Bone and mineral最新文献

Pig bone cells were isolated from fetuses or young animals. In culture, they proliferated for 6 days, became confluent and began differentiating. The effects of ascorbic acid (AsA) on cell proliferation, alkaline phosphatase (ALP) activity, non-collagenous protein (NCP) and collagen synthesis, were studied by adding AsA to the medium at different times during culture. AsA affected fetal and post-natal cells similarly: ALP activity, NCP and collagen synthesis were markedly reduced in cells treated before confluence, but were strongly and dose-dependently stimulated in cells treated after confluence. AsA also stimulated cell proliferation. The cell stage-dependent action of AsA suggests that it may interfere with differentiation. The effects of AsA on ALP activity and DNA content were not coupled to its effect on collagen synthesis, raising the question of whether AsA action is matrix-mediated.

There is controversy about how often elevated parathyroid hormone (PTH) levels are found in hip fracture patients. The aim of this study was to determine whether changes in PTH levels after fracture and surgery could explain some of the variation in published data. Blood samples were obtained from 24 elderly patients with hip fracture before surgery, immediately after surgery and at 2 weeks and 3 months after fracture. PTH levels were elevated (>5.5 pmol) in 33% initially and then fell significantly at 2 weeks in virtually all subjects (P < 0.001) and remained significantly lower after 3 months (n= 17). Although 25-hydroxyvitamin D levels were low (< 30 nmol) in 44% of the patients, the fall in PTH was not explained by alterations in vitamin D metabolites or other measured parameters. The cause of the variation in PTH levels is unknown but measurements immediately after fracture could overestimate the incidence of secondary hyperparathyroidism. Vitamin D deficiency is common in our hip fracture population and is not influenced by hospitalisation.

The effect of a single intravenous (i.v.) infusion of 5 mg alendronate was studied in ten patients with Paget's disease, six patients with primary hyperparathyroidism and ten osteopenic postmenopausal women. Urinary hydroxyproline excretion significantly decreased within few days in all patients (from 113 ± 67.9 to 58 ± 35 mmol/mol Cr in Paget's disease, from 21.8 ±9 to 12.9 ± 6 mmol/mol Cr in hyperparathyroidism, from 18.7 ± 9.5 to 8.5 ± 4.3 mmol/mol Cr in postmenopausal women). In the patients with Paget's disease urinary hydroxyproline remained suppressed over the 6 months of follow-up, whereas it rose toward pretreatment values within 4 and 6 weeks in the patients with primary hyperparathyroidism and in postmenopausal osteopenic women, respectively. Plasma alkaline phosphatase significantly fell only after 4–6 weeks in patients with primary hyperparathyroidism and in Pagetic patients. In the latter group alkaline phosphatase continued to decline thereafter and a plateau became apparent after 2 months. In postmenopausal women the serum alkaline phosphatase remained unchanged. Thus, the same dose of alendronate induces comparable fractional decreases of bone resorption in the three groups of patients, but the effect is persistent only in Paget's disease. This is consistent with the hypothesis that alendronate inhibits osteoclastic activity only at the level of the existing resorption sites. In osteoporotic and primary hyperparathyroid patients, as soon as the treatment is withdrawn, the appearance of new sites of resorption is not inhibited and bone turnover is resumed to pre-treatment values. In Pagetic lesions the bisphosphonate accumulates only at the level of focal skeletal lesion and it induces a long-term suppression of bone resorption at that level.

Osteoporosis is characterised by reduced bone mass and disruption of cancellous bone architecture; however, it is unknown whether these changes arise from a specific disease process or represent one extreme of physiological bone loss. We have quantitatively assessed cancellous structure in 35 patients with primary osteoporosis and 41 normal subjects. Cancellous microstructure was assessed by computerised strut analysis and by calculation of trabecular width, separation and number. Node to terminus ratio, node to node and node to loop strut length were significantly decreased in patients with osteoporosis when compared to normal subjects (P < 0.001), whereas terminus count and terminus to terminus strut length were significantly increased (P < 0.001). When two subgroups were matched for age these differences remained highly significant (P < 0.005). However, when two subgroups were matched for cancellous area, no significant differences were observed in any of the structural indices except terminus count (P <0.05). Mean trabecular width and number were significantly lower and trabecular separation significantly higher in the patients with osteoporosis before and after age-matching but their differences disappeared after matching for cancellous area. Multiple regression analysis confirmed highly significant correlations between cancellous bone area and structural indices after adjustment for age, sex and disease status (P < 0.001). Our data demonstrate that for a given cancellous area, structural changes in primary osteoporosis are similar to those observed during age-related bone loss in normal subjects. These findings support the hypothesis that primary osteoporosis is the result of greater biological ageing rather than a specific disease process and are consistent with evidence from other sources that low bone mass is associated with increased mortality from diseases unrelated to osteoporosis.

