bluuebunny/crossref_metadata_2025_split huggingface dataset:
Individual Smallest Detectable Difference in Bone Mineral Density Measurements
Authors: Ravaud P. , Reny J. L. , Giraudeau B. , Porcher R. , Dougados M. , Roux C. 
Published: April 2006

Abstract
Bone mineral density (BMD) measurement is a major outcome measure in osteoporosis. The BMD changes observed must exceed the variability inherent in the measurement process to be considered related to disease progression. The objective of the study was to estimate short-term variability of BMD measurement and to propose a cut-off value for the smallest detectable BMD changes for an individual. To estimate the short-term variability, 70 healthy postmenopausal women aged 53 ± 4 years (group 1) and 57 elderly osteoporotic postmenopausal women aged 80 ± 6 years (group 2) had two repeated BMD measurements of the lumbar spine (L2–L4) and the proximal femur with dual-energy X-ray absorptiometry, with complete repositioning within 1 h. Cut-offs derived from short-term variability were either estimated from the coefficient of variation (CV) (which is a function of the measured value) or from the standard deviation (SD), and applied to 330 postmenopausal women (group 3) who had BMD measurements at baseline and 2 years later. The short-term intrasubject variability was greater at the lumbar spine in group 2 versus group 1 (0.0123 vs. 0.0059 g/cm2, p &lt; 10–4), whereas it was not at the femoral neck (0.0098 vs. 0.0076 g/cm2, p = 0.28). There was no statistically significant correlation between short-term intrasubject variability (SD) and BMD as demonstrated with an analysis of covariance (p values ranging from 0.17 to 0.90). Cut-offs estimated with SD and CV were individually applied to group 3 patients. Using these two cut-offs, discrepancies in assessment of progression were observed in 1.7–8.6% of cases. Short-term BMD variability is constant in a wide range of BMD values. Consequently, to determine cut-off values for the smallest detectable differences in BMD at the individual level, precision errors should be based on SD (expressed in absolute units) rather than on CV (expressed in percentage).
Genetic Determination of Colles' Fracture and Differential Bone Mass in Women With and Without Colles' Fracture
Authors: Deng Hong-Wen , Chen Wei-Min , Recker Susan , Stegman Mary Ruth , Li Jin-Long , Davies K. Michael , Zhou Yan , Deng Hongyi , Heaney Robert , Recker Robert R. 
Published: April 2006

Abstract
Osteoporotic fractures (OFs) are a major public health problem. Direct evidence of the importance and, particularly, the magnitude of genetic determination of OF per se is essentially nonexistent. Colles' fractures (CFs) are a common type of OF. In a metropolitan white female population in the midwestern United States, we found significant genetic determination of CF. The prevalence (K) of CF is, respectively, 11.8% (±SE 0.7%) in 2471 proband women aged 65.55 years (0.21), 4.4% (0.3%) in 3803 sisters of the probands, and 14.6% (0.7%) in their mothers. The recurrence risk (K0), the probability that a woman will suffer CF if her mother has suffered CF is 0.155 (0.017). The recurrence risk (Ks), the probability that a sister of a proband woman will suffer CF given that her proband sister has suffered CF is 0.084 (0.012). The relative risk λ (the ratio of the recurrence risk to K), which measures the degree of genetic determination of complex diseases such as CF, is 1.312 (0.145; λ0) for a woman with an affected mother and 1.885 (0.276; λs) for a woman with an affected sister. A λ-value significantly greater than 1.0 indicates genetic determination of CF. The terms λ0 and λs are related to the genetic variances of CF. These parameters translate into a significant and moderately high heritability (0.254 [0.118]) for CF. These parameters were estimated by a maximum likelihood method that we developed, which provides a general tool for characterizing genetic determination of complex diseases. In addition, we found that women without CF had significantly higher bone mass (adjusted for important covariates such as age, weight, etc.) than women with CF.
Pyridinium Cross-Links in Bone of Patients with Osteogenesis Imperfecta: Evidence of a Normal Intrafibrillar Collagen Packing
Authors: Bank Ruud A. , Tekoppele Johan M. , Janus Guus J. M. , Wassen Maurice H. M. , Pruijs Hans E. H. , van der Sluijs Hans A. H. , Sakkers Ralph J. B. 
Published: April 2006

