bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Effects of Teriparatide on BMD After Treatment With Raloxifene or Alendronate
Authors: Ettinger Bruce , Martin San Javier , Crans Gerald , Pavo Imre 
Published: April 2006

Abstract
We investigated the effects of 18 months of treatment with teriparatide in patients previously treated with long-term antiresorptive therapy using bone turnover markers and bone densitometry. Previous raloxifene treatment allowed for teriparatide-induced early bone marker and BMD increases comparable with previously published results for treatment-naïve patients. Conversely, previous alendronate treatment reduced the bone marker and BMD response.
Introduction: Teriparatide [rhPTH(1–34)] has been shown to increase BMD and reduce the risk of fracture in postmenopausal women with osteoporosis. Our objective was to investigate the skeletal effects of 18 months of treatment with teriparatide in women whose osteoporosis was previously treated with either alendronate or raloxifene.
Materials and Methods: Daily subcutaneous injections of 20 μg teriparatide were administered for 18 months to 59 postmenopausal women, 60–87 years of age, with BMD T-scores ≤ −2.0 who had previously received either alendronate (ALN) or raloxifene (RLX) therapy for 18–36 months. All patients received daily calcium (1000 mg) and vitamin D (400 IU) supplementation. The primary study outcome was change in lumbar spine BMD measured by DXA. Secondary outcomes included changes in bone turnover markers, total hip BMD, and safety.
Results: Median baseline bone turnover marker levels in prior ALN patients were about one-half those of prior RLX patients. During teriparatide treatment, bone markers in prior ALN patients increased later and peaked at about one-third lower levels compared with prior RLX patients. During the first 6 months, there were statistically significant (p &lt; 0.05) group differences in BMD change at the hip (prior ALN −1.8% versus prior RLX +0.5%) and at the spine (prior ALN +0.5% versus prior RLX +5.2%). The positive slopes in hip and lumbar spine BMD were similar in both groups between 6 and 18 months. After 18 months, mean lumbar spine BMD increased 10.2% in prior RLX compared with 4.1% in prior ALN (p &lt; 0.05) patients. Furthermore, at 18 months, mean total hip BMD had significantly increased (1.8%, p &lt; 0.05) in prior RLX patients but was not different from baseline in prior ALN patients.
Conclusions: Teriparatide treatment stimulates bone turnover in patients pretreated with both RLX and ALN. Prior treatment with RLX allows for the expected teriparatide-induced BMD increases comparable with those previously reported for treatment-naïve patients. In contrast, prior treatment with ALN prevents increases in BMD, particularly in the first 6 months.
Cortical Bone in the Human Femoral Neck: Three-Dimensional Appearance and Porosity Using Synchrotron Radiation
Authors: Bousson Valérie , Peyrin Françoise , Bergot Catherine , Hausard Marc , Sautet Alain , Laredo Jean-Denis 
Published: April 2006

Abstract
A high-resolution CT system using synchrotron radiation allowed visualization of the 3D cortical bone microarchitecture and measurement of intracortical porosity of femoral neck cortical bone specimens from 19 female cadavers imaged at 10.13-μm resolution. 3D reconstruction of specimens showed osteonal system arrangement. Mean porosity was 15.88%. This technique will provide insights into the mechanisms involved in osteoporotic hip fractures.
Introduction: The purpose of this study was to show that a high-resolution CT system using synchrotron radiation (SR) allows visualization of the 3D cortical bone microarchitecture of the human femoral neck and quantification of intracortical porosity.
Materials and Methods: Bone specimens from the inferior femoral neck were obtained from 19 female cadavers with no hip fracture (mean, 86.9 ± 8.3 years). The specimens, consisting of embedded ∼7 × 7 × 12-mm cortical bone parallelepipeds, were imaged using SR at 10.13-μm resolution. Commercial software was used to visualize both the 660 × 660 × 660-voxel volumes and the 2D axial slices through each volume. Qualitative examination of 2D axial slices focused on the appearance of the vessel canal system, presence of small bright zones (fully mineralized tissue) in the osseous matrix, and presence of cracks. A method was developed to automatically measure 3D intracortical porosity after separating pure bone from pores and cortical bone from trabecular bone.
Results and Conclusions: 3D reconstruction of the specimens showed the entire structure and arrangement of the osteonal systems, parallel to the axis of the femoral neck. Bright zones were seen in the outer cortex. No cracks were observed. Porosity values varied widely from 4.96% to 38.87% (mean, 15.88 ± 9.87%). This study establishes that SR microtomography can be used to display the 3D bone microstructure of the human femoral neck cortex and to quantify intracortical porosity. This technique will provide insights into the mechanisms involved in cortical bone loss and osteoporotic hip fractures.
Treatment of Idiopathic Hyperphosphatasia With Intensive Bisphosphonate Therapy
Authors: Cundy Tim , Wheadon Lisa , King Alan 
Published: April 2006

