Longitudinal assessment of physical function in adults with X-linked hypophosphatemia following initiation of burosumab therapy.

Unlabelled: We assessed multiple components of muscle function in ten adults with X-linked hypophosphatemia (XLH) receiving burosumab treatment. Lower limb power (+ 9%), short physical performance battery (SPPB) score (+ 1.2 points), and physical activity (+ 65%) increased following 6 months of treatment, and hand grip increased (+ 10%) between 6 and 12 months of treatment.

Purpose: X-linked hypophosphatemia (XLH) is a rare genetic disorder of phosphate metabolism. Burosumab is a monoclonal antibody treatment shown to improve phosphate homeostasis and improve symptoms as well as fracture healing when used as a therapy for XLH in adults. However, little is known about its effects on the large deficits in multiple components of physical function previously reported in XLH.

Methods: Ten adults (6 females, age 41.1 ± 15.7 y) were recruited from specialist centres in London and Bristol. During clinical visits for initial burosumab treatment and at 6-month and 12-month follow-up, physical function, and physical activity (PA) assessments were performed. In detail, lower limb power was assessed by mechanography via a countermovement jump, mobility by short physical performance battery (SPPB), functional capacity by 6-min walk test (6MWT), upper limb strength by hand grip dynamometry, and PA via an International Physical Activity Questionnaire (IPAQ). Differences between baseline and 6-month follow-up, and in a subset of 5 patients between 6- and 12-month follow-up, were assessed.

Results: Lower limb power increased by 9% (P = 0.049) from baseline to 6 months, as did SPPB score (+ 1.2 points, P = 0.033) and total PA (+ 65%, P = 0.046) although hand grip and 6MWT did not differ. Only for hand grip was a significant improvement (+ 10%, P = 0.023) seen between 6 and 12 months.

Conclusions: Burosumab treatment is associated with improved lower limb function and mobility at 6 months, with improvement in hand grip strength at 12 months. Future studies should explore the underlying mechanisms and describe on function and other patient outcomes.