Incidence of Complications in 25 Adult Patients With X-linked Hypophosphatemia

Abstract

Context Adults with X-linked hypophosphatemia (XLH) present complications other than osteomalacia. Objective To describe the incidence and severity of comorbidities in adults with XLH. Design Observational retrospective study. Patients A total of 25 adults with XLH with thorough investigations, including spinal computed tomography scans, X-rays of hip/knee joints and Achilles tendons, abdominal ultrasounds and audiograms. Main outcome measures The index of ossification of the anterior/posterior longitudinal ligament and yellow ligament (OA/OP/OY index) and the sum of OA/OP/OY index (OS index) were utilized to evaluate the severity of spinal ligament ossification. The Kellgren-Lawrence (KL) classification was adopted to evaluate the severity of the hip/knee osteophytes. Results The participants consisted of 13 male patients and 12 female patients from 21 families, with a median age of 43 (range, 18-72) years. In all, 20 patients (80%) showed spinal ligament ossification. The median OA/OP/OY/OS indices were 2 (0-22), 0 (0-15), 6 (0-13) and 12 (0-41), respectively. Hip/knee osteophytes were reported in 24 (96%) and 17 cases (68%). The median KL grade was 3 in the hip joint and 2 in the knee joint, and 18 cases (72%) developed enthesopathy in the Achilles tendon. Nephrocalcinosis and hearing impairment were observed in 18 (72%) and eight (32%) cases. Conclusion This study revealed a high prevalence and severity of ectopic ossification and disclosed the incidence of nephrocalcinosis and hearing impairment in adults with XLH. In cases with severe spinal ligament ossification or noticeable osteophytes around the hip/knee joints, undiagnosed XLH should be considered as a possible underlying condition.

Lower Limb Deformity and Gait Deviations Among Adolescents and Adults With X-Linked Hypophosphatemia

“…Although there are studies showing extremely high rates of lower limb deformity (12,13,25), there is currently no detailed measurement data regarding lower limb deformities among adults with XLH. Therefore, lower limb deformity among adults with XLH cannot be described and quantified.…”

Adult Presentation of X-Linked Hypophosphatemia

“…As stated above, some clinicians used to believe that treatment could be terminated after epiphyseal closure, probably due to the normal or relatively high bone mineral density detected in the majority of adults with mild XLH [3,4]. Normal-to-high BMD observed in patients with mild XLH might stem from suppressed osteoclastic function and is probably due to the excessive ossification caused for the same reason XLH patients tend to develop enthesopathy [4].…”

“…As stated above, some clinicians used to believe that treatment could be terminated after epiphyseal closure, probably due to the normal or relatively high bone mineral density detected in the majority of adults with mild XLH [3,4]. Normal-to-high BMD observed in patients with mild XLH might stem from suppressed osteoclastic function and is probably due to the excessive ossification caused for the same reason XLH patients tend to develop enthesopathy [4]. However, the risk of pseudofractures and fractures in weightbearing bones (costa, pelvis, femoral head subchondral fragility fracture, diaphyses of femur/tibia/fibula, calcaneus, and metatarsal) is usually not correlated with BMD and is strongly associated with low turnover of bone (e.g., also shown in other hypophosphatemic rickets/otsteomalacia, hypophosphatasia, osteogenesis imperfecta, osteopetrosis, and long-term use of anti-osteoclastic reagents), as accumulated micro bone cracks with delayed healing in weight-bearing bones eventually lead to pseudofracture and fracture.…”

“…In contrast, adult XLH patients present variable symptoms, including complications resulting from its treatment, such as enthesopathy, early osteoarthritis, secondary/tertiary hyperparathyroidism (SHPT/THPT), and chronic kidney disease (CKD), in addition to characteristic phenotypes for osteomalacia, such as pseudofracture and fracture in weight-bearing bones [1,2]. Some clinicians believe that treatment could be terminated after epiphyseal closure even among patients with severe XLH; however, adult XLH patients are currently recognized to be at risk of pseudofractures and fractures in weight-bearing bones due to low turnover even with normal to high bone mineral density (BMD) [3,4]. The mechanism for the development of enthesopathy in adults with XLH is unknown, and even among adult XLH patients treated with active vitamin D and phosphate supplementation or burosumab, remarkable enthesopathies sometimes develop, and these patients experience significant difficulty in activities of daily life (ADL) and lower quality of life (QOL) with nervous symptoms due to ossification of the posterior longitudinal ligament (OPLL), ossification of the ligamentum Endocrines 2022, 3 376 flavum (OLF), and other ossification-related nerve entrapment, or impingement syndromes in the hip, and the development of osteoarthritis [4].…”

The Metabolic Bone Disease X-linked Hypophosphatemia: Case Presentation, Pathophysiology and Pharmacology

“…Serum levels of parathyroid hormone (PTH) vary. Short stature in patients with XLH is due to chronic hypophosphatemia and, as adults, patients with XLH often experience joint pain and osteoarthritis from childhood skeletal deformities, fractures, enthesopathy, spinal stenosis, and hearing loss [6][7][8].…”