, the prostate/breast cancer bone interface and continuum has continuously presented challenges and opportunities and were discussed at a recent workshop.