What physiologic factors influence bone age in children?

Physiologic Factors Affecting Bone Age in Children

Sex hormones—particularly estrogen in both sexes—are the primary physiologic drivers of bone maturation, with females demonstrating consistently advanced bone age compared to males throughout childhood and puberty. 1, 2

Hormonal Influences

Sex Steroids (Primary Determinant)

• Estrogen is essential for bone maturation and growth plate fusion in both sexes, as demonstrated by lower bone mineral density in females with late menarche and in males with estrogen receptor or aromatase gene mutations 1

• Females exhibit more advanced bone maturation than males at all ages, beginning before puberty when estrogen levels are already higher in girls than boys 2

• Androgens enlarge the cross-sectional area of long bones, promote trabecular bone development in young adulthood, and maintain cortical thickness through stimulation of periosteal apposition 1

• Pubertal onset occurs approximately 2 years earlier in females, resulting in accelerated bone age advancement during adolescence compared to males 2

Growth Hormone and Thyroid Hormones

• Growth hormone (GH) becomes increasingly important for skeletal growth during childhood after the period of infancy, working in concert with thyroid hormones 1

• Iron is crucial for thyroid function, and iron deficiency anemia is associated with thyroid dysfunction, particularly subclinical hypothyroidism, which can affect bone maturation 1

• Growth hormone deficiency leads to decreased bone turnover and delayed growth in children, ultimately resulting in low peak bone mass 1

Nutritional and Body Composition Factors

Lean and Fat Mass

• Height, lean mass, and fat mass all show independent positive associations with relative skeletal maturation in both boys and girls 3

• Body mass index (BMI) demonstrates a direct relationship with bone age advancement, with mean bone age Z-scores increasing progressively with higher BMI categories 4

• Inadequate lean mass acquisition, weight-bearing physical activity, and diet impair the attainment of peak bone mass, which is dependent on optimal bone growth during puberty 1

Micronutrients

• Iron plays a critical role in bone formation through collagen I synthesis, as hydroxylases required for collagen production are iron-dependent 1

• Calcium, phosphate, and vitamin D are fundamental for bone formation, with additional contributions from vitamin K, copper, magnesium, manganese, and zinc 1

• Peak bone mass is reached around age 30, with genetic traits contributing 60–80% and physical activity plus nutrition accounting for the remaining 20–40% of variation 1

Ethnic and Population Ancestry Factors

• African American children demonstrate advanced relative skeletal maturation independent of obesity, with advancement of approximately 0.19–0.29 years in girls and 0.20–0.29 years in boys even after accounting for growth, body composition, and puberty 3

• Black adolescent girls show bone age exceeding chronological age by approximately 10 months, while black adolescent boys demonstrate advancement of 5 months using Greulich-Pyle standards 5

• Hispanic adolescents exhibit bone age advancement of 9 months in girls and 11.5 months in boys, requiring consideration when applying standard bone age references 5

• Asian boys show significant delays in bone age during middle childhood (nearly 15 months behind chronological age), but demonstrate advancement of 9.5 months during adolescence 5

Physical Activity and Mechanical Loading

• Weight-bearing physical activity is essential for optimal bone development, with decreased activity or immobilization increasing bone resorption and negatively affecting bone mineral density 1

• Skeletal responses to disuse are highly variable but consistently detrimental to bone health 1

Bone Turnover and Remodeling

• Bone formation markers (procollagen type I N-propeptide, s-PINP) and resorption markers (C-terminal telopeptide, s-CTX) vary significantly according to age, gender, and pubertal stage, making interpretation challenging in pediatric populations 1

• Current findings show decreased bone formation and increased bone resorption in children undergoing cancer treatment, though alterations may trend toward recovery long-term 1

Critical Clinical Considerations

• Height age, bone age, and chronological age are tightly correlated in healthy children, with significant variation introduced by nutritional status and pubertal development 4

• After puberty onset, there is higher increment in bone age in girls and height age in boys, reflecting sex-specific patterns of maturation 4

• In children with short stature or growth delay, bone age results must be interpreted together with height Z-score to prevent misclassification of skeletal maturity 6

• The Greulich-Pyle standards, derived from white upper-socioeconomic children in 1931–1942, require ethnic-specific adjustments when applied to contemporary diverse populations 5