The use of bone turnover markers in chronic kidney disease‐mineral and bone disorders

Abstract

ABSTRACT:Bone turnover markers assist in fracture risk prediction, management and monitoring of osteoporosis in patients without chronic kidney disease (CKD). The use in CKD-mineral bone disorder (MBD) has been limited as many of these markers and breakdown products are renally excreted, including the most commonly used and well standardized procollagen type I N propeptide and C-terminal cross-linking telopeptide of type I collagen. Of the markers unaffected by renal function, bone specific alkaline phosphatase is associated with mortality and fracture rate in CKD subjects and is now available on several automated analysers. When used in combination with PTH, bone specific alkaline phosphatase as a bone formation marker correlated well with bone biopsy histomorphometry in predicting adynamic bone disease. Tartrate-resistant acid phosphatase 5b is a resorption marker that is under development for automation. Both high and low bone turnover in CKD-MBD patients are associated with increased fracture and mortality risk. Bone biopsy as the gold standard to differentiate between adynamic bone disease and osteitis fibrosa is limited by availability and cost. 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. Further efforts are required to develop markers unaffected by renal function with standardized cut-off values and fracture as well as vascular calcification end-points.

Emerging Role of Vitamins D and K in Modulating Uremic Vascular Calcification: The Aspect of Passive Calcification

“…In CKD patients, CKD-MBD caused by high or low bone turnover disease impaired the normal bone remodeling process. In high bone turnover diseases, secondary hyperparathyroidism activates receptor activator of nuclear factor kappa-Β ligand (RANKL) signaling as well as osteoclast activity to increase bone resorption [80]. In low bone turnover diseases, inert osteoblast activity decreases the utility of calcium and phosphate, and subsequently decreases the extraosseous calcium-phosphate deposits [81].…”

Stabilization of serum alkaline phosphatase in hemodialysis patients by implementation of local chronic kidney disease-mineral bone disorder management strategy: A quality improvement study

“…However, the recently revised 2017 KDIGO CKD-MBD guidelines recommend monitoring total or bone-specific serum AP activity in patients with advanced CKD [ 2 ]. Although bone formation rate was better correlated with plasma bone-specific AP levels than with either plasma total AP or intact PTH concentrations [ 13 , 14 ], serum total AP was used because of its feasibility for routine monitoring in patients on MHD. A large cohort study showed that increased serum total AP > 120 U/L was associated with mortality among patients on MHD [ 15 ].…”

Position Statement on the Use of Bone Turnover Markers for Osteoporosis Treatment

“…The combination of osteocalcin (<41 ng/L) and BSALP (<23 U/L) improved the positive predictive value for diagnosing adynamic bone disease to 77% in a CKD-5 cohort. [66]…”