bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of growth hormone, insulin-like growth factor I, basic fibroblast growth factor, and transforming growth factor β on cell proliferation and proteoglycan synthesis by avian postembryonic growth plate chondrocytes
Authors: Rosselot Gaston , Vasilatos-Younken Regina , Leach Roland M. 
Published: February 2010

Abstract
We examined the in vitro effects of pituitary-derived chicken growth hormone (cGH), recombinant human insulin-like growth factor-I (rhIGF-I), recombinant human basic fibroblast growth factor (rhbFGF), and porcine transforming growth factor β (pTGF-β) on proliferation ([3H]thymidine uptake) and matrix proteoglycan synthesis (35SO4 incorporation) by chicken epiphyseal growth plate chondrocytes. Factorial experiments were used to study the effect of these substances in a serum-free culture system. Basic FGF had to be present in the culture medium for mitogenesis to take place. In the presence of this peptide, TGF-β, TGF-β + IGF-I, and newborn calf serum (NCS) stimulated mitogenesis. The mitogenic activity of NCS could be duplicated by adding platelet-derived growth factor (PDGF) to the culture medium. For matrix synthesis, IGF-I was the key factor, with the addition of TGF-β, TGF-β + bFGF, or serum producing further stimulation in matrix synthesis. Using this culturing system, homologous cGH did not stimulate cell proliferation or proteoglycan synthesis. The lack of stimulatory activity of cGH was consistent, regardless of the age of the birds from which the chondrocytes were isolated, the zone of the growth plate, or the level of cGH used. None of the growth factors used in this study or several other systemic hormones were found to be permissive factors for GH to be active. Either other factors must be present for a direct effect of GH on growth plate chondrocytes, or the avian species differ from their mammalian counterpart.
Precision of measurement by dual-energy X-ray absorptiometry of bone mineral density and content in rat hindlimb in vitro
Authors: Sievänen Harri , Kannus Pekka , Järvinen Markku 
Published: February 2010

Abstract
Dual-energy x-ray absorptiometry (DXA) is a precise and effective method for measuring bone mineral density (BMD) and content (BMC) at various skeletal sites in the human, but its precision for measuring low BMD and BMC in tiny rat bones has scarcely been evaluated. The short-term precision of DXA (Norland XR-26) for eight regions of interest (ROI) was determined by measuring dissected, not totally defleshed hindlimbs from four rats of differently weights 10 times consecutively. The accuracy of the BMD (area) measurement was also evaluated. The following average precision values (coefficients of variation) with negligible reanalysis error were obtained for BMD and BMC measurements: 0.7 and 1.2% (total); 0.9 and 1.2% (femur); 1.3 and 2.8% (tibia); 1.3 and 2.1% (foot); 2.1 and 4.7% (proximal femur); 1.4 and 2.9% (femoral shaft); 1.8 and 5.6% (distal femur); and 2.7 and 7.6% (proximal tibia). As for the accuracy, BMD measured in tiny bones is likely to be markedly underestimated. We conclude that the standard DXA technique without additional modification for small animal measurements is a precise method for BMD and BMC measurements at multiple sites in rat hindlimb in vitro.
Effects of mild asymptomatic primary hyperparathyroidism on bone mass in women with and without estrogen replacement therapy
Authors: McDermott Michael T. , Perloff Jan J. , Kidd Gerald S. 
Published: February 2010

Abstract
Primary hyperparathyroidism (HPT) presents most commonly as a mild elevation of the serum calcium concentration in an asymptomatic individual. There are conflicting data regarding the effects of mild primary HPT on bone mass. This cross-sectional study was conducted to examine this question further and to determine whether estrogen replacement therapy (ERT) in postmenopausal women with primary HPT might be beneficial. We measured bone mass in 59 women with mild asymptomatic primary HPT, of whom 43 (HPT) had never taken and 16 (estrogen-replaced HPT) were currently taking ERT. We also studied 84 healthy normocalcemic women who were not on ERT (controls) and 45 who were on ERT (estrogen-replaced controls). After adjustment for age, height, and weight, mean bone mass values in the HPT group were significantly reduced in the midradius (20%), distal radius (20%), lumbar spine (17%), and femoral neck (11%) compared with the controls. The estrogen-replaced HPT group had mean bone mass values greater than those in the HPT group, similar to those in the controls, and lower than those in the estrogen-replaced controls. Mild asymptomatic primary HPT results in bone loss from both the appendicular and axial skeleton, and ERT in postmenopausal women with primary HPT may ameliorate this loss.
Bone functional changes in intact, ovariectomized, and ovariectomized, hormone-supplemented adult cynomolgus monkeys (Macaca fascicularis) evaluated by serum markers and dynamic histomorphometry
Authors: Dr. Jerome Christopher P. , Carlson C.S. , Register T.C. , Bain F.T. , Jayo M.J. , Weaver D.S. , Adams M.R. 
Published: February 2010

