bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced Peripheral Nerve Function Is Related to Lower Hip BMD and Calcaneal QUS in Older White and Black Adults: The Health, Aging, and Body Composition Study
Authors: Strotmeyer Elsa S , Cauley Jane A , Schwartz Ann V , de Rekeneire Nathalie , Resnick Helaine E , Zmuda Joseph M , Shorr Ronald I , Tylavsky Frances A , Vinik Aaron I , Harris Tamara B , Newman Anne B ,   for the Health ABC Study
Published: September 2006

Abstract
Bone tissue is innervated, and peripheral nerve function may impact BMD. Older black and white men and women (N = 2200) in the Health, Aging, and Body Composition Study with worse sensory and motor peripheral nerve function had lower hip BMD and calcaneal BUA independent of lean mass, strength, physical ability, and diabetes. Poor peripheral nerve function may directly affect bone.
Introduction: Bone tissue is innervated, yet little is known about the impact of nerve function on BMD. Poor peripheral nerve function may contribute to lower BMD and higher fracture risk, particularly in those with diabetic neuropathy.
Materials and Methods: The Health, Aging, and Body Composition (Health ABC) Study included annual exams in white and black men and women 70–79 years of age recruited from Pittsburgh and Memphis. Nerve function in legs/feet was assessed by 1.4- and 10-g monofilament detection, vibration threshold, and peroneal motor nerve conduction velocity (NCV) and amplitude (CMAP). Total hip BMD, heel broadband ultrasound attenuation (BUA), and total fat and lean mass were measured 1 year later (QDR 4500A, Sahara QUS; Hologic).
Results: Participants (N = 2200) were 48% men and 37% black. Poor nerve function (lower monofilament detection, higher vibration threshold, lower CMAP, lower NCV) was associated with 1.4–5.7% lower BUA and significant for all but NCV, adjusted for demographics, diabetes, body composition, and physical ability. Results were similar for adjusted hip BMD, with 1.0–2.9% lower BMD, significant for monofilament and CMAP testing. When considering the components of BMD, total hip area was 1.8–4.9% higher in those with the worst nerve function, although BMC showed little difference. Lower monofilament detection and CMAP were independently associated with lower heel BUA (p &lt; 0.01), and monofilament detection was associated with lower hip BMD (p &lt; 0.05) in regression additionally adjusted for lifestyle factors, bone-active medications, and diabetes-related complications.
Conclusions: Poor peripheral nerve function may directly related to lower BMD, likely through an increase in bone area in older adults, independent of lean mass, strength, physical ability, and diabetes. Whether those with impaired nerve function are at higher risk for fracture independent of falls needs to be studied.
T Lymphocyte–Deficient Mice Lose Trabecular Bone Mass With Ovariectomy
Authors: Lee Sun-Kyeong , Kadono Yuho , Okada Fumihiko , Jacquin Claire , Koczon-Jaremko Boguslawa , Gronowicz Gloria , Adams Douglas J , Aguila Hector L , Choi Yongwon , Lorenzo Joseph A 
Published: September 2006

Abstract
We examined OVX-induced bone loss in three TLD mouse models. In TLD mice, OVX caused trabecular bone loss equivalent to that of WT. In contrast, cortical bone loss with OVX was variable. We conclude that T lymphocytes do not influence OVX-induced trabecular bone loss.
Introduction: We examined ovariectomy (OVX)-induced bone loss in three T lymphocyte–deficient (TLD) mouse models: nude mice, recombination activating gene 2–deficient (RAG2 KO) mice, and T cell receptor α chain–deficient (TCRα KO) mice.
Materials and Methods: Bone mass was examined by DXA, μCT, and histomorphometry. We also examined the effect of OVX on T lymphocytes in the bone marrow and spleens of wildtype (WT) mice and on in vitro osteoclastogenesis and colony forming unit-granulocyte macrophage (CFU-GM) activity in the bone marrow of WT and nude mice.
Results: In WT mice, OVX did not alter T lymphocyte number in the bone marrow but did increase T lymphocytes in the spleen. Comparison of bone mass in nude, RAG2 KO, and TCRα KO mice with WT as measured by DXA showed decreased femoral bone mass in nude mice and increased vertebral bone mass in RAG2 KO mice. In TCRα KO mice, femoral, tibial, and vertebral bone mass were decreased. In vertebrae and long bones, bone loss with OVX was consistently present in WT mice but variably present in TLD mice as measured by DXA. In contrast, μCT and histomorphometry showed similar trabecular bone loss after OVX in all mice. However, femoral cortical bone loss occurred only in WT and RAG2 KO mice. OVX produced similar trabecular bone loss in WT and TCRα KO mice and also induced cortical bone loss in both. Histomorphometry showed that TRACP+ area in bones was increased by OVX in femurs from both WT and nude mice as was in vitro osteoclast-like cell formation and CFU-GM activity.
Conclusions: These results show that OVX caused similar trabecular bone loss in both WT and TLD mice. The ability of DXA and measurement of cortical bone loss to show OVX-induced effects on bone mass was variable. It seems that T lymphocytes are not critical for OVX-induced trabecular bone loss in these mouse models.
Nationwide Decline in Incidence of Hip Fracture
Authors: Kannus Pekka , Niemi Seppo , Parkkari Jari , Palvanen Mika , Vuori Ilkka , Järvinen Markku 
Published: September 2006

