•IOF and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) consider that Procollagen type I N-propeptide (PINP) and C-terminal telopeptide of type I collagen (β-CTX) are the reference bone turnover markers in osteoporosis.•Harmonization/standardization of PINP and β-CTX is mandatory for their clinical use.•Commutable reference materials and reference methods are needed to allow these steps. Procollagen type I N-propeptide (PINP) and the C-terminal telopeptide of type I collagen (β-CTX) in blood have been designated as reference bone turnover markers in osteoporosis by the International Osteoporosis Foundation (IOF) and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). The IFCC Committee on Bone Metabolism (C-BM) has examined current commercial assays and performed a multicentre study to examine the agreement between assays for PINP and β-CTX in serum and plasma. The results of these studies will inform our work towards the harmonization of PINP assays and the standardization of β-CTX assays in blood, with the development of common calibrators and reference measurement procedures in collaboration with the reagent manufacturing industry. Successful achievement of these goals will help develop universally acceptable practice guidelines for the management of osteoporosis with the inclusion of common reference intervals and treatment targets for PINP and β-CTX.