Abstract
The brittleness of bone in patients with osteogenesis imperfecta (OI) has been attributed to an aberrant collagen network. However, the role of collagen in the loss of tissue integrity has not been well established. To gain an insight into the biochemistry and structure of the collagen network, the cross-links hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) and the level of triple helical hydroxylysine (Hyl) were determined in bone of OI patients (types I, III, and IV) as well as controls. The amount of triple helical Hyl was increased in all patients. LP levels in OI were not significantly different; in contrast, the amount of HP (and as a consequence the HP/LP ratio and the total pyridinoline level) was significantly increased. There was no relationship between the sum of pyridinolines and the amount of triple helical Hyl, indicating that lysyl hydroxylation of the triple helix and the telopeptides are under separate control. Cross-linking is the result of a specific three-dimensional arrangement of collagens within the fibril; only molecules that are correctly aligned are able to form cross-links. Inasmuch as the total amount of pyridinoline cross-links in OI bone is similar to control bone, the packing geometry of intrafibrillar collagen molecules is not disturbed in OI. Consequently, the brittleness of bone is not caused by a disorganized intrafibrillar collagen packing and/or loss of cross-links. This is an unexpected finding, because mutant collagen molecules with a random distribution within the fibril are expected to result in disruptions of the alignment of neighboring collagen molecules. Pepsin digestion of OI bone revealed that collagen located at the surface of the fibril had lower cross-link levels compared with collagen located at the inside of the fibril, indicating that mutant molecules are not distributed randomly within the fibril but are located preferentially at the surface of the fibril.
Amylin and Bone Metabolism in Streptozotocin-Induced Diabetic Rats
Authors: Horcajada-Molteni Marie-Noëlle , Chanteranne Brigitte , Lebecque Patrice , Davicco Marie-Jeanne , Coxam Veronique , Young Andrew , Barlet Jean-Pierre 
Published: April 2006

Abstract
Amylin (AMY) is a 37 amino acid peptide cosecreted with insulin (INS) by pancreatic β-cells and absent in type 1 diabetes, a condition frequently associated with osteopenia. AMY binds to calcitonin receptors, lowers plasma calcium concentration, inhibits osteoclast activity, and stimulates osteoblasts. In the present study, we examined the effects of AMY replacement on bone loss in a streptozotocin (STZ)-induced rodent model type 1 diabetes. Of 50 male Wistar rats studied, 40 were made diabetic with intraperitoneal STZ (50 mg/kg; plasma glucose concentrations &gt;11 mM within 5 days). Ten nondiabetic control (CONT) rats received citrate buffer without STZ. Diabetic rats were divided into four groups (n = 10/group) and injected subcutaneously with rat AMY (45 mg/kg), INS (12 U/kg), both (same doses), or saline (STZ; diabetic controls) once per day. After 40 days of treatment and five 24-h periods of urine collection for deoxypyridinoline (DPD), the animals were killed, blood was sampled, and femurs were removed. The left femur was tested for mechanical resistance (three-point bending). The right femur was tested for total, diaphyseal (cortical bone), and metaphyseal (trabecular bone) bone densities using dual-energy X-ray absorptiometry (DXA). Bone was ashed to determine total bone mineral (calcium) content. None of the treatments had any significant effect on femoral length and diameter. Untreated diabetic rats (STZ; 145 ± 7N) had lower bone strength than did nondiabetic CONT (164 ± 38; p &lt; 0.05). Total bone mineral density (BMD; g/cm2) was significantly lower in STZ (0. 2523 ± 0. 0076) than in CONT (0.2826 ± 0.0055), as were metaphyseal and diaphyseal densities. Diabetic rats treated with AMY, INS, or both had bone strengths and bone densities that were indistinguishable from those in nondiabetic CONT. Changes in bone mineral content paralleled those for total BMD (T-BMD). Plasma osteocalcin (OC) concentration, a marker for osteoblastic activity, was markedly lower in untreated diabetic rats (7. 6 ± 0. 9 ng/ml); p &lt; 0. 05) than in nondiabetic CONT (29. 8 ± 1. 7; p &lt; 0. 05) or than in AMY (20. 1 ± 0. 7; p &lt; 0. 05). Urinary DPD excretion, a marker for bone resorption, was similar in untreated and AMY-treated diabetic rats (35.0 ± 3.1 vs. 35.1 ± 4.4 nmol/mmol creatinine), intermediate in rats treated with INS (49.9 ± 2.7), and normalized in diabetic rats treated with both agents (58.8 ± 8.9 vs. 63.2 ± 4.5 in CONT). Thus, in our STZ rat model of diabetic osteopenia, addition of AMY improved bone indices apparently by both inhibiting resorption and stimulating bone formation.
Cancellous Bone Remodeling Occurs in Specialized Compartments Lined by Cells Expressing Osteoblastic Markers
Authors: Hauge Ellen M. , Qvesel Dorte , Eriksen Erik Fink , Mosekilde Leif , Melsen Flemming 
Published: April 2006

