Journal List > J Korean Soc Endocrinol > v.20(1) > 1063807

Tae, Baek, Oh, Oh, Lee, Kim, Han, Cha, Lee, Son, Kang, Kim, and Kang: The Changes in the Serum RANKL and OPG levels after Bone Marrow Transplantation: Association with Bone Mineral Metabolism

Abstract

Background

The loss of bone mass is usually detected after bone marrow transplantation (BMT), particularly during the early post-transplant period. We recently reported that enhanced bone resorption following BMT was related to both the steroid dose and increase in IL-6. It was also suggested damage of the marrow microenvironment due to myeloablation and changes in bone growth factors contribute to post-BMT bone loss. Recently, the interactions of OPG and RANKL have been reported to be crucial in osteoclastogenesis and therefore in bone homeostasis. There are few data on the changes in RANKL/OPG status during the post-BMT period. This study investigated the changes in the levels of RANKL and OPG during the post-BMT period, and also assessed whether the changes in these cytokine levels actually influenced bone turnover and post-BMT bone loss.

Methods

We prospectively investigated 110 patients undergoing allogenic BMT and analyzed 36 (32.4±1.3 years, 17 men and 19 women) where DEXA was performed before and 1 year after the BMT. The serum bone turnover marker levels were measured before and 1, 2, 3, 4 and 12 wks, 6 Ms, and 1 yr after the BMT. The serum sRANKL and OPG levels were measured in all patients before and 1, 3 and 12 wks after the BMT.

Results

The mean bone losses in the lumbar spine and total proximal femur, which were calculated as the percent change from the baseline to 1 yr, were 5.2 (P<0.01) and 11.6% (P<0.01), respectively. The mean serum ICTP, a bone resorption marker, increased progressively until 3 and 6 months after the BMT, but decreased gradually thereafter, reaching the basal values after 1 year. The serum osteocalcin levels decreased progressively until 3 wks after the BMT, then increased transiently at 3 and 6 Ms, but returned to the basal level by 1 yr. The serum sRANKL and OPG levels had increased significantly by weeks 1 and 3 compared with the baseline (P<0.01), but decreased at 3 months. The sRANKL/OPG ratio increased progressively until 3 weeks, but then decreased to the basal values. During the observation period, the percent changes from the baseline in the serum RANKL levels and RANKL/OPG ratio showed positive correlations with the percent changes from the baseline serum ICTP levels. Patients with higher RANKL levels and RANKL/OPG ratio during the early post-BMT period lost more bone mass at the lumbar spine.

Conclusion

In conclusion, dynamic changes in the sRANKL and OPG levels were observed during the immediate post-BMT period, which were related to a decrease in bone formation and loss of L-spine BMD during the year following the BMT. Taken together, these results suggest that increased sRANKL levels and sRANKL/OPG ratios could be involved in a negative balance in bone metabolism following BMT.

Figures and Tables

Fig. 1
The changes in BMD before and after BMT. The mean bone loss in the lumbar spine and proximal femur calculated as the percent change from the basline to the level at 12 months after BMT was 5.2% (P<0.05) and 11.6% (P<0.01) respectively.
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Fig. 2
The changes of serum bone turnover markers, before and after BMT. Data are given as mean value±SEM. Immediately after BMT, ICTP was progressively increased, reaching its peak at 6 months. Thereafter it declined to the baseline at 12 months. Osteocalcin was progressively decreased, reaching its nadir at 3 weeks. Thereafter, it recovered back to the baseline level by 12 months. Serum creatinine levels were within the normal range throughout the entire observation period.
*, P<0.05; , P<0.01 against the basal value.
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Fig. 3
The changes in the OPG, sRANKL levels and sRANKL/OPG ratio in the peripheral blood before and after BMT. The data are reported as a mean value±SEM. A&B, After BMT, the serum OPG and sRANKL levels was progressively increased, reaching a peak at 3 week, which declined thereafter. C, The serum sRANKL/OPG ratio was highest at post-BMT 3 weeks. , p<0.01 against the basal value.
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Table 1
The Correlations Between the Percentage Changes from the Baseline to 1 year in the BMD at the Lumbar Spine and Proximal Femur and the Percentage Changes in OPG
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L2-4 (%): the percentage changes from the baseline to 1 yr in the BMD at the lumbar spine (lumbar vertebrae L2-L4)

femur (%): the percentage changes from the baseline to 1 yr in the BMD at the proximal femur.

sRANKL (%): the percentage changes from baseline in the sRANKL

OPG (%): the percentage changes from baseline in the OPG

sRANKL/OPG (%): the percentage changes from baseline in the sRANKL/OPG *, P<0.05

Table 2
The Correlations Between Serum OPG and Bone Turnover Markers Following BMT. Serum Levels of OPG and sRANKL were Determined Before BMT, and at 1 and 3 wk and 3 Months after BMT. Correlation Coefficients were Calculated from Matched time point. n=36. OC, Serum Osteocalcin; ICTP, Serum Collagen I Carboxy-Terminal Telopeptide
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Table 3
The Correlations Between the Percentage Changes in sRANKL and sRANKL/OPG and the Percentage Changes in ICTP Following BMT. Serum Levels of OPG and sRANKL were Determined Before BMT, and at 1 and 3 wk and 3 months after BMT. Correlation Coefficients were Calculated from Matched time Point
jkse-20-40-i003

ICTP(%): the percentage changes from baseline in the serum collagen I carboxy-terminal telopeptide.

sRANKL (%): the percentage changes from baseline in the sRANKL

sRANKL/OPG (%): the percentage changes from baseline in the sRANKL/OPG

*, P<0.05 Against the Basal Value.

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