Formononetin reverses established osteopenia in adult ovariectomized rats.
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 d) 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.
Divisions of Endocrinology, Central Drug Research Institute (Council of Scientific and Industrial Research), Chattar Manzil, Lucknow, India.
Abdul Malik
AM
Tyagi
Kamini
K
Srivastava
Anuj Kumar
AK
Singh
Avinash
A
Kumar
Bendangla
B
Changkija
Rashmi
R
Pandey
Shibani
S
Lahiri
Geet K
GK
Nagar
Dinesh Kumar
DK
Yadav
Rakesh
R
Maurya
Ritu
R
Trivedi
Divya
D
Singh
D000818:Animals; D001851:Bone Diseases, Metabolic / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D016723:Bone Remodeling / Q000187:drug effects; D005260:Female; D005269:Femur / Q000473:pathology; D007529:Isoflavones / Q000008:administration & dosage*; D010012:Osteogenesis / Q000187:drug effects; D053244:Osteoprotegerin / Q000235:genetics; D010052:Ovariectomy; D010446:Peptide Fragments / Q000097:blood; D048789:Phytoestrogens / Q000008:administration & dosage*; D011347:Procollagen / Q000097:blood; D053245:RANK Ligand / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000473:pathology
D007529:Isoflavones; D053244:Osteoprotegerin; D010446:Peptide Fragments; D048789:Phytoestrogens; D011347:Procollagen; D053245:RANK Ligand; D012333:RNA, Messenger; C506032:Tnfrsf11b protein, rat; C047202:procollagen Type I N-terminal peptide; C007768:formononetin