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21.
Summary Women with osteoporosis on raloxifene were randomized to 1-34hPTH + raloxifene or raloxifene alone for one year. In the PTH
+ raloxifene group, bone turnover increased 125–584%, spine BMD increased 9.6%, hip BMD increased 1.2–3.6% and radius BMD
declined 4.3%. During the follow-up year, on continued raloxifene, BMD declined slightly at all sites except the femoral neck.
Introduction The influence of prior antiresorptives on response to 1–34PTH and the ability to maintain BMD gains might differ for antiresorptive
agents with different potencies. The objectives were to evaluate biochemical and bone density responses to 1–34PTH in patients
on prior and ongoing raloxifene and to determine whether raloxifene maintains bone gains.
Methods Forty-two postmenopausal women with osteoporosis on raloxifene were randomized to raloxifene alone or 1–34PTH daily for 12 months
(continuing raloxifene). Women were then followed for 12 months on raloxifene alone. Bone turnover markers and BMD were measured
at baseline and at 3, 6, 12, 18 and 24 months.
Results Biochemical indices increased rapidly during PTH treatment with peak increments of 125–584% for the three markers (p < 0.001
vs. baseline). After one year of PTH, mean BMD increases were 9.6% for spine, 2.7% for total hip, 3.6% for trochanter (all
p < 0.005) and 1.2% in femoral neck (NS), while BMD declined 4.3% in the radius (p = 0.003). After PTH withdrawal, on continued
raloxifene, BMD declined slightly (0.7–2.9% losses; NS) at all sites, except the femoral neck, where BMD increased modestly
(p = 0.04). At 24 months, spine and femoral neck BMD remained significantly higher than baseline, while radius BMD remained
significantly lower (all p < 0.04).
Conclusion Substantial gains in BMD of the spine and hip, but not the radius, are seen with one year of PTH treatment in patients on
prior raloxifene. After PTH is discontinued, raloxifene partially maintains PTH-induced BMD gains in the spine and hip. 相似文献
22.
M. R. Allen E. Gineyts D. J. Leeming D. B. Burr P. D. Delmas 《Osteoporosis international》2008,19(3):329-337
Summary Changes in organic matrix may contribute to the anti-fracture efficacy of anti-remodeling agents. Following one year of treatment
in beagle dogs, bisphosphonates alter the organic matrix of vertebral trabecular bone, while raloxifene had no effect. These
results show that pharmacological suppression of turnover alters the organic matrix component of bone.
Introduction The collagen matrix contributes significantly to a bone’s fracture resistance yet the effects of anti-remodeling agents on
collagen properties are unclear. The goal of this study was to assess changes in collagen cross-linking and isomerization
following anti-remodeling treatment.
Methods Skeletally mature female beagles were treated for one year with oral doses of vehicle (VEH), risedronate (RIS; 3 doses), alendronate
(ALN; 3 doses), or raloxifene (RAL; 2 doses). The middle dose of RIS and ALN and the lower dose of RAL approximate doses used
for treatment of post menopausal osteoporosis. Vertebral trabecular bone matrix was assessed for collagen isomerization (ratio
of α/β C-telopeptide [CTX]), enzymatic (pyridinoline [PYD] and deoxypyridinoline [DPD]), and non-enzymatic (pentosidine [PEN])
cross-links.
Results All doses of both RIS and ALN increased PEN (+34–58%) and the ratio of PYD/DPD (+14–26%), and decreased the ratio of α/β CTX
(−29–56%) compared to VEH. RAL did not alter any collagen parameters. Bone turnover rate was significantly correlated to PEN
(R = −0.664), α/β CTX (R = 0.586), and PYD/DPD (R = −0.470).
Conclusions Bisphosphonate treatment significantly alters properties of bone collagen suggesting a contribution of the organic matrix
to the anti-fracture efficacy of this drug class. 相似文献
23.
24.
