Bone turnover in postmenopausal women during denosumab treatment: Biomarker analysis in naive and discontinuing patients

Objectives Osteoporosis is characterized by an imbalance in bone turnover, with increased resorption over formation. Antiresorptive treatment, such as denosumab (Dmab), aims to restore this balance, making monitoring of bone turnover markers useful. Key bone resorption parameters are serum C-terminal telopeptide of type I collagen (CTX) and urinary deoxypyridinoline/creatinine (DPD). Methods We retrospectively analyzed the bone turnover in a total of 96 postmenopausal women, 59 were treatment-naive before starting with Dmab, and 37 had discontinued prior Dmab therapy for ≥9 months before resumption. Bone turnover markers were measured every 6 months, and DXA scans were performed annually over 36 months. Comparative analysis included only treatment-naive patients with elevated baseline resorption markers (CTX or DPD above reference). Additionally, a large laboratory database ( n = 21,802) was used to examine the correlation between CTX and DPD. Results Both CTX and DPD decreased significantly within 6 months of Dmab initiation. Notably, while CTX was increased only in 5.1%, DPD was elevated in 32.2% in the treatment-naive group. At baseline, 26.3% of patients in the discontinued group showed elevated CTX levels, while DPD was elevated in all patients (100%). After resuming Dmab treatment following a treatment discontinuation, DPD remained elevated in 51.8% of patients despite normal CTX. Correlation analysis revealed a moderate association between CTX and DPD (r s = 0.431). Conclusions Our data suggest that urinary DPD may provide additional biochemical information in certain clinical contexts, particularly after denosumab discontinuation. Thus, simultaneous assessment of CTX and DPD may enhance diagnostic accuracy and may guide individualized osteoporosis management; however, prospective validation is needed.