J Bone Miner Metab (2006) 24:359–367 © Springer 2006

DOI 10.1007/s00774-006-0696-x

SPECIAL REPORT

Shinjiro Takata · Jun Hashimoto · Kiyoshi Nakatsuka

Noriko Yoshimura · Kousei Yoh · Ikko Ohno
Hiroo Yabe · Satoshi Abe · Masao Fukunaga
Masaki Terada · Masaaki Zamma · Stuart H. Ralston
Hirotoshi Morii · Hideki Yoshikawa, for the Japanese
Committee on Clinical Guideline of Diagnosis and
Treatment of Paget’s Disease of Bone in Japan
Osteoporosis Society

Guidelines for diagnosis and management of Paget’s disease of bone

in Japan

Received: September 5, 2005 / Accepted: February 28, 2006

Abstract We here propose guidelines for the diagnosis and
management of Paget’s disease of bone (PDB) in Japan.
These guidelines provide basic information on the epidemi-
S. Takata (*)
Department of Orthopedics, Institute of Health Biosciences, The
University of Tokushima Graduate School, 3-18-15 Kuramoto-cho,
Tokushima 770-8503, Japan
Tel. +81-88-633-7240; Fax +81-88-633-0178
e-mail: stakata@clin.med.tokushima-u.ac.jp
J. Hashimoto · I. Ohno · H. Yoshikawa
Department of Orthopaedics, Osaka University Medical School,
Osaka, Japan
K. Nakatsuka
Department of Metabolism, Endocrinology and Molecular Medicine,
Osaka City University Graduate School of Medicine, Osaka, Japan
N. Yoshimura
Department of Joint Disease Research, Graduate School of
Medicine, The University of Tokyo, Tokyo, Japan
K. Yoh
Department of Orthopedic Surgery, Hyogo College of Medicine,
Nishinomiya, Japan
H. Yabe
Department of Orthopedic Surgery, School of Medicine, Keio
University, Tokyo, Japan
S. Abe
Department of Orthopedic Surgery, Teikyo University School of
Medicine, Tokyo, Japan
M. Fukunaga
Department of Nuclear Medicine, Kawasaki Medical School,
Kurashiki, Japan
M. Terada
Department of Orthopaedic Surgery, Wakayama Medical College,
Wakayama, Japan
M. Zamma
Sumitomo Pharmaceuticals, Tokyo, Japan
S.H. Ralston
Rheumatic Diseases Unit, University of Edinburgh, Western
General Hospital, Edinburgh, UK
H. Morii
Japan Osteoporosis Society, Tokyo, Japan
ology, pathophysiology, clinical signs and symptoms, diag-
nosis, indications for treatment, and available therapy,
including orthopedic surgery. PDB is a chronic disorder
characterized by focal abnormalities of bone turnover. The
characteristic feature of PDB is excessive osteoclastic bone
resorption coupled to increased and disorganized bone
formation. The most common symptom of PDB is pain in
involved bones. The most serious complication of PDB is
malignant bone or soft-tissue tumor. PDB is uncommon in
Japan; our survey in 2003 found 169 patients with PDB. The
prevalence of PDB in Japan is 0.15/100 000; in patients aged
55 years or more, the proportion reaches 0.41/100 000. A
careful medical history and physical examination are essen-
tial for the diagnosis. The diagnosis of PDB is based on
finding the typical features on radiographs. Bone scintigra-
phy and measurement of serum alkaline phosphatase are
sensitive means of screening for PDB. Since PDB is a rare
disease in Japan, bone biopsy is quite often used to exclude
bone metastases. The only evidence-based indication for
treatment of PDB is pain in involved bones. In Japan,
etidronate and calcitonin are approved by the Ministry of
Health, Labour and Welfare for treating PDB, but currently
risedronate is also under development for treating PDB in
Japan. Indications for surgical intervention in PDB include
unstable fractures, osteoarthritis, malignant soft-tissue tu-
mor, osteosarcoma, and bone deformity.
Key words Paget’s disease of bone · guideline · diagnosis ·
treatment
Introduction
In 1877, Paget’s disease of bone (PDB) was first described
by Sir James Paget, an English surgeon, who named this
skeletal disorder osteitis deformans [1]. Although PDB is
uncommon in Japan, it is the second most common meta-
bolic bone disease in European countries [2–5].
360
The characteristic feature of PDB is excessive osteoclas-
tic bone resorption coupled with increased and disorga-
nized bone formation. Clinical signs and symptoms depend
on the location and number of involved bones and on the
rapidity of abnormal bone turnover. The most serious com-
plication of PDB is osteosarcoma, although this complica-
tion is rare. While special attention should be paid to the
complications of PDB, it is important to remember that
most patients with PDB are asymptomatic [4].
We here propose guidelines for diagnosis and manage-
ment of PDB in Japan to provide basic information on the
epidemiology, pathophysiology, clinical signs and symp-
toms, diagnosis, indications for treatment, and available
