bluuebunny/crossref_metadata_2025_split huggingface dataset:
Journal of Bone and Mineral Research
Authors: Avioli Louis V. 
Published: February 2010

Abstract
Hormonal control of skeletal growth, modeling, and remodeling is characterized by a complex interaction between the calciotropic hormones (25-hydroxycholecalciferol, 1,25-dihydroxycholecalciferol, parathyroid hormone, and calcitonin), growth, and thyroid hormones in addition to the estrogenic and androgenic gonadal hormones. Although both growth and thyroid hormones are essential for normal skeletal growth and modeling and also can produce detrimental skeletal effects in adults when circulating in excess concentrations, these hormones assume a minor role in the day-to-day bone remodeling of the mature skeleton. Following the attainment of the peak bone mass, bone mineral content begins to decline in the fourth and fifth decades of life, accelerating in females in the first 5–7 years after the menopause as a result of estrogen deficiency. Associated with this age-dependent loss in skeletal mass are decreases in calcitonin reserve primarily in the 5–7 years following the menopause, decreases in circulating 25-hydroxycholecalciferol, intestinal resistance to 1,25-dihydroxycholecalciferol, and a gradual progressive rise in blood parathyroid hormone. These changes in calciotropic hormone profiles, together with poor nutritional habits, anticonvulsant, glucocorticoid, and thyroid medications, diseases such as type I diabetes, immobilization, or decreased physical activity all serve to weaken the aging skeleton. The result is a gradual and subtle change in skeletal anatomy, which progresses to alterations in vertebral structure, such as kyphosis, scoliosis, and pseudospondylolisthesis, and a variety of sciatic and nerve entrapment syndromes. Vertebral, forearm, and hip fractures and edentulism ultimately comprise the syndrome of age-related bone loss, resulting in lifestyle disabilities, extensive morbidity, analgesic drug abuse, hospitalization, and escalating annual health care expenditures.
Journal of Bone and Mineral Research
Authors: Teitelbaum Steven L. 
Published: February 2010

Abstract
Bone remodeling is a process initiated by the osteoclast, and thus, its understanding is prerequisite to regulation of bone turnover. The last decade has witnessed major advances in our understanding of osteoclast biology, specifically as relates to the ontogeny of the cell and the mechanisms by which it degrades bone. It is now possible to isolate and generate osteoclasts and maintain them in relative purity. Using these models, a number of laboratories have shown that ion transport by the osteoclast plays a major role in its ability to resorb bone. Furthermore, osteoclast–bone matrix attachment, mediated at least in part by integrins, is pivotal to the resorptive process. These discoveries are likely to lead to insight into control of the remodeling process.
Absence of paramyxovirus RNA in cultures of pagetic bone cells and in pagetic bon
Authors: Dr. Birch M.A. , Taylor W. , Fraser W.D. , Ralston S.H. , Hart C.A. , Gallagher J.A. 
Published: February 2010

Abstract
It has been proposed that Paget's disease of bone is caused by the infection of bone cells with one or several paramyxoviruses. In this study we used the polymerase chain reaction (PCR), which allows the detection of very low levels of a target nucleic acid sequence, to study cultures of pagetic bone cells and samples of pagetic bone. Oligonucleotide primers were designed to flank a sequence of the nucleocapsid genome of measles virus and canine distemper virus (CDV). Within this fragment there were contrasting restriction endonuclease sites specific to measles or CDV that allowed identification of the original template. We were unable to detect paramyxovirus RNA in four strains of human bone cells outgrown from pagetic bone and one strain derived from an uninvolved site of a patient with Paget's disease. Furthermore, paramyxovirus sequences were not detected in cDNA prepared from six samples of pagetic bone biopsies. The work presented here further questions the role of measles and CDV in the abnormal remodeling observed in Paget's disease.
Regulation of insulin-like growth factor binding protein 4 by a specific insulin-like growth factor binding protein 4 proteinase in normal human osteoblast-like cells: Implications in bone cell physiology
Authors: Durham Susan K. , Kiefer Michael C. , Riggs Lawrence B. , Conover Cheryl A. 
Published: February 2010

