bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of resistance and endurance exercise on bone mineral status of young women: A randomized exercise intervention trial
Authors: Snow-Harter Christine , Bouxsein Mary L. , Lewis Barbara T. , Carter Dennis R. , Marcus Robert 
Published: February 2010

Abstract
A substantial body of cross-sectional data and a smaller number of intervention trials generally justify optimism that regular physical activity benefits the skeleton. We conducted an 8 month controlled exercise trial in a group of healthy college women (mean age = 19.9 years) who were randomly assigned to a control group or to progressive training in jogging or weight lifting. We measured the following variables: bone mineral density (BMD) of the spine (L2–4) and right proximal femur using dual-energy x-ray absorptiometry, dynamic muscle strength using the 1-RM method, and endurance performance using the 1.5 mile walk/run field test. A total of 31 women completed the 8 month study. For women completing the study, compliance, defined as the percentage of workout sessions attended, was 97% for the runners (range 90–1009/0) and 92% (range 88–100%) for the weight trainers. Body weight increased by approximately 2 kg in all groups (p &lt; 0.05). Weight training was associated with significant increases (p &lt; 0.01) in muscle strength in all muscle groups. Improvement ranged from 10% for the deep back to 54% for the leg. No significant changes in strength scores were observed in the control or running groups. Aerobic performance improved only in the running group (16%, p &lt; 0.01). Lumbar BMD increased (p &lt; 0.05) in both runners (1.3 ± 1.6%) and weight trainers (1.2 ± 1.8%). These results did not differ from each other but were both significantly greater than results in control subjects, in whom bone mineral did not change. No measure of bone mineral at the proximal femur changed significantly in any group. These results demonstrate that 8 months of supervised progressive training in either running or resistance exercise modestly increases lumbar spine mineral in young women.
Expression of mutant α(I)-procollagen in osteoblast and fibroblast cultures from a proband with osteogenesis imperfecta type IV
Authors: Chipman Stewart D. , Shapiro Jay R. , McKinstry Monique B. , Stover Mary Louise , Branson Philip , Rowe David W. 
Published: February 2010

Abstract
This study compares the synthesis of mutant type I collagen in cultured dermal fibroblasts and trabecular osteoblasts that were isolated from a patient with moderately severe osteogenesis imperfecta (type IV). Previous study of this patient's dermal fibroblasts revealed a 2000 dalton deletion located in cyanogen bromide peptide 4 of α2(D-collagen. The phenotype of the bone cell cultures was defined by a 3–4 day logarithmic phase doubling time, predominantly type I collagen production over type III and alkaline phosphatase activity 13.5 times dermal fibroblast levels. The current study revealed that both fibroblasts and osteoblasts synthesized a normal and a shortened α2(I) chain, each as the product of separate alleles. Following pepsin treatment of the procollagens, a shortened α1(I) chain was also seen in both cell types. Cyanogen bromide peptide mapping of osteoblast α-chains demonstrated the same deletions in the cyanogen bromide peptide 4 as observed in the fibroblast cyanogen bromide maps. PAGE analysis of oligonucleotide-specific cDNA that was reverse transcribed from RNA isolated from fibroblasts and osteoblasts also demonstrated the presence of two bands, one the normal size of α2(I) cDNA and a second species that was smaller by 54 base pairs. Sequencing of polymerase chain reaction-amplified cDNA fragments revealed an in-frame deletion of exon 12. This finding was confirmed by the RNase protection method. Genomic DNA sequencing detected a T→G point mutation in the second position of the 5′ splice donor site of intron 12. Therefore, in this patient with osteogenesis imperfecta there was no qualitative alteration in the osteoblast-specific expression of this mutant α2(I)-collagen allele compared to dermal fibroblasts.
Suppression of PTH and decreased action on bone are partially responsible for the low calcemic activity of 22-oxacalcitriol relative to 1,25-(OH)2D3
Authors: Finch Jane L. , Brown Alex J. , Mori Takashi , Nishii Yasuho , Slatopolsky Eduardo 
Published: February 2010

