Paget’s Disease of Bone 381 23 Paget’s Disease of Bone

Richard Williams Whitehouse and A. Mark Davies

CONTENTS Paget’s disease of bone has been considered a common disorder affecting approximately 3%– 23.1 Introduction 381 4% of the population over 40 years of age. Conse- 23.2 Aetiology 381 23.3 Epidemiology 382 quently it is the second commonest bone pathology 23.4 Imaging Appearances 382 of “metabolic” origin, after osteoporosis. However, 23.5 Complications 385 the prevalence of Paget’s disease varies considerably 23.5.1 Fracture and Deformity 385 around the world, being rare in the Far East and 23.5.2 Arthritis 386 commonest in the north west of England. Since the 23.5.3 Demineralisation 387 23.5.4 Tumour (Primary and Secondary) 387 1980’s, studies and reports from around the world 23.6 Treatment 389 have suggested a marked reduction in the incidence 23.6.1 Medical 389 of new cases of Paget’s disease of bone. In addition 23.6.2 Surgical 389 the age at first presentation appears to be increasing 23.7 Differential Diagnosis 390 whilst both the severity and extent of bone involve- 23.8 Conclusions 390 References 390 ment in new cases is decreasing. If substantiated and continued, these trends will result in the condition becoming rare. There has not, as yet been any report of a reduction in the incidence of the serious compli- cations of Paget’s disease, in particular the develop- 23.1 ment of bone sarcoma. Introduction

