Increased Sclerostin Levels after Further Ablation of Remnant Estrogen by Aromatase Inhibitors

Kim, Won-Jin; Chung, Yoonjung; Kim, Se Hwa; Park, Sehee; Bae, Jae Hyun; Kim, Gyuri; Lee, Su Jin; Kim, Jo Eun; Park, Byeong Woo; Lim, Sung Kil; Rhee, Yumie

doi:10.3803/enm.2015.30.1.58

Cited by 16 publications

(13 citation statements)

References 30 publications

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“…Surprisingly, exemestane also increased sclerostin and DKK-1 in femoral epiphysis but not in lumbar bones. Our results are in agreement with recent clinical reports where increased serum sclerostin following treatment with aromatase inhibitors has been reported in women with breast cancer [41,42]. However, in the latter study, DKK-1 levels reduced after 24 months of treatment with anastrozole [42].…”

Section: Discussionsupporting

confidence: 93%

Differential profile of letrozole and exemestane on bone turnover markers in vinylcyclohexene diepoxide treated ovotoxic female mice

Kalam

Talegaonkar

Vohora

2016

Fundamemntal Clinical Pharma

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The third generation aromatase inhibitors are currently the drugs of choice for treatment of early and advanced breast cancer in postmenopausal women. One of the significant limiting factor during therapy is their negative impact on bone health. In the present study, we compared the effects of a non-steroidal (letrozole) and a steroidal aromatase inhibitor (exemestane) on bone mineral density and markers of bone turnover including alkaline phosphatase (ALP), tartrateresistant acid phosphatase (TRAP), hydroxyproline (HxP), receptor activator of nuclear factor kappa-B ligand (RANKL), sclerostin and dickkopf-1 (DKK-1) in vinlycyclohexene di epoxide (VCD)-induced ovotoxic female mice. VCD administration for 15 days mimicked a postmenopausal state with reduced serum estradiol levels. Ovotoxicity was accompanied by reduced ALP, HxP and enhanced TRAP, sclerostin and DKK-1 activity in femoral epiphysis and lumbar vertebrae of mice. While letrozole (1mg/kg) administration for one month enhanced bone turnover in ovotoxic mice, exemestane (3.25 mg/kg) was devoid of such effects in both normal and ovotoxic mice. The latter, however, reduced ALP in femoral epiphysis of ovotoxic mice.Letrozole depleted estradiol levels in ovotoxic mice and enhanced RANKL activity while exemestane neither affected estradiol nor RANKL in both normal and ovotoxic mice, and enhanced sclerostin and DKK-1 in femoral epiphysis only. The study indicates that the two aromatase inhibitors possesses differential profile in terms of their effects on bone and that exemestane could be a better option for the treatment of breast cancer in postmenopausal women at least in terms of its effects on bone.

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Section: Discussionsupporting

confidence: 93%

Differential profile of letrozole and exemestane on bone turnover markers in vinylcyclohexene diepoxide treated ovotoxic female mice

Kalam

Talegaonkar

Vohora

2016

Fundamemntal Clinical Pharma

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“…AI-associated bone loss (AIBL) leads to a marked increase of bone resorption, with a 2–4 fold increased bone loss compared to physiologic postmenopausal BMD loss [12], [15], [17], [18], [19], [20], [21], [22], [23], [24]. As a result, women receiving adjuvant AI therapy for breast cancer are at increased risk for fractures [25], [26], [27], [28], which leads to increased morbidity and mortality [29].…”

Section: Introductionmentioning

confidence: 99%

Management of Aromatase Inhibitor-Associated Bone Loss (AIBL) in postmenopausal women with hormone sensitive breast cancer: Joint position statement of the IOF, CABS, ECTS, IEG, ESCEO, IMS, and SIOG

