9 research outputs found

    The effect of teriparatide treatment on circulating periostin and its relationship to regulators of bone formation and BMD in postmenopausal women with osteoporosis

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    Context: Treatment of postmenopausal osteoporosis with teriparatide (PTH 1-34) increases bone formation and improves bone microarchitecture. A possible modulator of this mechanism of action is periostin. In vitro experiments have shown that periostin may regulate osteoblast differentiation and bone formation through Wnt signaling. Periostin secretion is increased by PTH in preclinical models, but the effect of teriparatide treatment of postmenopausal osteoporosis on periostin is not currently known. Objectives, to: i) determine the effect of teriparatide treatment on circulating levels of periostin and other regulators of bone formation and ii) investigate how changes in periostin relate to changes in bone turnover markers, regulators of bone formation and bone mineral density. Participants and design: 20 women with postmenopausal osteoporosis, a two-year open-label single-arm study. Intervention: Teriparatide 20 mcg was administered by subcutaneous injection daily over 104 weeks. Periostin, sclerostin and DKK-1, PINP and CTX were measured in fasting serum collected at baseline (two visits) then at weeks 1,2,4,12,26,52,78 and 104. BMD was measured at the lumbar spine, total hip and femoral neck by DXA. Results: Periostin levels increased by 6.6% (95% CI -0.4, 13.5) after 26 weeks teriparatide treatment and significantly by 12.5% (95% CI 3.3,21.0, P<0.01) after 52 weeks. Change in periostin was positively correlated with change in lumbar spine BMD at week 52 (r=0.567(95% CI 0.137,0.817), P<0.05) and femoral neck BMD at week 104(r=0.682(95% CI 0.261,0.885), P<0.01). Conclusion: Teriparatide therapy increases periostin secretion; it is unclear whether this increase mediates the effect of the drug on bone

    Continuing outcomes relevant to Evista: Breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene

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    Background: The randomized, double-blind Multiple Outcomes of Raloxifene Evaluation (MORE) trial found that 4 years of raloxifene therapy decreased the incidence of invasive breast cancer among postmenopausal women with osteoporosis by 72% compared with placebo. We conducted the Continuing Outcomes Relevant to Evista (CORE) trial to examine the effect of 4 additional years of raloxifene therapy on the incidence of invasive breast cancer in women in MORE who agreed to continue in CORE. Methods: Women who had been randomly assigned to receive raloxifene (either 60 or 120 mg/day) in MORE were assigned to receive raloxifene (60 mg/day) in CORE (n = 3510), and women who had been assigned to receive placebo in MORE continued on placebo in CORE (n = 1703). Breast cancer incidence was analyzed by a log-rank test, and a Cox proportional hazards model was used to compute hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. Results: During the CORE trial, the 4-year incidences of invasive breast cancer and estrogen receptor (ER)-positive invasive breast cancer were reduced by 59% (HR = 0.41; 95% CI = 0.24 to 0.71) and 66% (HR = 0.34; 95% CI = 0.18 to 0.66), respectively, in the raloxifene group compared with the placebo group. There was no difference between the two groups in incidence of ER-negative invasive breast cancer during CORE (P = .86). Over the 8 years of both trials, the incidences of invasive breast cancer and ER-positive invasive breast cancer were reduced by 66% (HR = 0.34; 95 % CI = 0.22 to 0.50) and 76% (HR = 0.24; 95% CI = 0.15 to 0.40), respectively, in the raloxifene group compared with the placebo group. During the CORE trial, the relative risk of thromboembolism in the raloxifene group compared with that in the placebo group was 2.17 (95% CI = 0.83 to 5.70). This increased risk, also observed in the MORE trial, persisted over the 8 years of both trials. Conclusions: The reduction in invasive breast cancer incidence continues beyond 4 years of raloxifene treatment in postmenopausal women with osteoporosis. No new safety concerns related to raloxifene therapy were identified during CORE. © Oxford University Press 2004, all rights reserved
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