From the Guidelines
Bone turnover markers in Chronic Kidney Disease (CKD) include serum PTH and bone-specific alkaline phosphatase, which can be used to evaluate bone disease because markedly high or low values predict underlying bone turnover. These markers are essential in assessing bone metabolism abnormalities in CKD patients, particularly in those with evidence of CKD-Mineral and Bone Disorder (CKD-MBD) and/or risk factors for osteoporosis 1. Key markers include:
- Serum PTH
- Bone-specific alkaline phosphatase These markers help guide treatment decisions and are crucial in managing mineral bone disorder in CKD. It is also reasonable to perform a bone biopsy if knowledge of the type of renal osteodystrophy will impact treatment decisions, although this is not always necessary 1. In contrast, measurements of bone-derived turnover markers of collagen synthesis and breakdown are not recommended for routine use in CKD patients 1. Regular monitoring of serum PTH and bone-specific alkaline phosphatase can help maintain bone health while preventing vascular calcification, which contributes significantly to cardiovascular morbidity in CKD patients. The goal of using these markers is to assess fracture risk and guide treatment decisions regarding phosphate binders, vitamin D analogs, calcimimetics, and other interventions to manage CKD-MBD 1.
From the Research
Markers of Bone Turnover in Chronic Kidney Disease (CKD)
- Bone alkaline phosphatase (ALP) is a marker of bone turnover that reflects bone histomorphometry and predicts outcomes in hemodialysis patients 2
- Bone-specific alkaline phosphatase is associated with mortality and fracture rate in CKD subjects and is now available on several automated analyzers 3
- Parathyroid hormone (PTH) is considered the most sensitive marker of bone turnover, but it has many pitfalls in measurement 2
- Tartrate-resistant acid phosphatase 5b is a resorption marker that is under development for automation 3
- Intact procollagen type N-terminal propeptide of type I collagen, bone ALP, and tartrate-resistant acid phosphatase 5b are used in diagnosing renal osteodystrophy, predicting fractures, and guiding treatment in patients with CKD 4
- N-terminal midfragment osteocalcin (N-MID OC), β-isomerized C-terminal telopeptides (β-CTX), and total procollagen type 1 amino-terminal propeptide (tPINP) are bone turnover markers that are associated with parathyroid hormone (PTH) and other clinical characteristics of CKD 5
Bone Turnover Markers and Their Relationship with PTH
- The levels of bone turnover markers, including N-MID OC, β-CTX, and tPINP, are significantly higher in patients with advanced CKD stages compared to early disease stages 5
- PTH level is independently and positively associated with the bone turnover marker levels in patients with CKD 5
- CKD patients with secondary hyperparathyroidism (SHPT) have higher β-CTX and N-MID OC levels than patients with non-SHPT 5
Clinical Utility of Bone Turnover Markers
- Bone turnover markers assist in fracture risk prediction, management, and monitoring of osteoporosis in patients with CKD 3
- Appropriate use of bone turnover markers is vital in the decision to commence anti-resorptive agents and to monitor efficacy in order to avoid over suppression of bone turnover, which may lead to stress fractures 3
- Bone histomorphometry is the gold standard for renal osteodystrophy diagnosis, but it is labor-intensive and expensive, making bone turnover markers a useful alternative 4