A cross-sectional investigation of 914 adolescents aged 11 to 18 years in Tlaxcala, Mexico, has revealed that 94.7 percent exhibited suboptimal circulating vitamin D levels, comprising 44.3 percent with insufficiency and 50.4 percent with deficiency. Published in Pediatric Research, the study found that only 5.3 percent had sufficient 25-hydroxyvitamin D concentrations exceeding 30 ng/mL. The overall population had a median concentration of 19.8 ng/mL, with significant differences between sexes. Girls recorded a lower median concentration of 18.5 ng/mL compared to 22.1 ng/mL in boys, alongside a higher deficiency rate of 62.4 percent compared to 35.8 percent among male peers. By evaluating skeletal parameters alongside turnover proteins, the team assessed whether hypovitaminosis D influences bone integrity during adolescent growth. Multiple linear regression analyses adjusted for potential confounders showed that circulating 25-hydroxyvitamin D was positively associated with osteocalcin and osteopontin and negatively associated with osteoprotegerin specifically among girls, whereas ultrasound measures and regulatory hormones showed no significant relationships.
The physiological necessity of monitoring vitamin D during adolescence rests on the fact that over 85 percent of adult bone mass is consolidated by age 18. Maintaining optimal skeletal health ensures a resilient structural framework capable of enabling locomotion, shielding vital organs, sustaining hematopoiesis, and preserving mineral balance. Skeletal tissue functions dynamically through continuous remodeling coordinated between osteoclasts mediating bone resorption and osteoblasts directing bone formation. Freshly formed osteoid requires mineralization regulated by calcitriol, or 1-alpha,25-dihydroxyvitamin D3. Calcitriol enhances intestinal absorption of calcium and phosphate while promoting renal calcium reabsorption. Direct actions on osteoblasts stimulate differentiation and mineralization via the vitamin D receptor. Furthermore, osteoblasts express 1-alpha-hydroxylase, cubilin, and megalin, allowing local activation of calcitriol to regulate osteoclastogenesis and coupled remodeling. Cutaneous synthesis begins when epidermal 7-dehydrocholesterol absorbs solar ultraviolet B radiation to produce cholecalciferol, which the liver converts to 25-hydroxyvitamin D before renal 1-alpha-hydroxylase produces active calcitriol.
Vitamin D insufficiency and deficiency represent widespread public health challenges globally, with approximately half of the worldwide population estimated to possess suboptimal circulating levels. In Mexico, hypovitaminosis D is notably common in central and southern territories. National survey figures from 2012 documented deficiency in 33 percent of children aged 1 to 11 years, while subsequent investigations confirmed deficiency in 25.9 percent of preschool children and 36.6 percent of school-aged children. Despite extensive solar radiation across Latin America, few population-based surveys have evaluated biochemical and structural bone consequences during adolescence. In adults, prolonged deficiency causes osteopenia, osteoporosis, and elevated fracture rates. In growing adolescents, inadequate concentrations can impair longitudinal growth, hinder osteoid mineralization, and cause rickets. Risk factors include limited sun exposure, sunscreen application, indoor lifestyles, urban living, traditional clothing habits, air pollution, obesity, and genetic polymorphisms in metabolic genes that may explain up to half of observed deficiencies in Mexico.
The cross-sectional investigation recruited adolescents across three municipalities in Tlaxcala between September 2019 and March 2020. An initial pool of 964 candidates was selected from 18 public and private middle and high schools. Eligible students had to be between 11 and 18 years old, have no history of kidney disease, and possess at least one year of continuous residence in Tlaxcala. Following protocol approvals from the Institutional Ethics Committees of Hospital Infantil de México Federico Gómez and CINVESTAV-IPN, 914 adolescents provided written assent alongside parental consent. Caregiver surveys collected socio-environmental details and medical histories. Socioeconomic data indicated that 50.0 percent experienced moderate poverty, 7.0 percent lived in extreme poverty, and 42.9 percent were non-poor. The median age was 13 years with an interquartile range of 12 to 15 years, and girls represented 55.0 percent of participants. Anthropometric measurements utilizing stadiometers, digital scales, and CDC growth chart software revealed that 66.4 percent had normal weight, 18.7 percent were overweight, 12.6 percent were obese, and 2.3 percent were underweight.
Peripheral venous blood samples obtained from participants were centrifuged at 3500 revolutions per minute, separated, and transported on ice at 4 degrees Celsius before being stored at minus 80 degrees Celsius. Serum 25-hydroxyvitamin D concentrations were determined by direct competitive chemiluminescence immunoassay on a LIAISON analyzer using commercial kits and internal quality controls. Remodeling proteins, including parathyroid hormone, fibroblast growth factor 23, osteocalcin, osteopontin, and osteoprotegerin, were measured using a magnetic bead multiplex panel base kit. Soluble receptor activator of nuclear factor kappa ligand concentrations were quantified through an enzyme-linked immunosorbent assay kit from R&D Systems. Duplicate testing across all molecular assays showed precision values between 80 and 120 percent, with coefficients of variation ranging from 6 to 14 percent. These assays enabled the simultaneous quantification of bone formation proteins such as osteocalcin and osteopontin, endocrine mineral regulators including parathyroid hormone and FGF23, and remodeling regulators including osteoprotegerin and RANKL.
