bluuebunny/crossref_metadata_2025_split huggingface dataset:
Calciotropic Hormones and Bone Markers in the Elderly
Authors: Gallagher J. Christopher , Kinyamu H. Karimi , Fowler Sarah E. , Dawson-Hughes Bess , Dalsky Gail P. , Sherman Sherry S. 
Published: April 2006

Abstract
There is a lack of substantial data on changes in calciotropic hormones and bone markers in elderly subjects living in North America. Parathyroid hormone (PTH), serum 25-hydroxyvitamin D (25(OH)D) and bone markers (serum osteocalcin and urine N-telopeptide), were measured in 735 Caucasian subjects (235 men and 500 women) aged 65–87 years. There was a significant increase in serum osteocalcin and urine N-telopeptide with age in men, and a significant increase in serum osteocalcin with age in women. Serum PTH and 25(OH)D showed no significant change with age in men or women. After adjusting for age, calcium intake, serum creatinine, season, and weight, mean serum PTH (p = 0.01), serum osteocalcin (p = 0.0001) and 24 h urine N-telopeptide (p = 0.0001) were higher in women than men, and mean serum 25(OH)D (p = 0.0001) and 24 h urine calcium (p = 0.0001) were higher in men than women. Serum PTH was correlated with serum osteocalcin in men and women, r = 0.24, r = 0.17, p &lt; 0.001, but not with urine N-telopeptide. Serum PTH was inversely correlated with serum 25(OH)D (r = −0.25, r = −0.34, p &lt; 0.001), and positively correlated with serum creatinine (r = 0.14, r = 0.17, p &lt; 0.01) in men and women. The prevalence of serum 25(OH)D levels below 12 ng/ml was only 3.3% in females and 0.4% in men. Thus vitamin D deficiency was very uncommon in the U.S.A. compared with Europe. Although mean serum PTH was increased in the elderly, only 4–6% had PTH levels above the normal range. In summary, the increase in serum PTH in the elderly can be explained more by changes in vitamin D status than by declining renal function. These data also show significantly higher (p = 0.001) bone remodeling markers in women.
Bone Turnover Response to Changes in Calcium Intake Is Altered in Girls and Adult Women in Families with Histories of Osteoporosis
Authors: O'Brien Kimberly O. , Abrams Steven A. , Liang Lily K. , Ellis Kenneth J. , Gagel Robert F. 
Published: April 2006

Abstract
Heredity and environmental factors contribute to the development of osteoporosis. Because calcium is the major mineral in bone and adolescence is a key period in bone acquisition, we hypothesized that bone turnover would be less responsive to alterations in dietary calcium intake in both girls and adult women from families with histories of osteoporosis. To address this issue, we studied calcium kinetics in the maternal grandmother (age range 56–81 years), mother (age range 32–47 years), and granddaughter (age range 8–15 years) in 10 multigenerational families. In five families, the mother and/or grandmother had osteoporosis (bone mineral density ≥ 2 SD below the age-specific mean). To examine both active and passive calcium absorption, families consumed low- (279 ± 64 mg/day) and high- (1580 ± 385) calcium diets for 10 days prior to administration of oral (46Ca) and intravenous (42Ca) stable isotopes. Using repeated measures analysis of variance, fractional calcium absorption, true calcium absorption, bone calcium deposition, and the balance in bone calcium turnover were all significantly affected by diet (p &lt; 0.01). Females from nonosteoporotic families had decreased bone calcium resorption with little change in bone calcium deposition during the high-calcium study. In contrast, girls and adult women from osteoporotic families had increased both bone calcium deposition and resorption during the high-calcium period, leading to a less positive balance in bone calcium turnover. A significant interaction between bone status and diet was found for bone calcium resorption (p &lt; 0.05) and approached significance for bone calcium deposition (p &lt; 0.07), effects which were independent of generation. We conclude that girls and women from osteoporotic families have a significantly altered bone turnover response to acute changes in calcium intake.
Alendronate Does Not Block the Anabolic Effect of PTH in Postmenopausal Osteoporotic Women
Authors: Cosman Felicia , Nieves Jeri , Woelfert Lillian , Shen Victor , Lindsay Robert 
Published: April 2006

