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1.
We studied the effect of four continuous combined estradiol valerate (E2V) and medroxyprogesterone acetate (MPA) dose combinations in six treatment groups (n= 70 per group) receiving regimens containing 1 mg or 2 mg E2V combined to 2.5 mg or 5 mg MPA, on bone mineral density (BMD) and endometrium in 419 healthy postmenopausal women over 4
treatment years. In two groups the 1 mg dose of E2V was increased to 2 mg after the first 6 months, while the MPA doses remained constant (2.5 mg or 5 mg). The remaining four
groups received 1 E2V + 2.5 mg MPA, 1 mg E2V + 5 mg MPA, 2 mg E2V + 2.5 mg MPA, or 2 mg E2V + 5 mg MPA throughout the study. BMD at the spine and hip was measured by dual-energy X-ray absorptiometry and endometrial
biopsy samples were taken at 6, 12, 24, 36 and 48 month follow-ups. Combinations containing the low dose of 1 mg of E2V (with 2.5 mg or 5 mg MPA) resulted in a mean BMD increase of 6.2% at the spine and 2.9% at the femoral neck after 4 years
of treatment. With 2 mg E2V the corresponding increases were 7.4% and 2.9%, respectively. The largest increases in BMD were seen in women for whom the
E2V dose was doubled after the initial 6 months of treatment: 8.9% at the spine and 4.2% in the femoral neck. Both MPA doses
(2.5 mg and 5 mg) effectively prevented estrogen-induced stimulation of the endometrium. No endometrial hyperplasia was observed
in any of the treatment groups. Lower-dose combinations of continuous combined estrogen–progestin regimens are effective in
increasing and maintaining BMD and provide a good endometrial safety profile for the long-term prevention of osteoporosis
in postmenopausal women.
Received: 15 February 2000 / Accepted: 3 May 2000 相似文献
2.
C. L. Tofteng A. Kindmark H. Brändström B. Abrahamsen S. Petersen F. Stiger L. S. Stilgren J. E. B. Jensen P. Vestergaard B. L. Langdahl L. Mosekilde 《Calcified tissue international》2003,74(1):25-34
Polymorphisms in the androgen receptor (AR) gene and genes encoding enzymes involved in synthesis of sex steroids (e.g., the CYP19 gene encoding aromatase) have recently received attention in osteoporosis research. In the Danish Osteoporosis Prevention Study, recent postmenopausal women were allocated to either hormone replacement therapy (HRT) or no treatment. We genotyped 1792 women for the CYP19 (TTTA)n repeat [short (TTTA)n 7 or long (TTTA)n > 7] the CYP19 C1558-T, and the AR (CAG)n repeat polymorphism [short (CAG)n < 22, long (CAG)n 22], and investigated associations with bone mineral density (BMD) and 5-year change in BMD. The CYP19 polymorphisms were in strong linkage disequilibrium. Perimenopausal bone mass or bone loss in untreated women was not associated with the CYP19 polymorphisms. In hormone-treated women, BMD increase in the femoral neck was highest (+0.3%/year) for long CYP19 alleles, lowest (–0.09%/year) for short alleles, and intermediate (–0.002%/year) in heterozygous women, P = 0.015. Differences were also significant in the lumbar spine, total hip, and ultradistal forearm. The C1558-T T-allele was associated with a more pronounced response to HRT (P = 0.04, total hip). AR genotype was not related to BMD, but a modifying effect of sex hormone-binding globulin (SHBG) was present. In the highest SHBG quartile (SHBG > 95 nmol/1, n = 222), AR genotype was associated with baseline BMD (femoral neck: P < 0.001, total hip: P = 0.008), but without a clear gene dosage effect. We have demonstrated that polymorphisms in the CYP19 gene are associated with the magnitude of bone gain in response to HRT and that the (CAG)n repeat polymorphism in the AR gene is associated with bone mass in women with high levels of SHBG. These findings emphasize the complexity of the genetics of bone mass and bone loss.
Data was presented in part at the 30th European Symposium on Calcified Tissues, Rome, Italy, May 2003. 相似文献
3.
