bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Incidence of Vertebral Fractures in Men and Women: The Rotterdam Study
Authors: Van Der Klift Marjolein , De Laet Chris E. D. H. , Mccloskey Eugene V. , Hofman Albert , Pols Huibert A. P. 
Published: April 2006

Abstract
Vertebral fractures are considered the most common fractures in osteoporosis. Nevertheless, little is known about the epidemiology of these fractures, especially in men. Therefore, the incidence of vertebral fractures was studied in 3469 men and women from the Rotterdam Study. Spinal radiographs were obtained at baseline and again after a mean follow-up of 6.3 years. The follow-up radiographs were scored for vertebral fractures using the McCloskey-Kanis assessment method. Whenever a vertebral fracture was detected, the radiograph was compared with the baseline radiograph. If this fracture was not already present at baseline, it was considered an incident fracture. The incidence increased strongly with age, ranging from 7.8/1000 person years (PY) at ages 55-65 years to 19.6/1000 PY at ages over 75 years for women, and 5.2-9.3/1000 PY for men, respectively. Analyses repeated in strata of presence or absence of prevalent vertebral fractures showed that both in men and in women, the increase in incidence with age was almost exclusively observed in subjects with one or more prevalent fractures present at baseline. For both genders, the incidence of vertebral fractures doubled per SD decrease in lumbar spine or femoral neck bone mineral density (BMD). This study shows that overall, the incidence of vertebral fractures is higher in women than in men. In both genders, the incidence increases with age. Furthermore, the presence of a prevalent vertebral fracture and a low BMD are strong independent predictors of incident vertebral fractures in men and women.
Daily Oral Pamidronate in Women and Men With Osteoporosis: A 3-Year Randomized Placebo-Controlled Clinical Trial With a 2-Year Open Extension
Authors: Brumsen Caroline , Papapoulos Socrates E. , Lips Paul , Geelhoed-Duijvestijn Petronella H. L. M. , Hamdy Neveen A. T. , Landman Jan Otto , Mccloskey Eugene V. , Netelenbos J. Coen , Pauwels Ernest K. J. , Roos Jan C. , Valentijn Rob M. , Zwinderman Aeilko H. 
Published: April 2006

Abstract
The efficacy and safety of oral pamidronate was examined in a double-blind, placebo-controlled trial in women and men with established osteoporosis. Seventy-eight postmenopausal women and 23 men with at least one prevalent vertebral fracture were randomized separately to 150 mg/day of pamidronate or placebo for 3 years followed by 150 mg/day of pamidronate for an additional 2 years. In addition, all patients received 400 U/day of cholecalciferol and 500 mg/day of elemental calcium. Pamidronate increased significantly bone mineral density of the lumbar spine (LS-BMD) and of the femoral neck (FN-BMD). The total increase in BMD of the spine after 5 years of treatment was 14.3%. Lateral spine radiographs were obtained at baseline and after 3 years of treatment. Fractures of previously normal vertebrae occurred in 15 of 45 patients treated with placebo (33.3%) and in 5 of 46 patients treated with pamidronate (11%). The relative risk was 0.33 (95% CI, 0.14-0.77). Treatment was well tolerated and there was no difference in gastrointestinal toxicity between pamidronate and placebo-treated patients. One hundred fifty milligrams daily of pamidronate is an effective and safe treatment of women and men with established osteoporosis.
Four-Year Gain in Bone Mineral in Girls With and Without Past Forearm Fractures: A DXA Study
Authors: Jones Ianthe E. , Taylor Rachael W. , Williams Sheila M. , Manning Patrick J. , Goulding Ailsa 
Published: April 2006

