bluuebunny/crossref_metadata_2025_split huggingface dataset:
Grip strength and bone mineral density in older women
Authors: Kritz-Silverstein Donna , Dr. Barrett-Connor Elizabeth 
Published: February 2010

Abstract
Most previous literature on muscle strength and bone density examined the association between specific muscle groups and adjacent bones. This study examined the association of grip strength with bone density at distant sites, such as the spine and hip, as well as at the wrist and radius. Subjects were 649 postmenopausal women aged 65 years and older. Bone mineral density was measured at the ultradistal wrist and midshaft radius in the nondominant arm using single-photon absorptiometry and at the lumbar spine and hip using dual-energy x-ray absorptiometry. Grip strength was measured in both the dominant and nondominant hands using a dynamometer. Overweight women had significantly stronger grip strength in both hands (p &lt; 0.01 for dominant hand, p &lt; 0.05 for nondominant hand grip strengths). Exercisers had significantly stronger grip strength in the nondominant hand than nonexercisers (p &lt; 0.05). Women reporting arthritis had significantly weaker grip strength in both hands than women not reporting arthritis (p &lt; 0.001). There were no significant differences in grip strength by estrogen use, cigarette smoking, or thiazide use. Regression analyses adjusted for age, obesity, exercise, cigarette smoking, thiazide use, arthritis, years postmenopausal, and estrogen use indicated significant positive associations between grip strength and bone density at all sites. Regression analyses stratified by exercise indicated that only women who exercised had significant associations of grip strength with bone mineral density (all p &lt; 0.05). In this cohort of older women, grip strength was an independent indicator of general bone density. These results are compatible with the thesis that grip strength is a marker for overall fragility and general health and for the adequacy of skeletal loading exercise.
Long-term (3 years) prevention of trabecular postmenopausal bone loss with low-dose intermittent nasal salmon calcitonin
Authors: Reginster J.Y. , Denis D. , Deroisy R. , Lecart M.P. , de Longueville M. , Zegels B. , Sarlet N. , Noirfalisse P. , Franchimont P. 
Published: February 2010

Abstract
The long-term effect of intermittent low-dose nasal salmon calcitonin on trabecular early postmenopausal bone loss was assessed as follow-up to a previously published study. Randomized controlled group comparison was made of 287 healthy women with 6–36 months of natural menopause and no treatment interfering with calcium metabolism at an outpatient clinic for research in bone and cartilage metabolism. The 287 women were randomly allocated to 3 years of treatment with either 500 mg/day, 5 days/week of calcium or the same amount of calcium plus 50 IU/day, 5 days per week of nasal salmon calcitonin. A total of 186 women complied with the study protocol throughout. The main outcome measures were bone mineral density of the lumbar spine (DPA) and biochemical parameters reflecting bone turnover (serum alkaline phosphatases, urinary calcium/creatinine, and hydroxyproline/creatinine ratio). The average changes in bone mineral density after 36 months showed a positive (p &lt; 0.05) outcome (1.8 ± 5.7%; mean ± SD) in the group treated with salmon calcitonin and calcium and a significant (p &lt; 0.01) loss (-5.8 ± 4.8%) in patients receiving calcium alone. The difference between the evolution of the two groups was significantly (p &lt; 0.01) different after 6 months of treatment and remained so until the end of the study. No significant changes were recorded in biochemical parameters reflecting bone turnover. As previously shown during a 1 year follow-up, nasal salmon calcitonin given at low dose and intermittently, in association with calcium, can counteract trabecular postmenopausal bone loss.
Mechanical loading thresholds for lamellar and woven bone formation
Authors: Dr. Turner Charles H. , Forwood M.R. , Rho J.-Y. , Yoshikawa T. 
Published: February 2010

