bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of the OSCAR Promoter Polymorphism With BMD in Postmenopausal Women
Authors: Kim Ghi Su , Koh Jung-Min , Chang Jae Suk , Park Byung Lae , Kim Lyoung Hyo , Park Eui Kyun , Kim Shin-Yoon , Shin Hyoung Doo 
Published: April 2006

Abstract
In an effort to identify genetic polymorphisms in potential candidate genes for osteoporosis, 10 variants were identified in the OSCAR gene using direct DNA sequencing, and 560 postmenopausal women were genotyped at five SNP loci, using the TaqMan method. The rare allele (G allele) of OSCAR-2322A&gt;G (SNP in the 5′ flanking region) showed significant association with lower BMD at various bone sites in postmenopausal women (n = 560).
Introduction: BMD is the major factor for determining bone strength and osteoporotic fracture risk and is determined by both environmental and multiple genetic factors. The osteoclast-associated receptor (OSCAR) plays a critical role in osteoclast differentiation and thus is an important candidate gene for the modulation of BMD.
Materials and Methods: Through direct sequencing in 24 Korean individuals, 10 sequence variants were identified: 2 in the 5′ flanking region, 7 in the exons (including 6 nonsynonymous single-nucleotide polymorphisms [SNPs]), and 1 in an intron. Five of these polymorphisms were selected for larger-scale genotyping in postmenopausal women (n = 560). Areal BMD (g/cm2) of the anterior-posterior lumbar spine and the nondominant proximal femur was measured using DXA (Lunar Expert XL and Hologic QDR 4500-A). Lateral thoracolumbar radiographs were obtained in all subjects.
Results: Using multiple regression analysis and controlling for age, years since menopause, height, weight, and evaluation machine as covariates, the rare allele (G allele) of OSCAR-2322A&gt;G showed significant association with lower BMD at various bone sites in postmenopausal women.
Conclusion: These findings suggest that the promoter variant in OSCAR gene (OSCAR-2322A&gt;G) might be one of genetic determinants of BMD in postmenopausal women.
Characteristics and Familial Aggregation of Paget's Disease of Bone in Italy
Authors: Merlotti Daniela , Gennari Luigi , Galli Beatrice , Martini Giuseppe , Calabrò Anna , De Paola Vincenzo , Ceccarelli Elena , Nardi Paolo , Avanzati Annalisa , Nuti Ranuccio 
Published: April 2006

Abstract
This study examined the characteristics of 147 PDB cases from Italy. Our data showed a reduced clinical severity of PDB with respect to other populations and provided further support of the importance of environmental factors (rural area of residence and animal contact) in the pathogenesis of PDB. Familial aggregation was observed in 15% of cases.
Introduction: The etiology of Paget's disease of bone (PDB) remains unknown. Current evidence suggests that interactions among genetic or exogenous factors seem to be necessary for disease expression. Major epidemiological studies were performed in the United Kingdom and in other populations of British descent. To date, there are no reliable data on PDB characteristics among the Italian population, and its frequency in different areas of the country remains unknown.
Materials and Methods: In an attempt to evaluate clinical characteristics, the proportion of familial cases and the influence of environmental features on the occurrence of the disease, we studied 147 consecutive PDB patients. For all subjects, a detailed medical history was obtained, and constitutional features were recorded. Characteristics of PDB patients were compared with those obtained from 323 consecutive non-Pagetic outpatient control subjects.
Results and Conclusions: Of the 147 PDB patients, 22 (15%) had at least one other family member affected, 19 (13%) reported one family member with suspected features of PDB, and 106 (72%) were classified as sporadic PDB. Even though we observed a reduced clinical severity of PDB with respect to other populations (mean number of affected sites, 2.2 ± 1.6), we did not find any evidence of a decreased severity of the disease over time. We also found an association of PDB with animal contact (odds ratio [OR], 2.22; p &lt; 0.0005) and a significant prevalence of PDB in rural versus urban districts (OR, 2.42; p &lt; 0.0005). Osteoarthritis (45%), fractures (14%), hearing loss (14%), and valvular calcifications (15%) were the most observed complications. Interestingly, the geographical distribution of PDB showed a concentration of cases in rural areas of Campania and Tuscany. These areas may indicate local clustering of PDB cases in Italy, similar to that observed in other countries.
In Silico Modeling and Simulation of Bone Biology: A Proposal
Authors: Defranoux Nadine A , Stokes Cynthia L , Young Daniel L , Kahn Arnold J 
Published: April 2006