Abstract
In rodent osteoporosis models, anabolic activity of parathyroid hormone (PTH) is preserved in the presence of antiresorptive agents. Anabolic activity is also preserved when PTH is administered to estrogenized postmenopausal women. In contrast, in the ewe treated with tiludronate, PTH-induced stimulation of bone turnover did not occur. To determine whether PTH in combination with alendronate could be a viable treatment for osteoporosis, we performed a short-term study of postmenopausal women with osteoporosis (n = 10) already on alendronate 10 mg/day to determine whether PTH could increase bone formation assessed biochemically. Patients continued alendronate alone (n = 5) or continued alendronate with 400 IU/day subcutaneous human PTH(1–34) added for 6 weeks. Subjects receiving PTH had serum and urine sampling weekly during PTH treatment and for 5 weeks thereafter. Sampling was performed approximately biweekly for subjects who had been on alendronate alone for 11 weeks. Samples were analyzed for osteocalcin (OC), propeptide of type I procollagen (PICP), bone-specific alkaline phosphatase (BSAP), cross-linked urinary N-telopeptide (NTX), and free urinary pyridinoline (PYD). Markers of bone formation increased within 3 weeks in the PTH plus alendronate group, with mean peak levels at 5–7 weeks: OC 49%, p &lt; 0.01; PICP 61%, p &lt; 0.01; and BSAP 24%, p = 0.12. Levels returned to baseline after discontinuing PTH, with PICP declining the most rapidly. There were no significant changes at any time in the alendronate alone group. There were no increments in either urinary NTX or PYD in either treatment group throughout the observation period. The bone turnover marker changes seen with PTH plus alendronate were similar to those seen with PTH plus hormone replacement. These data suggest that: PTH can stimulate bone formation, evidenced by elevations of bone formation markers, even in the presence of a potent bisphosphonate; in the presence of alendronate, PTH-stimulated bone formation precedes stimulation of bone resorption, suggesting that PTH stimulates bone formation de novo; and the combination of PTH and alendronate may be a viable treatment option for postmenopausal women with osteoporosis.
Recombinant Human Basic Fibroblast Growth Factor Accelerates Fracture Healing by Enhancing Callus Remodeling in Experimental Dog Tibial Fracture
Authors: Nakamura Toshiyuki , Hara Yasushi , Tagawa Masahiro , Tamura Makoto , Yuge Takuro , Fukuda Hiroshi , Nigi Hideo 
Published: April 2006

Abstract
Effect of recombinant human basic fibroblast growth factor (bFGF) on fracture healing was investigated using a tibial fracture in beagle dogs. Transverse fractures in the middle of the diaphyses were created in the right tibiae and bFGF was injected into the fracture sites at a single dose of 200 μg. The time course of changes in callus volume and morphology of the fracture sites were evaluated at weeks 2, 4, 8, 16, and 32 after treatment, and the fracture strength was analyzed at weeks 16 and 32. At week 2, a radiogram of the fracture site showed obvious membranous ossification in the group injected with bFGF. Basic FGF extended the callus area at week 4 and increased the bone mineral content (BMC) in the callus at week 8. bFGF also increased the osteoclast number in the periosteal callus at weeks 2 and 4. In the bFGF group, a maximal increase in the osteoclast index was found at week 4, and an identical increase was recognized in the control group at weeks 8 and 16. These findings strongly suggested that bFGF stimulated not only callus formation but osteoclastic callus resorption. BMC in the bFGF group was followed by a rapid decrease from week 8, while that in the control group was identical from week 4. Fracture strength of the bFGF group showed significant recovery by week 16, and recovery was still evident by week 32. We conclude that bFGF promotes the fracture healing in dogs by the stimulation of bone remodeling.
No Difference in Intestinal Strontium Absorption After an Oral or an Intravenous 1,25(OH)2D3 bolus in Normal Subjects
Authors: Bianchi M. L. , Ardissino G. L. , Schmitt C. P. , Daccó V. , Barletta L. , Claris-Appiani A. , Mehls O. ,   FOR THE EUROPEAN STUDY GROUP ON VITAMIN D IN CHILDREN WITH RENAL FAILURE
Published: April 2006

