摘要:

AbstractWe measured type I procollagen carboxyl‐terminal propeptide (PICP) by a commercial radioimmunoassay and amino‐terminal propeptide (PINP) by an enzyme‐linked immunosorbent assay (ELISA) developed in our laboratory in serum from 75 normal women, 10 growing girls, 84 normal men, and 197 patients with various metabolic bone diseases. The molar concentrations of serum PINP were 100‐fold higher than those of PICP, suggesting differences in the metabolism of PICP and PINP. In normal women, serum PICP values correlated positively with age and serum PINP values correlated negatively with age (r= 0.28 and −0.32, respectively;P= 0.02). In normal men, however, PICP correlated negatively with age (r= −0.32,P= 0.003) whereas PINP did not change. As assessed by Z scores (SD from age‐ and sex‐specific predicted normal mean), changes in serum PICP and PINP values were concordant in hypoparathyroidism (mean Z scores for PICP and PINP, −0.63 and −1.48, respectively) and Cushing's syndrome (0.50 and 0.40) but were discordant in acromegaly (0.78 and −0.68), hyperthyroidism (1.33 and −0.66), untreated postmenopausal osteoporosis (‐0.11 and 0.40), fluoride‐treated postmenopausal osteoporosis (‐0.61 and 1.08), Paget's disease (4.05 and −0.20), and chronic renal failure (1.45 and −0.50). With either assay, deviations from normal were less pronounced than the deviations of concurrently measured serum osteocalcin and bone alkaline phosphatase values. The deviations in these latter two values agreed better with those of PICP than with those of PINP, except in untreated or fluoride‐treated osteoporotic patients. We conclude that for assessing abnormalities in bone formation in metabolic bone diseases, assays for serum PICP or PINP generally are inferior to those for serum osteoc

ISSN:0884-0431    

DOI:10.1002/jbmr.5650071118

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

年代:1992

数据来源: WILEY

摘要:

AbstractPeptides of low molecular weight that contain pyridinoline cross‐links were isolated from adolescent human urine. A fraction was selected that was enriched in the N‐telopeptide‐to‐helix intermolecular cross‐linking domain of bone type I collagen. Mouse monoclonal antibodies were generated against these urinary peptides conjugated to a carrier protein as immunogen. A high‐affinity antibody was identified that specifically bound to the trivalent peptides derived from the N‐telopeptide‐to‐helix pyridinoline cross‐linking site in type I collagen of human bone. This was confirmed by the direct isolation from human bone collagen of similar fragments recognized selectively by the antibody. A sensitive inhibition ELISA was established on microtiter plates that could quantify the bone‐derived peptides in human urine. The assay, which can be run directly on untreated urine, was thoroughly tested against samples from normal subjects and from patients with metabolic bone disease. For example, strong correlations with urinary hydroxyproline and total pyridinoline cross‐links were found in patients with Paget's disease of bone. The method shows considerable promise as a rapid and specific index of human bone resorption rates, with greatly improved specificity and convenience over total pyridinoline analysis. Potential applications include the study of normal metabolism, the diagnosis and monitoring of bone disease, and evaluating the effectiveness of a

ISSN:0884-0431    

DOI:10.1002/jbmr.5650071119

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

年代:1992

数据来源: WILEY

摘要:

AbstractVertebral fracture is the most prevalent manifestation of osteoporosis in women, but there is very little information concerning vertebral fracture in men. These studies begin to determine the prevalence, radiographic character, and relationship to bone mineral density of vertebral deformity in men. A group of 144 white men aged 34–94 years (83% between 50 and 80 years) were studied. Thoracic and lumbar spine radiographs were obtained using standardized techniques, and morphometric measures of vertebrae (T6–L5) were obtained using a computerized digitization pad. Vertebral deformities (wedge, midbody, and crush) were identified using several criteria. In addition, a skeletal radiologist independently identified vertebral deformities, as well as vertebrae affected by epiphysitis (Scheuermann's disease), using classic radiographic criteria. Bone mineral density was measured at lumbar spine and proximal femoral sites using dual‐photon absorptiometry. The prevalence of vertebral deformity was related to the criteria used for their identification. Utilizing vertebral‐specific criteria (anterior/posterior or midbody/posterior vertebral height more than 3 SD below vertebral specific mean), 10% of subjects had vertebral deformity. Wedge deformity occurred primarily in thoracic vertebrae and were more common than midbody deformity, which occurred more commonly in lumbar vertebrae. Crush deformities were not observed. Evidence of vertebral epiphysitis was present in 9% of subjects but was not responsible for vertebral deformity sufficient to be falsely identified using the more than −3 SD criterion. Bone mineral density in subjects with vertebral deformity was clearly reduced at both vertebral (p= 0.003) and proximal femoral (p= 0.002) measurements sites. The number of vertebral deformities was negatively correlated with vertebral bone mineral density. In summary, vertebral deformity in men is associated with generalized o

ISSN:0884-0431    

DOI:10.1002/jbmr.5650071120

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

年代:1992

数据来源: WILEY

摘要:

AbstractAcid phosphatase activity in medullary bone matrix and osteoclasts of laying Japanese quail was examined histochemically. To avoid nonspecific staining, the reactivity of the enzyme was evaluated using both the azo dye method and the lead salt method and nonembedded thick sections and resin‐embedded thin sections. The pH of the incubation medium was also varied from the acid range (pH 5.0 and 6.5) to the alkaline range (pH 8.5). Medullary bone osteoclasts contain both tartrate‐resistant acid phosphatase (TRAP) activity and fluoride‐resistant acid phosphatase (FRAP) activity, and no significant difference in intensity was detected between active and inactive osteoclasts. The entire matrix of medullary bone was positive for tartrate‐resistant, fluoride‐sensitive acid phosphatase activity. No reaction product was observed in sections incubated in substrate‐free and pH 8.5 media. The results demonstrate the existence of FRAP in medullary bone osteoclasts and suggest that medullary bone matrix includes TRAP throughout

ISSN:0884-0431    

DOI:10.1002/jbmr.5650071121

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

年代:1992

数据来源: WILEY

摘要:

AbstractA retrospective analysis of our experience with estrogen and fluoride treatment in 91 patients with postmenopausal osteopenia followed for 6–47 months has been performed. Treatment included calcium (1000 mg/day) and either conjugated estrogens (0.625 mg/day) or sodium fluoride (50 mg/day), or both. All patients had at least two serial dual‐photon spinal bone mineral density measurements performed 6 months or more apart. Estrogen treatment was associated with increased bone mineral density (5.3%/year), as was fluoride alone (7.5%/year). Estrogen and fluoride together were additive (9.6%/year). In women over age 65 the estrogen effect was just as great (6.9%/year) as in younger women. Estrogen benefit occurred predominantly in the first 18 months of treatment (7.0%/year), after which time changes in bone mineral density were similar to those in untreated controls, who showed stable bone mineral density. We conclude that aggressive estrogen and fluoride treatment tailored to the severity of the individual's postmenopausal osteopenia results in short‐term improvement in spinal bone mineral density. These data further support that elderly women respond to estrogen replacement therapy with absolute and relative increments in bone density similar to those in younger

ISSN:0884-0431    

DOI:10.1002/jbmr.5650071122

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

年代:1992

数据来源: WILEY

摘要:

AbstractSilicon in trace amounts enhances bone formation, and the silicon‐containing compound zeolite A (ZA) increases eggshell thickness in hens. In the studies reported here, treatment of nearly homogeneous strains of normal human osteoblast‐like cells for 48 h with ZA at 0.1–100 μg/ml induced a dose‐dependent increase (r= 0.35,P<0.001) in DNA synthesis (n= 31) to 162 ± 16% (mean ± SEM) of control and in the proportion of cells in mitosis (n= 4) from 9.1 ± 1.8 to 27.0 ± 4.5% (r= 0.69,P<0.005). ZA treatment also increased alkaline phosphatase activity (P<0.05) and osteocalcin release (P<0.05) but did not significantly affect collagen production per individual cell. The mitogenic action of ZA was dependent on cell seeding density over the range of 1250–40,000 cells per cm2, which is consistent with induction of an autocrine factors). TGF‐β is a potent mitogen for osteoblasts. ZA treatment increased the steady‐state mRNA levels of transforming growth factor β1(TGF‐β1) and induced the release of the latent form of TGF‐β protein into the conditioned medium within 6 h. We conclude that ZA induces the proliferation and differentiation of cells

