bluuebunny/crossref_metadata_2025_split huggingface dataset:
Calcium for Prevention of Osteoporotic Fractures in Postmenopausal Women
Authors: Cumming Robert G. , Nevitt Michael C. 
Published: April 2006

Abstract
A systematic review of the literature was conducted to assess the effectiveness of calcium supplements and/or dietary calcium for the prevention of osteoporotic fractures in postmenopausal women. Studies were identified by conducting a Medline search using the text words “fracture” and “calcium” for the period 1966 to March 1997 and by reviewing articles known to the authors. Only studies with fracture outcomes were eligible. There were 14 studies of calcium supplements (including 4 randomized trials), 18 studies of dietary calcium and hip fracture (no randomized trials), and 5 studies of dietary calcium and other fracture sites (no randomized trials). The 4 randomized trials of calcium supplements (mean calcium dose: 1050 mg) found relative risk (RR) reductions between 25% and 70%. Meta-analytic techniques for dose-response data were used to investigate and pool the findings of 16 observational studies of dietary calcium and hip fracture. These hip fracture studies were not consistent and heterogeneity of study findings (p = 0.02) was not easily explained by subject characteristics or study design. Pooling study results gave an odds ratio (OR) of 0.96 (95% confidence interval, (CI) 0.93–0.99) per 300 mg/day increase in calcium intake (the equivalent of one glass of milk). This is likely to be an underestimate of calcium's true effect because of inaccurate measurement of dietary calcium in observational studies. This review supports the current clinical and public health policy of recommending increased calcium intake among older women for fracture prevention.
Decreased β-Isomerization of the C-Terminal Telopeptide of Type I Collagen α1 Chain in Paget's Disease of Bone
Authors: Garnero Patrick , Fledelius Christian , Gineyts Evelyne , Serre Claire-Marie , Vignot Emanuelle , Delmas Pierre D. 
Published: April 2006

Abstract
In Paget's disease of bone, the normal lamellar bone is replaced by a woven structure with an irregular arrangement of collagen fibers. In this study, we investigated whether the degree of β-isomerization within C-telopeptide of α1 chain of type I collagen was altered in Paget's disease compared with other bone diseases with no alteration of bone structure. In Paget's disease (n = 26), but not in patients with primary hyperparathyroidism (n = 6) or hyperthyroidism (n = 17), the urinary excretion of nonisomerized (α) fragments derived from degradation of type I collagen C-telopeptide (CTX) was markedly increased compared with β-isomerized CTX (+ 13-fold vs. + 3.5-fold over controls) resulting in an urinary α CTX/β CTX ratio 3-fold higher than in controls (2.6 ± 1.0 vs. 0.8 ± 0.3, p &lt; 0.001). In five pagetic patients in complete remission, as demonstrated by normal total alkaline phosphatase activity, the α CTX/β CTX ratio was normal. The immunohistochemistry of normal and pagetic human bone sections showed a preferential distribution of α CTX within woven structure, while lamellar bone was intensely stained with an anti–β CTX antibody, suggesting a lower degree of β-isomerization of type I collagen in the woven pagetic bone. In collagenase digest of human bone specimens, we found a lower proportion of β-isomerized type I collagen molecules in pagetic bone (40% of β CTX) than in normal bone taken from trabecular (68%) and cortical compartments (71%). In conclusion, we found that in Paget's disease the α CTX/β CTX ratio in bone and in urine is markedly increased. This altered β isomerization can be accurately detected in vivo by measuring urinary degradation products arising from bone resorption.
Bone Mineral Density in Girls with Forearm Fractures
Authors: Dr. Goulding A. , Cannan R. , Williams S. M. , Gold E. J. , Taylor R. W. , Lewis-Barned N. J. 
Published: April 2006

