bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Bone Mass in a Female Hutterite Population
Authors: Wosje Karen S. , Binkley Teresa L. , Fahrenwald Nancy L. , Specker Bonny L. 
Published: April 2006

Abstract
We examined a Hutterite population (n = 243) to determine if their agriculturally diverse, self-sufficient communal lifestyle promotes optimal bone mass attainment because of adequate calcium intake and high physical activity levels during growth and young adulthood. We measured total body (TB) and lumbar bone mineral content (BMC) and bone mineral density (BMD) in 39 school-age (younger) females and 204 working (older) females. Forty-five percent of older females and 79% of younger females currently consumed ≥3 servings (svg) of dairy per day. Older females had lumbar (0.6 ± 1.3) and TB (1.1 ± 1.1) BMD Z scores greater than 0 (both, p &lt; 0.001). The lumbar BMD Z score of younger females was not different from 0 (−0.1 ± 1.0; p = 0.5). Both lumbar (r = 0.46; p &lt; 0.001) and TB (r = 0.20; p = 0.02) BMD Z scores increased with increasing age. In multiple regression analyses for older females, lumbar bone area (p &lt; 0.001), weight (p &lt; 0.001), current hours on feet per day (p = 0.01), colony workload (p &lt; 0.01), and estrogen status (p = 0.06) predicted lumbar BMC. TB bone area (p &lt; 0.001), current hours on feet per day (p &lt; 0.01), and colony workload (p &lt; 0.01) predicted TB BMC. For younger females, lumbar bone area (p &lt; 0.001), weight (p &lt; 0.01), years in present colony (p = 0.02), and menses (p &lt; 0.001) predicted lumbar BMC. TB bone area (p &lt; 0.001), height (p &lt; 0.01), years in present colony (p = 0.03), and menses (p &lt; 0.01) predicted TB BMC. The effect of colony workload could not be separated from other factors different by colony. A heritability estimate of 0.66 was calculated for lumbar BMD using mother and daughter Z scores. Adequate calcium intake during growth, high physical activity early in life, and genetic factors may be contributing to above normal BMD levels in adult female Hutterites.
Developmental Expression and Tissue Distribution of Phex Protein: Effect of the Hyp Mutation and Relationship to Bone Markers
Authors: Ruchon Andréa Frota , Tenenhouse Harriet S. , Marcinkiewicz Mieczyslaw , Siegfried Géraldine , Aubin Jane E. , Desgroseillers Luc , Crine Philippe , Boileau Guy 
Published: April 2006

Abstract
Mutations in PHEX, a phosphate-regulating gene with homology to endopeptidases on the X chromosome, are responsible for X-linked hypophosphatemia (XLH). The murine Hyp homologue has the phenotypic features of XLH and harbors a large deletion in the 3′ region of the Phex gene. We characterized the developmental expression and tissue distribution of Phex protein, using a monoclonal antibody against human PHEX, examined the effect of the Hyp mutation on Phex expression, and compared neprilysin (NEP), osteocalcin, and parathyroid hormone/parathyroid hormone-related protein (PTH/PTHrP) receptor gene expression in bone of normal and Hyp mice. Phex encodes a 100- to 105-kDa glycoprotein, which is present in bones and teeth of normal mice but not Hyp animals. These results were confirmed by in situ hybridization (ISH) and ribonuclease protection assay. Phex protein expression in femur and calvaria decreases with age, suggesting a correlation between Phex expression and bone formation. Immunohistochemical studies detected Phex protein in osteoblasts, osteocytes, and odontoblasts, but not in osteoblast precursors. In contrast to Phex, the abundance of NEP messenger RNA (mRNA) and protein is not significantly altered in Hyp bone. Similarly, osteocalcin and PTH/PTHrP receptor gene expression are not compromised in bone of Hyp mice. Our results are consistent with the hypothesis that loss of Phex function affects the mineralizing activity of osteoblasts rather than their differentiation.
Protein Geranylgeranylation Is Required for Osteoclast Formation, Function, and Survival: Inhibition by Bisphosphonates and GGTI-298
Authors: Dr. Coxon Fraser P. , Helfrich Miep H. , Van't Hof Robert , Sebti Saïd , Ralston Stuart H. , Hamilton Andrew , Rogers Michael J. 
Published: April 2006