Abstract
We have previously shown that girls with a recent distal forearm fracture have weaker skeletons than girls who have never fractured. This could be a transient or persistent phenomenon. The present study was undertaken to determine whether the bone mineral content (BMC) of girls with previous distal forearm fractures remains lower 4 years postfracture or if catch-up gain has occurred. We report baseline and follow-up dual energy X-ray absorptiometry (DXA) results for 163 girls: 81 girls from the original control group who remained free of fracture (group 1) and 82 girls from the original group with distal forearm fractures (group 2). In data adjusted for bone area, height, weight, and pubertal status, group 2 girls had 3.5-8.5% less BMC at the total body, lumbar spine, ultradistal radius, and hip trochanter than group 1 at baseline, and 2.4-5.7% less BMC at these sites at follow-up. Even girls from group 2 who did not experience another fracture after baseline (n = 58) did not display greater BMC at follow-up compared with baseline values at any site, indicating that the decreased BMC at the time of fracture had persisted. In group 2, the relative gain in BMC after adjusting for the initial BMC and current bone area, height, weight, and pubertal stage was less than or similar to, but not greater than that of group 1 (ratio [95% CI]: total body, 0.985 [0.972-0.998]; lumbar spine, 0.961 [0.935-0.987]; ultradistal radius, 0.968 [0.939-0.998]; hip trochanter, 0.955 [0.923-0.988]; femoral neck, 0.981 [0.956-1.007]; and 33% radius 0.999 [0.977-1.021]). These findings indicate that girls with distal forearm fractures do not improve their gain of BMC. We conclude that girls who have sustained a distal forearm fracture maintain their lower BMC at most sites for at least 4 years.
Cyclo-Oxygenase 2 Function Is Essential for Bone Fracture Healing
Authors: Simon Ann Marie , Manigrasso Michaele Beth , O'Connor J. Patrick 
Published: April 2006

Abstract
Despite the molecular and histological similarities between fetal bone development and fracture healing, inflammation is an early phase of fracture healing that does not occur during development. Cyclo-oxygenase 2 (COX-2) is induced at inflammation sites and produces proinflammatory prostaglandins. To determine if COX-2 functions in fracture healing, rats were treated with COX-2-selective nonsteroidal anti-inflammatory drugs (NSAIDs) to stop COX-2-dependent prostaglandin production. Radiographic, histological, and mechanical testing determined that fracture healing failed in rats treated with COX-2-selective NSAIDs (celecoxib and rofecoxib). Normal fracture healing also failed in mice homozygous for a null mutation in the COX-2 gene. This shows that COX-2 activity is necessary for normal fracture healing and confirms that the effects of COX-2-selective NSAIDs on fracture healing is caused by inhibition of COX-2 activity and not from a drug side effect. Histological observations suggest that COX-2 is required for normal endochondral ossification during fracture healing. Because mice lacking Cox2 form normal skeletons, our observations indicate that fetal bone development and fracture healing are different and that COX-2 function is specifically essential for fracture healing.
Risedronate Preserves Trabecular Architecture and Increases Bone Strength in Vertebra of Ovariectomized Minipigs as Measured by Three-Dimensional Microcomputed Tomography
Authors: Borah Babul , Dufresne Thomas E. , Chmielewski Paula A. , Gross Gary J. , Prenger Marla C. , Phipps Roger J. 
Published: April 2006

Abstract
Risedronate reduces the risk of new vertebral fractures up to 70% within 1 year of treatment in patients with osteoporosis. Both increases in bone mass and preservation of bone architecture are thought to contribute to antifracture effects. Our objectives were to determine the effects of risedronate on trabecular bone mass and architecture and to determine the relative contributions of mass and architecture to strength in the vertebra of ovariectomized (OVX) minipigs. The minipigs were OVX at 18 months of age and were treated daily for 18 months with either vehicle or risedronate at doses of 0.5 mg/kg per day or 2.5 mg/kg per day. The three-dimensional (3D) bone architecture of the L4 vertebral cores of Sinclair S1 minipigs was evaluated by 3D microcomputed tomography (μCT). Compared with the OVX control, the vertebral bone volume (bone volume/tissue volume [BV/TV]) was higher in both treated groups (p &lt; 0.05). The architectural changes were more significant at the 2.5-mg/kg dose and were more prevalent at the cranial-caudal ends compared with the midsection. At the higher dose, the trabecular thickness (Tb.Th), trabecular number (Tb.N), and connectivity were higher, and marrow star volume (Ma.St.V) and trabecular separation (Tb.Sp) were lower (p &lt; 0.05). The trabecular separation variation index(TSVI), a new measure to approximate structural variations, was smaller in the 2.5-mg/kg-treated group (p &lt; 0.05). In this group, a significant preservation of trabeculae orthogonal to the cranial-caudal axis was confirmed by a decrease in the degree of anisotropy (DA) and an increase in the percent Cross-strut (%Cross-strut; p &lt; 0.05). Both normalized maximum load (strength) and normalized stiffness of the same vertebral cores were higher in the 2.5-mg/kg risedronate group compared with the OVX group (p &lt; 0.05). BV/TV alone could explain 76% of the variability of the bone strength. The combination of bone volume and architectural variables explained &gt;90% of the strength. The study showed that risedronate preserved trabecular architecture in the vertebra of OVX minipigs, and that bone strength is tightly coupled to bone mass and architecture.
Bone Origin of the Serum Complex of Calcium, Phosphate, Fetuin, and Matrix Gla Protein: Biochemical Evidence for the Cancellous Bone-Remodeling Compartment
Authors: Price Paul A. , Caputo Jeffrey M. , Williamson Matthew K. 
Published: April 2006