therapy, including orthopedic surgery. These guidelines
stress the importance of bone biopsy to differentiate PDB
from secondary tumors such as metastases from prostate
cancer or breast cancer, and other sclerosing bone
dysplasias.
Epidemiology
In Japan, 169 patients with PDB were found in our survey in
2003 [6]. The prevalence of PDB in Japan is 0.15/100 000; in
patients aged 55 years or more, the proportion reaches 0.41/
100 000. Although PDB is rare in Japan, it is quite common
in most European countries, except for Scandinavia. Paget’s
disease is also common in Australia, New Zealand, and
North America [2]. Radiographic studies performed in the
1980s showed that the prevalence of PDB in hospitalized
patients aged more than 55 years in the UK was 4.6%, in
France 2.4%, in Ireland 0.7%–1.7%, in Spain and West
Germany 1.3%, and in Italy and Greece 0.5% [3]. Although
the UK still has the highest prevalence of PDB in the world,
a recent survey suggests that the disease has become less
common over recent years, and the radiological prevalence
in those aged over 55 years is now estimated as about 2%
[7]. The ethnic differences in the prevalence of PDB,
coupled with the change in prevalence over recent years,
indicate that both environmental and genetic factors most
likely contribute to the pathogenesis of PDB.
In Japan, as in other countries, PDB is rarely diagnosed
in patients under the age of 40 years. Our previous survey
revealed that the mean age of Japanese patients with PDB
was 68 years (ranging from 25 to 98 years), with an increase
in prevalence with increasing age [6].
The male/female ratio of PDB patients in Japan is 0.86
[6], indicating a slight female predominance. According to a
recent study [7], in a radiographical survey of PDB in 10
British centers, the overall age/gender standardized preva-
lence rate was 2% with a male/female ratio of 1.6.
PDB often shows familial clustering [8–11]. We have not
examined the frequency of a positive family history in
Japan, but studies in Europe and the US have indicated that
approximately 15%–30% of patients with PDB have a posi-
tive family history of the condition [8–11].
Pathophysiology
Since PDB shows geographical and ethnic clustering, two
hypotheses of the etiology of PDB have been proposed.
One hypothesis is that PDB results from a slow virus infec-
tion of osteoclasts with paramyxovirus [12,13]. The other is
that PDB is a genetic disease [14,15].
Paramyxovirus infection
Immunohistochemical study has revealed that staining for
measles virus antibodies is positive in cultured pagetic cells
and pagetic bone samples [16]. Osteoclasts from patients
with PDB have been found to exhibit characteristic nuclear
inclusions consisting of paracrystalline arrays that resemble
nucleocapsids of paramyxoviruses [17–19]. This led to the
suggestion that PDB is caused by a chronic paramyxovirus
infection. However, these nuclear inclusions are not specific
for PDB and the role of paramyxovirus infection in the
pathogenesis of PDB is still controversial [20].
Genetics
Family studies in the US have shown that 12.3% of patients
had at least one affected relative, compared with only 2.1%
of controls [8]. Similar findings have been reported in the
UK [11]. Severely affected patients with PDB frequently
have a positive family history of PDB [21], and patients who
have a positive family history have an earlier onset of the
disease than patients who do not [8].
Genome-wide scans have identified susceptibility loci of
PDB and related conditions on chromosomes 18q21 [22],
chromosome 5q35 [23], chromosome 5q31 [23], chromo-
some 2q36, and chromosome 10p13 [24]. Mutations in four
genes have been discovered as a cause of PDB or related
syndromes. These are receptor activator of nuclear factor
kappa B (RANK) [9], osteoprotegerin (OPG) [25],
sequestosome (SQSTM1) [23], and valosin-containing
protein (VCP) [26]. Mutations affecting RANK, OPG, and
VCP have been excluded as a cause of classical PDB [27–
29]. However, mutations of SQSTM1 are a common cause
of PDB and occur in between 40%–50% of Caucasian pa-
tients with familial PDB and in 8%–20% of patients who do
not have a family history of PDB [30].
Signs and symptoms
Clinical signs and symptoms depend on the location and
number of affected bones and on the rapidity of the abnor-
mal turnover of bone. The clinical manifestations of PDB
are shown in Table 1 and include bone pain, local warmth,
and bone deformity [31]. Pain in the involved bones is the
most common symptom of PDB and may be most severe at
night. Bone pain can also result from pathological fracture
and osteoarthritis.

