Impact of 4-methylbenzylidene camphor, daidzein, and estrogen on intact and osteotomized bone in osteopenic rats

• Published in: Journal of endocrinology Vol. 211; no. 2; pp. 157 - 168
• Main Authors: Komrakova, Marina, Sehmisch, Stephan, Tezval, Mohammad, Schmelz, Ulrich, Frauendorf, Holm, Grueger, Thomas, Wessling, Thomas, Klein, Carolin, Birth, Miriam, Stuermer, Klaus M, Stuermer, Ewa K
• Format: Journal Article
• Language: English
• Published: Bristol BioScientifica 01.11.2011
• Subjects: Acid Phosphatase - genetics; Adaptations; Alkaline Phosphatase - blood; Alkaline Phosphatase - genetics; Animals; Biological and medical sciences; Biomechanical Phenomena; Bone (cancellous); Bone and Bones - drug effects; Bone and Bones - metabolism; Bone and Bones - surgery; Bone Density - drug effects; Bone Diseases, Metabolic - physiopathology; Bone healing; Bone mineral density; Bone turnover; Bony Callus - drug effects; Bony Callus - metabolism; Callus; Camphor - administration & dosage; Camphor - analogs & derivatives; Camphor - pharmacology; Computed tomography; daidzein; Diet; Diets; Diseases of the osteoarticular system; Estrogens; Estrogens - administration & dosage; Estrogens - pharmacology; Female; Fractures; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; Insulin-like growth factor I; Insulin-Like Growth Factor I - genetics; Isoenzymes - genetics; Isoflavones - administration & dosage; Isoflavones - pharmacology; Lumbar Vertebrae - drug effects; Lumbar Vertebrae - pathology; Lumbar Vertebrae - physiopathology; Medical sciences; Menopause; Osteocalcin; Osteocalcin - blood; Osteocalcin - genetics; Osteoporosis; Osteoporosis. Osteomalacia. Paget disease; Osteotomy; Ovariectomy; Rats; Rats, Sprague-Dawley; Regular papers; Reverse Transcriptase Polymerase Chain Reaction; Spine (lumbar); Tartrate-Resistant Acid Phosphatase; Tibia; Tibia - drug effects; Tibia - pathology; Tibia - physiopathology; Tomography, X-Ray Computed - methods; Vertebrates: endocrinology; Rat; Diseases of the osteoarticular system; Rodentia; Estrogen; Ovarian hormone; Phytoestrogen; Osteoarticular system; Vertebrata; Mammalia; Animal; Camphor; Daidzein; Bone; Sex steroid hormone; Osteopenia
• ISSN: 0022-0795; 1479-6805
• DOI: 10.1530/JOE-11-0096

The study investigated the influence of 4-methylbenzylidene camphor (4-MBC), daidzein, and estradiol-17β-benzoate (E2) on either intact or osteotomized cancellous bone in ovariectomized (Ovx) rats. Three-month old Ovx rats were fed with soy-free (SF) diet over 8 weeks; thereafter, bilateral transverse metaphyseal osteotomy of tibia was performed and rats were divided into groups: rats fed with SF diet and SF diet supplemented with 4-MBC (200 mg), daidzein (50 mg), or E2 (0.4 mg) per kilogram body weight. After 5 or 10 weeks, computed tomographical, biomechanical, histological, and ashing analyses were performed in lumbar spine and tibia of 12 rats from each group. 4-MBC and E2 improved bone parameters in lumbar spine and tibia, were not favorable for osteotomy healing, and decreased serum osteocalcin level. However, daidzein improved bone parameters to a lesser extent and facilitated osteotomy healing. For lumbar spine, the bone mineral density was 338±9, 346±5, 361±6, and 360±5 mg/cm3 in SF, daidzein, 4-MBC, and E2, respectively, after 10 weeks. For tibia, the yield load was 98±5, 114±3, 90±2, and 52±4 N in SF, daidzein, 4-MBC, and E2, respectively, after 10 weeks. Serum daidzein was 54±6 ng/ml in daidzein group and equol was not detected. Alp and Igf1 genes were down-regulated in callus after daidzein and E2 compared with 4-MBC (week 5). The response of bone tissue and serum markers of bone metabolism could be ordered: daidzein<4-MBC<E2. Treatments were more effective after 5 vs 10 weeks. In SF group, bone structure was impaired after 5 weeks and improved after 10 weeks probably due to adaptation mechanisms to osteoporosis. In conclusion, it is conceivable that 4-MBC may improve bone tissue in osteoporotic organisms; osteoporotic patients with fractures could benefit from daidzein treatment.