Tofteng CL Kindmark A Brändström H Abrahamsen B Petersen S Stiger F Stilgren LS Jensen JE Vestergaard P Langdahl BL Mosekilde L;Danish Osteoporosis Prevention Study 《Calcified tissue international》2004,74(1):25-34
Polymorphisms in the androgen receptor ( AR) gene and genes encoding enzymes involved in synthesis of sex steroids (e.g., the CYP19 gene encoding aromatase) have recently received attention in osteoporosis research. In the Danish Osteoporosis Prevention Study, recent postmenopausal women were allocated to either hormone replacement therapy (HRT) or no treatment. We genotyped 1792 women for the CYP19 (TTTA)(n) repeat [short (TTTA)(n 7)] the CYP19 C(1558)-T, and the AR (CAG)(n) repeat polymorphism [short (CAG)(n < 22), long (CAG)(n >or= 22)], and investigated associations with bone mineral density (BMD) and 5-year change in BMD. The CYP19 polymorphisms were in strong linkage disequilibrium. Perimenopausal bone mass or bone loss in untreated women was not associated with the CYP19 polymorphisms. In hormone-treated women, BMD increase in the femoral neck was highest (+0.3%/year) for long CYP19 alleles, lowest (-0.09%/year) for short alleles, and intermediate (-0.002%/year) in heterozygous women, P = 0.015. Differences were also significant in the lumbar spine, total hip, and ultradistal forearm. The C(1558)-T T-allele was associated with a more pronounced response to HRT ( P = 0.04, total hip). AR genotype was not related to BMD, but a modifying effect of sex hormone-binding globulin (SHBG) was present. In the highest SHBG quartile (SHBG > 95 nmol/1, n = 222), AR genotype was associated with baseline BMD (femoral neck: P < 0.001, total hip: P = 0.008), but without a clear gene dosage effect. We have demonstrated that polymorphisms in the CYP19 gene are associated with the magnitude of bone gain in response to HRT and that the (CAG)(n) repeat polymorphism in the AR gene is associated with bone mass in women with high levels of SHBG. These findings emphasize the complexity of the genetics of bone mass and bone loss. 相似文献
4.
Fogelman I Fordham JN Fraser WD Spector TD Christiansen C Morris SA Fox J 《Calcified tissue international》2008,83(2):85-92
Treatment of postmenopausal osteoporosis (PMO) is based primarily on antiresorptive agents, including hormone replacement therapy (HT). To evaluate whether anabolic therapy together with HT provides additional benefits in the treatment of PMO, we evaluated the effects of parathyroid hormone (PTH) 1-84 in postmenopausal women with low bone mineral density (BMD) who were receiving chronic (>/=6 months) HT. Subjects were randomized to receive 100 mug PTH(1-84) or placebo injections daily for 24 months (n = 90/group). The primary efficacy outcome was change from baseline in lumbar spine BMD. Secondary end points included changes in hip and distal radius BMD, bone turnover markers, and fracture incidence. The study was terminated early following recommendations regarding HT for PMO. At 18 months, the mean increase in lumbar spine BMD was 7.9% for PTH(1-84) subjects vs. 1.5% for those receiving HT alone; between-group differences were significant at 6 months and persisted throughout the study. Lumbar spine BMD increased in 94% of women receiving PTH(1-84) compared to 59% for HT alone. Femoral neck BMD and bone turnover markers were significantly higher in PTH(1-84)-treated subjects, but the changes in total hip and distal radius BMD were not significant. PTH(1-84) treatment was generally well-tolerated, with hypercalciuria, hypercalcemia, nausea, vomiting, and dizziness reported more frequently in the HT + PTH(1-84) group. In conclusion, addition of PTH(1-84) to stable HT produced marked increases in lumbar spine BMD and may represent an additional approach to the treatment of PMO women receiving HT. 相似文献
5.
