bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk Factors for Fractures of the Proximal Humerus: Results From the EPIDOS Prospective Study
Authors: Lee Sun H. , Dargent-Molina Patricia , Bréart Gérard 
Published: April 2006

Abstract
Fracture of the proximal humerus is one of the most frequent fractures attributable to osteoporosis; yet, it has seldom been studied. Two types of factors (related to bone fragility and falls) were evaluated to identify risk factors for proximal humerus fractures as well as to examine possible interactions between them. Subjects were 6901 white women aged ≥75 years and all participated in the EPIDOS study of risk factors for osteoporotic fractures (France, 1992-1998). The baseline examination included measurements of femoral neck bone mineral density (BMD) and calcaneal ultrasound parameters (speed of sound [SOS] and broadband ultrasound attenuation [BUA]), a functional clinical examination, and completing a questionnaire on health status and lifestyle. During a mean of 3.6 (0.8) years of follow-up, 165 women had a humeral fracture. Using multivariate Cox regression models, we identified three predictors related to bone fragility—low BMD (relative risk [RR] = 1.4; 95% CI, 1.1-1.7), low SOS (RR = 1.3; 95% CI, 1.0-1.6), and maternal history of hip fracture (RR = 1.8; 95% CI, 1.0-3.0)—and four fall-related predictors—a previous fall (RR = 3.0; 95% CI, 1.5-6.1), a low level of physical activity (RR = 2.2; 95% CI, 1.1-4.4), impaired balance (RR = 1.8; 95% CI, 1.1-2.9), and pain in lower limb extremity (RR = 1.4; 95% CI, 1.0-2.1). The effect of these fall-related predictors varied according to the BMD level; they were significantly associated with proximal humerus fractures in women with osteoporosis (BMD T score &lt; −2.5) but not in nonosteoporotic women. The incidence of proximal humerus fracture in women with osteoporosis and a low fall risk score (5.1 per 1000 woman-years) was only slightly higher than in nonosteoporotic women (4.6 per 1000 woman-years) and similar to the incidence in women without osteoporosis but a high fall risk score (5.3 per 1000 woman-years). On the other hand, the incidence in women who had both types of risk factors was more than two times higher (12.1 per 1000 woman-years) than in women with only one of the two risk factors. These results suggest that women who have both types of risk factors should receive the highest priority for prevention.
Systemic Regulation of Distraction Osteogenesis: A Cascade of Biochemical Factors
Authors: Weiss S. , Baumgart R. , Jochum M. , Strasburger C. J. , Bidlingmaier M. 
Published: April 2006

Abstract
This study investigates the systemic biochemical regulation of fracture healing in distraction osteogenesis compared with rigid osteotomy in a prospective in vivo study in humans. To further clarify the influence of mechanical strain on the regulation of bone formation, bone growth factors (insulin-like growth factor [IGF] I, IGF binding protein [IGFBP] 3, transforming growth factor [TGF] β1, and basic FGF [bFGF]), bone matrix degrading enzymes (matrix-metalloproteinases [MMPs] 1, 2, and 3), human growth hormone (hGH), and bone formation markers (ALP, bone-specific ALP [BAP], and osteocalcin [OC]) have been analyzed in serum samples from 10 patients in each group pre- and postoperatively. In the distraction group, a significant postoperative increase in MMP-1, bFGF, ALP, and BAP could be observed during the lengthening and the consolidation period when compared with the baseline levels. Osteotomy fracture healing without the traction stimulus failed to induce a corresponding increase in these factors. In addition, comparison of both groups revealed a significantly higher increase in TGF-β1, IGF-I, IGFBP-3, and hGH in the lengthening group during the distraction period, indicating key regulatory functions in mechanotransduction. The time courses of changes in MMP-1, bone growth factors (TGF-β1 and bFGF), and hGH, respectively, correlated significantly during the lengthening phase, indicating common regulatory pathways for these factors in distraction osteogenesis. Significant correlation between the osteoblastic marker BAP, TGF-β1, and bFGF suggests strain-activated osteoblastic cells as a major source of systemically increased bone growth factors during callus distraction. The systemic increase in bFGF and MMP-1 might reflect an increased local stimulation of angiogenesis during distraction osteogenesis.
The Structural and Hormonal Basis of Sex Differences in Peak Appendicular Bone Strength in Rats
Authors: Kim Bom-Taeck , Mosekilde Lis , Duan Yunbo , Zhang Xin-Zhou , Tornvig Lise , Thomsen Jesper Skovhus , Seeman Ego 
Published: April 2006