Abstract
Insulin-like growth factor binding protein 4 (IGFBP-4) is secreted by normal human osteoblast-like cells (hOB) and is a potent inhibitor of insulin-like growth factor (IGF) action in vitro. In previous studies, IGF treatment of hOB in culture led to markedly reduced medium levels of IGFBP-4 as detected by western ligand blotting. In the present study, incubation of hOB-conditioned medium (hOB-CM) with IGF under cell-free conditions resulted in a similar loss of IGFBP-4. Both IGF-I and IGF-II were capable of inducing a decrease in IGFBP-4; however, IGF-II was more effective. When the six characterized IGFBP were added to hOB-CM, only IGFBP-4 disappeared in response to IGF-II addition. This IGF-regulated loss of IGFBP-4 was inhibited by metalloproteinase inhibitors and appeared to be due to a proteinase that cleaved IGFBP-4 in 18 and 14 kD fragments identified by western immunoblotting. Conditioned media from eight of eight different donor hOB lines tested exhibited IGFBP-4 proteinase activity. To assess the biologic consequences of IGF-II-induced IGFBP-4 proteolysis, we treated hOB with IGF-II for 5 h, which decreased medium IGFBP-4 by 70%, and then measured IGF-I and insulin stimulation of [3H]thymidine incorporation. IGF-II itself was not mitogenic and had no effect on insulin-stimulated [3H]thymidine incorporation. However, pretreatment of cultured hOB with IGF-II enhanced IGF-I-stimulated [3H]thymidine incorporation threefold. In conclusion, these data indicate that (1) regulation of IGFBP-4 availability can occur via an IGF-dependent, IGFBP-4 proteinase secreted by normal hOB, and (2) IGF-II-induced IGFBP-4 proteolysis is associated with enhanced hOB response to IGF-I. The IGFBP-4/IGFBP-4 proteinase system may be involved in local regulation of IGF action in bone.
Accuracy, precision, and utility of spine and whole-skeleton mineral measurements by dxa in rats
Authors: Dr. Mitlak Bruce H. , Schoenfeld David , Neer Robert M. 
Published: February 2010

Abstract
We evaluated the precision and accuracy of dual-energy x-ray bone densitometry (DXA) in 38 male and female rats aged 1–10 months. The coefficients of variation (CV) estimated from same-day paired measurements of bone mineral content (BMC) were 1.26% at the lumbar spine and 0.69% at the whole skeleton, and the corresponding CV for BMC corrected for projected bone area (i.e., bone mineral density, BMD) were 0.57 and 0.66%. BMC, measured in vivo, correlated closely with the subsequently determined ash weights (spine r2 = 0.94, whole-skeleton r2 = 0.97). The long-term CV for BMC measurements, assessed by measuring a frozen animal daily for 4 weeks, were 1.28% for the spine and 1.03% for the whole skeleton; for BMD the corresponding CV were 0.88 and 1.15%. To examine the utility of serial DXA measurements we followed female rats subjected to ovariectomy (OVX) or sham operation at 10 months of age and male rats given daily subcutaneous injections of hPTH-(1–34) or vehicle starting at 10 months of age every 3 weeks for 15 weeks. In the OVX rats a progressive decrease in spine BMC was observed that was most rapid during the first 6 weeks. By 15 weeks the mean spine BMC decreased by 17% in the OVX rats (p &lt; 0.007 versus sham operation). OVX did not affect the accuracy of DXA measurements as assessed by comparison with the ash weight at the end of the 15 week study. PTH treatment increased spine BMC by a mean of 32% and increased whole-skeleton BMC by a mean of 19% within 15 weeks. The long-term in vivo variation was estimated by fitting a model for BMC and BMD in the vehicle-treated male rats and sham-operated female rats, assuming a linear rate of change over the 15 weeks and a different slope and intercept for each animal; the residual root mean squared error was taken as an estimate of variability. Defined in this manner, the long-term variation for BMC measurements in vivo is 5% for the spine and 3% for the whole skeleton; for BMD the corresponding figures are 3 and 2%. This variability is significantly greater than that attributable to instrumental variation and/or same-day repositioning and must be considered when designing experiments requiring serial measurements.XS
Monitoring bone resorption in early postmenopausal women by an immunoassay for cross-linked collagen peptides in urine
Authors: Gertz B.J. , Shao P. , Hanson D.A. , Quan H. , Harris S.T. , Genant H.K. , Chesnut C.H. , Eyre D.R. 
Published: February 2010

