What is bone-specific alkaline phosphatase (ALP) lab?

Bone-Specific Alkaline Phosphatase (B-ALP) Laboratory Test

Bone-specific alkaline phosphatase (B-ALP) is a serum biomarker that measures the activity or protein mass of the bone isoform of alkaline phosphatase, reflecting osteoblastic activity and bone formation rates. 1

What B-ALP Measures

B-ALP is an enzyme produced by osteoblasts during bone formation and remodeling. 1 The test specifically isolates the bone isoform from other alkaline phosphatase sources (liver, intestine, placenta) through:

• Immunoradiometric assays that measure protein mass using monoclonal antibodies raised against purified bone ALP 2, 3
• Immunocapture enzyme assays that measure enzymatic activity after immunoselection 3, 4

The bone isoform differs from liver and kidney ALP only through post-translational modification of carbohydrate side chains, despite being encoded by the same gene. 5

Clinical Applications

Detecting Bone Metastases in Cancer Patients

B-ALP serves as a sensitive predictor of bone metastases in patients with advanced malignancies. 1 In cancer patients:

• Early increases in serum B-ALP levels predict short skeletal-related event (SRE)-free survival and reduced overall survival in prostate cancer patients with bone metastases receiving zoledronic acid 1
• B-ALP combined with other markers (P1NP, tartrate-resistant acid phosphatase 5b) significantly predicts development of bone metastases 1
• Multiple clinical trials (BOLERO-2, Fizazi et al., Stopeck et al.) have used B-ALP as a biomarker measurement in breast and prostate cancer bone metastasis studies 1

Assessing Metabolic Bone Disease

B-ALP demonstrates superior sensitivity compared to total ALP for metabolic bone disorders:

• In postmenopausal women, B-ALP increases by 82% compared to premenopausal women, versus only 18% for total ALP 2
• Highest B-ALP values occur in Paget's disease, bone metastases, hyperparathyroidism, and maintenance hemodialysis patients 2
• B-ALP distinguishes high-turnover from low-turnover osteoporosis, showing significantly higher levels in high-turnover patients 2

Monitoring Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD)

B-ALP is more reliable than PTH alone for assessing bone turnover in CKD patients because inactive PTH fragments accumulate and cross-react with intact PTH assays. 6

• Measure B-ALP every 12 months in CKD stages G4-G5D, or more frequently if PTH is elevated 6
• B-ALP should be measured alongside serum calcium, phosphate, PTH, and 25(OH) vitamin D 6
• Elevated B-ALP predicts fracture risk in dialysis patients (hazard ratio 1.04-1.21) 6

Differentiating Elevated Total ALP Sources

When total ALP is elevated, B-ALP measurement clarifies whether the source is hepatobiliary or skeletal:

• Normal gamma-glutamyl transferase (GGT) with elevated total ALP suggests bone origin, making B-ALP measurement useful for confirmation 7, 6
• B-ALP is less useful when liver ALP is already elevated, as accurate measurement becomes difficult 7

Normal Values and Interpretation

• Healthy adults (mean age 29 years): 18.5 ± 4.1 U/L 3
• Premenopausal women (mean age 39 years): 20.3 ± 6.5 U/L 3
• Postmenopausal women (mean age 57 years): 31.1 ± 11.1 U/L 3
• B-ALP increases linearly with age in both sexes, with more pronounced age-related increases in women 2, 3

Assay Characteristics

Modern B-ALP assays demonstrate:

• Intra- and inter-assay coefficients of variation less than 4% 3
• Sensitivity of 0.7 U/L with linearity from 2 to 140 U/L 3
• Recovery of added B-ALP standard: 94-106% 3
• Correlation coefficient of 0.94 with polyacrylamide gel electrophoresis method 3
• Relative antibody activity: 100% with bone ALP, 8.7% with liver ALP, 0% with placental and intestinal ALP 3

Important Clinical Considerations

Bone markers including B-ALP vary according to circadian rhythms, with levels generally peaking in the morning, so timing of sample collection should be standardized. 6

B-ALP reflects whole-body bone turnover and does not provide information about specific lesion sites. 1 Changes in B-ALP levels are not disease-specific but reflect alterations in skeletal metabolism regardless of underlying cause. 1

Treatments like bisphosphonates and denosumab alter B-ALP levels despite underlying pathology—for example, alendronate produces a mean 34% decrease in B-ALP after 3-6 months of treatment. 7, 4