摘要:

AbstractNot all children with X‐linked hypophosphatemia (XLH) have demonstrated improved linear growth with calcitriol [1,25‐(OH)2D3] and inorganic phosphate (Pi) therapy. To assess which factors are associated with a favorable growth response during this treatment, we retrospectively compared demographics and biochemical parameters of bone metabolism to the linear growth patterns of 20 children with XLH who were prepubertal and had not required osteotomy. A total of 15 patients had family histories consistent with XLH; 5 appeared to be sporadic cases. During 3 years of therapy, the growth velocities of 12 patients had been at or above the mean for age (good growers) and those of 8 patients had been below the mean (poor growers). Data from the two groups were contrasted. We found no difference between the good growers and poor growers before or after the 3 year period of therapy in mean age, dietary calcium, calcitriol dose or compliance, or Pidose or compliance. Both groups increased their mean fasting serum Pilevels with treatment. The TmP/GFR (x+ SEM) of the good growers improved with therapy (1.9 + 0.2 to 2.6 + 0.2 mg/dl,p= 0.01), and their posttreatment value was higher compared to that of the poor growers (2.6 + 0.1 versus 2.2 + 0.1 mg/dl,p= 0.02). However, their enhanced TmP/GFR was not associated with a reduction in serum iPTH levels (before, 693 + 50; after, 688 + 76 pg/ml;p= 0.9). TheZtest for binomial proportions showed that the group that grew well contained a disproportionate number of girls (10 of 12,p= 0.04). Our findings suggest that calcitriol may exert a direct effect on the renal tubule to improve Pireclamation in XLH. The observation that heterozygous girls appear to respond better than hemizygous boys to calcitriol and Pitherapy provides evidence for a gene dosage effect in the expression of this X‐linked dominant dis

ISSN:0884-0431    

DOI:10.1002/jbmr.5650070602

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 effect of Tiludronate on bone was studied in 72 growing monkeys (Papio papio), 36 males and 36 females, aged 4–7 years. They were randomly allocated into four groups (18 animals per group, 9 males and 9 females): group I, controls; group II, 10 mg/kg/day; group III, 20 mg/kg/day; and group IV, 40 mg/kg/day of Tiludronate. A total of 12 animals (6 males and 6 females) in each group were sacrificed at the end of treatment (1 year) and 6 animals (3 males and 3 females) per group 1 year later. Bone mineral density (BMD) was measured by dual‐photon absorptiometry. Biomechanical properties were evaluated by an impact torsion test and by resonant frequency analysis. Bone mineral measurements indicated that at the end of 1 year of treatment BMD was significantly higher, especially at the distal epiphysis of the radius, than in controls. No significant differences between groups were found in BMD 1 year after stopping treatment. Biomechanical analyses indicated that torsional stiffness increased after treatment. No differences between groups were found 1 year after stopping treatment. Results of resonant frequencies indicated an increased calculated transversal stiffness after treatment and 1 year later and an increased buckling strength 1 year after stopping treatment. In conclusion, the results on the effect of Tiludronate in growing monkeys indicate a profound effect of this drug on bone density and biomechanical properties. The biomechanical results indicate that this drug is safe, with conservation of bone strength despite a change in intrinsic mechanical properties of the b

ISSN:0884-0431    

DOI:10.1002/jbmr.5650070603

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:

AbstractRecruitment of osteoclasts from monocytic precursors is modulated by local signals. We previously showed that monoblastic differentiation in U937 cells is stimulated by 1,25‐(OH)2D3and cAMP in series. We investigate here the combined effects of these agents to stimulate differentiation of osteoclast‐like cells from mouse marrow. Cells from mouse marrow were harvested and cultured in α‐MEM with 10% fetal bovine serum. The appearance of tartrate‐resistant acid phosphatase‐containing multinuclear cells was measured after 8 days in culture by cytochemical staining. Continuous exposure of cultures to 10 nM 1,25‐(OH)2D3positively stimulated development of these cells after 8 days (101 + 3 cells per well,n= 74). No osteoclast‐like cells were found when 1,25‐(OH)2D3was added for the first 4 days followed by 4 days more with no treatment. PGE2(1 μM) as a single agent added during the last 4 days of culture was not able to recruit osteoclast‐like cells. However, cultures exposed to 1,25‐(OH)2D3during the first 4 days and 1 μM PGE2during the second 4 days developed osteoclast‐like cells at 8 days [66 + 8% of the formation seen with 1,25‐(OH)2D3alone,p<0.05]. Dibutyryl cAMP (1 μM to 3 mM) was also not effective used as a single agent, but was able to stimulate formation of TRAP‐positive multinuclear cells when 1,25‐(OH)2D3preceded its addition to culture medium. cAMP analogs therefore mimicked the effect of 1 μM PGE2, but these experiments do not allow us to assign the PGE2action entirely to activation of cAMP second messenger. We postulate that continuous 1,25‐(OH)2D3stimulation is alone sufficient to recruit osteoclasts from precursors but that the effect of cAMP to stimulate osteoclast formation occurs only when combined with a

