摘要:

AbstractPeak bone mass is determined mainly by genetic‐ethnic factors, but environmental factors such as calcium intake and physical activity during childhood and adolescence could play a role. We have measured the bone mineral density (BMD) of 151 healthy children and adolescents, ages 7–153 years. Density was measured by dual X‐ray absorptiometry (DXA) at two sites (lumbar verterbrae L1–L4 and the upper femur), and the data were analyzed in terms of the height, weight, sexual maturation, spontaneous calcium intake, and physical activity. Of the children, 57–71% had calcium intakes below 1000 mg/day. BMD increased with pubertal maturation from 0.68 ± 0.08 to 0.92 ± 0.09 g/cm2(vertebral bone density, VBD) and from 0.87 ± 0.10 to 1.03 ± 0.09 g/cm2(femoral bone density, FBD) between Tanner stage 1 and 5. Multiple regression analysis showed that body weight and Tanner stage were main determinants of bone density when expressed as g/cm2. The weekly duration of sports activity also influenced both the vertebral (p<0.001) and femoral (p= 0.01) sites, especially in girls and during puberty. Dietary calcium appeared to be another independent determinant of BMD, especially before puberty, at the vertebral (p= 0.02) site. Most important, dietary calcium was found to be the main determinant of vertebral mineral density, when expressed as z score, in both sexes. Moreover, 93% of the 28 children with low vertebral z score values (below –1) and 84% of the 31 children with low femoral z score values (below –1) had dietary calcium intakes

ISSN:0884-0431    

DOI:10.1002/jbmr.5650100502

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1995

数据来源: WILEY

摘要:

AbstractDuring normal growth of the rat ulna, bone is resorbed from the medial periosteal surface. This occurs as part of the modeling process by which the bone achieves its adult shape. By attaching strain gauges to the ulnae of rats in vivo, we measured the strains imposed on that surface of the bone during normal locomotion. We then applied mechanical loads to the ulnae of other rats in vivo for 6 consecutive days, inducing strains approximately double those we had measured. Fluorochromes were given on the 1st and 5th days. The histology of the medial ulnar periosteal surface was correlated with the amount of fluorochrome incorporation and tartrate resistant acid phosphatase (TRAP) activity in serial sections. In the nonloaded ulnae, the surfaces were lined with bone resorbing cells. Corresponding areas of the loaded bones were lined with osteoid and osteoblasts. There was insignificant label incorporation in the nonloaded bones but almost continuous label incorporation in the corresponding regions of the loaded bones, which was significantly different from the nonloaded bones. TRAP activity of the periosteal cells in the loaded bones was significantly less than in the nonloaded limbs. It is widely acknowledged that loading induces bone formation, and this implies that it also has the ability to inhibit resorption. However, to date there has been little direct evidence for the inhibition of resorption in vivo by mechanical loading. The changes we have observed are similar to the sequence of cellular events that occur during the reversal phase of bone remodeling, in which osteoclastic resorption ceases and osteoblasts are recruited and begin formation. This model may help increase understanding of that process.

ISSN:0884-0431    

DOI:10.1002/jbmr.5650100503

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1995

数据来源: WILEY

摘要:

AbstractThe recently discovered osteogenic growth peptide (OGP) has been shown to regulate proliferation in fibroblastic and osteoblastic cell lines derived from rats and mice and also alkaline phosphatase activity in the latter was found to be affected. In vivo the OGP enhances bone formation and trabecular bone density. The results of the current study indicate that the OGP is also a potent regulator of marrow stromal cells from man and rabbit, as well as rabbit muscle fibroblasts. The main OGP activity in both marrow systems is a marked stimulation of alkaline phosphatase activity and matrix mineralization. In the rabbit‐derived cell culture this enhancement is accompanied by a reciprocal inhibition of proliferation. On the other hand, the human cells show a concomitant increase of both parameters. The proliferative effect of the OGP is similar to that of growth hormone (GH) and basic fibroblast growth factor (bFGF). The combined activity of the OGP with GH is smaller than that of each of the polypeptides alone. The OGP and bFGF potentiate each other. Of the three polypeptides tested, OGP is the most potent enhancer of alkaline phosphatase activity and mineralization. bFGF has no influence on these characteristics of osteogenic maturation. The OGP maturational activity is unaffected by either GH or bFGF. These data suggest that the marrow stromal cells serve as targets for the OGP that mediate the OGP‐induced increase in osteogenesis. The effect on the human cells implies a role for the OGP in clinical situations where the osteogenic potential of bone marrow is invol