Abstract
Bisphosphonates are the important class of antiresorptive drugs used in the treatment of metabolic bone diseases. Although their molecular mechanism of action has not been fully elucidated, recent studies have shown that the nitrogen-containing bisphosphonates can inhibit protein prenylation in macrophages in vitro. In this study, we show that the nitrogen-containing bisphosphonates risedronate, zoledronate, ibandronate, alendronate, and pamidronate (but not the non nitrogen-containing bisphosphonates clodronate, etidronate, and tiludronate) prevent the incorporation of [14C]mevalonate into prenylated (farnesylated and geranylgeranylated) proteins in purified rabbit osteoclasts. The inhibitory effect of nitrogen-containing bisphosphonates on bone resorption is likely to result largely from the loss of geranylgeranylated proteins rather than loss of farnesylated proteins in osteoclasts, because concentrations of GGTI-298 (a specific inhibitor of geranylgeranyl transferase I) that inhibited protein geranylgeranylation in purified rabbit osteoclasts prevented osteoclast formation in murine bone marrow cultures, disrupted the osteoclast cytoskeleton, inhibited bone resorption, and induced apoptosis in isolated chick and rabbit osteoclasts in vitro. By contrast, concentrations of FTI-277 (a specific inhibitor of farnesyl transferase) that prevented protein farnesylation in purified rabbit osteoclasts had little effect on osteoclast morphology or apoptosis and did not inhibit bone resorption. These results therefore show the molecular mechanism of action of nitrogen-containing bisphosphonate drugs in osteoclasts and highlight the fundamental importance of geranylgeranylated proteins in osteoclast formation and function.
EXT 1 Gene Mutation Induces Chondrocyte Cytoskeletal Abnormalities and Defective Collagen Expression in the Exostoses
Authors: Legeai-Mallet Laurence , Rossi Antonio , Benoist-Lasselin Catherine , Piazza Rocco , Mallet Jean-François , Delezoide Anne-Lise , Munnich Arnold , Bonaventure Jacky , Zylberberg Louise 
Published: April 2006

Abstract
Hereditary multiple exostoses (HME), an autosomal skeletal disorder characterized by cartilage-capped excrescences, has been ascribed to mutations in EXT 1 and EXT 2, two tumor suppressor-related genes encoding glycosyltransferases involved in the heparan sulfate proteoglycan (HSPG) biosynthesis. Taking advantage of the availability of three different exostoses from a patient with HME harboring a premature termination codon in the EXT 1 gene, morphological, immunologic, and biochemical analyses of the samples were carried out. The cartilaginous exostosis, when compared with control cartilage, exhibited alterations in the distribution and morphology of chondrocytes with abundant bundles of actin filaments indicative of cytoskeletal defects. Chondrocytes in the exostosis were surrounded by an extracellular matrix containing abnormally high amounts of collagen type X. The unexpected presence of collagen type I unevenly distributed in the cartilage matrix further suggested that some of the hypertrophic chondrocytes detected in the cartilaginous caps of the exostoses underwent accelerated differentiation. The two mineralized exostoses presented lamellar bone arrangement undergoing intense remodeling as evidenced by the presence of numerous reversal lines. The increased electrophoretic mobility of chondroitin sulfate and dermatan sulfate proteoglycans (PGs) extracted from the two bony exostoses was ascribed to an absence of the decorin core protein. Altogether, these data indicate that EXT mutations might induce a defective endochondral ossification process in exostoses by altering actin distribution and chondrocyte differentiation and by promoting primary calcification through decorin removal.
Mice Lacking the Plasminogen Activator Inhibitor 1 Are Protected from Trabecular Bone Loss Induced by Estrogen Deficiency
Authors: Daci E. , Verstuyf A. , Moermans K. , Bouillon R. , Carmeliet G. 
Published: April 2006

Abstract
Bone turnover requires the interaction of several proteases during the resorption phase. Indirect evidence suggests that the plasminogen activator/plasmin pathway is involved in bone resorption and turnover, and recently we have shown that this cascade plays a role in the degradation of nonmineralized bone matrix in vitro. To elucidate the role of the plasminogen activator inhibitor 1 (PAI-1) in bone turnover in vivo, bone metabolism was analyzed in mice deficient in the expression of PAI-1 gene (PAI-1−/−) at baseline (8-week-old mice) and 4 weeks after ovariectomy (OVX) or sham operation (Sham) and compared with wild-type (WT) mice. PAI-1 inactivation was without any effect on bone metabolism at baseline or in Sham mice. However, significant differences were observed in the response of WT and PAI-1−/− mice to ovariectomy. The OVX WT mice showed, as expected, decreased trabecular bone volume (BV/TV) and increased osteoid surface (OS/BS) and bone formation rate (BFR), as assessed by histomorphometric analysis of the proximal tibial metaphysis. In contrast, no significant change in any of the histomorphometric variables studied was detected in PAI-1−/− mice after ovariectomy. As a result, the OVX PAI-1−/− had a significantly higher BV/TV, lower OS/BS, lower mineral apposition rate (MAR) and BFR when compared with the OVX WT mice. However, a comparable decrease in the cortical thickness was observed in OVX PAI-1−/− and WT mice. In addition, the cortical mineral content and density assessed in the distal femoral metaphysis by peripheral quantitative computed tomography (pQCT), decreased significantly after ovariectomy, without difference between PAI-1−/− mice and WT mice. In conclusion, basal bone turnover and bone mass are only minimally affected by PAI-1 inactivation. In conditions of estrogen deficiency, PAI-1 inactivation protects against trabecular bone loss but does not affect cortical bone loss, suggesting a site-specific role for PAI-1 in bone turnover.
The Predictive Value of Biochemical Markers of Bone Turnover for Bone Mineral Density in Postmenopausal Japanese Women
Authors: Chaki Osamu , Yoshikata Iromi , Kikuchi Ritsuko , Nakayama Masaki , Uchiyama Yukimi , Hirahara Fumiki , Gorai Itsuo 
Published: April 2006

