C-Telopeptide (CTX): The Collagen Fragment Measured as a Bone-Breakdown Marker

What it is

Bone is mostly type I collagen, a protein, with minerals laid on it. When bone-resorbing cells called osteoclasts break bone down, the collagen is cut up and small fragments escape into the blood and urine. C-telopeptide (CTX) is one of those fragments: it comes from the tail at the C-terminal end of the collagen chain, the part called the telopeptide. Measuring it shows how fast bone is being broken down at that moment.

Its partner on the other side of the chain is NTX, the N-terminal telopeptide. On the building side, P1NP is a piece cut off when new collagen is made; the library's osteocalcin entry covers another bone-formation marker.

Why CTX became the reference

In 2011 a joint working group of the International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) reviewed the evidence from 2000 to 2010 (Osteoporos Int 2011, PMID 21184054). It recommended serum CTX as the reference marker of bone resorption and serum P1NP as the reference marker of bone formation, to be used in clinical studies so results could be compared across trials and labs.

The same review is plain about the limits. It says high bone-turnover markers may predict fracture risk independently of bone density in postmenopausal women, but "there is still a need for stronger evidence on which to base practice", and that their value for monitoring individual treatment is limited by variability and poor quality control.

Why the sample conditions matter

CTX is unusually sensitive to how and when blood is taken. The National Bone Health Alliance's 2017 recommendations (Osteoporos Int 2017, PMID 28631236) state:

• CTX samples must be collected consistently in the morning, in the fasted state;
• EDTA plasma is preferred for CTX because it is more stable;
• P1NP needs less care, because it varies little through the day and is not affected by food;
• factors nobody can control — age, sex, pregnancy, immobility, a recent fracture, other illnesses, osteoporosis drugs and other medicines — must be considered when a result is read.

The NBHA notes that poor reproducibility within one person and between laboratories is the main reason bone markers have not been widely adopted in routine practice.

What is not established

• A single CTX result is not a diagnosis. The 2011 review does not support using one level on its own to decide anything, and this entry gives no reference ranges: they differ by assay and laboratory.
• Fracture prediction: supported by observational studies in postmenopausal women, with the review's own call for stronger evidence.
• The fragment's exact length in each commercial assay was not re-checked in this run.

Where it stands

Related reading

Medicines that change bone turnover, and so change CTX, include teriparatide, the PTHrP analogue abaloparatide and calcitonin. The osteocalcin entry covers a bone-formation marker made by bone-building cells.