Abstract
Bone formation was measured in rat tibiae after 12 days of applied loading. Bending forces were applied using a four-point loading apparatus. Sham loads were applied at the same magnitudes as bending forces but the loading pads were arranged so that bending was minimized. Bending and sham loading were applied to the right tibiae of rats and the left tibiae served as contralateral controls. Loading was applied as a sine wave with a frequency of 2 Hz for 18 s (36 cycles) per day. The peak magnitude of applied load was 27, 33, 40, 52, and 64 N. Woven bone was observed on the periosteal surface in all animals subjected to loads of 40 N or greater. Periosteal woven bone formation occurred in both bending and sham loading groups. Woven bone formation on the periosteal surface was either absent or responded at a maximal rate if the stimulus threshold was surpassed. The amount of new woven bone and the woven bone-forming surface were independent of the magnitude of applied strain. Bone formation on the endocortical surface was exclusively lamellar. Lamellar bone formation was stimulated by applied bending of the tibia but not by sham loading. Bending strains above a loading threshold of 40 N or about 1050 μstrain increased both bone-forming surface and the mineral apposition rate and subsequently increased the bone formation rate as much as sixfold. No evidence of increased bone formation was seen for applied strains below 1050 μstrain. Examination of bulk stained sections from animals exposed to the highest applied loads showed no evidence of microcracks. Thus, microcracks have not been implicated as a causal factor for the observed increases in bone formation rate.
Pp60 c-src expression and activity in MG-63 osteoblastic cells modulated by PTH but Not required for PTH-mediated adenylate cyclase response
Authors: Izbicka E. , Niewolna M. , Yoneda T. , Lowe C. , Boyce B. , Mundy G. 
Published: February 2010

Abstract
A role for pp60c-src (c-src) tyrosine kinase in bone resorption was recently demonstrated in vivo. However, it is not known whether expression of this ubiquitous tyrosine kinase is essential in osteoblasts or osteoclasts. In this work, we have examined the expression of c-src in osteoblast-like cells. We found that c-src was expressed in the MG-63 osteoblastic osteosarcoma cell line as assessed by immunocytochemistry. When MG-63 cells were treated for 30 minutes with parathyroid hormone (PTH), the levels of tyrosine phosphorylation of c-src were increased in comparison with the untreated control. On the other hand, no changes in total c-src protein were observed after PTH treatment. The increase in c-src tyrosine phosphorylation due to PTH treatment was paralleled by an increase in c-src tyrosine kinase activity. Calcitonin had no effect on c-src phosphorylation, c-src protein level, or tyrosine kinase activity. To determine if c-src tyrosine kinase was required for normal bone cell function and PTH responsiveness, osteoblastic cells were isolated from the calvaria of a src-deficient mouse. The cyclic AMP response to PTH in this cell was identical to that seen in freshly isolated calvarial cells from normal mice. These results suggest that the activity of c-src in MG-63 cells is regulated by PTH as a result of tyrosine phosphorylation. Expression of src is not required for PTH responsiveness in osteoblastic cells as assessed by adenylate cyclase activation. The mode of signal transduction from the PTH receptor to nonreceptor c-src tyrosine kinase is not known at present.
Synthetic peptide containing Arg-Gly-Asp inhibits bone formation and resorption in a mineralizing organ culture system of fetal rat parietal bones
Authors: Gronowicz Gloria A. , Derome Mary E. 
Published: February 2010

Abstract
The role of integrins, cell surface receptors involved in cell adhesion to the matrix, was studied in a mineralizing organ culture system. Integrin-mediated cell attachment to matrix proteins has been shown to depend partially on the amino acid sequence Arg-Gly-Asp (RGD), present in the extracellular matrix proteins. Therefore, the effect of RGD peptides on bone formation and resorption was studied in the mineralizing organ culture system derived from 18 day fetal rat parietal bones. Addition of 0.1–50 μM GRGDSPK to bones cultured for 4 days inhibited mineralization in a dose-dependent manner as determined by measuring calcium content and % bone/unit area of tissue. A maximal decrease in calcium content and % bone/unit area of 32.5 and 42.9%, respectively, was found with 50 μM GRGDSPK. With 10 and 50 μM GRGDSPK, bone morphology was dramatically altered, with a disruption of osteoblast and mineralized matrix organization. To assess the effect of the peptides on bone resorption, fetal bones were prelabeled in vivo with 45Ca and resorption was stimulated in vitro with parathyroid hormone in the presence or absence of the peptide. A significant decrease in 45Ca release was found with 10 and 50 μM GRGDSPK. Osteoclast number was also significantly decreased on the bone surface. The peptide was not cytotoxic, since no effect on DNA content, dry weight, or collagen synthesis was found. GRADSP, a control peptide, had no significant effect on mineralization, resorption, or other parameters of bone growth. Visualization of β1 and α2 integrin in GRGDSPK-treated bones by indirect immunofluorescence demonstrated a decreased in integrin staining, particularly in the osteoblast layer, compared to control bones and bones treated with GRADSP. The inhibition of bone formation and resorption by an RGD-containing peptide in a mineralizing organ culture system suggests that integrins have an important role in osteoblast and osteoclast-mediated bone remodeling.
Proton-induced physicochemical calcium release from ceramic apatite disks
Authors: Bushinsky David A. , Sessler Nelson E. , Glena Richard E. , Featherstone John D.B. 
Published: February 2010