Abstract
We describe a sinus, referred to as a bone remodeling compartment (BRC), which is intimately associated with cancellous bone remodeling. The compartment is lined on its marrow side by flattened cells and on its osseous side by the remodeling bone surface, resembling a roof of flattened cells covering the bone surface. The flat marrow lining cells are in continuity with the bone lining cells at the margins of the BRC. We examined a large number of diagnostic bone biopsy specimens received during recent years in the department. Furthermore, 10 patients (8 women and 2 men, median age 56 [40–69] years) with the high turnover disease of primary hyperparathyroidism who were treated with parathyroidectomy and followed for 3 years were included in the histomorphometric study. Bone samples for the immuno-enzyme staining were obtained from an amputated extremity of child. The total cancellous bone surface covered by BRC decreases by 50% (p &lt; 0.05) following normalization of turnover and is paralleled by a similar 50% decrease in remodeling surface (p &lt; 0.05). The entire eroded surface and two-thirds of the osteoid surface are covered by a BRC. BRC-covered uncompleted walls are 30% (p &lt; 0.05) thinner than those without a BRC. This indicates that the BRC is invariably associated with the early phases of bone remodeling, that is, bone resorption, whereas it closes during the late part of bone formation. Immuno-enzyme staining shows that the flat marrow lining cells are positive for alkaline phosphatase, osteocalcin, and osteonectin, suggesting that they are bone cells. The first step in cancellous bone remodeling is thought to be the lining cells digesting the unmineralized matrix membrane followed by their disappearance and the arrival of the bone multicellular unit (BMU). We suggest that the lining cell barrier persists during bone remodeling; that the old lining cells become the marrow lining cells, allowing bone resorption and bone formation to proceed under a common roof of lining cells; that, at the end of bone formation, new bone lining cells derived from the flattened osteoblasts replace the marrow lining cells thereby closing the BRC; and that the two layers of lining cells eventually becomes a single layer. The integrity of the osteocyte-lining cell system is reestablished by the new generation of lining cells. The BRC most likely serves multiple purposes, including efficient exchange of matrix constituents and minerals, routing, monitoring, or modulating bone cell recruitment, and possibly the anatomical basis for the coupling of bone remodeling.
Association of Collagen Iα 1 Sp1 Polymorphism with the Risk of Prevalent Fractures: A Meta-Analysis
Authors: Efstathiadou Zoe , Tsatsoulis Agathocles , Ioannidis John P. A. 
Published: April 2006

Abstract
Several studies have addressed the effect of the Sp1 polymorphism of the collagen Iα 1 (COLIA1) gene on the prevalence of fractures. The results are not in full agreement on whether this polymorphism is associated with fracture risk. To clarify this uncertainty, we performed a meta-analysis including 13 eligible studies with 3641 subjects. The COLIA1 Sp1 polymorphism showed a dose-response relationship with the prevalence of fractures. The risk was 1.25-fold (95% CI, 1.09–1.45) in Ss heterozygotes versus SS homozygotes, 1.68-fold (95% CI, 1.35–2.10) in ss homozygotes versus SS&gt; homozygotes, and 1.35 (95% CI, 1.04–1.75) for ss homozygotes versus Ss heterozygotes by random effects calculations. There was modest heterogeneity for these three effect estimates (p value for heterogeneity, 0.17, 0.16, and 0.08, respectively). The Sp1 polymorphism effects possibly were larger when the analysis was limited to studies considering only vertebral fractures (pooled risk ratios [RR], 1.30, 2.07, and 1.46, respectively). Conversely, the Sp1 polymorphism effects tended to be smaller in studies with mean patient age ≥65 years than in studies with younger patients on average, but the differences were not formally significant. We estimated the total average attributable fraction (AF) of fractures due to the s allele in European/U.S. populations as 9.4%. The meta-analysis suggests an important role for the Sp1 polymorphism in the regulation of fracture risk; however, potential heterogeneity across ethnic groups, age groups, and skeletal sites may be important to clarify in future studies. Very large studies or meta-analyses are required to document subtle genetic differences in fracture risk.
Cross-Sectional Evaluation of Bone Metabolism in Men
Authors: Szulc P. , Garnero P. , Munoz F. , Marchand F. , Delmas P. D. 
Published: April 2006

