Phytomedicine 15 (2008) 595–601 Dietary L-carnitine supplementation improves bone mineral density by suppressing bone turnover in aged ovariectomized rats Shirin Hooshmand a , Anju Balakrishnan b , Richard M. Clark b , Kevin Q. Owen c , Sung I. Koo b,Ã , Bahram H. Arjmandi a,Ã a Department of Nutrition, Food & Exercise Sciences, Florida State University, 436 Sandels Building, Tallahassee, FL 32306, USA b Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA c Lonza, Inc., Allendale, NJ 07401, USA Abstract Postmenopausal bone loss is a major public health concern. Although drug therapies are available, women are interested in alternative/adjunct therapies to slow down the bone loss associated with ovarian hormone deficiency. The purpose of this study was to determine whether dietary supplementation of L-carnitine can influence bone density and slow the rate of bone turnover in an aging ovariectomized rat model. Eighteen-month-old Fisher-344 female rats were ovariectomized and assigned to two groups: (1) a control group in which rats were fed ad libitum a carnitine-free (CN) diet (AIN-93M) and (2) another fed the same diet but supplemented with L-carnitine (+CN). At the end of 8 weeks of feeding, animals were sacrificed and bone specimens were collected for measuring bone mineral content (BMC) and density (BMD) using dual energy X-ray absorptiometry. Femoral microarchitectural properties were assessed by microcomputed tomography. Femoral mRNA levels of selected bone matrix proteins were determined by northern blot analysis. Data showed that tibial BMD was significantly higher in the rat fed the +CN diet than those fed the CN (control) diet. Dietary carnitine significantly decreased the mRNA level of tartrate-resistant acid phosphatase (TRAP), an indicator of bone resorption by 72.8%, and decreased the mRNA abundance of alkaline phosphatase (ALP) and collagen type-1 (COL), measures of bone formation by 63.6% and 61.2%, respectively. The findings suggest that carnitine supplementation slows bone loss and improves bone microstructural properties by decreasing bone turnover. r 2008 Elsevier GmbH. All rights reserved. Keywords: Osteoporosis; Estrogen; L-carnitine; Female rats; Aging Introduction Increased rate of bone turnover with the rate of bone resorption exceeding that of bone formation leads to bone loss and consequently increases fracture risk. Examples of conditions in which bone turnover is increased include hyperthyroidism (Pantazi and Papa- petrou, 2000), Paget’s disease (Langston and Ralston, 2004), fibrous dysplasia, oophorectomy (Nozaki et al., 1998), and early menopause (Fink et al., 2000). There- fore, agents that can slow the rate of bone turnover may be of benefit to individuals suffering from these conditions. Several therapies in this category have been approved by the US Food and Drug Administration ARTICLE IN PRESS www.elsevier.de/phymed 0944-7113/$ - see front matter r 2008 Elsevier GmbH. All rights reserved. doi:10.1016/j.phymed.2008.02.026 Ã Corresponding authors. Tel.: +1 850 644 1828; fax: +1 850 645 5000 (Bahram H. Arjmandi), Tel.: +1 860 486 3495; fax: +1 860 486 3674 (Sung I. Koo). E-mail addresses: sung.koo@uconn.edu (S.I. Koo), barjmandi@fsu.edu (B.H. Arjmandi).