Introduction Patients with cystic fibrosis (CF) are known to be at risk for early osteoporosis, and the mechanisms that mediate bone loss
are still being delineated. The aim of the present investigation was to investigate if a correlation exists in these patients
between skeletal measurements by dual-energy x-ray absorptiometry (DXA) and two anabolic factors, dehydroepiandrosterone (DHEA)
and insulin-like growth factor I (IGF-I), and proresorptive factors such as the cytokines interleukin-1β, tumor necrosis factor α,
and interleukin-6.
Methods We studied 32 outpatients (18 females; mean age: 26.2 ± 7.9 years) at a tertiary care medical center. The subjects had venous
samples obtained, underwent anthropometric and bone mineral density (BMD) measurements, and completed a health survey. Serum
IGF-I concentrations were below the age-adjusted mean in 78% of the participants, and DHEA sulfate (DHEAS) concentrations
were low in 72%. Serum concentrations of all cytokines were on the low side of normal; nonetheless, there was a modest inverse
correlation between IL-1β and BMD at all sites.
Results In univariate analyses, IGF-I and DHEAS were significant correlates of BMD or bone mineral content. In final multivariate
models controlling for anthropometric and other variables of relevance to bone density, only IGF-I was identified as a significant
independent skeletal predictor. While alterations in DHEAS, IGF-I, and specific cytokines may contribute to skeletal deficits
in patients with CF, of these factors a low IGF-I concentration appears to be most strongly correlated with BMD.
Conclusions These findings may have therapeutic implications for enhancing bone density in these patients. 相似文献
The effects of daily oral administration of a high dose of 10 mg norethisterone acetate (NET-Ac.)/kg/day over 14 weeks on serum lipid and lipoprotein parameters as well as on blood coagulation were investigated in female monkeys (M. fascicularis). Measurements of lipids and lipoprotein cholesterol were performed in weeks —5 and — 1 before treatment and in weeks 4, 8 and 12 after treatment. In addition, various blood coagulation and fibrinolytic parameters were determined in weeks 11–14 after treatment with NET-Ac. Furthermore, the serum levels of norethisterone (NET) were determined in order to monitor the real systemic compound exposure and revealed that Cmax and AUC (0–3 h) values reached for norethisterone in this experiment in monkeys were about 25 times higher than those obtained after an oral contraceptive dose of NET-Ac. in women.
The results of lipid and lipoprotein cholesterol determinations showed decreases in serum total lipids, phospholipids, triglycerides and total cholesterol associated with similar decreases in HDL-, LDL- and VLDL-cholesterol fractions after NET-Ac.-treatment in monkeys. These effects were observed from week 4 onwards and maintained their magnitude up to week 12 after treatment. Since both HDL- and LDL-cholesterol fractions decreased, the HDL/LDL-ratio remained almost unchanged. Thus, the results obtained in this study after high-dose treatment with NET-Ac. in monkeys did not indicate any changes of lipid and lipoprotein parameters which in humans are supposed to be associated with an increased risk of cardiovascular lesions, namely a decrease in HDL- and increase in LDL-cholesterol fractions.
The results of blood coagulation and fibrinolytic parameters showed increased antithrombin-III and plasminogen levels besides minor changes in other parameters, thus indicating that NET-Ac. -treatment does not contribute to an increased risk of cardiovascular thrombotic events in the cynomolgus monkey. 相似文献
Risedronate treatment reduces the risk of vertebral fracture in women with existing vertebral fractures, but its efficacy
in prevention of the first vertebral fracture in women with osteoporosis but without vertebral fractures has not been determined.