Table 1. Complications of Paget’s disease of bone [31]
Musculoskeletal complications
Skeletal pain
Skeletal deformities
Fractures (fissure fracture, chalk-stick fracture)
Secondary osteoarthritis
Local warmth
Neurologic complications
Hearing deficit
Cranial nerve deficits
Mottled retinal degeneration, angioid streaks
Basilar impression
Hydrocephalus
Myelopathy
Radicular neuropathies
Spinal stenosis
Spinal vascular steal syndrome
Cardiovascular complications
Increased cardiac output
Congestive heart failure
Generalized atherosclerosis
Aortic valve calcification
Endocardial calcification
Metabolic complications
Hypercalciuria
Hypercalcemia with immobilization
Hyperparathyroidism (controversial)
Gouty diathesis
Neoplastic complications
Sarcoma (osteosarcoma, chondrosarcoma, fibrosarcoma)
Metastatic carcinoma
Hematologic malignancies
Giant-cell tumor
PDB of the monostotic type involves a single bone or
portion of a bone, whereas PDB of the polyostotic type
affects two or more bones. Approximately 49% of PDB in
Japan is polyostotic [6], whereas in Caucasians, approxi-
mately 66% is polyostotic PDB [32].
PDB patients also suffer from an increased risk of devel-
oping osteoarthritis, probably due to the bowing deformity
of affected limbs. Abnormal stress and strains on the joints
nearby cause osteoarthritis in PDB. Femurs are frequently
affected, as are the knee joints. van Staa et al. [33] reported
that PDB patients in England and Wales had a significantly
increased risk of osteoarthritis (OA; RR, 1.7; 95% CI, 1.5–
1.9), hip arthroplasty (RR, 3.1; 95% CI, 2.4–4.1), and knee
arthroplasty (RR, 1.6; 95% CI, 1.0–2.6), when compared
with age-matched controls.
The skull is also a common site of PDB, resulting in an
increase in head size. Enlargement of the skull causes defor-
mity and can also lead to neurological problems if the cra-
nial nerve foraminae are affected. If the temporal bone is
involved, the patients suffer from hearing loss [34] as well as
headaches and visual loss [4].
Enlarged vertebrae can cause compression myelopathy
and nerve root injury. If the lumbar spine is affected, pa-
tients can experience numbness, tingling of the feet, gait
disturbance, motor disturbance of the legs, and urinary
bladder and bowel dysfunction.
The most serious complication of PDB is malignant neo-
plasm, which invariably occurs in bones affected by PDB.
The incidence of osteosarcoma in PDB patients is low at
approximately 0.1%. However, this incidence is several
361
thousand-fold higher than that found in the general popula-
tion [35]. The most common site of osteosarcoma is the pelvis
[36]. Both pagetic and sporadic osteosarcoma exhibit tumor-
specific loss of constitutional heterozygosity (LoH) for all
or part of the distal portion of chromosome 18q, between
D18S60 and D18S42. This has led to the suggestion that the
gene for 18q-mediated PDB and the tumor suppressor gene
may be one and the same [37]. However, since this observa-
tion, mutations in RANK were discovered to be the cause
of familial expansile osteolysis and early onset PDB [38],
whereas no mutations of RANK have so far been identified
in sporadic or pagetic osteosarcoma [39]. Malignant fibrous
histiocytoma in PDB has also been reported [40].
Diagnosis
Figure 1 shows a flowchart for the diagnosis of PDB. A
careful medical history and physical examination are
essential for the diagnosis. The diagnosis of PDB is based
on finding the typical features on radiographs, but bone
scintigraphy and measurement of serum alkaline phos-
phatase are sensitive means of screening for PDB.
Bone biopsy is rarely required to establish the diagnosis
in European countries [4]. However, since PDB is a rare
disease in Japan, bone biopsy is quite often used to exclude
bone metastases and to make a positive diagnosis of PDB.