Abstract
When bone is cultured in acid medium there is net calcium efflux (JCa) and proton influx (JH) relative to the mineral. The acid medium appears to induce physicochemical mineral dissolution as well as cell-mediated bone resorption. To determine the independent effect of acid medium on physicochemical dissolution, we utilized cell-free synthetic ceramic apatite (CAP) disks, which contain carbonate (5.5%) in an apatite structure chemically similar to mammalian bone. CAP disks were cultured in control (Ctl, pH ≅ 7.44) or acid (Met, pH ≅ 7.11) medium for 48 h and compared to similarly treated neonatal (4–6 days old) mouse calvariae. Medium was changed and analyzed at 3, 24, and 48 h. At 3, 24, and 48 h there was significantly greater JCa from the CAP disks and calvariae incubated in Met compared to Ctl; over the entire 48 h time period there was a greater progressive increase in JCa from the CAP disks than the calvariae incubated in Met. There was no significant JCa at 3, 24, or 48 h from CAP disks or calvariae incubated in Ctl. At 3 h there was significantly greater JH into the CAP disks and calvariae incubated in Met compared to Ctl; JH was greater into the CAP disks than the calvariae. Utilizing a synthetic model of bone mineral we demonstrated that acid medium induces physicochemical calcium efflux and proton influx relative to the mineral.
Use of a rat model for the simultaneous assessment of pharmacokinetic and pharmacodynamic aspects of bisphosphonate treatment: Application to the study of intravenous 14C-labeled 1-hydroxy-3-(1-pyrrolidinyl)-propylidene-1,1-bisphosphonate
Authors: Koopmans Sietse J. , Van Der Wee-Pals Lianne , Löwik Clemens W.G.M. , Papapoulos Socrates E. 
Published: February 2010

AbstractBisphosphonates are drugs that suppress osteoclast-mediated bone resorption and are used with increasing frequency in the treatment of skeletal disorders. Therapeutic regimens are largely based on pharmacodynamic information because of difficulties in obtaining and interpreting pharmacokinetic data. We describe here the application of a permanently cannulated rat model, previously used in other areas of endocrine research, to the simultaneous study of pharmacokinetic and pharmacodynamic properties of the newly developed bisphosphonate EB-1053 [1-hydroxy-3-(1-pyrrolidinyl)propylidene-1,1-bisphosphonate]. Two groups of five rats each received daily intravenous injections of [14C]EB-1053 (0.025 and 0.1 mg/day, respectively); a third group (n = 7) received only normal saline injections and served as control. Treatment was given for at least 20 days. A fourth group (n = 3) received IV injections of the bisphosphonate on three separate occasions. Following IV administration, EB-1053 was rapidly cleared from the circulation. Urinary excretion of radioactivity reached about 55% of the daily administered dose within 48 h and remained at this level during the whole treatment period, indicating continuing retention of the bisphosphonate. Bone resorption, assessed biochemically as the hydroxyproline to creatinine ratio in urine, was suppressed effectively with both doses used. Suppression reached a maximum around day 4 and remained at the same level until the end of treatment. Accumulation of the bisphosphonate in the skeleton was therefore not associated with a cumulative effect on bone resorption. This strongly suggests that in treatment planning a distinction should be made between surface-bound and hence biologically active bisphosphonate from the drug which is incorporated in bone during bone turnover. The rat model used in these studies may also allow the examination of other issues of bisphosphonate pharmacology, such as sequential changes in biochemical parameters of bone metabolism in plasma and urine of the same animal, which are necessary for the planning of long-term therapy with uninterrupted administration of these compounds.
Characterization of immunoreactive forms of human osteocalcin generated in vivo and in vitro
Authors: Garnero Patrick , Grimaux Marc , Seguin Patrick , Dr. Delmas Pierre D. 
Published: February 2010

