Abstract
ABSTRACTInfants and children with hypophosphatasia (HPP) treated with asfotase alfa show improvement in bone mineralization and motor function, but it is unclear whether the medication can affect fracture healing in adult HPP patients. We present the course of fracture healing in two adults with HPP on enzyme replacement. Case 1 is a 41‐year‐old female with infantile‐onset HPP who was wheelchair‐bound due to a nonhealing tibial fragility fracture sustained 3 years before and also had nonhealing femoral pseudofracture sustained 17 years before starting asfotase alfa therapy in December 2015. One month after medication initiation, she underwent elective osteotomy of tibia and fibula with intramedullary nail fixation. After 3 months of enzyme replacement, she was full weight‐bearing and radiographs demonstrated callus formation at osteotomy sites, and at 11 months of therapy, radiographs showed union of the osteotomies. By 11 months of asfotase alfa therapy, there was near resolution of the femoral pseudofracture without interval surgery at this site. Case 2 is a 61‐year‐old male who showed nonunion of a fragility fracture of the right femur 8 years prior, intramedullary nail fixation 6 years prior, and stress fracture of the left femoral diaphysis sustained 1 year before starting asfotase alfa in October 2015. A trial of teriparatide was unsuccessful in healing of these fractures. On asfotase alfa, radiographs revealed interval healing of the left femur fracture after 12 months and complete healing of the right femur fracture and near resolution of the left femur fracture after 16 months of medical therapy. These two adult patients with HPP showed significant clinical and radiographic improvements in a total of four recalcitrant fractures on enzyme replacement therapy with asfotase alfa. © 2018 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
Highlights
Hypophosphatasia (HPP), known as Rathbun disease, is a rare, heritable inborn error of metabolism that has both autosomal dominant and recessive inheritance patterns due to loss-of-function mutations in the alkaline phosphatase gene (ALPL) located on the short arm of chromosome 1, which encodes the tissue nonspecific isozyme of alkaline phosphatase (TNSALP).(1–4) Clinical features of HPP include low serum alkaline phosphatase (ALP) activity, defective mineralization of bone, and elevated levels of ALP substrates such as pyridoxal-5-phosphate
We report two adult patients with HPP who started asfotase alfa therapy with resulting healing of a total of four fractures
Radiographs showed tibial bone healing in Case 1 at a rate just slightly slower than the average range observed in normal patients, who are expected to show some callus formation after tibial osteotomy by 4 to 6 weeks and complete fracture healing by 5 to 8 months
Summary
Hypophosphatasia (HPP), known as Rathbun disease, is a rare, heritable inborn error of metabolism that has both autosomal dominant and recessive inheritance patterns due to loss-of-function mutations in the alkaline phosphatase gene (ALPL) located on the short arm of chromosome 1, which encodes the tissue nonspecific isozyme of alkaline phosphatase (TNSALP).(1–4) Clinical features of HPP include low serum alkaline phosphatase (ALP) activity, defective mineralization of bone, and elevated levels of ALP substrates such as pyridoxal-5-phosphate (vitamin B6). We present two cases of adults with HPP who initiated asfotase alfa therapy, suggesting that may aid in fracture healing. Serial radiographs after the procedure demonstrated callus formation by 1 month postoperatively (2 months after initiating enzyme replacement therapy; Fig. 1B).
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