Abstract
We previously described the discovery of a fetuin-matrix Gla protein (MGP)-mineral complex in the serum of rats treated with the bone-active bisphosphonate etidronate and showed that the appearance of this complex in serum correlates with the inhibition of bone mineralization by etidronate. In this study we show that the inhibition of bone resorption by treatment with the hormone calcitonin, the cytokine osteoprotegerin, or the drug alendronate, completely inhibits the generation of the fetuin-mineral complex in response to etidronate injection. These observations can be explained best by the bone-remodeling compartment (BRC), a cancellous bone compartment in which the concentrations of calcium and phosphate are determined directly by the combined actions of the osteoclast and the osteoblast. When bone mineralization is acutely inhibited by etidronate, the BRC model predicts that the continuing action of osteoclasts will cause a sharp rise in the concentrations of calcium and phosphate in the aqueous solution of the BRC with the consequent spontaneous formation of calcium phosphate crystal nuclei in which growth then would be arrested by formation of a complex with fetuin. When the inhibition of bone resorption by calcitonin, osteoprotegerin, or alendronate is combined with the acute inhibition of bone mineralization with etidronate, the BRC model correctly predicts that there will no longer be a sharp rise in calcium and phosphate, and, therefore, there will no longer be the formation of the fetuin-mineral complex. The vascular nature of the BRC is supported by the observations that the fetuin component of the fetuin-mineral complex is derived from plasma fetuin and that the fetuin mineral complex appears in plasma within minutes of the inhibition of bone mineralization with etidronate.
International Variations in Hip Fracture Probabilities: Implications for Risk Assessment
Authors: Kanis John A. , Johnell Olof , De Laet Chris , Jonsson Bengt , Oden Anders , Ogelsby Alan K. 
Published: April 2006

Abstract
It is recommended that intervention thresholds should be based on absolute fracture risk, but there is a large variation in hip fracture incidence from different regions of the world. The aim of this study was to examine heterogeneity of hip fracture probability in different regions from recent estimates of hip fracture incidence and mortality to adjust intervention thresholds. Ten-year probabilities of hip fracture were computed in men and women at 10-year intervals from the age of 50 years and lifetime risks at the age of 50 years from the hazard functions of hip fracture and death. Lifetime risk at the age of 50 years varied from 1% in women from Turkey to 28.5% in women from Sweden. High lifetime risks in women were associated with high lifetime risks in men (r = 0.83). There also were significant correlations of 10-year risk at any age between men and women. Ten-year probability was standardized to that of men and women from Sweden (set at 1.0). There was a 15-fold range in 10-year probability from 1.24 in Norway to 0.08 in Chile. Countries were categorized by 10-year probabilities comprising very high risk (Norway, Iceland, Sweden, Denmark, and the United States), high risk (China [Taiwan {TW}], Germany, Switzerland, Finland, Greece, Canada, The Netherlands, Hungary, Singapore, Italy, United Kingdom, Kuwait, Australia, and Portugal), medium risk (China [Hong Kong {HK}], France, Japan, Spain, Argentina, and China), and low risk (Turkey, Korea, Venezuela, and Chile). The categorization of hip fracture probabilities can be used to adjust intervention thresholds based on age, sex, and relative risk from a reference population such as Sweden.
Genetic and Environmental Determinants of Peak Bone Mass in Young Men and Women
Authors: Mcguigan Fiona E. A. , Murray Liam , Gallagher Alison , Davey-Smith George , Neville Charlotte E. , Van't Hof Rob , Boreham Colin , Ralston Stuart H. 
Published: April 2006