Abstract
Three monoclonal antibodies recognizing the 5–13, 25–37, and 43–49 sequence of the human osteocalcin were used in competitive and two-site radioimmunoassays (RIA) to characterize specifically various immunoreactive forms of circulating human osteocalcin. The intact molecule accounts for 36% of total in normals (2.6 nM), 46% in patients with osteoporosis (3.1 nM), and 26% in chronic renal failure (6.9 nM). Four fragment were detected in addition to the intact molecule in the serum of healthy adults and patients with metabolic bone disease. N-terminal, mid, and mid C-terminal fragments were present in minute amounts (each accounting for 5–14% of the total circulating osteocalcin immnoreactivity). In contrast, the N-terminal mid-fragment, probably resulting from the cleavage around amino acids 43–44, represents about 30% (2 nM) of the total osteocalcin immunoreactive level in normals and patients with osteoporosis and up to 50% (13 nM) in patients with chronic renal failure. This large N-terminal midfragment, representing 75–80% of the intact osteocalcin level, is not lower when the plasma assay is performed immediately after sampling (within 20 minutes at 4°C with proteinase inhibitors), indicating that it circulates in vivo. In addition, this fragment was detected in the supernatant of osteoblastic cells, representing about 28% of the intact peptide. Levels of N-terminal midfragment were not changed after treatment of patients with metabolic bone disease (Paget's disease, reflex sympathetic dystrophy, fibrous dysplasia, and osteoporosis) by bisphosphonate, suggesting that it is not released during bone resorption. The osteocalcin level measured with the two-site immunoradiometric assay specific for the intact molecule or with a conventional bovine RIA was rapidly decreased after incubation of serum at room temperature (-20 and −15%, respectively, after 3 h), whereas the total level of intact osteocalcin plus N-terminal midfragment was not changed. Intact osteocalcin loss can be partially avoided by proteinase inhibitors and by incubating serum at 4°C. In conclusion, we characterized multiple immunoreactive forms of osteocalcin that circulate in addition to the intact molecule, none of them being specifically altered in osteoporosis. The N-terminal midfragment circulates in a large amount, probably resulting from cleavage of the intact molecule in the circulation and/or at peripheral sites. These fragments can also be generated in vitro by proteolytic degradation of the intact molecule. To obtain reliable intact osteocalcin values but also reliable levels measured with conventional competitive RIA, careful control of the sampling conditions is warranted.
Clinical trial of fluoride therapy in postmenopausal osteoporotic women: Extended observations and additional analysis
Authors: Riggs B.L. , O'Fallon W.M. , Lane A. , Hodgson S.F. , Wahner H.W. , Muhs J. , Chao E. , Melton L.J. 
Published: February 2010

Abstract
In a 4 year clinical trial in 202 postmenopausal osteoporotic women receiving NaF at 75 mg/day or placebo (both groups received supplementary calcium at 1500 mg/day), we found (N Engl J Med 322:801, 1990) that NaF increased bone mineral density in the lumbar spine (LS-BMD) substantially but did not decrease vertebral fracture rate (VFR), and it increased the nonvertebral fracture rate. Additional analyses and extended observations are now available on 50 women from the NaF group followed for up to 6 years of treatment. In these women, LS-BMD increased linearly over the 6 years (median rate, 8.7%/year or 0.063 g/cm2/year). Because during the 4 year trial the NaF dosage was decreased (because of side effects) in 54 of the 101 women randomized to NaF, dose-response relationships could be evaluated. For the entire study population, serum F level correlated directly with increase in LS-BMD (r = 0.61, P &lt; 0.001). When individual person-years of observation were grouped by deciles of LS-BMD, VFR (per 100 person-years) decreased to a nadir of 24 as mean LS-BMD for the group increased from 0.6 to 1.2 g/cm2 and then doubled to 52 in the group with mean LS-BMD of 1.6 g/cm2. Multivariate analyses and inspection of three-dimensional plots revealed a complex pattern in which VFR was influenced by interaction of several variables. When the effects of LS-BMD, changes in LS-BMD, and serum F were assessed simultaneously, VFR was seen to decrease with increasing LS-BMD except when the higher LS-BMD was associated with rapid rate of increase in LS-BMD or a large increase from baseline serum F. For some patients (noncompliers or nonresponders), serum F or LS-BMD failed to increase. Thus, it is possible that lower dosages of NaF produce moderate decreases in VFR.
Course of bone mass during and after hormonal replacement therapy with and without addition of nandrolone decanoate
Authors: Erdtsieck R.J. , Pols H.A.P. , van Kuijk C. , Birkenhäger-Frenkel D.H. , Zeelenberg J. , Kooy P.P.M. , Mulder P. , Birkenhäger J.C. 
Published: February 2010

