Bone Healing after Fracture and Osteotomy: Radiographic and Clinical Improvement after Asfotase Alfa Therapy for Hypophosphatasia

Presentation Number: SUN 302
Date of Presentation: April 2nd, 2017

Jacqueline Laura Severt*1, Steven Wai Ing2 and Jason Payne3
1The Ohio State University College of Medicine, Columbus, OH, 2Ohio State University Wexner Medical Center, Columbus, OH, 3The Ohio State University Wexner Medical Center, Columbus, OH

Abstract

Background:Hypophosphatasia (HPP) is an inborn error of metabolism caused by loss of function mutations in the ALPL gene, which encodes tissue nonspecific isozyme of alkaline phosphatase (TNSALP) and characterized by low serum alkaline phosphatase activity and defective mineralization of bone. In 10/2015 the FDA approved asfatase alfa, a bone-targeted human recombinant TNSALP replacement therapy in perinatal-, infantile- and juvenile-onset HPP. Asfotase alfa-treated HPP patients show improvement in bone mineralization and motor function, but it is unclear whether the medication can affect fracture healing.

Clinical Case:We present a 41-year-old female diagnosed with juvenile-onset HPP who started asfotase alfa therapy in 12/2015. At the time, she ambulated in a wheelchair due to a nonhealing fragility fracture of left tibia, which she sustained in 2012 upon stepping off a sidewalk curb. The fracture did not healed after initial treatment including casting, walking boot, cane, walker, and eventually by full non-weight bearing in a wheel chair. One month after medication initiation, she underwent elective osteotomy of left tibia and fibula with intramedullary nail fixation. She was able to regain independent ambulation after two months of physical therapy. Serial radiographs demonstrated callus formation by 5 months postoperatively and progressive bridging callus. By 11 months of uninterrupted asfotase alpha therapy, she has continued to ambulate independently with increasing walking tolerance up to 4 miles and radiographs showed union of left tibia and fibular osteotomies. Moreover, bilateral femoral shaft fractures sustained in 1998 from a fall down a flight of stairs, treated with intramedullary rod placement at the time, showed very little remodeling of the right femur fracture before starting asfotase alfa (16 years post-fracture). Radiographs showed marked healing with near resolution of the fracture line in 11/2016, coinciding with enzyme replacement therapy.

Conclusion:This case shows significant clinical and radiographic improvement in bone healing after fracture and osteotomy in an adult patient with juvenile-onset HPP on asfotase alpha therapy.

 

Disclosure: SWI: Consultant, Alexion. Nothing to Disclose: JLS, JP