Abstract
To identify the structural and hormonal basis for the lower incidence of fractures in males than females, sex differences in femoral mid-shaft geometry and breaking strength were studied in growth hormone (GH)-replete and -deficient male and female rats. Sexual dimorphism appeared during growth. Cortical thickening occurred almost entirely by acquisition of bone on the outer (periosteal) surface in males and mainly on the inner (endocortical) surface in females. By 8 months of age, males had 22% greater bone width and 33% greater breaking strength than females. Gonadectomy (Gx) at 6 weeks reduced sex differences in bone width to 7% and strength to 21% by halving periosteal bone formation in males and doubling it in females. Gx had no net effect on the endocortical surface in males but abolished endocortical bone acquisition in females. GH deficiency halved periosteal bone formation and had no net effect on the endocortical surface in males, but abolished bone acquisition on both surfaces in females, leaving males with 17% greater bone width and 44% greater breaking strength than females. Sex hormone deficiency produces greater bone fragility in males than females by removing a stimulator of periosteal growth in males and removing an inhibitor of periosteal growth in females. GH deficiency produces less bone fragility in males than females because males retain androgen-dependent periosteal bone formation while bone acquisition on both surfaces is abolished in females. Thus, periosteal growth is independently and additively stimulated by androgens and GH in males, inhibited by estrogen, and stimulated by GH in females. The hormonal regulation of bone surfaces establishes the amount and spatial distribution of bone and so the sexual dimorphism in its strength.
The Dynamic Mobility of Vertebral Compression Fractures
Authors: McKiernan Fergus , Jensen Ron , Faciszewski Tom 
Published: April 2006

AbstractWe have observed that some osteoporotic vertebral compression fractures (VCFs) are mobile. The purpose of this report was to document the existence of dynamic fracture mobility, estimate the frequency of dynamic mobility in patients referred for vertebroplasty, define the magnitude and nature of dynamic mobility, and consider the implications of the dynamic mobility of osteoporotic VCFs. This was a prospective radiographic analysis of 41 consecutive patients with 65 VCFs who underwent vertebroplasty. Preoperative standing lateral radiographs of the fractured vertebrae were compared with supine cross-table lateral radiographs to determine the presence or absence of dynamic mobility. Postoperative standing lateral radiographs were evaluated to document fracture mobility and assess final vertebral height restoration. Radiographs were manually digitized to calculate vertebral body morphometrics. Dynamic fracture mobility was demonstrated in 44% of patients (35% of treated vertebrae) who underwent vertebroplasty. Postoperatively, in mobile fractures, average anterior vertebral height increased 106% compared with initial fracture height (absolute increase, 8.41 ± 0.4 mm). Mean lateral vertebral area increased from 48% to 80% of normal, and kyphotic angle decreased 40%. Mobile fractures dominated at the thoracolumbar junction. Intravertebral clefts were defined and identified in every mobile fracture and were absent from every nonmobile (fixed) fracture. This radiographic series documents the previously unrecognized occurrence of dynamic fracture mobility in many osteoporotic VCFs. Fracture mobility can be substantial and clinically significant. Any intervention that claims vertebral height restoration must control for the occurrence of dynamic fracture mobility.
Trabecular Bone Tissue Strains in the Healthy and Osteoporotic Human Femur
Authors: Van Rietbergen B , Huiskes R , Eckstein F , Rüegsegger P 
Published: April 2006