Abstract
A new immunoassay using an ELISA approach for measuring urinary excretion of cross-linked N-telopeptides of type 1 collagen was evaluated as a specific measure of bone resorption. The assay was applied to 65 early postmenopausal women who participated in a placebo-controlled trial of the aminobisphosphonate, alendronate sodium. Eight blood and urine samples were collected over a 9 month interval. Baseline cross-linked peptide excretion varied from 26 to 216 pmol BCE (bone collagen equivalents)/μmol Cr. Within-subject variability (CV) for cross-linked peptide excretion was 20.2% over the 9 months in placebo-treated subjects, substantially less than that observed for other biochemical markers of bone resorption: 45, 53, and 63% for fasting urinary calcium and hydroxyproline and 24 h urinary lysylpyridinoline (HPLC assay), respectively. Baseline cross-linked peptide excretion correlated significantly (p &lt; 0.001) with baseline total urine lysylpyridinoline and serum osteocalcin, but not with the other biochemical markers. Initial peptide excretion also correlated inversely with lumbar spine bone mineral density at entry (r = −0.26, p &lt; 0.05). Treatment for 6 weeks with alendronate produced a dose-dependent suppression of cross-linked peptide excretion (0 ± 8, 29 ± 6, 56 ± 5, and 64 ± 3% for 0, 5, 20, and 40 mg, respectively, p &lt; 0.01 versus placebo for treatment effect), with a return toward pretreatment values during follow-up. Measurement of the urinary cross-linked N-telopeptides of type I collagen by this new ELISA approach appears promising as a simple and reliable method to assess overall bone resorption. It may prove especially useful in monitoring the treatment of osteoporotic women with antiresorptive therapy. Its utility in identifying those women in the high resorption range at menopause who may be at greater risk for osteoporosis should also be assessed in future studies.
Effect of long-term tamoxifen therapy on cancellous bone remodeling and structure in women with breast cancer
Authors: Wright C.D.P. , Garrahan N.J. , Stanton M. , Gazet J.-C. , Mansell R.E. , Dr. Compston J.E. 
Published: February 2010

Abstract
The effects of long-term tamoxifen therapy on bone remodeling were studied in 41 women with breast cancer, 22 treated with tamoxifen for a minimum of 15 months (mean 33) and 19 untreated. Transiliac crest bone biopsies were obtained and a comprehensive histomorphometric analysis performed using a semiautomatic image analysis system. There were no statistically significant differences between the two groups in bone area, osteoid perimeter and area, or osteoid width. Mineral appositional rate, adjusted appositional rate, and mineralization lag time were also similar in the two groups; however, tissue-based bone formation rate was significantly lower in the tamoxifen-treated women (p = 0.05) and the remodeling period significantly longer (p &lt; 0.05). Mean and maximum resorption cavity depth and cavity area were significantly reduced in the tamoxifen-treated patients compared to the untreated patients (p &lt; 0.01, p &lt; 0.01, and p &lt; 0.03, respectively). Calculated and directly measured indices of cancellous bone structure were similar in the two groups, although the data indicated a trend toward greater connectedness in the tamoxifen-treated group. These data indicate that tamoxifen does not exert an antiestrogenic effect on bone remodeling in the human and are consistent with a weak estrogenic effect.
Dietary boron modifies the effects of vitamin D3 nutrition on indices of energy substrate utilization and mineral metabolism in the chick
Authors: Hunt Curtiss D. , Herbel Jo L. , Idso Joseph P. 
Published: February 2010

Abstract
An experiment was designed to test part of the hypothesis that physiologic amounts of dietary boron enhance utilization of or, alternatively, compensate for, inadequate concentrations of active vitamin D metabolites to normalize energy substrate utilization and mineral metabolism. Day-old cockerel chicks were fed a ground corn, high-protein casein, corn oil-based diet (&lt;0.18 mg B/kg) supplemented with physiologic amounts of boron (as orthoboric acid) at 0 (non-PSB) or 1.4 (PSB) mg/kg and vitamin D3 (as vitamin D3 powder in corn endosperm carrier) at 3.13 (inadequate, IVD) or 15.6 (adequate, AVD) μg/kg. After 26 days, IVD decreased food consumption and plasma calcium concentrations and increased plasma concentrations of glucose, β-hydroxybutyrate, triglycerides, triiodothyronine, cholesterol, and alkaline phosphatase activity. In the IVD chicks, PSB returned plasma glucose and triglycerides to concentrations exhibited by the AVD chicks and increased food consumption in both IVD and AVD chicks. Histologic findings suggested that PSB enhanced maturation of the growth plate. A ninefold increase in dietary boron yielded only a twofold increase in plasma boron concentration and no increase in femur boron concentration, which suggests that boron is under homeostatic control. The findings suggest that boron acts on at least three separate metabolic sites because it compensates for perturbations in energy substrate utilization induced by vitamin D3 deficiency, enhances major mineral content in bone, and, independently of vitamin D3, enhances some indices of growth cartilage maturation.
Bone response to alternate-day mechanical loading of the rat tibia
Authors: Raab-Cullen D.M. , Akhter M.P. , Kimmel D.B. , Recker R.R. 
Published: February 2010