Abstract
We previously showed that OCT, an analog of 1,25-(OH)2D3 with little calcemic activity, can decrease PTH mRNA levels in normal rats and inhibit PTH secretion in cultured bovine parathyroid cells with the same potency as 1,25-(OH)2D3 and that in normal rats fed a normal calcium diet, administration of OCT (500 ng) for 5 days did not increase plasma Ca. Thus, to determine if PTH suppression by OCT contributes to its lack of calcemic activity and to further characterize the effects of OCT on Ca metabolism, we performed several studies in parathyroidectomized (PTX) rats. PTX rats, maintained on a normal diet (0.9% Ca), received daily injections of vehicle, 1,25-(OH)2D3 (200 ng/day), or OCT (200 ng/day) for 6 days. Plasma Ca was measured daily. Plasma Ca in control rats stayed between 6.60 and 7.40 mg/dl, whereas Ca increased to 12.9 ± 0.42 mg/dl in 1,25-(OH)2D3-treated rats and to 9.53 ± 0.35 mg/dl in OCT-treated rats after 6 days. With a Ca-deficient diet, control rats maintained a plasma Ca between 4.25 and 4.60 mg/dl, but Ca increased to 13.7 ± 0.24 mg/dl with 1,25-(OH)2D3 and to 7.29 ± 0.17 mg/dl with OCT. Since the elevation in Ca by OCT was similar with both diets, OCT appears to act primarily on bone. PTX rats were infused with PTH (1.84 μg/kg/day) via an Alzet pump to achieve normal plasma Ca and then treated daily with either vehicle or OCT (200 ng/day). After 6 days, OCT increased serum Ca to 10.7 ± 0.21 mg/dl over a control value of 8.58 ± 0.29 mg/dl. Thus, even when normocalcemic conditions were maintained with a nonsuppressible source of PTH, OCT had calcemic activity. These data demonstrate that OCT has calcemic activity, mainly in the bone, that is masked by its suppressive action on PTH. When compared to 1,25-(OH)2D3, however, the intrinsic calcemic activity of OCT is much less but its effects on PTH secretion are similar. Thus, OCT may be ideal for the treatment of the secondary hyperparathyroidism of chronic renal failure.
Maintenance of cancellous bone connectivity in primary hyperparathyroidism: Trabecular strut analysis
Authors: Parisien May , Mellish Robert W. E. , Silverberg Shonni J. , Shane Elizabeth , Lindsay Robert , Bilezikian John P. , Dempster David W. 
Published: February 2010

Abstract
We previously demonstrated an increase in cancellous bone volume and trabecular number in patients with mild primary hyperparathyroidism (PHPT). To test the hypothesis that this increase is due to preservation of cancellous bone architecture, we conducted a trabecular strut analysis using a new method that measures trabecular connectivity. Iliac crest biopsies from 37 patients with PHPT, 14 men (28–68 years) and 23 women (26–68 years), were examined histomorphometrically and compared to cadaveric samples from 24 age-matched subjects, 17 men and 7 women. Two-dimensional indices of cancellous structure–node number (N.Nd), terminus number (N.Tm), node to node (Nd.Nd), node to terminus (Nd.Tm), and terminus to terminus (Tm.Tm) strut lengths, and total strut length (TSL)–were measured and the ratio of node number to terminus number (N.Nd/N.Tm) calculated. TSL, N.Nd, and Nd.Nd were significantly higher in patients than in controls. TSL and Nd.Nd, but not N.Nd or Nd/Tm, decreased significantly with age in PHPT, indicating that age-related bone loss in PHPT occurs without significant loss of trabecular connectivity. Two-dimensional indices reflecting connectivity or the amount of bone, that is, N.Nd, Nd.Nd, N.Nd/N.Tm, and TSL, correlated positively with cancellous bone volume (BV/TV) and trabecular number (Tb.N) and negatively with trabecular spacing (Tb.Sp) in both PHPT and controls. Trabecular thickness (Tb.Th) correlated positively with Nd.Nd and Tb.N and negatively with Tm.Tm in PHPT but not in controls. The present data show that in PHPT there is not only greater cancellous bone volume and trabecular number but preserved trabecular connectivity as well. The data further support the hypothesis that in PHPT cancellous bone architecture is maintained.
Nitroblue tetrazolium reduction and bone resorption by osteoclasts in vitro inhibited by a manganese-based superoxide dismutase mimic
Authors: Ries William L. , Key Lyndon L. , Rodriguiz Ramona M. 
Published: February 2010

