Lasofoxifene in Postmenopausal Women with Osteoporosis

Cummings, Steven R.; Ensrud, Kristine E.; Delmas, Pierre D.; LaCroix, Andrea Z.; Vukičević, Slobodan; Reid, David M.; Goldstein, Steven R.; Sriram, Usha; Lee, Andy; Thompson, John R.; Armstrong, R; Thompson, David D.; Powles, Trevor J.; Zanchetta, José R.; Kendler, David L.; Neven, Patrick; Eastell, Richard

doi:10.1056/nejmoa0808692

Cited by 344 publications

(195 citation statements)

References 36 publications

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“…The incidence of ductal carcinoma in situ (DCIS) was also reduced (HR 0.72; 95% CI 0.57-0.92), but the frequency of estrogen receptor-negative breast cancers was non-significantly increased (HR 1.13; 95% CI 0.86-1.49). Similar results were achieved if other SERMS such as raloxifene [23,24,25,26] or the third-generation substances lasofoxifene and arzoxifene were used [27,28,29,30]. In the meta-analysis [22,] overall reduction in breast cancer (including DCIS) was 38% (p < 0.0001) for all SERMs.…”

Section: Risk Reduction By Selective Estrogen Receptor Modulatorssupporting

confidence: 65%

Medical Prevention of Breast Cancer

Stubert¹,

Dieterich²,

Gerber³

2014

Breast Care

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Breast cancer is the most common cancer of women in Western Europe and North America. Effective strategies of medical prevention could reduce the burden of breast cancer mortality. The best evidence for a risk reduction exists for hormonal agents such as tamoxifen and raloxifene (22-72%) or aromatase inhibitors (50-65%). However, the severity of side effects and the lack of evidence for an improved survival compromise the risk/benefit balance. In this review the results of chemoprevention studies, including new treatment approaches, are summarized with critical discussion of their use in clinical practice.

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Section: Risk Reduction By Selective Estrogen Receptor Modulatorssupporting

confidence: 65%

Medical Prevention of Breast Cancer

Stubert¹,

Dieterich²,

Gerber³

2014

Breast Care

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“…Estrogen replacement therapy has been the most popular treatment for osteoporosis in the last decade [4]. However, prolonged use of estrogen increases the risk of breast cancer and endometrial cancer, coronary heart disease or stroke, and venous thromboembolic diseases [5][6][7][8]. Biophosphonate therapy though it inhibits bone resorption by osteoclasts, could cause severe incapacitating bone, joint, and/or muscle pain [9,10].…”

Section: Introductionmentioning

confidence: 99%

<i>Panax Notoginseng</i> Saponins Promote Osteogenic Differentiation of Bone Marrow Stromal Cells Through the ERK and P38 MAPK Signaling Pathways

Liu

Chang

et al. 2011

Cell Physiol Biochem

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The Chinese medicinal herb, Panax notoginseng, has long been used to treat bone fractures and Panax notoginseng saponins (PNS) could promote bone formation. Here, we investigated whether PNS could promote osteogenesis of bone marrow stromal cells (BMSCs) through modulating the MAPK signaling pathways, which are implicated in BMSC osteogenesis. We found that PNS markedly increased the mineralization of BMSCs by alizarin red S assays and stimulate alkaline phosphatase activity of these cells. Additionally, PNS significantly increased the mRNA levels of alkaline phosphatase, core-binding factor a1, and bone sialoprotein while decreasing PPAR 2 mRNA levels. Furthermore, inhibitors of ERK, PD98059, and p38, SB203580 inhibited the osteogenesis-potentiating effects by PNS. PNS stimulated the activation of ERK and p38 as evidenced by increased phosphorylation of these proteins, which was inhibited by PD98059 and SB203580. Our findings indicate that PNS could promote BMSC osteogenesis by activating the ERK and p38 signaling pathways.

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“…Bazedoxifene, available in Europe, and combined with conjugated estrogen in the USA, has been studied in fracture prevention but the effects to prevent or treat breast cancer are unknown [45]. Lasofoxifene, another SERM in development, reduced vertebral fracture risk and ER-positive breast cancers in postmenopausal as well [46].…”

Section: Other Sermsmentioning

confidence: 99%

Adjuvant Endocrine Therapy and Bone Health in Breast Cancer

Clines

Choksi

Poznak

2015

Curr Osteoporos Rep

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Breast cancer is one of the most common malignancies of women. The majority of breast cancers express estrogen and/or progesterone receptors, permitting anticancer targeting strategies to reduce estrogen signaling in the cancer cells and thereby lowering the risk of breast cancer recurrence. The development of the selective estrogen receptor modulator (SERM) tamoxifen marked a significant milestone in breast cancer care that transcended older estrogen ablative strategies such as oophorectomy and ovarian irradiation. An unintended benefit of tamoxifen in postmenopausal women was bone density preservation. The third generation of aromatase inhibitors (AIs) have demonstrated superior efficacy to tamoxifen in improving disease-free survival in postmenopausal women. However, the AIs significantly increase bone resorption, reduce bone mineral density, and increase the risk of fracture above that of tamoxifen. As a consequence of this, clinical oncologists have assumed a larger role in the screening and treatment of the skeletal complications of breast cancer therapies. The key features of managing bone health in women with early stage breast cancer receiving adjuvant endocrine therapy are reviewed here.

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Lasofoxifene in Postmenopausal Women with Osteoporosis

Cited by 344 publications

References 36 publications

Medical Prevention of Breast Cancer

Medical Prevention of Breast Cancer

<i>Panax Notoginseng</i> Saponins Promote Osteogenic Differentiation of Bone Marrow Stromal Cells Through the ERK and P38 MAPK Signaling Pathways

Adjuvant Endocrine Therapy and Bone Health in Breast Cancer

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