F. Cosman S. J. de Beur M. S. LeBoff E. M. Lewiecki B. Tanner S. Randall R. Lindsay 《Osteoporosis international》2014,25(10):2359-2381
The Clinician’s Guide to Prevention and Treatment of Osteoporosis was developed by an expert committee of the National Osteoporosis Foundation (NOF) in collaboration with a multispecialty council of medical experts in the field of bone health convened by NOF. Readers are urged to consult current prescribing information on any drug, device, or procedure discussed in this publication. 相似文献
6.
Osteoporosis is a major public health problem characterized by low bone mineral density (BMD) that presently has no biochemical
test useful for its diagnosis. The cytokine TGF-β has been postulated to play a role in controlling bone density by regulating
the fine balance between bone matrix deposition by osteoblasts and its resorption by osteoclasts. We explored whether measurement
of serum levels of different TGF-β isoforms could be useful as a clinical tool in osteoporosis. We measured the concentration
of TGF-β1 antigen using the BDA19 capture sandwich enzyme-linked immunosorbent assay (ELISA), TGF-β2 antigen concentration
using a Quantikine sandwich ELISA kit and TGF-β3 antigen concentration using a modified version of the TGF-β1 Quantikine sandwich
ELISA kit. Subjects were 41 women with osteoporosis (with nontraumatic vertebral fracture or lumbar spine BMD Z-score <−1.5 SD) and a total of 199 control women from different sources. Serum concentrations of TGF-β1 and TGF-β2 were similar
in all groups. However, detectable levels of TGF-β3 (>0.2 ng/ml) were found in 35 of 41 patients with osteoporosis (median
7.2 (5.2–8.9) ng/ml) compared with 11 of 36 controls or 24 of 89 healthy women of unknown bone density. Differences among
the groups could not be accounted for by age, weight, medications, use of hormone replacement therapy or the presence of osteoarthritis.
Using the optimal cut-off of ≥2 ng/ml, the test was able to detect an individual with low spine BMD (Z-score <−1.5) with a sensitivity of 84% and a specificity of 53%, with similar results for the femoral neck. The odds ratio
for osteoporosis associated with a positive test at this level was 5.93 (95% CI 2.41–11.59), and 4.1 (95% CI 1.66–10.11) using
the WHO cut-off of T-score <−2.5. Serum TGF-β3 concentration is raised in osteoporotic women and the test appears to have potential as a marker
for osteoporosis. The underlying mechanisms and the relationships between TGF-β3 and bone turnover and fractures remain to
be explored.
Received: 4 April 1998 / Accepted: 21 September 1998 相似文献
7.
Effect of Estrogen–Progestogen Hormonal Replacement Therapy on Periurethral and Bladder Vessels 总被引:4,自引:1,他引:3
R. M. Endo M. J. B. C. Gir?o M. G. F. Sartori M. J. Sim?es E. C. Baracat G. Rodrigues de Lima 《International urogynecology journal》2000,11(2):120-123
This study assessed the effect of hormone replacement therapy using estrogens and/or progestogens on the number of vessels
in the proximal and distal urethra, vesicourethral junction and bladder of castrated adult female rats. Forty-five virgin
adult rats (Rattus norvegicus albinus) castrated for at least 30 days were used. They were assigned to five groups; group I (control) received no medication; the
others received via the subcutaneous route, respectively, 17-β-estradiol (group II), medroxyprogesterone acetate (group III),
a maize oil and benzyl acid solution – placebo (group IV) and 17-β-estradiol combined with medroxyprogesterone acetate (group
V), for a minimum of 28 days. Increased vascularization throughout the urinary tract, except in the distal urethra, was found
following estrogen replacement alone. In the group that received combined estrogens and progestogens, no increase was found.
It was concluded that estrogen replacement in castrated rats significantly increased the number of vessels in the lower urinary
tract. 相似文献
8.
9.