Abstract
To examine the predictive value of biochemical markers of bone turnover for bone loss pre- and postmenopausally, we measured two markers of bone formation, bone-specific alkaline phosphatase (BALP) and intact osteocalcin (OC); four markers of bone resorption, urinary cross-linked N-telopeptides of type I collagen (NTx), type I collagen C-telopeptide breakdown products (CTx), hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP); serum OC N-terminal (OC-N); and two serum cytokines, soluble interleukin-6 receptor (sIL-6R) and IL-1r antagonist at baseline and 1 year, as well as lumbar spine bone mineral density (BMD) at baseline and 1, 2, 3, 4, and 5 years after trial in 82 premenopausal (44.8 ± 5.4 years old) and 325 postmenopausal (60.2 ± 6.1 years old) healthy Japanese women. In premenopausal women, stratification of the baseline value of each biochemical marker into quartiles did not cause any significant difference in the change in BMD. Stratification of the NTx baseline value in postmenopausal women showed significant differences in rate of bone loss to the first year among those subjects with each quartile (Q1 [0.28 ± 0.28%], Q2 [−0.32 ± 0.34%], Q3 [−1.50 ± 0.31%], and Q4 [−2.43 ± 0.35%]) except for the difference between Q1 and Q2. The predictive value of NTx for BMD was greater in early postmenopausal women within 5 years after menopause than in late postmenopausal women with more than 5 years since menopause (YSM). Quartile analysis of the other biochemical markers and serum cytokines did not show any significant capacity for differentiating between bone loss rates. Moreover, when the changes in the lumbar spine BMD to the second and third years were stratified into quartiles by the baseline NTx, the ratios of bone loss to the second and the third years were significantly higher in those women with higher NTx (Q4; −3.15 ± 0.56% and −4.06 ± 0.57%, respectively) than in those with lower NTx (Q1; −0.74 ± 0.44% and −1.03 ± 0.51%, respectively). In conclusion, baseline urinary NTx was the most sensitive predictor of bone loss in the lumbar spine after 1, 2, and 3 years. Markers of bone resorption can be used clinically to predict future BMD in postmenopausal women.
Interpretation of Calcaneus Dual-Energy X-Ray Absorptiometry Measurements in the Assessment of Osteopenia and Fracture Risk
Authors: Wren Tishya A. L. , Yerby Scott A. , Beaupré Gary S. , Carter Dennis R. 
Published: April 2006

Abstract
Dual-energy X-ray absorptiometry (DXA) of the calcaneus is useful in assessing bone mass and fracture risk at other skeletal sites. However, DXA yields an areal bone mineral density (BMD) that depends on both bone apparent density and bone size, potentially complicating interpretation of the DXA results. Information that is more complete may be obtained from DXA exams by using a volumetric density in addition to BMD in clinical applications. In this paper, we develop a simple methodology for determining a volumetric bone mineral apparent density (BMAD) of the calcaneus. For the whole calcaneus, BMAD = (BMC)/ADXA3/2, where BMC and ADXA are, respectively, the bone mineral content and projected area measured by DXA. We found that ADXA3/2 was proportional to the calcaneus volume with a proportionality constant of 1.82 ± 0.02 (mean ± SE). Consequently, consistent with theoretical predictions, BMAD was proportional to the true volumetric apparent density (ρ) of the bone according to the relationship ρ = 1.82 BMAD. Also consistent with theoretical predictions, we found that BMD varied in proportion to ρV1/3, where V is the bone volume. We propose that the volumetric apparent density, estimated at the calcaneus, provides additional information that may aid in the diagnosis of osteopenia. Areal BMD or BMD2 may allow estimation of the load required to fracture a bone. Fracture risk depends on the loading applied to a bone in relation to the bone's failure load. When DXA is used to assess osteopenia and fracture risk in patients, it may be useful to recognize the separate and combined effects of applied loading, bone apparent density, and bone size.
Generalized Low Areal and Volumetric Bone Mineral Density in Adolescent Idiopathic Scoliosis
Authors: Cheng J. C. Y. , Qin L. , Cheung C. S. K. , Sher A. H. L. , Lee K. M. , Ng S. W. E. , Guo X. 
Published: April 2006

