Circulating semaphorin-4D and plexin-B1 levels in postmenopausal women with low bone mass: the 3-month effect of zoledronic acid, denosumab or teriparatide treatment

Anastasilakis, Athanasios D.; Polyzos, Stergios A.; Makras, Polyzois; Gkiomisi, Athina; Sakellariou, G; Savvidis, M.; Παπαθεοδώρου, Αθανάσιος; Kokkoris, Panagiotis; Terpos, Evangelos

doi:10.1517/14728222.2014.983078

Cited by 16 publications

(12 citation statements)

References 10 publications

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“…It was also reported that another bone resorption inhibitor, denosumab, increased sclerostin levels at 6 months and maintained the levels thereafter [ 10 ]. On the other hand, no significant increase in PTH was observed after 3 months of treatment with denosumab [ 24 ], suggesting that the relationship between changes in levels of PTH and levels of sclerostin may differ depending on the type of bone resorption inhibitor used for treatment.…”

Section: Discussionmentioning

confidence: 99%

Relationship Between Changes in Serum Levels of Intact Parathyroid Hormone and Sclerostin After a Single Dose of Zoledronic Acid: Results of a Phase 1 Pharmacokinetic Study

Kuroda

Shiraki

Nakamura³

et al. 2021

Calcif Tissue Int

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Although changes in serum sclerostin levels at 12 months after infusion of zoledronic acid have been reported, the changes in sclerostin levels at earlier time points are poorly understood. We reanalyzed the study data of a previous phase 1 pharmacokinetic study and investigated the correlation between changes in sclerostin levels and relevant factors in calcium metabolism. A total of 24 Japanese female subjects with primary postmenopausal osteoporosis were administered a single 4- or 5-mg dose of zoledronic acid. Serum and urine samples were collected on days 15, 29, 90, 180, and 365 after administration. Serum levels of calcium, phosphate, intact parathyroid hormone (iPTH), and sclerostin were measured. Levels of serum sclerostin were unchanged from baseline on days 15 and 29, but increased significantly on day 90, subsequently decreased significantly on day 180, and returned to baseline levels on day 365. A significant negative correlation was observed between changes in iPTH levels at early time points and sclerostin levels at later time points. This suggests that sclerostin was negatively regulated by iPTH, and the decrease in sclerostin may indicate the start of bone formation during later time points after zoledronic acid injection.

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Section: Discussionmentioning

confidence: 99%

Relationship Between Changes in Serum Levels of Intact Parathyroid Hormone and Sclerostin After a Single Dose of Zoledronic Acid: Results of a Phase 1 Pharmacokinetic Study

Kuroda

Shiraki

Nakamura³

et al. 2021

Calcif Tissue Int

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“…Different effects of bone-targeted therapies on Sema4D have already described in postmenopausal women suffering from low bone mass. Circulating levels of Sema4D were increased by denosumab, but decreased following treatment with teriparatide [26]. Sema4D is produced by osteoclasts and suppresses IGF-1 signaling in osteoblasts, thereby inhibiting bone formation [2].…”

Section: Discussionmentioning

confidence: 99%

Plasma levels of Semaphorin 4D are decreased by adjuvant tamoxifen but not aromatase inhibitor therapy in breast cancer patients

Göbel

Kuhlmann

Link

et al. 2019

Journal of Bone Oncology

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Background Semaphorin 4D (Sema4D) is a glycoprotein that inhibits bone formation and has been associated with cancer progression and the occurrence of bone metastases. Recently, Sema4D expression has been linked to estrogen signaling in breast cancer. Endocrine therapies like tamoxifen and aromatase inhibitors (AI) are a standard therapeutic approach in hormone receptor positive breast cancers. Tamoxifen exerts ER-agonistic effects on bone, whereas AI negatively affect bone health by increasing resorption and fracture risk. The effect of endocrine therapies on circulating Sema4D levels in breast cancer patients has not been investigated yet. Methods We measured circulating Sema4D plasma levels at primary diagnosis and in a follow-up sample 12 months after surgery in a cohort of 46 pre- and postmenopausal women with primary estrogen receptor positive breast cancer receiving adjuvant tamoxifen or AI. Results The mean baseline levels ± SD for Sema4D were 441.6 ± 143.4 pmol/l. No significant differences in total plasma Sema4D were observed when stratifying the patients according to age, menopausal status, tumor subtype, nodal and hormone receptor status, or tumor size. However, Sema4D levels were significantly reduced by 28% ( p <0.001) in tamoxifen treated patients 12 months after surgery, whereas no alteration was observed in patients treated with AI. Conclusion This finding potentially represents an additional mechanism of the bone-protective properties of tamoxifen and further emphasizes a link between Sema4D and estrogen receptor signaling.

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“…In the case of Plexin-B1, the secreted ectodomain may be the result of alternative splicing or of proteolytic cleavage of the full-length protein from the cell membrane (Tamagnone et al, 1999;Artigiani et al, 2003;Ito et al, 2014). Recently, increased levels of a soluble, circulating Plexin-B1 portion were found in postmenopausal women with low bone mass (Anastasilakis et al, 2015); a secreted extracellular part of Plexin-B1 was also detected in proteomics studies (Farrah et al, 2011). Moreover, we detected soluble forms of Plexin-B1 of ∼70 kD in size released from lymphatic endothelial cells (HMV ECs).…”

Section: Discussionmentioning

confidence: 99%

A reverse signaling pathway downstream of Sema4A controls cell migration via Scrib

Sun

Liu

Kaur

et al. 2016

Journal of Cell Biology

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Circulating semaphorin-4D and plexin-B1 levels in postmenopausal women with low bone mass: the 3-month effect of zoledronic acid, denosumab or teriparatide treatment

Cited by 16 publications

References 10 publications

Relationship Between Changes in Serum Levels of Intact Parathyroid Hormone and Sclerostin After a Single Dose of Zoledronic Acid: Results of a Phase 1 Pharmacokinetic Study

Relationship Between Changes in Serum Levels of Intact Parathyroid Hormone and Sclerostin After a Single Dose of Zoledronic Acid: Results of a Phase 1 Pharmacokinetic Study

Plasma levels of Semaphorin 4D are decreased by adjuvant tamoxifen but not aromatase inhibitor therapy in breast cancer patients

A reverse signaling pathway downstream of Sema4A controls cell migration via Scrib

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