Neurofibromatosis type 1 (NF1) is associated with lower bone mass and increased risk of fracture. Children with NF1 display faltering growth from mid-childhood. However, to date tibia bone development in children with NF1 across childhood and the role of body size have not been explored.
Therefore, we recruited 24 children with NF1 (12 girls, mean age 8.2 ± 1.1y) and 104 children without NF1 (52 girls, mean age 11 ± 1.7y). Tibia and fibula bone characteristics were assessed at 4% and 38% distal-proximal tibia length in all children at baseline using peripheral quantitative computed tomography (pQCT). Longitudinal scans were obtained in 21 children with NF1 (12 girls) over 3.4 ± 0.3y and 71 children without NF1 (34 girls) over 1.1 ± 0.1y, such that at follow-up mean age of both groups (NF1 10.9 ± 1.3y, controls 11.4 ± 1.4y) were similar. Effects of group (NF1/control) on bone outcomes as well as group-by-age interactions, indicating differences in rate of change in bone outcome bone outcomes were assessed via linear mixed effects models with adjustment for sex, age, pubertal status and in additional models with adjustment for height and weight Z-scores.
Group (NF1/control)-by-age interactions indicated a slower rate of tibia and fibula bone mass accrual in children with NF1 at all measured sites. These associations were attenuated by 25–50% by adjustment for height and weight Z-scores. At the 4% site, deficits in bone mass at older ages were related to slower trabecular BMD accrual. At the 38% site, group-by-age interactions suggested that bone mass deficits resulted from poorer accrual of cortical CSA and to a lesser extent cortical BMD.
Lower limb bone mass deficits evident in children with NF1 appear to be progressive and emerge in mid-childhood. In part, they are related to development of a similar pattern of deficits in longitudinal growth and body weight in NF1. Interventions promoting muscle development or physical activity may be partially effective in attenuating bone mass accrual deficits in this population.