Abstract
Oxygen-derived free radicals are produced by osteoclasts. Oxygen radical formation occurs at the osteoclast/bone surface interface. This location next to bone implies that oxygen radicals, including but not limited to superoxide, are needed for bone resorption. Compounds that scavenge superoxide are being developed as pharmaceutical agents to inhibit the damaging effects of oxygen radical formation on tissues. One such scavenger is the Desferal-manganese complex (DMnC). DMnC reduced the amount of formazan staining produced by the interaction of oxygen radicals with nitroblue tetrazolium (NBT) in both individual mouse calvarial osteoclasts in tissue explants and isolated osteoclasts. As a result of the reduced concentrations of oxygen radicals, DMnC inhibited bone resorption by calvarial explants and isolated osteoclasts. Superoxide dismutase (SOD) inhibited NBT reduction and bone resorption by isolated osteoclasts but to a lesser degree than DMnC. Inhibition of bone resorption in the isolated osteoclast system increased in parallel to the concentration of DMnC in cultures. Desferal without Mn had no effect on bone resorption by isolated osteoclasts. These results support the hypothesis that osteoclasts produce oxygen radicals as part of the process of bone resorption.
Localization of parathyroid hormone-related protein mrna expression in breast cancer and metastatic lesions by in situ hybridization
Authors: Vargas Socorro J. , Gillespie Matthew T. , Powell Gerard J. , Southby Justine , Danks Janine A. , Moseley Jane M. , Martin John T. 
Published: February 2010

Abstract
Parathyroid hormone-related protein (PTHrP) has been identified immunohistochemically in 60% of breast carcinoma(1) and in 92% of breast cancer metastases in bone.(2) To establish whether the localization of the PTHrP antigen reflects protein synthesis and also to investigate the role of PTHrP in metastatic disease, as part of an ongoing study, we used in situ hybridization to study the localization of PTHrP mRNA in a retrospective series of primary breast tumors and their metastatic lesions. Paraffin sections of 17 primary and 26 metastatic lesions, 11 of which were in bone, were available for the study: 10 of the 17 (59%) primary lesions, 8 of 11 (73%) breast cancer metastases to bone, and 3 of 15 (20%) metastases to non-bone sites showed specific localization of PTHrP mRNA. These findings establish that PTHrP is commonly synthesized by primary breast cancers and support previous immunohistochemical studies reporting a higher incidence of PTHrP-positive tumor cells in skeletal metastases than in nonskeletal metastases.
Responsiveness to 1,25-Dihydroxyvitamin D3 is reduced in lymphocytes from osteoporotic women
Authors: Dr. Koren R. , Ravid A. , Liberman U.A. , Narinsky R. , Maron L. , Weisman M. , Samuel R. 
Published: February 2010

Abstract
The purpose of this work was to test the hypothesis that reduced responsiveness of target organs to 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] is associated with osteoporosis. Peripheral blood mononuclear (PBM) cells have been previously shown to be a valid model for the action of 1,25-(OH)2D3 on its classic target organs in various pathologic and physiologic situations. The responsiveness of lymphocytes to the hormone can be assessed by the extent of inhibition it exerts on the proliferative response to mitogenic lectins. A group of 39 postmenopausal women, at least 10 years after the menopause, participated in the study. Osteoporosis, defined as the presence of at least one nontraumatic vertebral crush fracture, was diagnosed in 19 subjects. Mitogenesis of PBM cells stimulated by phytohemagglutinin and cultured for 72 h in the presence or absence of 1,25-(OH)2D3 (0.03–1 nmol/liter) was assessed by [3H]thymidine incorporation during a 4 h pulse. The maximal inhibitory effect of 1,25-(OH)2D3 at saturating concentration (1 nM/liter) was 74.6 ± 2.8% (mean ± SEM) for normal compared to 65.3 ± 2.9% for osteoporotic women (P = 0.015). The geometric mean of the ED50 values of 1,25-(OH)2D3 was 60% higher in the osteoporotic than in the normal group (P = 0.035). Our data are consistent with the notion that reduced responsiveness of target organs to 1,25-(OH)2D3 is associated with osteoporosis.
Site-matched calcaneal measurements of broad-band ultrasound attenuation and single X-ray absorptiometry: Do they measure different skeletal properties?
Authors: Glüer C.C. , Vahlensieck M. , Faulkner K.G. , Engelke K. , Black D. , Genant H.K. 
Published: February 2010