Paget’s disease of bone, named after the nineteenth century British surgeon Sir James Paget, remains a 23.2 condition of disputed aetiology, with virus infec- Aetiology tion and genetic susceptibility both implicated. Although sporadic and seemingly random in the Paget’s disease remains of uncertain and disputed sites and extent of bone involvement in individuals, aetiology. The two main theories are of “slow” virus because markedly altered bone turnover and cel- infection and genetic abnormality. Ownership of lular activity are histologically and biochemically dogs not vaccinated against canine distemper virus characteristic of the condition, it is often placed with appears to increase the risk of developing Paget’s metabolic bone diseases. disease, but so does ownership of cats or birds The pelvis, sacral and lumbar spine and femora (Khan et al. 1996) or a history of measles (Renier are the commonest locations for this condition, with et al. 1996b). Contact with cattle, ingestion of meat the pelvis (including the sacrum) involved in about from sick livestock and frequent ingestion of brains two thirds of cases. or bovid viscera during youth are also risk factors (López et al. 1997). There are regional variations in the significance of these risk factors. These observa- tions support one or more transmissible agents as R. W. Whitehouse, MD aetiological in Paget’s disease. Department of Clinical Radiology, Manchester Royal Infi r- On electron microscopy, the nuclei of osteoclasts mary, Oxford Road, Manchester, M13 9WL, UK A. M. Davies, MD from pagetic bone contain lesions similar to “viral Consultant Radiologist, The MRI Centre, Royal Orthopaedic inclusion bodies” seen in other virally mediated con- Hospital, Birmingham, B31 2AP, UK ditions. In some centres, in-situ hybridisation tech- 382 R. W. Whitehouse and A. M. Davies niques have demonstrated messenger RNA (mRNA) ciated with osteoprotegerin deficiency caused by transcripts derived from various paramyxoviruses homozygous deletion of the gene encoding osteo- in bone cells from pagetic lesions, with measles and protegerin (TNFRSF11B) (Whyte et al. 2002). canine distemper virus being the most often found. Other environmental causes for Paget’s disease The findings of these studies have proved difficult have been suggested, for example calcium arsenate to replicate in other centres (Helfrich et al. 2000; (Lever 2002), a pesticide used in the cotton industry Ooi et al. 2000). Recently, in one study using an in- has been suggested as a possible cause of the marked situ reverse transcriptase polymerase chain reac- variation in prevalence of Paget’s disease in Lanca- tion technique, canine distemper virus mRNA has shire. Oral bacterial flora have also been suggested been found in 100% of material from pagetic bone as causative agents (Dickinson 1999). Evidence for (Mee et al. 1998). It has however been claimed that these hypotheses is extremely limited. measles virus is only found in laboratories that sup- port a measles virus aetiology and canine distemper virus in laboratories that support the latter virus as the causative agent (Ralston and Helfrich 1999). 23.3 Osteoclast precursors transduced with measles Epidemiology virus genes can produce osteoclast like cells with features similar to Pagetic osteoclasts (Kurihara Paget’s disease varies widely in prevalence both et al. 2000; Reddy et al. 2001). An infectious virus within and between countries (Armas et al. 2002). has never been isolated from pagetic bone but a It has been historically commonest in the North full length viral gene has now been sequenced from West of England, rare in the Far East (Yip et al. pagetic bone (Friedrichs et al. 2002). Difficulties 1996) and commoner in other countries with high of contamination and reproducibility of these tests proportions of Caucasians, particularly of Western have dogged interpretation of the results of these European origin. A high prevalence of the disease viral gene studies. is found in Buenos Aires, for example, where 95% of Genetic studies have also been inconsistent patients were of European descent, particularly Ital- (Good et al. 2001; Nance et al. 2000). Paget’s disease ian and Russian (Gómez and Mautalen 2001). An is commoner than expected in first degree relatives archaeological study of 2770 skeletons from Humber of patients with the condition. However, there are in England dating from 900 to 1850 AD showed a both familial and sporadic forms of Paget’s disease prevalence of 2.1% in those aged over 40 years, with different genetic abnormalities. At least six with a non-significant increase from 1.7% to 3.1% mutations in the ubiquitin-associated domain of the pre- and post-1500 AD (Rogers et al. 2002). More SQSTM1 (p62-sequestosome 1) gene have been iden- recently, comparative surveys of pelvic radiographs tified in patients with familial Paget’s disease and and biochemical tests from many studies around the a proportion, but not all of sporadic cases (Hock- world have suggested a marked reduction in inci- ing et al. 2002; Eekhoff et al. 2004; Johnson et al. dence of new cases of Paget’s disease (Cundy et al. 2003). Familial Paget’s disease has an earlier age of 1997, 1999; Cooper et al. 1999; Doyle et al. 2002), onset and greater fracture rate than sporadic forms. reduced severity and number of sites involved in In an American study, familial cases were less likely new cases (Morales et al. 2002)and an older age to record the US or Canada as their grandparents’ at presentation over the last 25 years (Rapado et al. birthplace, strengthening a case for genetic rather 1999; Cundy et al. 1997), typically finding a halv- than local environmental factors in the develop- ing of incidence over this period (van Staa et al. ment of the disease (Seton et al. 2003). Mutations in 2002). The condition is slightly commoner in men the TNFRSF11A gene causing early onset Paget like and is also slightly commoner in the right side of disease have also been described (Nakatsuka et al. the body. 2003). Differences in the genetic polymorphism of the oestrogen receptor-alpha gene and the calcium sensing receptor gene between pagetic and non- pagetic patients have also been detected, which may 23.4 contribute to genetic susceptibility to the disease Imaging Appearances (Donáth et al. 2004). Hyperphosphatasemia (Juvenile Paget’s disease) Both the incidental demonstration of Paget’s dis- is genetically distinct from Paget’s disease and asso- ease and its diagnosis is most often accomplished by Paget’s Disease of Bone 383 radiography. Biochemically, Paget’s disease may be suspected, or activity of known disease monitored by measurement of urinary hydroxyproline and serum total alkaline phosphatase (Fraser 1997). Further evaluation of biochemically suspected Paget’s dis- ease and the identification of extent and severity of disease is usually by radiographs and bone scintig- raphy. The imaging appearances of Paget’s disease are consequently primarily by reference to those modalities (Hoffman 1998). Paget’s disease is described as passing through three phases, as demonstrated on conventional radi- ography. An initial lytic phase, a mixed phase and a sclerotic phase. The lytic phase is infrequently seen, being most often identified in the skull (because it may persist in this location, known as osteoporo- sis circumscripta) and in long bones. It is usually Fig. 23.1. AP radiograph showing mixed lytic and sclerotic of short duration, rapidly progressing to the mixed Paget’s disease involving the entire pelvis, both femora and lower lumbar spine phase. In this second phase abnormally coarsened and disorganised new bone is formed, resulting in thickening and heterogeneous density of the bone cortex and coarsening of the trabecular bone. These changes in both the cortex and medullary bone results in loss of definition of the margin between cortical and trabecular bone. The affected bone enlarges and distorts as if softened and has a spongy textural appearance on imaging (Fig. 23.1). His- tologically, haversian systems in cortical bone are destroyed and the new bone formed to replace them is in irregular plates creating a mosaic appearance. The final, sclerotic phase represents reduction in the previously overactive osteoclastic bone resorp- tion present in the first two phases, whilst osteoblast activity continues, resulting in increasing bone den- sity and “filling in” of previously lytic areas, with a resultant more amorphous appearance to the bone Smith 2002 Fig. 23.2. AP radiograph showing sclerotic Paget’s disease of (Fig. 23.2) ( et al. ). Eventually the dis- the pelvis, right femur and lower lumbar spine. There is a mild ease becomes quiescent. left sided pelvic deformity The bone marrow may be involved in active dis- ease, with increased bone vascularity and develop- ment of a fibro-vascular stroma which replaces the (Renier et al. 1996). The involved region ends with usually fatty marrow. More often, marrow appears a “V” shaped zone of transition to normal bone. This uninvolved, particularly in the later stages of the dis- “V” or flame shaped end gives the impression of a ease, with fat attenuation on CT scanning (Fig. 23.3) progressing lesion growing along the bone, though and fat equivalent signal characteristics on MR the speed of progression of this edge on serial scanning in the interstices between coarsened tra- films is often disproportionately slow compared beculae (Whitehouse 2002). to the length of bone already involved and appar- In long bones, such as the femur, Paget’s disease ent duration of the disease. Typical rate of progres- characteristically involves a bone end (subarticular sion in the femur is about 9 mm/year (Renier and region) and extends in a confluent fashion for a vari- Audran 1997a). This has led to the suggestion that able distance along the shaft. Pagetic lesions most Paget’s disease has an earlier age of onset than gen- commonly arise in the proximal ends of long bones, erally appreciated, possibly in the second or third in the cancellous part of an epiphysis or metaphysis decade. Although Paget’s disease is considered rare 384 R. W. Whitehouse and A. M. Davies

