Copyright @ 2008 The North American Menopause Society. Unauthorized reproduction of this article is prohibited. Menopause: The Journal of The North American Menopause Society Vol. 15, No. 5, pp. 934/939 DOI: 10.1097/gme.0b013e31816665a7 * 2008 by The North American Menopause Society Relationship among insulinlike growth factor I concentrations, bone mineral density, and biochemical markers of bone turnover in postmenopausal women: a population-based study Iraj Nabipour, MD, 1 Bagher Larijani, MD, 2 Saeideh Beigi, MD, 1 Seyed Mojtaba Jafari, MSc, 1 Mohammad Amiri, MD, 1 Majid Assadi, MD, 1 Raha Pazoki, MD, 1 Zahra Amiri, MSc, 1 and Zahra Sanjdideh, MSc 1 Abstract Objective: To assess the association among serum insulinlike growth factor I (IGF-I) concentrations, bone mineral density (BMD), and biochemical markers of bone turnover in a large group of postmenopausal women from the general population. Design: As an extension of a larger epidemiological study, the Iranian Multicentral Osteoporosis Study, a total of 406 healthy postmenopausal women (age, 59.0 T 7.6 years) were randomly selected from 13 clusters in Bushehr Port. IGF-I, serum CrossLaps, degradation products of C-terminal telopeptides of type I collagen, and osteocalcin were measured by highly specific enzyme-linked immunosorbent assay. BMD was determined for the lumbar spine (L2Y4) and proximal femur using dual-energy x-ray absorptiometry. Results: The mean (T SD) serum IGF-I concentration for all postmenopausal women was 183.35 T 65.60 ng/mL. In age-adjusted analyses, there was no correlation between IGF-I and BMD at the lumbar spine and femoral neck. Compared with women in the lowest quartile of IGF-I, women in the highest quartile had a significantly greater means of osteocalcin (P = 0.04) and alkaline phosphatase (P = 0.01). Analysis by quartiles of IGF-I did not reveal an association with serum CrossLaps. Conclusions: Circulating IGF-I is associated with biochemical markers of bone formation, but there is no relationship among IGF-I, degradation products of C-terminal telopeptides of type I collagen, and BMD in postmenopausal women. Clearly more work will be needed before serum IGF-I can be used in clinical practice as a risk predictor for postmenopause-associated loss of bone mass. Key Words: Insulinlike growth factor Y Menopause Y Osteocalcin Y CrossLaps Y Bone mineral density. G rowth hormone (GH) plays a crucial role in main- taining bone mass in adults by regulating bone remodeling through a complex interaction of circu- lating GH, insulinlike growth factors (IGFs), IGF-binding proteins (IGFBPs), and locally produced IGFs and IGFBPs acting in autocrine and paracrine ways. 1 In serum, the majority (70%<80%) of the IGFs exist in a 150-kd complex composed of one IGF molecule, IGFBP-3, and the acid labile subunit (ALS). The liver is the principal source of circulating IGF-I, IGFBP-3, and ALS, which are synthesized by hepatocytes in a GH-dependent manner. 2 The IGF-I, like other growth factors, acts on bone directly. After binding to osteoblast receptors, it stimulates the expression of mRNA procollagen type I and collagen synthesis. Moreover, IGF-I inhibits collagen degradation by inhibiting the activity of osteoblast collagenase. The activated osteoformation is characterized by an increased local pro- duction of IGF-I and some binding proteins (IGFBP-5) with subsequent stimulation of further osteoblasts and enhanced apposition of bone matrix. 3 The activity of the hypothalamus-GH-IGF-I axis decreases with age, and some of the catabolic changes of aging, including bone loss and muscle atrophy, have been attributed to the somatopause. 4 It has been reported that IGF-I and IGFBP-3 are useful for predicting the severity of osteo- porosis, particularly the risk of spinal fractures associated with osteoporosis, suggesting that the GH-IGF-I axis is important for maintaining bone mineral density (BMD). 5 In addition, several clinical trials have established the potential utility of markers of bone turnover to identify patients with rapid bone loss, to aid in therapeutic decision Received October 11, 2007; revised and accepted December 26, 2007. From the 1 Department of Endocrine and Metabolic Diseases, The Persian Gulf Tropical Medicine Research Center, Bushehr University of Medical Sciences, Bushehr; and 2 Tehran Endocrine Research Center, Tehran University of Medical Science, Tehran, Iran. Funding/support: This project was supported in joint by a grant from joint Ministry of Health, Tehran Endocrine Research Center, Tehran University of Medical Science, Tehran, Iran and Bushehr Province Research Committee. Financial disclosure: None reported. Address correspondence to: Iraj Nabipour, MD, Bushehr University of Medical Science, Moallem Street, PO Box 3631, Bushehr, I.R. Iran. E-mail: inabim@yahoo.com 934 Menopause, Vol. 15, No. 5, 2008