Salivary Parathyroid Hormone-related Protein (PTHrP) and Alkaline Phosphatase (ALP) as biomarkers for skeletal maturity
Abstract: Background: Skeletal maturity assessment is critical to determine the amount of remaining facial growth and contributes in the diagnosis and treatment of patients under orthodontic therapy. Since most of the skeletal maturation indicators are invasive and require radiographic exposure, new non-invasive biomarkers have been suggested to assess skeletal maturity. Alkaline phosphatase (ALP)... read morein serum has been reported to be correlated with mandibular growth spurt and to assist in skeletal maturity prediction. In addition, parathyroid hormone-related protein (PTHrP) in serum has been associated with skeletal maturation. The goal of this study was to investigate the relationship between salivary ALP and PTHrP levels and skeletal maturation in growing orthodontic patients as non-invasive biomarkers for skeletal maturity assessment. Materials & methods: This cross-sectional study included 79 subjects (48 females, 31 males; aged 7 to 23 years) categorized into 5 cervical vertebral maturation stages (CVMS) based on an evaluation of lateral cephalograms by three different examiners. Unstimulated whole saliva samples were collected from all subjects, centrifuged and stored at -80°C until use. Total protein levels, ALP activity and PTHrP in unstimulated whole saliva samples were analyzed. The statistical analysis included Cohen's kappa statistics for inter-examiner reliability and Kruskal-Wallis test, with Dunn's test and Bonferroni correction used for post-hoc comparison. The Mann-Whitney U test was used to compare ALP activity between genders. The associations between age and CVMS and between age and ALP activity were assessed via Spearman's correlation. Five multinomial logistic regression models were utilized to predict CVMS. Results: ALP activity in CVMS I was significantly higher than CVMS II (P < 0.001) and CVMS V (P = 0.0014). Total protein levels in CVMS I were significantly lower than CVMS III (P = 0.005). The chronological age was positively correlated with CVMS (rs= 0.763, p < 0.001), but weakly correlated with ALP activity (rs= 0.108, p > 0.05). The combination of chronological age (p < 0.001) and ALP activity (p =0.002) were significant in predicting the CVMS with model's overall correct classification rate of 53.2%. PTHrP was not detected in unstimulated whole saliva in our study. Conclusions: Salivary ALP activity was higher at early pubertal stage and then declined with a statistically significant difference between CVMS I and CVMS II and between CVMS I and CVMS V. Therefore, salivary ALP may to be a promising diagnostic tool for pre-pubertal growth prediction. The combination of salivary ALP activity and chronological age showed the best prediction for CVMS compared to the other models. However, salivary ALP alone presented modest contribution to CVMS prediction. Further longitudinal studies with a larger sample size are warranted in order to validate the potential use of salivary ALP activity as a non-invasive biomarker for skeletal maturity.
Thesis (M.S.)--Tufts University, 2017.
Submitted to the Dept. of Orthodontics.
Advisor: Evangelos Papathanasiou.
Committee: Carroll Ann Trotman, Driss Zoukhri, and Matthew Finkelman.
Keyword: Dentistry.read less