A seasonal component to bone loss has been reported in some postmenopausal women. We hypothesized that elderly women in northern New England would be at high risk for bone loss during winter because of their age, diet and lack of sunlight. Eighteen elderly but healthy women (mean age 77 years) started a 2-year observational study in a remote area of northwestern Maine (Greenville: 45.5°N latitude). Fifteen women completed the study. Bone mineral density of the spine (L-BMD) and hip (F-BMD) and biochemical markers of bone turnover were measured biannually. In vitro photo-conversion of provitamin D₃ to previtamin D₃ was determined in the winter and spring. Initial calcium and vitamin D intake averaged 700 ± 72 mg/day and 6.2 ± 1.2 μg/day, respectively. During the first year L-BMD dropped 4.2% (P = 0.002) while F-BMD dropped 2.4% (P = 0.09), primarily because of steep declines during the fall and winter (August to February: L-BMD: 3.6%, P = 0.001; F-BMD: 3.0%, P = 0.04). In that 6-month period, serum 25 hydroxyvitamin D (25(OH)D) fell 13 ± 6% (P = 0.06) and PTH rose 27 ± 11% (P = 0.01). Additionally, there was no detectable in vitro conversion of provitamin D to previtamin D over 8 h of one sunny winter day. In the summer, PTH and 25(OH)D reverted to basal levels and significant in vitro photoconversion of provitamin D to previtamin D was detected. In the 2nd year of the study, vitamin D consumption increased (+2.0 ± 1.2 μg/day, P = 0.03 vs. baseline), L-BMD increased slightly (+1.8%, P = 0.05) and F-BMD did not change (+0.5%, P = NS). Again, changes in BMD and vitamin D were seasonal: L-BMD and F-BMD were constant during fall and winter but both sites showed increases during summer (L-BMD: +1.7%, P = 0.04, F-BMD: +1.6%, P = 0.25). In the second winter, serum 25(OH)D fell nearly 20% and PTH rose 17%. Increased dietary consumption of vitamin D was positively correlated with changes in F-BMD at 18 months (r = 0.61, P = 0.02) and resulted in slightly greater serum 25(OH)D concentrations during the second winter than the first. The difference in serum 25(OH)D between the first and second winter was the strongest predictor of lumbar bone accretion during the second year of the study (r = 0.59, P = 0.04). In this 24-month observational study, significant seasonal changes in BMD, 25(OH)D and PTH were reported. Winter was the time of lowest serum 25(OH)D and the greatest decline in measurable bone mass, while summer was associated with modest increases in serum 25(OH)D and BMD.

To determine the effects of ovariectomy and 17β-estradiol (E₂) on serum IGF-I and its binding proteins, female Sprague-Dawley rats, aged 95 days, were divided into four groups. Group 1 was sham-operated; groups 2, 3, and 4 were ovariectomized. Groups 3 and 4 received daily injections of 200 ng (low dose) and 5000 ng (high dose) E₂/kg body wt./day, respectively and the others were given solvent vehicle. Ovariectomy resulted in a significant increase in serum IGF-I (P < 0.001) at 30 and 35 days post-surgery; the increase was prevented in animals that received low-dose E₂ while high-dose E₂ reduced serum IGF-I levels below those of the sham-operated controls (P < 0.01). Serum IGF-binding proteins (IGFBPs) were determined by IGF-ligand blot analysis, and the resulting autoradiograms quantified by laser densitometry. The intensity of the IGFBP-3 bands changed in parallel with serum IGF-I levels. Ovariectomy increased, low-dose E₂ restored, and high-dose E₂ reduced serum IGFBP-3 levels compared to the levels for the sham-operated controls. The intensities of binding protein bands smaller than those of IGFBP-3 appeared unchanged by the treatment regimens. A Western immunoblot analysis with IGFBP-3 antiserum confirmed the ligand-blot data. The changes in the levels of IGF-I and its binding proteins were accompanied by ovariectomy-induced increase in osteoblast and osteoclast numbers and loss of cancellous bone that were attenuated by E₂ administration. We conclude that there is a possible role for IGF-I in the pathogenesis of the increased bone turnover that occurs early in ovarian hormone deficiency.

Apparent velocity of ultrasound (AVU) through the patella was measured in 160 Japanese women without specific diseases affecting the skeletal system. AVU averaged 1955 ± 64 m/s (mean ± S.D.) in healthy premenopausal women. Twenty patients with postmenopausal osteoporosis over the age of 50 years with at least one atraumatic vertebral fracture had significantly lower average AVU (1757 ± 89.6 m/s) than that of the same age group without compression fracture (1838 ± 78.0 m/s, P < 0.05). Perimenopausal women without vertebral fracture in their 50s were divided into two groups, premenopausal (n = 11) and postmenopausal (n = 28), and both AVU through the patella and spinal BMD (L-2–4) using DXA were measured. A significant difference was found in AVU between the two groups (premenopausal, 1953 ± 58 m/s; postmenopausal, 1885 ± 73 m/s, P < 0.01), in the absence of a difference either in the mean age (premenopausal, 52.7 ± 2.0; menopausal, 54.2 ± 2.4) or in the spinal BMD as assessed by DXA (premenopausal, 0.930 ± 0.080 g/cm²; postmenopausal, 0.851 ± 0.148 g/cm²). The apparent difference in AVU without corresponding difference in BMD suggests that perhaps AVU measures something about the bone that is not reflected in BMD in women in their 50s in the immediate postmenopausal period. When AVU of our test subjects was compared with that in Caucasians reported by Heaney RP et al. (Osteoporotic bone fragility: detection by ultrasound transmission velocity. J Am Med Assoc 1989;261:2986–2990) no difference was found in AVU between Japanese and Caucasians. Since AVU is said to be proportional to the product of bone quantity (density) and bone quality, and bone quantity measured as bone mineral density was shown to be lower in Japanese than in Caucasians, there might possibly be some difference in bone quality between the two populations. Cross-cultural exploration of the bone properties and causes of differences in the incidence of hip fracture may help in understanding the causes and background of osteoporosis.