Abstract
Adolescent idiopathic scoliosis (AIS) may be associated with generalized low bone mineral status. The bone mineral density (BMD) of 75 girls of 12–14 years of age and diagnosed as having AIS were compared with 94 age-matched female control subjects. Areal BMD (aBMD) of the lumbar spine (L2-L4) and the bilateral proximal femur were measured using -energy X-ray absorptiometry (DEXA), and volumetric BMD (vBMD) of the nondominant distal radius and bilateral distal tibias was measured with peripheral quantitative computer tomography (pQCT). Relevant anthropometric parameters and the severity of the spinal deformity (Cobb's angle) also were evaluated and correlated with the BMD measurements. Results revealed the presence of a generalized lower bone mineral status in AIS patients. Detailed analysis showed that the aBMD and vBMD measured at the bilateral lower extremities were significantly lower in AIS patients when compared with the same in the normal controls. The most significant effect was seen in the trabecular BMD (tBMD) of the distal tibias. Of all the AIS girls, 38% of the aBMD and 36% of the vBMD were below −1 SD of the normal. BMD was found to correlate better with “years since menarche” (YSM) than with chronological age. When the BMD was evaluated for the 3 YSM groups, aBMD of the proximal femur and tBMD of distal tibias were found to be significantly lower in the AIS patients. Neither the aBMD nor the vBMD of AIS patients was found to be associated with the severity of spinal deformity. In addition, anthropometric measurements showed significantly longer arm span and lower extremities in the AIS girls. We concluded that the AIS girls had generalized lower aBMDs and vBMDs.
Phalangeal Osteosonogrammetry Study: Age-Related Changes, Diagnostic Sensitivity, and Discrimination Power
Authors: Wüster C. , Albanese C. , De aloysio D. , Duboeuf F. , Gambacciani M. , Gonnelli S. , Glüer C. C. , Hans D. , Joly J. , Reginster J. Y. , De Terlizzi F. , Cadossi R. 
Published: April 2006

Abstract
Phalangeal osteosonogrammetry was introduced as a method for bone tissue investigation in 1992. It is based on the measure of the velocity of ultrasound (amplitude-dependent speed of sound [AD-SoS]) and on the interpretation of the characteristics of the ultrasound signal. In this study we have collected a database of 10,115 subjects to evaluate the performance of AD-SoS and to develop a parameter that is able to quantify the signal characteristics: ultrasound bone profile index (UBPI). The database only includes females of which 4.5% had documented vertebral osteoporotic fractures, 16% lumbar spine dual X-ray absorptiometry (DXA), and 6% hip DXA. The analysis of the ultrasound signal has shown that with aging the UBPI, first wave amplitude (FWA), and signal dynamics (SDy) follow a trend that is different from the one observed for AD-SoS; that is, there is no increase during childhood. In the whole population, the risk of fracture per SD decrease for AD-SOS was odds ratio (OR) 1.71 (CI, 1.58-1.84). The AD-SoS in fractured subjects was significantly lower than in a group of age-matched nonfractured subjects (p &lt; 0.0001). In a small cohort of hip-fractured patients UBPI proved to be lower than in a control age-matched group (p &lt; 0.0001). When the World Health Organization (WHO) working group criteria were applied to this population to identify the T score value for osteoporosis, for AD-SoS we found a T score of −3.2 and for UBPI we found a T score of −3.14. Sixty-six percent of vertebral fractures were below the AD-SoS −3.2 T score and 62% were below UBPI −3.14. We observed the highest incidence of fractures (63.6%) among subjects with AD-SoS who had both DXA T score values below the threshold. We conclude from this study that ultrasound investigation at the hand phalanges is a valid methodology for osteoporosis assessment. It has been possible to quantify signal changes by means of UBPI, a parameter that will improve the possibility of investigating bone structure.
Utilization of Bone Morphogenetic Protein Receptors During Chondrocyte Maturation
Authors: Volk Susan W. , D'Angelo Marina , Diefenderfer David , Dr. Leboy Phoebe S. 
Published: April 2006