ISSN:0884-0431    

DOI:10.1002/jbmr.5650070604

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 effects of long‐term running exercise were studied in 20 beagle dogs. A total of 10 dogs ran from the age of 15 weeks to the age of 70 weeks in a progressive program for up to 40 km/day. A total of 10 sister dogs spent the study period in individual cages. When the dogs were 70 weeks old, bone mineral density of the vertebrae, hip, and radius was analyzed by dual‐energy x‐ray absorptiometry (DEXA; Lunar) and the vertebrae were also assessed by quantitative computed tomography (QCT; Siemens DR 1). Mineral density was lower in the running dogs than in the controls. The difference was greatest in the spine in the QCT analysis. Blood chemistry analyses revealed that the metabolism of the bone was significantly accelerated. The estradiol levels showed the trend to be reduced in the running group. The beneficial effect of exercise on mineral density has been shown in many earlier studies. However, in this study we demonstrate the possibility of adverse effects of long‐term exercise on bone tissue. The change was associated with a decrease of serum estradio

ISSN:0884-0431    

DOI:10.1002/jbmr.5650070605

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:

AbstractAge‐related changes in bone density contribute to the risk of fractures. To describe the relationship between age and bone mass in elderly women, we studied a large cohort of women over age 65 years who were recruited from population‐based lists in four cities in the United States. Bone density in g/cm2was measured by single‐photon absorptiometry (SPA) and dual x‐ray absorptiometry (DXA) at the distal and proximal radius, the calcaneus, the lumbar spine, and the proximal femur. Centralized data collection was used to control data quality and consistency. We found a strong inverse relationship between bone density and age for most sites. Decrements in bone density between women aged 65–69 years and women 85 years and older exceeded 16% in all regions except the spine, where the difference between the two age groups was 6%. Ward's triangle and the calcaneus exhibited the largest decrements, with 26 and 21%, respectively. The estimates of annual changes in bone mineral density by linear regression at sites other than the spine ranged from ‐0.82% at the femoral neck and trochanter to ‐1.30% at Ward's triangle. Correlations between the different regions ranged fromr= 0.51 between the proximal radius and Ward's triangle tor= 0.66 between the distal radius and calcaneus. We conclude that the inverse relationship between age and bone mass measured by absorptiometry techniques in white women continues into the ninth decade of life. The relationship is strongest for bone density of Ward's triangle and the calcaneus and weakest

ISSN:0884-0431    

DOI:10.1002/jbmr.5650070606

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:

AbstractTo determine whether measurement of hip and spine bone mass by dual‐energy x‐ray absorptiometry (DEXA) predicts fractures in women and to compare the predictive value of DEXA with that of single‐photon absorptiometry (SPA) of appendicular sites, we prospectively studied 8134 nonblack women age 65 years and older who had both DEXA and SPA measurements of bone mass. A total of 208 nonspine fractures, including 37 wrist fractures, occurred during the follow‐up period, which averaged 0.7 years. The risk of fracture was inversely related to bone density at all measurement sites. After adjusting for age, the relative risks per decrease of 1 standard deviation in bone density for the occurrence of any fracture was 1.40 for measurement at the proximal femur (95% confidence interval 1.20–1.63) and 1.35 (1.15–1.58) for measurement at the spine. Results were similar for all regions of the proximal femur as well as SPA measurements at the calcaneus, distal radius, and proximal radius. None of these measurements was a significantly better predictor of fractures than the others. Furthermore, measurement of the distal radius was not a better predictor of wrist fracture (relative risk 1.64: 95% CI 1.13–2.37) than other sites, such as the lumbar spine (RR 1.56; CI 1.07–2.26), the femoral neck (RR 1.65; CI 1.12–2.41), or the calcaneus (RR 1.83; CI 1.26–2.64). We conclude that the inverse relationship between bone mass and risk of fracture in older women is similar for absorptiometric measurements made at the hip, spine, and

ISSN:0884-0431    

DOI:10.1002/jbmr.5650070607

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:

AbstractAppendicular bone mass is inversely related to the risk of hip fracture in short‐term prospective studies, but hip fractures typically occur about 30 years after menopause. We developed a model that estimates a woman's lifetime risk of hip fracture based on measurement of radial bone mass at age 50 using short‐term prospective data relating bone mass to hip fracture, the correlation between bone mass at age 50 and later years, the age‐specific incidence of hip fracture and mortality, and prospective data about bone mass and mortality. We estimate that a 50‐year‐old white woman has a 19% lifetime risk of hip fracture if her radial bone mass is at the 10th percentile for her age and an 11% lifetime risk if her bone mass is at the 90th percentile. Improved measurement techniques that have a higher predictive value for hip fracture in short‐term studies could substantially increase this gradient of lifetime risk and therefore be more clinic

ISSN:0884-0431    

DOI:10.1002/jbmr.5650070608

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:

AbstractRadial bone mineral density (BMD) of 217 white women aged 22–54 years from a single rural community was evaluated in 1984 using single‐photon absorptiometry. BMD was measured at a site one‐third the distance from the wrist to the elbow, a site that represents predominantly cortical bone tissue. Most of these women (181; 83%) were reexamined 5 years later. The overall average 5 year radial BMD loss was ‐5.6%. The average rate of loss was ‐4.5% for women retaining positive estrogen status at follow‐up (n= 108) and ‐7.4% for women who were in negative estrogen status at follow‐up (n= 73). Baseline radial BMD measures were highly predictive of the follow‐up BMD values (r= 0.80). Women with positive estrogen status and greater baseline BMD also had less BMD change. Greater baseline BMD did not predict the amount of change in women with negative estrogen status. The bone turnover markers osteocalcin and bone‐specific alkaline phosphatase were significantly associated with BMD change in women with negative, but not positive estrogen status. There was no conclusive evidence of a “peak age” in the baseline and follow‐up BMD measures. Based on rates of BMD change, “peak” bone mineral content appears to occur before age 25 years. Factors significantly associated with lower levels of BMD were menopause without estrogen replacement, nulliparity, smoking, and age at first pregnancy. Factors associated with more bone loss were menopause without estrogen replacement, smoking, shorter duration of oral contraceptive use, and older age. Quetelet index, muscle area, number of lost pregnancies, ever breast‐feeding, or calcium intake were not associated with BMD level or its 5 year rate of loss. Physical activity and alcohol intake were not associated with BMD level or change after data were adju

ISSN:0884-0431    

DOI:10.1002/jbmr.5650070609

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 present cross‐sectional study was carried out to determine the influence of oophorectomy (OPX) on serum levels of sex steroids and bone metabolism, as well as bone mineral density (BMD), in OPX subjects in comparison with age‐ and body size‐matched controls. Quantitative computed tomography (QCT) and dual‐photon absorptiometry (DPA) demonstrated a remarkable reduction in BMD in OPX subjects. In particular, the QCT of the centrum of vertebral bone (QCT‐C) in these subjects was no more than 69.33 + 3.40% (X+ SEM) of the control value, and this parameter was much lower than the QCT integral (QCT‐I) value of total lumbar vertebrae. This means that BMD decreases specifically in spongy portions after OPX. The serum level of estrone (E1) was significantly lower in OPX subjects than in controls. The hormonal action of E1on target organs has been thought to be only one‐third of that of estradiol (E2), but the marked reduction in serum E1level seemed to be a significant cause of the reduction in BMD. The serum level of androstenedione (Δ4) significantly decreased in OPX subjects and appeared to affect bone metabolism negatively. Both bone formation and bone resorption were found to be stimulated following OPX, but the rate of bone resorption was found to be higher than that of bone formation: there was an imbalance between bone formation and bone resorption in OPX subjects. However, it was not possible to prove a relationship between Ca regulating hormone and this phenomenon. In conclusion, the QCT‐C value reflects the changes in spongy vertebral BMD more sensitively than the QCT‐I value or DPA. It is also necessary to limit the region of interest strictly to the spongy portion to grasp

ISSN:0884-0431    

DOI:10.1002/jbmr.5650070610

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 response of the parathyroid gland to low Ca2+may be mediated in part by protein kinase C (PKC). We assessed the effect of two PKC activators, SC‐9 and SC‐10, and one PKC inhibitor, H‐7, on Ca2+‐regulated PTH release and degradation in primary cultures of bovine parathyroid cells. Both SC‐9 and SC‐10 stimulated PTH release, compared to high Ca2+alone, in parathyroid cells incubated in high Ca2+, with maximal PTH release of at least twofold occurring at a concentration of either activator of 10 nM (p<0.05). We have previously shown that another PKC activator, PMA, not only enhances PTH release in the presence of high Ca2+but suppresses low Ca2+‐stimulated PTH secretion. In the present study, neither SC‐9 nor SC‐10 caused a comparable suppression of PTH release at low Ca2+. However, the PKC inhibitor, H‐7 (1 μM), blocked low Ca2+‐stimulated (compared to the low Ca2+control) PTH secretion by approximately 50% (p<0.01) and did not affect high Ca2+suppression of PTH secretion. H‐7 (1 μM) was able to oppose the stimulation of PTH release by the PKC activators SC‐9, SC‐10, and PMA at high Ca2+and negated the PTH release‐inhibiting effect of PMA at low Ca2+. Culture medium from these experiments was subjected to reversed‐phase HPLC and the eluted fractions analyzed by RIA for the presence of intact and C‐terminal fragments of PTH. The release of C‐terminal fragments of PTH, when expressed as a percentage of total (fragment plus intact) PTH released, was greatest at high Ca2+(∼80%) and considerably less at low Ca2+(∼57%). Although the relative proportion of intact PTH released was increased when SC‐9 and SC‐10 stimulated PTH secretion at high Ca2+, analysis of variance suggests that the level of extracellular Ca2+was the major determinant of PTH degradation to C‐terminal fragments. At low Ca2+, H‐7 blocked the previously reported ability of PMA to suppress PTH secretion but did not block the ability of PMA to enhance PTH degradation. These results indicate that (1) PKC activation is an important component of low Ca2+‐stimulated PTH release, (2) the Ca2+effect on PTH degradation may not be entirely mediated by PKC, and (3) the PMA ef

ISSN:0884-0431    

DOI:10.1002/jbmr.5650070611

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