Images below require Macromedia's Flash Player to view

Neuroradiology Case of the Week

Case 431

August 2009

Derek Lasher, Ashwani Sharma MD, P-L Westesson MD, PhD, DDS,
and Richard White, DO

Clinical Presentation: Clinical history is unknown.

Imaging Findings: See below

Diagnosis: Paget disease

Discussion: Paget’s disease was accurately documented in 1876 by Sir James Paget, when he presented five cases of what he called osteitis deformans to the Medical and Chirurgical Society of London [1]. These cases detailed an illness characterized by marked remodeling of the adult skeleton. Approximately 3-4% of the population over 40 years old and 10-11% of those over 80 years old are afflicted. Only 3% of all reported cases are under the age of 40 years. Males are found to have a higher incidence than females, with ratio estimates ranging from 3:2 to 4:1 [2,3]. Additionally, those of European decent, especially Great Britain, have an increased chance of developing Paget’s disease, whereas the illness is virtually nonexistent in those of African or Asian decent [4-6].
     Paget’s disease is most commonly found in the pelvis (30-75% of cases), spine (30-75%), skull (25-65%), and the proximal long bones (25-30%), but is liable to affect any bone, including sesamoid bones [1 6]. Likewise, Paget’s disease can be widespread, affecting the entire skeleton, or it can be isolated to a small number of bones.
     Pathology of the disease is divided into three stages, the lytic phase, the mixed phase, and the blastic phase. The early lytic stage is illustrated by increased and abnormal activity of the osteoclasts at the site of incidence, increasing bone resorption as a result. This activity is up to 20 times faster than normal osteoclast activity, due to an increase in the number of nuclei from 5-10 nuclei in normal osteoclasts up to 100 nuclei in affected cells. This increased resorption leads to the mixed phase, characterized by marked increases in the formation of bone with increased numbers of osteoblasts that remain normal morphologically. However, all the newly manufactured bone is flawed, as a result of imperfect ordering of the new collagen fibers. In the final sclerotic, blastic phase, new bone formation takes place in a woven pattern as opposed to the normal linear structure of adult bone [3]. Advanced Paget’s disease, know as a “burnt out” stage, results from bone marrow infiltrating this fibrous web, causing a heterogeneous ossification. This is condition does not necessarily spread to surrounding bones, however, there is no cure [6,7].
     Radiography is the most useful tool in diagnosing Paget’s disease, though CT and MR can be used, especially to rule out other diagnoses. Three fundamental signs are seen on x-ray that make Paget’s disease the clear diagnosis. They are as follows: loss of distinct limits between cortical and trabecular bones, irregular condensation with a blotchy appearance, and hypertrophy of affected bones [8]. The lytic stage is characterized by osteolysis on x-rays. This is easily seen in cases afflicting the skull (usually the frontal and occipital bones) as a well-defined area of radiolucency. Osteolysis is seen as an advancing wedge of lucency in the long bones, often with characteristic well-defined margins, often said to resemble a flame or blade of grass [1,6]. The mixed phase is when the majority of cases of Paget’s disease are detected. The radiographs show thickening of the cortex and trabecular pattern. When seen in the pelvis, Paget’s disease tends to become evident with thickening of the cortical and sclerosis of the iliopectineal and ischiopubic lines [9]. In the spine, osteoblastic activity is noted on all four sides of the vertebral body corticals, differentiating it from rugger jersey vertebrae in renal osteodystrophy, which afflicts only the superior and inferior endplate [6]. X-rays of the final, blastic phase of the disease show development of sclerosis which can destroy areas of trabecular thickening. This stage also sees the highest rates of bone enlargement, as well as the development of focal areas of opacity, knows as having a “cotton wool” appearance [1]. In some cases of Paget’s disease, deformity can arise from the replacement of normal lamellar structure with imperfect woven bone. It is most often seen as bending and bowing of long bones [8]. Increased bone fragility is also common, leading to high incidence of fractures among patients.
     The top differential diagnoses include otosyphilis and Cochlear otosclerosis. The first being a systemic illness which appears as “moth-eaten” on CT scans, and shows labyrinthine enhancement on T1 weighted images with contrast. The second is a disease that tends to afflict much younger patients and appears on CT scans as a plaque-like demineralization of the otic capsule [2].
     Increased skeletal radiodensity may be seen in a large number of conditions, including Paget's disease, bone metastasis, myelofibrosis, renal osteodystrophy, fibrous dysplasia, fluorosis, and hyperparathyroidism, among others. Additional findings characteristic of these disorders, however, assist in their recognition. For example, hepatosplenomegaly is found in myelofibrosis, subperiosteal and subchondral bone resorption and the "rugger-jersey" spine in renal osteodystrophy, bowing deformities and "ground glass" appearance in fibrous dysplasia, and focal radiodensity in tuberous sclerosis. Although bony sclerosis of Paget's disease can mimic osteoblastic metastasis, the asymmetric distribution, thickened trabecula and cortices, and the enlargement of the involved bone are all typical of Paget's disease. When considering Paget's disease, it is extremely helpful to note whether there is associated bony enlargement. This is extremely common in Paget's disease but extremely uncommon with a blastic metastasis. Another finding classic for Paget's disease is that it almost always starts at one end of a bone and then spreads toward the other end of the bone.
     Treatment of Paget’s disease has included multiple agents, such as calcitonin, biphosphonates, gallium nitrate, and mithramycin [1,6,9]. The realistic goal of therapy is pain management, not a return to normal bone tissue. Each of these medications reduces bone resorption, and are effective in decreasing and controlling patients’ pain levels. These courses of treatment may bring about positive changes in radiographic findings, but they can be subtle [1,6].

References:

1. Resnick D. Diagnosis of Bone and Joint Disorders. 3rd ed., Philadelphia: WB Saunders; 1988; 4:1923-1968.
2. Harnsberger HR, Wiggins RH, III, Hudgins PA, Michel MA, Swartz J, Davidson HC, Macdonald AJ, Glastonbury CM, Curé JK, Branstetter B, IV. Diagnostic Imaging Head and Neck. Manitoba: Amirsys; 2006. I:2:206-209.
3. Carbone LD, Driver K, Lohr KM, Navarro MJ. Paget Disease. eMedicine. Oct 6, 2008. http://emedicine.medscape.com/article/334607-overview
4. Whyte MP. Clinical practice. Paget's disease of bone. N Engl J Med. 2006 Aug 10;355(6):593-600. PMID: 16899779 [PubMed]
5. Whitehouse RW. Paget's disease of bone. Semin Musculoskelet Radiol. 2002 Dec;6(4):313-22. PMID: 12541188 [PubMed]
6. Smith SE, Murphey MD, Motamedi K, Mulligan ME, Resnik CS, Gannon FH. From the archives of the AFIP. Radiologic spectrum of Paget disease of bone and its complications with pathologic correlation. Radiographics. 2002 Sep-Oct;22(5):1191-216. PMID: 12235348 [PubMed]
7. Kanis JA. Pathophysiology and Treatment of Paget’s Disease of Bone. 2nd ed. London: Martin Dunitz, 1998.
8. Rousière M, Michou L, Cornélis F, Orcel P. Paget's disease of bone. Best Pract Res Clin Rheumatol. 2003 Dec;17(6):1019-41. PMID: 15123049 [PubMed]
9. Dalinka MK, Aronchick JM, Haddad JG Jr. Paget's disease. Orthop Clin North Am. 1983 Jan;14(1):3-19. PMID: 6219329 [PubMed]