ISSN:0884-0431    

DOI:10.1002/jbmr.5650100504

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1995

数据来源: WILEY

摘要:

AbstractAn investigative study was carried out for 2 years involving 124 randomly selected early postmenopausal women with spine bone mineral density (BMD) below the mean value of a normal premenopausal subject. After random division into three groups, the first 42 patients were treated with transcutaneous 17‐β‐estradiol (50 μg daily), the second 42 were treated with cyclical intravenous clodronate (200 mg/month iv infusion), and the third group of 40 (controls) was left untreated. After 2 years, the total drop in BMD within the control group was more than 7% as opposed to the values of –0.14% ± 0.93 in the estradiol group and 0.67% ± 0.84 in the clodronate group. A change in BMD of<1% was considered satisfactory, and this result was obtained in 32% of the controls, in 79% of the estradiol group where the percentage change in BMD moderately correlated with serum estradiol levels (r= 0.399), and in 90% of the clodronate‐treated patients, in whom the percentage change in BMD inversely correlated with basal values of markers of bone turnover. Both estrogen and clodronate prevent postmenopausal bone loss. The response to transcutaneous hormone replacement therapy may be influenced by transcutaneous absorption and by a lower sensitivity to estrogen. Response to cyclical clodronate seems to be influenced by the rate of bone turnover. An interdosage interval ranging from 2–4 weeks appears suitable for

ISSN:0884-0431    

DOI:10.1002/jbmr.5650100505

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1995

数据来源: WILEY

摘要:

AbstractWhile calcium release from intracellular stores is a signaling mechanism used universally by cells responding to hormones and growth factors, the compartmentalization and regulated release of calcium is cell type‐specific. We employed thapsigargin and 2,5,‐di‐(tert‐butyl)‐1,4‐benzohydroquinone (tBuHQ), two inhibitors of endoplasmic reticulum (ER) Ca2+‐ATPase activity which block the transport of Ca2+into intracellular stores, to characterize free Ca2+compartmentalization in UMR 106–01 osteoblastic osteosarcoma cells. Each drug elicited transient increases in cytosolic free Ca2+([Ca2+]i), followed by a stable plateau phase which was elevated above the control [Ca2+]i. The release of Ca2+from intracellular stores was coupled to an increased plasma membrane Ca2+permeability which was not due to L‐type Ca2+channels. Thapsigargin and tBuHQ emptied the intracellular calcium pool which was released in response to either ATP or thrombin, identifying it as the inositol 1,4,5‐trisphosphate‐sensitive calcium store. The results of sequential and simultaneous additions of thapsigargin and tBuHQ indicate that both drugs depleted the same Ca2+store and inhibited the same

ISSN:0884-0431    

DOI:10.1002/jbmr.5650100506

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1995

数据来源: WILEY

摘要:

AbstractIncreasing peak bone mineral density (BMD) or content (BMC) in young women may help to reduce the incidence of osteoporosis. Identifying the age when peak bone content or density is attained is essential to develop strategies aimed at optimizing peak BMD and BMC. Total body bone mineral density (TBBMD) and content (TBBMC) were measured by a dual X‐ray absorptiometer in healthy females (n= 247, aged 11–32 years). TBBMD and TBBMC were modeled separately as a nonlinear function of age. By age 22.1 ± 2.5 years, 99% of peak BMD is attained, and by age 26.2 ± 3.7 years, 99% of peak BMC is attained. Nonlinear relationships between weight and TBBMD or TBBMC were also modeled. In this model, the influence of several parameters, including age, weight, and height, on BMC and BMD were simultaneously assessed. A model with age and weight described the best fit for TBBMD, whereas age, weight, and height described the best fit for total body

