Biomarkers of Bone Metabolism: Collagen Cross-Linked NTx (urine)

Optimal Takeaways

N-telopeptide (NTx) is a protein fragment found in type 1 collagen, the type of collagen that makes up 90% of bone matrix. Bone breakdown will cause a release of NTx which is then excreted in the urine. Urinary levels are found to correlate well with serum levels and can be used for monitoring bone health and integrity. 

Standard Range: 0 - 64 nmol BCE/mmol creatinine

The ODX Range: 0 - 38 nmol BCE/mmol creatinine

Low levels of NTx can be seen with hypothyroidism, hypoparathyroidism, cortisol therapy, and kidney disease. Antiresorptive therapies will reduce elevated NTx (Pagana 2019).

High levels of NTx reflect increased bone breakdown and can be seen with bone tumors, osteoporosis, vitamin D insufficiency, Paget’s bone disease, acromegaly, hyperthyroidism, and hyperparathyroidism. Levels of NTx can increase significantly with age and with smoking (Gossiel 2014, Pagana 2019).

Overview

Collagen cross-linked N-telopeptide (NTx) is a biomarker that reflects bone turnover, i.e., bone formation by osteoblasts and bone resorption by osteoclasts. NTx can be monitored over time to detect improvement in bone mineral density, particularly during therapeutic interventions.

NTx is a component of type 1 collagen, the compound that makes up 90% of bone. When bone breaks down and excess resorption takes place, NTx is one of the protein fragments released into circulation and then excreted via urine. Levels in the serum and urine (normalized for creatinine) correlate well and will decline as bone breakdown and resorption decrease.

In healthy, premenopausal women, levels as low as 15 BCE/mmol creatinine are observed (Gossiel 2014). Levels increase sharply approaching menopause and then decline 1-2 years after menopausal transition but remain ~20% higher than premenopausal levels. Increases in NTx are most pronounced in women with a BMI of less than 25 (Sowers 2013).

Estrogen has anti-resorptive properties and its therapeutic use after menopause can decrease levels of NTx, bone loss, and risk of osteoporosis (Pagana 2019). Measurement of NTx will be confounded in liver or kidney disease (Shetty 2016).

References

Baxter, I et al. “Evaluation of urinary N-telopeptide of type I collagen measurements in the management of osteoporosis in clinical practice.” Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA vol. 24,3 (2013): 941-7. doi:10.1007/s00198-012-2097-4

Gossiel, Fatma et al. “Establishing reference intervals for bone turnover markers in healthy postmenopausal women in a nonfasting state.” BoneKEy reports vol. 3 573. 3 Sep. 2014, doi:10.1038/bonekey.2014.68

Pagana, Kathleen Deska; Pagana, Timothy J.; Pagana, Theresa N. Mosby's Diagnostic and Laboratory Test Reference. Elsevier Health Sciences. 2019.

Shetty, Sahana et al. “Bone turnover markers: Emerging tool in the management of osteoporosis.” Indian journal of endocrinology and metabolism vol. 20,6 (2016): 846-852. doi:10.4103/2230-8210.192914

Sowers, MaryFran R et al. “Changes in bone resorption across the menopause transition: effects of reproductive hormones, body size, and ethnicity.” The Journal of clinical endocrinology and metabolism vol. 98,7 (2013): 2854-63. doi:10.1210/jc.2012-4113