Abstract
Cartilage from the upper, cephalic portion of embryonic chick sternums undergoes hypertrophy, while the lower, caudal portion of the sternum remains as cartilage. Bone morphogenetic proteins (BMPs) induce type X collagen (colX) in cultured upper but not lower sternal chondrocytes (LSCs). We have examined the utilization of BMP receptors (BMPRs) by upper sternal chondrocytes (USCs) and LSCs both by analyzing receptor expression and by overexpressing mutant BMPRs. Reverse-transcription polymerase chain reaction (RT-PCR) analyses indicate that both upper and lower chondrocytes produce messenger RNA (mRNA) for all three receptors: BMPR type IA (BMPR-IA), BMPR type IB (BMPR-IB), and BMPR type II (BMPR-II). Infection of USC with retroviral vectors expressing constitutively active (CA) BMPRs showed that CA-BMPR-IB, like exogenous BMP-4, induced both colX mRNA and elevated alkaline phosphatase (AP), while CA-BMPR-IA was markedly less potent. However, expression of activated receptors in LSC cultures resulted in only minimal induction of hypertrophic markers. Consistent with the results seen for CA receptors, dominant negative (DN) BMPR-IB blocked BMP-induced hypertrophy in USCs more effectively than DN-BMPR-IA. These results imply that the major BMPR required for BMP induction of chondrocyte hypertrophy is BMPR-IB, and that difference between permanent and prehypertrophic chondrocytes is not caused by absence of receptors required for BMP signaling.
Corticosteroid Osteoporosis: Practical Implications of Recent Trials
Authors: Sambrook Philip N. 
Published: April 2006

Abstract
Corticosteroids are widely used and effective agents for control of many inflammatory diseases, but osteoporosis is a common problem associated with their long-term use. Several large double-blind controlled clinical trials in patients with corticosteroid osteoporosis recently have been published, indicating it is possible to prevent or reverse this bone loss. Ultimately, the aim of treatment is to prevent fractures, especially vertebral fractures that are the most common type of fracture associated with corticosteroid therapy, yet it remains unclear exactly which patients should receive prophylaxis. Understanding the differences between these trials is key to interpreting the results, which have important practical implications for patient management.
Type V Osteogenesis Imperfecta: A New Form of Brittle Bone Disease
Authors: Glorieux Francis H. , Rauch Frank , Plotkin Horacio , Ward Leanne , Travers Rose , Roughley Peter , Lalic Ljiljana , Glorieux Delphine F. , Fassier François , Bishop Nicholas J. 
Published: April 2006

Abstract
Osteogenesis imperfecta (OI) is commonly subdivided into four clinical types. Among these, OI type IV clearly represents a heterogeneous group of disorders. Here we describe 7 OI patients (3 girls), who would typically be classified as having OI type IV but who can be distinguished from other type IV patients. We propose to call this disease entity OI type V. These children had a history of moderate to severe increased fragility of long bones and vertebral bodies. Four patients had experienced at least one episode of hyperplastic callus formation. The family history was positive for OI in 3 patients, with an autosomal dominant pattern of inheritance. All type V patients had limitations in the range of pronation/supination in one or both forearms, associated with a radiologically apparent calcification of the interosseous membrane. Three patients had anterior dislocation of the radial head. A radiodense metaphyseal band immediately adjacent to the growth plate was a constant feature in growing patients. Lumbar spine bone mineral density was low and similar to age-matched patients with OI type IV. None of the type V patients presented blue sclerae or dentinogenesis imperfecta, but ligamentous laxity was similar to that in patients with OI type IV. Levels of biochemical markers of bone metabolism generally were within the reference range, but serum alkaline phosphatase and urinary collagen type I N-telopeptide excretion increased markedly during periods of active hyperplastic callus formation. Qualitative histology of iliac biopsy specimens showed that lamellae were arranged in an irregular fashion or had a meshlike appearance. Quantitative histomorphometry revealed decreased amounts of cortical and cancellous bone, like in OI type IV. However, in contrast to OI type IV, parameters that reflect remodeling activation on cancellous bone were mostly normal in OI type V, while parameters reflecting bone formation processes in individual remodeling sites were clearly decreased. Mutation screening of the coding regions and exon/intron boundaries of both collagen type I genes did not reveal any mutations affecting glycine codons or splice sites. In conclusion, OI type V is a new form of autosomal dominant OI, which does not appear to be associated with collagen type I mutations. The genetic defect underlying this disease remains to be elucidated.