1.
Efficacy of Pharmacological Therapies for the Prevention of Fractures in Postmenopausal Women: A Network Meta-Analysis.
Barrionuevo, P, Kapoor, E, Asi, N, Alahdab, F, Mohammed, K, Benkhadra, K, Almasri, J, Farah, W, Sarigianni, M, Muthusamy, K, et al
The Journal of clinical endocrinology and metabolism. 2019;(5):1623-1630
Abstract
BACKGROUND Osteoporosis and osteopenia are associated with increased fracture incidence in postmenopausal women. We aimed to determine the comparative effectiveness of various available pharmacological therapies. METHODS We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ISI Web of Science, and Scopus for randomized controlled trials that enrolled postmenopausal women with primary osteoporosis and evaluated the risk of hip, vertebral, or nonvertebral fractures. A network meta-analysis was conducted using the multivariate random effects method. RESULTS We included 107 trials (193,987 postmenopausal women; mean age, 66 years; 55% white; median follow-up, 28 months). A significant reduction in hip fractures was observed with romosozumab, alendronate, zoledronate, risedronate, denosumab, estrogen with progesterone, and calcium in combination with vitamin D. A significant reduction in nonvertebral fractures was observed with abaloparatide, romosozumab, denosumab, teriparatide, alendronate, risedronate, zoledronate, lasofoxifene, tibolone, estrogen with progesterone, and vitamin D. A significant reduction in vertebral fractures was observed with abaloparatide, teriparatide, parathyroid hormone 1-84, romosozumab, strontium ranelate, denosumab, zoledronate, risedronate, alendronate, ibandronate, raloxifene, bazedoxifene, lasofoxifene, estrogen with progesterone, tibolone, and calcitonin. Teriparatide, abaloparatide, denosumab, and romosozumab were associated with the highest relative risk reductions, whereas ibandronate and selective estrogen receptor modulators had lower efficacy. The evidence for the treatment of fractures with vitamin D and calcium remains limited despite numerous large trials. CONCLUSIONS This network meta-analysis provides comparative effective estimates for the various available treatments to reduce the risk of fragility fractures in postmenopausal women.
2.
Relationship Between Breast Density and Selective Estrogen-Receptor Modulators, Aromatase Inhibitors, Physical Activity, and Diet: A Systematic Review.
Ekpo, EU, Brennan, PC, Mello-Thoms, C, McEntee, MF
Integrative cancer therapies. 2016;(2):127-44
Abstract
Background Lower breast density (BD) is associated with lower risk of breast cancer and may serve as a biomarker for the efficacy of chemopreventive strategies. This review explores parameters that are thought to be associated with lower BD. We conducted a systematic review of articles published to date using the PRISMA strategy. Articles that assessed change in BD with estrogen-receptor modulators (tamoxifene [TAM], raloxifene [RLX], and tibolone) and aromatase inhibitors (AIs), as well as cross-sectional and longitudinal studies (LSs) that assessed association between BD and physical activity (PA) or diet were reviewed. Results Ten studies assessed change in BD with TAM; all reported TAM-mediated BD decreases. Change in BD with RLX was assessed by 11 studies; 3 reported a reduction in BD. Effect of tibolone was assessed by 5 RCTs; only 1 reported change in BD. AI-mediated BD reduction was reported by 3 out of 10 studies. The association between PA and BD was assessed by 21 studies; 4 reported an inverse association. The relationship between diet and BD was assessed in 34 studies. All studies on calcium and vitamin D as well as vegetable intake reported an inverse association with BD in premenopausal women. Two RCTs demonstrated BD reduction with a low-fat, high-carbohydrate intervention. Conclusion TAM induces BD reduction; however, the effect of RLX, tibolone, and AIs on BD is unclear. Although data on association between diet and BD in adulthood are contradictory, intake of vegetables, vitamin D, and calcium appear to be associated with lower BD in premenopausal women.
3.
Prevention of bone resorption by intake of phytoestrogens in postmenopausal women: a meta-analysis.