Abstract
Several parameters of bone mass and function were investigated in three experiments involving intact, ovariectomized, or hormone-supplemented ovariectomized female cynomolgus monkeys. Ovariectomized animals had increased serum levels of alkaline phosphatase and acid phosphatase compared with intact and hormone-supplemented animals. Vertebral bone mass measured ex vivo by dual-photon absorptiometry was reduced by 11–19% in ovariectomized animals compared with intact and hormone-supplemented animals. The most dramatic effects observed with ovariectomy were markedly increased (30–60%) bone formation rates in vertebral cancellous bone, primarily caused by higher activation frequency of basic multicellular units of bone. In addition, combined resorption and reversal periods were decreased and formation period increased in untreated ovariectomized animals. Changes in static histomorphometry parameters were less dramatic, cancellous bone volume being 1–14% lower in ovariectomized animals compared with intact or ovariectomized hormone-supplemented animals. The data indicate that changes in bone resorption are primarily responsible for the lower bone mass of estrogen deficiency and increased bone mass in hormone-supplemented animals. Bone changes in ovariectomized cynomolgus monkeys resemble those in women after menopause and similarly respond positively to hormone supplementation. As such, cynomolgus monkeys are an excellent model for studying the basic mechanisms of osteoporosis and for the development of suitable therapeutic regimens.
Isolation and sequence of the vitamin K-dependent matrix Gla protein from the calcified cartilage of the soupfin shark
Authors: Rice Jeffrey S. , Williamson Matthew K. , Dr. Price Paul A. 
Published: February 2010

Abstract
High levels of the vitamin K-dependent matrix Gla protein (MGP) have been found in the calcified costal cartilage of the cow and the calcified vertebral cartilage of the soupfin shark (Galeorhinus galeus). In both species, MGP accounts for 35–40% of the total protein in the acid demineralization extract of calcified cartilage, and the mineral content of calcified cartilage is comparable to that of bovine cortical bone. Shark and bovine MGP are both nearly insoluble in neutral buffers, a conserved property that indicates that self-aggregation could be important to the as yet unknown function of MGP. The complete amino acid sequence of shark MGP was determined to compare the structure of the elasmobranch protein to the several currently known mammalian MGP sequences. Shark MGP contains 4 residues of the vitamin K-dependent amino acid γ-carboxyglutamic acid in its 102 residue sequence and has a calculated molecular weight = 12,770 daltons. The first 76 residues of shark MGP are homologous in sequence to mammalian MGPs, with 37% sequence identity, but the C-terminal 23 residues of the shark protein have no counterpart in the mammalian MGPs. This C-terminal segment of shark MGP contains 8 basic residues and no acidic residues. Among the features conserved in shark MGP, in all mammalian MGPs, and in all other currently known vitamin K-dependent mammalian proteins are a 15-residue region of sequence homology that has been shown to function as the γ-carboxylase recognition sequence and an invariant sequence of unknown function, Gla-Xaa-Xaa-Xaa-Gla-Xaa-Cys.
Risk of hip fracture in women with vertebral fracture
Authors: Kotowicz Mark A. , Dr. Melton L. Joseph , Cooper Cyrus , Atkinson Elizabeth J. , O'Fallon W. Michael , Riggs B. Lawrence 
Published: February 2010

AbstractIn a population-based retrospective cohort study, Rochester women aged 35–69 years who were first diagnosed with one or more vertebral fractures in 1950–1979 were followed for the development of a subsequent hip fracture. The 336 women with no history of hip fracture at the time of their vertebral fracture experienced 52 proximal femur fractures in 4788 person-years of follow-up. The standardized morbidity ratio (SMR) of observed to expected hip fractures was 1.8 (95% CI, 1.3–2.4) and was higher for intertrochanteric than cervical femoral fractures (SMR, 2.3 versus 1.3; P = 0.07). Hip fracture risk among women with symptomatic vertebral fractures was slightly less than in those with asymptomatic vertebral fractures (SMR, 1.8 versus 2.3; not significant), and younger women had no higher risk of a subsequent hip fracture than women who were ≥60 years of age at the time of their vertebral fracture (SMR, 1.4 versus 1.8; not significant). Alternative explanations are possible, but these data are consistent with heterogeneity in the pathogenesis of different osteoporotic fractures.
Effects of increasing doses of 1α-hydroxyvitamin D2 on calcium homeostasis in postmenopausal osteopenic women
Authors: Gallagher J.C. , Bishop Charles W. , Knutson Joyce C. , Mazess Richard B. , Deluca Hector F. 
Published: February 2010