ease causing ankylosis and extension of disease over several spinal segments has also been described. Bone scintigraphy is routinely used to demon- strate extent and distribution of Paget’s disease as markedly increased activity is seen in active disease and can be used to quantify disease activity and response to treatment (Hain and Fogelman 2002). Occasionally activity may be low in lytic disease and is also less impressive, though higher than normal, in quiescent disease. The typical distribution of pag- etic disease in long bones, including the flame edge, is clearly demonstrated on bone scans. In the spine, characteristically the whole vertebra, including the Fig. 23.3. CT of the pelvis demonstrating mixed Paget’s disease posterior elements is involved, giving rise to an iso- of the left ilium. The inset is a soft tissue window of the ilium, tope bone scan appearance described as a “clover”, confi rming the fat attenuation of the marrow space (–51 CT “heart” (Rotés et al. 2004) or “mouse’s face” shape units) (Fig. 23.4) (C.K Kim et al. 1997). PET scanning may in patients under 40 years of age, approximately also show increased metabolic activity in Pagetic 10% of patients with Paget’s disease were under 40 bone (Cook et al. 2002), even when biochemically in one series (Choma et al. 2004). It may be that the inactive with normal alkaline phosphatase and ala- rate of progress of Paget’s disease through bone is nine amino transferase levels (Spieth et al. 2003). not linear, being very rapid initially and slower, or Computed tomography (CT) of the abdomen and even halted, by the time of diagnosis. Alternatively, pelvis may demonstrate incidental Paget’s disease. Paget’s disease may progress in a series of waves CT can be useful in early, difficult or unusual Pagetic (Renier and Audran 1997b). Treatment with lesions and may demonstrate altered trabecular pat- bisphosphonates also halts progression of the dis- terns characteristic of Paget’s disease (Chrétien ease, making prospective study of the progression 1995). Large intertrabecular spaces may allow the of disease problematic. The flame edge is lytic but marrow CT number to be measured, the confirma- changes to mixed disease towards the articular sur- tion of fatty marrow density being useful to exclude face of “origin” of the pagetic bone. a marrow infiltrate (Fig. 23.3). CT can also be used Pelvic involvement is usually seen as mixed or to guide biopsy, needles of 14–17 G providing ade- sclerotic disease. Bilateral skeletal involvement in Paget’s disease is usually asymmetrical, the pelvis being the only site likely to be involved bilaterally in an individual patient with polyostotic disease (Renier and Audran 1997b). Progression of disease through the pelvis is slow, typically taking 13 years to spread to all the bones around the obturator foramen and 30 years to spread through the entire pelvis. The generic radiographic changes described above are seen as loss of trabeculae with coarsening of those remaining and thickening and splitting of the iliopectineal line and teardrop. Enlargement of the ilium is particularly noticeable if the other ilium is unaffected. The bone softening results in pelvic deformity, particularly protrusio acetabuli. At diagnosis Paget’s disease may be monostotic or polyostotic and subsequent development of new sites of disease seems uncommon, though it does occur. Progression of disease from one bone to an Fig. 23.4. Bone scintigraphy demonstrating increased activity adjacent bone is also unusual unless the intervening in the left hemipelvis and L2 vertebra, from Paget’s disease. joint is already bridged by ankylosis or osteophytes, Note the uniform involvement of the spinous process and although again, this has been described. Paget’s dis- pedicles, giving rise to the “mouse’s face” shaped activity Paget’s Disease of Bone 385