Abstract
Contemporary, computer-based mathematical modeling techniques make it possible to represent complex biological mechanisms in a manner that permits hypothesis testing in silico. This perspective shows how such approaches might be applied to bone remodeling and therapeutic research.
Currently, the dominant conceptual model applied in bone research involves the dynamic balance between the continual build-up and breakdown of bone matrix by two cell types, the osteoblasts and osteoclasts, acting together as a coordinated, remodeling unit. This conceptualization has served extraordinarily well as a focal point for understanding how mutations, chemical mediators, and mechanical force, as well as external influences (e.g., drugs, diet) affect bone structure and function. However, the need remains to better understand and predict the consequences of manipulating any single factor, or combination of factors, within the context of this complex system's multiple interacting pathways. Mathematical models are a natural extension of conceptual models, providing dynamic, quantitative descriptions of the relationships among interacting components. This formalization creates the ability to simulate the natural behavior of a system, as well as its modulation by therapeutic or dietetic interventions. A number of mathematical models have been developed to study complex bone functions, but most include only a limited set of biological components needed to address a few specific questions. However, it is possible to develop larger, multiscale models that capture the dynamic interactions of many biological components and relate them to important physiological or pathological outcomes that allow broader study. Examples of such models include Entelos' PhysioLab platforms. These models simulate the dynamic, quantitative interactions among a biological system's biochemicals, cells, tissues, and organs and how they give rise to key physiologic and pathophysiologic outcomes. We propose that a similar predictive, dynamical, multiscale mathematical model of bone remodeling and metabolism would provide a better understanding of the mechanisms governing these phenomena as well as serve as an in silico platform for testing pharmaceutical and clinical interventions on metabolic bone disease.
Amelioration of Osteoporosis and Hypovitaminosis D by Sunlight Exposure in Hospitalized, Elderly Women With Alzheimer's Disease: A Randomized Controlled Trial
Authors: Sato Yoshihiro , Iwamoto Jun , Kanoko Tomohiro , Satoh Kei 
Published: April 2006

Abstract
In a random and prospective study, Alzheimer's disease (AD) patients were assigned to regular sunlight exposure (n = 132) or sunlight deprivation (n = 132) and followed for 1 year. Serum 25-OHD level increased by 2.2-fold in the sunlight-exposed group. Eleven patients sustained fractures in the sunlight-deprived group, and three fractures occurred among the sunlight-exposed group (p = 0.0362; odds ratio = 3.7).
Introduction: A high incidence of fractures, particularly of the hip, represents an important problem in patients with Alzheimer's disease (AD), who are prone to falls and have osteoporosis. We previously showed that 25-hydroxyvitamin D (25-OHD) deficiency caused by sunlight deprivation with compensatory hyperparathyroidism causes reduced BMD in elderly women with AD. This study was undertaken to address the possibility that sunlight exposure with calcium supplementation may maintain BMD and reduce the incidence of nonvertebral fractures in elderly women with AD.
Materials and Methods: In a random and prospective study, AD patients were assigned to regular sunlight exposure (n = 132) or sunlight deprivation (n = 132) and followed for 1 year. BMD of the second metacarpal bone was measured using a computed X-ray densitometer (CXD). The CXD method measures BMD and cortical thickness at the middle of the second metacarpal bone on a radiogram of the hand and an aluminum step wedge as a standard (20 steps; 1 mm/step). Incidence of nonvertebral fractures in the two patient groups during the 1-year follow-up period was assessed.
Results and Conclusion: At baseline, average hospitalization period was 1.7 years in both groups, and activity of daily living (ADL) was decreased. Patients of both groups showed vitamin D deficiency caused by sunlight deprivation and decreased dietary intake of vitamin D with compensatory hyperparathyroidism. The exposed group patients were exposed to sunlight (3615 minutes/year). BMD increased by 2.7% in the sunlight-exposed group and decreased by 5.6% in the sunlight-deprived group (p &lt; 0.0001). Serum 25-OHD level increased from 24.0 to 52.2 nM in the sunlight-exposed group. Eleven patients sustained fractures in the sunlight-deprived group, and three fractures occurred among the sunlight-exposed group (p = 0.0362; odds ratio = 3.7). Sunlight exposure can increase the BMD of vitamin D-deficient bone by increasing 25-OHD concentration and lead to the prevention of nonvertebral fractures.
Serum TRACP 5b Is a Useful Marker for Monitoring Alendronate Treatment: Comparison With Other Markers of Bone Turnover
Authors: Nenonen Arja , Cheng Sulin , Ivaska Kaisa K , Alatalo Sari L , Lehtimäki Terho , Schmidt-Gayk Heinrich , Uusi-Rasi Kirsti , Heinonen Ari , Kannus Pekka , Sievänen Harri , Vuori Ilkka , Väänänen H Kalervo , Halleen Jussi M 
Published: April 2006