Abstract
In childhood, the most common site of fracture is the distal forearm. To determine whether young girls with these fractures have low bone density more commonly than fracture-free controls, we measured bone density at the radius, spine, hip, and whole body and total body bone mineral content, lean tissue mass, and fat mass by dual-energy X-ray absorptiometry in 100 Caucasian girls aged 3–15 years with recent distal forearm fractures and 100 age- and gender-matched controls. Bone density (age-adjusted ratios of all cases:controls with 95% confidence intervals) was lower in cases at the ultradistal radius 0.963 (0.930–0.996), 33% radius 0.972 (0.945–0.999), lumbar spine 0.945 (0.911–0.980), hip trochanter 0.952 (0.918–0.988), and total body 0.978 (0.961–0.995). Moreover, osteopenia (defined as Z score below −1), was more common in cases than controls (p &lt; 0.05) in the forearm, spine, and hip, with one third of fracture cases having low spinal density. Odds ratios (95% confidence intervals) for low bone density were: ultradistal radius, 2.2 (1.1–4.6); lumbar spine, L2-L4, 2.6 (1.3–4.9); and femur trochanter, 2.0 (1.0–3.9). Fracture patients aged 8-10 years weighed more (mean ± SD) than age-matched controls (37.2 ± 8.0 kg vs. 32.5 ± 6.6 kg, p &lt; 0.01) while older patients reported lower current and past calcium intakes than matched controls (p &lt; 0.05). We conclude that low bone density is more common throughout the skeleton in girls with forearm fractures than in those who have never broken a bone, supporting the view that low bone density may contribute to fracture risk in childhood.
Inhibition of Avian Osteoclast Bone Resorption by Monoclonal Antibody 121F: A Mechanism Involving the Osteoclast Free Radical System
Authors: Collin-Osdoby Patricia , Li Li , Rothe Linda , Anderson Fred , Kirsch David , Oursler Merry Jo , Osdoby Philip 
Published: April 2006

Abstract
Osteoclasts generate high levels of superoxide anions during bone resorption that contribute to the degradative process, although excessive levels of this free radical may be damaging. One mechanism for their removal is via superoxide dismutase (SOD), a protective superoxide scavenging enzyme. We have previously described a novel developmentally regulated 150 kDa plasma membrane glycoprotein of avian osteoclasts which is reactive with the osteoclast-specific monoclonal antibody (Mab) 121F and is related immunologically, biochemically, and in protein sequence to mitochondrial Mn2+/Fe2+ SOD. We hypothesized that this unusual osteoclast surface component may be involved in protection against superoxides generated during active bone resorption. Increasing concentrations of monovalent Fab fragments prepared from Mab 121F, but not those from another antiosteoclast Mab designated 29C, markedly inhibited both bone particle and bone pit resorption by avian osteoclasts, while reducing tartrate-resistant acid phosphatase activity and causing the morphological contraction of osteoclasts on bone. Thus, the SOD-related membrane antigen may be essential for osteoclast bone resorption. Osteoclast superoxide production, monitored kinetically by cytochrome c reduction and histochemically by nitroblue tetrazolium reduction staining, was significantly greater in the presence of 121F, but not 29C, Fab treatment. Furthermore, the release of another free radical known as nitric oxide, which is produced by osteoclasts, can scavenge superoxides, and acts to potently inhibit osteoclast bone resorption, was dose-dependently increased by 121F Fab in resorbing osteoclast cultures. Therefore, Mab 121F binding may block the potential protective function of the osteoclast plasma membrane SOD-related glycoprotein, leading to a rapid elevation of superoxide levels and a subsequent rise in osteoclast nitric oxide release, feedback messages which may be sensed by the osteoclast as signals to cease active bone resorption.
Association of a Polymorphism of the Transforming Growth Factor-β1 Gene with Genetic Susceptibility to Osteoporosis in Postmenopausal Japanese Women
Authors: Yamada Yoshiji , Miyauchi Akimitsu , Goto Junki , Takagi Yasuyuki , Okuizumi Hiroyasu , Kanematsu Masahiro , Hase Makoto , Takai Hiroyuki , Harada Atsushi , Ikeda Kyoji 
Published: April 2006