Abstract
This epidemiologic study determined the trend in the number and incidence (per 100,000 persons) of hip fracture among older adults in Finland, an EU country with a well-defined white population of 5.2 million, between 1970 and 2004. The results show that the alarming rise in the fracture incidence from early 1970s until late 1990s has been now followed by declining fracture rates. Reasons for this are largely unknown, but a cohort effect toward a healthier aging population and increased average body weight and improved functional ability among elderly Finns could partly explain the phenomenon.
Introduction: Although osteoporotic fractures of older adults are said to be a major public health concern in modern societies with aging populations, fresh nationwide information on their secular trends is limited.
Materials and Methods: This epidemiologic study determined the current trend in the number and incidence (per 100,000 persons) of hip fracture among older adults in Finland, an EU country with a well-defined white population of 5.2 million, by taking into account all persons ≥50 years of age who were admitted to our hospitals for primary treatment of such fracture in 1970–2004.
Results: The number of hip fractures among ≥50-year-old Finns rose very constantly between 1970 (1857 fractures) and 1997 (7122 fractures), but since then, the rise has leveled off (7083 fractures in 2004). After this and because of a continuous rise in population at risk, the crude incidence of hip fracture (showing a clear rise in 1970–1997) decreased between 1997 and 2004, from 438 (per 100,000 persons) in 1997 to 374 in 2004. Concerning the age-adjusted fracture incidence, findings were similar. Until 1997, the age-adjusted incidence of hip fracture clearly increased in both women and men, but thereafter, this incidence declined in both sexes: in women, from 494 in 1997 to 412 in 2004, and in men, from 238 in 1997 to 223 in 2004.
Conclusions: The rise in the incidence of hip fracture in Finland from the early 1970s until the late 1990s has been followed by declining fracture rates. Exact reasons for this are unknown, but a cohort effect toward a healthier aging population and increased average body weight and improved functional ability among elderly Finns cannot be ruled out.
Clinical Vignette: Monostotic Fibrous Dysplasia of the Proximal Femur and Liposclerosing Myxofibrous Tumor: Which One Is Which?
Authors: Corsi Alessandro , De Maio Fernando , Ippolito Ernesto , Cherman Natasha , Robey Pamela Gehron , Riminucci Mara , Bianco Paolo 
Published: September 2006

Abstract
Clinical, histological, and genetic studies of two cases of isolated fibro-osseous lesions of the femur in adults show the overlap between monostotic fibrous dysplasia (MFD) of the proximal femur and the so-called liposclerosing myxofibrous tumor. The two cases highlight how the incomplete understanding of the natural history of MFD may result in diagnostic pitfalls or incorrect classification of individual lesions.
Advanced Molecular Profiling in Vivo Detects Novel Function of Dickkopf-3 in the Regulation of Bone Formation
Authors: Aslan Hadi , Ravid-Amir Osnat , Clancy Brian M , Rezvankhah Saeid , Pittman Debra , Pelled Gadi , Turgeman Gadi , Zilberman Yoram , Gazit Zulma , Hoffmann Andrea , Gross Gerhard , Domany Eytan , Gazit Dan 
Published: September 2006

