bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inactivation of theNa-Cl Co-Transporter(NCC) Gene Is Associated With High BMD Through Both Renal and Bone Mechanisms: Analysis of Patients With Gitelman Syndrome andNccNull Mice
Authors: Nicolet-Barousse Laurence , Blanchard Anne , Roux Christian , Pietri Laurence , Bloch-Faure May , Kolta Sami , Chappard Christine , Geoffroy Valérie , Morieux Caroline , Jeunemaitre Xavier , Shull Gary E , Meneton Pierre , Paillard Michel , Houillier Pascal , De Vernejoul Marie-Christine 
Published: April 2006

AbstractChronic thiazide treatment is associated with high BMD. We report that patients and mice with null mutations in the thiazide-sensitive NaCl cotransporter (NCC) have higher renal tubular Ca reabsorption, higher BMD, and lower bone remodeling than controls, as well as abnormalities in Ca metabolism, mainly caused by Mg depletion.Introduction: Chronic thiazide treatment decreases urinary Ca excretion (UVCa) and increases BMD. To understand the underlying mechanisms, Ca and bone metabolism were studied in two models of genetic inactivation of the thiazide-sensitive NaCl cotransporter (NCC): patients with Gitelman syndrome (GS) and Ncc knockout (Ncc−/−) mice.Materials and Methods: Ca metabolism was analyzed in GS patients and Ncc−/− mice under conditions of low dietary Ca. BMD was measured by DXA in patients and mice, and bone histomorphometry was analyzed in mice.Results: GS patients had low plasma Mg. They exhibited reduced UVCa, but similar serum Ca and GFR as control subjects, suggesting increased renal Ca reabsorption. Blood PTH was lower despite lower serum ionized Ca, and Mg repletion almost corrected both relative hypoparathyroidism and low UVCa. BMD was significantly increased in GS patients at both lumbar (+7%) and femoral (+16%) sites, and osteocalcin was reduced. In Ncc−/− mice, serum Ca and GFR were unchanged, but UVCa was reduced and PTH was elevated; Mg repletion largely corrected both abnormalities. Trabecular and cortical BMD were higher than in Ncc+/+ mice (+4% and +5%, respectively), and despite elevated PTH, were associated with higher cortical thickness and lower endosteal osteoclastic surface.Conclusions: Higher BMD is observed in GS patients and Ncc−/− mice. Relative hypoparathyroidism (human) and bone resistance to PTH (mice), mainly caused by Mg depletion, can explain the low bone remodeling and normal/low serum Ca despite increased renal Ca reabsorption.
Early Changes in Biochemical Markers of Bone Formation Predict BMD Response to Teriparatide in Postmenopausal Women With Osteoporosis
Authors: Chen Peiqi , Satterwhite Julie H , Licata Angelo A , Lewiecki E Michael , Sipos Adrien A , Misurski Derek M , Wagman Rachel B 
Published: April 2006