Abstract
Transforming growth factor-β (TGF-β) is both abundant in bone and an important regulator of bone metabolism. A T→C transition at nucleotide 29 in the signal sequence region of the TGF-β1 gene results in a Leu→Pro substitution at amino acid position 10. The possible association of this polymorphism with bone mass and the prevalence of osteoporosis has now been investigated in a total of 287 postmenopausal women from two regions (Obu City, Aichi Prefecture, and Sanda City, Hyogo Prefecture) of Japan. A significant association of TGF-β1 genotype with bone mass was detected in both populations; bone mineral density (BMD) at the lumbar spine was greater in individuals with the CC genotype than in those with the TT or TC genotype. The frequency of vertebral fractures was significantly lower in individuals with the CC genotype than in those with the TC or TT genotypes. For each region, multivariable logistic regression analysis revealed that the frequency of the T allele was significantly higher in subjects with osteoporosis than in controls. Also, the serum concentration of TGF-β1 in individuals with the CC genotype was significantly higher than that in age-matched subjects with the TC or TT genotype in osteoporotic or osteopenic as well as healthy control groups. These results suggest that the T/C polymorphism of the TGF-β1 gene is one of the genetic determinants of bone mass and that the T allele is an independent risk factor for the genetic susceptibility to osteoporosis in postmenopausal Japanese women. Thus, analysis of the TGF-β1 genotype may be useful in the prevention and management of osteoporosis.
The Effects of Twelve Weeks of Bed Rest on Bone Histology, Biochemical Markers of Bone Turnover, and Calcium Homeostasis in Eleven Normal Subjects
Authors: Zerwekh Joseph E. , Ruml Lisa A. , Gottschalk Frank , Pak Charles Y. C. 
Published: April 2006

Abstract
This study was undertaken to examine the effects of 12 weeks of skeletal unloading on parameters of calcium homeostasis, calcitropic hormones, bone histology, and biochemical markers of bone turnover in 11 normal subjects (9 men, 2 women; 34 ± 11 years of age). Following an ambulatory control evaluation, all subjects underwent 12 weeks of bed rest. An additional metabolic evaluation was performed after 12 days of reambulation. Bone mineral density declined at the spine (−2.9%, p = 0.092) and at the hip (−3.8%, p = 0.002 for the trochanter). Bed rest prompted a rapid, sustained, significant increase in urinary calcium and phosphorus as well as a significant increase in serum calcium. Urinary calcium increased from a pre-bed rest value of 5.3 mmol/day to values as high as 7.3 mmol/day during bed rest. Immunoreactive parathyroid hormone and serum 1,25-dihydroxyvitamin D declined significantly during bed rest, although the mean values remained within normal limits. Significant changes in bone histology included a suppression of osteoblastic surface for cancellous bone (3.1 ± 1.3% to 1.9 ± 1.5%, p = 0.0142) and increased bone resorption for both cancellous and cortical bone. Cortical eroded surface increased from 3.5 ± 1.1% to 7.3 ± 4.0% (p = 0.018) as did active osteoclastic surface (0.2 ± 0.3% to 0.7 ± 0.7%, p = 0.021). Cancellous eroded surface increased from 2.1 ± 1.1% to 4.7 ± 2.2% (p = 0.002), while mean active osteoclastic surface doubled (0.2 ± 0.2% to 0.4 ± 0.3%, p = 0.020). Serum biochemical markers of bone formation (osteocalcin, bone-specific alkaline phosphatase, and type I procollagen extension peptide) did not change significantly during bed rest. Urinary biochemical markers of bone resorption (hydroxyproline, deoxypyridinoline, and N-telopeptide of type I collagen) as well as a serum marker of bone resorption (type I collagen carboxytelopeptide) all demonstrated significant increases during bed rest which declined toward normal during reambulation. Thus, under the conditions of this study, the human skeleton appears to respond to unloading by a rapid and sustained increase in bone resorption and a more subtle decrease in bone formation.
Parathyroid Hormone-Related Protein mRNA and Protein Expression in Multiple Myeloma: A Case Report
Authors: Schneider Hans-Gerhard , Kartsogiannis Vicky , Zhou Hong , Chou S. T. , Martin T. John , Grill Vivian 
Published: April 2006

Abstract
Multiple myeloma frequently leads to complications, such as osteolytic lesions, hypercalcemia, and pathological fractures. Increased bone resorption in myeloma is due to osteoclast activation. The nature of the osteoclast activator(s) remains unclear. We describe a case of multiple myeloma with marked hypercalcemia and skeletal complications that progressed rapidly despite chemotherapy. The patient had marked hypercalcemia at diagnosis (4.5 mmol/l), and elevated parathyroid hormone-related protein (PTHrP) levels were found in plasma. Analysis of the bone marrow trephine biopsy showed PTHrP gene transcription and protein in myeloma cells. These results provide strong evidence for the production of significant amounts of PTHrP by human myeloma cells. PTHrP has been measured as elevated in the plasma of patients with myeloma and might be an important contributor to the skeletal complications in this disease.
Evaluation of Low Density Spine Software for the Assessment of Bone Mineral Density in Children
Authors: Leonard Mary B. , Feldman Harold I. , Zemel Babette S. , Berlin Jesse A. , Barden Elizabeth M. , Stallings Virginia A. 
Published: April 2006