Abstract
We studied clinical performance of serum TRACP 5b and other bone turnover markers, including S-CTX, U-DPD, S-PINP, S-BALP, and S-OC, for monitoring alendronate treatment. TRACP 5b had higher clinical sensitivity, area under the ROC curve, and signal-to-noise ratio than the other markers.
Introduction: The purpose of this study was to compare the clinical performance of serum TRACP 5b (S-TRACP5b) with that of other markers of bone turnover in the monitoring of alendronate treatment.
Materials and Methods: This double-blinded study included 148 healthy postmenopausal women that were randomly assigned into two groups: one receiving 5 mg alendronate daily (n = 75) and the other receiving placebo (n = 73) for 12 months. All individuals in both groups received calcium and vitamin D daily. The bone resorption markers S-TRACP5b, serum C-terminal cross-linked telopeptides of type I collagen (S-CTX), and total urinary deoxypyridinoline (U-DPD), and the serum markers of bone formation procollagen I N-terminal propeptide (S-PINP), bone-specific alkaline phosphatase (S-BALP), and total osteocalcin (S-OC) were assessed at baseline and at 3, 6, and 12 months after initiation of treatment. Lumbar spine BMD (LBMD) was measured at baseline and 12 months.
Results: Compared with the placebo group, LBMD increased, and all bone markers decreased significantly more in the alendronate group (p &lt; 0.001 for each parameter). The decrease of S-TRACP5b after first 3 months of alendronate treatment correlated significantly with the changes of all other markers except S-OC, the best correlation being with S-CTX (r = 0.60, p &lt; 0.0001). The changes of LBMD at 12 months only correlated significantly with the changes of S-TRACP5b (r = −0.32, p = 0.005) and S-CTX (r = −0.24, p = 0.037) at 3 months. Based on clinical sensitivity, receiver operating characteristic (ROC) curves, and signal-to-noise ratio, S-TRACP5b, S-CTX, and S-PINP were the best markers for monitoring alendronate treatment. Clinical sensitivity, area under the ROC curve, and signal-to-noise ratio were higher for S-TRACP5b than for the other markers.
Conclusion: These results show that S-TRACP5b, S-CTX, and S-PINP are useful markers for monitoring alendronate treatment.
Free Testosterone Is a Positive, Whereas Free Estradiol Is a Negative, Predictor of Cortical Bone Size in Young Swedish Men: The GOOD Study
Authors: Lorentzon Mattias , Swanson Charlotte , Andersson Niklas , Mellström Dan , Ohlsson Claes 
Published: April 2006

Abstract
In this study, we evaluated the predictive roles of sex steroids for skeletal parameters in young men (n = 1068) at the age of peak bone mass. Serum free estradiol was a negative predictor, whereas free testosterone and SHBG were positive predictors of cortical bone size.
Introduction: Previous studies have shown that free estradiol in serum is an independent predictor of areal BMD (aBMD) in elderly men. The aim of this study was to determine whether sex steroids are predictors of volumetric BMD (vBMD) and/or size of the trabecular and cortical bone compartments in young men at the age of peak bone mass.
Materials and Methods: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study consists of 1068 men, 18.9 ± 0.6 years of age. Serum levels of testosterone, estradiol, and sex hormone binding globulin (SHBG) were measured, and free levels of testosterone and estradiol were calculated. The size of the cortical bone and the cortical and trabecular vBMDs were measured by pQCT.
Results: Regression models including age, height, weight, free estradiol, and free testosterone showed that free estradiol was an independent negative predictor of cortical cross-sectional area (tibia β = −0.111, p &lt; 0.001; radius β = −0.125, p &lt; 0.001), periosteal circumference, and endosteal circumference, whereas it was a positive independent predictor of cortical vBMD (tibia β = 0.100, p &lt; 0.003; radius β = 0.115, p = 0.001) in both the tibia and radius. Free testosterone was an independent positive predictor of cortical cross-sectional area (tibia β = 0.071, p = 0.013; radius β = 0.064, p = 0.039), periosteal circumference, and endosteal circumference in both the tibia and radius. Neither cortical nor trabecular vBMD was associated with free testosterone. SHBG was an independent positive predictor of parameters reflecting the size of the cortical bone, including cross-sectional area (β = 0.078, p = 0.009), periosteal circumference, and endosteal circumference.
Conclusions: Free estradiol is a negative, whereas free testosterone is a positive, predictor of cortical bone size in young men at the age of peak bone mass. These findings support the notion that estrogens reduce, whereas androgens increase, cortical bone size, resulting in the well-known sexual dimorphism of cortical bone geometry.
Enhanced Coactivator Binding and Transcriptional Activation of Mutant Vitamin D Receptors From Patients With Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets by Phosphorylation and Vitamin D Analogs
Authors: Liu Yan , Shen Qi , Malloy Peter J , Soliman Emad , Peng Xiaorong , Kim Sungtae , Pike J Wesley , Feldman David , Christakos Sylvia 
Published: April 2006