ISSN:0884-0431    

DOI:10.1002/jbmr.5650100507

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1995

数据来源: WILEY

摘要:

AbstractIt has been previously reported that parathyroid cells express endothelin (ET) receptors and secrete ET‐1 in an extracellular Ca2+concentration ([Ca2+]e)‐dependent manner. Here, we examined the effects of ET‐1 on intracellular signaling and parathyroid hormone (PTH) secretion in dispersed bovine parathyroid (bPT) cells, which comprise several cell types including epithelial and endothelial cells, in two cell lines, the rat parathyroid epithelial (PT‐r) and the bovine parathyroid endothelial (BPE‐1) cells. An RNA‐polymerase chain reaction analysis revealed that both ETAand ETBreceptors are expressed in bovine parathyroid tissue and BPE‐1 cells, and only the ETAreceptor is expressed in PT‐r cells. PT‐r cells also expressed an inositol 1,4,5‐trisphosphate (Ins[1,4,5]P3) receptor, and ionomycin induced an increase in the intracellular Ca2+concentrations ([Ca2+]i) in a Ca2+‐deficient medium, indicating the presence of an operative intracellular Ca2+pool in these cells. In cells bathed in 1 mM [Ca2+]e, ET‐1 induced a rapid and transient increase in the Ins(1,4,5)P3production, which was associated with a similar profile of increase in [Ca2+]iand with a peak response of about 800 nM. No changes in the profile of [Ca2+]iresponses were observed in ET‐1–stimulated cells in the presence of Ca2+channel blockers, or in Ca2+‐deficient medium, indicating that Ca2+mobilization was not associated with Ca2+entry. Furthermore, a sustained stimulation with ET‐1 induced a decrease in [Ca2+]ibelow the prestimulatory level in a large population of cells, and the percentage of the cell population that shows the sustained decrease of [Ca2+]iincreased in higher ET‐1 concentrations. [Ca2+]iin PT‐r cells was also controlled by a [Ca2+]e‐dependent mechanism that changed [Ca2+]ifrom 28 to 506 nM in a 0.1–3 mM concentration range with an EC50of 1.2 mM, which is comparable to that reported for bPT cells. In the same range of [Ca2+]e, PTH secretion from bPT cells was inhibited with an IC50of 1 mM, and ET‐1 increased PTH release in a dose‐dependent manner but without affecting the IC50for the [Ca2+]e‐dependent inhibition. Thus, the parathyroid epithelial cells appear to respond to ET‐1 in a unique way, and the ET autocrine system can be regarded as a possible mechanism to modulate t

ISSN:0884-0431    

DOI:10.1002/jbmr.5650100508

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1995

数据来源: WILEY

摘要:

AbstractStaphylococcus aureusinfections are associated with rapid bone destruction in conditions such as osteomyelitis, bacterial arthritis, and infected orthopedic implant failure. How this bacterium induces bone destruction has not been defined. In studies of the role of oral Gram‐negative bacteria in periodontal pathology, we have established that cell surface‐associated proteins (SAPs) are potent stimulators of bone resorption. The surface‐associated components fromS. aureushave now been isolated and demonstrated to be extremely potent stimulators of bone resorption in the murine calvarial bone resorption assay. Bone resorption appears to be due to proteins, is not the result of contamination with lipoteichoic acid or muramvl dipeptide, and is potently inhibited by indomethacin and can be completely blocked by high concentrations of interleukin‐1 receptor antagonist or TN3–19.12, a neutralizing monoclonal antibody to murine TNF. The SAP fraction can stimulate fibroblasts or monocytes to release osteolytic cytokines, but only at high concentrations. Fractionation of the SAPs by high performance liquid chromatography demonstrated that a number of fractions were osteolytically active. The most active contained a heterodimeric protein of molecular weight 32–36 kD. The presence of this osteolytically active surface‐associated fraction may account for the bone resorption associated with local infection

