The Many Faces of Paget's Disease of Bone and Its Complications as Demonstrated by Nuclear Scintigraphy

1. The Many Faces of Paget's Disease of Bone and Its Complications as Demonstrated by Nuclear Scintigraphy Stephen Leighton, M.D. Yale Pollak, M.D Glenn Kaplan, M.D. William Smoak, M.D. Manuel Viamonte, Jr., M.D.

2. Paget’s Disease First described by Sir James Paget in 1877 as a chronic infection which causes slow remodeling of the bone. Over a century later the etiology of Paget’s disease still continues to be a mystery. Current theory attributes a viral infection of osteoclasts which causes abnormal bone resorption. Despite the abnormal appearance and increased activity of osteoclasts, a virus has never been successfully cultured from “Pagetic” bone to support this theory.

3. Paget’s Disease Paget’s disease is characterized by abnormal remodeling of bone. Three phases are described: the active phase (osteolytic), mixed phase, and the quiescent phase (osteoblastic). The active phase is characterized by aggressive bone resorption. The mixed phase is a combination of active and quiescent phases of Paget’s disease with evidence of resorption and new bone formation. The quiescent phase is often referred to as “burned out” Paget's disease in which minimal bone remodeling occurs.

4. Paget’s Disease The disease afflicts approximately 3% of patients over forty, and in patients over 80 years the incidence has been reported as high as 10%. Rarely is Paget’s disease found in patients under the age of 40 years old. There appears to be certain demographic and racial characteristics: It is common in white western Europeans and North Americans. It is rarely found in the Far East or among Africans. Despite a slightly increased incidence among family members, no definable DNA gene mapping has ever been established to support a genetic linkage.

5. Clinical Features Patients are usually asymptomatic and the diagnosis is frequently made as an incidental finding on radiographs or elevated serum alkaline phosphatase levels. If patients are symptomatic they may complain of local tenderness or enlargement of an extremity. Deformed joints may lead to symptomatic arthritis. Severe neurologic deficits from enlarging bones at the base of the skull or vertebral bodies can lead to cranial nerve or spinal cord impingement. In patients with extensive disease, the rare complication of high-output congestive heart failure may occur from increased blood flow to bone. Symptomatic patients may require further diagnostic imaging to identify the complications of Paget’s Disease, such as fracture, severe arthritis, and malignant degeneration.

6. Laboratory Features Laboratory values in Paget’s disease usually demonstrate markedly elevated serum alkaline phosphatase. Urine hydroxyproline is a marker of osteoclastic activity and is elevated in the osteolytic and mixed phase of Paget’s disease. In the osteoblastic stage urine hydroxyproline should decrease (relative to active and mixed phases) while alkaline phosphatase will remain elevated.

7. Pathophysiology In the osteolytic phase there is increased activity of the osteoclasts with respect to the osteoblasts. Bone resorption occurs, and this is later followed by an osteoblastic response which attempts to lay down bone. The new bone created by the osteoblasts does not have the same structural integrity or architecture as normal bone. The change to blastic or mixed phase is not abrupt but rather occurs over time. In the mixed phase there is decreased activity of the osteoclast in comparison to the active phase. Lastly, in the osteoblastic phase, there is a further decrease of osteoblasts and osteoclasts with almost no bone remodeling.

8. Widespread Paget’s disease involving appendicular and axial skeleton. Paget’s Disease in multiple bones in different phases of activity.

9. Skull Patterns Cotton wool appearance of the skull. Cotton wool refers to the increased areas of sclerosis on plain film.

10. Osteolytic and osteoblastic phases of the skull. Osteoporosis circumscripta, osteolysis of the calvarium, is indicated by the arrow.

11. Multifocal osteoblastic Paget’s Disease of the skull.

12. Extensive osteoblastic involvement of the skull. Note the characteristic sparing of the mandible.

13. Focal Paget’s disease of the skull.

14. Multi-focal involvement of the skull with basilar invagination at the base of the skull (arrow). Basilar invagination of the skull is observed in one-third of patients with advanced involvement of Paget’s disease. Cranial nerve palsy and other neurologic deficits can result from thickening of the base of the skull with impingement of the exiting nerves.

