Fracture Healing in Two Adult Patients With Hypophosphatasia After Asfotase Alfa Therapy

Abstract

Infants 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.

Outcome of Teriparatide Treatment on Fracture Healing Complications and Symptomatic Bone Marrow Edema in Four Adult Patients With Hypophosphatasia

“…In pediatric patients, treatment with teriparatide is generally not recommended because the development of osteosarcoma during the rapid phase of longitudinal skeletal growth has been found in rats . In younger HPP patients, temporary AA treatment might be considered for persistent symptomatic BME as it was recently found that AA shows good effects on fracture healing in 2 adult HPP patients . Yet, there are no data available so far to draw any conclusions on the effects of teriparatide and AA on BME in HPP patients.…”

“…(46) In younger HPP patients, temporary AA treatment might be considered for persistent symptomatic BME as it was recently found that AA shows good effects on fracture healing in 2 adult HPP patients. (47) Yet, there are no data available so far to draw any conclusions on the effects of teriparatide and AA on BME in HPP patients.…”

Bisphosphonate Use and Fractures in Adults with Hypophosphatasia

“…In HPP, teriparatide's effects are also short-lived. (15) Klidaras and colleagues used short-term treatment with asfotase alfa, the novel enzyme replacement therapy approved for infantile, childhood and juvenile HPP, in 2 adult subjects with bi-allelic mutations, with good effect on fracture healing, (23) but this treatment is unlikely to be widely available for adults. (34) There is clearly still much to learn about adult HPP, in particular how to manage the frequently encountered patients with osteoporosis alongside mild or asymptomatic HPP with a single ALPL mutation.…”

“…Table summarizes data from published case reports and series that have described femoral fractures in adults with HPP confirmed by genetic analysis. The Table also includes data on 3 patients who had multiple fractures (but not including a femoral fracture) . Fifteen of the 34 subjects had been exposed to bisphosphonates.…”

“…The Table also includes data on 3 patients who had multiple fractures (but not including a femoral fracture). (3)(4)(5)(6)(7)(8)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24) Fifteen of the 34 subjects had been ; PLPD = premature loss of primary dentition; NS = not stated. exposed to bisphosphonates.…”