Abstract
There are relatively few data concerning age-related changes of bone turnover in men. The aim of the study was to evaluate age-related changes of the levels of serum and urinary biochemical markers of bone metabolism in a large cohort of 934 men aged 19–85 years and to investigate their association with bone mineral density (BMD). Bone formation was evaluated using serum levels of osteocalcin (OC), bone alkaline phosphatase (BAP), and N-terminal extension propeptide of type I collagen (PINP). Bone resorption was evaluated by measurement of urinary excretion of β-isomerized C-terminal telopeptide of collagen type I (β-CTX) of free deoxypyridinoline (fDpyr) and total Dpyr (tDPyr) and of the serum level of β-CTX. Levels of biochemical bone markers were very high in young men and decreased rapidly until the age of 40 years and then more slowly until 60 years of age. After the age of 60 years, markers of bone formation remained stable while resorption markers showed a moderate and variable increase with aging. Serum and urinary β-CTX levels were elevated only in about 5% of elderly men. The age-related increase of urinary excretion of tDpyr and of its free and peptide-bound fractions was related to the presence of elevated levels in a subgroup of about 15% of elderly men. Before 60 years of age, levels of biochemical bone markers were not correlated with BMD, whereas after 60 years of age, they were correlated negatively with BMD. After adjustment for age and body weight, BMD in men with the highest levels of biochemical bone markers (i.e., in the upper quartile) was 1.8–12.5% (i.e., 0.25–0.89 SD) lower than in men with levels of biochemical bone markers in the lowest quartile. In conclusion, bone turnover in men is high in young adults and decreases to reach a nadir at 55–60 years of age. After the age of 60 years, bone resorption markers—but not bone formation markers—increase in some men and are associated with lower BMD, suggesting that this imbalance is responsible for increasing bone loss in elderly men.
Gnathodiaphyseal Dysplasia: A Syndrome of Fibro-Osseous Lesions of Jawbones, Bone Fragility, and Long Bone Bowing
Authors: Riminucci Mara , Collins Michael T. , Corsi Alessandro , Boyde Alan , Murphey Mark D. , Wientroub Shlomo , Kuznetsov Sergei A. , Cherman Natasha , Robey Pamela Gehron , Bianco Paolo 
Published: April 2006

Abstract
We report an unusual generalized skeletal syndrome characterized by fibro-osseous lesions of the jawbones with a prominent psammomatoid body component, bone fragility, and bowing/sclerosis of tubular bones. The case fits with the emerging profile of a distinct syndrome with similarities to previously reported cases, some with an autosomal dominant inheritance and others sporadic. We suggest that the syndrome be named gnathodiaphyseal dysplasia. The patient had been diagnosed previously with polyostotic fibrous dysplasia (PFD) elsewhere, but further clinical evaluation, histopathological study, and mutation analysis excluded this diagnosis. In addition to providing a novel observation of an as yet poorly characterized syndrome, the case illustrates the need for stringent diagnostic criteria for FD. The jaw lesions showed fibro-osseous features with the histopathological characteristics of cemento-ossifying fibroma, psammomatoid variant. This case emphasizes that the boundaries between genuine GNAS1 mutation-positive FD and other fibro-osseous lesions occurring in the jawbones should be kept sharply defined, contrary to a prevailing tendency in the literature. A detailed pathological study revealed previously unreported features of cemento-ossifying fibroma, including the participation of myofibroblasts and the occurrence of psammomatoid bodies and aberrant mineralization, within the walls of blood vessels. Transplantation of stromal cells grown from the lesion into immunocompromised mice resulted in a close mimicry of the native lesion, including the sporadic formation of psammomatoid bodies, suggesting an intrinsic abnormality of bone-forming cells.
Familial Hypocalciuric Hypercalcemia Caused by an R648stop Mutation in the Calcium-Sensing Receptor Gene
Authors: Yamauchi Mika , Sugimoto Toshitsugu , Yamaguchi Toru , Yano Shozo , Wang Junning , Bai Mei , Brown Edward M. , Chihara Kazuo 
Published: April 2006