Abstract
In a family with IH, a rare high turnover bone disease, two older siblings were wheelchair-bound with severe skeletal deformity by age 15. Their youngest affected sibling was treated intensively with intravenous bisphosphonates for 3 years. The treatment was well tolerated and prevented the development of deformity and disability.
Introduction: Idiopathic hyperphosphatasia (IH, also known as juvenile Paget's disease) is a rare genetic bone disease characterized by very high bone turnover and progressive bony deformity. Inhibitors of bone resorption have been used to suppress bone turnover in the short term, but there is no published data on long-term efficacy.
Materials and Methods: An 11-year-old girl with IH, who had two severely affected older siblings, presented with progressive deformity and deafness and long bone fractures. Conventional pediatric doses of pamidronate had failed to prevent clinical deterioration or suppress bone turnover completely. Intensive bisphosphonate therapy (frequent 5-mg ibandronate infusions) was given to try and arrest progression of the skeletal disease. Growth and development, pure tone audiometry, biochemistry, radiology, densitometry (DXA), and bone histology were monitored.
Results: A total of 45 mg ibandronate was given over 3 years until skeletal maturity was reached (20, 15, and 10 mg for years 1–3, respectively). Ibandronate treatment was well tolerated, and biochemical markers of bone turnover suppressed to within the age-appropriate normal range There was some progression of her thoracic kyphosis, but she had no further fractures and remained mobile and active at an age when her siblings had become wheelchair-bound. A significant recovery of hearing (p &lt; 0.01) was documented, particularly at low frequencies. Radiographs showed improvement in spinal osteoporosis and cortical bone dimensions and arrest of progressive acetabular protrusion. Areal bone density increased substantially (lumbar spine z-score from −2.2 to + 1.8). Tetracycline-labeled bone biopsy specimens were taken before and after 18 months of intensive treatment. The second biopsy showed suppression of bone turnover and a doubling of trabecular thickness, with no mineralization defect, and no osteopetrosis.
Conclusions: Intensive bisphosphonate treatment prevented the development of deformity and disability and improved hearing in this child with IH. The dose of bisphosphonate, which is substantially greater than is usually used in pediatric bone disease, had no adverse effects, in particular on bone mineralization.
Low Magnitude Mechanical Loading Is Osteogenic in Children With Disabling Conditions
Authors: Ward Kate , Alsop Chrissie , Caulton Janette , Rubin Clinton , Adams Judith , Mughal Zulf 
Published: April 2006