AbstractPeak bone mass is an important risk factor for the development of osteoporosis in later life. Previous work has suggested that genetic, intrauterine, and environmental factors all contribute to the regulation of bone mass, but the ways in which they interact with each other to do so remain poorly understood. In this study, we investigated the relationship between peak bone mass and polymorphisms of the vitamin D receptor (VDR), estrogen receptor (ER) α, and collagen type Iα1 (COLIA1) genes in relation to other factors such as birth weight, lifestyle diet, and exercise in a population-based cohort of 216 women and 244 men in their early 20s. Stepwise multiple regression analysis showed that body weight was the strongest predictor of bone mineral density (BMD) in women, accounting for 16.4% of the variance in spine BMD and 8.4% of the variance in femoral neck BMD. Other significant predictors were VDR genotype (3.8%) and carbohydrate intake (1.6%) at the spine and vitamin D intake (3.4%) and ER genotype (3.4%) at the femoral neck. Physical activity was the strongest predictor of BMD in men, accounting for 6.7% of the variance at the spine and 5.1% at the hip. Other significant predictors were body weight (5%) and ER PvuII genotype (2.8%) at the spine and weight (3.4%) and alcohol intake (2%) at the femoral neck. Birth weight was not a significant predictor of BMD at either site but COLIA1 genotype significantly predicted birth weight in women, accounting for 4.3% of the variance. We conclude that peak bone mass is regulated by an overlapping but distinct set of environmental and genetic influences that differ in men and women. However, much of the variance in BMD was unexplained by the variables studied here, which suggests that either most of the genes that regulate BMD remain to be discovered or major environmental influences on BMD exist that have not yet been identified.
Orientation of Mineral Crystallites and Mineral Density During Skeletal Development in Mice Deficient in Tissue Nonspecific Alkaline Phosphatase
Authors: Tesch W , Vandenbos T , Roschgr P , Fratzl-Zelman N , Klaushofer K , Beertsen W , Fratzl P 
Published: April 2006

Abstract
Tissue nonspecific alkaline phosphatase (TNALP) is thought to play an important role in mineralization processes, although its exact working mechanism is not known. In the present investigation we have studied mineral crystal characteristics in the developing skeleton of TNALP-deficient mice. Null mutants (n = 7) and their wild-type littermates (n = 7) were bred and killed between 8 and 22 days after birth. Skeletal tissues were processed to assess mineral characteristics (small angle X-ray scattering, quantitative backscattered electron imaging), and to analyze bone by light microscopy and immunolabeling. The results showed a reduced longitudinal growth and a strongly delayed epiphyseal ossification in the null mutants. This was accompanied by disturbances in mineralization pattern, in that crystallites were not orderly aligned with respect to the longitudinal axis of the cortical bone. Among the null mutants, a great variability in the mineralization parameters was noticed. Also, immunolabeling of osteopontin (OPN) revealed an abnormal distribution pattern of the protein within the bone matrix. Whereas in the wild-type animals OPN was predominantly observed in cement and reversal lines, in the null mutants, OPN was also randomly dispersed throughout the nonmineralized matrix, with focal densities. In contrast, the distribution pattern of osteocalcin (OC) was comparable in both types of animals. It is concluded that ablation of TNALP results not only in hypomineralization of the skeleton, but also in a severe disorder of the mineral crystal alignment pattern in the corticalis of growing long bone in association with a disordered matrix architecture, presumably as a result of impaired bone remodeling and maturation.
Intravenous Neridronate in Adults With Osteogenesis Imperfecta
Authors: Adami S , Gatti D , Colapietro F , Fracassi E , Braga V , Rossini M , Tatò L 
Published: April 2006

Abstract
Osteogenesis imperfecta (OI) is a heritable disease of connective tissue, characterized by increased bone fragility. Bisphosphonates currently seems to be the most promising therapy, at least in children. We tested IV neridronate, an amino-bisphosphonate structurally similar to alendronate and pamidronate in adults with OI. Twenty-three men and 23 premenopausal women with OI were randomized to either iv neridronate (100 mg infused intravenously for 30 minutes every 3 months) or no treatment with a ratio of 2 to 1. Control patients were given the same bisphosphonate therapy at the end of the first year. Clinical evaluation included bone densitometry measurements using dual energy X-ray absorptiometry (DXA), fasting serum and urinary biochemistry every 6 months, and radiographs of the spine taken at baseline and after 12 and 24 months of follow-up. Spine and hip bone mineral density rose by 3.0 ± 4.6% (SD) and by 4.3 ± 3.9%, respectively, within the first 12 months of treatment, whereas small insignificant changes were observed in the control group. During the second year of follow-up, additional 3.91% and 1.49% increases were observed at the spine and hip, respectively. Markers of skeletal turnover significantly fell during neridronate treatment. Fracture incidence during neridronate treatment was significantly lower than before therapy and compared with controls. Neridronate iv infusions, administered quarterly, significantly increase bone mineral density and lowered the risk of clinical fracture in adults with OI. Bisphosphonate therapy seems to provide clinical benefits, not only to children with OI, but also to adult patients.
The Skeletal Response to Teriparatide Is Largely Independent of Age, Initial Bone Mineral Density, and Prevalent Vertebral Fractures in Postmenopausal Women With Osteoporosis
Authors: Marcus Robert , Wang Ouhong , Satterwhite Julie , Mitlak Bruce 
Published: April 2006