Abstract
A bioinformatics-based analysis of endochondral bone formation model detected several genes upregulated in this process. Among these genes the dickkopf homolog 3 (Dkk3) was upregulated and further studies showed that its expression affects in vitro and in vivo osteogenesis. This study indicates a possible role of Dkk3 in regulating bone formation.
Introduction: Endochondral bone formation is a complex biological process involving numerous chondrogenic, osteogenic, and angiogenic proteins, only some of which have been well studied. Additional key genes may have important roles as well. We hypothesized that to identify key genes and signaling pathways crucial for bone formation, a comprehensive gene discovery strategy should be applied to an established in vivo model of osteogenesis.
Materials and Methods: We used in vivo implanted C3H10T1/2 cells that had been genetically engineered to express human bone morphogenetic protein-2 (BMP2) in a tetracycline-regulated system that controls osteogenic differentiation. Oligonucleotide microarray data from the implants (n =4 repeats) was analyzed using coupled two-way clustering (CTWC) and statistical methods. For studying the effects of dickkopf homolog 3 (Dkk3) in chondrogenesis and osteogenesis, C3H10T1/2 mesenchymal progenitors were used.
Results: The CTWC revealed temporal expression of Dkk3 with other chondrogenesis-, osteogenesis-, and Wnt-related genes. Quantitative RT-PCR confirmed the expression of Dkk3 in the implants. C3H10T1/2 cells that expressed Dkk3 in the presence of BMP2 displayed lower levels of alkaline phosphatase and collagen I mRNA expression than control C3H10T1/2 cells that did not express Dkk3. Interestingly, the levels of collagen II mRNA expression, Alcian blue staining, and glucose aminoglycans (GAGs) production were not influenced by Dkk3 expression. In vivo μCT and bioluminescence imaging revealed that co-expression of Dkk3 and BMP2 by implanted C3H10T1/2 cells induced the formation of significantly lower quantities of bone than cells expressing only BMP2.
Conclusions: A bioinformatics analysis enabled the identification of Dkk3 as a pivotal gene with a novel function in endochondral bone formation. Our results showed that Dkk3 might have inhibitory effects on osteogenesis, but no effect on chondrogenesis, indicating that Dkk3 plays a regulatory role in endochondral bone formation. Further mechanistic studies are required to reveal the mechanism of action of Dkk3 in endochondral bone formation.
Calcitonin Deficiency in Mice Progressively Results in High Bone Turnover
Authors: Huebner Antje K , Schinke Thorsten , Priemel Matthias , Schilling Sarah , Schilling Arndt F , Emeson Ronald B , Rueger Johannes M , Amling Michael 
Published: September 2006

Abstract
Although the pharmacological action of calcitonin (CT) as an inhibitor of bone resorption is well established, there is still some controversy regarding its physiological function. Unexpectedly, Calca-deficient mice lacking CT and α-calcitonin gene-related peptide (αCGRP) were described to have a high bone mass phenotype caused by increased bone formation with normal bone resorption. Here we show that these mice develop a phenotype of high bone turnover with age, suggesting that CT is a physiological inhibitor of bone remodeling.
Introduction: The absence of significant changes in bone mineral density caused by decline or overproduction of CT in humans has raised the question, whether the pharmacological action of CT as an inhibitor of bone resorption is also of physiological relevance. To study the physiological role of mammalian CT, we have analyzed the age-dependent bone phenotype of two mouse models, one lacking CT and αCGRP (Calca−/−), the other one lacking only αCGRP (αCGRP−/−).
Materials and Methods: Bones from wildtype, Calca−/−-mice and αCGRP−/−-mice were analyzed at the ages of 6, 12 and 18 months using undecalcified histology. Differences of bone remodeling were quantified by static and dynamic histomorphometry as well as by measuring the urinary collagen degradation products. To rule out secondary mechanisms underlying the observed phenotype, we determined serum concentrations of relevant hormones using commercially available antibody-based detection kits.
Results: Whereas αCGRP−/−-mice display an osteopenia at all ages analyzed, the Calca−/−-mice develop a phenotype of high bone turnover with age. Histomorphometric analysis performed at the age of 12 months revealed significant increases of bone formation and bone resorption specifically in the Calca−/−-mice. This severe phenotype that can result in hyperostotic lesions, can not be explained by obvious endocrine abnormalities other than the absence of CT.
Conclusions: In addition to the previously described increase of bone formation in the Calca-deficient mice, we have observed that there is also an increase of bone resorption with age. This suggests that CT has a dual action as an inhibitor of bone remodeling, which may explain why alterations of CT serum levels in humans do not result in major changes of bone mineral density.
Transmigration: A New Property of Mature Multinucleated Osteoclasts
Authors: Saltel Frédéric , Chabadel Anne , Zhao Yingshe , Lafage-Proust Marie-Hélène , Clézardin Philippe , Jurdic Pierre , Bonnelye Edith 
Published: September 2006

