Sara Akhtar Ali1, Harsimar Kang2, Robert Olney3, Leigh Ramos-Platt4, Anna Ryabets-Lienhard5, Senta Georgia6, Pisit Pitukcheewanont5. 1. Center For Endocrinology, Diabetes and Metabolism, Children's Hospital Los Angeles (CHLA), United States of America. Electronic address: saakhtar@chla.usc.edu. 2. University of Southern California, United States of America. 3. Division of Endocrinology, Nemour Children's Hospital, Jacksonville, FL, United States of America. 4. Center For Neurology, CHLA, United States of America. 5. Center For Endocrinology, Diabetes and Metabolism, Children's Hospital Los Angeles (CHLA), United States of America. 6. Saban Research Institute, CHLA, United States of America; Diabetes & Obesity Program, Center for Endocrinology, Diabetes and Metabolism, CHLA and Keck School of Medicine of USC, United States of America.
Abstract
BACKGROUND: There have been new advances in understanding bone remodeling on a molecular level including the RANKL-OPG pathway, leading to advancements in targeted therapeutic intervention. There is however limited data in pediatrics with little known on normative values in healthy children. This is the largest cohort to quantify RANKL, OPG, and RANKL: OPG levels in healthy children as well as study the influence of age, gender, Tanner stage, and BMI in this population. METHODS: Healthy subjects, 1-21 years of age, were recruited from general pediatric clinics affiliated with CHLA and in collaboration with samples stored from a previously completed study. Healthy children were defined as those with no chronic disease, daily medication, or fractures in the past six months. Free soluble RANKL and OPG levels were quantified using a sandwich ELISA. RESULTS: Three hundred samples were collected with overall serum concentrations of RANKL, OPG and RANKL: OPG of 0.28 pmol/L, 3.56 pmol/L and 0.08 pmol/L, respectively. Serum RANKL and RANKL: OPG concentrations were significantly different by age (p = 0.0001 and 0.0027, respectively). There was an overall downward trend by age except in the 11-15-year age group where a slight increase was noted. RANKL concentrations were also significantly different between Tanner stages, with highest concentrations seen at Tanner 3 (p = 0.0481), and zBMI (p = 0.001). OPG was inversely correlated with zBMI, but not influenced by gender, age, or Tanner stage. CONCLUSION: We showed significant difference in RANKL levels by age, Tanner stage, and zBMI. OPG was inversely correlated with zBMI. Insight into circulating levels of RANKL, OPG and RANKL: OPG in healthy children may be a potential tool to better understand disease states in pediatrics. Future studies are needed to evaluate the clinical significance of RANKL and OPG levels for diagnostic and therapeutic purposes in this population.
BACKGROUND: There have been new advances in understanding bone remodeling on a molecular level including the RANKL-OPG pathway, leading to advancements in targeted therapeutic intervention. There is however limited data in pediatrics with little known on normative values in healthy children. This is the largest cohort to quantify RANKL, OPG, and RANKL: OPG levels in healthy children as well as study the influence of age, gender, Tanner stage, and BMI in this population. METHODS: Healthy subjects, 1-21 years of age, were recruited from general pediatric clinics affiliated with CHLA and in collaboration with samples stored from a previously completed study. Healthy children were defined as those with no chronic disease, daily medication, or fractures in the past six months. Free soluble RANKL and OPG levels were quantified using a sandwich ELISA. RESULTS: Three hundred samples were collected with overall serum concentrations of RANKL, OPG and RANKL: OPG of 0.28 pmol/L, 3.56 pmol/L and 0.08 pmol/L, respectively. Serum RANKL and RANKL: OPG concentrations were significantly different by age (p = 0.0001 and 0.0027, respectively). There was an overall downward trend by age except in the 11-15-year age group where a slight increase was noted. RANKL concentrations were also significantly different between Tanner stages, with highest concentrations seen at Tanner 3 (p = 0.0481), and zBMI (p = 0.001). OPG was inversely correlated with zBMI, but not influenced by gender, age, or Tanner stage. CONCLUSION: We showed significant difference in RANKL levels by age, Tanner stage, and zBMI. OPG was inversely correlated with zBMI. Insight into circulating levels of RANKL, OPG and RANKL: OPG in healthy children may be a potential tool to better understand disease states in pediatrics. Future studies are needed to evaluate the clinical significance of RANKL and OPG levels for diagnostic and therapeutic purposes in this population.