Abstract
Mechanical loading of the living skeleton influences bone formation, mass, and strength. The primary purpose of the present study was to examine the influence of different loading schedules (days/week) on the bone response to external loading using an in vivo rat tibia four-point bending model. Three studies were conducted to (1) characterize the loaded region, (2) examine the variation of the response within the loaded region, and (3) test the response to different loading schedules. In all studies adult female retired breeder Sprague-Dawley rats were used (6 months, 285 g). First, the location of the loaded region during four-point bending was determined by radiogrammetry of 7 rats. Second, 5 rats were externally loaded for 8 of 10 days at 31 N, 36 cycles, and 2 Hz (1349 ± 244 μϵ). The extent of labeled (forming) periosteal and endocortical surface in the loaded region was compared both among four serial sections from the same tibia and between the loaded and the contralateral tibiae. Finally, 50 rats were randomized into five groups: two nonloaded, control and sham, and three loaded, alternate day, Monday, Wednesday, and Friday, and daily. The rats were externally loaded for 3 weeks at 35 N, 36 cycles, and 2 Hz (1533 ± 308 μϵ). The tibia and fibula were studied for labeled surfaces and mineral apposition rate. For adult female rats with tibial length 39 mm, the loaded region was located 3.5–14 (±0.7) mm proximal to the tibia-fibula junction (TFJ). With multiple repositionings in the same rat, the location of the distal inner pad varied from 3.2 to 3.8 mm proximal to the TFJ (95% confidence interval). The response to loading was consistent within the loaded region and reliably sampled by two cross sections from the loaded region. The bone response under the loading pads was not different from that at other points within the loaded region. There were no differences in the response to external mechanical loading among the three loading schedules (daily, alternate day, and Monday-Wednesday-Friday). Loading created greater formation surface on the medial periosteum of the tibia (70%) and on the fibula (92%) of externally loaded legs than in nonloaded legs. Loading had no effect on the lateral periosteal formation surface or on the endocortical surface of the tibia. Loading created greater mineral apposition rate in loaded than nonloaded tibia (28–72% greater) at all periosteal surfaces. The pattern of response to loading was the same in both studies 2 and 3. In an adult rat, this model produces a predictable bone response to external mechanical loading in a defined region of the tibial diaphysis. External loading 3 or 4 days/week is as effective as daily loading for increasing periosteal bone formation surface and mineral apposition rate.
Loss of parathyroid hormone-stimulated 1,25-dihydroxyvitamin D3 production in aging does not involve protein kinase A or C pathways
Authors: Friedlander Jason , Janulis Mark , Tembe Vrishali , Ro Heung Kyu , Wong Man-Sau , Dr. Favus Murray J. 
Published: February 2010

Abstract
Intestinal calcium absorption declines with aging as a result of decreased renal 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] biosynthesis. At least part of the decline in 1,25-(OH)2D3 may be due to acquired resistance to parathyroid hormone (PTH) stimulation of renal 25-hydroxyvitamin D1-hydroxylase (1-OHase) activity. To test whether aging rats can increase 1,25-(OH)2D3 production in response to PTH, male rats of the same litter were fed a normal Ca diet and were sacrificed at 175–225 g (young rats) or 3 months later at 350–425 g (aging rats). At sacrifice, basal serum 1,25-(OH)2D3 levels (88 ± 16 versus 49 ± 8 pg/ml, P &lt; 0.05) and in vitro renal proximal tubule 1-OHase activity (178 ± 15 versus 77 ± 5 pmol/mg protein/5 minutes, n = 6, P &lt; 0.001) were lower in aging animals. rPTH-(1–34) (10−11 or 10−11 M) increased in vitro 1,25-(OH)2D3 secretion by perifused renal proximal tubules from young but not aging rats. For young and aging rats, rPTH-(1–34) (10−7 M) increased proximal tubule cAMP-dependent protein kinase (PKA) activity, and lower concentrations (10−11 M) stimulated translocation of protein kinase C (PKC) activity from cytosolic to soluble membrane proximal tubule cell fractions. The results of this study show that PTH activation of 1,25-(OH)2D3 production may involve both signaling pathways, with the PKC pathway responsive to lower concentrations of the hormone. The acquired resistance to PTH stimulation of 1,25-(OH)2D3 production in aging appears not to involve the hormonal activation of PKA or PKC.
Bone loss accompanying voluntary weight loss in obese humans
Authors: Jensen Lars Bjørn , Quaade Flemming , Sørensen Ole Helmer 
Published: February 2010