Abstract
It has been suggested that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) stimulates intestinal calcium absorption less via the intravenous (iv) than the oral route, because the first avoids direct contact of the drug with the enterocytes. However, no study has addressed the issue directly. This investigation was designed to measure the effect of a single oral or iv dose of 1,25(OH)2D3 on calcium absorption, using stable strontium (Sr) as a surrogate for calcium, and measuring the Sr fractional absorbed dose (FAD%) over 240 minutes after Sr administration. In 10 healthy volunteers, five tests were performed in a cross-over design, with a wash-out period between two consecutive tests: Sr absorption without 1,25(OH)2D3 (test A); Sr absorption immediately after either oral (test B) or iv (test C) 1,25(OH)2D3 (1.5 μg/m2 of body surface area [BSA]); Sr absorption (24 hr after either oral (test D) or iv (test E) 1,25(OH)2D3 (1.5 μg/m2 BSA). The concurrent administration of 1,25(OH)2D3 and Sr (tests B and C) did not significantly change the area under the Sr FAD%–time curve with respect to test A (test A: 4090 ± 345; test B: 4510 ± 345; test C: 4210 ± 345), whereas Sr absorption was significantly increased (p &lt; 0.001) when Sr was given 24 hr after either oral or iv 1,25(OH)2D3 (test D: 5710 ± 345; test E: 5510 ± 345). It was concluded that 1,25(OH)2D3 is likely to influence calcium absorption significantly only via its genomic effect, independent of its administration route.
Recurrence of Vertebral Fracture with Cyclical Etidronate Therapy in Osteoporosis: Histomorphometry and X-Ray Microanalysis Evaluation
Authors: Thomas Thierry , Barou Odile , Vico Laurence , Alexandre Christian , Lafage-Proust Marie-Helene 
Published: April 2006

Abstract
In an open prospective study, we evaluated differences between patients with (wRVF group) and without recurrence of vertebral fracture (woRVF group) during cyclical etidronate therapy for osteoporosis. Thirty-two patients (age 64 ± 1.8 years) characterized by at least one osteoporotic VF were treated during 1 year. At baseline, body mass index was significantly lower (23.3 ± 0.6 vs. 26.9 ± 1.0 kg/m2, p&lt; 0.05), the number of previous VFs was higher (4.0 ± 0. 4 vs. 2.4 ± 0.4, NS), and patients were older in the wRVF group as compared with the woRVF group (67.8 ± 3 vs. 62.6± 2.2 year, NS). Trabecular bone volume (11.6 ± 1.2 vs. 15 ± 0.9%, p&lt; 0.05) and trabecular number (1.06 ± 0.08 vs. 1.27 ± 0.05, p &lt; 0.05) were significantly lower in the wRVF group. None of the baseline resorptive variables differed, whereas the bone formation rate (BFR) was 2-fold lower in the wRVF group (p&lt; 0. 05). After 1 year of treatment, osteoclast number, active eroded surfaces, and resorption depth dramatically decreased in both groups (p&lt; 0.01). To a lesser extent, the mineral apposition rate and serum alkaline phosphatase level were significantly reduced (p&lt; 0.05). No impaired mineralization was observed. Using X-ray microanalysis, we found no abnormality in bone mineral but a significant increase of the calcium/phosphorus ratio during treatment in the wRVF group. Our results demonstrate that recurrence of VFs within the first year of cyclical etidronate therapy was related neither to a lack of histologic response to the treatment nor induction of an abnormality of mineralization. VFs were more likely in the presence of a decreased BFR and lower trabecular connectivity, providing support for treating osteoporotic patients with etidronate early in the course of the disease.
Mechanism of Bone Loss After Liver Transplantation: A Histomorphometric Analysis
Authors: Vedi Shobna , Greer Shaun , Skingle Susan J. , Garrahan Nigel J. , Ninkovic Mary , Alexander Graeme A. , Dr. Compston Juliet E. 
Published: April 2006

Abstract
Organ transplantation is associated with increased bone loss and high fracture risk, but the pathophysiological mechanisms responsible have not been established. We have performed a histomorphometric analysis of bone remodeling before and 3 months after liver transplantation in 21 patients (14 male, 7 female) aged 38–68 years with chronic liver disease. Eight-micrometer undecalcified sections of trans-iliac biopsies were assessed using image analysis. Preoperatively, bone turnover was low with a tendency toward reduced wall width and erosion depth. The bone formation rate increased from 0.021 ± 0.016 (mean ± SD) to 0.067 ± 0.055 μm2/μm/day after transplantation (p &lt; 0.0002) and activation frequency from 0.24 ± 0.21/year−1 to 0.81 ± 0.67/year−1 (p &lt; 0.0001). No significant change was observed in wall width, but there was a trend toward an increase in indices of resorption cavity size. There was a small increase in osteoid seam width postoperatively (p&lt; 0.02) and decrease in mineralization lag time (p &lt; 0.001). No significant changes in indices of cancellous bone structure were observed in the postoperative biopsies. These results demonstrate a highly significant and quantitatively large increase in bone turnover in the first 3 months after liver transplantation. Although no significant disruption of cancellous bone structure was demonstrated during the time course of the study, the observed changes in bone remodeling predispose to trabecular penetration and may thus result in long-term adverse effects on bone strength.
Vitamin D Receptor Gene Fok1 Polymorphism Predicts Calcium Absorption and Bone Mineral Density in Children
Authors: Ames Sharla K. , Ellis Kenneth J. , Gunn Sheila K. , Copeland Kenneth C. , Abrams Steven A. 
Published: April 2006