We examined the risk of first vertebral fracture in postmenopausal women who were enrolled in four placebo-controlled clinical
trials of risedronate and who had low lumbar spine bone mineral density (BMD) (mean T-score =–3.3) and no vertebral fractures at baseline. Subjects received risedronate 5 mg (n= 328) or placebo (n= 312) daily for up to 3 years; all subjects were given calcium (1000 mg daily), as well as vitamin D supplementation (up
to 500 IU daily) if baseline serum 25-hydroxyvitamin D levels were low. The incidence of first vertebral fracture was 9.4%
in the women treated with placebo and 2.6% in those treated with risedronate 5 mg (risk reduction of 75%, 95% confidence interval
37% to 90%; P= 0.002). The number of patients who would need to be treated to prevent one new vertebral fracture is 15. When subjects were
stratified by age, similar significant reductions were observed in patients with a mean age of 64 years (risk reduction of
70%, 95% CI 8% to 90%; P= 0.030) and in those with a mean age of 76 years (risk reduction of 80%, 95% CI 7% to 96%; P= 0.024). Risedronate treatment therefore significantly reduces the risk of first vertebral fracture in postmenopausal women
with osteoporosis, with a similar magnitude of effect early and late after the menopause.
Received: 12 September 2001 / Accepted: 11 December 2001 相似文献
A new range of stand magnifiers has been released by the COIL company in the United Kingdom. Examination of these magnifiers reveals that they fail to deliver the rated magnifications labelled prominently on the appliances, as a result of the manufacturer's conformance with the requirements of the German DIN standard and the use of back vertex power (F'v) rather than equivalent dioptric power (Fm) of the magnifier. In this study we provide information on the optometric parameters of these new stand magnifiers that will assist the more accurate specification of improvements in vision expected from their use. 相似文献
This double-masked, placebo-controlled study was undertaken to determine the efficacy and safety of oral clodronate in the
prevention of bone loss in early postmenopausal women with vertebral osteopenia. Altogether 610 women with a mean age of 53
years were recruited for the study. They were 1–5 years postmenopausal and their lumbar spine bone mineral density (BMD) was
at least 1 standard deviation below the mean of premenopausal women (T-score ≤−1). The subjects were randomized into five study groups to receive either placebo, clodronate 65 mg, 400 mg or 800
mg daily, or intermittent clodronate in 3 month cycles with 400 mg daily for 15 days followed with no treatment for 75 days
for 3 years. One hundred and eighty-seven of 509 women who completed the primary study continued in the extension study of
2 years in which previous placebo users were switched to clodronate 800 mg daily, while previous users of 400 mg or 800 mg
of clodronate used either placebo or 800 mg of clodronate daily. In the primary study clodronate was administered in the evening,
and in the extension 1 h before breakfast on an empty stomach. In the primary study mean changes in lumbar spine BMD were
−3.4% in the placebo group and +0.4% in 800 mg clodronate group [difference between groups at 3 years 3.8% (95% CI 2.7% to
4.9%, p<0.0001)], and in the trochanter area BMD −1.1% in the placebo group, and + 0.4% in the 800 mg clodronate group [difference
between groups at 3 years 1.5% (95% CI 0.05% to 2.9%)]. During the extension study mean changes in lumbar spine BMD were +1.5%
in the clodronate group and −0.2 % in the placebo group [difference between groups 1.7% (CI 0.4% to 3.0%, p = 0.010)] and in trochanter BMD were +2.5% in the clodronate group and no change in the placebo group [difference between
groups 2.1% (CI 0.3% to 3.9%, p = 0.007)]. No statistically significant differences between the placebo and 800 mg clodronate groups were found in the femoral
neck BMD. In the primary study the urinary excretion of type I collagen aminoterminal telopeptide (NTX) decreased by 44% (p<0.0001 compared with placebo) and that of deoxypyridinoline by 18% (p<0.0001) in the clodronate 800 mg group. In the extension study urinary NTX decreased by 51% (p<0.0001) in those who were switched to 800 mg of clodronate and increased by 67% (p<0.0001) in those who stopped using that dose. There was no difference in the frequency of gastrointestinal complaints between
clodronate- and placebo-treated patients in the primary study, but they were more common among women who received clodronate
in the extension phase. Clodronate in daily doses of 400–800 mg caused a slight elevation of aminotransferase levels, usually
within the reference range. In bone biopsies no defect in mineralization was found. In conclusion, clodronate in a daily dose
of 800 mg prevents early postmenopausal bone loss at the sites of the skeleton in which cancellous bone predominates. It effectively
reduces bone resorption and bone turnover rate. Antifracture efficacy of clodronate remains to be established by prospective,
placebo-controlled trials.
Received: 4 March 2002 / Accepted: 9 July 2002 相似文献