METABOLIC CONDITIONS

Paget’s Disease Paget’s disease, or osteitis deformans, is a chronic, slowly progressive

metabolic disorder of bone of undetermined cause (Box 15-1). Etiologic theories include
infection by paramyxovirus and mutations in several genes that are involved in
osteoclastogenesis. Altered osteoclast development and function result in abnormal bone
remodeling. Osteoblast function may also be abnormal in Paget’s disease. This condition
generally progresses through several stages that include an initial resorptive phase,
followed by a vascular phase, and eventually by a sclerosing phase.
Clinical Features. Paget’s disease is a hyperactive bone turnover state that typically occurs
in patients older than 50 years. It is relatively common and has been reported to occur in
3% to 4% of the middle-aged population and in as many as 10% to 15% of the elderly. In
approximately 14% of cases, a positive family history can be elicited. Paget’s disease has a
3 : 2 male predilection, and it seems to occur more often in patients of Northern European
descent. The most common sites of involvement include the pelvis, skull, tibia, vertebrae,
humerus, and sternum. The jaws are affected in approximately 20% of patients, and the
maxilla is involved twice as often as the mandible (Figure 15-1). At initial presentation,
symptoms often relate to deformity or pain in the affected bone(s).
Bone pain is described as deep and aching. A perception of elevated skin temperature
over the affected bone is often noted because of the hypervascularity of the underlying
bone. Neurologic complaints— including headache, auditory or visual disturbances, facial
paralysis, vertigo, and weakness—may be related, in large part, to narrowing of the skull
foramina, resulting in compression of vascular and neural elements. Approximately 10% to
20% of patients are asymptomatic and are incidentally diagnosed after radiographic or
laboratory studies are performed for unrelated problems.

Classically, dental patients who wear complete dentures may complain of newly acquired
poor prosthetic adaptation and function as the maxilla symmetrically enlarges. The
alveolar ridge ultimately widens, with relative flattening of the palatal vault. When teeth
are present, increased spacing, as well as loosening, is noted. In severe cases, continued
enlargement of the maxilla or mandible can make closure of the lips difficult or
impossible. Classic radiographic findings in the late stage of Paget’s disease are due to
bony sclerosis providing a patchy radiopaque pattern described as resembling cotton or
wool. In the jaws, this pattern of bone change may be associated with hypercementosis or
resorption of tooth roots, loss of lamina dura, and obliteration of the periodontal ligament
space (Figures 15-2 and 15-3).
Histopathology. In the initial resorptive phase, random overactive osteoclastic bone
resorption is evident. Resorbed bone is replaced by vascularized connective tissue in
company with prominent osteolysis and osteogenesis. Bone eventually develops a dense
mosaic pattern as a result of reversal lines in increasingly sclerotic bone, as osteoclasts
give way to osteoblasts (Figures 15-4 and 15-5). The laboratory can provide important
information about the diagnosis of Paget’s disease. Serum calcium and serum phosphate
levels are normal in the presence of markedly elevated alkaline phosphatase levels. The
intense osteoblastic activity in this metabolically active bone is believed to be responsible
for the elevated alkaline phosphatase levels. The amount of bone resorption may be
correlated with increases in urinary calcium and hydroxyproline levels.
Treatment. The primary indicator for therapeutic intervention is patient discomfort.
Elevation of alkaline phosphatase levels to twice normal levels is also an indication for
treatment. Therapy has been directed at controlling osteoclast formation and function.
The use of calcitonin and bisphosphonate has been effective. Both suppress bone
resorption and deposition, as reflected in a reduction in the biochemical indices, including
alkaline phosphatase and urinary hydroxyproline levels. A 50% reduction in either index
constitutes a good therapeutic response (see Chapter 13 for complications of
bisphosphonate therapy). Paget’s disease is a slowly progressive disorder, but it is seldom
fatal. Relief of symptoms, particularly bone pain, with oral or intravenous
bisphosphonates is beneficial.
Complications include skeletal deformity, weakened bones, neurologic deficits, and
pathologic fracture. Heart failure may also be an important complication of Paget’s
disease as a consequence of the hypervascular bone. In the early vascular phase, bleeding
following any type of bone surgery (e.g., tooth extraction) can be problematic. In a small
percentage of cases, malignant transformation into osteosarcoma may occur. Depending
on the series reported, this has ranged from 1% to 15%.