Elevated ALP
- Liver (liver ALP): Cholestasis, cholecystitis, cholangitis, cirrhosis, primary biliary cholangitis, fatty liver, sarcoidosis, liver tumor, liver metastases, drug intoxication (Drugs: e.g. verapamil, carbamazepine, phenytoin, erythromycin, allopurinol, ranitidine)
- Bone disease (bone ALP): Pagets disease, osteosarcoma, bone metastases of prostatic cancer (High / very high ALP values), Other bone metastases, Renal osteodystrophy, Fractured bone
- Skeletal involvement of other primary diseases: Osteomalacia, rickets, vitamin D deficiency (moderate rise), Malignant tumors (ALP originating from tumor), Renal disease (secondary hyperparathyroidism), Primary hyperthyroidism
Example-1
82 year male with backache, alkaline phosphatase=430, serum parathyroid hormone=397, very low vitamin-D = less than 5. What is the possibilities?
Differential considerations:
- Secondary Hyperparathyroidism due to Vitamin D deficiency
- Very low vitamin D → poor calcium absorption.
- Hypocalcemia (not given here, but likely low/low-normal) stimulates parathyroid hormone (PTH).
- PTH rises → increases bone turnover → high ALP.
- Backache could be due to osteomalacia or bone demineralization.
- Primary Hyperparathyroidism (less likely here)
- Would expect high calcium, high PTH, variable vitamin D.
- ALP may rise if there is bone involvement.
- But in this case, vitamin D is severely deficient, making secondary hyperparathyroidism the more likely explanation.
- Osteomalacia due to Vitamin D deficiency
- Severe deficiency in elderly → defective bone mineralization → bone pain/backache.
- ALP elevated (marker of osteoblastic activity trying to repair bone).
- Secondary rise in PTH (secondary hyperparathyroidism).
- Other possibilities to keep in mind:
- Paget’s disease of bone (can raise ALP and cause back pain) → but PTH is usually not this high.
- Metastatic bone disease → backache + ALP rise, but doesn’t explain very high PTH and very low vitamin D.