Abstract
Even though it is assumed that multinucleated osteoclasts are migrating cells on the bone surface to be resorbed, we show that they can also selectively transmigrate through layers of cells usually found in the bone microenvironment. This activity is associated with c-src and MMPs and can be stimulated by bone metastatic breast cancer cells, a process blocked by bisphosphonate treatment.
Introduction: Osteoclasts have an hematopoietic origin and are bone-resorbing cells. Monocytic precursors migrate to the bone surface where they fuse to form multinucleated osteoclasts able to migrate over the bone surface. We studied whether multinucleated osteoclasts were also able to transmigrate through tissues.
Materials and Methods: Murine spleen-derived and green fluorescent protein (GFP)-Raw derived osteoclasts were seeded on osteoblasts and several other cell types. The cells were fixed for 20 minutes, 4 or 12 h after osteoclast seeding, and stained with phalloidin to visualize actin using confocal microscopy. Drugs such as PP2 and GM6001, inhibitors of c-src and matrix metalloproteinases (MMPs), respectively, and risedronate were used to determine osteoclast transmigration regulating factors.
Results: We observed by confocal microscopy that multinucleated osteoclasts specifically transmigrate through confluent layers of various cell types present in the bone microenvironment in vitro. This is an efficient process associated with c-src and MMPs but is independent of podosomes. Moreover, conditioned medium from bone metastatic breast cancer cells stimulates osteoclast transmigration in vitro, a process inhibited by bisphosphonate treatment.
Conclusions: Our data describe a new property of mature multinucleated osteoclasts to transmigrate through various cell types. The ability to control this highly regulated osteoclast transmigration process may offer new therapeutic strategies for bone diseases associated with an imbalance in bone remodeling caused by excessive osteoclast resorption.
Evidence for Increased Clinical Severity of Familial and Sporadic Paget's Disease of Bone in Campania, Southern Italy
Authors: Rendina Domenico , Gennari Luigi , De Filippo Gianpaolo , Merlotti Daniela , de Campora Enrico , Fazioli Flavio , Scarano Gioacchino , Nuti Ranuccio , Strazzullo Pasquale , Mossetti Giuseppe 
Published: September 2006

Abstract
The analysis of 236 Italian patients with Paget's bone disease showed higher clinical severity and greater frequency of neoplastic degeneration among patients who live or descend from individuals living in the Campania region (southern Italy). A prevalent involvement of the spine and the skull, the sites preferentially involved in giant cell tumors complicating Paget's disease, was also shown in familial cases from this geographical region.
Introduction: The Campania region in southern Italy has been recently indicated as a high prevalence area for Paget's disease of bone (PDB), and most pagetic families with multiple occurrence of neoplasms in affected members were from this geographical region.
Materials and Methods: We evaluated the PDB epidemiological characteristics in 125 patients from Campania in comparison with 111 patients from other Italian regions. Twenty-three patients from Campania and 26 patients from other Italian areas had at least one first-degree relative affected by PDB (familial cases). The remaining patients made up the sporadic cases.
Results: Among subjects from Campania, the patients in the familial group tended to come from larger families and showed at diagnosis higher serum total alkaline phosphatase, larger extension of disease, and earlier mean age with respect to patients with PDB of the sporadic group. The skull, spine, and humerus were the sites preferentially involved in the familial cases. In contrast, no such differences were observed between familial and sporadic PDB cases among patients from the other geographical areas, except for a lower age at diagnosis. An increased PDB clinical severity was finally observed in the PDB cohort from Campania in comparison with patients from other Italian regions. Neoplastic degeneration of pagetic bones (osteosarcoma and giant cell tumor) was exclusively observed in patients with polyostotic PDB from Campania.
Conclusions: We showed a higher clinical severity of PDB with occurrence of neoplastic degeneration in the high prevalence area of Campania, with its maximum expression in cases with familial disease. This peculiar pattern might be traced to genetic predisposition and/or to the abnormal impact of a still undefined environmental trigger.
Accentuated Ovariectomy-Induced Bone Loss and Altered Osteogenesis in Heterozygous N-Cadherin Null Mice
Authors: Lai Chung Fang , Cheng Su-Li , Mbalaviele Gabriel , Donsante Christine , Watkins Marcus , Radice Glenn L , Civitelli Roberto 
Published: September 2006

