Musculoskeletal Features in Adults With X-linked Hypophosphatemia: An Analysis of Clinical Trial and Survey Data

Abstract

Purpose To describe the burden of musculoskeletal features and associated surgeries across the lifespan of adults with X-linked hypophosphatemia (XLH). Methods Three groups of adults were analyzed: subjects of a clinical trial, participants in an online survey, and a subgroup of the online survey participants considered comparable to the clinical trial subjects (according to Brief Pain Inventory worst pain scores of ≥4). In each group, the adults were categorized by age: 18–29, 30–39, 40–49, 50–59, and ≥60 years old. Rates of five prespecified musculoskeletal features and associated surgeries were investigated across these age bands for the three groups. Results Data from 336 adults were analyzed. In all three groups, 43–47% had a history of fracture, with the proportions increasing with age. The overall prevalence of osteoarthritis was >50% in all three groups, with a rate of 23–37% in the 18–29-year-old group, increasing with age. Similar patterns were observed for osteophytes and enthesopathy. Hip and knee arthroplasty was reported even in adults in their 30s. Spinal stenosis was present at a low prevalence, increasing with age. The proportion of adults with ≥2 musculoskeletal features was 59.1%, 55.0%, and 61.3% in the clinical trial group, survey group, and survey pain subgroup, respectively. Conclusions This analysis confirmed high rates of multiple musculoskeletal features beginning as early as age 20 years among adults with XLH and gradually accumulating with age.

Approach to Hypophosphatemic Rickets

“…Adults with XLH also have a substantial burden of disease, related to ongoing effects of hypophosphatemia, osteomalacia, enthesopathy, osteoarthritis, bone pain, and fractures ( 39 ). A 24-week, randomized, double-blind, placebo-controlled trial in adults with XLH and chronic pain demonstrated improvements in serum phosphorus, while bone turnover markers increased, with improvements in pain, stiffness, physical function, and mobility ( 42 , 118 ).…”

“…While enthesopathy and osteoarthritis are often debilitating features in adults with XLH, there are no data that conventional therapy or burosumab prevents or improves these in humans or mouse models ( 39 , 119-121 ). The burosumab trials could not evaluate changes in structural abnormalities of osteophytes and enthesopathy, since enthesopathy and osteoarthritis develop over many years.…”

“…Chiari malformation and craniosynostosis also may occur in XLH ( 37 , 38 ). Importantly, XLH causes lifelong hypophosphatemia, and adults may have muscle weakness, bone pain from osteomalacia, gait abnormalities from bone deformities, osteoarthritis, and enthesopathy ( 39 ). Bone density is typically not low in patients with XLH ( 40 ).…”

“…However, osteomalacic pseudofractures are common, especially in adults with XLH. Patients with XLH often are unaware of their existing or past pseudofractures or of the difference between fractures, pseudofractures, or stress fractures, and more recent articles have tended to report these grouped together without distinguishing them, indicating high rates of “fractures/pseudofractures” in XLH, based on skeletal surveys ( 42 ) or on survey self-reporting ( 39 , 43 ).…”

X-Linked Hypophosphatemia Transition and Team Management

“…Since XLH presents with a number of symptoms and signs in addition to the musculoskeletal system, the expert in metabolic bone diseases needs to be at the center of patient care and coordinate and collaborate with other professionals. Evidence for the disease burden of XLH during adulthood, as early as 20 years of age, is accumulating [2,[18][19][20][21][22][23][24]. In addition, a new therapy targeting FGF23 has been developed and applied to clinical practice for children and adults [25][26][27].…”