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Formononetin reverses established osteopenia in adult ovariectomized rats

Tyagi, Abdul Malik MSc1; Srivastava, Kamini MSc1; Singh, Anuj Kumar MSc1; Kumar, Avinash MSc1; Changkija, Bendangla PhD1; Pandey, Rashmi MSc1; Lahiri, Shibani MSc1; Nagar, Geet K. BSc1; Yadav, Dinesh Kumar MSc, PhD2; Maurya, Rakesh PhD2; Trivedi, Ritu PhD1; Singh, Divya PhD1

doi: 10.1097/gme.0b013e31824f9306
Original Articles

Objective Formononetin (Formo) prevents ovariectomy (Ovx)-induced bone loss in rats. However, there are no reports on the curative effects of Formo. The objective of this study was to investigate the ability of Formo in restoring trabecular microarchitecture and promoting new bone formation in osteopenic rats.

Methods Adult Sprague-Dawley rats were ovariectomized and left for 90 days for osteopenia to develop. After 90 days, Formo (10.0 mg kg−1 d−1) was given orally for the next 12 weeks to Ovx rats in a therapeutic protocol. Sham-operated, Ovx + vehicle, and Ovx + parathyroid hormone (PTH) groups served as controls. Trabecular microarchitecture, osteoid formation, bone turnover/resorption markers, and bone osteoprotegerin–to–receptor activator for nuclear κB ligand ratio were studied. One-way analysis of variance was used to test significance of effects.

Results Formo treatment significantly restored the lost trabecular microarchitecture in the femurs and tibia of osteopenic Ovx rats and promoted new bone formation. Formo was devoid of any uterine estrogenicity. Serum levels of type I collagen N-terminal propeptide, which is a reliable marker of bone formation, were increased in Ovx rats treated with Formo compared with Ovx + vehicle group, and the levels were comparable with those in the sham group. Formo prevented the Ovx-induced increase in bone turnover markers, including serum osteocalcin and urinary type I collagen degradation product. Furthermore, Formo-treated Ovx rats had an increased bone osteoprotegerin–to–receptor activator for nuclear κB ligand ratio compared with the Ovx + vehicle group.

Conclusions Daily oral administration of Formo for 12 weeks has a substantial anabolic effect, thus raising the possibility of its use in postmenopausal osteoporosis.

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From the Divisions of 1Endocrinology and 2Medicinal and Process Chemistry, Central Drug Research Institute (Council of Scientific and Industrial Research), Chattar Manzil, Lucknow, India.

Received July 27, 2011; revised and accepted December 15, 2011.

Support/funding: Generous funding was received from the Ministry of Health and Family Welfare and Department of Science and Technology, Government of India.

Funding: Fellowship grants were received from the Council of Scientific and Industrial Research (A.M.T., K.S., D.K.Y.), Indian Council of Medical Research (A.K.), Department of Biotechnology (B.C.), and University Grant Commission (R.P.), Government of India.

Financial disclosure/conflicts of interest: None reported.

A.M.T. and K.S. contributed equally to this work.

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Address correspondence to: Divya Singh, PhD, Division of Endocrinology, Central Drug Research Institute (Council of Scientific and Industrial Research), Chattar Manzil, PO Box 173, Lucknow-226001, U.P., India. E-mail:, CDRI Communication number: 248/2011/DS

©2012The North American Menopause Society