Abstract
The relationship between early changes in biochemical markers of bone turnover and the subsequent BMD response to daily teriparatide therapy in women with postmenopausal osteoporosis was studied. Changes in five biochemical markers, obtained from a subset of women enrolled in the Fracture Prevention Trial, were examined. Early increases in the PICP and the PINP were the best predictors of BMD response to teriparatide in this analysis.
Introduction: Early reductions in biochemical markers of bone turnover with antiresorptive therapy negatively correlate with subsequent increases in BMD. We undertook this analysis to determine if early changes in biochemical markers with teriparatide therapy predict subsequent increases in BMD.
Materials and Methods: In the Fracture Prevention Trial, 1637 postmenopausal women with osteoporosis were randomized to receive daily, self-administered, subcutaneous injections of placebo, teriparatide 20 μg/day, or teriparatide 40 μg/day. Serum concentrations of two bone formation markers (bone-specific alkaline phosphatase [bone ALP] and the carboxy-terminal extension peptide of procollagen type 1 [PICP]) and urinary concentrations of two bone resorption markers (free deoxypyridinoline [DPD] and N-terminal telopeptide [NTX]) were assessed in a trial population subset (n = 520) at baseline and at 1, 3, 6, and 12 months. We also assessed serum concentrations of another bone formation marker, the amino-terminal extension peptide of procollagen type 1 (PINP), in a subset of 771 women at baseline and 3 months. Lumbar spine (LS) BMD was measured by DXA at baseline and 18 months. Femoral neck BMD was measured at baseline and 12 months.
Results and Conclusion: Baseline bone turnover status correlated positively and significantly with BMD response. The highest correlations occurred for the LS BMD response to teriparatide 20 μg/day. Among all studied biochemical markers, increases in PICP at 1 month and PINP at 3 months correlated best with increases in LS BMD at 18 months (0.65 and 0.61, respectively; p &lt; 0.05). The relationships between these two biochemical markers and the LS BMD response were stronger than the corresponding relationships for the femoral neck BMD response. Using receiver operator curve analysis, we determined that the increases in PICP at 1 month and PINP at 3 months were the most sensitive and accurate predictors of the LS BMD response.
Growth Patterns at Distal Radius and Tibial Shaft in Pubertal Girls: A 2-Year Longitudinal Study
Authors: Wang Qingju , Alén Markku , Nicholson Patrick , Lyytikäinen Arja , Suuriniemi Miia , Helkala Erkki , Suominen Harri , Cheng Sulin 
Published: April 2006

Abstract
Bone changes, in terms of both size and BMD, were assessed longitudinally in pubertal girls. Before puberty, BMD at the distal radius declined, whereas bone size increased, suggesting that normal growing girls experience a transient period of increased bone fragility. This could explain the elevated low-trauma forearm fracture rates reported in earlier studies.
Introduction: Longitudinal data on bone growth during puberty are sparse. Such information is needed to understand the sequence of biological changes, the physical and mechanical consequences for the growing skeleton, and the implications for later life.
Materials and Methods: The geometric properties and volumetric BMD (vBMD) of the distal radius and tibial shaft were measured using pQCT in 258 pubertal girls followed over 2 years. A new hierarchical linear statistical modeling approach was used to determine true longitudinal trends.
Results: The growth rates of cross-sectional area (CSA) and BMC of the distal radius peaked at 16 and 9 months before menarche, respectively. This growth asynchrony between bone size and mass meant that total vBMD of the distal radius declined until 1 year before menarche. At the tibial shaft, total vBMD and cortical vBMD increased monotonically without any such transient reduction. Cortical thickness increased linearly, which was accounted for mainly by bone formation at the periosteal surface before menarche, but by both periosteal and endocortical apposition after menarche. During puberty, the ratio of cortical-to-total CSA of the tibial shaft increased and that of marrow-to-total CSA decreased.
Conclusions: The temporal pattern of bone growth during puberty differs at the distal radius and tibial shaft. A transient decrease in vBMD, arising from asynchronous bone size and mass growth, occurs only at the radius. In the tibia, the mechanism of cortical thickening changes from periosteal apposition premenarche to both periosteal and endocortical apposition postmenarche.
Enamel Matrix Protein Interactions
Authors: Wang HongJun , Tannukit Sissada , Zhu DanHong , Snead Malcolm L , Paine Michael L 
Published: April 2006

Abstract
The recognized structural proteins of the enamel matrix are amelogenin, ameloblastin, and enamelin. While a large volume of data exists showing that amelogenin self-assembles into multimeric units referred to as nanospheres, other reports of enamel matrix protein-protein interactions are scant. We believe that each of these enamel matrix proteins must interact with other organic components of ameloblasts and the enamel matrix. Likely protein partners would include integral membrane proteins and additional secreted proteins.
Introduction: The purpose of this study was to identify and catalog additional proteins that play a significant role in enamel formation.
Materials and Methods: We used the yeast two-hybrid assay to identify protein partners for amelogenin, ameloblastin, and enamelin. Once identified, RT-PCR was used to assess gene transcription of these newly identified and potential “enamel” proteins in ameloblast-like LS8 cells.
Results: In the context of this yeast assay, we identified a number of secreted proteins and integral membrane proteins that interact with amelogenin, ameloblastin, and enamelin. Additionally, proteins whose functions range from the inhibition of soft tissue mineralization, calcium ion transport, and phosphorylation events have been identified as protein partners to these enamel matrix proteins. For each protein identified using this screening strategy, future studies are planned to confirm this physiological relationship to biomineralization in vivo.
Conclusion: Identifying integral membrane proteins of the secretory surface of ameloblast cells (Tomes' processes) and additional enamel matrix proteins, based on their abilities to interact with the most abundant enamel matrix proteins, will better define the molecular mechanisms of enamel formation at its most rudimentary level.
Serum Retinoids and β-Carotene as Predictors of Hip and Other Fractures in Elderly Women
Authors: Barker Margo E , McCloskey Eugene , Saha Shikha , Gossiel Fatma , Charlesworth Diane , Powers Hilary J , Blumsohn Aubrey 
Published: April 2006

