Fisher, AlexanderFisher, LeonSrikusalanukul, WichatSmith, Paul2021-12-052021-12-05Fisher A, Fisher L, Srikusalanukul W, Smith PN. Bone Turnover Status: Classification Model and Clinical Implications. Int J Med Sci 2018; 15(4):323-338. doi:10.7150/ijms.22747. Available from https://www.medsci.org/v15p0323.htm1449-1907http://hdl.handle.net/1885/254514Aim: To develop a practical model for classification bone turnover status and evaluate its clinical usefulness. Methods: Our classification of bone turnover status is based on internationally recommended biomarkers of both bone formation (N-terminal propeptide of type1 procollagen, P1NP) and bone resorption (beta C-terminal cross-linked telopeptide of type I collagen, bCTX), using the cutoffs proposed as therapeutic targets. The relationships between turnover subtypes and clinical characteristic were assessed in 1223 hospitalised orthogeriatric patients (846 women, 377 men; mean age 78.1 +/- 9.50 years): 451(36.9%) subjects with hip fracture (HF), 396(32.4%) with other non-vertebral (non-HF) fractures (HF) and 376 (30.7%) patients without fractures. Results: Six subtypes of bone turnover status were identified: 1 - normal turnover (P1NP>32 mu g/L, bCTX <= 0.250 mu g/L and P1NP/bCTX>100.0[(median value]); 2-low bone formation (P1NP <= 32 mu g/L), normal bone resorption (bCTX <= 0.250 mu g/L) and P1NP/bCTX>100.0 (subtype2A) or P1NP/bCTX<100.0 (subtype 2B); 3-low bone formation, high bone resorption (bCTX>0.250 mu g/L) and P1NP/bCTX<100.0; 4-high bone turnover (both markers elevated) and P1NP/bCTX>100.0 (subtype 4A) or P1NP/bCTX<100.0 (subtype 4B). Compared to subtypes 1 and 2A, subtype 2B was strongly associated with nonvertebral fractures (odds ratio [OR] 2.0), especially HF (OR 3.2), age>75 years and hyperparathyroidism. Hypoalbuminaemia and not using osteoporotic therapy were two independent indicators common for subtypes 3, 4A and 4B; these three subtypes were associated with in-hospital mortality. Subtype 3 was associated with fractures (OR 1.7, for HF OR 2.4), age>75 years, chronic heart failure (CHF), anaemia, and history of malignancy, and predicted post-operative myocardial injury, high inflammatory response and length of hospital stay (LOS) a bove 10 days. Subtype 4A was associated with chronic kidney disease (CKD), anaemia, history of malignancy and walking aids use and predicted LOS>20 days, but was not discriminative for fractures. Subtype 4B was associated with fractures (OR 2.1, for HF OR 2.5), age>75 years, CKD and indicated risks of myocardial injury, high inflammatory response and LOS>10 days. Conclusions: We proposed a classification model of bone turnover status and demonstrated that in orthogeriatric patients altered subtypes are closely related to presence of nonvertebral fractures, comorbidities and poorer in-hospital outcomes. However, further research is needed to establish optimal cut points of various biomarkers and improve the classification model.application/pdfen-AU© 2018 Ivyspring International Publisherhttps://creativecommons.org/licenses/by-nc/4.0/bone turnover markersclassificationnonvertebral fractureprediction2018-02-0110.7150/ijms.227472021-12-03Creative Commons Attribution (CC BY-NC) license