H. Sumino S. Ichikawa S. Kasama T. Takahashi H. Kumakura Y. Takayama T. Kanda M. Murakami M. Kurabayashi 《Maturitas》2009
Objectives
Hormone replacement therapy (HRT) increases skin elasticity in postmenopausal women. However, the effects of raloxifene, a selective estrogen receptor modulator (SERM), on skin degenerative changes in postmenopausal women remain unknown. We investigated whether raloxifene increases skin elasticity, similar to HRT, in postmenopausal women.Methods
In a 12-month trial, 17 postmenopausal women (mean age, 66.4 ± 7.8 years) received continuous raloxifene treatment (60 mg/day), 19 women (56.2 ± 6.4 years) received continuous 17-β estradiol treatment using a patch (0.72 mg/2 days) plus cyclic medroxyprogesterone acetate (2.5 mg/day, for 12 days/month), and 11 women (58.1 ± 7.3 years) did not receive either therapy. In each subject, the skin elasticity of the forearm was measured using a suction device at baseline and at 12 months after the start of the study.Results
Raloxifene and HRT significantly increased skin elasticity from 52.4 ± 3.8% and 64.1 ± 7.2% at baseline to 55.1 ± 4.7% and 67.4 ± 7.4% after 12 months, respectively (P < 0.05, each), but the untreated subjects did not exhibit any significant change in skin elasticity during the study. The delta value for skin elasticity was significantly higher among the raloxifene and HRT subjects than among the untreated subjects (P < 0.05, each).Conclusions
These findings suggest that raloxifene may have a beneficial effect on skin elasticity, which undergoes degenerative changes in postmenopausal women, in addition to its effects on bone metabolism. 相似文献25.
26.
Antiremodeling agents reduce bone loss in part through direct actions on osteoclasts. Their effects on osteoblasts and bone
formation activity are less clear and may differ at sites undergoing modeling vs. remodeling. Skeletally mature intact beagles,
1–2 years old at the start of the study, were treated daily with clinically relevant doses of alendronate (0.10 or 0.20 mg/kg),
risedronate (0.05 or 0.10 mg/kg), raloxifene (0.50 mg/kg), or vehicle (1 mL/kg). Dynamic bone formation parameters were histologically
assessed on periosteal, endocortical/trabecular, and intracortical bone envelopes of the rib. Raloxifene significantly increased
periosteal surface mineral apposition rate (MAR), a measure of osteoblast activity, compared to all other treatments (+108
to +175%, P < 0.02), while having no significant effect on MAR at either the endocortical/trabecular or intracortical envelope. Alendronate
(both 0.10 and 0.20 doses) and risedronate (only the 0.10 dose) significantly (P ≤ 0.05) suppressed MAR on the endocortical/trabecular envelope, while none of the bisphosphonate doses significantly altered
MAR at either the periosteal or intracortical envelopes compared to vehicle. Based on these results, we conclude that (1)
at clinically relevant doses the two classes of antiremodeling agents, bisphosphonates and selective estrogen receptor modulators,
exert differential effects on osteoblast activity in the canine rib and (2) this effect depends on whether modeling or remodeling
is the predominant mechanism of bone formation.
M. R. Allen and H. Follet contributed equally to this work. 相似文献
27.
Cakmak A Posaci C Dogan E Caliskan S Guclu S Altunyurt S 《American journal of obstetrics and gynecology》2005,193(2):347-351
OBJECTIVE: The purpose of this study was to investigate the effect of raloxifene on leptin and insulin-like growth factor-I levels and their relation with the biochemical markers of bone metabolism in postmenopausal women. STUDY DESIGN: Sixty-four women were given 60 mg/d raloxifene for 6 months. Serum leptin, insulin-like growth factor-I, alkaline phosphatase, calcium, osteocalcin, and collagen type I cross-link C-telopeptide levels were measured before and after the treatment. The patients were grouped as obese (body mass index, > or =25 kg/m2) or non-obese (body mass index, <25 kg/m2). RESULTS: The mean basal leptin level was significantly higher (P < .001), and the mean cross-link C-telopeptide level was significantly lower (P = .001) in obese patients. Raloxifene therapy increased leptin levels (P < .001) and decreased insulin-like growth factor-I, alkaline phosphatase, and cross-link C-telopeptide levels significantly (P < .001). There was a strong negative correlation between leptin and cross-link C-telopeptide (r = -0.703; P < .001). Insulin-like growth factor-I was not correlated with any parameter. CONCLUSION: Raloxifene increases serum leptin levels while decreasing bone resorption in postmenopausal women. 相似文献
28.