quate specimens for bone diseases including Paget’s density (Laroche et al. 1999). High DXA values may disease (Jelinek et al. 1996). therefore alert to the possibility of Paget’s disease Magnetic resonance imaging in uncomplicated but may result in underestimation of the fracture Paget’s disease usually demonstrates a normal risk if Paget’s disease is not appreciated. marrow signal on all sequences, whilst the small size of the images and low spatial resolution may render the coarsened trabecular pattern and thickened cortex inconspicuous (Fig. 23.5). In active Paget’s 23.5 disease marrow signal abnormality may be present, Complications due to increased vascularity and cellularity, particu- larly in paratrabecular and endosteal areas. Conse- 23.5.1 quently bones with high trabecular content such as Fracture and Deformity the pelvis and spine may show marked and complex marrow signal alterations during the active phase of Lytic pagetic bone is prone to fracture, particularly the disease (Vande-Berg et al. 2001). Recognition of after biopsy, resulting in the recommendation that the appearances of Paget’s disease on MR and cor- biopsy be avoided if the diagnosis is secure. This relation with other imaging is important so as not complication is however rarely seen due to the tran- to mistake it for more sinister pathology (Whitten sient nature of lytic Paget’s disease. Pagetic bone in and Saifuddin 2003). Complications of Paget’s dis- the later stages is also more prone to insufficiency- ease, in particular tumour development and spinal type stress fracture than the bone density would neurological compromise are in particular best suggest. Incremental incomplete fractures develop evaluated by MR imaging (Boutin et al. 1998). on the convexity of bowed pagetic bones, in particu- The results of bone mineral densitometry will be lar the femur or tibia, and may be multiple. These significantly influenced if Paget’s disease of bone is may complete to transverse fractures of the shaft. present in the measurement region. With respect to Transverse fractures also occur without preced- the pelvis and hips, this is particularly relevant to ing incremental fracture. These fractures are more dual energy X-ray absorptiometry (DXA) of the hip. common in women and healing is poorer than in Typically, pagetic bone is 25%–35% denser than non- normal bone. Described sites of Pagetic pathological pagetic bone, on DXA measurement. Bisphospho- fracture include the tibia/fibula, vertebrae, femur nate treatment results in a small further increase in and less commonly the pelvis, humerus and skull pagetic bone density, but a reduction in normal bone (Fig. 23.6). With the exception of vertebral and rib

a b

Fig. 23.5. a Coronal T1-weighted image demonstrating normal fatty marrow signal but thickened cortex in Paget’s disease of the pelvis and both femora. b coronal STIR image demonstrating subtle increased signal within the cortex of the left femur due to active lytic Paget’s disease. [Reproduced with permission from Whitehouse (2002)] 386 R. W. Whitehouse and A. M. Davies

