摘要:

AbstractThere is general agreement that bone density falls with age and is higher in heavy people than light people. We have studied a variety of potential correlates of vertebral, ankle, and hip bone density to evaluate other potential influences on the skeleton. We recruited 196 healthy women who were more than 10 years past the menopause and collected a diet and activity record, a 24 h urine, and a fasting blood and urine specimen. These blood and urine samples were analyzed for factors related to calcium homeostasis. We then measured bone density at lumbar vertebrae 1–4 and the hip and the ankle bone density of the nondominant leg. Correlations between vertebral, hip, and ankle bone density and other measured variables were explored using the statistical package SPSS PC. At the vertebral site, in addition to correlations with age and body mass index (BMI), a negative correlation with a measure of bone resorption, the hydroxyproline creatinine ratio (OHPCR), was noted. At the ankle site, in addition to correlation with age, BMI, and OHPCR, a positive correlation with activity and a negative correlation with serum calcitriol were noted. At the hip site, as well as age, BMI, and OHPCR, significant correlations with GFR and dietary calcium intake were noted. These data suggest that even in women 10 years past the menopause bone resorption has a significant effect on bone density, that renal function may account for some of the variance in bone density at the hip, and that activity effects are more marked at sites of greater loading, namely the ankl

ISSN:0884-0431    

DOI:10.1002/jbmr.5650081102

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

年代:1993

数据来源: WILEY

摘要:

AbstractX‐linked hypophosphatemia, a common metabolic bone disease in humans and mice (theHypandGymutations), is characterized by decreased plasma phosphate, decreased renal tubular reabsorption of phosphate, rickets, and osteomalacia. The question of whether intestinal malabsorption of calcium contributes to the bone disease is controversial. Intestinal absorption of45Ca was studied in three different mouse colonies:Gyon B6C3H background,Hypon B6C3H background, andHypon C57BL/6J background, all at 4 weeks of age. The duodenum was isolated by sutures, and45Ca in a 150 mM NaCl and 2 mM CaCl2solution at pH 7.2 was injected into the lumen. Absorption was measured by the amount of45Ca remaining in the lumen and by the plasma isotope level. TheGyandHypmice of both sexes significantly malabsorbed45Ca at 4 weeks of age compared to normal littermates. Following the 4 week study, intestinal absorption was measured at 2, 7–8, and 12 weeks of age in normal andGymice on the B6C3H background. At 2 and 7–8 weeks of age, theGymales significantly malabsorbed45Ca compared to their normal littermates. Serum 1,25‐dihydroxyvitamin D was not significantly altered inGymales at 4 weeks of age. This suggests the possibility of resistance of the intestine to stimulation. Malabsorption of calcium in youngGyandHypmice may exacerbate the low mineralization in their rachitic bone

ISSN:0884-0431    

DOI:10.1002/jbmr.5650081103

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

年代:1993

数据来源: WILEY

摘要:

AbstractIn a study of the osteogenesis capability of the human posterior longitudinal ligament of the spine, ligament cells were isolated and cultured. The effect of bone‐seeking hormones, such as parathyroid hormone (PTH), calcitonin (CT), prostaglandin E2(PGE2), and 1,25‐dihydroxycholecalciferol [1,25‐(OH)2D3], on the ligament cells was investigated with respect to DNA synthesis, adenosine‐3′,5′‐cyclic monophosphate (cAMP) levels, alkaline phosphatase (ALP) activity, and acid phosphatase (ACP) activity. Cell lines obtained from nonossified sites in patients with ossification of the posterior longitudinal ligament of the spine (OPLL) were found to have several different phenotypic characteristics for osteoblasts: high ALP activity, PTH‐ and PGE2‐stimulated increases in cAMP, and responses to both CT and 1,25‐(OH)2D3. It is clear that proliferation and differentiation in such ligament cells are controlled by various types of bone‐seeking hormones, and it was suggested that many cells with osteoblast‐like characteristics are present. These results are considered important with respect to the etiology of OPLL, and an experimental system using cultured ligament cells appears to be use

ISSN:0884-0431    

DOI:10.1002/jbmr.5650081104

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

年代:1993

数据来源: WILEY

摘要:

