Changes in serum RANKL and OPG with sexual development and their associations with bone turnover and bone mineral density in a cohort of girls.
OBJECTIVE
To characterize the variations of serum osteoprotegerin (OPG) and RANK ligand (RANKL) with sexual development in adolescent girls, and to estimate their associations with bone turnover and bone mineral density (BMD).


METHODS
We studied 300 girls evaluated at 13 and 17years of age. Fasting blood samples were collected and the following substances were quantified: RANKL, OPG, C-terminal telopeptide of type I collagen (CTX), and procollagen type I N propeptide (PINP). BMD was measured at the distal forearm. Correlation coefficients were used to quantify associations between those variables at 13 and 17 years of age. Random-effects linear models were used to quantify associations between bone parameters and sexual development (years from menarche).


RESULTS
RANKL was positively correlated with bone resorption (CTX) in early and late adolescence (r13=0.15 and r17=0.23) and the OPG/RANKL ratio correlated inversely with CTX at 17 (r17=-0.24). No significant associations were found between RANKL and OPG and bone formation (PINP). In early adolescence, there was an inverse correlation of BMD with CTX (r13=-0.52) but no significant correlations were found between osteoclast regulators and BMD. We observed a linear decrease in serum RANKL with increasing sexual development (-0.09 pmol/L per year, 95% CI: -0.10, -0.07) alongside an increase in OPG (0.02pmol/L, 95% CI: 0.01, 0.04).


CONCLUSIONS
Serum RANKL and OPG levels varied markedly with sexual development in adolescence. These cytokines were not predictive of bone turnover or BMD at 13, but serum RANKL bioactivity was associated with bone resorption in late adolescence.
Institute of Public Health of the University of Porto, Porto, Portugal; Department of Hygiene and Epidemiology, University of Porto Medical School, Porto, Portugal. Electronic address: rlucas@med.up.pt.
Raquel
R
Lucas
Institute of Public Health of the University of Porto, Porto, Portugal; Department of Hygiene and Epidemiology, University of Porto Medical School, Porto, Portugal.
Elisabete
E
Ramos
Department of Hygiene and Epidemiology, University of Porto Medical School, Porto, Portugal.
Margarida
M
Prata
Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal; Serviço de Reumatologia e Doenças Ósseas Metabólicas, Hospital de Santa Maria, Lisbon, Portugal.
Ana Maria
AM
Rodrigues
Serviço de Reumatologia, Hospital de São João, Porto, Portugal.
Lúcia
L
Costa
Institute of Public Health of the University of Porto, Porto, Portugal; Department of Hygiene and Epidemiology, University of Porto Medical School, Porto, Portugal.
Milton
M
Severo
Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal; Serviço de Reumatologia e Doenças Ósseas Metabólicas, Hospital de Santa Maria, Lisbon, Portugal.
Helena
H
Canhão
Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal; Serviço de Reumatologia e Doenças Ósseas Metabólicas, Hospital de Santa Maria, Lisbon, Portugal.
João Eurico
JE
Fonseca
Institute of Public Health of the University of Porto, Porto, Portugal; Department of Hygiene and Epidemiology, University of Porto Medical School, Porto, Portugal.
Henrique
H
Barros
D000293:Adolescent; D015519:Bone Density; D015331:Cohort Studies; D005260:Female; D006801:Humans; D053244:Osteoprotegerin / Q000097:blood*; D053245:RANK Ligand / Q000097:blood*; D012741:Sexual Maturation
D053244:Osteoprotegerin; D053245:RANK Ligand; C505688:TNFSF11 protein, human
Adolescence; Bone mineral density; Bone turnover; Longitudinal study; Osteoprotegerin; RANK ligand