Reference intervals for serum concentrations of three bone turnover markers for men and women

•To adequately interpret bone turnover markers (BTMs), sex-, age- and method-specific reference intervals are needed.•We determined age- and sex-specific reference intervals for serum concentrations of three BTMs measured on the IDS-iSYS Automated System.•BTMs: intact amino-terminal propeptide of type I procollagen (PINP), bone-specific alkaline phosphatase, carboxy-terminal telopeptide of type I collagen (CTX)•Reference intervals were determined for 1107 men and 544 premenopausal and 498 postmenopausal women living in northeast Germany.

ObjectiveBone turnover markers (BTMs) reflect the metabolic activity of bone tissue and can be used to monitor osteoporosis therapy. To adequately interpret BTMs, method-specific reference intervals are needed. We aimed to determine reference intervals for serum concentrations of intact amino-terminal propeptide of type I procollagen (PINP), bone-specific alkaline phosphatase (BAP) and carboxy-terminal telopeptide of type I collagen (CTX).Material and methodsWe established a healthy reference population of 1107 men as well as 382 pre- and 450 postmenopausal women, who participated in the first follow-up of the Study of Health in Pomerania. Serum PINP, BAP and CTX concentrations were measured on the IDS-iSYS Automated System (Immunodiagnostic Systems, Frankfurt am Main, Germany). The reference interval was defined as the central 95% range. We determined age-specific reference intervals for PINP, BAP, and CTX for men by quantile regression. Reference intervals for women were age-independent.ResultsReference intervals for men for PINP and CTX decreased with age (25-29 year-old men: PINP 31.1-95.9 ng/mL, CTX 0.12-0.83 ng/mL; 75-79 year-old men: PINP 15.7-68.1 ng/mL, CTX 0.05-0.58 ng/mL). The reference interval for men for BAP did not significantly change with age (25-29 year-old men: 7.4-27.7 ng/mL; 75-79 year-old men: 7.6-24.4 ng/mL). The reference intervals for 30-54 year-old premenopausal women were: PINP 19.3-76.3 ng/mL, BAP 6.0-22.7 ng/mL, and CTX 0.05-0.67 ng/mL. The reference intervals for 50-79 year-old postmenopausal women were: PINP 18.2-102.3 ng/mL, BAP 8.1-31.6 ng/mL, and CTX 0.09-1.05 ng/mL.ConclusionAn intensively characterized, large reference population free of bone-related diseases allowed us to determine robust reference intervals for serum concentrations of PINP, BAP and CTX. Our normative data may aid to interpret bone turnover in adult men and pre- and postmenopausal women.