AbstractQuantitative information about bone tissue‐level loading is essential for understanding bone mechanical behavior. We made microfinite element models of a healthy and osteoporotic human femur and found that tissue‐level strains in the osteoporotic femoral head were 70% higher on average and less uniformly distributed than those in the healthy one.Introduction: Bone tissue stresses and strains in healthy load‐adapted trabecular architectures should be distributed rather evenly, because no bone tissue is expected to be overloaded or unused. In this study, we evaluate this paradigm with the use of microfinite element (μFE) analyses to calculate tissue‐level stresses and strains for the human femur. Our objectives were to quantify the strain distribution in the healthy femur, to investigate to what extent this distribution is affected by osteoporosis, to determine if osteoporotic bone is simply bone adapted to lower load levels, and to determine the “safety factor” for trabecular bone.Materials and Methods: μFE models of a healthy and osteoporotic proximal femur were made from microcomputed tomography images. The models consisted of over 96 and 71 million elements for the healthy and osteoporotic femur, respectively, and represented their internal and external morphology in detail. Stresses and strains were calculated for each element and their distributions were calculated for a volume of interest (VOI) of trabecular bone in the femoral head.Results: The average tissue‐level principal strain magnitude in the healthy VOI was 304 ± 185 microstrains and that in the osteoporotic VOI was 520 ± 355 microstrains. Calculated safety factors were 8.6 for the healthy and 4.9 for the osteoporotic femurs. After reducing the force applied to the osteoporotic model to 59%, the average strain compared with that of the healthy femur, but the SD was larger (208 microstrains).Conclusions: Strain magnitudes in the osteoporotic bone were much higher and less uniformly distributed than those in the healthy one. After simulated joint‐load reduction, strain magnitudes in the osteoporotic femur were very similar to those in the healthy one, but their distribution is still wider and thus less favorable.
TRACP as an Osteopontin Phosphatase
Authors: Andersson Göran , Ek-Rylander Barbro , Hollberg Karin , Ljusberg-SjÖLander Jenny , Lång Pernilla , Norgård Maria , Wang Yunling , Zhang Shi-Jin 
Published: April 2006

Abstract
TRACP is synthesized as a latent proenzyme requiring proteolytic processing to attain maximal phosphatase activity. Excision of an exposed loop domain abolishes the interaction between the loop residue Asp146 and a ligand to the redox-sensitive iron of the active site, most likely Asn91, providing a mechanism for the enzyme repression. Both cathepsin K and L efficiently cleave in the loop domain and activate the latent enzyme, and we propose that cathepsin K acts as a physiological activator of TRACP in osteoclasts, whereas cathepsin L might fulfill a similar role in different types of macrophages. Considering the rather broad substrate specificity of TRACP, a tight regulation of its activity in the cell appears warranted. Besides proteolytic cleavage, the enzyme should need a specific local environment with a slightly acidic pH and reducing equivalents to keep the enzyme fully active. Cellular subcompartments where these required conditions prevail are potential subcellular site(s) of TRACP action. Of bone phosphoproteins shown to be substrates for TRACP, both osteopontin and bone sialoprotein are colocalized with TRACP in the resorption lacuna of the osteoclasts, and dephosphorylation of OPN impair its ability to promote adhesion as well as migration of osteoclasts in vitro. A role for TRACP as an osteopontin phosphatase in bone is therefore suggested. The expression of TRACP as well as OPN in other tissues with possible interactions between the two could suggest a more general function for TRACP as a regulator of OPN phosphorylation and bioactivity.
Associations Among Disease Conditions, Bone Mineral Density, and Prevalent Vertebral Deformities in Men and Women 50 Years of Age and Older: Cross-Sectional Results From the Canadian Multicentre Osteoporosis Study
Authors: Hanley DA , Brown JP , Tenenhouse A , Olszynski WP , Ioannidis G , Berger C , Prior JC , Pickard L , Murray TM , Anastassiades T , Kirkland S , Joyce C , Joseph L , Papaioannou A , Jackson SA , Poliquin S , Adachi JD 
Published: April 2006

Abstract
This cross-sectional cohort study of 5566 women and 2187 men 50 years of age and older in the population-based Canadian Multicentre Osteoporosis Study was conducted to determine whether reported past diseases are associated with bone mineral density or prevalent vertebral deformities. We examined 12 self-reported disease conditions including diabetes mellitus (types 1 or 2), nephrolithiasis, hypertension, heart attack, rheumatoid arthritis, thyroid disease, breast cancer, inflammatory bowel disease, neuromuscular disease, Paget's disease, and chronic obstructive pulmonary disease. Multivariate linear and logistic regression analyses were performed to determine whether there were associations among these disease conditions and bone mineral density of the lumbar spine, femoral neck, and trochanter, as well as prevalent vertebral deformities. Bone mineral density measurements were higher in women and men with type 2 diabetes compared with those without after appropriate adjustments. The differences were most notable at the lumbar spine (+0.053 g/cm2), femoral neck (+0.028 g/cm2), and trochanter (+0.025 g/cm2) in women, and at the femoral neck (+0.025 g/cm2) in men. Hypertension was also associated with higher bone mineral density measurements for both women and men. The differences were most pronounced at the lumbar spine (+0.022 g/cm2) and femoral neck (+0.007 g/cm2) in women and at the lumbar spine (+0.028 g/cm2) in men. Although results were statistically inconclusive, men reporting versus not reporting past nephrolithiasis appeared to have clinically relevant lower bone mineral density values. Bone mineral density differences were −0.022, −0.015, and −0.016 g/cm2 at the lumbar spine, femoral neck, and trochanter, respectively. Disease conditions were not strongly associated with vertebral deformities. In summary, these cross-sectional population-based data show that type 2 diabetes and hypertension are associated with higher bone mineral density in women and men, and nephrolithiasis may be associated with lower bone mineral density in men. The importance of these associations for osteoporosis case finding and management require further and prospective studies.
Children and the Risk of Fractures Caused by Oral Corticosteroids
Authors: van Staa TP , Cooper C , Leufkens Hgm , Bishop N 
Published: April 2006

Abstract
Oral corticosteroids are known to increase the risk of fracture in adults, but their effects in children remain uncertain. The medical records of general practitioners in the United Kingdom (from the General Practice Research Database) were used to estimate the incidence rates of fracture of children ages 4-17 years taking oral corticosteroids (n = 37,562) and of control children taking nonsystemic corticosteroids (n = 345,748). Each child with a fracture (n = 22,846) was subsequently matched by age, sex, practice, and calendar time to one child without a fracture. The average duration of treatment was 6.4 days (median, 5 days). The risk of fracture was increased in children with a history of frequent use of oral corticosteroids; children who received four or more courses of oral corticosteroids had an adjusted odds ratio (OR) for fracture of 1.32 (95% CI, 1.03-1.69). Of the various fracture types, the risk of humerus fracture was doubled in children who received four or more courses of oral corticosteroids (adjusted OR, 2.17 [1.01-4.67]). Fracture risk was also increased among children using 30 mg prednisolone or more each day (adjusted OR for fracture, 1.24 [1.00-1.52]) and among those receiving four or more courses of oral corticosteroids (OR, 1.32 [1.03-1.69]). Children who stopped taking oral corticosteroids had a comparable risk of fracture to those in the control group. Our findings suggest that children who require more than four courses of oral corticosteroid as treatment for underlying disease are at increased risk of fracture. It is not entirely clear whether this relates directly to oral corticosteroid use or the underlying disease and its severity. Irrespective of these issues, this group of children is at increased risk of fracture.
Aging of Microstructural Compartments in Human Compact Bone
Authors: Akkus Ozan , Polyakova-Akkus Anna , Adar Fran , Schaffler Mitchell B 
Published: April 2006

