Evaluation of diagnostic potential of the collagen osteogenesis marker (P1NP) compared with osteocalcin in Cushing’s disease

Background: Secondary osteoporosis is a significant problem, especially in patients with endocrine pathology, which is not accompanied constantly by distinct clinical symptoms. Markers of bone origin are needed, which could be used in osteoporosis diagnosis to clarify its genesis, especially in young people who have secondary osteoporosis more often than older patients. In Cushing’s disease (CD), such a marker, in addition to osteocalcin, could be another bone formation marker, procollagen type 1 N-terminal propeptide (P1NP).

Aims: To study the diagnostic potential of P1NP as an additional marker of endogenous hypercortisolism (Cushing’s disease) compared to osteocalcin.

Materials and methods: The study involved patients with Cushing’s disease and healthy volunteers, matched by gender, age, and body mass index. The levels of osteocalcin and P1NP were assessed in both groups, the electrochemiluminescence method for P1NP (Cobas e411 (Roche, Switzerland)) and for osteocalcin (Cobas 6000 Module e601 (Roche, Switzerland)) was used. ROC analysis was performed with the calculation of sensitivity and specificity of the method to determine the cut-off point for P1NP in CD diagnosis.

Results: 29 patients with Cushing’s disease and 27 healthy individuals from the control group were included in the study. There were no differences in age, sex and body mass index (p = 0.488, 0.426 and 0.531, respectively). Both studied bone formation markers (osteocalcin and P1NP) were reduced in patients with CD: 8.53 ng/ml (Q25%;Q75% 5.40; 12.41) versus 22.45 ng/ml (Q25%;Q75% 17.36; 26.31) (p <0.001) and 28.50 ng/ml (Q25%;Q75% 18.00; 44.00) versus 56.50 ng/ml (Q25%;Q75% 39.50; 65.50) (p <0.001), respectively. The area under the receiver operating characteristic curve (AUC) was 0.808 (95% CI 0.693–0.924) for P1NP and 0.925 (95% CI 0.857–0.992) for osteocalcin, that indicates the greater diagnostic value of osteocalcin for CD verification in healthy controls. Optimal cut-off points were obtained: 53.4 ng/ml (values below are more typical for patients with CD; sensitivity of the method is 96.55%, specificity 57.69%) for P1NP and 15.285 ng/ml (below for patients with CD; sensitivity was 92.59%, specificity 77.78 %) for osteocalcin.

Conclusions: The diagnostic potential of osteocalcin to detect Cushing’s disease in the population is higher compared to P1NP. However, applying of P1NP can be useful because, unlike osteocalcin, it is a direct indicator of the formation of bone matrix collagen structures, that is important for assessing the degree of inhibition of collagen type 1 synthesis in CD and deterioration of bone tissue due to glucocorticoid-induced osteoporosis.

P1NP, osteocalcin, bone remodeling, osteoporosis, pituitary ACTH hypersecretion

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