Point-of-Care Bone Age Evaluation: The Increasing Role of US in Resource-limited Populations

Abstract

HomeRadiologyVol. 296, No. 1 PreviousNext Reviews and CommentaryFree AccessEditorialPoint-of-Care Bone Age Evaluation: The Increasing Role of US in Resource-limited PopulationsJonathan R. Dillman , Rama S. AyyalaJonathan R. Dillman , Rama S. AyyalaAuthor AffiliationsFrom the Department of Radiology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, 3333 Burnet Ave, Cincinnati, OH 45229 (J.R.D.); Department of Diagnostic Imaging, Rhode Island Hospital–Hasbro Children’s Hospital, Warren Alpert Medical School of Brown University, Providence, RI (R.S.A.).Address correspondence to J.R.D. (e-mail: [email protected])Jonathan R. Dillman Rama S. AyyalaPublished Online:Apr 28 2020https://doi.org/10.1148/radiol.2020201168MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In See also the article by Nicholas et al in this issue.Dr Dillman is a pediatric radiologist and associate chief of research in the Department of Radiology at Cincinnati Children’s Hospital Medical Center. His primary clinical and research interests relate to the development and use of US and MRI biomarkers in pediatric liver and intestinal diseases. Dr Dillman is on the board of governors of the American Institute of Ultrasound in Medicine and the board of directors of the Society for Pediatric Radiology, and he is the principal investigator on multiple NIH grants.Download as PowerPointOpen in Image Viewer Dr Ayyala is a pediatric radiologist and assistant professor in the Department of Diagnostic Imaging at Rhode Island Hospital–Hasbro Children’s Hospital. Her primary clinical and research interests include neonatal and fetal imaging, use of US in children, and application of artificial intelligence to bone age evaluation. Dr Ayyala is the chair of the Society for Pediatric Radiology’s neonatal committee.Download as PowerPointOpen in Image Viewer Poor or stunted growth, defined as abnormally low height for one’s age, represents a reduced growth rate in human development due to factors such as malnutrition, poor sanitation, and recurrent infections. Stunted growth is a serious global public health concern, affecting more than 150 million children worldwide. Long-term consequences affect many aspects of life, including overall health and well-being—such as failure to achieve an expected final height and weight, reduced cognition, and a higher risk of premature death, while also affecting the final education level attained and future socioeconomic status. Stunted growth is most prevalent in children living in Asia and Africa; however, it is present to a lesser degree throughout much of the world, including North America (1).There are a limited number of diagnostic tools available to public health officials, medical workers, and researchers to detect and quantify stunted growth in poor and underdeveloped countries, particularly those who are “in the field.” In this issue of Radiology, Nicholas et al sought to use tablet-based point-of-care US performed in the home, a low-cost and innovative portable imaging solution, to measure bone age and evaluate its association with anthropometry (height) and diet in children living in rural Ecuador (2).Radiography of the wrist and hand (such as the Greulich and Pyle method) is most often used to assess skeletal maturity in the developed world, including the United States (3). The radiographic pattern of ossification and the appearance of the bones is used to determine bone age. Radiographic bone age is generally accurate and reproducible and can be used to direct patient care (eg, identification and treatment of endocrine disorders, use of growth hormone therapy in certain children with short stature) (3). However, a radiography (x-ray) machine may not be available in many areas of the world because of limited economic means. In contrast, US is becoming cheaper and more portable. A few studies to date have shown that a standardized US examination of the hand and wrist can be used to assess bone age by evaluating the degree of ossification of specific bones in prescribed planes, with slight differences in scanning protocol for boys and girls (4,5). In a study of children up to 6 years of age by Bilgili et al using the Greulich and Pyle method to compare US and radiographic bone age assessment, 84.4% of boys and 88.5% of girls had an estimated bone age difference of less than 6 months between the techniques (5).Nicholas and colleagues (2) used a tablet-based point-of-care US system to measure bone age in a pediatric population living in rural Ecuador. The authors wanted to evaluate the associations between US-based bone age and other predictors of bone age, such as diet and anthropometry. In 128 children, mean bone age was lower in children with stunted (n = 63) versus nonstunted (n = 65) growth (bone age z score [BAZ], −1.42 vs −0.98; P = .04), with 49% of the children showing stunted growth based on height. Multivariable analysis showed that BAZ was independently positively associated with height, female sex, and dietary factors (eg, number of times eggs were eaten in the past 24 hours) and was negatively associated with ownership of pigs as livestock (a result the authors struggle to explain and suggest needs further investigation).The authors did not identify any US-detectable cases of rickets, despite the high prevalence of stunted growth and associated malnutrition. This may reflect adequate calcium intake as well as satisfactory vitamin D levels from considerable sun exposure, given the geographic location of the studied population. The authors concluded that bone age, as determined using tablet-based US, was lower in rural Ecuadorian children who had stunted growth and was associated with dietary factors.So, why is the determination of bone age using US important in these resource-limited settings? First, US is inexpensive, portable, and ever more available. This imaging study can be performed in the clinic, in the community, or at home (as in the current study) with minimal operator training and experience. Either a medical student or a public health graduate student performed the US examinations in this study, suggesting a wide range of personnel can perform portable US (public health workers, researchers, medical trainees, physicians, and sonographers). Second, the current study proposes using US to identify children with delayed bone age and to help confirm the specific diagnosis of stunted growth and underdevelopment likely secondary to malnutrition or other chronic exposure, and thus exclude short stature representing normal variation or so-called familial short stature (ie, a child is short because her or his parents are short). Third, US can help monitor the impact of interventions on delayed bone age and stunted growth due to alterations in diet or medical therapy. Finally, US could serve as an end point for clinical trials requiring bone age evaluation of young children (eg, birth to 6 years of age) both in resource-limited and non–resource-limited environments, allowing serial imaging while minimizing the use of resources and radiation exposure.The current study had a few noteworthy limitations. First, there is the question of generalizability to other populations. The study population was children living in rural Ecuador with a mean age of 33.9 months and a narrow age range of only 30 to 38 months. Furthermore, bone age was determined based on the descriptions and standards created by Greulich and Pyle (6), an atlas first published in 1950 and based on children of a different ethnicity from the midwestern United States (Cleveland, Ohio) (3). Second, one radiologist interpreted US bone age assessment, which raises the possibility of bias. A blinded assessment of US bone age by a second reader could help mitigate this potential limitation. Finally, the study was small, and a larger study might serve to identify additional predictors that impact the relationship of US-based bone age assessment and stunted growth.With this study serving as a model, US bone age assessment could also be used in areas of developed countries with limited resources or as a population health instrument, such as in school screening for stunted growth and underdevelopment due to malnutrition or unrecognized chronic illness. While current practicing pediatric radiologists may be uncomfortable and even resistant to this US-based technique, the standardized scan protocol described—and appropriate radiologist knowledge of hand and wrist ossification patterns, likely can generate accurate and reproducible results. However, additional validation studies are necessary for adoption of US bone age assessment into more routine clinical practice in the United States. This includes evaluation of interreader agreement, agreement with Greulich and Pyle radiographic descriptions and standards (or more modern bone age descriptions and standards), and correlations with important clinical outcomes. As US systems continue to become less expensive and more portable, both radiologists and nonradiologists, including public health researchers, will undoubtedly continue to identify novel applications for US. We are excited to see what comes next!Disclosures of Conflicts of Interest: J.R.D. disclosed no relevant relationships. R.S.A. disclosed no relevant relationships.