ISSN:0884-0431    

DOI:10.1002/jbmr.5650071107

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

年代:1992

数据来源: WILEY

摘要:

AbstractMuscle strength has been shown to predict bone mineral density (BMD) in women. We examined this relationship in 50 healthy men who ranged in age from 28 to 51 years (average 38.3 years). BMD of the lumbar spine, proximal femur, whole body, and tibia were measured by dual‐energy x‐ray absorptiometry (Hologic QDR 1000W). Dynamic strength using one repetition maximum was assessed for the biceps, quadriceps, and back extensors and for the hip abductors, adductors, and flexors. Isometric grip strength was measured by dynamometry. Daily walking mileage was assessed by 9 week stepmeter records and kinematic analysis of video filming. Subjects were designated as exercisers and nonexercisers. Exercisers participated in recreational exercise at least two times each week. The results demonstrated that BMD at all sites correlated with back and biceps strength (p<0.01 top= 0.0001). Body weight correlated with tibia and whole‐body BMD (p<0.001); age negatively correlated with Ward's triangle BMD (p<0.01). In stepwise multiple regressions, back strength was the only independent predictor of spine and femoral neck density (R2= 0.27). Further, back strength was the most robust predictor of BMD at the trochanter, Ward's triangle, whole body, and tibia, although biceps strength, age, body weight, and leg strength contributed significantly to BMD at these skeletal sites, accounting for 35–52% of the variance in BMD. Exercisers and nonexercisers were similar for walking (3.97 versus 3.94 miles/day), age (37.8 versus 38.5 years), and weight (80.0 versus 77.7 kg). However, BMD and muscle strength were significantly greater in exercisers than in nonexercisers. In conclusion, in young to middle‐aged men, (1) muscle strength makes important contributions to bone mineral density; (2) strength of back extensors more powerfully predicts BMD than age, body weight, or strength of other muscle groups; and (3) recreational exercise is a better predictor of BMD than habitual dail

ISSN:0884-0431    

DOI:10.1002/jbmr.5650071108

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

年代:1992

数据来源: WILEY

摘要:

AbstractWe have reported that numerous tartrate‐resistant acid phosphatase‐positive osteoclast‐like multinucleated cells (TRAP+MNCs) are formed when mouse osteoblastic cells and spleen cells are cocultured in the presence of 1α25‐dihydroxyvitamin D3[1α,25‐(OH)2D3] (Endocrinology123:2600, 1988). In this study, we prepared a TRAP+MNC population using a modified coculture system and examined its osteoclastic properties. TRAP+MNCs were formed in cocultures of mouse osteoblastic cells and marrow cells on 10 cm collagen gelcoated dishes. The TRAP+MNC population was prepared by treating the dishes with 0.2% bacterial collagenase followed by density gradient centrifugation. The yield of TRAP+MNCs was 20,000–40,000 cells per dish, much higher than that of osteoclasts (OCLs) isolated from neonatal rat bones (∼ 1000 cells per head). The purity of TRAP+MNCs was 5.6 ± 0.6% in cell number and about 30% in the number of nuclei. The recovery of TRAP+MNCs after density gradient centrifugation was 30–40%. Acid production by MNCs was demonstrated by vital staining with acridine orange. Numerous resorption pits were formed when the MNC population was cultured for 48 h on bone slices. Autoradiography using [125I]salmon calcitonin (CT) showed abundant CT binding in most TRAP+MNCs. Saturation analysis of [125I]salmon CT indicated a dissociation constantKdfor TRAP+MNCs of 8.9 ± 0.7 × 1010M and 16.5 ± 1.5 ± 106binding sites per cell. These results were similar to the value (3.5 × 10−10M) and the number of binding sites (3.3 × 106per cell) in isolated rat OCLs. Displacement curves for [125I]salmon CT with unlabeled salmon and human CT were similar in MNC and OCL preparations. Salmon and human CT increased cAMP production (maximal response: salmon CT at 10−10M, human CT at 10−8M; ED50: salmon CT, 2.2 × 10−11M, human CT, 1.3 × 10−9M) in the MNC preparation. These results indicate that a large number of mouse TRAP+MNCs possessing OCL characteristics can be easily prepared from in vitro cultures. This procedure will facilitate ex