Abstract
In this study, we report that the function of certain mutant VDRs from patients with hereditary HVDRR can at least be partially restored by phosphorylation and hexafluoro 1,25(OH)2D3 analogs. Our study provides new insights into mechanisms involved in enhancement of mutant VDR function.
Introduction: 1,25-Dihydroxyvitamin D-resistant rickets (HVDRR) is a rare genetic disorder caused by inactivating mutations in the vitamin D receptor (VDR). In this study, we examined VDR from patients with HVDRR having mutations in the ligand-binding domain (F251C, I268T, H305Q, E420K). We examined methods of restoring transcriptional activity of these mutants and the mechanisms involved.
Materials and Methods: Reporter gene transcriptional assays were used to examine the activation of mutant VDRs. Western-blot analysis, glutathione S-transferase (GST) pull-down assays, and chromatin immunoprecipitation (ChIP) assays were also used in this study.
Results: Using mutant VDRs, H305Q, F251C, I268T, and 10−8 M 1,25(OH)2D3, only 10–30% of the activity of wildtype (WT) VDR in activating 24(OH)ase transcription was observed. The transcriptional response of mutant VDR mutants was significantly enhanced 2- to 3-fold by co-treatment of VDR mutant transfected COS-7 cells with 1,25(OH)2D3 and okadaic acid (OA; inhibitor of phosphatase; 50 nM). The H305Q mutant was the most responsive (90% of the response exhibited by WT VDR was restored). The E420K mutant was unresponsive to 1,25(OH)2D3 in the presence or absence of OA. The increased transcriptional response correlated with an increase in the interaction between DRIP205 and the mutant VDR. We further provide evidence that OA induces the phosphorylation of CREB-binding protein (CBP), indicating for the first time a correlation between phosphorylation of CBP and enhanced VDR function. Hexafluoro 1,25(OH)2D3 analogs (RO-26-2198 and RO-4383561) also resulted in at least a partial restoration of the transcriptional responsiveness of mutant VDRs I268T, F251C, and H305Q. Our data indicate that the enhanced potency of the hexafluoro analogs may be caused by increased DRIP205 and glucocorticoid receptor interacting protein 1 (GRIP-1) binding to VDRs and enhanced association of VDRs with DNA, as suggested by results of ChIP assays.
Conclusion: Our study provides new insights into the mechanisms involved in the enhancement of VDR function by both phosphorylation and hexafluoro analogs and forms a basis for future study of vitamin D analogs or specifically designed kinase activity mediators as potential therapy for the treatment of selected patients with HVDRR.
Sustained Nonvertebral Fragility Fracture Risk Reduction After Discontinuation of Teriparatide Treatment
Authors: Prince Richard , Sipos Adrien , Hossain Anwar , Syversen Unni , Ish-Shalom Sophia , Marcinowska Ewa , Halse Johan , Lindsay Robert , Dalsky Gail P , Mitlak Bruce H 
Published: April 2006