Abstract
There is debate about the possible deleterious effect of excessive vitamin A exposure on fracture risk. In this nested case control study in older women (312 cases and 934 controls), serum retinol, retinyl palmitate, and β-carotene were not associated with fracture risk, and there was no evidence of excess risk with multivitamin or cod liver oil supplementation.
Introduction: Recent studies have suggested that higher vitamin A intake may account for a component of fracture risk within the general population and that supplemental vitamin A may be harmful even within recommended limits. No studies have examined the relationship between biochemical retinol status and fracture in older women.
Materials and Methods: We examined serum retinol, retinyl palmitate, and β-carotene as predictors of incident hip and other fractures in a large prospective study of British women over the age of 75 years (n = 2606, 312 incident osteoporotic fractures, 92 incident hip fractures; mean follow-up duration, 3.7 years). Fasting blood samples (9:00-11:00 a.m.) were collected at baseline. Using a case-control design (three controls per case), serum retinol, retinyl palmitate, and β-carotene were assessed as univariate predictors of incident osteoporotic fracture or hip fracture. Baseline BMD at the total hip, age, 25(OH)D, serum β Crosslaps, bone-specific alkaline phosphatase, weight, height, and smoking were considered as covariates in a multivariate model.
Results: Serum retinol, retinyl palmitate, and β-carotene were not significant univariate predictors of either hip fracture or any fracture (all p &gt; 0.05; Cox proportional hazards regression). For all osteoporotic fractures, the hazard ratio (HR) was 0.92 (95% CI, 0.81-1.05) per 1 SD increase in serum retinol. Risk of any osteoporotic fracture was slightly less in the highest quartile of serum retinol compared with the lowest quartile (HR, 0.85; 95% CI, 0.69-1.05; p = 0.132) There was a tendency for increased serum retinol to predict benefit rather than harm in terms of BMD (r = 0.09, p = 0.002). Multivitamin or cod liver oil supplementation was associated with a significantly lower risk of any fracture (HR, 0.76; 95% CI, 0.60-0.96; p = 0.021). In multivariate analysis, only age, total hip BMD, and weight were associated with fracture risk (p &lt; 0.05).
Conclusions: We found no evidence to support any skeletal harm associated with increased serum indices of retinol exposure or modest retinol supplementation in this population.
A Frequent Regulatory Variant of the Estrogen-Related Receptor α Gene Associated With BMD in French-Canadian Premenopausal Women
Authors: Laflamme Nathalie , Giroux Sylvie , Loredo-Osti J Concepción , Elfassihi Latifa , Dodin Sylvie , Blanchet Claudine , Morgan Kenneth , Giguère Vincent , Rousseau François 
Published: April 2006

