Common bone turnover markers, their properties, and pros and cons

Markers of bone formationMeasured inDiurnal variationRenal function variationProsCons
Bone-specific alkaline phosphatase (BSAP)SerumNoNoNo postprandial changes
Stable sample due to half-life of 1–2 days
Widely available
Roughly 20% cross-reaction with other types of alkaline phosphatase
N-terminal propeptide of type I procollagen (PINP)SerumYesYesWell studied in clinical trials
Relatively low intra-individual variability
PINP measures response to therapy more effectively than BSAP
Hepatic function can affect levels depending on the assay and form of propeptide being measured
Increased in patients on hemodialysis
Procollagen type I carboxyterminal propeptide (PICP)SerumYesRenal variation unknownLess studied than other bone formation markers
OsteocalcinSerum and urineYesYesCorrelates well with bone turnoverLess stable; must process within hours
Production is dependent upon vitamin K and can decrease in response to vitamin K antagonists (eg, warfarin)
Markers of bone resorptionMeasured inDiurnal variationRenal function variationProsCons
C-terminal telopeptide of type I collagen (CTX)Serum and urineYesYesStable biomarker
Rapidly decreases with antiresorptive therapy
Postprandial variability
Can be impacted by hepatic function
N-terminal telopeptide of type I collagen (NTX)Serum and urine (24-hour urine collection or second morning void)YesYesMinimal postprandial variabilityFasting measurements recommended
Impacted by hepatic function
Pyridinoline and deoxypyridinolineUrine (24-hour urine collection or second morning void with creatinine correction)YesYesCan be renally adjustedImpacted by hepatic function
Tartrate-resistant acid phosphatase 5bSerumYesNoNo change with renal functionPredominately from but not exclusive to bone
Unstable at room temperature
Increases immediately after exercise
  • Based on data from references 1820.