Abstract
Because of the differences in the interactions of ultrasound and x-ray waves with bone, quantitative ultrasound (QUS) techniques may yield information about skeletal status not accessible by regular bone densitometry (BD) techniques. However, relatively strong correlations have been reported between broad-band ultrasound attenuation (BUA) and several x-ray-based BD methods. We assessed the precision and association of single x-ray absorptiometry (SXA) and BUA of the calcaneus. We examined both BUA and SXA at the calcaneus using special software for matching the regions of interest. An algorithm was derived and applied to correct the observed correlation coefficients for the attenuation effect caused by the precision errors for BUA and SXA. In a group of 33 volunteers covering a wide range of age and calcaneal bone mineral densities, the site-matched and precision-adjusted correlation coefficient between BUA and SXA was r = 0.58, with a standard error of the estimate (SEE) of 14.41 dB/MHz, or 17.08%. For the subgroup of 25 women the correlation was stronger, with r = 0.72 and SEE = 11.53 dB/MHz, or 14.33%. SXA precision was 0.79% for the regular region of interest (ROI) and 1.22% for the site-matched ROI. BUA precision was 2.76% for the entire subject group and 1.63% for women of age 40 or older. The observed correlation coefficient between ultrasound and x-ray based techniques of the order of 0.7 is significant, but it leaves about 50% of the variability unexplained. It remains to be investigated to what extent the unexplained 50% is related to bone strength or structure or whether it reflects a variability unrelated to osteoporosis status.
Rapid publication: Hypocalcemic actions of amylin amide in humans
Authors: Wimalawansa Sunil J. , Gunasekera Ranjan D. , Datta Harish K. 
Published: February 2010

Abstract
Amylin (also known as islet amyloid polypeptide and diabetes-associated peptide) has recently been shown by us to have a potent hypocalcemic effect in rat and rabbit owing to inhibition of osteoclast-mediated bone resorption. The hypocalcemic potency of amylin was found to be second only to that of calcitonin (CT) and is 100-fold more potent than calcitonin gene-related peptide. Here we demonstrate that amylin has a hypocalcemic effect in patients with Paget's disease of bone. Both human CT (hCT) and amylin induced a maximum hypocalcemic effect 2 h following intravenous administration of the peptides (p &lt; 0.001). Although on a molar basis amylin is less potent than CT, it exhibits a significantly prolonged hypocalcemic effect compared to hCT. Here we demonstrate for the first time a profound hypocalcemic effect of amylin in the human, despite sharing only 15% amino acid sequence identity with hCT.
Prostaglandin E2 stimulates synthesis of insulin-like growth factor binding protein-3 in rat bone cells in vitro
Authors: Schmid Christoph , Schläpfer Irene , Waldvogel Margaretha , Zapf Jürgen , Froesch E. Rudolf 
Published: February 2010

Abstract
Prostaglandin E2 is produced by bone cells and increases cyclic AMP in these cells. Like PTH and dibutyryl cyclic AMP, PGE2 is a potent stimulator of IGF-I synthesis in cultured rat osteoblasts and inhibits DNA synthesis and type I procollagen gene expression. In addition, PGE2 inhibits the response of the cells toward IGF-I after 1 day but not after 4 days of incubation. Rat calvaria osteoblasts constitutively release IGFBPs into the culture medium, in particular IGFBP-2 and IGFBP-3. Like growth hormone, PGE2 stimulates the accumulation of IGFBP-3. PGE2 rapidly increases IGF-I and IGFBP-3 mRNA expression in calvaria cells, with a time course clearly different from that observed in response to growth hormone. Thus, PGE2 modifies not only the synthesis of IGF-I but also that of IGFBP-3 in skeletal tissue.
Osteogenesis associated with bone gla protein gene expression in diffusion chambers by bone marrow cells with demineralized bone matrix
Authors: Dr. Dohi Yoshiko , Ohgushi Hajime , Tabata Shiro , Yoshikawa Takafumi , Dohi Kazuhiro , Moriyama Tadashige 
Published: February 2010

Abstract
Diffusion chambers with rat bone marrow cells and demineralized bone matrix (DBM) were implanted subcutaneously to syngeneic 8-week-old rats and were harvested every week 3–7 weeks after implantation, and histochemical examination, determination of alkaline phosphatase activity, total calcium and phosphorus, the bone-specific vitamin K-dependent gla-containing protein (BGP) content, and detection of BGP mRNA relative to mineralization were performed. Alkaline phosphatase in diffusion chamber implants reached the highest activity at 4 weeks and then decreased. Calcium and phosphorus deposits occurred at 4 weeks after implantation and were followed by marked increases until 7 weeks, which was comparable to the accumulation of BGP. The BGP gene within the diffusion chambers began to be expressed at 5 weeks, and its expression increased markedly at 7 weeks after implantation. At 4–5 weeks after implantation, new bone adjacent to the membrane filters and cartilage toward the center of the diffusion chamber were observed histochemically. Light microscopic and immunohistologic examinations of chambers with marrow cells and DBM revealed production of mineralized matrices, typical of bone characterized by the appearance of BGP and mineralized nodules. In contrast, bone marrow cells alone did not show extensive bone formation and yielded very low values for these biochemical parameters. The present experiments demonstrate the potential of bone marrow cells and DBM to produce not only cartilage formation but also membranous bone formation associated with increasing expression of BGP mRNA during the later stages of bone formation, as well as a marked accumulation of BGP.
Racial differences in pre- and postmenopausal bone homeostasis: Association with bone density
Authors: Meier Diane E. , Luckey Marjorie M. , Wallenstein Sylvan , Lapinski Robert H. , Catherwood Bayard 
Published: February 2010