Hadji

Aapro

Body

et al. 2017

Journal of Bone Oncology

222

182

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BackgroundSeveral guidelines have been reported for bone-directed treatment in women with early breast cancer (EBC) for averting fractures, particularly during aromatase inhibitor (AI) therapy. Recently, a number of studies on additional fracture related risk factors, new treatment options as well as real world studies demonstrating a much higher fracture rate than suggested by randomized clinical controlled trials (RCTs). Therefore, this updated algorithm was developed to better assess fracture risk and direct treatment as a position statement of several interdisciplinary cancer and bone societies involved in the management of AI-associated bone loss (AIBL).Patients and methodsA systematic literature review identified recent advances in the management of AIBL. Results with individual agents were assessed based on trial design, size, follow-up, and safety.ResultsSeveral fracture related risk factors in patients with EBC were identified. Although, the FRAX algorithm includes fracture risk factors (RF) in addition to BMD, it does not seem to adequately address the effects of AIBL. Several antiresorptive agents can prevent and treat AIBL. However, concerns regarding compliance and long-term safety remain. Overall, the evidence for fracture prevention is strongest for denosumab 60 mg s.c. every 6 months. Additionally, recent studies as well as an individual patient data meta-analysis of all available randomized trial data support additional anticancer benefits from adjuvant bisphosphonate treatment in postmenopausal women with a 34% relative risk reduction in bone metastasis and 17% relative risk decrease in breast cancer mortality that needs to be taken into account when advising on management of AIBL.ConclusionsIn all patients initiating AI treatment, fracture risk should be assessed and recommendation with regard to exercise and calcium/vitamin D supplementation given. Bone-directed therapy should be given to all patients with a T-score<−2.0 or with a T-score of <–1.5 SD with one additional RF, or with ≥2 risk factors (without BMD) for the duration of AI treatment. Patients with T-score>−1.5 SD and no risk factors should be managed based on BMD loss during the first year and the local guidelines for postmenopausal osteoporosis. Compliance should be regularly assessed as well as BMD on treatment after 12 - 24 months. Furthermore, because of the decreased incidence of bone recurrence and breast cancer specific mortality, adjuvant bisphosphonates are recommended for all postmenopausal women at significant risk of disease recurrence.

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“…Much attention has been drawn to the osteocyte‐derived factor Sclerostin in the recent years . Circulating Sclerostin levels are increased in postmenopausal women with endocrine responsive breast cancer and in patients with prostate cancer, particularly in individuals receiving androgen deprivation therapy . High levels of SOST/Sclerostin have also been detected in breast cancer cells .…”

Section: Osteocytes and Dysregulation Of Bone Remodeling In Bone Colomentioning

confidence: 99%

The Emerging Role of Osteocytes in Cancer in Bone

Atkinson

Delgado‐Calle

2019

JBMR Plus

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Advances in the last decade have established the osteocyte, the most abundant cell in bone, as a dynamic and multifunctional cell capable of controlling bone homeostasis by regulating the function of both osteoblasts and osteoclasts. In addition, accumulating evidence demonstrates that osteocyte function is altered in several skeletal disorders, and targeting osteocytes and their derived factors improves skeletal health. Despite the remarkable progress in our understanding of osteocyte biology, there has been a paucity of information regarding the role of osteocytes in the progression of cancer in bone. Exciting, recent discoveries suggest that tumor cells communicate with osteocytes to generate a microenvironment that supports the growth and survival of cancer cells and stimulates bone destruction. This review features these novel findings and discussions regarding the impact of chemotherapy on osteocyte function and the potential of targeting osteocytes for the treatment of cancer in bone. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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Increased Sclerostin Levels after Further Ablation of Remnant Estrogen by Aromatase Inhibitors

Cited by 16 publications

References 30 publications

Differential profile of letrozole and exemestane on bone turnover markers in vinylcyclohexene diepoxide treated ovotoxic female mice

Differential profile of letrozole and exemestane on bone turnover markers in vinylcyclohexene diepoxide treated ovotoxic female mice

Management of Aromatase Inhibitor-Associated Bone Loss (AIBL) in postmenopausal women with hormone sensitive breast cancer: Joint position statement of the IOF, CABS, ECTS, IEG, ESCEO, IMS, and SIOG

The Emerging Role of Osteocytes in Cancer in Bone

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