Abstract
Genes are important BMD determinants. We studied the association of an ESRRA gene functional variant with BMD in 1335 premenopausal women. The ESRRA genotype was an independent predictor of L2-L4 BMD, with an effect similar to smoking and equivalent to a 10-kg difference in weight.
Introduction: Several genetic polymorphisms have been associated with osteoporosis or osteoporosis fractures, but no functional effect has been shown for most of these gene variants. Because functional studies have implicated estrogen-related receptor α (ESRRA) in bone metabolism, we evaluated whether a recently described regulatory variant of the ESRRA gene is associated with lumbar and hip BMD as measured by DXA and with heel bone parameters as measured by quantitative ultrasound (QUS).
Materials and Methods: Heel bone parameters were measured by right calcaneal QUS in 1335 healthy French-Canadian premenopausal women, and one-half of these women also had their BMD evaluated at two sites: femoral neck and lumbar spine (L2-L4) by DXA. All bone measures were tested separately for association with the ESRRA genotype by analysis of covariance. The significance of the ESRRA contribution to the model was also assessed by two different permutation tests.
Results: A statistically significant association between ESRRA genotype and lumbar spine BMD was observed: women carrying the long ESRRA genotype had a 3.9% (0.045 g/cm2) higher lumbar spine BMD than those carrying the short ESRRA genotype (p = 0.004), independently of other risk factors measured. This effect of ESRRA genotype is similar to the effect of smoking and equivalent to a 10-kg difference in weight. This association was confirmed by permutation tests (p = 0.004). The same trend was observed for femoral neck BMD (2.6%, p = 0.07). However, no association was observed between ESRRA and QUS heel bone measures.
Conclusion: These results support the genetic influence of this ESRRA regulatory variant on BMD.
What Proportion of Incident Radiographic Vertebral Deformities Is Clinically Diagnosed and Vice Versa?
Authors: Fink Howard A , Milavetz Donna L , Palermo Lisa , Nevitt Michael C , Cauley Jane A , Genant Harry K , Black Dennis M , Ensrud Kristine E 
Published: April 2006

Abstract
We prospectively examined, in a large cohort of older women, the proportion of incident radiographic vertebral deformities diagnosed as incident clinical vertebral fractures in the same women at the same vertebral level. The proportion of deformities clinically diagnosed ranged from &lt;15% for milder deformities to nearly 30% for more severe deformities.
Introduction: The relationship between radiographic and clinical vertebral fractures is incompletely understood. No previous study has prospectively compared the agreement between incident radiographic vertebral deformities and incident community-recognized, radiographically confirmed vertebral fractures in the same women at the same vertebral level(s).
Materials and Methods: This analysis of data from the Fracture Intervention Trial included all participants who completed both baseline and at least one scheduled follow-up lateral spinal radiograph (n = 6084). Incident vertebral deformities were defined at a given vertebral level as a reduction between baseline and closeout radiographs of ≥20% and 4 mm in any vertebral height and subdivided into two severity categories. Incident clinical vertebral fractures were those reported to clinical centers by participants and confirmed by the study radiologist, who compared the community spinal radiograph with the participant's baseline study radiograph using semiquantitative methods.
Results: A total of 446 incident radiographic vertebral deformities were identified in 330 women, whereas 121 women experienced one or more confirmed incident clinical vertebral fracture. Of incident radiograpic vertebral deformities, 22.6% were also clinically diagnosed as incident vertebral fractures, with clinical diagnoses made for 28.4% of the deformities that exceeded 30% and 4 mm height loss (severe deformity) compared with 14.3% for deformities that involved ≥20% and 4 mm but &lt;30% height loss (milder deformity). Of incident clinical vertebral fractures, 72.7% were morphometrically identified as incident deformities, most of them as severe deformities. More than 20% of incident clinical fractures were not identified as incident deformities by even the most liberal morphometric criterion used in this study.
Conclusions: Approximately one-fourth of incident radiographic vertebral deformities were clinically diagnosed as new vertebral fractures, although the proportion clinically diagnosed was increased for more severe deformities. Whereas most incident clinical vertebral fractures were identified as severe morphometric deformities, approximately one-fourth did not meet even the most liberal study criterion for morphometric deformity. Further study of factors that may explain the discordance between incident vertebral deformities and incident clinical vertebral fractures is important.
Long-Term Strontium Ranelate Administration in Monkeys Preserves Characteristics of Bone Mineral Crystals and Degree of Mineralization of Bone
Authors: Farlay Delphine , Boivin Georges , Panczer Gérard , Lalande Agnès , Meunier Pierre Jean 
Published: April 2006