AbstractThis study is the first reported administration of 1α-hydroxyvitamin D2 (1α-OHD2) to human subjects. A total of 15 postmenopausal osteopenic women were given increasing oral doses of 1α-OHD2, beginning with a low dose of 0.5 μg/day. In 15 subjects, the doses were raised at weekly intervals to 1.0, 2.0, 4.0, and 5.0 μg/day, and in 5 of these subjects, the dose was further increased to 8.0 or 10.0 μg/day. Mean urine calcium ± SEM showed a dose-related increase from 134 ± 17 mg/24 h on 0.5 μg/day to 198 ± 21 mg/24 h on 4.0 μg/day (p &lt; 0.05) and to 241 ± 35 mg/24 h on 5.0 μg/day (p &lt; 0.05). No subjects had hypercalciuria (&gt;350 mg/24 h, the upper limit of the laboratory normal range) at doses less than 5.0 μg/day; 5 subjects had hypercalciuria at or above 5.0 μg/day (3 at 5.0 μg/day, 1 at 8.0 μg/day, and 1 at 10.0 μg/day). Mean serum calcium increased slightly on the 4.0 μg dose only (p &lt; 0.05) but remained well within the normal range. Mean creatinine clearance and BUN, used as measures of renal function, showed no significant changes. Routine blood and urine assays also showed no significant changes. Serum osteocalcin, a marker of osteoblast activity, showed mean ± SEM dose-related increases of 10 ± 7% on 1.0 μg/day (p &lt; 0.05), 19 ± 7% on 2.0 μg/day (p &lt; 0.05), 21 ± 6% on 4.0 μg/day (p &lt; 0.05), and 28% on 5.0 μg/day (p &lt; 0.05); in the 5 subjects receiving higher dosages, mean serum osteocalcin increased 32 ± 12% on 8.0 μg/day and 55 ± 29% on 10.0 μg/day. Mean urine hydroxyproline/creatinine ratios did not change significantly at any dose of 1α-OHD2 but trended downward with increasing dosages. These findings indicate that 1α-OHD2 is well tolerated at dosages that stimulate osteoblastic activity, as evidenced by increased serum osteocalcin, and that 1α-OHD2 may be a useful agent for treating postmenopausal osteoporosis.
Efficacy and tolerability of a new formulation of oral tiludronate (tablet) in the treatment of paget's disease of bone
Authors: Reginster J.Y. , Treves R. , Renier J.C. , Amor B. , Sany J. , Ethgen D. , Picot C. , Franchimont P. 
Published: February 2010

Abstract
We sought to assess efficacy and safety of a new oral formulation (tablet) of tiludronate in Paget's disease of bone. We studied 128 patients with Paget's disease in an open-label uncontrolled trial. Patients received a daily dose of 400 mg oral tiludronate (two tablets). Treatment was for 6 months. Serum alkaline phosphatase activity (SAP) and fasting urinary excretion of hydroxyproline/creatinine (OH/Cr) were measured every 3 months, as were biochemical parameters reflecting renal, hepatic, and hematologic functions. Analgesic efficacy was self-evaluated from a visual analog scale (VAS). Statistical analysis revealed a significant reduction from baseline in SAP and OH/Cr levels, as well as VAS scores. In the whole population with evaluation under treatment, there was a reduction in initial SAP activity after 3 months (47.2 ± 2.2%, mean ± SEM) and 6 months (58.3 ± 2.3%). In the population with SAP levels above twice the upper limit at inclusion and with evaluation at month 3 and month 6 (n = 96), the reduction in SAP levels was 49.3 ± 2.4% after 3 months and of 59.5 ± 2.6% after 6 months (ANOVA time effect, p = 0.0001). Aside from mild gastrointestinal disturbances, as experienced with other oral bisphosphonates, clinical tolerance was good. Exhaustive biochemical investigation failed to reveal significant toxicity of tiludronate tablets at the dose of 400 mg/day. The dose of 400 mg daily of this new formulation appears to be a satisfactory tiludronate regimen for the treatment of Paget's disease of bone.
Muscle contraction increases the in vivo structural strength to the same degree in osteopenic and normal rat tibiae
Authors: Nordsletten Lars , Kaastad Trine S. , Obrant Karl J. , Skjeldal Sigmund , Kirkeby Ole J. , Stokke Oddvar , Ekeland Arne 
Published: February 2010

