Musculoskeletal abnormalities common in adult X-linked hypophosphatemia
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Abnormal bony projections in joint spaces and at attachments of tendons or ligaments were common among a small cohort of middle-aged adults with X-linked hypophosphatemia, progressively impairing joint range of motion, gait and physical function and warranting a longitudinal care plan, according to findings published in The Journal of Clinical Endocrinology & Metabolism.
“X-linked hypophosphatemia, or XLH, is a lifelong and progressive disorder, with pain and significant musculoskeletal comorbidities dominating the adult clinical picture,” Carolyn M. Macica, PhD, associate professor in the department of medical sciences at the Frank H. Netter, MD, School of Medicine at Quinnipiac University in North Haven, Connecticut, told Healio. “This study illustrates striking, and often bilateral, radiological similarities of the upper and lower body between participants. The findings similarly translate into a comparable impact on joint range of motion, function and ambulation consistent with a ‘waddling gait,’ a gait associated with limited hip and knee movement and with gait compensation to achieve foot clearance.”
Macica and colleagues analyzed data from nine adults aged 60 years or younger with a confirmed diagnosis of XLH and a self-reported musculoskeletal disability (five men; mean age, 54 years), as well as nine age-approximated and sex-matched controls. Those unable to walk independently were excluded. Participants underwent full-body radiologic imaging, goniometric range of motion measurements, general performance tests and kinematic gait analysis. Musculoskeletal function was also assessed by questionnaires.
Musculoskeletal comorbidities
The researchers observed enthesophytes, or abnormal bony projections at the attachment of a tendon or ligament, as well as degenerative arthritis and osteophytes, which are abnormal bony projections in joint spaces, that were “consistently bilateral and diffusely present” at the spine and synovial joints across participants. Predominance was at the weight-bearing joints.
Compared with controls, adults with XLH displayed decreased passive range of motion at the cervical spine, hip, knee and ankle. Those with XLH also exhibited increased step width, markedly increased lateral trunk sway, and physical restriction at the hip, knees and ankle joints.
“Patients with XLH should be managed by an interprofessional health care team that also includes physical therapy, occupational therapy and social work, with the goal of establishing a longitudinal plan of care that considers the physical manifestations of XLH across the life span,” Macica said. “In addition, newer therapies used during childhood need to be carefully monitored to determine their impact on the onset and progression of the musculoskeletal comorbidities as patients progress into adulthood.”
As Healio recently reported, conservative estimates suggest that the prevalence of XLH has more than tripled in the past 25 years in the United Kingdom, with researchers noting a concerning reduction in survival among patients with the disease. In main analyses, prevalence increased from 3.1 per million in 1995-1999 (95% CI, 1.5-6.7) to 14 per million in 2012-2016 (95% CI, 10.8-18.1). Using the conservative definition of XLH, corresponding estimates were 3 per million in 1995-1999 (95% CI, 1.4-6.5) to 8.1 per million in 2012-2016 (95% CI, 5.8-11.4). During follow-up, nine (7.4%) possible cases and 14 (2.9%) controls died (median age, 64 vs. 73 years, respectively).
Mechanisms unclear
Macica said basic and translational studies are needed to understand the cellular mechanisms that underlie the progressive physical nature of XLH and other phosphate-wasting disorders.
“We are expanding upon our prior published findings in a murine model of XLH and are conducting biomechanical studies to investigate the impact of therapy on the material and mechanical properties of the subchondral and fibrocartilaginous enthesis extracellular matrix and the articular cartilage extracellular matrix to better understand the role of phosphate-wasting on these properties as a contributing factor,” Macica said. “Even while the coincidental interpretation of these two interdependent data are difficult to dissect, the ultimate goal of these studies should be to diminish the burden of disease on this population.” – by Regina Schaffer
For more information:
Carolyn M. Macica, PhD, can be reached at Department of Medical Sciences, Frank H. Netter, MD, School of Medicine at Quinnipiac University, 275 Mount Carmel Ave., Hamden, CT 06518; email: carolyn.macica@quinnipiac.edu.
Disclosures: The authors report no relevant financial disclosures.
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