Takuo Fujita Masao Fukunaga Akira Itabashi Kiichiro Tsutani Toshitaka Nakamura 《Calcified tissue international》2014,94(2):170-175
We conducted a randomized, double-blind trial to assess the effect of 28.2 μg teriparatide versus placebo (1.4 μg teriparatide) on reduction of the incidence of vertebral fractures. Individuals enrolled in this study included patients with primary osteoporosis with one to five vertebral fractures and capable of self-supported walking. Attention was focused on incident vertebral fractures, change in bone mineral density (BMD) of the lumbar spine, and safety. A total of 316 subjects participated in the study, which lasted up to 131 weeks. Incident vertebral fractures occurred in 3.3 % of subjects in the 28.2 μg teriparatide-treated group and 12.6 % of subjects in the placebo group during the 78-weeks study period. Kaplan–Meier estimates of risk after 78 weeks were 7.5 and 22.2 % in the teriparatide and placebo groups, respectively, with a relative risk reduction of 66.4 % by teriparatide (P = 0.008). Lumbar BMD in the 28.2 μg teriparatide group increased significantly by 4.4 ± 4.7 % at 78 weeks, which was significantly higher than the corresponding data in the placebo group (P = 0.001). Adverse events were observed in 86.7 % of individuals in the teriparatide group and 86.1 % of those in the placebo group. In conclusion, weekly injection of a low-dose of teriparatide (28.2 μg) reduced the risk of incident vertebral fractures and increased lumbar BMD. 相似文献
10.
11.
Takuya Nakai Kiyotaka Okuno Hiroshi Kitaguchi Hajime Ishikawa Mitsuo Yamasaki 《World journal of surgery》2013,37(8):1919-1926
Background
Hepatic arterial infusion (HAI) or systemic chemotherapy has been used to treat unresectable colorectal liver metastases. The prognosis of the disease in recent years has been improved because chemotherapy is performed before hepatectomy to reduce tumor size (conversion therapy). The purpose of this study was to investigate the safety and efficacy of conversion therapy following HAI immunochemotherapy.Methods
Hepatic arterial infusion of 5-fluorouracil (5-FU)/polyethylene glycol (PEG)-IFNα-2a was performed in 21 patients. The primary endpoint was the safety of HAI and hepatectomy. The secondary endpoints were response rate, rate of conversion to hepatectomy, survival rate, and prognostic factors.Results
With regard to side effects, drugs were discontinued temporarily in one patient because of a decrease in white blood cell count; however, other patients continued chemotherapy. The response rate with HAI was 61.9 %, and the conversion rate was 38.1 %. Hepatectomy was completed successfully without mortality. Median progression-free survival (PFS) was 11.5 months (with and without conversion, 16.7 and 4.8 months, respectively; p = 0.021). Median overall survival was 34.6 months (with and without conversion, 48.4 and 26.6 months, respectively; p = 0.003). Prognosis was poor when the number of metastatic tumors was ≥10 [PFS: hazard ratio (HR) 32.21, p = 0.003; overall survival (OS): HR 9.13, p = 0.07], but prognosis improved after hepatectomy (OS: HR 0.08, p = 0.09).Conclusions
Hepatic arterial infusion immunochemotherapy with 5-FU/PEG-IFNα-2a was performed safely without major side effects. Prognosis is expected to improve after successful conversion to hepatectomy. 相似文献12.
We have evaluated the effect of aging, menopause and osteoporosis on the measurements of both nonisomerized type I collagen
C-telopeptide breakdown products (α-CTx) by radioimmunoassay (RIA) and β-isomerized type I collagen C-telopeptide breakdown
products (β-CTx) by enzyme-linked immunosorbent assay (ELISA). In 86 premenopausal healthy women (PRE), 144 postmenopausal
healthy women (POST), 74 patients with vertebral fractures (VX) and 61 patients with hip fractures (HX), urinary CTx excretion
was measured by both ELISA and RIA assays. Samples were collected more than 6 months after fracture in the VX group and within
48 h after fracture in the HX group. In all subjects a highly significant correlation was found between α-CTx and β-CTx (r= 0.85). The values of β-CTx in the POST group greatly increased compared with those in the PRE group (% mean increase: 82%),
while the values of α-CTx in the POST group moderately increased compared with those in the PRE group (% mean increase: 47%).
