Bone turnover markers to monitor oral bisphosphonate therapy

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TABLE 1

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

Markers of bone formation	Measured in	Diurnal variation	Renal function variation	Pros	Cons
Bone-specific alkaline phosphatase (BSAP)	Serum	No	No	No 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)	Serum	Yes	Yes	Well 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)	Serum	Yes	Renal variation unknown		Less studied than other bone formation markers
Osteocalcin	Serum and urine	Yes	Yes	Correlates well with bone turnover	Less 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 resorption	Measured in	Diurnal variation	Renal function variation	Pros	Cons
C-terminal telopeptide of type I collagen (CTX)	Serum and urine	Yes	Yes	Stable 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)	Yes	Yes	Minimal postprandial variability	Fasting measurements recommended Impacted by hepatic function
Pyridinoline and deoxypyridinoline	Urine (24-hour urine collection or second morning void with creatinine correction)	Yes	Yes	Can be renally adjusted	Impacted by hepatic function
Tartrate-resistant acid phosphatase 5b	Serum	Yes	No	No change with renal function	Predominately from but not exclusive to bone Unstable at room temperature Increases immediately after exercise

TABLE 2

An 82-year-old postmenopausal woman treated with oral alendronate for osteoporosis

Background: Left proximal humerus fracture 4 years prior due to a fall from standing height during a syncopal event Left femural neck T-score of −2.5 on dual-energy x-ray absorptiometry No history of celiac disease, paraproteinemia, or bariatric surgery Renal function and vitamin D levels were normal Patient concerned about falls and balance; another fall 6 months prior without fracture. After ruling out secondary causes of osteoporosis, oral alendronate 70 mg once weekly was initiated.
Bone mineral density and bone turnover markers:
	Before treatment	At 3 months	At 1 year
T-scores:
Lumbar spine	−1.6		−1.7
Left femoral neck	−2.5		−2.4
Right femoral neck	−2.2		−2.1
Bone turnover marker: C-terminal telopeptide of type I collagen	520 pg/mL	177 pg/mL (66% reduction from baseline)	273 pg/mL (48% reduction from baseline)

TABLE 3

A 63-year-old postmenopausal woman treated with oral alendronate for osteoporosis

Background: History of breast cancer treated with lumpectomy, radiation therapy, and 5 years of tamoxifen Outside DXA scans showed a progressive decline in her lumbar spine T-score from −3.1 to −3.3 Femoral neck bone density was stable Past medical history was otherwise unremarkable No history of lactose intolerance, celiac disease, or chronic glucocorticoid use She did not take calcium supplements, but took over-the-counter vitamin D No history of antifracture therapy. The patient was prescribed oral alendronate 70 mg once weekly.
Bone mineral density and bone turnover markers:
	Before treatment	3 months	1 year
T-scores:
Lumbar spine	NA	−2.6
Left femoral neck	NA	−1.5
Right femoral neck	NA	−1.5
Bone turnover marker: C-terminal telopeptide of type I collagen	653 pg/mL	361 pg/mL (45% reduction from baseline)	188 pg/mL (72% reduction from baseline)