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Changes in the Serum Growth Factors and Osteoprotegerin after Bone Marrow Transplantation: Impact on Bone and Mineral Metabolism

Department of Internal Medicine (K.H.B., H.S.K., J.H.H., M.I.K., B.Y.C., K.W.L., H.Y.S., S.K.K.) and Hematopoietic Stem Cell Transplantation Center (C.C.K.), The Catholic University of Korea, College of Medicine, and Sungkyunkwan University School of Medicine (W.Y.L.), Mizmedi Hospital (K.W.O.), Seoul 150-010, Korea

Address all correspondence and requests for reprints to: Moo-Il Kang, M.D., Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Mary’s Hospital, The Catholic University of Korea, No. 62 Yoido-dong Youngdeungpo-Gu, Seoul 150-010, Korea. E-mail: mikang{at}catholic.ac.kr.

The loss of bone mass often occurs after bone marrow transplantation (BMT), particularly during the early posttransplant period. There are few reports on the role of growth factors and osteoprotegerin (OPG) in the post-BMT bone loss.

This study prospectively investigated 110 patients undergoing BMT and analyzed 36 patients who had dual-energy x-ray absorptiometry performed before BMT and 1 yr after BMT. The biochemical markers of bone formation and resorption were measured at the short-term intervals during the year-long follow-up. The serum IGF-I, IGF binding protein (IGFBP)-3, fibroblast growth factor-2, macrophage-colony stimulating factor (M-CSF), and OPG levels were measured before and 1 wk, 3 wk, and 3 months after BMT.

The mean bone loss in the lumbar spine and the total proximal femur, which was calculated as the percent change from the baseline to the level at 1 yr, was 5.2% (P < 0.05) and 11.6% (P < 0.01), respectively. During the immediate post-BMT period, bone formation decreased, whereas bone resorption increased, which was indicated by the biochemical markers of bone turnover. The serum IGF-I levels also decreased progressively until 3 wk and then increased to the basal values at 3 months. The serum IGFBP-3 levels decreased progressively until 3 months. The serum fibroblast growth factor-2 levels decreased to the nadir at 1 wk and gradually recovered to the basal values at 3 months. The serum M-CSF levels increased immediately after BMT, which declined to its baseline level by 3 months. The serum OPG levels increased progressively, reached a peak at 3 weeks, and declined thereafter. There were significant correlations between the IGF-I and osteocalcin levels before BMT and at 3 wk after BMT (r = 0.45, P < 0.01; r = 0.54, P < 0.01). During the observation period, the serum IGFBP-3 and M-CSF levels showed positive correlations with the osteocalcin and serum collagen I carboxyl-terminal telopeptide levels, respectively. Although statistically not significant, the OPG levels tended to be positively associated with the serum collagen I carboxyl-terminal telopeptide levels. Significant correlations were observed between the percent changes from the baseline to 1 yr in the bone mineral density at the proximal femur and the serum IGF-I levels at 3 wk and 3 months after BMT (r = 0.52, P < 0.01; r = 0.41, P < 0.05).

This work was supported by a grant from the Korean Ministry of Health and Welfare (01-PJ1-PG1-01CH08-0001).

K.H.B. and W.Y.L. contributed equally to the work reported.

A section of these results was presented in abstract form at the 24th Annual Meeting of the ASBMR, San Antonio, TX, 2002.

Abbreviations: BMD, Bone mineral density; BMT, bone marrow transplantation; CV, coefficient(s) of variation; FGF, fibroblast growth factor; GVHD, graft-vs.-host disease; ICTP, collagen I carboxyl-terminal telopeptide; IGFBP, IGF binding protein; M-CSF, macrophage-colony stimulating factor; OPG, osteoprotegerin; RANKL, receptor activator of NFB ligand; TBI, total body irradiation.

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