Population-based reference intervals for bone turnover markers in black African adults and initial assessment of the Bone Balance Index

Background Bone turnover markers (BTMs) are increasingly used to assess bone remodeling and to monitor osteoporosis treatment. However, reference intervals remain largely undefined for African populations, limiting their clinical utility in these settings. Methods We established reference intervals for intact procollagen type I N-propeptide (iPINP) and C-terminal telopeptide of type I collagen (β-CTX-I) in a rigorously selected cohort of healthy adult Black African blood donors from Côte d'Ivoire. Participants were screened for factors affecting bone metabolism, including kidney function, vitamin D status, and infectious diseases. Serum samples were processed under standardized conditions and analyzed using the IDS iSYS platform. Reference intervals were determined according to the CLSI C28-A3 guideline using the bootstrap non-parametric method, complemented by a Box-Cox transformation to verify robustness. The Bone Balance Index (BBI), defined as the standardized difference between observed and expected β-CTX-I based on IPINP, was also explored in women >45 years. Results In men ( n = 90), β-CTX-I concentrations showed reference interval of 181–610 ng/L (90 % CI: 168–196 / 480–745), and in women ≤45 years ( n = 86), 167–378 ng/L (90 % CI: 166–166 / 343–413). For iPINP, the corresponding reference intervals were 30–169 μg/L (90 % CI: 19–41 / 151–187) in men and 28–142 μg/L (90 % CI: 24–33 / 107–176) in women ≤45 years. Box–Cox–based intervals were comparable, confirming the robustness of the bootstrap results. Compared to published data in non-African populations, β-CTX-I values were generally lower, while iPINP values, particularly in men, tended to be higher. Among 27 women > 45 years, BBI values ranged from −1.36 to +8.59, with a median of 0.13; 20 (74 %) showed BBI > 0, suggesting a predominance of resorption, while 2 (7 %) had BBI < −1. Conclusions This study provides the first rigorously derived reference intervals for β-CTX-I and iPINP in a sub-Saharan African population, enabling more accurate interpretation of BTMs in African clinical contexts. The BBI may further help characterize bone remodeling balance at the individual level, though its clinical significance warrants further study.