reduced articular cartilage thickness in pagetic hips compared to non-pagetic hips (mean 3 mm compared to 4 mm) but no significant difference in other osteo- arthritic features (cysts, sclerosis or osteophytes), though the latter may be obscured by the Paget’s disease. Significant osteoarthritis (Kellgren and Lawrence grade 2+) was commoner in non-pagetic hips (19 of 352 hips) than pagetic hips (5 of 129 hips) (Helliwell and Porter 1999). Pagetic coxarthropa- thy may therefore be a secondary chondropathy, with progression to significant osteoarthritis being depen- dent on factors other than Paget’s disease. A smaller study of rheumatology patients found Paget’s disease adjacent to 100 joints in 69 patients with Paget’s dis- ease, 86 being hips, with osteoarthritic changes more severe on the pagetic side, though severity grading of arthritis in the pagetic joints was dependent on the presence of osteoarthritis elsewhere in the same Fig. 23.6. AP radiograph showing sclerotic Paget’s disease of patient (Helliwell 1995). Thus Paget’s disease the hemipelvis with an undisplaced insuffi ciency fracture of and hip osteoarthritis may be largely co-inciden- the ischium tal rather than causal (Fig. 23.7). Despite this, pain is the commonest symptom of Paget’s disease and fracture, the risk of fractures in non-pagetic bone osteoarthritis appears to be the commonest cause of of patients with Paget’s disease is not increased. pain in patients with Paget’s disease (Altman 1999). Whilst this may be a surveillance effect, it does A survey of patients with Paget’s disease gave deaf- suggest that patients with Paget’s disease may be at ness and bowed limbs as the commonest complica- increased risk of vertebral fracture and should be tions that patients complained of (30%–40%), whilst managed accordingly (Melton et al. 2000). Long arthritis, described as a co-morbidity, was present term bisphosphonate treatment may reduce bone in 64% (Gold et al. 1996). Careful identification of density in non-pagetic parts of the skeleton, with the features of both conditions is therefore a relevant consequent increase in the risk of fracture in non- radiological challenge. The treatment of hip arthritis pagetic bones (Gutteridge et al. 2003). by joint replacement is technically more challenging There is a case report of a minor fracture of a pag- in the presence of Paget’s disease, with a higher fail- etic coccyx causing a cauda equina syndrome from ure rate for some prostheses but the outcome is still local haemorrhage (Davis et al. 1999), more com- usually good. monly vertebral fractures or pagetic vertebral bone When the sacroiliac joint is involved by Paget’s dis- hypertrophy at higher levels would carry this risk ease, confluent pagetic bone may be present across the (Poncelet 1999). joint. There is evidence that Paget’s disease can cross The deformity caused by enlargement of the bone joints, but the sacroiliac joint is frequently ankylosed and plastic deformation results in lateral bowing of giving bone continuity when involved by Paget’s dis- the femur and protrusio acetabuli in the pelvis. ease. This may be due to pre-existing osteophytic bridges or ankylosing spondylitis or by cartilage loss secondary to the adjacent Paget’s disease. The pres- 23.5.2 ence of pre-existing ankylosing spondylitis may allow Arthritis more extensive Paget’s disease of bone throughout confluent bone from the pelvis, sacrum and lumbar Altered load-bearing and deformity of sub-articular spine (Peel et al. 1996). In addition, chondrocalci- bone surfaces by Paget’s disease are mechanisms by nosis has been demonstrated in the sacroiliac joints which arthritis may develop secondary to Paget’s dis- in some cases (Bezza et al. 1999). In uncomplicated ease. Being most often involved by Paget’s disease Paget’s disease in the spine and around the sacroiliac and also a major weight bearing joint, the hip is a joints, MR imaging does not contribute additional prime site for pagetic arthritis. One study of arthritis information to radiographic evaluation (Oostveen and Paget’s disease in the hip demonstrated slightly and van deLaar 2000). Paget’s Disease of Bone 387