Abstract
Dual-energy x-ray absorptiometry was performed in 51 obese patients before and after 15 weeks on a low-calorie diet. Of these patients 39 were scanned 6 months later. Total and regional body bone mineral, fat mass, and fat free mass were measured. In the control group, 9 normal volunteers were scanned with up to 23 kg lard distributed anteriorly, and 9 volunteers were scanned with 15 kg lard posteriorly. The lard was then gradually removed to simulate the fat loss found in the patient group. In the patient group the mean weight loss was 12,273 g, the mean fat loss was 11,014 g, and the mean bone mineral loss was 171.6 g after 15 weeks. Close correlation between the fat loss and the bone loss was found and calculated to be 16.5 g bone mineral per kg fat in the patient group, in contrast with 0.5 g bone mineral per kg fat in the control group. In the control group, 15 kg lard placed posteriorly had no statistically significant effect on the bone measurements. If weight and fat were regained at the scanning time 6 months later, the bone mineral was regained as well. Patients with further weight loss continued to lose bone mineral. One patient lost 754 g bone mineral in 9 months. Her weight loss was 45 kg in that period, and the bone mineral content remained within the range for normal women at her age. Methodologic and pathogenetic problems are discussed. It is concluded that the observed bone loss should be regarded as physiologic normalization accompanying a diet-induced weight loss in the obese.
Normalization of spine densitometry
Authors: Mazess Richard B. , Barden Howard , Mautalen Carlos , Vega Eduardo 
Published: February 2010

Abstract
We investigated several transformations of bone mineral content (BMC) and area density (BMD), in particular volumetric density (BMAD), to ascertain the influence on (1) body size dependence, (2) diagnostic sensitivity, and (3) precision. These transformations were examined in a group of 657 normal postmenopausal women and 327 women with osteoporotic fracture. First, expression of results as BMAD removed some of the slight dependence on body size; 21% of the variation in BMC and 15% of the variation in BMD were associated with body weight, but only 8% with BMAD. Second, the Z scores compared with those for age-matched controls for BMD and BMC were −1.85 and −1.71, respectively; the Z score for BMAD was −1.64. Third, the precision error for BMC was reduced by expressing results as BMD (1.1 versus 0.5%); BMAD degraded precision slightly (0.7%). BMD appeared to be the optimal expression for bone densitometry because it provided the best diagnostic sensitivity and lowest precision error; there was a minimal influence of body size on BMD results. This study also showed that osteoporotic women, even in the first postmenopausal decade, had low spine BMD, small vertebral area, and low body weight. Such women may be particularly at risk of crush fracture.
Effects of epidermal growth factor on parathyroid hormone-related protein production by mammary epithelial cells
Authors: Ferrari S.L. , Rizzoli R. , Bonjour J.-P. 
Published: February 2010

Abstract
Parathyroid hormone-related protein (PTHrP) plays a prominent role in the pathogenesis of humoral hypercalcemia of malignancy. However, it is also expressed in various nonmalignant tissues, particularly during fetal organogenesis and tissue differentiation. Thus, PTHrP is synthesized in skin, placenta, and mammary gland during lactation. Little is known, however, about the regulation of PTHrP synthesis and release in nontumoral cells. We investigated the regulation of PTHrP production by epidermal growth factor (EGF), a factor of major importance in the development of lactating breast, in primary cultures of rat mammary epithelial cells. EGF stimulated the production of immunoreactive and bioactive PTHrP in a time- and concentration-dependent manner. A 12 h incubation with 10 ng/ml of EGF increased PTHrP production by 36.0 ± 7.1% (n = 7 experiments, p &lt; 0.01). This was accompanied by an increase in PTHrP mRNA steady-state levels. The production of PTHrP was stimulated by the protein kinase C (PKC) activator phorbol-12-myristate-13-acetate (PMA) by 82.9 ± 9.7% (n = 4 experiments, p &lt; 0.01). The effects of PMA and EGF were additive. The EGF-induced stimulation appeared to be independent of extracellular calcium concentration, prostaglandin, or cAMP synthesis, but may have involved tyrosine kinase-mediated mechanisms. These results indicate that EGF was capable of increasing the production of PTHrP by cultured mammary epithelial cells. They also suggest that factors activating the PKC pathway are involved in the upregulation of PTHrP expression in mammary epithelial cells.