Abstract
The vitamin D receptor (VDR) gene has been implicated as one of the major genetic components of osteoporosis. We evaluated the relationship between markers of mineral status and restriction fragment length polymorphisms of the VDR gene in 72 healthy children age 7–12 years. Using stable isotope techniques and dual-energy X-ray absorptiometry, we measured dietary calcium absorption, bone calcium deposition rates, and total body bone mineral density (BMD). The Fok1 polymorphism at the VDR translation initiation site was significantly associated with BMD (p = 0.02) and calcium absorption (p = 0.04). Children who were FF homozygotes had a mean calcium absorption that was 41.5% greater than those who were ff homozygotes and 17% greater absorption than Ff heterozygotes. BMD was 8.2% greater in the FF genotype than the ff genotype and 4.8% higher than the Ff genotype. These results suggest a substantial relationship between the VDR gene and bone metabolism at one or more levels, including dietary absorption of calcium and BMD in growing children.
Developmental Expression of Creatine Kinase Isoenzymes in Chicken Growth Cartilage
Authors: Hobson Grace M. , Funanage Vicky L. , Elsemore Jennifer , Yagami Machiko , Rajpurohit Ramesh , Perriard Jean-Claude , Hickok Noreen J. , Shapiro Irving M. , Tuan Rocky S. 
Published: April 2006

Abstract
We have shown previously that creatine kinase (CK) activity is required for normal development and mineralization of chicken growth cartilage and that expression of the cytosolic isoforms of CK is related to the biosynthetic and energy status of the chondrocyte. In this study, we have characterized changes in isoenzyme activity and mRNA levels of CK (muscle-specific CK, M-CK; brain-type CK, B-CK; and mitochondrial CK subunits, MiaCK and MibCK) in the growth plate in situ and in chondrocyte culture systems that model the development/maturation program of the cartilage. The in vitro culture systems analyzed were as follows: tibial chondrocytes, which undergo hypertrophy; embryonic cephalic and caudal sternal chondrocytes, which differ from each other in their mineralization response to retinoic acid; and long-term micromass cultures of embryonic limb mesenchymal cells, which recapitulate the chondrocyte differentiation program. In all systems analyzed, B-CK was found to be the predominant isoform. In the growth plate, B-CK expression was highest in the most calcified regions, and M-CK was less abundant than B-CK in all regions of the growth plate. In tibial chondrocytes, an increase in B-CK expression was seen when the cells became hypertrophic. Expression of B-CK increased slightly over 15 days in mineralizing, retinoic acid–treated cephalic chondrocytes, but it decreased in nonmineralizing caudal chondrocytes, while there was little expression of M-CK. Interestingly, in limb mesenchyme cultures, significant M-CK expression was detected during chondrogenesis (days 2–7), whereas hypertrophic cells expressed only B-CK. Finally, expression of MiaCK and MibCK was low both in situ and in vitro. These observations suggest that the CK genes are differentially regulated during cartilage development and maturation and that an increase in CK expression is important in initiating chondrocyte maturation.
Parathyroid Hormone Regulates the Expression of Fibroblast Growth Factor-2 mRNA and Fibroblast Growth Factor Receptor mRNA in Osteoblastic Cells
Authors: Hurley Marja M. , Tetradis Sotirios , Huang Yu-Feng , Hock Janet , Kream Barbara E. , Raisz Lawrence G. , Sabbieti Maria Giovanna 
Published: April 2006

