Bone Formation Markers in Adults with Mild Osteogenesis Imperfecta

Abstract

Abstract Background: Plasma concentrations of procollagen peptides are decreased in osteogenesis imperfecta (OI), whereas other bone formation markers may be increased. We examined the utility of combining these markers in the diagnosis of OI in adults. Methods: We measured plasma concentrations of procollagen-1 N-peptide (P1NP), osteocalcin, and bone alkaline phosphatase in 24 patients with nondeforming OI, 25 patients with low bone mass due to other causes, and 38 age- and sex-matched controls. The discriminant ability of various test combinations was assessed by the construction of ROC curves. Results: The median (range) ratio of osteocalcin to P1NP was significantly greater in patients with type I OI [1.75 (0.80–3.86)] than in controls [0.59 (0.34–0.90)] and patients with other causes of low bone mass [0.48 (0.05–1.38); P <0.0001]. This ratio allowed nearly complete differentiation between healthy controls and patients with type I OI, but not patients with type IV OI. With a cutoff of 0.97 for osteocalcin:P1NP, the sensitivity and specificity were maximized at 95% (95% CI 76%–100%) and 88% (69%–97%), respectively, for patients with other causes of low bone mass vs those with type I OI only. For patients with other causes of low bone mass vs all OI patients, sensitivity and specificity were 83% (63%–95%) and 88% (69%–97%), respectively. The addition of bone alkaline phosphatase data did not improve the discriminant ability of the osteocalcin:P1NP ratio. Conclusions: The osteocalcin:P1NP ratio is a sensitive and specific test for type I OI in adults, but it has less utility in the diagnosis of other types of nondeforming OI.