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Circulating amounts of osteoprotegerin and RANK ligand: genetic influence and relationship with BMD assessed in female twins.
Bone 2005; 36(4):727-35BONE

Abstract

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 (h(2)) 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 (h(2) = 0, 95% CI: 0 to 0.31). Serum OPG was determined almost exclusively by individual environment (e(2) = 0.79), with a small, non-significant contribution from shared environment (c(2) = 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.

Authors+Show Affiliations

Department of Endocrinology, Odense University Hospital, Denmark. b.abrahamsen@dadlnet.dkNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Twin Study

Language

eng

PubMed ID

15781001

Citation

Abrahamsen, Bo, et al. "Circulating Amounts of Osteoprotegerin and RANK Ligand: Genetic Influence and Relationship With BMD Assessed in Female Twins." Bone, vol. 36, no. 4, 2005, pp. 727-35.
Abrahamsen B, Hjelmborg JV, Kostenuik P, et al. Circulating amounts of osteoprotegerin and RANK ligand: genetic influence and relationship with BMD assessed in female twins. Bone. 2005;36(4):727-35.
Abrahamsen, B., Hjelmborg, J. V., Kostenuik, P., Stilgren, L. S., Kyvik, K., Adamu, S., ... Langdahl, B. L. (2005). Circulating amounts of osteoprotegerin and RANK ligand: genetic influence and relationship with BMD assessed in female twins. Bone, 36(4), pp. 727-35.
Abrahamsen B, et al. Circulating Amounts of Osteoprotegerin and RANK Ligand: Genetic Influence and Relationship With BMD Assessed in Female Twins. Bone. 2005;36(4):727-35. PubMed PMID: 15781001.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Circulating amounts of osteoprotegerin and RANK ligand: genetic influence and relationship with BMD assessed in female twins. AU - Abrahamsen,Bo, AU - Hjelmborg,Jacob Vb, AU - Kostenuik,Paul, AU - Stilgren,Lis S, AU - Kyvik,Kirsten, AU - Adamu,Stephen, AU - Brixen,Kim, AU - Langdahl,Bente L, PY - 2004/09/15/received PY - 2004/11/17/revised PY - 2004/12/01/accepted PY - 2005/3/23/pubmed PY - 2005/10/5/medline PY - 2005/3/23/entrez SP - 727 EP - 35 JF - Bone JO - Bone VL - 36 IS - 4 N2 - UNLABELLED: 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 (h(2)) 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 (h(2) = 0, 95% CI: 0 to 0.31). Serum OPG was determined almost exclusively by individual environment (e(2) = 0.79), with a small, non-significant contribution from shared environment (c(2) = 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. SN - 8756-3282 UR - https://www.unboundmedicine.com/medline/citation/15781001/Circulating_amounts_of_osteoprotegerin_and_RANK_ligand:_genetic_influence_and_relationship_with_BMD_assessed_in_female_twins_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S8756-3282(04)00478-8 DB - PRIME DP - Unbound Medicine ER -