Abstract
We examined the effect of parathyroid hormone (PTH) on basic fibroblast growth factor-2 (FGF-2) and FGF receptor (FGFR) expression in osteoblastic MC3T3-E1 cells and in neonatal mouse calvariae. Treatment of MC3T3-E1 cells with PTH(1–34) (10–8M) or forskolin (FSK; 10–5M) transiently increased a 7 kb FGF-2 transcript with a peak at 2 h. The PTH increase in FGF-2 mRNA was maintained in the presence of cycloheximide. PTH also increased FGFR-1 mRNA at 2 h and transiently increased FGFR-2 mRNA at 1 h. FGFR-3 and FGFR-4 mRNA transcripts were not detected in MC3T3-E1 cells. In cells transiently transfected with an 1800-bp FGF-2 promoter-luciferase reporter, PTH and FSK increased luciferase activity at 2 h and 4 h. Immunohistochemistry showed that PTH and FSK increased FGF-2 protein labeling in the nuclei of MC3T3-E1 cells. PTH also increased FGF-2 mRNA, and FGFR-1 and FGFR-2 mRNA levels within 30 minutes in neonatal mouse calvarial organ cultures. We conclude that PTH and cAMP stimulate FGF-2 mRNA abundance in part through a transcriptional mechanism. PTH also regulated FGFR gene expression. We hypothesize that some effects of PTH on bone remodeling may be mediated by regulation of FGF-2 and FGFR expression in osteoblastic cells.
Prevalent Vertebral Deformities Predict Hip Fractures and New Vertebral Deformities but Not Wrist Fractures
Authors: Black Dennis M. , Arden Nigel K. , Palermo Lisa , Pearson Jim , Cummings Steven R. ,   for the Study of Osteoporotic Fractures Research Group
Published: April 2006

Abstract
Although vertebral deformities are known to predict future vertebral deformities, little is known about their ability to predict other osteoporotic fractures. We examined the association between prevalent vertebral deformities and incident osteoporotic fractures in the Study of Osteoporotic Fractures, a prospective study of 9704 women aged 65 years and older. Prevalent vertebral deformities were determined morphometrically from spinal radiographs at baseline and incident deformities from repeat spinal radiographs after a mean of 3.7 years. Appendicular fractures were collected by postcard every 4 months for a mean of 8.3 years. During follow-up, 389 women with new vertebral deformities, 464 with hip fractures, and 574 with wrist fractures were identified. Prevalent vertebral deformities were associated with a 5-fold increased risk (relative risk 5.4, 95% confidence interval [CI] 4.4, 6.6) of sustaining a further vertebral deformity; the risk increased dramatically with both the number and severity of the prevalent deformities. Similarly, the risks of hip and any nonvertebral fractures were increased with baseline prevalent deformity, with relative risks of 2.8 (95% CI 2.3, 3.4) and 1.9 (95% CI 1.7, 2.1), respectively. Risk increased with number and severity of deformities. These associations remained significant after adjustment for age and calcaneal bone mineral density (BMD). Although there was a small increased risk of wrist fracture, this was not significant after adjusting for age and BMD. In conclusion, the presence of prevalent morphometrically defined vertebral deformities predicts future vertebral and nonvertebral fractures, including hip but not wrist fractures. Spinal radiographs identifying prevalent vertebral deformities may be a useful additional measurement to classify further a woman's risk of future fracture.
Failure to Detect the Extracellular Calcium-Sensing Receptor (CasR) in Human Osteoblast Cell Lines
Authors: Pi Min , Hinson Todd K. , Quarles L. Darryl 
Published: April 2006

Abstract
Whether the known calcium-sensing receptor (CasR) is present in osteoblasts is a source of considerable controversy. Prior studies failed to detect CasR in osteoblasts, but more recent investigations purport the detection of CasR in several osteoblast cell lines by immunoblot analysis with polyclonal anti-CasR antisera (4637) and low stringency reverse transcriptase-polymerase chain reaction (RT-PCR). To explain these disparate findings, we performed immunoblot analysis with the 4637 anti-CasR antisera and a highly specific monoclonal antibody to CasR (ADD), and we compared the ability of low and high stringency RT-PCR to amplify CasR transcripts. We found that the ADD antibody detected the anticipated CasR immunoreactive bands, including a ∼165 kDa and ∼140 kDa glycosylated doublet and a &gt;250 kDa dimerized receptor, in positive control mouse kidney, human parathyroid, and human embryonic kidney (HEK) 293 cells transfected with rat CasR, but we did not detect these bands in either wild-type HEK 293 cells or Saos2, MG-63, or U-2 OS osteoblast-like cell lines. Standard two-step RT-PCR using CasR-specific primers confirmed these results by detecting CasR transcripts in positive controls but not in negative control HEK 293 cells or osteoblast cell lines. In contrast, the 4637 antisera did not recognize CasR by immunoblot analysis under the conditions studied and our low stringency RT-PCR procedure amplified nonspecific products in wild-type HEK 293 cells and osteoblasts. Since we failed to detect CasR in human osteoblast cell lines using either the highly specific ADD antibody or RT-PCR under standard conditions, it is possible that the cation response in osteoblasts is mediated by a functionally similar but molecularly distinct calcium sensing receptor.