Abstract
A follow-up in 1262 women was conducted after the discontinuation of teriparatide. The hazard ratio for combined teriparatide group (20 and 40 μg) for the 50-month period after baseline was 0.57 (p = 0.002), suggesting a sustained effect in reducing the risk of nonvertebral fragility fracture.
Introduction: Treatment with teriparatide {rhPTH(1-34)} 20 and 40 μg once-daily subcutaneous dosing significantly reduced the risk of nonvertebral fragility fractures over a median exposure of 19 months.
Materials and Methods: All participants in the Fracture Prevention Trial were invited to participate in a follow-up study. Prior treatment assignments were revealed, and patients were able to receive osteoporosis treatments without restriction.
Results: Approximately 60% of the 1262 patients received an osteoporosis treatment at some time during follow-up, with greater use in the former placebo group than in the combined former teriparatide group (p &lt; 0.05). The hazard ratios for nonvertebral fragility fractures in each teriparatide group relative to placebo were statistically significant for the 50-month period including treatment and follow-up (p &lt; 0.03). In the follow-up period, the hazard ratio was significantly different between the 40 μg and combined groups versus placebo but not for the 20 μg group versus placebo. However, the 20 and 40 μg groups were not different from each other. Kaplan-Meier analysis of time to fracture showed that the fracture incidence in the former placebo and teriparatide groups diverged during the 50-month period including teriparatide treatment and follow-up (p = 0.009). Total hip and femoral neck BMD decreased in teriparatide-treated patients who had no follow-up treatment; BMD remained stable or further increased in patients who received a bisphosphonate after teriparatide treatment.
Conclusions: While the study design is observational, the results support a sustained effect of teriparatide in reducing the risk of nonvertebral fragility fractures up to 30 months after discontinuation of treatment.
Are We Treating Women With Postmenopausal Osteoporosis for Their Low BMD or High Fracture Risk?
Authors: Api Murat 
Published: April 2006

Abstract
In the field of postmenopausal osteoporosis, the quality of bone has gained more attention than the quantity, so the most important part of anti-osteoporotic efficacy of an agent translates its capacity to reduce osteoporotic fractures. Ten years' experience with alendronate has a lot of conflicting data that have to be discussed in detail. Health care professionals in the field of postmenopausal osteoporosis question the antifracture efficacy of a drug more quickly than its favorable effects on BMD. The aim of this paper is to present the complexity of the results in this 10-year trial that has caused difficulty in its interpretation. Ten-year data of alendronate resulted in inconclusive evidence because of the small sample size, high drop-out rate, heterogeneous distribution of subjects in each arm of the trial, and biologically unexplainable results of the fracture rates. The need for further well-designed trials on long-term antifracture efficacy of antiosteoporotic drugs still remains.
Primary Hyperparathyroidism and Osteosarcoma: Examination of a Large Cohort Identifies Three Cases of Fibroblastic Osteosarcoma
Authors: Jimenez Camilo , Yang Ying , Kim Hyung-Woo , Al-Sagier Fozia , Berry Donald A , El-Naggar Adel K. , Patel Shreyaskumar , Vassilopoulou-Sellin Rena , Gagel Robert F 
Published: April 2006

Abstract
To study a possible relationship between hyperparathyroidism and osteosarcoma, we reviewed 1234 osteosarcoma patients. In this cohort, only three patients had a diagnosis of both hyperparathyroidism and fibroblastic osteosarcoma. These results indicate that hyperparathyroidism is not more prevalent in patients with osteosarcoma than in the general population. However, the presence of hyperparathyroidism may modify the histologic and cytologic features of osteosarcoma.
Introduction: The finding of osteosarcoma in rats receiving human PTH(1-34) raised the question of whether hyperparathyroidism might be a risk factor for development of osteosarcoma in humans.
Materials and Methods: To study a possible relationship between hyperparathyroidism and osteosarcoma, we reviewed the medical records of 1234 osteosarcoma patients seen at The M.D. Anderson Cancer Center since 1948. Our study focused on clinical, biochemical, radiologic, and histopathologic findings indicative of primary hyperparathyroidism and the features of osteosarcoma.
Results: Of the 1234 cases reviewed, 3 patients had a diagnosis of both primary hyperparathyroidism and osteosarcoma. In two cases, hyperparathyroidism preceded the osteosarcoma, and in one case, both conditions were diagnosed at the same time. In two cases with concomitant hyperparathyroidism and osteosarcoma, features of osteitis fibrocystica were identified. The third patient was treated for hyperparathyroidism 3 years before osteosarcoma was diagnosed. All three patients had histologic features of fibroblastic osteosarcoma, a type that accounts for no more than 20% of osteosarcomas. To assess whether the prevalence of hyperparathyroidism was greater than expected in the normal population, we compared the age- and sex-specific prevalence in our cohort to a population of healthy individuals in Tromso, Norway. This analysis showed no significant differences between the two populations, despite the fact that a higher prevalence of hyperparathyroidism (6.9% versus 1.6%) was noted in the 60- to 69-year-old female osteosarcoma age group.
Conclusions: Our results indicate that hyperparathyroidism is not more prevalent in affected individuals with osteosarcoma than in the general population. The finding of fibroblastic osteosarcoma in all three patients raises the question of whether coexistent hyperparathyroidism may modify the cytologic and histologic features of the malignancy.