Salari Sharif, P, Nikfar, S, Abdollahi, M
Age (Dordrecht, Netherlands). 2011;(3):421-31
Abstract
Phytoestrogens as selective estrogen receptor modulators like compounds may consider as a therapeutic option in osteoporosis. In this regard, the effect of phytoestrogens on bone biomarkers was examined in several trials which their results are controversial. We aimed this meta-analysis to evaluate the net effect of phytoestrogens on bone markers. A thorough search was conducted from 2000 to 2010 in English articles. All randomized clinical trials were reviewed, and finally, 11 eligible randomized clinical trials were selected for meta-analysis. Totally 1,252 postmenopausal women were enrolled in the study by considering the changes of pyridinoline (Pyd), desoxypyridinoline (Dpyd), bone alkaline phosphatase, and osteocalcin concentrations in urine and serum after phytoestrogens consumption. The urine Pyd and Dpyd levels decreased significantly in phytoestrogens consumers. Effect size and effect size for weighted mean difference of urine Pyd levels showed -1.229171 (95% confidence interval (CI) = -1.927639 to -0.530703) and -9.780623 (95% CI = -14.240401 to -5.320845), respectively, a significant results in comparison to control group and significant results for Dpyd -0.520132 (95% CI = -0.871988 to -0.168275) and -0.818582 (95% CI = -1.247758 to -0.389407), respectively. Meta-analysis indicates that phytoestrogens intake can prevent bone resorption, but its benefits on bone formation are not significant. This favorable effect was observed in low doses and in at least 3 weeks of phytoestrogens intake.
4.
Meta-analyses of therapies for postmenopausal osteoporosis. IV. Meta-analysis of raloxifene for the prevention and treatment of postmenopausal osteoporosis.
Cranney, A, Tugwell, P, Zytaruk, N, Robinson, V, Weaver, B, Adachi, J, Wells, G, Shea, B, Guyatt, G, ,
Endocrine reviews. 2002;(4):524-8
Abstract
OBJECTIVE To review the effect of raloxifene on bone density and fractures in postmenopausal women. DATA SOURCE We searched MEDLINE from 1966 to 2000 and examined citations of relevant articles and the proceedings of international osteoporosis meetings. STUDY SELECTION We included seven trials that randomized women to raloxifene or placebo, with both groups receiving similar calcium and vitamin D supplementation, and measured bone density for at least one year. DATA EXTRACTION For each trial, three independent reviewers abstracted the data and assessed the methodological quality using a validated tool. DATA SYNTHESIS Data from one large dominating trial suggest a reduction in vertebral fractures with a relative risk (RR) of 0.60 [95% confidence interval (CI) 0.50-0.70, P < 0.01]. The RR of nonvertebral fractures in patients given 60 mg or more of raloxifene in the larger study was 0.92 (95% CI 0.79-1.07, P = 0.27). Raloxifene resulted in positive effects on the percentage change in bone density, which increased over time and was independent of dose. At the final year, point estimates and 95% CIs for the differences in percent change in bone density (95% CI) between raloxifene and placebo groups were 1.33 (95% CI 0.37-2.30) for total body, 2.51 (95% CI 2.21-2.82) for lumbar spine, 2.05 (95% CI 0.71-3.39) for combined forearm, and 2.11 (95% CI 1.68-2.53) for combined hip (P < 0.01 at all four sites). Results were similar across studies, and formal tests of heterogeneity did not approach conventional statistical significance. Raloxifene slightly increased rates of withdrawal from therapy as a result of adverse effects (RR 1.15, 95% CI 1.00-1.33, P = 0.05). The pooled RR was significant for hot flashes 1.46 (95% CI 1.23-1.74, P < 0.01) and nonsignificant for leg cramps 1.64 (95% CI 0.84-3.20, P = 0.15). CONCLUSION Raloxifene increases bone density, and the effect increases over 2 yr. The data suggest a positive impact of raloxifene on vertebral fractures. There was little effect of raloxifene on nonvertebral fractures.