Abstract
Pediatric dual-energy X-ray absorptiometry spine scans often cannot be analyzed with standard software due to a failure to identify the bone edges of low density vertebrae. Low density spine (LDS) software improves bone detection compared with standard software. The objective of this study was to compare bone mineral density (BMD) measurements obtained with the standard and LDS software in 27 healthy nonobese, 32 obese, and 41 chronically ill children, ages 2–18 years. Lumbar spine (L1–L4) BMD, measured by standard analysis, ranged from 0.531–1.244 gm/cm2. Reanalysis with the LDS software resulted in a systematic increase (mean ± SD) in estimated bone area of 17.0 ± 5.0%, an increase in bone mineral content of 6.1 ± 6.3%, and a mean decrease in BMD of 8.7 ± 1.7% (all p &lt; 0.001). This resulted in a mean decrease in BMD Z score of 0.7 ± 0.2. Linear regression models, predicting standard BMD from LDS BMD, were fit for the three subject groups (R2 = 0.993–0.995). Small differences in slopes were detected across groups (p = 0.07); LDS BMD predicted higher standard BMD in obese subjects. In conclusion, LDS analysis resulted in a clinically significant decrease in measured BMD. The association between analysis methods was exceptionally high (R2 &gt; 0.99), indicating that LDS BMD accurately predicts standard BMD. Although LDS BMD in obese subjects predicts higher standard BMD results than in nonobese subjects, the small difference is of questionable clinical significance. LDS software is a useful tool for the assessment of BMD in children.
Human Osteoclast Formation and Activity In Vitro: Effects of Alendronate
Authors: Breuil V. , Cosman F. , Stein L. , Horbert W. , Nieves J. , Shen V. , Lindsay R. , Dempster D. W. 
Published: April 2006

Abstract
Recent advances in technique have made it possible to study human osteoclast (OC) formation and activity in vitro. The object of the present study was to determine the effects of alendronate (ALN) on human OCs generated from precursors obtained from standard peripheral blood samples. Peripheral blood mononuclear cells from 14 postmenopausal women were cocultured with ST2 stromal cells on bone slices in the presence of 10−7 M 1,25-dihydroxyvitamin D3, 10−8 M dexamethasone, and 25 ng/ml human macrophage colony-stimulating factor. After 21 days, the cultures contained numerous OCs, which were characterized by multinuclearity, the presence of tartrate-resistant acid phosphatase, calcitonin and vitronectin receptors, and the ability to resorb substantial amounts of bone, which was inhibited by calcitonin. The percentage area of bone resorbed per slice was highly correlated (r = 0.89, p &lt; 0.001) with the concentration of Type I collagen cross-linked C-telopeptides (CTx) released into the culture medium. When added to the medium, ALN inhibited bone resorption at concentrations ≤10−7 M. At 10−7 M, inhibition was achieved primarily by a reduction in OC activity without a marked effect on OC number. At the highest concentration studied (10−5 M), both OC number and resorption were profoundly decreased. Overnight preincubation of bone slices in ALN, without further exposure to ALN, resulted in an inhibition of resorption that was similar to that seen when ALN was present in the medium throughout the entire culture period. We conclude that, except at very high concentrations, the predominant mechanism of action of ALN is to inhibit the activity of differentiated human OCs with little or no effect on recruitment. Interaction between the OC and ALN on the bone surface is an important component of the inhibitory mechanism. Measurement of CTx in tissue culture medium is a convenient method for assessment of bone resorption in human OC cultures and offers a number of advantages over morphometric analysis of the bone slice.
Treatment of Established Postmenopausal Osteoporosis with Raloxifene: A Randomized Trial
Authors: Lufkin Edward G. , Whitaker Michael D. , Nickelsen Thomas , Argueta Rodolfo , Caplan Robert H. , Knickerbocker Ronald K. , Riggs B. Lawrence 
Published: April 2006

