Histological quantification of lesion growth rate in hyperostosis frontalis interna (HFI)

Hyperostosis frontalis interna (HFI) is a human skeletal disease characterized by nodules of hyperplastic bone and thickening of the frontal bone's inner surface. Despite its high prevalence in older adults and well-demonstrated neurological comorbidities, HFI's etiology and pathogenesis are poorly understood, including the growth rates of HFI lesions. This lack of information on the rate of progression has obvious consequences for the development of treatment and prevention protocols. Therefore, the aim of this study is to use histopathologic assessment of HFI lesions to directly quantify the growth rate of bone tissue in HFI. To quantify growth rates within HFI lesions, we prepared histological sections of HFI-affected frontal bone from anonymized human cadaver specimens donated to the Anatomical Board of the State of Florida. We measured lamellar breadths from lesioned as well as unlesioned bone to estimate a daily secretion rate (DSR) for the bone tissue, calibrated using dental enamel growth increments from the same individuals. Our data support a median DSR of ~0.9 μm, yielding a lesion expansion rate of approximately 3 years per millimeter of bone thickness. Comparisons of lesioned and unlesioned bone suggest HFI is not associated with a significantly higher osteoblast secretion rate in lesioned bone. Our data suggest that typical HFI progression is a slow, cumulative process, without any clear evidence of acceleration in the osteoblast secretory rate. The slow progression of HFI provides ample opportunity for early identification and clinical interventions before it progresses to cause neurological deficits.