AbstractAnchorage‐dependent cultures of a population of cells derived from the outer part of the rat calvaria demonstrated decreased net accumulation of radiolabeled chondroitin sulfate (CS) and hyaluronic acid (HA) per cell as the cell density of the cultures increased. The addition of TGF‐β1resulted in large stimulations of the net CS, but not of the net HA, accumulating in the medium at all cell densities and an abolition of the density‐dependent effect. These effects were largely due to increases in newly synthesized CS appearing in the medium. Supplementation of the culture media with CS had complex but relatively small effects on the stimulation of the net accumulation of radiolabeled medium CS by TGF‐β1. The addition of TGF‐β1also resulted in a biphasic effect on cell growth that depended on the plating density, but cell growth differences could not account for the marked stimulation of CS synthesis by TGF‐β1. Experiments with cycloheximide and β‐xyloside and isolation of the intact anionic glycoconjugates (AG) indicated that although synthesis of core protein was the limiting factor in CS synthesis, TGF‐β1stimulated the synthesis of CS chain when sufficient β‐xyloside acceptor was available. The overall results suggest that, in this cell system, the action of TGF‐β1on the synthesis of the major extracellular AGs is characterized by a relatively specific upregulation of CS proteoglycan (PG) synthesis and an uncoupling of the inhibitory effect of high cell

ISSN:0884-0431    

DOI:10.1002/jbmr.5650081105

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

年代:1993

数据来源: WILEY

摘要:

AbstractA pilot study was conducted to investigate the combined effects of ovariectomy (OVX) with preceding and concomitant mild dietary calcium restriction on the minipig skeleton. Minipigs 4 months old were fed diets containing 0.9, 0.75, or 0.5% calcium (Ca). At 10 months, the 0.75 and 0.5% pigs were OVX and the 0.9% were either sham operated or OVX. All pigs were maintained on their respective diets for an additional 6 months. Excised lumbar vertebrae and long bones were evaluated by densitometry and histomorphometry, and vertebral cancellous bone samples were tested biomechanically. In pigs fed the 0.9% Ca diet, OVX alone effected decreases of 6% in vertebral bone mineral density (BMD), 15% in trabecular bone volume (BV/TV), and 13% in trabecular number (Tb.N), an increase of 15% in trabecular separation (Tb.Sp), and a nonsignificant increase (p<0.056) in vertebral cancellous final erosion depth (F.E.De) compared with the 0.9% Ca sham‐operated group. Decreasing dietary Ca to 0.5% in combination with OVX effected an 8% reduction in vertebral BMD that was not associated with any significant alterations in parameters of vertebral cancellous bone microstructure or remodeling compared with the 0.9% Ca sham‐operated pigs. Increases in serum PTH noted in the 0.5% Ca OVX group were generally paralleled by increases in calcitriol. In OVX pigs fed a diet containing 0.75% Ca, a 10% reduction in vertebral BMD was observed. This was associated with significant increases in F.E.De and vertebral marrow star volume (Ma.St.V) compared with the 0.9% Ca sham‐operated pigs and the other OVX groups. In addition, Tb.Sp was increased and Tb.N decreased compared with the 0.9% Ca sham‐operated pigs. Increases in serum PTH in this group were not accompanied by increases in calcitriol. Midradial and midfemoral BMD values were reduced in the 0.75 and 0.5% Ca OVX groups compared with the 0.9% Ca sham‐operated pigs. Histomorphometric analyses of cortical bone suggested the reduction in cortical bone mass in the 0.75% Ca OVX group may have been largely due to net loss on the endocortical surface versus possible failure to accrue bone in the 0.5% Ca OVX group. Ash density and biomechanical parameters for vertebral cancellous bone decreased progressively in the 0.9% sham‐operated, 0.9% Ca OVX, and 0.75% Ca OVX groups and then increased in the 0.5% Ca OVX group. After normalization for bone mass (ash), mechanical changes were still apparent, particularly for the 0.75% Ca OVX group compared with other OVX groups, reflecting that structural changes had taken place in the trabecular network. In minipigs, OVX results in increases in resorptive cell function at the level of the remodeling unit that effect minor alterations in cancellous bone microstructure. Imposing moderate calcium restriction (0.5%) in combination with OVX appears to blunt rather than exaggerate resorptive cell function in vertebral cancellous bone, essentially preserving microstructure; this effect may be a consequence of the combined increase in PTH and calcitriol. OVX in combination with mild dietary calcium restriction (0.75%) results in excessive resorptive cell function at the level of the remodeling unit associated with vertebral cancellous osteopenia and reduced biomechanical competence of vertebral cancellous bone. The reduction in cancellous bone in this group appears to be due, at least in part, to trabecular perforation. The alterations in remodeling may be a consequence of elevated PTH unopposed by calcitriol. The calcium‐restricted (0.75%) Sinclair S‐1 OVX minipig appears to be a model of primarily cancellous osteopenia associated with increased resorptive cell function at the level of the remodeling unit and trabecular plate perforation. This animal model may be valuable for studying the consequences of alterations of remodeling and resorptive cell function on cancellous bone microstructure and strength and may be useful for modeling certain aspects of perimenopausal bon