Abstract
Raloxifene is a selective estrogen receptor modulator that in experimental animals acts as an estrogen receptor antagonist in breast and endometrium but as an estrogen receptor agonist in the skeletal and cardiovascular systems. We conducted a 1-year prospective, randomized, double-blind trial in 143 postmenopausal osteoporotic women (mean ± SD age, 68.4 ± 5.0 years) with at least one prevalent vertebral fractures and low bone mineral density (BMD), comparing groups receiving raloxifene at 60 mg/day (RLX60) or 120 mg/day (RLX120) and a control group receiving supplements of 750 mg/day of calcium and 400 IU/day of vitamin D. There were no differences among groups in the occurrence of uterine bleeding, thrombophlebitis, breast abnormalities, or increased endometrial thickness (assessed by ultrasonography). As compared with controls, the changes in values over 1 year for RLX60 and RLX120, respectively, were significant for serum bone alkaline phosphatase (−14.9%, −8.87%), serum osteocalcin (−20.7%, −17.0%), and urinary C-telopeptide fragment of type I collagen/creatinine (−24.9%, −30.8%), markers of bone turnover; for serum total cholesterol (−7.0% for RLX60) and low density lipoprotein cholesterol (LDL) (−11.4% for RLX60) and for the LDL/HDL cholesterol ratio (−13.2%, −8.3%). BMD increased significantly in the total hip (1.66% for RLX60) and ultradistal radius (2.92%, 2.50%). There were nonsignificant trends toward increases over controls in BMD for lumbar spine, total body, and total hip (for RLX120). Using a &gt;15% cutoff definition, raloxifene had no effect on incident fractures, but using a &gt;30% cutoff, there was a dose-related reduction (p = 0.047). We conclude that raloxifene therapy is well tolerated, reduces serum lipids, and does not stimulate the uterus or breasts. It has beneficial effects on bone, although, under the conditions of this study, these appear to be of a smaller magnitude than have been reported with estrogen therapy.
Intermittent Use of Nitrates Increases Bone Mineral Density: The Study of Osteoporotic Fractures
Authors: Jamal Sophie A. , Browner Warren S. , Bauer Douglas C. , Cummings Steven R. 
Published: April 2006

Abstract
Nitric oxide slows bone remodeling and bone loss in animals. Because nitroglycerin and other nitrates increase nitric oxide levels, we hypothesized that nitrate use may be associated with greater bone mineral density (BMD) and decreased risk of fracture in humans. Further, intermittent nitrate use may be associated with greater benefits than daily nitrate use, which results in tachyphylaxis. We tested this hypothesis using data from the Study of Osteoporotic Fractures. We prospectively studied 6201 elderly women of whom 317 took nitrates on a daily basis and 74 used them intermittently. We measured BMD at the hip and the heel and adjusted all comparisons for multiple potential confounders. We found that women taking daily nitrates had slightly greater hip BMD (difference, 1.3%; 95% confidence interval [CI], 0.14–4.1%) but the same heel BMD (difference, 0%; 95% CI −2.6–2.6%) as nonusers. By contrast, women using nitrates intermittently had substantially greater hip (difference, 2.6%; 95% CI, 0.4–6.8%) and heel BMD (difference, 5.3%; 95% CI, 2.6–11%) than nonusers. This study suggests that the intermittent administration of nitrates may enhance BMD.
Mechanical Loading Stimulates Bone Formation by Reactivation of Bone Lining Cells in 13-Week-Old Rats
Authors: Chow J. W. M. , Wilson A. J. , Chambers T. J. , Fox S. W. 
Published: April 2006

Abstract
The bone formation that occurs in response to mechanical stimulation is generally considered to be a means by which bone adapts to changes in its mechanical environment. We have previously shown that the expression of genes for bone matrix proteins is maximal 72 h after a single 5-minute episode of loading of tail vertebrae of 13-week-old female rats, that the predominant increase in mineralization occurs after 3 days, and that the osteogenic response to mechanical stimulation is not dependent on prior bone resorption. We have now investigated the cellular correlates of this osteogenic response. No proliferation was detected, by pulse or flash labeling, in the trabecular bone surface cells of animals killed 1 h to 10 days after the loading episode. Ultrastructural examination revealed that most of the cells covering the trabecular bone surface of control vertebrae were flat bone lining cells. After mechanical stimulation, the trabecular bone surface cells developed ultrastructural features of osteoblastic differentiation and activity, with acquisition of an increasingly cuboidal shape, rounded nuclei, and abundant rough endoplasmic reticulum. Morphometric analysis of the mean cell area, mean nuclear area, and cell and nuclear height showed that they were all maximal 48 h after loading. By 120 h after loading, the appearances of bone surface cells had reverted to those of control vertebrae. Thus, mechanical loading appears to activate lining cells, with a temporal sequence that correlates with bone matrix production.