Serious complications of bone biopsy are rare with an expe-
rienced operator, but local pain and bruising are relatively
common. Infection and serious bleeding are rare, but an
aseptic technique should be employed to avoid introducing
infection, and patients should have a coagulation screen
prior to the biopsy to exclude a bleeding diathesis.
Imaging diagnosis
Most patients with PDB are diagnosed based on character-
istic X-ray findings as follows.
Plain radiography
The distribution of PDB in Japan is similar to that in Euro-
pean countries. The well-known radiographic features of
PDB include an advancing resorption front, coarsening and
accentuation of the trabecular pattern along lines of stress,
thickening of the cortices, and enlargement of bone
contours [41].
Tubular bone (Fig. 2)
Characteristic findings on a plain X-ray film in the tubular
bones in PDB are cortical thickening, expansion or enlarge-
ment, mixed areas of lucency and sclerosis, bowing defor-
mity, coarsening of trabecular markings, and typical lytic
and sclerotic changes.
Pelvis and hip joint (Fig. 2)
Characteristic findings on plain X-ray film in the pelvis are
cortical thickening, expansion or enlargement, and mixed
362
Fig. 1. Flowchart for the diagnosis of Paget’s disease of bone (PDB).
The differential diagnosis of PDB includes secondary tumors such as
metastasis from prostate cancer or breast cancer, and sclerosing bone
dysplasia. Typical abnormal findings on plain X-ray film include an
advancing resorption front, coarsening and accentuation of the trabe-
Fig. 2. Plain radiography of pelvis and femur in a patient with PDB.
Characteristic findings on a plain X-ray film of the femur and pelvis in
PDB are cortical thickening, expansion or enlargement, mixed areas of
lucency and sclerosis, coarsening of trabecular markings, and typical
lytic and sclerotic changes. A plain X-ray film reveals bowing deformity
of the femur in PDB
areas of lucency and sclerosis. Subchondral bone enlarge-
ment alters the normal congruity between the surfaces of
the hip joint, which cause osteoarthritis of the hip. In addi-
tion, the bowing deformity of an involved femur causes
osteoarthritis of the hip joint.
cular pattern along lines of stress, thickening of the cortices, and en-
largement of bone contours. AP, alkaline phosphatase; BAP, bone-
specific alkaline phosphatase; NTX, type I collagen cross-linked N
telopeptides; DPD, deoxypyridinoline
Skull (Fig. 3)
The most typical radiographic findings in the skull are a
cotton wool appearance, reflecting new bone formation. An
isolated area of bone resorption without evident bone scle-
rosis is called osteoporosis circumscripta.
Spine (Fig. 4)
In the spine, an involved vertebral body is typically enlarged
compared with the normal vertebrae and a picture frame
effect may occur due to cortical thickening of the vertebral
bodies.
Radionuclide bone scan (Fig. 5)
A radionuclide bone scan is the most sensitive means of
detecting PDB and is useful to determine the full extent of
skeletal involvement in a patient with PDB. The typical
appearance is one of markedly increased tracer uptake in
the affected bones.
Laboratory examination
Serum levels of alkaline phosphatase (AP) are elevated in
approximately 89.6% of Japanese patients with PDB [6]. In
Caucasians, serum total AP is elevated in approximately
85% of patients [42]. Accordingly, there is no significant
difference in the proportion of patients with an elevated
serum AP between Japan and other countries. Bone-
specific AP is more sensitive and specific than serum total
AP [43], but it is not usually necessary to measure bone-
specific AP in the majority of patients with PDB [4].
 363
Fig. 3. Plain radiography of the
skull in a patient with PDB.
Cotton wool appearance of an
enlarged pagetic skull is the most
typical radiological finding