ISSN:0884-0431    

DOI:10.1002/jbmr.5650081106

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

年代:1993

数据来源: WILEY

摘要:

AbstractElectrical fields have been implicated in accelerated bone healing and as a transduction mechanism for mechanically driven bone remodeling. Applied mechanical or electrical stimulation of bone remodeling suggests that this depends on the magnitude, frequency, and duration of the stimulus. The magnitude of endogenous electrical fields, manifest by streaming potentials (SPs) across canine cortical bone, were measured as a function of bending frequency in vivo and then in vitro at healing drill holes and at remodeling (ipsilateral) and normal, intact (contralateral) control sites in canine tibia. SP magnitudes normalized to periosteal strain were smaller for drill holes at 2 and 4 weeks postsurgery relative to either remodeling (P<0.05 at 10 Hz) or normal intact (P<0.001 at 10 Hz) controls both in vivo and in vitro. SPs of 12 week drill holes were similar to SPs of remodeling controls and tended to be smaller than SPs of normal intact controls. Mean SP normalized to bone impedance was approximately the same for all sites, suggesting that the smaller SPs during healing and remodeling relate to smaller bone impedance and/or larger porosity. SP as a function of bending frequency for normal sites was similar to that observed previously. SP versus frequency for drill holes and remodeling controls was more variable, probably because of variations in bone microstructure, and displayed a higher frequency content. The observed differences in SP magnitude and frequency response to loading associated with stages of healing indicate that endogenous electrical fields do indeed respond to the structural changes in healing and remodeling and are therefore capable of providing structural feedback information for the repair and remodeling process.

ISSN:0884-0431    

DOI:10.1002/jbmr.5650081107

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe lymphokine interleukin‐4 (IL‐4) is an important lymphocyte growth factor, and it also has a modulatory role on hematopoiesis. It was recently reported that IL‐4 has an inhibitory effect on bone resorption in vitro, but the underlying mechanisms are not well known. We studied its effects on the formation of osteoclast‐like cells in mouse bone marrow cultures and in cocultures of spleen cells and stromal cells. The addition of recombinant mouse IL‐4 (0.01–10 ng/ml) induced a marked dose‐dependent inhibition on the formation of TRAP‐positive multinucleated cells (MNC) in bone marrow cultures. The effect was blocked by anti‐IL‐4 antibodies and was not related to a decreased production of IL‐6. The inhibitory effect required the presence of IL‐4 during the second half of the culture period. Time course experiments showed that IL‐4 impaired the formation of osteoclast‐like cells rather than inducing the disappearance of previously formed cells. This inhibitory effect was associated with increased numbers of esterase‐positive cells. Moderately high doses of IL‐4 (1–10 ng/ml) also induced the formation of abundant macrophage polykaryons that did not form resorption pits. IL‐4 had a similar inhibitory effect on the formation of osteoclast‐like cells in cocultures of mouse spleen cells and stromal cells. Our results suggest that IL‐4 acts on uncommitted macrophage‐osteoclast precursors, inducing a preferential differentiation toward the macrophage lineage and thus decreasi

ISSN:0884-0431    

DOI:10.1002/jbmr.5650081108

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

年代:1993

数据来源: WILEY

摘要:

AbstractWe previously found that bone loss occurs as soon as 1 month after ovariohysterectomy (OHX) in beagle dogs. Indirect evidence pointed to an early dramatic increase in bone resorption. To verify this hypothesis and evaluate the effects of a newly developed bisphosphonate, BM 21.0955 (Boehringer Mannheim), 36 beagle dogs were subjected to OHX and 12 dogs were sham operated (Sham). OHX dogs were divided into six groups (n= 6 each) and received subcutaneous injections of vehicle or BM 21.0955 at various doses (0.1, 0.3, 1, 10, and 100 μg/kg/day) for 1 month. Sham dogs were given vehicle (n= 6) or BM 21.0955 (1 μg/kg/day,n= 6). Iliac crest biopsies and blood drawings were done at baseline and at month 1. OHX dogs given vehicle exhibited a decrease in cancellous bone volume associated with an increase in erosion depth and a decrease in serum levels of 1,25‐dihydroxyvitamin D. BM 21.0955 prevented the bone loss at a dose ≥ 1 μg/kg and the increase in erosion depth and the decrease in serum levels of 1,25‐(OH)2D at a dose ≥ 0.3 μg/kg. No osteomalacia was observed at any dose of BM 21.0955. Bone turnover was reduced only when BM 21.0955 was administered at doses of 10 or 100 μg/kg. There were no changes in body weight or serum levels of calcium, phosphorus, creatinine, parathyroid hormone, or osteocalcin in all groups. The increase in erosion depth in OHX dogs given vehicle proves that the early rapid bone loss after cessation of ovarian function is related to an increase in osteoclastic activity. The antiosteoclastic activity of BM 21.0955 at a dose ≥ 1 μg/kg prevents this increase and preserves bone volume. The absence of any signs of osteomalacia at any dose confers a relatively wide therapeutic margin to BM 21.0955. BM 21.0955 at a dose ≥ 10 μg/kg also acts as an inhibitor of bone turnover. This is not observed at a dose of 1 μg/kg, at least after 1 mont