Abstract
The increase in structural capacity due to muscle contraction in the lower leg was investigated in osteopenic and normal rats. Osteopenia was induced by ovariectomy combined with a low-calcium diet (0.01%). The control rats were sham operated and fed a diet containing 1.1% calcium. After 7 weeks the right lower leg of all animals were fractured in three-point ventral cantilever bending during muscle contraction induced by electrical stimulation of the ischiatic nerve. The left tibiae were resected and fractured as each animal's control. During muscle contraction in vivo, the ultimate bending moment, energy absorption, bending stiffness, and deflection were significantly lower in the osteopenic than in the sham-operated animals. However, the increase in mechanical parameters due to muscle contraction comparing the in vivo and resected tibiae in each animal were equally high in the osteopenic and sham-operated animals. Ultimate bending moment in the resected tibiae was 10% higher in the sham-operated animals compared with the ovariectomized, proving mechanically weaker tibiae in the osteopenic rats. In accordance with this, the medullary area of the osteopenic rats was 46% larger in the distal tibial diaphysis, and the ultimate stress the tibiae could withstand was 15% lower in the osteopenic compared with the sham-operated rats. The trabecular bone volume in the distal tibial metaphysis of the osteopenic rats was reduced by 70% compared with the sham operated. This study shows that muscle protection against fracture can be substantial in osteopenic tibia and that it is of the same magnitude as in rats with normal bone mass.
Dual-energy X-ray absorptiometry of raloxifene effects on the lumbar vertebrae and femora of ovariectomized rats
Authors: Dr. Sato Masahiko , McClintock Cindy , Kim John , Turner Charles H. , Bryant Henry U. , Magee David , Slemenda Charles W. 
Published: February 2010

Abstract
A new potential therapeutic agent for postmenopausal osteoporosis, raloxifene, previously known as keoxifene, was evaluated by x-ray densitometry and more traditional techniques in quantitating the short-term (4–5 weeks) effects of ovariectomy on bones from 6-month-old rats. A Hologic QDR 1000/W and, to a limited extent, a Lunar DPXL, was used to quantitate ovariectomy, estrogen replacement, and raloxifene effects on vertebrae, femora, and tibiae. Both instruments performed well with precisions of 1.6% (Hologic) and 0.9% (Lunar) for anesthetized rats, which improved to 0.4% (Hologic) and 0.5% (Lunar) when the same rats were frozen. The lumbar vertebrae L1–4 showed a 12% decrease in bone mineral density 4 weeks after ovariectomy, compared with a 9% decrease for femora. Tibiae were also examined, but edge-detection problems prevented reproducible analysis of this site in vivo. The decrease in bone mineral density postovariectomy, especially for femora, was found to include both an increase in the projected area and a slight but not significant decrease in the bone mineral content of L1–4 and femora. These changes in density parameters of femora were supported by a decrease in dry weight and volume and a marginal increase in the second moment of inertia I for the identical femora examined ex vivo. Examination of individual lumbar vertbrae L1–5 suggested that the bone mineral density of L3 changes most dramatically in response to ovariectomy, but present techniques lack the spatial resolution and precision to quantitate bone changes reliably in individual vertebrae. 17β-Estradiol administered at 100 μg/kg/day subcutaneously inhibited ovariectomy effects on L1–4 bone mineral density, femoral moment of inertia, dry weight, and volume and to a lesser extent, femoral bone mineral density. A nonsteroidal compound, raloxifene HC1, at 1 mg/kg/day per os, had bone effects and effects on body weight that were largely indistinguishable from those of 17β-estradiol; however, raloxifene did not produce the uterotrophic effects observed with estrogen. The half-maximal efficacious dose of raloxifene on L1–4 bone mineral density was between 0.1 and 1.0 mg/kg/day per os. These data show that dual-energy x-ray absorptiometry compares favorably with traditional methods in quantitating bone changes caused by ovariectomy in small rodents, that L1–4 is a more sensitive region than whole femora in evaluating the effect of estrogen deficiency on bone loss, and the raloxifene may have promise as a treatment for conditions characterized by excessive bone loss after ovariectomy.
Reduced femoral neck bone density in the daughters of women with hip fractures: The role of low peak bone density in the pathogenesis of osteoporosis
Authors: Dr. Seeman Ego , Tsalamandris Con , Formica Carmelo , Hopper John L. , McKay John 
Published: February 2010

