Bone-specific alkaline phosphatase as a marker of bone formation: Clinical and imaging correlates

Abstract

Bone-specific alkaline phosphatase (BSAP) is a biochemical marker of bone formation, reflecting osteoblast function and bone turnover. Unlike bone mass and structure measurements using dual-energy X-ray absorptiometry or high-resolution peripheral quantitative computed tomography, BSAP does not directly measure bone mass or microarchitecture but provides dynamic information on bone metabolism. BSAP has high specificity for bone formation with low biological variability and consistent levels across many clinical conditions, making it a reliable biochemical indicator of bone turnover, especially early response to anabolic treatment and in high-turnover bone conditions. Biologically, BSAP is synthesized by osteoblasts and is important in matrix maturation and mineralisation. In clinical practice, BSAP increases with anabolic treatment, often before changes in bone density, and is thus a predictor of early treatment response. Low levels of BSAP are found in conditions with delayed fracture healing, such as hypophosphatasia, and high levels are found in high-turnover conditions such as Paget’s disease. BSAP also has a role in conditions such as chronic kidney disease, where it can discriminate between states of bone turnover. However, its use is hampered by variability between laboratories, the absence of reference ranges, and the lack of normative data in different populations. Novel methods combining BSAP with innovative imaging techniques have the potential to improve personalised diagnosis, but need further research. This review highlights the potential of BSAP as an adjunct biomarker in use in early diagnosis, monitoring therapeutic intervention and overall assessment of bone metabolism for clinical decision making in metabolic bone diseases in conjunction with imaging.

Keywords: Bone-specific alkaline phosphatase; Osteoblast; Wnt/β-catenin; Skeletal metabolism; Bone formation

Core Tip: Bone-specific alkaline phosphatase (BSAP) is a good indicator of osteoblastic bone formation, released by osteoblasts as the matrix matures and becomes mineralized. In contrast to imaging, BSAP reflects metabolic activity, increasing early with anabolic therapies and helping to differentiate bone disorders, including Paget’s disease, hypophosphatasia and chronic kidney disease-related bone disease. However, due to the difficulties in standardization and in having norm values, BSAP’s combination with imaging and artificial intelligence models holds the promise of a more accurate and personalized approach to skeletal health.