Abstract
Ovariectomy-induced bone loss is accentuated in mice with germline Cdh2 haploinsufficiency, the result of a decreased osteoblastogenesis in the face of normal osteoclast number. Reduced N-cadherin abundance in these mice decreases cell—cell adhesion and alters signaling pathways important for osteoblast commitment and differentiation, thus providing in vivo evidence that N-cadherin—mediated cell—cell interactions are involved in homeostatic responses to increased bone remodeling.
Introduction: We have shown that targeted expression of a dominant negative truncated form of N-cadherin (Cdh2) delays acquisition of peak bone mass in mice and retards osteoblast differentiation. We tested the role of this molecule in the skeletal homeostatic response to ovariectomy in mice with germline Cdh2 haploinsufficiency.
Materials and Methods: Heterozygous Cdh2 null (Cdh2+/−) and wildtype mice were ovariectomized and followed up to 13 weeks by in vivo radiodensitometric and ex vivo histologic assessment of bone mass and turnover. Cells isolated from wildtype and Cdh2+/− mice were used to determine the alterations in bone cell function produced by partial loss of N-cadherin.
Results: Bone mass was not significantly different between Cdh2+/− and wildtype littermates, but on ovariectomy, bone loss in Cdh2+/− mice was initially slower, but with time it became significantly greater than in wildtype mice. This accentuated bone loss was associated with lower osteoblast number and serum osteocalcin levels, with no differences in bone resorption. Although development of calcified nodules was faster in calvaria cells isolated from Cdh2+/− mice relative to Cdh2+/+ cells, bone marrow osteogenic precursors were lower in the former than in the latter genotypes. Cdh2 expression was downregulated with differentiation in wildtype calvaria cells, whereas cadherin-11 abundance remained unchanged. Furthermore, cell—cell adhesion (postconfluence) was decreased among heterozygous calvaria cells, as was cell proliferation (preconfluence), relative to wildtype cells. Finally, the abundance and cellular distribution of β-catenin was minimally decreased in Cdh2+/− cells, whereas mitogen-activated protein kinase (MAPK) signaling was more active in Cdh2 insufficient cells.
Conclusions: Cdh2 is involved in the homeostatic bone formation response to ovariectomy, presumably by regulating osteoprogenitors number and differentiation through stabilization of cell—cell adhesion and/or signaling modulation.
Passing Ability Tester for Self-Consolidating Concrete
Authors: Dhonde HB , Mo YL , Hsu TTC 
Published: September 2006

Abstract
Passing ability is one of the most important workability properties of self-consolidating concrete (SCC) and self-consolidating fiber reinforced concrete (SCFRC). The popular J-ring apparatus which measures the passing ability indirectly in terms of the difference in drop levels or the unrestricted and restricted slump flow of SCC/SCFRC, could not determine the passing ability in a consistent manner. A simple, accurate, and practical passing ability tester (PAT) is proposed as a substitute to the conventionally used methods (J-ring, L-box, and U-box). PAT measures the passing ability directly and consistently by weighing the concrete that has passed through the reinforcing bar screen and expressing it as the percentage of the total concrete sampled. This paper presents the test results of various SCC/SCFRC mixes to verify the performance of PAT, including the correlation between the test results of PAT and J-ring.
Basics of Polymeric Scaffolds for Tissue Engineering
Authors: Agrawal CM , Carter J , Ong JL 
Published: September 2006

Abstract
This review article argues the case that there is a need for careful scaffold science for successful tissue engineering. Polymeric scaffolds should possess certain essential properties. However, these properties are not independent of each other and thus the development of a scaffold requires an optimization process. The article reviews several scaffold fabrication processes to highlight the complexity of the field. Issues related to porosity, permeability, and the need for adequate diffusion characteristics are discussed. Several previous studies on the effects of mixing in bioreactors are reviewed. Lastly, surface modification techniques are presented. In particular, recent work related to glow discharge gas plasma modification of biodegradable polymers is discussed.