The values of both α-CTx and β-CTx in the HX group were significantly higher than those in the other groups, but particularly
the increase in mean α-CTx (211% for HX versus POST) was very high compared with the increase in mean β-CTx (68% for HX versus
POST). Moreover, the α-CTx/β-CTx ratio in the HX group was significantly higher than in the other groups. These results suggest
that both assays well reflect the increase in bone resorption associated with high bone turnover, especially, in osteoporotic
patients with hip fracture. However, there was a difference between the urinary excretion of α-CTx and β-CTx in patients with
hip fracture, so the α-CTx/β-CTx radio might be a good indicator reflecting the characteristics of bone metabolism for osteoporosis
with hip fracture.
Received: 9 March 1998 / Accepted: 21 September 1998 相似文献
13.
A. J. Shipman G. W. G. Guy I. Smith S. Ostlere W. Greer R. Smith 《Osteoporosis international》1999,9(5):420-426
The vertebral bone mineral density (BMD), bone mineral content (BMC) and bone area of the lumbar spine were measured using
a bone densitometer in 8789 women aged 33–73 years who had had no previous hormone replacement therapy (HRT). The overall
relationship between BMD and age was analyzed on a year-by-year basis, and comprised three separate regions that could each
be described by a straight line: 33–46 years (gradient = 0.00166 g cm−2/year), 47–63 years (gradient = 0.0121 g cm−2/year) and 64–73 years (gradient = 0.0045 g cm−2/year). Above the age of 50 years our results were higher than the BMD in most previous reports. In those 3198 women who knew
the time of their last menstrual period (mean age 49.25 years, SD 4.83) bone loss was most rapid in the first 10 menopausal
years. In the whole group, the relationship between BMC and age was found to be similar to that of BMD, with three distinct
regions, including a rapid drop between the ages of 47 and 63 years (gradient 0.781 g/year). Bone area showed a much more
gradual (though significant) decrease with age. Based on WHO definitions and using BMD as an indicator, the percentage of
women with osteoporosis varied from zero in the younger age group to about 30% of women aged over 70 years; in contrast, where
BMC was used, although the trend with age had a similar shape, the percentages at each year were about half those derived
from the corresponding BMD values. Osteopenia derived in the same way occurred in about 50% of women over 70 years using either
BMD or BMC. The results presented here provide a reliable local reference range for lumbar spine bone densitometry measurements.
They also show that for this site BMD and BMC cannot be used interchangeably to define osteoporosis.
Received: 13 March 1998 / Accepted: 23 September 1998 相似文献
14.
Rizzoli R Reginster JY Boonen S Bréart G Diez-Perez A Felsenberg D Kaufman JM Kanis JA Cooper C 《Calcified tissue international》2011,89(2):91-104
The pharmacological management of disease should involve consideration of the balance between the beneficial effects of treatment
on outcome and the probability of adverse effects. The aim of this review is to explore the risk of adverse drug reactions
and drug–drug interactions with treatments for postmenopausal osteoporosis. We reviewed evidence for adverse reactions from
regulatory documents, randomized controlled trials, pharmacovigilance surveys, and case series. Bisphosphonates are associated
with gastrointestinal effects, musculoskeletal pain, and acute-phase reactions, as well as, very rarely, atrial fibrillation,
atypical fracture, delayed fracture healing, osteonecrosis of the jaw, hypersensitivity reactions, and renal impairment. Cutaneous
effects and osteonecrosis of the jaw are of concern for denosumab (both very rare), though there are no pharmacovigilance
data for this agent yet. The selective estrogen receptor modulators are associated with hot flushes, leg cramps, and, very
rarely, venous thromboembolism and stroke. Strontium ranelate has been linked to hypersensitivity reactions and venous thromboembolism
(both very rare) and teriparatide with headache, nausea, dizziness, and limb pain. The solidity of the evidence base depends
on the frequency of the reaction, and causality is not always easy to establish for the very rare adverse reactions. Drug–drug
interactions are rare. Osteoporosis treatments are generally safe and well tolerated, though they are associated with a few
very rare serious adverse reactions. While these are a cause for concern, the risk should be weighed against the benefits
of treatment itself, i.e., the prevention of osteoporotic fracture. 相似文献
15.