Lucena MI Andrade RJ Vicioso L González FJ Pachkoria K García-Muñoz B 《World journal of gastroenterology : WJG》2006,12(32):5244-5246
Assigning causality in drug-induced liver injury is challenging particularly when more than one drug could be responsible. We report a woman on long-term therapy with raloxifen who developed acute cholestasis shortly after starting fenofibrate. The picture evolved into chronic cholestasis. We hypothesized that an interaction at the metabolic level could have triggered the presentation of hepatotoxicity after a very short time of exposure to fenofibrate in this patient. The findings of an overexpression of vascular endothelial growth factor in the liver biopsy suggest that angiogenesis might play a role in the persistance of toxic cholestasis. 相似文献
29.
S. Yamano N. Nakamoto S. Toki 《Xenobiotica; the fate of foreign compounds in biological systems》2013,43(9):917-930
1. Rat liver cytosol produced exclusively 6β-naloxol from naloxone in the presence of either NADPH or NADH at pH 7.4. The amount of 6β-naloxol formed with NADPH was about four times that with NADH. The enzyme responsible for this reaction, termed naloxone reductase, was purified to a homogeneous protein by various chromatographic techniques. 2. The purified enzyme is a monomeric protein with a molecular weight of 34000 and an isoelectric point of 5.9, and it has a dual co-factor specificity for NADPH and NADH. The enzyme catalysed the reduction of various carbonyl compounds as well as naloxone analogues, and the dehydrogenation of 3α-hydroxysteroids and alicyclic alcohols. Indomethacin, quercetin and sulphhydryl reagents potently inhibited the enzyme, but pyrazole and barbital had no effect on the enzyme activity. 3. Identity of naloxone reductase and 3alpha-hydroxysteroid dehydrogenase in rat liver was demonstrated by comparing the elution profiles of the two enzyme activities during purification, the ratios of the two enzyme activities at each purification steps, and thermal stability and susceptibility to inhibitors for the two enzyme activities. 4. Amino acid sequences of five peptides obtained by proteolytic digestion of the purified enzyme were completely identical to the corresponding regions of previously reported 3alpha-hydroxysteroid dehydrogenase. 相似文献
30.
《Current medical research and opinion》2013,29(7):1425-1436
ABSTRACTBackground: During the years following menopause, estrogen levels decline leading to accelerated bone loss and an increased risk of osteoporosis and osteoporosis-related fractures.Methods: Using a Markov model and decision analytic techniques, the long-term costs and outcomes of five treatment and secondary prevention strategies for osteoporosis were compared: ‘no intervention’, alendronate, etidronate, risedronate, and raloxifene. The base case analysis examined postmenopausal (65 year old) osteoporotic women without prior fracture. Probabilistic sensitivity analysis (PSA) was used to incorporate the impact of parameter uncertainty, and deterministic sensitivity analysis (DSA) was used to compare alternative patient populations and modeling assumptions. Life years and Quality Adjusted Life Years (QALYs) were used as measures of effectiveness.Results: In the base case analysis, risedronate was dominated by etidronate and alendronate. Alendronate and etidronate were projected to have similar costs and QALYs, and the efficiency frontier was represented by ‘no intervention’, etidronate, alendronate, and raloxifene (Can$32?571, Can$38?623 and Can$114?070 per QALY respectively). Alternative assumptions of raloxifene's impact on CHD and breast cancer, alternative discount rates and alternative patient risk factors (e.g., starting age of therapy, CHD risk, and prior fracture risk) had significant impacts on the overall cost-effectiveness results for both the bisphosphonates and raloxifene.Discussion: Using conventionally quoted benchmarks and compared to no therapy, alendronate, etidronate, and raloxifene would all be considered cost-effective alternatives for treating women with osteoporosis. Potential limitations of this study include the usual caveats and cautions associated with long-term projection models and the fact that not all inputs into the model are Canadian data sources. 相似文献