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