OBJECTIVE:Hypophosphatasia (HPP) is a rare inherited metabolic bone disease from deficient activity of the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). Reportedly, teriparatide (parathyroid hormone 1-34) can benefit the adult form of HPP, including fracture healing. We studied 2 women with adult HPP given teriparatide and reviewed the reports of 6 additional patients.
METHODS:A 68-year-old black woman (patient 1) described low-trauma fractures and had subnormal serum alkaline phosphatase (ALP) activity. Biochemical findings were consistent with HPP. Mutation analysis revealed a heterozygous defect in exon 10 of TNSALP (ALPL). Teriparatide was injected daily for 2 years. Four years later, she fractured her right hip. Treatment was resumed for 8 months without further fractures. A 53-year-old white woman (patient 2) reported low-trauma fractures and had subnormal serum ALP. Mutation analysis revealed a heterozygous defect in exon 8 of TNSALP. She injected teriparatide daily for 2 years. One year later, bone mineral density (BMD) declined and treatment was resumed for 3 months. When she sustained a sacral fracture, teriparatide was administered for a further 18 months.
RESULTS:Patient 1's serum ALP increased while receiving teriparatide and returned to baseline after its discontinuation. BMD remained unchanged, but no fractures were sustained. Patient 2's serum ALP increased, but the improvement was not sustained. Femoral neck BMD increased significantly during the first cycle, declined significantly afterwards, and was regained during a second course of teriparatide.
CONCLUSION:Teriparatide shows some benefit for adult HPP.
ABBREVIATIONS:ALP = alkaline phosphatase BMD = bone mineral density BSAP = bone-specific alkaline phosphatase CTX = C-telopeptide DXA = dual-energy X-ray absorptiometry FN = femoral neck HPP = hypophosphatasia LS = lumbar spine PEA = phosphoethanolamine PLP = pyridoxal 5'-phosphate PTH = parathyroid hormone SQ = subcutaneous TNSALP = tissue-nonspecific isoenzyme of alkaline phosphatase TPTD = teriparatide.