Structural bone status was assessed in a randomly chosen subset of 400 participants using a Sunlight Omnisense 8000 P quantitative ultrasound device. Armed with a handheld probe containing four transducers emitting pulsed acoustic waves at 1.25 MHz, trained personnel performed scans at the distal third of the radius and the midshaft tibia of the non-dominant limb. The device computed speed of sound values in meters per second and standardized Z-scores based on sex- and age-matched pediatric reference data. The median speed of sound reached 3882 m/s at the radius and 3809 m/s at the tibia. Normal Z-scores were recorded in 81.3 percent of participants at the radius and 75.7 percent at the tibia. However, low bone mineral density, defined as a Z-score at or below minus 1.0 standard deviation, was identified in 18.7 percent of radius assessments and 24.3 percent of tibial measurements. Statistical comparisons showed no significant differences in speed of sound or low bone mineral density prevalence across vitamin D status categories.
Serum concentrations of 25-hydroxyvitamin D revealed widespread hypovitaminosis D across the population. Normal levels exceeding 30 ng/mL were observed in only 48 participants, representing 5.3 percent of the cohort. Insufficiency was identified in 44.3 percent and deficiency in 50.4 percent of adolescents. Clear sex differences appeared: median concentrations were 18.5 ng/mL in girls and 22.1 ng/mL in boys, with the lowest individual concentration reaching 6.9 ng/mL among girls compared to 8.5 ng/mL among boys. Deficient status was more common in girls at 62.4 percent compared to 35.8 percent in boys, whereas insufficiency occurred in 55.5 percent of boys versus 35.2 percent of girls. Smoothing curves indicated that concentrations in boys rose slightly with age, whereas levels in girls remained flat. Multivariable linear regression indicated that male sex was associated with higher vitamin D levels (beta = 3.5, p < 0.001). Conversely, lower vitamin D concentrations were associated with overweight status (beta = -1.1, p = 0.021), obesity (beta = -2.5, p < 0.001), and living in poverty (beta = -1.1, p = 0.003).
Biochemical markers exhibited notable patterns across vitamin D categories, specifically regarding bone formation indicators. Multiple comparison analysis revealed significant differences in osteocalcin between participants with normal or insufficient status and those with deficiency (p = 0.0007), alongside a marked decrease in osteopontin among deficient individuals (p < 0.0001). Conversely, concentrations of parathyroid hormone, fibroblast growth factor 23, RANKL, and osteoprotegerin showed no significant differences across categorical vitamin D classifications. In simple linear regression across all participants, continuous 25-hydroxyvitamin D was positively associated with osteocalcin (beta = 0.39, p < 0.001) and osteopontin (beta = 0.46, p < 0.001), and inversely associated with osteoprotegerin (beta = -1.08, p = 0.038). When models were adjusted for age, sex, body mass index, and poverty, only the inverse relationship with osteoprotegerin remained significant in the overall cohort (beta = -1.16, p = 0.037). However, sex-stratified adjusted models revealed that these associations persisted exclusively among girls: 25-hydroxyvitamin D was positively associated with osteocalcin (beta = 0.28, p = 0.013) and osteopontin (beta = 0.28, p = 0.034), and inversely associated with osteoprotegerin (beta = -1.86, p = 0.050).
The restriction of significant remodeling associations to female participants likely reflects sex-specific developmental dynamics occurring during puberty. Girls undergo accelerated pubertal growth and skeletal maturation earlier than boys, creating heightened nutritional and mineral requirements during this developmental period. These heightened metabolic demands may amplify skeletal sensitivity to circulating vitamin D variations, influencing bone formation and osteoclastogenesis signaling pathways before overt density changes manifest. Moreover, the lack of correlation between circulating vitamin D and quantitative ultrasound parameters indicates that these modalities reflect distinct biological dimensions.
The investigators noted several limitations, emphasizing that the cross-sectional design precludes inferring causality between vitamin D concentrations and bone outcomes. In addition, quantitative ultrasound possesses lower diagnostic precision than dual-energy X-ray absorptiometry, and the study lacked standardized quantification of direct sun exposure or nutritional supplement intake. Contextualizing their results internationally, the researchers noted that elevated pediatric deficiency is documented across the globe, citing rates of 54.5 percent in Germany, 77 percent in Brazil, 27 to 60 percent in Chile, 52 to 87 percent in Argentina, 34 to 37 percent in the United States, and 46 percent in Guatemala. The authors concluded that widespread hypovitaminosis D in central Mexico constitutes an urgent public health challenge that disproportionately affects girls, individuals living in poverty, and youth with higher body mass index. Because no individual biomarker is currently sufficient to diagnose mineralization defects, the study authors emphasized the need for targeted nutritional monitoring, public supplementation programs, and prospective longitudinal studies to establish age-specific reference ranges.
Subject of Research: Serum vitamin D levels and their association with bone turnover biomarkers and quantitative ultrasound parameters in Mexican adolescents
Article Title: Vitamin D deficiency, quantitative ultrasound parameters and bone biomarkers in adolescents
Article References: Rubio-Gutiérrez, J. C., Jiménez-Córdova, M. I., Ortega-Romero, M., Rojas-Lima, E., Méndez-Hernández, P., Méndez-Polonieski, D. Z., Esparza-García, M., Narváez-Morales, J., Cerón-Meza, R., Medeiros, M., & Barbier, O. C. (2026). Vitamin D deficiency, quantitative ultrasound parameters and bone biomarkers in adolescents. Pediatric Research. https://doi.org/10.1038/s41390-026-05530-2
Image Credits: AI Generated
DOI: 10.1038/s41390-026-05530-2
Keywords: Vitamin D deficiency, Bone turnover markers, Adolescent health, Quantitative ultrasound, Osteocalcin, Osteopontin, Osteoprotegerin, Speed of sound, Bone mineral density, Tlaxcala Mexico, Pediatric endocrinology, Parathyroid hormone, Fibroblast growth factor 23, RANKL, Calcitriol, Skeletal mineralization, Sex-specific differences, Sunlight Omnisense