Abstract
Low bone density in women with hip fractures (“senile” osteoporosis) may be due to excessive bone loss or low peak bone density. If excessive bone loss is responsible, then no reduction in bone density is expected in their daughters. If low peak bone density is responsible, then bone density should also be reduced in their daughters because genetic and family environmental factors influence the variability in bone density. Bone density was measured using dual-photon absorptiometry and expressed as a standardized deviation or Z score relative to 697 controls, adjusting for age, height, weight, and menopausal status. In 74 women with hip fractures, the Z score (mean ± SEM) was −0.52 ± 0.14 (P &lt; 0.001) at the femoral neck, −1.04 ± 0.17 (P &lt; 0.001) at the femoral shaft, and −0.43 ± 0.10 (P &lt; 0.001) at the lumbar spine. In their 41 daughters, the Z score was −0.40 ± 0.17 (P &lt; 0.05) at the femoral neck, −0.41 ± 0.19 (P &lt; 0.001) at the femoral shaft, and 0.23 ± 0.13 (NS) at the lumbar spine. We conclude that daughters of women with hip fractures are likely to be at increased risk for hip fractures themselves because they have reduced femoral neck bone density. Femoral neck fractures may not be entirely attributable to trauma; reduced bone density is likely to contribute and may be caused by the attainment of a lower peak femoral neck bone density.
Preclinical pharmacology of CGP 42′446, a new, potent, heterocyclic bisphosphonate compound
Authors: Green Jonathan R. , Müller Klaus , Jaeggi Knut A. 
Published: February 2010

Abstract
We have investigated the pharmacologic effects of a new bisphosphonate compound, CGP 42′446 [2-(imidazol-1-yl)-1-hydroxyethylidene-1,1-bisphosphonate], on bone metabolism. The compound exhibited potent inhibitory activity on the bone resorption induced by 1,25-dihydroxyvitamin D3 both in vivo in the thyroparathyroidectomized rat (ED50 0.072 μg/kg SC) and in vitro in mouse calvarial cultures (IC50 0.002 μM). A comparison of the in vivo and in vitro inhibitory potencies of a total of nine bisphosphonates revealed an excellent correlation between the two assays (r = 0.97). CGP 42′446 also potently inhibited calvarial bone resorption induced by parathyroid hormone (1–34), parathyroid hormone-related protein (1–34), and recombinant human interleukin-1β. Short-term treatment of growing rats with CGP 42′446 dose-dependently increased the radiographic density of the tibial proximal metaphysis (ED50 1.7 μg/kg SC) as well as increasing the calcium and hydroxyproline content of femoral trabeculae (ED50 values 0.17 and 1.1 μg/kg SC, respectively), but there was no detectable effect on cortical bone. On a molar basis in this range of in vivo screening assays, CGP 42′446 was between 940-fold (thyroparathyroidectomized rat) and 87-fold (rat femoral trabecular calcium content) more potent than pamidronate. It is concluded that CGP 42′446 is a promising new, highly potent bisphosphonate for the suppression of the increased bone resorption associated with various diseases.
Interleukin-6 antisense deoxyoligonucleotides inhibit bone resorption by giant cells from human giant cell tumors of bone
Authors: Reddy Sakamuri V. , Takahashi Shunji , Dallas Mark , Williams Ronald E. , Neckers Leonard , Roodman G. David 
Published: February 2010

Abstract
The effects of antisense constructs to IL-6 on the bone-resorbing capacity of purified giant cells from giant cell tumors of bone were examined to further define the role of IL-6 in human osteoclastic bone resorption. In addition, we wanted to determine the utility of antisense constructs to cytokines produced by osteoclasts as probes to identify the molecular events responsible for the bone-resorptive process. Giant cells were cultured on sperm whale dentin for 24 h in the presence of fluoresceinated antisense or scrambled antisense deoxyoligonucleotides complementary to IL-6 mRNA. The giant cells actively incorporated these oligonucleotides, as evidenced by their intense fluorescence. The number of resorptive lacunae formed and the area of the dentin resorbed were significantly decreased in cultures of giant cells treated with antisense IL-6 constructs compared with control cultures treated with scrambled antisense constructs to IL-6 (60 ± 13 versus 12 ± 6 lacunae and 1.2 ± 0.3 versus 0.26 ± 0.1 × 105 μm2). IL-6 levels in conditioned media from giant cell cultures treated with IL-6 antisense constructs were fourfold lower than those in control media obtained from giant cells treated with scrambled antisense constructs to IL-6. These data confirm the capacity of IL-6 antisense oligomers to block IL-6 production by these cells. These observations show that IL-6 plays an important role in the bone-resorptive process of human osteoclasts and suggest that antisense constructs to cytokines produced by bone cells may be useful for determining the molecular events occurring during bone resorption.