Bone scan findings of Paget's disease of bone in patients with VCP Multisystem Proteinopathy 1

Abstract

Multisystem Proteinopathy 1 (MSP1) disease is a rare genetic disorder caused by mutations in the Valosin-Containing Protein (VCP) gene with clinical features of inclusion body myopathy (IBM), frontotemporal dementia (FTD), and Paget's disease of bone (PDB). We performed bone scan imaging in twelve patients (6 females, 6 males) with confirmed VCP gene mutation six (50%) of which has myopathy alone, four (33%) with both PDB and myopathy, and two (15%) were presymptomatic carriers. We aim to characterize the PDB in diagnosed individuals, and potentially identify PDB in the myopathy and presymptomatic groups. Interestingly, two patients with previously undiagnosed PDB had positive diagnostic findings on the bone scan and subsequent radiograph imaging. Among the individuals with PDB, increased radiotracer uptake of the affected bones were of typical distribution as seen in conventional PDB and those reported in other MSP1 cohorts which are the thoracic spine and ribs (75%), pelvis (75%), shoulder (75%) and calvarium (15%). Overall, we show that technetium-99m bone scans done at regular intervals are a sensitive screening tool in patients with MSP1 associated VCP variants at risk for PDB. However, diagnostic confirmation should be coupled with clinical history, biochemical analysis, and skeletal radiographs to facilitate early treatment and prevention complications, acknowledging its limited specificity.

Figure 1

Whole body 99mTc-MDP bone Scan and Radiographic findings in patient 1 (ID 1). A 60-years-old female with back pain and leg pain, limb girdle distribution of myopathy and Paget disease revealed (a) increased uptake in the skull, thoracic and lumbar vertebrae on whole-body bone scan, increased uptake in the knees due to associated arthritis, (b) radiograph images reveal corresponding bone lesions of the skull bilaterally (blue arrows), (c) thoracic T10 vertebrae (orange arrow) and lumbar L3 vertebrae (yellow arrow).

Figure 2

Whole body 99mTc-MDP bone scan and multiple spot views images of patient 2 (ID 2). A 43-years-old male with inclusion body myopathy, and previously diagnosed Paget’s disease revealed positive tracer uptake in the spine (blue arrow), left iliac bone (orange arrow) and right ankle (green arrow).

Figure 3

Whole body 99mTc-MDP bone scan images and multiple spot views of patient 4. A 49-years-old male with inclusion body myopathy, and Paget’s disease revealed positive bone scan findings of the left mandible (blue arrow), left hemipelvis (green arrow), multiple levels of the thoracic and lumbar spine (purple arrow) and proximal left fibula (yellow arrow).

Figure 4

Whole body 99mTc-MDP bone scan and skull radiographs in two newly diagnosed PDB in myopathy only patients. (a) A 28-years-old female (ID 6) with increased uptake in the skull on the bone scan corresponding to a mixed lytic and sclerotic bone lesion in the left parietal calvarium on the AP and lateral views of the plain radiographs (purple arrows). (b) A 38-years-old female (ID 10) with increased uptake in the right ischium and acetabulum on whole-body bone scan (orange arrows).