TY - JOUR
T1 - Circulating amounts of osteoprotegerin and RANK ligand
T2 - Genetic influence and relationship with BMD assessed in female twins
AU - Abrahamsen, Bo
AU - Hjelmborg, Jacob v.B.
AU - Kostenuik, Paul
AU - Stilgren, Lis S.
AU - Kyvik, Kirsten
AU - Adamu, Stephen
AU - Brixen, Kim
AU - Langdahl, Bente L.
PY - 2005/4
Y1 - 2005/4
N2 - Osteoprotegerin (OPG) is a circulating receptor that inhibits osteoclastogenesis by binding to RANK ligand (RANKL). OPG knock-out animals develop severe osteoporosis. Treatment with OPG lowers bone resorption and increases BMD. OPG production is influenced by a wide range of hormones and cytokines. The influence of genetic factors on circulating amounts of OPG and RANKL is not known. BMD has been demonstrated to have a high heritability and there is evidence also that bone turnover and bone loss rates are controlled at least in part by genetic factors. Objective. Assessing the genetic impact on serum OPG and RANKL in women and estimation of the relative contribution of this inheritance to the total heritability of BMD. Methods. 188 female twins (52 DZ and 42 MZ pairs) from the Danish Twin Registry were included in the study. Mean age was 35 years (range 19-64 years), average spine BMD was 1.04 ± 0.11 g/cm2. Serum levels of OPG and RANKL were measured by ELISA (Biomedica, Vienna, Austria). This register covers twins born in Denmark since 1870. Heritability and environmental influence was assessed using a maximum-likelihood model for genetic pleiotropy. Results. RANKL levels showed a negative correlation with age and lower values in smokers. OPG levels were higher in postmenopausal women. Heritability (h2) was 85% for spine BMD and 52% for serum RANKL after adjustment for age, smoking and BMI. By contrast, there was no significant genetic influence on OPG levels (h2 = 0, 95% CI: 0 to 0.31). Serum OPG was determined almost exclusively by individual environment (e2 = 0.79), with a small, non-significant contribution from shared environment (c2 = 0.21). Restricting analyses to the 158 premenopausal twins did not alter the findings. Conclusions. Serum OPG and RANKL levels have only a weak relation to BMD in healthy women. Phenotype correlations indicate that the genes that contribute to twin similarity for BMD are not genes regulating serum levels of RANKL or OPG. The weak correlation with BMD appears to consist in shared environmental factors.
AB - Osteoprotegerin (OPG) is a circulating receptor that inhibits osteoclastogenesis by binding to RANK ligand (RANKL). OPG knock-out animals develop severe osteoporosis. Treatment with OPG lowers bone resorption and increases BMD. OPG production is influenced by a wide range of hormones and cytokines. The influence of genetic factors on circulating amounts of OPG and RANKL is not known. BMD has been demonstrated to have a high heritability and there is evidence also that bone turnover and bone loss rates are controlled at least in part by genetic factors. Objective. Assessing the genetic impact on serum OPG and RANKL in women and estimation of the relative contribution of this inheritance to the total heritability of BMD. Methods. 188 female twins (52 DZ and 42 MZ pairs) from the Danish Twin Registry were included in the study. Mean age was 35 years (range 19-64 years), average spine BMD was 1.04 ± 0.11 g/cm2. Serum levels of OPG and RANKL were measured by ELISA (Biomedica, Vienna, Austria). This register covers twins born in Denmark since 1870. Heritability and environmental influence was assessed using a maximum-likelihood model for genetic pleiotropy. Results. RANKL levels showed a negative correlation with age and lower values in smokers. OPG levels were higher in postmenopausal women. Heritability (h2) was 85% for spine BMD and 52% for serum RANKL after adjustment for age, smoking and BMI. By contrast, there was no significant genetic influence on OPG levels (h2 = 0, 95% CI: 0 to 0.31). Serum OPG was determined almost exclusively by individual environment (e2 = 0.79), with a small, non-significant contribution from shared environment (c2 = 0.21). Restricting analyses to the 158 premenopausal twins did not alter the findings. Conclusions. Serum OPG and RANKL levels have only a weak relation to BMD in healthy women. Phenotype correlations indicate that the genes that contribute to twin similarity for BMD are not genes regulating serum levels of RANKL or OPG. The weak correlation with BMD appears to consist in shared environmental factors.
KW - Bone mineral density
KW - Genetics
KW - Osteoprotegerin
KW - RANK ligand
KW - Twins
UR - http://www.scopus.com/inward/record.url?scp=18044394042&partnerID=8YFLogxK
U2 - 10.1016/j.bone.2004.12.015
DO - 10.1016/j.bone.2004.12.015
M3 - Article
C2 - 15781001
AN - SCOPUS:18044394042
SN - 8756-3282
VL - 36
SP - 727
EP - 735
JO - Bone
JF - Bone
IS - 4
ER -