Abstract
Composition of microstructural compartments in compact bone of aging male subjects was assessed using Raman microscopy. Secondary mineralization of unremodeled fragments persisted for two decades. Replacement of these tissue fragments with secondary osteons kept mean composition constant over age, but at a fully mineralized limit. Slowing of remodeling may increase fracture susceptibility through an increase in proportion of highly mineralized tissue.
In this study, the aging process in the microstructural compartments of human femoral cortical bone was investigated and related to changes in the overall tissue composition within the age range of 17-73 years. Raman microprobe analysis was used to assess the mineral content, mineral crystallinity, and carbonate substitution in fragments of primary lamellar bone that survived remodeling for decades. Tissue composition of the secondary osteonal population was investigated to determine the composition of turned over tissue volume. Finally, Raman spectral analysis of homogenized tissue was performed to evaluate the effects of unremodeled and newly formed tissue on the overall tissue composition. The chemical composition of the primary lamellar bone exhibited two chronological stages. Organic matrix became more mineralized and the crystallinity of the mineral improved during the first stage, which lasted for two decades. The mineral content and the mineral crystallinity did not vary during the second stage. The results for the primary lamellar bone demonstrated that physiological mineralization, as evidenced by crystal growth and maturation, is a continuous process that may persist as long as two decades, and the growth and maturation process stops after the organic matrix becomes “fully mineralized.” The average mineral content and the average mineral crystallinity of the homogenized tissue did not change with age. It was also observed that the mineral content of the homogenized tissue was consistently greater than the osteons and similar to the “fully mineralized” stage of primary bone. The results of this study demonstrated that unremodeled compartments of bone grow older through maturation and growth of mineral crystals in a protracted fashion. However, the secondary osteonal remodeling impedes this aging process and maintains the mean tissue age fairly constant over decades. Therefore, slowing of remodeling may lead to brittle bone tissue through accumulation of fully mineralized tissue fragments.
T-Cells Mediate an Inhibitory Effect of Interleukin-4 on Osteoclastogenesis
Authors: Mirosavljevic Danijela , Quinn Julian Mw , Elliott Jan , Horwood Nicole J , Martin T John , Gillespie Matthew T 
Published: April 2006

Abstract
IL-4 is an important cytokine that can influence bone. We identified two distinct actions of IL-4 to inhibit osteoclast formation: one direct on osteoclast progenitors and the second through the production of a novel T-cell surface-associated molecule(s). These data show a new link between the immune system and bone.
The Th2 cytokine interleukin (IL)-4 inhibits osteoclast formation in vitro but also acts on other cell types found in bone, including T-cells and macrophages. Because some osteoclastogenesis inhibitors (e.g., IL-12) act indirectly through T-cells, we investigated IL-4 action on osteoclastogenesis in the presence of T-cells. Osteoclast formation from murine spleen cells treated with RANKL and macrophage colony-stimulating factor (M-CSF) was blocked by IL-4 even when spleen cells were depleted of T-cells (Thy 1.2+) and/or B-cells (B220+). Also, IL-4 inhibited osteoclastogenesis in RANKL/M-CSF-stimulated adherent spleen cells, Rag1−/− (lymphocyte-deficient) spleen cells, and bone marrow macrophages, indicating an action on myelomonocytic cells to block osteoclastogenesis. In contrast, IL-4 did not inhibit osteoclastogenesis in cells from IL-4 receptor null mice (IL-4R−/−). However, when wildtype T-cells were added to IL-4R−/− spleen cell cultures, IL-4 inhibited osteoclast formation, indicating a T-cell-dependent action. Osteoclast formation in RANKL-stimulated RAW 264.7 cells was not inhibited by IL-4 unless T-cells were added to the culture. Separation of RAW 264.7 cells and T-cells by semipermeable membrane ablated this action of IL-4, suggesting the induction of a membrane-associated osteoclastogenesis inhibitor. However, membrane-bound inhibitors thymic shared antigen-1 (TSA-1) and osteoclast inhibitory lectin (OCIL) were not regulated by IL-4. In summary, at least two mechanisms of IL-4-mediated osteoclastogenesis inhibition exist, including a direct action on myelomonocytic progenitors (from which osteoclasts derive) and an indirect action through T-cells that may involve novel anti-osteoclastic factors.