Abstract
In this study, we report an 84-year-old female proband in a Japanese family with familial hypocalciuric hypercalcemia (FHH) caused by an R648stop mutation in the extracellular calcium-sensing receptor (CaR) gene. At the age of 71 years, she presented with hypercalcemia (11.4 mg/dl), hypocalciuria (Cca/Ccr = 0.003), hypermagnesemia (2.9 mg/dl), and a high-serum parathyroid hormone (PTH) level (midregion PTH, 3225 [160–520] pg/ml). At the age of 74 years, a family screening was carried out and revealed a total of 9 hypercalcemic individuals (all intact PTH values &lt;62 pg/dl) among 17 family members tested, thus, being diagnosed as FHH. Two and one-half of three clearly enlarged parathyroid glands were resected, because persistently high PTH levels (intact PTH, 292 pg/ml; midregion PTH, 5225 pg/ml) and the presence of a markedly enlarged parathyroid gland by several imaging modalities (ultrasonography, computed tomography [CT], magnetic resonance imaging [MRI], and subtraction scintigraphy) suggested coexistent primary hyperparathyroidism (pHPT); however, hypercalcemia persisted postoperatively. Histological and immunohistochemical examination revealed that the resected parathyroid glands showed lipohyperplasia as well as normally expressed Ki67, vitamin D receptor (VDR), and the CaR. Sequence analysis disclosed that the proband and all affected family members had a heterozygous nonsense (R648stop) mutation in the CaR gene. This mutation is located in the first intracellular loop; thus, it would be predicted to produce a truncated CaR having only one transmembrane domain (TMD) and lacking its remaining TMDs, intracellular loops, and C-terminal tail. Western analysis of biotinylated HEK293 cells transiently transfected with this mutant receptor showed cell surface expression of the truncated protein at a level comparable with that of the wild-type CaR. The mutant receptor, however, exhibited no increase in intracellular free calcium concentration (Ca2+i) when exposed to high extracellular calcium concentrations (Ca2+o). The proband's clinical course was complicated because of associated renal tubular acidosis (RTA) and nephrotic syndrome. However, it was unclear whether their association affected the development of elevated serum PTH and parathyroid gland enlargement. This report is the first to show that an R648stop CaR mutation yields a truncated receptor that is expressed on the cell surface but is devoid of biological activity, resulting in FHH.
Increased Bone Morphogenetic Protein-6 Expression in Mouse Long Bones After Estrogen Administration
Authors: Plant Andrea , Tobias Jonathan H. 
Published: April 2006

Abstract
High-dose estrogen administration is known to induce new bone formation in mouse long bones. To study the role of regulatory proteins in this response, we examined associated changes in femoral messenger RNA (mRNA) for candidate factors. 17β-estradiol (E2) 0.5 mg was administered to intact female mice by weekly injection, and Northern blot analysis was performed 1, 2, 4, 8, 12, and 16 days after the first injection. In contrast to other factors, an increase was observed in mRNA for bone morphogenetic protein-6 (BMP-6), which reached significance at day 8 and subsequent time-points. Estrogen-induced changes in BMP-6 protein expression were assessed by immunocytochemistry in longitudinal femoral sections. In untreated animals, BMP-6 was expressed by a significant proportion of growth plate chondrocytes and a subpopulation of bone marrow cells. In contrast, osteoblasts were consistently BMP-6 negative. From as early as 4 days after starting estrogen, clusters of slightly elongated BMP-6-positive cells were observed within the marrow cavity; the majority were close to active bone formation surfaces. Double immunolabeling studies revealed that only approximately 10% of BMP-6-positive bone marrow cells co-expressed the osteoblast transcription factor Cbfa1 suggesting that they are largely distinct from the osteoblast precursor population generated concurrently. BMP-6-positive cells expressed neither leukocyte nor erythroid markers (CD45 and TER-119, respectively), consistent with a stromal origin. We conclude that estrogen-induced osteogenesis in female mice is associated with increased levels of BMP-6 mRNA in mouse femurs, which seems to reflect the emergence of clusters of BMP-6 positive stromal cells adjacent to active bone formation surfaces. These findings raise the possibility that BMP-6 serves as a paracrine mediator of estrogen's osteogenic action in mice.