ISSN:0884-0431    

DOI:10.1002/jbmr.5650071109

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

年代:1992

数据来源: WILEY

摘要:

AbstractThere are several indications that the functions of human osteoblasts and osteoclasts have circadian rhythms with peak activities occurring at night. It is not known, however, whether the principal function of these cells, namely synthesis and degradation of the organic matrix of bone, of which about 90% is type I collagen, also has a circadian rhythm. This was therefore investigated for both the formation of type I collagen and the degradation of type I collagen in bone using two newly developed serum markers: the serum concentration of the carboxy‐terminal propeptide of type I procollagen (PICP) as a marker of formation and the serum concentration of the carboxy‐terminal pyridinoline cross‐linked telopeptide of type I collagen (ICTP) as a marker of degradation. PICP and ICTP were measured by RIA in samples taken every 3 h over a 24 h period in 12 healthy premenopausal women (age 32 ± 5 years, mean ± SD). Both PICP (p= 0.003) and ICTP (p= 0.00003) showed a significant circadian rhythm, with about 20% higher values at night than in the afternoon. We conclude that serum markers of both the formation of new type I collagen and the degradation of old type I collagen in bone exhibit a clear circadian rhythm, with increased activity of both osteoblasts and osteoclasts at night. The etiology of this circadian rhythm is still

ISSN:0884-0431    

DOI:10.1002/jbmr.5650071110

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

年代:1992

数据来源: WILEY

摘要:

AbstractThe ability of low‐dose tetracyclines to inhibit collagenase activity and inactivate osteoclasts suggests that these compounds have great potential as a prophylaxis for metabolic bone disease. However, the cellular mechanism by which tetracyclines interact with skeletal tissue is not yet clear. To better understand the effects of tetracyclines on bone metabolism, we examined their effect on osteoclast activity in vitro. Because tetracyclines can enter the cell and bind calcium and have been reported to directly interact with osteoclasts, we postulated that exposure to either of two tetracyclines, minocycline or doxycycline, would alter cytosolic Ca2+regulation in rat osteoclasts. [Ca2+]iwas measured in single rat osteoclasts utilizing fura‐2. Addition of extracellular Ca2+(5 mM CaCl2), a potent osteoclast inhibitor, increased [Ca2+]iin all osteoclasts, but 10−6M salmon calcitonin (sCT) did so only in a subpopulation of osteoclasts. Neither minocycline nor doxycycline (10 μg/ml) altered steady‐state osteoclast [Ca2+]i. Further, neither minocycline nor doxycycline pretreatment affected the sCT‐mediated increases in [Ca2+]i. However, tetracycline pretreatment significantly decreased the cytosolic Ca2+response to extracellular CaCl2. Our results strongly suggest that tetracyclines have a specific effect on extracellular Ca2+‐stimulated cytosolic Ca2+mobilization in osteoclasts, which is not solely dependent on their ability to buffer Ca2+. Furthermore, these results point to the potential use of tetracyclines as probes to study cytosolic Ca2+regulation. However, that tetracyclines attenuate a signal response associated with decreased osteoclastic resorption suggests that the reported antiresorptive attributes of tetracyclines must be achieved independently of an effect on osteoclastic cy

ISSN:0884-0431    

DOI:10.1002/jbmr.5650071111

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

年代:1992

数据来源: WILEY