15. CT demonstration of mixed phases with cortical thickening of the base of the skull. Hearing loss as a result of cortical thickening and narrowing of the 7th and 8th nerve foramen frequently occurs.

16. Spine & Axial Skeleton Patterns Isolated vertebral body involvement with extension into the transverse processes and spinous process. Metastatic disease rarely extends into the transverse or spinous processes.

17. CT scan shows “picture frame” sclerosis and thickening of the cortex with extension to posterior elements. This is differentiated from secondary hyperparathyroidism because it involves the anterior cortex and extends into the posterior elements. Spinal stenosis and radiculopathy are complications of Paget’s disease.

18. “KILROY” WAS HERE Paget’s disease involving the pedicles and spinous process resembles WWII cartoon “Kilroy”. Each hand resembles a pedicle and the nose represents a thickened spinous process.

19. Thickened spinous process at L4 and L5 (arrows). Note the enlargement of the L3 vertebra in comparison to the normal L2. Mixed sclerotic and osteolytic involvement of the right hemi-pelvis. L3

20. Vertebral body with involvement of adjacent rib (arrow). Paget’s rarely involves a rib without also involving the adjacent vertebral body.

21. Pelvis Patterns Fig. A Fig. B Examples of Paget’s disease involving the pelvis. Examples of unilateral (Fig. A), and bilateral enlargement (Fig. B) of the pelvis.

22. Radiographic demonstration of the left iliopectineal cortical thickening (arrows). Paget’s Disease of the pelvis is characterized by this finding.

23. Classic scintigraphic demonstration of the iliopectineal line thickening (arrow).

24. CT correlation showing thickened cortex and disorganized trabeculae of the right ilium (arrow).

25. Paget’s Disease crossing the sacroiliac and pubic symphysis.

26. Unilateral joint destruction with acetabular protrusio. Also cortical thickening of inferior pubic rami without obliteration of medullary space.

27. Acetabular protrusio of the femoral head after hip replacement. This is a common complication after hip surgery. Pagetic bone is soft and frequently cannot support the new prosthesis.

28. Appendicular Skeleton Characteristics Paget’s disease involving the appendicular skeleton typically begins at the epiphysis. It frequently crosses the adjacent joint space (arrow).

29. Thickening of the cortex and trabecula of the capitellum and the entire ulna. Paget’s Disease frequently extends from epiphysis to epiphysis.

30. Classic example of “blade of grass” or “flame shaped” (arrow) deformity of the tibia. The fibula is typically uninvolved.

31. Flow study demonstrates increased blood flow in Paget’s Disease. In severe cases this can lead to high-output congestive heart failure secondary to increased blood flow.

32. Isolated osteolytic Paget’s disease of the humeral head. This can mimic an epiphyseal based tumour.

33. Complicationsof Paget’s Disease of Appendicular Skeleton Common complications of Paget’s disease of the long bones include bowing, sheppard's crook deformity, and fracture.

34. Advanced bowing deformity of the tibia.

35. Sheppard’s crook deformity of right femur Sheppard’s Crook deformity

36. Fracture Paget’s involvement of the femur with resulting fracture.

37. Other Common Sites of Involvement Paget’s disease involving the shoulder. Unlike metastatic disease, Paget’s disease frequently will involve the coracoid and glenoid (arrow).

38. Calcaneus involvement with Paget’s Disease. The small bones of the hands and feet are rarely involved.

39. Malignant Degeneration of Paget’s Disease Fig. B Fig. A. Patient with long history of Paget’s Disease who presented with new onset of left hip pain. Example of lytic osteosarcoma (arrow) with cortical and medullary destruction. Flow study shows focal hyperemia (Fig. B). Photopenic defect on static image, Fig. C. Fig. C.

40. Complete evaluation with bone scintigraphy and plain films should be performed in patients with symptomatic Paget’s disease. Malignant degeneration while rare (less than 1%) usually affects men over the age of 55 years old with advanced Paget’s disease. The pelvis and femur are the most common sites of malignant degeneration. In addition to osteosarcoma, fibrosarcoma and chondrosarcoma can result from Paget’s disease. Less frequently Giant cell tumors can also arise from Pagetic bone. Giant cell tumors usually arise in the skull and facial bones and usually are benign in nature.