**Background:** Osteoporosis is a major public health problem, with 30% of the population suffering fractures after age 50. Peak bone mass is acquired during childhood and adolescence and is the greatest determinant of adult fracture risk. Growth hormone (GH) promotes linear growth and osteoblastic activity. The transition phase (puberty to age 30) is critical for bone mass accrual. Modifiable factors (calcium, vitamin D, exercise) and non-modifiable factors (genetics, ethnicity) influence bone mineral gain. Few studies have examined ethnic differences in bone mass among Brazilian adolescents treated with recombinant human growth hormone (rhGH), despite the country's significant miscegenation. This study aimed to compare bone mass and osteometabolic profile between white and Afro-descendant Brazilian adolescents in the transition phase who were treated with rhGH during childhood.
**Methods:** This cross-sectional study included 38 individuals (14–20 years, 17 females, 21 males) from the Transitional Outpatient Clinic of the Instituto da Criança, Hospital das Clínicas, University of São Paulo, recruited between May 2017 and April 2019. Inclusion criteria: regular rhGH treatment for at least 3 consecutive years prior to study entry. Exclusion criteria: chronic diseases affecting bone mass (chronic renal failure, type 1 diabetes mellitus, osteopathy, complex syndromes, chronic corticosteroid use). The transition phase was defined as completed pubertal development, final height (growth velocity <2 cm/year), bone age ≥14 years (girls) or ≥16 years (boys). rhGH was interrupted for at least one month before serum measurements. Bone mineral density (BMD) and bone mineral content (BMC) of lumbar spine and total body were measured by DXA (Hologic, Discovery W), with Z scores adjusted for sex, age, and height. Low bone mass risk was defined as Z score between -1 and -2; low bone mass as ≤-2 SD. Serum measurements included calcium, phosphorus, alkaline phosphatase (AF), 25(OH)D, IGF-I, and CTX-I. Daily calcium intake was estimated from dietary inquiry; adequate intake was defined as 1300 mg/day. Vitamin D sufficiency was defined as 25(OH)D >20 ng/mL. Physical activity was recorded as yes/no. Subjects were divided by ethnicity into Afro-descendant and white. Statistical analysis used Student's t-test, Mann-Whitney test, Fisher's test, Chi-square test, and Pearson's correlation, with significance at p<0.05.
**Key Results:** Mean age was 16.8±1.6 years. Overall, 66% (25/38) had inadequate calcium intake, 34% (13/38) had vitamin D insufficiency, and 44.7% (17/38) were physically inactive. Only 20% (5/38) were on cholecalciferol supplementation. Afro-descendants (group A, n=21) had significantly lower mean body weight than whites (group B, n=17): 47.3±10.2 kg vs 57.9±15 kg (p=0.03). Height was similar between groups (p=0.21). There were no significant differences in proportions of adequate calcium intake (23.8% vs 41.2%, p=0.1), vitamin D insufficiency (28.6% vs 41.2%, p=0.4), or physical exercise. Serum values showed no significant differences between groups: 25(OH)D (24.7±10.5 vs 24.5±7.4 ng/mL, p=0.92), calcium (9.6±0.5 vs 9.6±0.4 mg/dL, p=0.14), phosphorus (4.1±0.4 vs 4.2±0.4 mg/dL, p=0.95), CTX-I (1.21 vs 1.14 ng/mL, p=0.31), alkaline phosphatase (137 vs 104 U/L, p=0.76), and IGF-I (218 vs 176 ng/dL, p=0.12). However, lumbar spine Z scores were significantly lower in Afro-descendants (-1.5±1.2 vs -0.9±0.6, p=0.04), as were total body Z scores (-1.6±1.0 vs -0.82±0.9, p=0.03). Lumbar spine BMD (0.825±0.1 vs 0.875±0.08 g/cm², p=0.14) and BMC (41.6±9.6 vs 46.5±8.5 g, p=0.12) and total body BMD (0.850 vs 0.885 g/cm², p=0.16) and BMC (1166.8 vs 1443.7 g, p=0.09) did not reach statistical significance.
**Clinical Implications:** The high prevalence of vitamin D insufficiency (34%), inadequate calcium intake (66%), and physical inactivity (44.7%) in this cohort of rhGH-treated adolescents highlights the need for routine monitoring of lifestyle factors and supplementation of calcium and cholecalciferol during and after rhGH therapy. Contrary to literature suggesting Afro-descendants typically have higher bone mass, Afro-descendant Brazilian adolescents in this study had significantly lower spine and total body Z scores than whites, possibly due to Brazil's extensive miscegenation. Lower body weight in Afro-descendants may contribute to lower bone mass, as weight positively correlates with BMD through mechanical loading. The authors recommend: (1) initial DXA and osteometabolic profile assessment in the prepubertal phase for rhGH users; (2) annual osteometabolic profile and DXA in the transition phase for those with normal results; (3) biannual osteometabolic profile, regular osteogenic exercise, and DXA at puberty onset and transition for those at risk or with low bone mass; (4) calcium and cholecalciferol supplementation when necessary. Limitations include small sample size (n=38), dietary calcium estimation, lack of data on protein/macronutrient intake and socioeconomic status, and geographic restriction to São Paulo state. This is the first study using DXA to compare ethnic differences in bone mass among Brazilian adolescents treated with rhGH. Further studies with larger samples and healthy controls are needed.