Bone-Specific Alkaline Phosphatase in Patients Who Have Undergone the Fontan Operation

Abstract

Bone-specific alkaline phosphatase (BALP) is produced by osteoblasts. A recent series noted a positive association between cardiac index (CI) and BALP in patients with Fontan circulation. CI is low at baseline in these patients, and small decreases in CI may result in diverting of blood away from bone. We prospectively enrolled 15 patients (males ≤ 14 yo, females ≤ 12 yo) who had previously undergone Fontan operation and were undergoing cardiac catheterization. Serum BALP was measured at catheterization, and analysis performed to evaluate association between age-/gender-specific BALP z-score and CI as well as other patient variables. The median age at catheterization was 5.6 years (3.1-13.1), and time from Fontan was 1.5 years (0.1-12.1). The median superior vena cava saturation (SVC) was 65 % (52-74), median average between SVC and inferior vena cava (IVC) saturations was 62.5 % (51-70), and median CI was 3.8 L/min/m(2) (2.0-8.4). The median BALP was 65 IU/L and BALP z-score was -2.1 (-3.2 to 0.9). BALP z-score was not associated with CI (ρ = -0.1, p = 0.7), but a positive correlation was noted with the average of SVC and IVC saturation (ρ = 0.5, p = 0.052) and with SVC saturation (ρ = 0.4, p = 0.07), both nearly reaching statistical significance. In our cohort of children with Fontan circulation undergoing catheterization, BALP z-score was not associated with CI, but an association with estimates of mixed venous saturation was noted that nearly reached statistical significance. We hypothesize that BALP is a marker of oxygen delivery in those with Fontan circulation and may represent a valuable biomarker in this population.

Fontan Circulation Associated Organ Abnormalities Beyond the Heart, Lungs, Liver, and Gut: A Systematic Review

“…Hypoxia may increase osteoclast activity and bone resorption ( 39 , 99 ). Reduced circulation of bone marrow, in the context of reduced cardiac output, may impair bone formation ( 103 ). Disturbances in the calcium-vitamin D-parathyroid hormone axis have been reported in Fontan patients ( 68 , 99 , 100 , 102 ).…”

“…Serum biomarkers related to bone development have been studied in Fontan patients. Bone Specific Alkaline Phosphatase (BALP) serum levels, a biomarker produced by osteoblasts, are reduced in Fontan patients compared to controls ( 103 ). Osteopontin, a component of the bone matrix, is decreased in the serum of Fontan patients compared to controls ( 102 ).…”

“…No studies directly related BALP or osteopontin to BMD or clinical outcomes. The clinical implications of these biomarkers in Fontan patients are currently unclear, but they might represent a biomarker of bone metabolism that is easily obtained in clinical practice ( 103 ).…”

“…Decreased cardiac output may lead to decreased perfusion of organs. This has been implicated as a cause of among others renal dysfunction ( 41 , 48 ), decreased BMD ( 103 ), and decreased brain volumes ( 11 , 19 ).…”