Sains Malaysiana 48(9)(2019): 2007–2019

http://dx.doi.org/10.17576/jsm-2019-4809-22

Osteoporosis: Possible Pathways Involved and the Role of Natural Phytoestrogens in Bone Metabolism

(Osteoporosis: Laluan yang Mungkin Terlibat dan Peranan Fitoestrogen Semula Jadi dalam Metabolisme Tulang)

ZAR CHI THENT¹, SRIJIT DAS²*, PASUK MAHAKKANUKRAUH³ & VIRGINIA LANZOTTI⁴

¹Anatomy Discipline, Basic Medical Science Cluster, Faculty of Medicine, Sungai Buloh Campus, Universiti Teknologi MARA, 47000 UiTM Sungai Buloh, Selangor Darul Ehsan, Malaysia

²Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Federal Territory, Malaysia

³Forensic Osteology Research and Training Centre, Excellence Center of Osteology Research and, Training Center & Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand

⁴Department of Agricultural Sciences, Università di Napoli Federico II, Napoli, Italy

Diserahkan: 17 Mei 2019/Diterima: 5 Julai 2019

ABSTRACT

The incidence of post-menopausal osteoporosis is increasing globally. In post-menopausal osteoporosis, there is deficiency in oestrogen level resulting in bone loss and fractures. Bone formation is under the control of different hormones. In the present review, we highlight few pathways such as RANKL/RANK, apoptosis and Wnt/β-catenin signalling pathways and phytoestrogens involved in the bone metabolism. RANKL/RANK signalling is responsible for regulating the formation and activation of multinucleated osteoclasts from their precursors which is responsible for the survival of normal bone remodelling. Apoptosis regulates the development, growth and maintains the bone tissues. The Wnt pathway is an important pharmacological target for bone anabolic drugs and its future discovery. In today’s world, herbal remedies are used to treat post-menopausal osteoporosis as these products contain phytoestrogens. These phytoestrogens are oestrogen like compounds which influence bone metabolism. The phytoestrogens provide better therapeutic effect in reducing the RANKL, osteoclastogenesis, inflammatory markers, and increase the osteogenic markers in the bone cells or osteoblasts. We discuss the mechanism of action of few phytoestrogens such as genistein, daidzein and equol which are beneficial for improvement of the bone health. Daidzein enhances osteoblast growth via the upregulation of BMP expression in primary osteoblast cells and it is a potential antiosteoporotic agent. Genistein also possesses antioestrogenic property by virtue of its competitive binding to the same receptors as oestradiol. Equol regulates the bone loss via hemopoiesis and inflammatory cytokine production. Thus, phytoestrogens could be efficiently used as osteoprotective agents for the treatment of individuals with post-menopausal osteoporosis.

Keywords: Fracture; oestrogen; pharmacology; post-menopausal; treatment

ABSTRAK

Kejadian osteoporosis selepas menopaus meningkat secara global. Dalam osteoporosis selepas menopaus, terdapat penurunan aras estrogen yang mengakibatkan kehilangan tulang dan patah tulang. Pembentukan tulang dikawal oleh hormon yang berbeza. Dalam ulasan kepustakaan ini, kami menyerlahkan beberapa laluan isyarat seperti RANKL/ RANK, apoptosis dan Wnt/β-catenin serta fitoestrogens yang terlibat dalam metabolisme tulang. Isyarat RANKL/RANK bertanggungjawab mengawal pembentukan dan pengaktifan osteoklas multinukleus daripada prekursor mereka yang terlibat dalam proses pembentukan semula tulang yang normal. Apoptosis mengawal perkembangan, pertumbuhan dan penyelenggaraan tisu tulang. Laluan Wnt adalah sasaran farmakologi yang penting untuk ubat anabolik tulang dan penemuan masa depannya. Di dunia hari ini, banyak ubat-ubatan herba digunakan untuk merawat osteoporosis Osteoporosis: Possible menopaus kerana produk ini mengandungi fitoestrogen. Fitoestrogen mempunyai struktur seperti estrogen yang mempengaruhi metabolisme tulang. Fitoestrogen memberikan kesan terapeutik yang lebih baik dalam mengurangkan RANKL, osteoklastogenesis, penanda inflamasi dan meningkatkan penanda osteogenik dalam sel-sel tulang atau pun osteoblas. Kami membincangkan mekanisme tindakan beberapa fitoestrogen seperti genistein, daidzein dan equol yang bermanfaat untuk kesihatan tulang. Daidzein meningkatkan pertumbuhan osteoblas melalui peningkatan ekspresi BMP dalam sel osteoblas primer dan ia adalah agen antiosteoporotik yang berpotensi. Genistein juga mempunyai harta antioestrogenik berdasarkan daya saingnya yang kompetitif kepada reseptor yang sama seperti oestradiol. Equol mengawal kehilangan tulang melalui hemopoiesis dan penghasilan sitokin inflamasi. Oleh itu, fitoestrogen boleh digunakan sebagai agen osteoperlindungan untuk rawatan osteoporosis selepas menopaus.

Kata kunci: Estrogen; farmakologi; patah tulang; selepas menopaus; rawatan

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