Magnetic Resonance Imaging Features as Surrogate Markers of X-Linked Hypophosphatemic Rickets Activity

Abstract

Objective: X-linked hypophosphatemic rickets (XLH) is the most common form of inheritable rickets. Rickets treatment is monitored by assessing alkaline phosphatase (ALP) levels, clinical features, and radiographs. Our objectives were to describe the magnetic resonance imaging (MRI) features of XLH and to assess correlations with disease activity. Study Design: Twenty-seven XLH patients (median age 9.2 years) were included in this prospective single-center observational study. XLH activity was assessed using height, leg bowing, dental abscess history, and serum ALP levels. We looked for correlations between MRI features and markers of disease activity. Results: On MRI, the median maximum width of the physis was 5.6 mm (range 4.8-7.8; normal <1.5), being >1.5 mm in all of the patients. The appearance of the zone of provisional calcification was abnormal on 21 MRI images (78%), Harris lines were present on 24 (89%), and bone marrow signal abnormalities were present on 16 (59%). ALP levels correlated with the maximum physeal widening and with the transverse extent of the widening. Conclusions: MRI of the knee provides precise rickets patterns that are correlated with ALP, an established biochemical marker of the disease, avoiding X-ray exposure and providing surrogate quantitative markers of disease activity.

Hypophosphatemic Rickets

“…Figure 7 shows the differences between radiographic bone features between a patient with XLH and one with no disease. In individuals without disease, the physis appears as a flat disc between the epiphysis and metaphysis, while the normal zone of provisional calcification (ZPC) is visualized as a continuous, thin band (Lempicki et al, 2017). In the XLH patient, the ZPC is undefined and the physis is widened.…”

“…Both forms of radiographic imaging expose patients to radiation that can lead to tissue damage and increase the patient's risk to cancer (Carpenter et al, 2011). This is especially true in children who are more sensitive to radiation than adults, especially considering that radiographs are often performed on a regular basis for patients with hypophosphatemic rickets (Lempicki et al, 2017). MRI is a form of imaging that uses strong magnetic fields and radio waves to produce detailed images of the body.…”

“…In order to be eligible for participation, patients were required to: 1) be under the age of 18 years; 2) be monitored at the same clinic (French Reference Center for Rare Disorders of Calcium and Phosphate Metabolism); 3) present with hypophosphatemic rickets due to XLH with a confirmed PHEX mutation; 4) currently receiving standard of care treatment; 5) consent to an MRI scan of the distal left femur (or, if not possible, the distal right femur); and 6) not require sedation for the MRI scan. Twenty-four of the 27 patients had a frontal radiograph of the distal left femur within 1 year of their MRI (Lempicki et al, 2017). The frontal radiographs were part of the participants' standard follow up for XLH.…”

“…Results seen in Figure 8 display the comparison of X-ray and MRI radiographs in patients with XLH. X-ray and MRI examples of patients with XLH (a 13-year-old and 11-year-old with XLH) show ill-defined ZPC and physis lines in the X-rays, whereas the MRI images enables precise analysis of the region due to presence of image hyperintensity (Lempicki et al, 2017).…”

“…(d) In the same 11-year-old boy, note the abnormal epiphyseal abnormalities (thick arrows) and metaphyseal Harris lines (arrowhead), which are lines of increased bone density caused by bone-growth arrest. (e) and (f) indicate medial femoral osteochondritis (arrows) in an asymptomatic 13-year-old girl with XLH who displays round-shaped abnormal hyperintensity in the subchondral area (Lempicki et al, 2017).…”