Daniel CW Robinson S Silberstein GB 《Journal of mammary gland biology and neoplasia》1996,1(4):331-341
Evidence that transforming growth factor beta (TGF-)4 influences pattern formation in the developing mammary gland and negatively regulates ductal growth is reviewed. In the mouse, overexpression of TGF- transgenes during puberty reduces the rate of growth of the ductal tree and simplifies the pattern of arborization, while expression during pregnancy also interferes with lactation. Expression studies in the normal mouse gland indicate that TGF- is synthesized in the mammary epithelium, with the three isoforms showing somewhat different spatial and temporal distributions. Exogenous TGF- applied directly to the glandin situ inhibits epithelial cell division within hours, and strongly stimulates extracellular matrix synthesis over a longer time course. Normal human breast cells as well as certain breast cancer cell lines also secrete TGF- and are themselves inhibited by it, suggesting an autoregulatory feedback circuit, that in some cases appears to be modulated by estradiol. Taken together, the evidence suggests a model in which growth and patterning of the mammary ductal tree are regulated, at least in part, by TGF- operating through an autocrine feedback mechanism and by paracrine circuits associated with epithelial-stromal interactions. 相似文献
16.
17.
BleedingandpainarethecommonsideeffectsofIUDuse.TwokindsofnewIUDscontainingindomethacinandcopperhavebeendevelopedsince1986,bythenameofmedicatedr-IUD,andmedicatedstainlesssteelring165.ThereafterVCu--IUDwithindomethacin,medicatedLu--T--IUDandmedicateduterinecavityshapedIUDetc.havealsobeendeveloped.Amongthem,r--IUDistheonlyonethathasbeenobservedwithalargenumberofsubjectsandsystematicallyfollowedupforalongterm(morethan10years).Thispaper,whichisdividedin4parts,istoreporttheclinicalperforma… 相似文献
18.
Estrogens are important for the development and function of the normal mammary gland as well as for development of mammary cancer. The frontline therapy for treatment of estrogen receptor (ER)4 positive breast cancer is antiestrogens. A second estrogen receptor (ER) is also expressed in the breast but it has not been measured because it is not detected by the immunoassays used to detect ER. In many cell systems ER has actions which are opposite to those of ER and this finding has raised questions about the role of ER in the development and treatment of breast cancer. 相似文献
19.
S. Pomer R. Thiele V. Daniel R. Weimer H. Löhrke V. Schirrmacher G. Staehler 《World journal of urology》1991,9(4):223-227
Summary Thirty patients with advanced renal cell carcinoma (RCC), 23 of whom had distant metastases in at least one organ, were entered after nephrectomy into a protocol involving vaccination with Newcastle disease virus (NDV)-modified autologous tumour material, with a subsequent induction week and repetitive bi-weekly cycles of interleukin-2 (rIL-2) and interferon 2b/rIFN-2b at a lower s. c. dose (1.5 million Cetus units m–2 day–1 every 12 h on 2 days and 3 million IU/m2 once a day on days 1, 3 and 5). The inpatient treatment was followed by a maintenance phase during which 0.3 million Cetus units/m2 rIL-2 was given s. c. every 12 h on days 1–5 and 3 million IU m–2 day–1 rIFN-2b was administered on days 1, 3, and 5 on an outpatient basis. All but 3 patients completed the induction week and 6 weeks of outpatient therapy. No grade 3 or 4 toxicities occurred during the therapy. Therapy was discontinued for 3 patients because of rapid tumour progression. Of the 23 evaluable RCC patients, 3 exhibited a complete response and 4 displayed partial remission, 7 showed stable disease during 1–18 months (median = 5 months) of therapy, and progression was seen in 9. We conclude that vaccination with autologous tumour material combined with s. c. rIL-2 and rIFN-2b administration can induce regressions in patients with advanced RCC and that even in non-responding patients a more favourable course of the disease can be achieved. 相似文献