Fig. 4. Plain radiography of the

spine in a patient with PDB. The
characteristic findings of an in-
volved spine are enlarged verte-
bral bodies and a picture frame
appearance of the spine (arrows)

The level of serum total AP is correlated with the extent
and activity of PDB [44]. The level of serum total AP in
patients with polyostotic PDB is higher than the level in
those with monostotic PDB. Some cases of monostotic PDB
show a normal level of serum total AP, however, and it is
important to remember that a normal AP value does not
exclude a diagnosis of PDB [4].
The degree of elevation of both bone formation markers
and bone resorption markers indicates the approximate
severity of abnormal bone turnover. The rate of bone
resorption in PDB is significantly elevated, which triggers
acceleration of bone formation. The level of serum total
AP increases in association with bone resorption markers,
such as urinary N-telopeptide of human type I collagen,
C-telopeptide of human type I collagen, and deoxypyri-
dinoline. Serum total AP is sufficient to monitor the re-
sponse to treatment of PDB in most cases [4].
Histological diagnosis
Osteoclasts in PDB are morphologically abnormal and are
larger than normal osteoclasts. The number and size of
osteoclasts are markedly increased in PDB, and such osteo-
364
Fig. 5. Radionuclide bone scan of PDB. Radionuclide bone scan
reveals a marked increase in the uptake in pagetic skull
clasts contain up to 100 nuclei per cell [45]. Histologically,
pagetic bones have a high level of vascularity and an excess
of fibrous connective tissue in the bone marrow. The bone
strength in PDB is decreased, resulting in bone deformities
such as bowing and fracture.
In the destructive phase of PDB, the increased rate of
both bone formation and bone resorption result in an in-
crease in the number of reversal fronts and cement lines,
which gives rise to the classic mosaic pattern. Polarized light
reveals disorganization of bone architecture and lamellar
texture [46].
Differential diagnosis
The differential diagnosis of PDB includes secondary
tumors such as metastasis from prostate cancer or breast
cancer, and sclerosing bone dysplasias.
Treatment
Medication
The only evidence-based indication for treatment of PDB is
bone pain [47]. In Japan, etidronate and calcitonin are ap-
proved by the Ministry of Health, Labour and Welfare for
treating PDB, but currently risedronate is also under devel-
opment for treating PDB in Japan.
Bisphosphonate
The development of bisphosphonates has brought about
major changes in the treatment of PDB. The recom-
mended regimens for bisphosphonates use in various parts
of the world are shown in Table 2 [48]. Currently, five
bisphosphonates (pamidronate, etidronate, tiludronate,
alendronate, and risedronate) are approved by the United
States Food and Drug Administration (FDA) for the treat-
ment of PDB [49]. Bisphosphonates are antiresorptive
agents that inhibit the activity of osteoclasts in both pagetic
and normal bone. Bisphosphonate treatment produces long-
term biochemical remission of PDB and is an ideal agent for
relieving bone pain [50,51]. Oral calcium and vitamin D
supplementation is generally recommended for patients
with PDB who are being treated with bisphosphonates to
prevent the occurrence of hypocalcemia [49].
Etidronate is a first generation of bisphosphonate, and
was the first bisphosphonate to be used clinically for the
treatment of PDB. In Japan, a clinical trial revealed that
etidronate disodium (EHDP) relieved clinical manifesta-
tions in patients with PDB [52]. Currently EHDP is ap-
proved by the Ministry of Health, Labour and Welfare for
treating PDB in Japan. EHDP reduces levels of AP and
bone pain [53]. EHDP in doses of more than 5 mg/kg/day
carries a risk of osteomalacia [54], and this might be espe-
cially relevant in patients with low body weight since only
200-mg and 400-mg tablets are available. It should be noted
that vitamin D metabolites do not prevent EHDP-induced
osteomalacia in PDB [55].
Alendronate is an aminobisphosphonate that has been
found to relieve bone pain and reduce bone turnover in
PDB [56] and has been shown to stimulate healing of lytic
lesions [57,58]. Pamidronate is an aminobisphosphonate
that has been used extensively in the management of PDB
in Europe. It is given intravenously and has been found to
improve bone pain and reduce bone turnover [47].
Tiludronate is a sulfur-containing bisphosphonate that
has been found to be effective in the treatment of PDB.
Comparative trials have shown that it is more effective at
reducing bone turnover than etidronate in PDB [59], al-
though interestingly, the same study showed no difference
between tiludronate and etidronate in the relief of bone
pain [59].
Risedronate is an aminobisphosphonate which is highly
effective in the treatment of PDB. Risedronate is currently
under development for use in the treatment of PDB in
Japan. Treatment with risedronate leads to a 60%–70%
reduction of the level of serum AP in PDB and relieves
bone pain [60]. Studies in Caucasian populations have re-
vealed that it is more effective at reducing elevated bone
turnover in PDB than etidronate [60].
Calcitonin
Calcitonin is approved by the Ministry of Health, Labour
and Welfare of Japan. In Japan, Takahashi et al. [61] showed
that intravenous injection of 40 units of eel calcitonin deriva-
tive reduced pain and the level of serum AP in patients with
 365

