Acute severe hypercalcemia after traumatic fractures and immobilization in hypophosphatasia complicated by chronic renal failure

Michael P. Whyte, Rattana Leelawattana, William R. Reinus, Chang Yang, Steven Mumm, Deborah V. Novack

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Context: Hypophosphatasia (HPP) features deficient activity of the "tissue-nonspecific" isoenzyme of alkaline phosphatase (TNSALP) due to loss-of-function mutation(s) within the TNSALP gene. Consequently, inorganic pyrophosphate, a TNSALP substrate and inhibitor of mineralization, accumulates extracellularly. This can cause rickets or osteomalacia. Objective: We report a 55-year-old man with HPP and chronic renal failure (CRF) requiring hemodialysiswhodeveloped severe hypercalcemia acutely after traumatic fracturesandimmobilization. He manifested HPP in childhood and in middle age received hemodialysis for CRF attributed to hypertension and anti-inflammatory medication. He took2gof calcium carbonate orally each day to bind dietary phosphorus, but never aluminum hydroxide or any form of vitamin D. Pretrauma serum levels of calcium spanned 8.4-10.7 mg/dL (normal [Nl], 8.6 -10.3), inorganic phosphate 5.8-6.4 mg/dL (Nl, 2.5- 4.5), and PTH 63-75 pg/mL (Nl, 10-55). Results: Rapid succession falls fractured multiple major bones. Six hours later, he became confused. Serum calcium was 14.9 mg/dL, ionized calcium was 7.4 mg/dL (Nl, 4.5-5.1), and PTH was 16 pg/mL. Hemodialysis quickly corrected his hypercalcemia and confusion. Low serum alkaline phosphatase persisted, and follow-up skeletal histopathology showed that his osteomalacia was severe. Conclusion: Hemodialysis does not heal the skeletal disease of HPP. During sudden fracture immobilization in HPP, sufficient calcium can emerge from bone, perhaps from a rapidly exchangeable calcium pool, to cause acute severe hypercalcemia if the kidneys cannot compensate for the mineral efflux. Hence, we worry that acute hypercalcemia might accompany sudden immobilization in CRF patients without HPP if they have adynamic bone disease.

Original languageEnglish
Pages (from-to)4606-4612
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Issue number12
StatePublished - Dec 2013


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