Abstract
The osteogenic potential of short durations of low-level mechanical stimuli was examined in children with disabling conditions. The mean change in tibia vTBMD was +6.3% in the intervention group compared with −11.9% in the control group. This pilot randomized controlled trial provides preliminary evidence that low-level mechanical stimuli represent a noninvasive, non-pharmacological treatment of low BMD in children with disabling conditions.
Introduction: Recent animal studies have demonstrated the anabolic potential of low-magnitude, high-frequency mechanical stimuli to the trabecular bone of weight-bearing regions of the skeleton. The main aim of this prospective, double-blind, randomized placebo-controlled pilot trial (RCT) was to examine whether these signals could effectively increase tibial and spinal volumetric trabecular BMD (vTBMD; mg/ml) in children with disabling conditions.
Materials and Methods: Twenty pre-or postpubertal disabled, ambulant, children (14 males, 6 females; mean age, 9.1 ± 4.3 years; range, 4–19 years) were randomized to standing on active (n = 10; 0.3g, 90 Hz) or placebo (n = 10) devices for 10 minutes/day, 5 days/week for 6 months. The primary outcomes of the trial were proximal tibial and spinal (L2) vTBMD (mg/ml), measured using 3-D QCT. Posthoc analyses were performed to determine whether the treatment had an effect on diaphyseal cortical bone and muscle parameters.
Results and Conclusions: Compliance was 44% (4.4 minutes per day), as determined by mean time on treatment (567.9 minutes) compared with expected time on treatment over the 6 months (1300 minutes). After 6 months, the mean change in proximal tibial vTBMD in children who stood on active devices was 6.27 mg/ml (+6.3%); in children who stood on placebo devices, vTBMD decreased by −9.45 mg/ml (−11.9%). Thus, the net benefit of treatment was +15.72 mg/ml (17.7%; p = 0.0033). In the spine, the net benefit of treatment, compared with placebo, was +6.72 mg/ml, (p = 0.14). Diaphyseal bone and muscle parameters did not show a response to treatment. The results of this pilot RCT have shown for the first time that low-magnitude, high-frequency mechanical stimuli are anabolic to trabecular bone in children, possibly by providing a surrogate for suppressed muscular activity in the disabled. Over the course of a longer treatment period, harnessing bone's sensitivity to these stimuli may provide a non-pharmacological treatment for bone fragility in children.
Assessing Bone Status Beyond BMD: Evaluation of Bone Geometry and Porosity by Quantitative Ultrasound of Human Finger Phalanges
Authors: Sakata Satoru , Barkmann Reinhard , Lochmüller Eva-Maria , Heller Martin , Glüer Claus-Christian 
Published: April 2006

Abstract
In an in vitro study, we found significant associations between QUS variables and properties and geometrical parameters of the compact bone of human finger phalanges. QUS variables were not only related to BMD but also to other skeletal properties, which explained 70% of the variability of speed of sound.
Introduction: Transverse transmission quantitative ultrasound (QUS) measurements at the finger phalanges are known to be correlated with BMD and to predict osteoporotic fractures. To determine which other skeletal properties are affected by ultrasound, we investigated the impact of density, geometry, and porosity on QUS variables in vitro.
Materials and Methods: Ultrasound variables were correlated with density, porosity, and geometrical characteristics of cortical bone. Additionally, we tested which combinations of geometry and bone properties best predicted the ultrasound results observed. Forty-four proximal phalanges from the middle finger were investigated at their distal metaphysis, similar to the typical clinical measurement procedure. Donor age ranged from 52 to 98 years (15 males and 29 females; mean age, 80.9 ± 9.4 years). QUS variables were measured on the metaphysis of the phalanges using the DBMSonic 1200. Quantitative CT was used for the measurement of BMD, and high-resolution MRI was used for the measurement of porosity and geometrical variables.
Results: Speed of sound (SOS) and the clinically used variable AD-SOS correlated significantly with area, relative area, density, and porosity of the compact bone (R2 = 0.28-0.58, p &lt; 0.0001). Signal amplitude correlated significantly only with relative area of the compact bone and area of the medullary canal (R2 = 0.18-0.20, p &lt; 0.01). The combination of cortical area, density, and porosity improved the determination of SOS to R2 = 0.70, with a residual unexplained variability of 54 m/s (3.2%).
Conclusions: These results clarify the impact of skeletal properties on QUS variables. SOS is affected by cortical area, cortical bone density, and cortical porosity, whereas attenuation only depends on geometry of the medulla. AD-SOS, the variable routinely measured in clinical practice, is primarily affected by cortical area. QUS of the finger phalanges is not only related to BMD but also to other skeletal properties.
Genetics of Bone Mineral Density: Evidence for a Major Pleiotropic Effect From an Intercontinental Study
Authors: Livshits Gregory , Deng Hong-Wen , Nguyen Tuan V , Yakovenko Konstantin , Recker Robert R , Eisman John A 
Published: April 2006

