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beta – CrossLaps – Degradation products of type I collagen
(Serum C-terminal telopeptide of type I collagen – Bone Resorption Marker)
Synonyms
- β-CrossLaps
- β-CTX
- CTX-I
- C-telopeptide
- C-terminal telopeptide of type I collagen
- Bone resorption marker
- Type I collagen breakdown product
Units of Measurement
- ng/mL
- ng/dL
- ng/100 mL
- ng%
- ng/L
- pg/mL
Description
β-CrossLaps (β-CTX) are fragments of type I collagen released into blood when bone is resorbed by osteoclasts.
Since ~90% of bone matrix is type I collagen, β-CTX is one of the most sensitive markers of bone resorption.
Used to assess:
- Osteoporosis
- Fracture risk
- Monitoring antiresorptive therapy (bisphosphonates, denosumab)
- Metabolic bone disease
- Hyperthyroidism & secondary causes of high bone turnover
β-CTX reflects current bone resorption rate, with rapid response to treatment (weeks).
Physiological Role & Biology
- Type I collagen is degraded by osteoclasts → releases CTX fragments
- Serum β-CTX is the specific β-isomer associated with bone turnover
- Has a strong circadian rhythm
- Highest in early morning
- Lowest in afternoon/evening
- Highest in early morning
Fasting morning samples are recommended for accuracy (IOF/IFCC).
Clinical Significance
Elevated β-CTX
Indicates high bone turnover, seen in:
1. Postmenopausal Osteoporosis
Most common cause.
2. Hyperthyroidism
Accelerated osteoclast activity.
3. Hyperparathyroidism
Primary or secondary (CKD).
4. Glucocorticoid-induced bone loss
5. Paget Disease of Bone
6. Rheumatoid Arthritis, Immobility, Chronic Inflammation
7. Metastatic Bone Disease
High turnover from osteolysis.
Low β-CTX
Seen in:
- Potent antiresorptive therapy
- Bisphosphonates
- Denosumab
- SERMs
- Bisphosphonates
- Hypoparathyroidism
- Low bone turnover states (e.g., adynamic bone disease in CKD)
Reference Intervals
(IFCC + IOF standardization + Mayo + ARUP)
(Reference intervals vary by assay and age.)
Premenopausal Women
- 0.100 – 0.700 ng/mL
Postmenopausal Women
- 0.200 – 1.000 ng/mL
(Increases markedly after menopause)
Men
- 0.100 – 0.800 ng/mL
Therapeutic Targets
- Successful bisphosphonate therapy →
≥25–50% reduction in β-CTX within 3 months - Denosumab → rapid fall to very low levels
(often <0.100 ng/mL)
Unit Meanings
| Unit | Meaning |
| ng/mL | nanogram per milliliter |
| ng/dL | nanogram per deciliter |
| ng/100 mL | ng% (same as ng/dL) |
| ng% | nanogram per 100 mL |
| ng/L | nanogram per liter |
| pg/mL | picogram per milliliter |
Diagnostic Uses
1. Osteoporosis Diagnosis & Monitoring
- High β-CTX → high turnover osteoporosis
- Used with bone density (DXA) and clinical risk factors
2. Monitoring Therapy
Most important clinical use:
- Measure baseline (fasting morning)
- Recheck at 3-6 months
- Falling β-CTX confirms treatment adherence and efficacy
3. Secondary Causes of Bone Loss
High β-CTX supports:
- Hyperthyroidism
- Hyperparathyroidism
- Multiple myeloma or metastasis
- CKD-related bone disease (specific interpretation needed)
4. Predicting Fracture Risk
High β-CTX correlates with increased future fracture risk.
Analytical Notes
- Fasting morning sample recommended (due to strong circadian variation).
- High variability → use same time of day for follow-up.
- Pre-analytical factors affecting β-CTX:
- Feeding (↓ 20–30%)
- Exercise (↑)
- Menstrual cycle variation
- Vitamin D deficiency
- Feeding (↓ 20–30%)
- Assay: Electrochemiluminescence (Roche Elecsys CTX)
- Avoid high-dose biotin (interference)
Clinical Pearls
- β-CTX is the most reliable marker for early response to osteoporosis therapy.
- High β-CTX in postmenopausal women strongly suggests increased fracture risk.
- Monitor β-CTX if DXA stable but clinical suspicion of high turnover persists.
- In CKD patients, β-CTX must be interpreted alongside PTH and bone-specific ALP.
- Dramatically low β-CTX with denosumab is expected and normal.
Interesting Fact
β-CTX testing provides a real-time snapshot of bone resorption, making it one of the few biochemical markers that changes within weeks, unlike DXA which changes over years.
References
- Tietz Clinical Chemistry and Molecular Diagnostics, 8th Edition - Bone Metabolism.
- IFCC/IOF Consensus on Bone Turnover Markers.
- Mayo Clinic Laboratories - CTX Test.
- ARUP Consult - Metabolic Bone Disease Interpretation.
- International Osteoporosis Foundation (IOF) - β-CTX Guidelines.
- AACE/Endocrine Society - Osteoporosis Treatment Monitoring.
- NIH / MedlinePlus - Bone Turnover Marker Overview.