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Changes in bone turnover markers in patients without bone metastases receiving immune checkpoint inhibitors: An
Francesco Pantano1, Flavia Tramontana2, Michele Iuliani1
1Medical Oncology Department, Campus Bio-Medico University of Rome, Rome, Italy.
Abstract:
Immune checkpoint inhibitors (ICIs) has revolutionized the treatment of different advanced solid tumors, but most patients develop severe immune-related adverse events (irAEs). Although a bi-directional crosstalk between bone and immune systems is widely described, the effect of ICIs on the skeleton is poorly investigated. Here, we analyze the changes in plasma levels of type I collagen C-terminal telopeptide (CTX-I) and N-terminal propeptide of type I procollagen (PINP), reference makers of bone turnover, in patients treated with ICIs and their association with clinical outcome. A series of 44 patients affected by advanced non-small cell lung cancer or renal cell carcinoma, without bone metastases, and treated with ICIs as monotherapy were enrolled. CTX-I and PINP plasma levels were assessed at baseline and after 3 months of ICIs treatment by ELISA kits. A significant increase of CTX-I with a concomitant decreasing trend towards the reduction of PINP was observed after 3 months of treatment. Intriguingly, CTX-I increase was associated with poor prognosis in terms of treatment response and survival. These data suggest a direct relationship between ICIs treatment, increased osteoclast activity and potential fracture risk. Overall, this study reveals that ICIs may act as triggers for skeletal events, and if confirmed in larger prospective studies, it would identify a new class of skeletal-related irAEs.
Insights
Immune checkpoint inhibitors (ICIs) may increase bone turnover, indicated by higher CTX-I levels, potentially leading to skeletal issues. This finding suggests a new category of immune-related adverse events affecting bone health.
Area of Science:
- Oncology
- Immunology
- Bone Biology
Background:
- Immune checkpoint inhibitors (ICIs) have transformed advanced solid tumor treatment but cause immune-related adverse events (irAEs).
- The skeletal effects of ICIs are not well understood, despite known bone-immune system interactions.
Purpose of the Study:
- To investigate the impact of ICIs on bone turnover markers.
- To explore the association between changes in bone turnover markers and clinical outcomes in patients receiving ICIs.
Main Methods:
- Assessed plasma levels of CTX-I and PINP (bone turnover markers) in 44 patients with advanced non-small cell lung cancer or renal cell carcinoma treated with ICIs.
- Measurements were taken at baseline and 3 months post-treatment using ELISA kits.
Main Results:
- A significant increase in CTX-I and a decreasing trend in PINP were observed after 3 months of ICI treatment.
- Elevated CTX-I levels correlated with poorer treatment response and survival outcomes.
Conclusions:
- ICI treatment appears to increase osteoclast activity, suggesting a potential fracture risk.
- ICIs may trigger skeletal events, potentially representing a novel class of skeletal irAEs requiring further investigation.
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