Radiographic imaging, densitometry and disease severity in Autosomal dominant osteopetrosis type 2.

To characterize relationships between quantitative computed tomography bone mineral density measurements and other qualitative and quantitative imaging measures, as well as clinical metrics, in patients with autosomal dominant osteopetrosis type 2 (ADO2). Clinical and radiologic parameters of 9 adults and 3 children with autosomal dominant osteopetrosis type 2 were assessed including lumbar spine quantitative computed tomography (QCT), radiographic skeletal survey (skull base thickening; Erlenmeyer flask deformity; endobone pattern; and spine density pattern (endplate sclerosis, "anvil" appearance, or diffuse sclerosis)), dual-energy x-ray absorptiometry (DXA), tibial peripheral quantitative computed tomography (pQCT) volumetric bone mineral density (vBMD), bone turnover markers, and bone marrow failure or visual impairment. The skeletal parameter most divergent from normal was lumbar spine QCT Z-score (+ 3.6 to + 38.7). Lumbar QCT Z-score correlated positively with pQCT tibial diaphysis vBMD (Pearson correlation r = 0.73, p = 0.02) and pQCT tibial metaphysis vBMD (r = 0.87, p < 0.01). A trend towards positive lumbar QCT Z-score correlation with serum P1NP/CTX ratio (r = 0.54, p = 0.10) and lumbar DXA Z-score (r = 0.55, p = 0.10) were observed. Bone marrow failure and vision impairment occurred in those with most severe quantitative and qualitative measures, while those with less severe radiographic features had the lowest QCT Z-scores. Lumbar spine QCT provided the most extreme skeletal assessment in ADO2, which correlated positively with other radiologic and clinical markers of disease severity. Given the quantification of trabecular bone and greater variation from normal with wider range of values, lumbar QCT Z-scores may be useful to determine or detect impact of future treatments.