Evaluation of Two Methods of Bone Age Assessment in Peripubertal Children in Zimbabwe

Abstract

Objectives: Bone age (BA) measurement in children is used to evaluate growth and maturity and helps in the diagnosis and management of growth disorders in children. The two most used methods are Greulich and Pyle (GP), and Tanner and Whitehouse 3 (TW3), both based upon assessment of a hand-wrist radiograph. To our knowledge no study has compared and validated the two methods in sub-Saharan Africa (SSA), and only a few have determined BA despite it being a region where childhood growth is often impaired for example by HIV and malnutrition. This study aimed to compare BA as measured by two methods (GP and TW3) against chronological age (CA) hence determine which method is applicable in peripubertal children in Zimbabwe.

Methods: We conducted a cross-sectional study of boys and girls who tested negative for HIV. Children and adolescents were recruited by stratified random sampling from six schools in Harare, Zimbabwe. Non-dominant hand-wrist radiographs were taken, and BA assessed manually using both GP and TW3. Paired sample student t-tests were used to calculate the mean differences between BA and chronological age (CA) in boys and girls. Bland-Altman plots compared CA to BA as determined by both methods, and agreement between GP and TW3 BA. All radiographs were graded by a second radiographer and 10% of participants of each sex were randomly selected and re-graded by the first observer. Intraclass correlation coefficient assessed intra- and inter-rater reliability and coefficient of variation assessed precision.

Results: We recruited 252 children (111 [44%] girls) aged 8.0-16.5 years. The boys and girls were of similar mean ±SD CA (12.2 ±2.4 and 11.7 ±1.9 years) and BA whether assessed by GP (11.5 ±2.8 and 11.5 ±2.1 years) or TW3 (11.8 ±2.5 and 11.8 ±2.1 years). In boys BA was lower than CA by 0.76 years (95% CI: -0.95, -0.57) when using GP, and by 0.43 years (95% CI: -0.61, -0.24) when using TW3. Amongst the girls there was no difference between BA and CA by either GP [-0.19 years (95% CI: -0.40, 0.03)] or TW3 [0.07 years (95% CI: -0.16, 0.29)]. In both boys and girls, there were no systematic differences between CA and TW3 BA across age groups whereas agreement improved between CA and GP BA as children got older. Inter-operator precision was 1.5% for TW3 and 3.7% for GP (n=252) and intra-operator precision was 1.5% for TW3 and 2.4% for GP (n=52).

Conclusion: The TW3 BA method had better precision than GP and did not systematically differ from CA, meaning that TW3 is the preferred method of assessment of skeletal maturity in Zimbabwean children and adolescents. TW3 and GP methods do not agree for estimates of BA and therefore cannot be used interchangeably. The systematic differences in GP BA assessments over age means it is not appropriate for use in all age groups or stages of maturity in this population.

Note:

Funding Information: PhD funding support from the University of Southampton Global Challenges Research Fund and Faculty of Medicine, and part-funding from UK Medical Research Council Program U105960371. RAF is funded by the Wellcome Trust (206316_Z_17_Z). The IMVASK study was funded by the Wellcome Trust through a fellowship to RR (206764/Z/17/Z).

Declaration of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Ethics Approval Statement: Ethics approval was granted by the Medical Research Council of Zimbabwe (Harare; reference MRCZ/A/2297) and the University of Southampton, UK (ERGO II 62773). Written informed consent was provided by the parents/guardian, and the children provided written assent.

Keywords: age, radiograph, skeletal maturity, Africa, children, growth