Abstract
The disparity in fracture incidence and bone mass in women of European (white) and African (black) ancestry is of unknown etiology. To determine if racial differences in bone mass reflected racial differences in the mechanisms of bone turnover underlying bone mineral loss, we measured serum osteocalcin, serum alkaline phosphatase, fasting urinary calcium and hydroxyproline excretion, 24 h urinary excretion of calcium and sodium, and dietary intakes of calcium and vitamin D in 263 healthy pre-, peri-, and postmenopausal white and black women. In addition, radial and spinal bone density were measured cross-sectionally for comparison with biochemical measures of bone turnover. The biochemical parameters thought to reflect bone resorption (fasting urinary calcium and hydroxyproline excretions) were lower in black than in white women throughout the age and menopausal stages studied. The parameters thought to reflect bone formation (alkaline phosphatase and osteocalcin), were similar in the two racial groups among the premenopausal women, but osteocalcin was significantly lower among the peri- and postmenopausal blacks. Cross sectionally measured radial bone density increased with age in premenopausal black women, but it did not change with age in the white premenopausal subjects, a statistically significant difference. In peri- and postmenopausal women radial density declined significantly with years after menopause in both racial groups, but the rate of decline was significantly slower in the black women. Lumbar bone density in premenopausal white and black women did not change with age. After menopause lumbar bone density declined significantly and similarly in both racial groups. The biochemical findings and the densitometric data at the radial site are consistent, both suggesting lower bone resorption and lower rates of cortical bone loss in pre- and postmenopausal black women than in whites. Together these findings indicate that racial differences in bone density result, at least in part, from measurable racial differences in bone homeostasis and support the hypothesis of a more positive bone balance in both pre- and postmenopausal black women.
Prostaglandin E2 alleviates cyclosporin a-induced bone loss in the rat
Authors: Katz I.A. , Jee W.S.S. , Joffe I.I. , Stein B. , Takizawa M. , Jacobs T.W. , Setterberg R. , Lin B.Y. , Tang L.Y. , Ke H.Z. , Zeng Q.Q. , Berlin J. , Dr. Epstein S. 
Published: February 2010

Abstract
Cyclosporine A (CsA) administered to the male and female rat produces high-turnover osteopenia. Prostaglandins have both bone-resorbing and bone-forming properties, but administration of prostaglandin E2 (PGE2) to the rat in vivo produces a net increase in cancellous bone. To investigate the effects of PGE2 on CsA-induced alteration in bone mass, 43 male Sprague-Dawley rats (9 weeks old) were administered 15 mg/kg of CsA by oral gavage and/or 6 mg/kg of PGE2 by subcutaneous injection daily for 21 days according to the following protocol: group A was an age-matched control; group B received CsA only; group C received PGE2 only; and group D received CsA and PGE2. Serum was assayed on days 0, 7, 14, and 21 for bone gla protein (BGP), PTH, and 1,25-dihydroxyvitamin D [1,25-(OH)2D]. A computerized image analysis system was used for bone histomorphometry of the proximal tibial metaphysis after double tetracycline labeling. Compared to control animals (group A), treatment with CsA alone (group B) and PGE2 alone (group C) significantly elevated BGP levels. Combination therapy (group D) resulted in BGP levels that were significantly higher on days 7 and 14 than with either agent alone. 1,25-(OH)2D was significantly elevated in the CsA group only (group B). Therapy with CsA alone (group B) resulted in a significant osteopenia. The concurrent administration of PGE2 with CsA (group D) alleviated the altered bone mass induced by CsA alone by adding a significant amount of additional bone. This report confirms and extends the current knowledge of the different effects of CsA and PGE2 on bone mineral metabolism and demonstrates that PGE2 can alleviate the deleterious effects of CsA on bone.