Changes in the serum levels of osteoprotegerin and soluble receptor activator for nuclear factor kappaB ligand after estrogen-progestogen therapy and their relationships with changes in bone mass in postmenopausal women.
OBJECTIVE
To investigate changes in the serum levels of osteoprotegerin (OPG) and soluble receptor activator for nuclear factor kappaB ligand (sRANKL) after estrogen plus progestogen therapy (EPT) and to determine their relationships with changes in bone mineral density (BMD) and bone turnover markers in postmenopausal women.


METHODS
Serum levels of OPG, sRANKL, and bone turnover markers, such as osteocalcin and type I C-telopeptide breakdown products, parathyroid hormone, calcitonin, calcium, and phosphorus, and BMD at the lumbar spine and proximal femur were measured in 297 postmenopausal Korean women. In all, 143 women were treated with sequential EPT for 1 year.


RESULTS
Before EPT, serum OPG and sRANKL levels and RANKL/OPG ratios were not related to BMD at the lumbar spine and proximal femur, except for a negative correlation (r = -0.13, P < 0.05) between serum OPG and BMD at the trochanter. Of the bone markers, serum parathyroid hormone alone correlated negatively with serum OPG (r = -0.19, P < 0.005) and positively with serum sRANKL (r = 0.23, P < 0.001) and sRANKL/OPG ratios (r = 0.28, P < 0.001). After 6 months of EPT, serum OPG and sRANKL levels were unchanged, but sRANKL/OPG ratios and serum levels of bone turnover markers, such as osteocalcin, type I C-telopeptide breakdown products, and phosphorus decreased significantly. The 1-year change in BMD at the lumbar spine and proximal femur after EPT was not found to be correlated with basal levels of serum OPG, sRANKL, and sRANKL/OPG ratios and their changes at 6 months after EPT. After 6 months of EPT, changes in all bone markers were not associated with changes in circulating OPG, sRANKL levels, and sRANKL/OPG ratios.


CONCLUSIONS
After EPT, sRANKL/OPG ratios in the circulation decreased, but changes in this OPG-sRANKL system have no association with changes in any bone marker or BMD. The OPG-sRANKL system in the circulation might be involved in reduced bone resorption after EPT, but does not seem to be clinically useful for predicting BMD or bone turnover status and bone response after hormone therapy.
Kim
Jung Gu
JG
Department of Obstetrics and Gynecology, College of Medicine, Seoul National University, Seoul, Korea. kimjg@plaza.snu.ac.kr
Kim
Jung Hwa
JH
Lee
Dong Ock
DO
Kim
Hoon
H
Kim
Ja Yeon
JY
Suh
Chang Suk
CS
Kim
Seok Hyun
SH
Choi
Young Min
YM
D000368:Aged; D015519:Bone Density / Q000187:drug effects*; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology*; D005260:Female; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D008875:Middle Aged; D053244:Osteoprotegerin / Q000187:drug effects*; D017698:Postmenopause; D053245:RANK Ligand / Q000187:drug effects*
D004966:Estrogens, Conjugated (USP); D053244:Osteoprotegerin; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D017258:Medroxyprogesterone Acetate