N-telopeptide (NTx, Crosslinks, uNTX, Urine NTx, Pyridinoline Cross-Links, PYD, DPD)

Bone marker measurements may be useful in assessment of bone turnover in metabolic bone disease, especially osteoporosis and Paget’s disease and particularly in monitoring response to therapy. There may also be some value in monitoring metastatic tumour infiltration of the bone marrow. The peptide analyte NTx is derived from an N-telopeptide cross-linking site that joins collagen molecules in the organic matrix of bone. It is generally considered to be a better marker of bone turnover and resorption than urinary pyridinoline, deoxypyridinoline or hydroxyproline. The assay is standardised against collagenase-digested bone collagen and reported in terms of the ratio of bone collagen equivalent (nmol/L) to urine creatinine concentration (mmol/L).

The most useful application of NTx measurement is to monitor the response to anti-resorptive therapy in metabolic bone disease, eg. the treatment of osteoporosis with bisphosphonate drugs, such as zolendronate/alendronate. Serial samples on the same patient are measured before therapy and after 3 and 6 months on therapy.

Reference ranges for pre- and post-menopausal women and men have been assigned and the urine NTx value may be used as an indication of bone turnover status of an individual.

Female pre-menopausal: 5-65 BCE nmol/mmol creatinine Male: <51 BCE nmol/mmol creatinine

The least significant change for urine NTx is ±40 %

Note that post-menopausal reference ranges are poorly defined, and patients who are being treated for osteoporosis should be targeted to reduce their bone turnover into the bottom half of the pre-menopausal range.

A post-menopausal reference range is available on request and is suitable for research studies only.

No reference ranges are available for children but values may be 5-fold higher than adult ranges during growth spurts (although maybe considerably higher in neonates; urine NTx may be between 10,000-20,000 BCE nmol/mmol, particularly in the case of premature neonates). Young adults (16-18 years) may have slightly higher bone turnover than the above reference ranges, reflecting the gradual falling-off after the growth spurt.

Time of collection: if monitoring response to treatment, samples should be collected at the same time of day e.g. always a morning clinic, or always an afternoon clinic. Ideally a morning fasting sample should be collected (ideally a second void urine sample for NTx). Serial measurements on the same patient are recommended before therapy and at 3 and 6 months after therapy (and at subsequent 3, 6 or 12 monthly intervals as required).

If monitoring response to treatment, samples should be collected at the same time of day, eg. always a morning clinic, or always an afternoon clinic. Ideally a morning fasting sample should be collected (ideally a second void urine sample for NTx).

Samples analysed from Wednesday 1 November 2023 will no longer be UKAS accredited.

Any samples analysed after this date will contain a suitable comment to this effect. This will affect all laboratories previously offering NTx analysis via the Osteomark method. If you would like to discuss this matter please contact the laboratory (imperial.proteinlabqueries@nhs.net, 020331 15185/15187).

This test is not currently accredited