Changes in the serum sex steroids, IL-7 and RANKL-OPG system after bone marrow transplantation: influences on bone and mineral metabolism.
This study prospectively investigated the changes of the serum levels of the sex steroids, IL-7, soluble receptor activator of nuclear factor kappaB ligand (sRANKL) and osteoprotegerin (OPG) in bone marrow transplantation (BMT) recipients. This study also examined whether the changes of these cytokine levels and sex steroids actually influence bone turnover and post-BMT bone loss by correlation analysis. Data were analyzed from 39 patients (33.6+/-6.4 years, 19 men and 20 women) who had DXA performed before BMT and at 1 year after BMT. The bone turnover markers, sex steroids and the cytokine levels were measured before BMT and serially after BMT. The mean bone loss in the lumbar spine and the total proximal femur was 5.9% (P < 0.01) and 11.3% (P < 0.01), respectively. During the immediate post-BMT period, bone formation decreased, whereas the bone resorption increased. For the female recipients, the estradiol levels declined at 1 week after BMT, and they did not recover to the basal levels. For the male recipients, the testosterone levels decreased at 1 week and then it increased to its baseline level. The IL-7 levels reached their maximum at 1 week and then declined to baseline level by 3 months. The serum sRANKL, OPG levels and the sRANKL/OPG ratio showed their peak at post-BMT 3 weeks. The mean daily dose of steroid was associated with suppressed bone formation, enhanced bone resorption and increased sRANKL levels. The IL-7 levels were also noted to be either positively correlated with the levels of ICTP or they were negatively correlated with the levels of osteocalcin at 1 and 3 weeks after BMT. Bone loss at the lumbar spine and the proximal femur was influenced by the decreased sex steroids and increased IL-7 levels. During the observation period, the IL-7 levels showed positive correlations with the sRANKL levels and the sRANKL/OPG ratio. For the female patients, the serum IL-7 levels were negatively associated with the estradiol levels at 1 and 3 weeks after BMT. All these findings suggest that IL-7 plays an important role for post-BMT bone loss, and this possibly happens via the RANKL pathway. These data also suggest that the up-regulation of IL-7 during the early post-BMT period may result from a deficiency of estrogen.
Baek
Ki Hyun
KH
Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Mary's Hospital, The Catholic University of Korea, # 62 Yoido-dong Youngdeungpo-Gu, Seoul 150-713, Republic of Korea.
Oh
Ki Won
KW
Lee
Won Young
WY
Tae
Hyun Jung
HJ
Rhee
Eun Jung
EJ
Han
Je Ho
JH
Cha
Bong Yun
BY
Kim
Yoo Jin
YJ
Lee
Kwang Woo
KW
Son
Ho Young
HY
Kang
Sung Koo
SK
Kim
Chun Choo
CC
Kang
Moo Il
MI
D000328:Adult; D015519:Bone Density; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology / Q000502:physiology*; D016723:Bone Remodeling / Q000276:immunology / Q000502:physiology; D001862:Bone Resorption / Q000097:blood / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism*; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D015851:Interleukin-7 / Q000097:blood*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D053244:Osteoprotegerin / Q000097:blood*; D053245:RANK Ligand / Q000097:blood*; D012995:Solubility; D013739:Testosterone / Q000097:blood
D012739:Gonadal Steroid Hormones; C508605:IL7 protein, human; D015851:Interleukin-7; D053244:Osteoprotegerin; D053245:RANK Ligand; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone