Introduction
Osteoporosis—Diagnosis and Burden of Disease
Measuring Bone Turnover
Measurement medium | |
---|---|
Bone formation markers
| |
Bone alkaline phosphatase | Serum |
PICP | Serum |
Osteocalcin | Serum, urine |
PINPa | Serum |
Bone resorption markers
| |
CTX-Ia | Plasma, serum*, urine |
ICTP | Serum |
NTX | Serum, urine |
Trap5b | Serum |
Factors Affecting Levels of Bone Turnover Markers
Effect | Recommendation | Importance | |
---|---|---|---|
Controllable sources
| |||
Circadian rhythm | High BTM concentrations at night and early morning, lowest in the afternoon | Collect serum samples in the morning (7.30–10.00 h) | High |
Food intake | Decrease in BTMs, especially bone resorption markers (about 20–40%) after food intake | Collect samples of bone resorption markers after overnight fast | High |
Exercise | Intense exercise can decrease bone resorption and increase bone formation markers | Ask patient to refrain from intense exercise the day prior to blood sampling | Low |
Alcohol intake | Alcohol consumption decreases BTMs | Ask patient to refrain from excessive alcohol intake the day prior to blood sampling | Low |
Seasonal | Higher levels of BTMs in winter | In research, take samples in the same season or adjust for seasonal variation | Low |
Medications | |||
-oral GC | Rapid and dose-dependent decrease in bone formation markers, small effect on bone turnover markers | Consider dose of oral GC | High |
-aromatase inhibitors | Increase in BTMs | ||
Uncontrollable sources
| |||
Age | Postmenopausal women have higher BTMs than premenopausal women | Use age-based reference intervals | High |
Bed rest/immobility | Bone resorption markers increase and formation markers decrease | Consider different expected baseline level when evaluating BTMs | High |
Ethnicity | Small differences. Lower osteocalcin in African Americans vs. Caucasians | Unclear if different reference intervals are needed for different ethnicities | Low |
Fracture | BTMs increase after fracture, with maximum effect 2–12 weeks, but remains elevated up to 52 weeks | Limits evaluation in patients with recent fracture | High |
Menopause | BTMs increase at the time of the final menstrual period | Use reference intervals considering menopausal status | Moderate |
Current Recommendations of Use of Bone Turnover Markers in Clinical Guidelines
Aim
Methods
Results and Discussion
Preferred Bone Markers
The Role of Bone Turnover Markers in the Diagnosis of Osteoporosis and Patient Evaluation
Predicting Bone Loss Using Bone Turnover Markers
The Role of Bone Turnover Markers in Fracture Risk Prediction
The Use of Bone Turnover Markers in the Monitoring of Osteoporosis Treatment
Bisphosphonates
Denosumab
Anabolic Treatment
Conclusion
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The bone formation marker serum PINP and resorption marker serum βCTX-I are the preferred markers for evaluating bone turnover in the clinical setting.
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Bone turnover markers cannot be used to diagnose osteoporosis but can be of value in patient evaluation and can improve the ability to detect some causes of secondary osteoporosis.
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Serum βCTX-I and PINP correlate only moderately with bone loss in postmenopausal women and with osteoporosis medication-induced gains in BMD. Therefore, the use of bone turnover markers cannot be recommended to monitor osteoporosis treatment effect in individual patients.
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Adding data on serum βCTX-I and PINP levels in postmenopausal women can only improve fracture risk prediction slightly in addition to clinical risk factors and BMD and therefore has limited value.
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Bisphosphonates are the most commonly used osteoporosis medications, but adherence to oral bisphosphonates falls below 50% within the first year of treatment. Monitoring PINP and βCTX-I is effective in monitoring treatment adherence and can be defined as the sufficient suppression of these markers (by more than the LSC or to the lower half of the reference interval for young and healthy premenopausal women).