Abstract
BMD is a primary predictor of osteoporotic fracture, and its genetic determination is still unclear. This study showed that the correlation between BMD at different skeletal sites is caused by an underlying genetic structure of common genetic effects. In addition to possible shared (pleiotropic) genetic and environmental effects, each of the BMD variables may also be determined by site-specific genetic factors.
Introduction: BMD is a primary predictor of osteoporotic fracture and a key phenotype for the genetic study of osteoporosis. The interindividual variation in BMD measured at a given skeletal site is largely regulated by genetic factors. A strong phenotypic covariation exists for BMD at different skeletal sites. This study tests the hypothesis that the covariation is in fact caused by an underlying genetic structure of common genetic effects and that, in addition to possible shared (pleiotropic) genetic effects, each of the BMD variables may also be determined by site-specific genetic factors
Materials and Methods: A bivariate complex segregation analysis as implemented in statistical package PAP was conducted to explore various models of pleiotropic genetic and environmental transmission in lumbar spine and femoral neck BMD, as well as in compact and spongious segments of hand phalanges. The BMD was obtained in three ethnically, culturally, and socially heterogeneous samples of white pedigrees, with 2549 individuals between 18 and 100 years of age, from Australia, Europe, and North America.
Results and Conclusions: The genetic correlation between BMD measures ranged between 0.50 ± 0.09 and 0.79 ± 0.04 in the three samples. In each sample, the model incorporated a major locus pleiotropic effect, and residual correlation was found to be the most parsimonious model. Estimated parameters from the model indicated a significant pleiotropic major gene effect on both lumbar spine and femoral neck BMD, with the existence of a significant residual correlation (0.51 ± 0.07 to 0.66 ± 0.04). These results suggest that the covariation in BMD at different skeletal sites, and between mostly compact versus mostly trabecular bone, was largely determined by common genetic factors that are pleiotropic or in close linkage and linkage disequilibirum, while at the same time, exhibiting considerable evidence of shared environmental effects. The results, for the first time, suggest that the possibility of pleiotropic genetic effect may be controlled by a major genetic locus. Identification of the major locus could open new opportunity to understanding the liability and pathogenic processes in which they are involved in the determination of fracture risk.
Female Premenopausal Fracture Risk Is Associated With Gc Phenotype
Authors: Lauridsen Anna Lis , Vestergaard Peter , Hermann Anne Pernille , Moller Holger Jon , Mosekilde Leif , Nexo Ebba 
Published: April 2006

Abstract
The phenotype of the vitamin D binding and macrophage activating protein, Gc, is a predictor of premenopausal bone fracture risk, possibly mediated through activation of osteoclasts. This was concluded from a study on 595 Danish perimenopausal women 45-58 years of age (30,040 person years).
Introduction: The multifunctional plasma protein Gc, also known as group-specific component, Gc globulin, or vitamin D binding protein (DBP), has two functions with relation to bone tissue: it is the major carrier protein of vitamin D in the circulation, and deglycosylation converts it into a very potent macrophage- and osteoclast-activating factor (Gc-MAF). There are several phenotypes of Gc, and in this study, we examined the relation between Gc phenotype and bone fragility.
Materials and Methods: By isoelectric focusing we identified the Gc phenotype of 595 white recent postmenopausal women enrolled into the Danish Osteoporosis Prevention Study (DOPS) and identified three groups: Gc1-1 (n = 323), Gc1-2 (n = 230), and Gc2-2 (n = 42). Differences between the three groups were examined with respect to number of fractures before enrollment, BMC and BMD, and various biochemical and clinical parameters, including the concentration of Gc measured by immunonephelometry and the concentration of the macrophage marker soluble CD163 measured by ELISA.
Results and Conclusions: The risk of having at least one premenopausal bone fracture (total number of women with fracture = 179) differed significantly (p = 0.017) in women with phenotype Gc1-1 (110/323 = 0.34), Gc1-2 (63/230 = 0.27), and Gc2-2 (6/42 = 0.14). The differences were even more striking (p = 0.005) for fractures caused by low-energy traumas. Using logistic regression, we found the relative risk of premenopausal fracture to be 0.32 (0.13-0.80) in Gc2-2 compared with Gc1-1. We propose that the Gc phenotypes cause differences in osteoclast activity, a theory supported by our finding of lower levels of Gc and of soluble CD163 in women with Gc2-2 compared with Gc1-1.
A Meta-Analysis of Prior Corticosteroid Use and Fracture Risk
Authors: Kanis John A , Johansson Helena , Oden Anders , Johnell Olof , de Laet Chris , Melton L Joseph , Tenenhouse Alan , Reeve Jonathan , Silman Alan J , Pols Huibert AP , Eisman John A , McCloskey Eugene V , Mellstrom Dan 
Published: April 2006

