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Age-Related Changes in Cortical Bone Content of Insulin-Like Growth Factor Binding Protein (IGFBP)-3, IGFBP-5, Osteoprotegerin, and Calcium in Postmenopausal Osteoporosis: A Cross-Sectional Study

Department of Endocrinology (T.U., J.B.) and Research Institute for Internal Medicine National (T.U.), University Hospital, N-0027 Oslo, Norway; Department of Endocrinology C (K.B.), Aarhus University Hospital, Department of Cell Biology (Li.M.), University of Aarhus, DK-8000 Aarhus; Department of Endocrinology (Le.M.), Odense University Hospital, DK-5000 Odense, Denmark; and Medical Research Laboratories (A.F.), Aarhus University Hospital, DK-8000 Aarhus, Denmark

Address all correspondence and requests for reprints to: Dr. Thor Ueland, Department of Endocrinology, National University Hospital, N-0027 Oslo, Norway. E-mail: thor.ueland{at}klinmed.uio.no.

Serum GH and IGF-I levels decline with increasing age, whereas osteoprotegerin (OPG) increases. IGFs as well as OPG are present in bone matrix and mediate the effects of many upstream hormones (e.g. estrogen). To evaluate whether changes in these proteins may to some extent explain the decrease in bone mass in postmenopausal or senile osteoporosis, we measured bone contents of IGF-I, IGF-II, IGF binding protein (IGFBP)-3, IGFBP-5, and OPG in combined extracts obtained after EDTA and guanidine hydrochloride extraction in 60 postmenopausal women aged 47–74 (mean, 63) yr with a previous distal forearm fracture and a hip or spine Z-score less than 0. We found age-related increases in IGFBP-3 (r = 0.35; P < 0.01), IGFBP-5 (r = 0.59; P < 0.001), and OPG (r = 0.36; P < 0.01) in cortical bone, significantly inversely correlated with femoral neck and lumbar spine BMD. A correlation between age and OPG was also detected in trabecular bone (r = 0.27; P < 0.05). A pronounced age-related decrease in cortical calcium contents (r = -0.60; P < 0.001), positively correlated with femoral neck and lumbar spine BMD, was also found. No age-related changes were detected for IGF-I or IGF-II. The present study demonstrates age-related changes in cortical bone contents of IGFBPs, calcium, and OPG, possibly related to the pathophysiology of postmenopausal osteoporosis. As for OPG, our findings probably represent compensatory responses to increased osteoclastic resorption.

Abbreviations: BMD, Bone mineral density; ICTP, carboxy-terminal telopeptide of type I collagen; IGFBP, IGF binding protein; OPG, osteoprotegerin; RANKL, receptor activator of nuclear factor-B ligand; s, serum; sAP, serum alkaline phosphatase.

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