Table 2. Bisphosphonates and calcitonin approved by the Japanese Ministry of Health, Labour and Welfare and the FDA in the US for the
treatment of Paget’s disease of bone
Generic name Trade name Administration and dosage

Drugs approved by the Japanese Ministry of Health, Labour and Welfare

Bisphosphonate
Etidronate disodium Didronel Tablet: 200–400 mg daily for 6 months
(Sumitomo Pharmaceuticals) Course of etidronate should not exceed 6 months
Repeat courses can be given after rest periods of at least
3 months
Etidronate can be increased up to 1000 mg daily. In this
case, the period of administration should not exceed
3 months
Calcitonin
Eel calcitonin Elcitonin Intramuscular injection: 40 units daily or three times per
(Asahi Kasei Pharma) week
Agent under development in Japan
Risedronate sodium Benet (Takeda Pharmaceutical Under development
Company)
Actonel (Aventis Pharma Japan)
(Eisai)
Drugs approved by the FDA in the United States
Bisphosphonate
Etidronate disodium Didronel (Procter and Gamble) Tablet: 200–400 mg daily for 6 months
Course of etidronate should not exceed 6 months
Risedronate sodium Actonel (Procter and Gamble) Tablet: 30 mg once daily for 2 months
Pamidronate disodium Aredia (Novartis) Intravenous: 30–60 mg infusion over 4 h on three
consecutive days
Alendronate sodium Fosamax (Merck) Tablet: 40 mg once daily for 6 months
Tiludronate disodium Skelid (Sanofi-Synthelabo) Tablet: 400 mg (two 200-mg tablets) once daily for 3
months
Calcitonin
Salmon calcitonin Miacalcin (Novartis Pharma) Injection: 50–100 units daily or three times per week for
6–18 months