ISSN:0884-0431    

DOI:10.1002/jbmr.5650100509

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1995

数据来源: WILEY

摘要:

AbstractThe role of basic fibroblast growth factor (bFGF) and insulin‐like growth factor I (IGF‐I) in cartilage growth was studied in primary cultures of rat rib growth plate chondrocytes. Growth factors effects on expression of the proto‐oncogene c‐fos, DNA synthesis, differentiation, and morphological changes were analyzed by in situ hybridization,3H‐thymidine incorporation, and light and fluorescence microscopy. In serum‐deprived cells, bFGF induced a transient expression of c‐foswith a maximal effect 15–30 minutes after stimulation. After 24 h of culture it had a slightly lower stimulatory effect on DNA synthesis than IGF‐I, but became a significantly more potent mitogen than IGF‐I after 48 and 72 h. The stimulatory effect of bFGF on DNA synthesis coincided with a decrease in collagen type II and IGF‐II expression. In contrast, IGF‐I alone stimulated expression of these genes. In bFGF‐treated cultures, cell morphology and the appearance of actin filaments was changed. Polygonal chondrocytes became elongated, fibroblast‐like, and the smooth actin filaments were brush‐like and disrupted. Addition of IGF‐I reduced these changes without affecting c‐fosexpression induced by bFGF. Our results suggest that bFGF stimulates cell proliferation by preventing terminal differentiation of chondrocytes. This effect is mediated by induction of c‐fosexpression and a decrease in the steady‐state levels of t

ISSN:0884-0431    

DOI:10.1002/jbmr.5650100510

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1995

数据来源: WILEY

摘要:

AbstractCa2+and other divalent cations like Sr2+, Ba2+, and Mg2+stimulate rapid and sustained increases in intracellular Ca2+([Ca2+]i) and 1,4,5‐inositol trisphosphate (1,4,5‐InsP3) presumably by interacting with recently identified parathyroid cell membrane Ca2+receptors. We used thapsigargin (THAPS), an inhibitor of the microsomal Ca2+‐ATPase, to deplete InsP3‐sensitive intracellular Ca2+stores to determine whether sustained increases in [Ca2+]idue to divalent cations require intact cytosolic Ca2+pools. In Fura 2‐loaded parathyroid cells, THAPS produced a gradual increase in [Ca2+]iwhich reached a steady‐state level by 2–3 minutes. The effect of THAPS (3 × 10−6M) was substantial with [Ca2+]i, rising from 281 ± 27 nM at 0.5 mM Ca2+to a peak value of 684 ± 30 nM (p<0.0001). The addition of Sr2+to cells at 0.5 mM extracellular Ca2+induced an immediate 2‐to 3‐fold increase in [Ca2+]iwhich stabilized at a [Ca2+]iabove baseline for ≥10 minutes. THAPS (3 × 10−6M) pretreatment for ≥5 minutes blocked this sustained‐phase increment in [Ca2+]idue to Sr2+. In the absence of extracellular Ca2+, there was a slight but nonsignificant effect of THAPS on [Ca2+]i. Incubation of cells with THAPS did not change the levels of3H‐inositol phosphates (InsP3, InsP2, and InsP1) or alter Sr2+‐induced accumulation of InsP3, InsP2, and InsP1. THAPS substantially reduced parathyroid hormone secretion at 1.0 mM Ca2+by 20 ± 16, 57 ± 8, 75 ± 10, and 83 ± 9% at 10−7, 3 × 10−7, 10−6, and 3 × 10−6M THAPS, respectively. We conclude that depletion of intracellular Ca2+stores by THAPS stimulates Ca2+mobilization, presumably from extracellular sources, and that this agent and divalent cations such as Sr2+activate the same pathway for sustained Ca2+mobilization. The inhibition of secretion by THAPS supports the idea that increases in [Ca2+]iplay a suppressive role in

ISSN:0884-0431    

DOI:10.1002/jbmr.5650100511

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1995

数据来源: WILEY