Abstract
In monkeys, long-term strontium ranelate administration results in a dose-dependent bone strontium uptake (mainly into newly formed bone) that preserves the degree of mineralization of bone and the bone mineral at the crystal level, showing its safety at bone mineral level.
Introduction: Strontium ranelate simultaneously increases bone formation and decreases bone resorption, leading to prevention of bone loss and increase in bone mass and bone strength in normal and ovariectomized rats. This study investigated the interactions of stable strontium (Sr) with bone mineral in monkeys after long-term strontium ranelate treatment and after a period of treatment withdrawal.
Materials and Methods: Iliac bone was obtained from untreated monkeys, monkeys at the end of a 52-week strontium ranelate administration (200, 500, 1250 mg/kg/day orally), and in parallel groups 10 weeks after the end of strontium ranelate administration (same three doses; n = 3–7). Sr uptake and distribution in bone mineral were quantified by X-ray microanalysis, changes at the crystal level by X-ray diffraction, and the degree of mineralization of bone (DMB) by quantitative microradiography.
Results: After strontium ranelate administration, dose-dependent Sr uptake occurred into cortical and cancellous bone, with higher content (1.6 times) in new than in old bone. This Sr uptake decreased (50%) 10 weeks after treatment withdrawal; the decrease occurred almost exclusively in new bone. At the end of strontium ranelate treatment and after its withdrawal, a preservation of crystal characteristics was observed, suggesting that Sr was only faintly linked to crystals by ionic substitution and of DMB.
Conclusions: These results show the absence of a deleterious effect of long-term strontium ranelate treatment on bone mineralization, confirming the histomorphometric observations made in postmenopausal osteoporotic women treated with strontium ranelate.
Differential Effect of BMP4 on NIH/3T3 and C2C12 Cells: Implications for Endochondral Bone Formation
Authors: Li Guangheng , Peng Hairong , Corsi Karin , Usas Arvydas , Olshanski Anne , Huard Johnny 
Published: April 2006

Abstract
After intramuscular implantation, BMP4-expressing NIH/3T3 fibroblasts and BMP4-expressing C2C12 myoblasts can promote ectopic cartilage and bone formation. Fibroblasts tend to undergo chondrogenesis, whereas myoblasts primarily undergo osteogenesis. These results suggest that endochondral bone formation may involve different cell types, a finding that could have major implications for the tissue engineering of bone and cartilage.
Introduction: The delivery of BMP4 through cell-based gene therapy can trigger ectopic endochondral bone formation in skeletal muscle. We hypothesized that, when stimulated with or transduced to express BMP4, different types of cells residing within skeletal muscle might participate in different stages of endochondral bone formation.
Materials and Methods: We compared the responses of a fibroblast cell line (NIH/3T3), a myoblast cell line (C2C12), primary fibroblasts, and primary myoblasts to BMP4 stimulation in vitro. We then transduced the four cell populations to express BMP4 and compared their ability to promote ectopic endochondral bone formation in skeletal muscle.
Results: Under the influence of BMP4 in vitro and in vivo, NIH/3T3 cells differentiated toward both chondrogenic and osteogenic lineages, whereas most C2C12 cells underwent primarily osteogenic differentiation. NIH/3T3 cells genetically modified to express BMP4 induced delayed but more robust cartilage formation than did genetically modified C2C12 cells, which promoted rapid ossification. These differences in terms of the timing and amount of cartilage and bone formation persisted even after we introduced a retrovirus encoding dominant negative Runx2 (DNRunx2) into the C2C12 cells, which interferes with the function of Runx2. Superior osteogenic potential was also displayed by the primary myoblasts in vitro and in vivo compared with the primary fibroblasts. The different proliferation abilities and differentiation potentials exhibited by these cells when influenced by BMP4 may at least partially explain the differing roles that BMP4-expressing myogenic cells and BMP4-expressing fibroblastic cells play in endochondral bone formation.
Conclusions: Our findings suggest that the process of endochondral bone formation in skeletal muscle after delivery of BMP4 involves different cell types, including fibroblastic cells, which are more involved in the chondrogenic phases, and myoblastic cells, which are primarily involved in osteogenesis. These findings could have important implications for the development of tissue engineering applications focused on bone and cartilage repair.