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Causes of high alkaline phosphatase include bone growth, healing fracture, acromegaly, osteogenic sarcoma, liver or bone metastases, leukemia, myelofibrosis, and rarely myeloma. Alkaline phosphatase is used as a tumor marker.^3,4

In rickets and osteomalacia, serum calcium and phosphorus are low to normal, and alkaline phosphatase may be normal or increased.

Hypervitaminosis D may cause elevations in alkaline phosphatase.

In Paget disease of bone there is often isolated elevation of serum alkaline phosphatase. Some of the highest levels of serum ALP are seen in Paget disease.

Hyperthyroidism, by its effects upon bone, may elevate alkaline phosphatase. There is evidence that thyroid hormone (T₃) acts to stimulate bone alkaline phosphatase activity through an osteoblast nuclear receptor-mediated process.⁵

Hyperparathyroidism, in some patients. Pseudohyperparathyroidism.

Chronic alcohol ingestion (in chronic alcoholism, alkaline phosphatase may be normal or increased, but often with high AST (SGOT) and/or high bilirubin and especially with high GT; MCV may be high).

Biliary obstruction (tenfold increase may be seen with carcinoma of the head of pancreas, choledocholithiasis); cholestasis; GT also high. Cholecystitis with cholangitis. (In most patients with cholecystitis and cholangitis who do not have a common duct stone, alkaline phosphatase is within normal limits or only slightly increased.) Sclerosing cholangitis (eg, with ulcerative colitis), although importantly, 3% of cases of symptomatic sclerosing cholangitis may have normal serum ALP.⁶ Endoscopic retrograde cholangiography might be considered then in patients with diseases known to be associated with primary sclerosing cholangitis and with appropriate symptomatology even though ALP level is normal. Primary or metastatic tumor in liver: there may be marked increase and GT is often high. Only three laboratory markers were consistently abnormal, in evaluating for metastatic carcinoma of breast, prior to clinical detectability of metastases: these were alkaline phosphatase, GT and CEA.⁴