Abstract
The relationship between use of corticosteroids and fracture risk was estimated in a meta-analysis of data from seven cohort studies of ∼42,000 men and women. Current and past use of corticosteroids was an important predictor of fracture risk that was independent of prior fracture and BMD.
Introduction: The aims of this study were to validate that corticosteroid use is a significant risk factor for fracture in an international setting and to explore the effects of age and sex on this risk.
Materials and Methods: We studied 42,500 men and women from seven prospectively studied cohorts followed for 176,000 patient-years. The cohorts comprised the EPOS/EVOS study, CaMos, the Rotterdam Study, Dubbo Osteoporosis Epidemiology Study (DOES), and prospective cohorts at Sheffield, Rochester, and Gothenburg. The effect of ever use of corticosteroids, BMD, age, and sex on all fracture, osteoporotic fracture, and hip fracture risk alone was examined using Poisson regression in each cohort and for each sex. The results of the different studies were merged from the weighted β coefficients.
Results: Previous corticosteroid use was associated with a significantly increased risk of any fracture, osteoporotic fracture, and hip fracture when adjusted for BMD. Relative risk of any fracture ranged from 1.98 at the age of 50 years to 1.66 at the age of 85 years. For osteoporotic fracture, the range of relative risk was 2.63-1.71, and for hip fracture 4.42-2.48. The estimate of relative risk was higher at younger ages, but not significantly so. No significant difference in risk was seen between men and women. The risk was marginally and not significantly upwardly adjusted when BMD was excluded from the model. The risk was independent of prior fracture. In the three cohorts that documented current corticosteroid use, BMD was significantly reduced at the femoral neck, but fracture risk was still only partly explained by BMD.
Conclusion: We conclude that prior and current exposure to corticosteroids confers an increased risk of fracture that is of substantial importance beyond that explained by the measurement of BMD. Its identification on an international basis validates the use of this risk factor in case-finding strategies.
Arthritis Induces Lymphocytic Bone Marrow Inflammation and Endosteal Bone Formation
Authors: Görtz Birgit , Hayer Silvia , Redlich Kurt , Zwerina Jochen , Tohidast-Akrad Makyieh , Tuerk Birgit , Hartmann Christine , Kollias George , Steiner Günter , Smolen Josef S , Schett Georg 
Published: April 2006

Abstract
Arthritis can destroy the cortical bone barrier and expose bone marrow to synovial tissue. This study examines bone marrow changes in arthritis and its effects on cortical bone remodeling. Bone marrow next to arthritic lesions exhibits B-lymphocyte-rich infiltrates, which express BMPs and stimulate endosteal bone formation. Thus, bone marrow actively participates in the arthritic process.
Introduction: Imaging studies have shown that bone marrow changes occur in patients with rheumatoid arthritis (RA). To examine whether bone marrow is affected during arthritis, human TNF transgenic (hTNFtg) mice, which constitute an established animal model of human RA, were examined for bone marrow changes.
Materials and Methods: The hind paws (tarsal area) of 22 untreated hTNFtg mice, 5 hTNFtg mice treated with anti-TNF (infliximab), and 5 wildtype (WT) mice were examined histologically, immunohistochemically, and by means of mRNA in situ hybridization.
Results and Conclusions: All untreated hTNFtg mice with moderate (n = 10) and severe (n = 7) disease developed inflammatory bone marrow lesions during the course of disease, whereas no such lesions appeared in hTNFtg mice with mild disease (n = 5) and WT mice. Bone marrow infiltrates were almost exclusively composed of lymphocytes, and the overwhelming proportion (&gt;80%) was B-cells. Presence and extent of bone marrow infiltrates were closely linked to severity of arthritis. In addition, blockade of TNF effectively reduced bone marrow inflammation. Interestingly, osteoblast numbers were increased at the endosteal surface in the vicinity of these lesions. Moreover, osteoid deposition; expression of bone matrix proteins, such as osteocalcin and osteopontin; and mineralization were enhanced, suggesting that inflammatory bone marrow infiltrates induce bone formation. Indeed, B-lymphocytes of these lesions expressed bone morphogenetic protein (BMP)-6 and −7, which are important stimulators of new bone formation. Thus, we conclude that bone marrow actively participates in destructive arthritis by generating B-lymphocyte-rich bone marrow lesions and inducing endosteal bone formation.