Abstract
A total of 33 women with postmenopausal osteoporosis were matched pairwise by age, years since menopause, and body mass index and randomized to receive either cyclic estrogen-progestagen replacement treatment (group 1) or the same treatment plus nandrolone decanoate (ND; group 2). Both groups were treated during 3 years and subsequently followed for another year off treatment. A year after cessation of the treatment the distal forearm bone mineral content in group 2 was significantly higher than that in group 1. Bone mass measurements in the axial skeleton already showed a significant difference in favor of group 2 after 3 years treatment, which persisted during the year off treatment. The decline in lumbar bone mineral mass and density in the 1 year off treatment was similar in both groups. Correction for body mass did not change these results. Bone turnover parameters did not show significant differences between the two groups after cessation of treatment. A higher muscle mass, induced by ND, could partly explain the differences between the groups since even 1 year after treatment was stopped an increased serum creatinine level was still observed in group 2.
Diagnostic value of estimated volumetric bone mineral density of the lumbar spine in osteoporosis
Authors: Peel N.F.A. , Dr. Eastell R. 
Published: February 2010

Abstract
Bone mineral density (BMD) measurements by dual-energy x-ray absorptiometry (DXA) are planar measurements. By measuring planar BMD in anteroposterior (AP) and lateral projections, it is possible to estimate the volumetric BMD by assuming that the vertebral body is an ellipsoid cylinder. Correction for the third dimension could improve the diagnostic accuracy of spinal BMD measurement in osteoporosis. The aims of this study were (1) to determine the effect of aging on volumetric BMD compared to planar measurements; and (2) to evaluate the diagnostic accuracy of volumetric BMD in comparison to planar measurements. We studied 26 postmenopausal women with osteoporotic vertebral fractures and 114 age- and sex-matched controls without vertebral fractures from a population-based group. AP and lateral decubitus BMD of the lumbar spine were measured by DXA using a Lunar DPX (precision error for AP measurement, 0.8%; for lateral measurement of vertebra L3, 6.4%). Between the ages of 51 and 85 years the decreases in volumetric BMD of L3 (vol L3), lateral BMD of L3 (lat L3), AP BMD of L3 (AP L3), and AP BMD of L2–4 (AP L2–4) were 31, 28, 17, and 17%, respectively. The decrease in BMD compared to controls in the osteoporotics for vol L3, lat L3, AP L3, and AP L2–4 were 31, 34, 23, and 23%; expressed as Z scores, the decreases were −1.36, −1.33, −1.46, and −1.47 standard deviation units. The areas under ROC analysis curves for vol L3, lat L3, AP L3, and AP L2–4 were 85, 86, 87, and 87%, respectively. We conclude that there is a greater decrease in volumetric and lateral BMD of vertebra L3 than the AP measurements, both with age and in postmenopausal osteoporosis compared to age-matched controls. However, the diagnostic accuracy was not improved by correcting BMC for vertebral volume. The greater decreases observed with aging may result from the high proportion of cancellous bone in the vertebral body. The lack of improvement in diagnostic accuracy may be because of the large precision error in lateral decubitus (and hence volumetric) BMD measurements. It is possible that the diagnostic accuracy of estimated volumetric BMD may improve with the use of lateral supine DXA, a measurement with lower precision error.