ISSN:0884-0431    

DOI:10.1002/jbmr.5650081109

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

年代:1993

数据来源: WILEY

摘要:

AbstractOsteoid nodules form in cultures of fetal rat calvarial (RC) cells grown in medium containing 10% FBS and 50 μg/ml of ascorbic acid. When 10 mM β‐glycerophosphate (β‐GP) is added, osteoid nodules mineralize in two phases: an initiation phase, which is dependent upon alkaline phosphatase activity for conversion of β‐GP to Pi, and a progression phase that proceeds independently of alkaline phosphatase activity and does not require exogenous phosphate. We have now used this system to investigate the effects of fluoride (F−) on mineralization. In cultures in which osteoid was formed and mineralization initiated in the presence of F−, a dose‐dependent inhibition of the initiation of mineralization occurred over a concentration range of 25–500 μM F−(p<0.001 in all cases). The initiation of mineralization was not inhibited if F−was removed from the cultures at the time when mineralization was initiated with β‐GP. In osteoid nodules grown in the absence of F−, addition of F−resulted in a dose‐dependent inhibition of the initiation of mineralization, with significant decreases in45Ca uptake occurring at F−concentrations of 3 μM (p<0.01) and higher. However, if F−was added to cultures after mineralization was initiated in the absence of F−, a stimulation of45Ca uptake was observed at F−concentrations of 250 μM and above (p<0.001). F−(1–1000 μM) did not affect the conversion of β‐GP to Pior alkaline phosphatase activity in the cultures. The data show that mineralization of osteoid formed in the presence of F−is unaffected when F−is removed before initiation, that F−inhibits the initiation phase of mineralization at concentrations as low as 3 μM, and that F−stimulates mineralization during the progression phase. These data agree with clinical observations of hypermineralization of existing bone and hypomineralization of

ISSN:0884-0431    

DOI:10.1002/jbmr.5650081110

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

年代:1993

数据来源: WILEY

摘要:

AbstractEstrogen deficiency is associated with bone loss, and estrogen replacement is an effective treatment of this osteoporotic process. This study examines the early (5–120 s) effects of 17β‐estradiol on the intracellular calcium and phospholipid metabolism in confluent female rat osteoblasts. The cytosolic free Ca2+concentration ([Ca2+]i) was determined using fura‐2/AM as Ca2+probe. Cells were labeled with myo‐[2‐3H]inositol or [14C]arachidonic acid for inositol or lipid determination. Inositol 1,4,5‐trisphosphate (IP3) and diacylglycerol (DAG) production were determined by either mass measurement or anion‐exchange chromatography or by thin‐layer chromatography, respectively. 17β‐Estradiol (1 pM to 1 nM) increased [Ca2+]iin a biphasic manner within 10 s via Ca2+influx from the extracellular milieu, as shown by the effects of the calcium chelator EGTA and the Ca2+channel blockers nifedipine and verapamil, and via Ca2+mobilization from the endoplasmic reticulum (ER), as shown by the effects of thapsigargin. 17β‐Estradiol (1 pM to 1 nM) induced a biphasic and concomitant increase in IP3and DAG formation. Estradiol immobilized on bovine serum albumin (BSA) [E‐(O‐carboxymethyl)oxime BSA] and its derivative (O‐carboxymethyl)oxime rapidly increased ([Ca2+]i, IP3, and DAG and were full agonists, although they were less potent than the free estradiol. They had the same action time course and acted via Ca2+influx and Ca2+mobilization from ER. Tamoxifen, a potent inhibitor of genomic steroid responses, did not block the rapid increase in Ca2+, IP3, and DAG induced by estradiol. Finally, inhibitor of phospholipase C (neomycin) and pertussis toxin abolished the effects of 17β‐estradiol on IP3and DAG formation. These results suggest that female rat osteoblasts bear non‐genomic unconventional cell surface receptors for estradiol, belonging to the class of the membrane receptors coupled to a phospholipase C via a pe

ISSN:0884-0431    

DOI:10.1002/jbmr.5650081111

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

年代:1993

数据来源: WILEY