PDB. Calcitonin inhibits osteoclast-mediated bone resorp-
tion by a direct action and if a patient with PDB cannot
tolerate bisphosphonate, calcitonin can be given either sub-
cutaneously or intramuscularly [53]. Long-term administra-
tion of calcitonin may cause an escape phenomenon,
possibly due to downregulation of its receptors on osteo-
clasts, thereby reducing its therapeutic effect.
Orthopedic treatment
Indications for surgical intervention in PDB include
unstable fractures, osteoarthritis, malignant soft-tissue
tumors, osteosarcoma [62,63], and bone deformity [4].
Pagetic bones are hypervascularized, which leads to an in-
crease in the risk of serious blood loss during an operation.
It is sometimes recommended that bisphosphonates [49,64]
or calcitonin [65,66] be given to reduce disease activity prior
to surgery to prevent excessive intraoperative blood loss,
but in fact there is no evidence to show that preoperative
antiresorptive therapy actually reduces blood loss in PDB
patients.
pseudofractures, and pathological fractures occur in areas
of high mechanical stress, particularly in weight-bearing
bones of the lower extremities [65]. Severe bowing defor-
mity of weight-bearing bones, especially the femur and
tibia, predisposes these deformed bones to transverse fis-
sure lines on the convex side, leading to complete fracture
[69]. An increased rate of malunion in pagetic bone frac-
ture, particularly in proximal femur fracture, has been re-
ported [70]. The major complications of fractures in PDB
are delayed union, nonunion, malunion, excessive bleeding,
compartment syndrome, focal disuse osteopenia, hypercal-
cemia, and hypercalciuria [65].
Plate and screw fixation requires extensive exposure,
and fixation of screws in pagetic bone is less secure than
in normal bone. Plate and screw for fracture of diaphysis
has been superseded by locked intramedullary nailing. In-
tramedullary nailing is available only for mild bowing defor-
mities [66]. An Ilizarov external fixator can be used for
treatment of a fracture of tubular bone with severe bowing
deformity [66].
Osteoarthritis

Fracture Osteoarthritis is one of the most common complications of

Pathological fractures are the most common complication
of PDB [65,67]. There is no evidence that any antiresorptive
agent reduces the risk of fracture or alters the healing
of fractures in PDB [4,68]. Painful fissure fractures,
PDB. Bowing deformity of affected limbs causes the devel-
opment of osteoarthritis. Femurs are frequently affected, as
are knee joints. There is no evidence that bisphosphonate
affects the development or the progression of osteoarthritis
[49].
366
Total hip arthroplasty is highly effective for relieving hip
pain and restoring motion of the hip joint [65]. There is no
objective evidence that bisphosphonates can prevent loos-
ening of prosthetic joints. The representative complications
of total joint arthroplasty in PDB are aseptic loosening,
varus deformity, heterotopic ossification, and excessive
bleeding [65].
Osteotomy for correcting bowing deformity
Bowing deformity of the femur and tibia predisposes these
bones to fracture [69]. Axial realignment is important for
preventing refracture after treatment for fracture of pagetic
bones [71]. High tibial osteotomy reduces knee pain in pa-
tients with severe bowing deformity of the tibia if degenera-
tion of articular cartilage is not advanced [65]. High tibial
osteotomy allows bowing deformity of the tibia to realign
the knee joints, decreasing mechanical stress [72]. Based on
these findings, correction osteotomy for bowing-deformed
bones can be performed using an external fixator [65].
Corrective osteotomy of the tibia using an Ilizarov external
fixator has been performed for treatment of bowing
deformity [65].
Follow-up for patients with PDB
Serum AP should be measured annually in untreated pa-
tients with mild cases. In treated patients, serum AP should
be monitored every 3–4 months. It is not necessary to rou-
tinely repeat imaging procedures unless complications are
suspected (such as the development of osteoarthritis or
fractures).
Conclusion
PDB is uncommon in Japan. The diagnosis of PDB is based
on finding the typical features on radiographs. Bone scintig-
raphy and measurement of serum AP are sensitive means to
screen for PDB. These guidelines emphasize the impor-
tance of bone biopsy to differentiate PDB from secondary
tumors such as metastases from prostate cancer or breast
cancer, and other sclerosing bone dysplasias. In Japan,
EHDP and calcitonin are approved for the treatment of
PDB. Risedronate is currently under development for use
in the treatment of PDB in Japan.
Acknowledgments This study was supported by the Research Encour-
agement Award from the Japan Osteoporosis Society.
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