Abstract
In a recent study of women with postmenopausal osteoporosis, treatment with teriparatide for a median of 19 months increased bone mineral density and decreased the risk of vertebral and nonvertebral fractures. Using the same cohort, the current study evaluated the relationship between these therapeutic effects and the patient's baseline age, vertebral bone mineral density, and prevalent vertebral fractures. In women over 65 years of age, treatment resulted in a greater increase in vertebral bone mineral density than in younger women (treatment-by-age interaction, p = 0.037), but baseline age had no effect on the relative risk reduction for vertebral fractures (treatment-by-age interaction, p = 0.558). In women receiving placebo (with calcium and vitamin D), there was an inverse relationship between baseline vertebral bone mineral density and vertebral fracture risk. When compared across bone mineral density tertiles, the effects of teriparatide on the relative risk for developing new vertebral fractures and increase in vertebral bone mineral density did not differ significantly (p = 0.817 and p = 0.615, respectively). Teriparatide treatment significantly decreased vertebral fracture risk in patients with a vertebral bone mineral density T score of less than −3.3 or a score between −2.1 and −3.3 (p &lt; 0.001 and p = 0.027, respectively) and showed a trend toward reduced fracture risk in the group with a T score greater than −2.1 (p = 0.115). Placebo-treated women with two or more prevalent vertebral fractures had a significantly greater risk of developing new vertebral fractures than women with zero or one prevalent vertebral fracture (p &lt; 0.001). When compared within prevalent vertebral fracture subgroups, the effects of teriparatide on the relative risk for developing new vertebral fractures were similar. The results of this study indicate that teriparatide offers clinical benefit to patients across a broad range of age and disease severity.
Ascorbic Acid Induces Collagenase-1 in Human Periodontal Ligament Cells but Not in MC3T3-E1 Osteoblast-Like Cells: Potential Association Between Collagenase Expression and Changes in Alkaline Phosphatase Phenotype
Authors: Shiga Momotoshi , Kapila Yvonne L , Zhang Qin , Hayami Takayuki , Kapila Sunil 
Published: April 2006

Abstract
Ascorbic acid (AA) enhances osteoblastic differentiation by increasing collagen accumulation, which in turn, results in increased alkaline phosphatase (AP) expression in some osteogenic cells. However, in other cells, including human periodontal ligament (PDL) cells, additional osteoinductive agents are required for this response. To understand the potential basis for the maintenance of the AP phenotype of PDL cells exposed to AA, we examined the modulation of the tissue-degrading matrix metalloproteinases (MMPs) and their inhibitors by AA in short-term cell cultures. Early passage PDL cells in serum-free medium were exposed to AA for 5 days. The samples were analyzed for MMPs and their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), AP, collagen I(α1), and osteocalcin. We found that AA dose-dependently increased the expression of collagenase-1, and minimally TIMP-1, but not stromelysin-1 or TIMP-2. Additionally, AA caused substantial increases in levels of type I collagen. AA was unable to increase AP activity or osteocalcin messenger RNA in PDL cells. However, the cells retained the ability to show a significantly greater AP expression in high- versus low-density cultures, and increased osteocalcin as well as AP levels when cultured in the presence of dexamethasone. Moreover, in cells exposed to dexamethasone, increases in AP and osteocalcin were accompanied by a repression of collagenase-1 expression. In contrast to PDL cells, AA did not induce collagenase but produced a significant increase in AP expression in MC3T3-E1 cells. These findings provide the first evidence that AA, by modulating both collagen and collagenase-1 expression in PDL cells, most likely contributes to a net matrix remodeling response in these cells. Furthermore, the relationship between changes in collagenase expression and alterations in AP activity in PDL and MC3T3-E1 cells suggests a potential role for collagenase in modulating the AP phenotype of cells with osteoblastic potential.