albeit rare (Fenton and Resnick 1991). It is esti- mated to occur in less than 1% of patients with Paget’s disease and is most common in the elderly, those with long duration Paget’s disease and those with polyostotic Paget’s disease. Exceptions will occur and sarcoma has been described in mono- stotic disease. The most commonly affected bones in descending order of frequency are the femur, pelvis and humerus. Pagetic sarcoma is often histologi- cally heterogeneous but classified according to the most aggressive component; consequently most are osteosarcomas. Late presentation and histologically aggressive tumours in an elderly population may be factors contributing to the extremely poor prog- nosis for pagetic sarcoma, median survival being Fig. 23.7. CT scan through the hips demonstrating Paget’s disease 9 months (Grimer et al. 2003). Pagetic osteogenic of the right acetabulum and osteoarthritis of the left hip. disease sarcoma may rarely be multifocal at presentation Whitehouse (Reproduced with permission from (2002)] (Vuillemin et al. 2000). The majority of Paget’s sarcomas are predomi- 23.5.3 nantly lytic on radiographs (65%) (Fig. 23.9a). The Demineralisation lysis usually appears ill-defined or permeative within a pre-existing area of Paget’s disease. It may Demineralisation of bone is the earliest radiographic arise within the lytic, sclerotic or mixed phases of feature of Paget’s disease, producing the “lytic” the underlying disease. Cortical destruction in three phase of the disease. Even after this has progressed quarters of cases and a soft tissue mass in over half to mixed disease, immobilisation can induce a rapid are the cardinal features that should suggest the and severe demineralisation of Pagetic bone (Wal- diagnosis of malignancy, albeit not necessarily a sar- lace et al. 1996). This may be seen after immo- coma (López et al. 2003). Periosteal new bone forma- bilisation for fracture treatment or other surgical tion and dense tumour mineralization is uncommon procedure such as hip joint replacement. Subsequent (Fig. 23.9b). Unlike most sarcomas of bone Paget’s pathological fracture through the osteopenic pag- sarcoma may appear paradoxically photopenic on etic bone is common. The radiographic appearances bone scintigraphy. MR imaging of Paget’s sarcoma of immobilisation osteolysis, with or without patho- shows replacement of marrow fat with intermediate logical fracture, can be mistaken for bone destruc- or low signal intensity tumour tissue on T1-weighted tion and malignant transformation. MR imaging is images with correspondingly high signal intensity particularly valuable in distinguishing osteolysis in on T2-weighted and short tau inversion recovery Paget’s disease from more sinister complications, (STIR) images. The exception is seen if the tumour the demonstration of high signal (fatty) marrow on is particularly densely mineralised. T1 weighted imaging being reassuring (Fig. 23.8), The involvement of Pagetic bone by metastatic whilst areas of low signal may represent malignant disease is well documented, but whether Pagetic degeneration (Sundaram et al. 2001). Occasionally, bone is a preferential site for bone metastases or the the use of bisphosphonates in Paget’s disease may opposite remains controversial. Multiple myeloma lead to osteomalacia. The radiographic appearances (Neitzschman 1997) and lymphoma (Yu et al. of osteomalacia superimposed on Paget’s disease, 1997) have rarely occurred in Pagetic bone and one may simulate marrow infiltration with malignancy family with Kaposi’s sarcoma and Paget’s disease (López et al. 2003). has also been described (Hale and Kelly 1998). As the imaging features of these different malignancies occurring in association with Paget’s disease cannot 23.5.4 be distinguished biopsy diagnosis is mandatory as Tumour (Primary and Secondary) management and prognosis can vary (Fig. 23.10). Giant cell tumours have been described in Paget’s The development of primary bone sarcoma in pre- disease of bone (Fig. 23.11). These are most often in existing Paget’s disease of bone is well recognised, the facial skeleton and also seem to be familial in 388 R. W. Whitehouse and A. M. Davies

a b

Fig. 23.8a–c. a AP radiograph showing a hip replacement and sclerotic Paget’s disease. b At 3 years later there is migration of the prosthesis into a region of massive osteolysis. c Coronal T1-weighted image confi rms pagetic bone with fatty marrow c and no soft tissue mass

a b

Fig. 23.9a,b. Two cases of osteosarcoma arising in Paget’s disease. a Lytic tumour in the right ilium. b Mineralised tumour in the left ischium Paget’s Disease of Bone 389

23.6 Treatment

23.6.1 Medical

The medical treatment of Paget’s disease is now predominantly by bisphosphonates. The more recently developed highly potent bisphosphonates are preferred (Drake et al. 2001). Adequate treat- ment appears to halt progression of the disease and alleviates the pain associated with active disease (Siris 1999). The hope that other complications of Paget’s disease may be also be averted by bisphos- phonate therapy has not yet been proven. Chronic bisphosphonate treatment may be detrimental to the rest of the skeleton, with an increased risk of osteoporotic fracture at other sites. This risk may Fig. 23.10. Lymphoma arising in Paget’s disease. Note the simi- be reduced by concomitant treatment with calcium larity to the osteosarcoma in Fig. 23.9a and calcitriol (Stewart et al. 1999). Paget’s disease resistant to one bisphosphonate is uncommon and may respond to an alternative formulation (Joshua et al. 2003). Other causes of pain in Paget’s disease should be considered, particularly arthritis (being common), as treatment response to bisphosphonates will be poor if the cause is arthritis (Vasireddy et al. 2003).

23.6.2 Fig. 23.11. Extensive Paget’s disease. The lytic lesion in the Surgical right femoral neck proved to be a giant cell tumour. (Case courtesy of Dr D Ritchie) Surgical treatment of Paget’s disease in the pelvis and femora includes fracture management, osteot- omy for correction of femoral bowing deformity and hip replacement for arthropathy or femoral neck an Italian population (Rendina et al. 2004), and fracture. Fracture healing is slower and poorer in familial with facial and pelvic locations in a Korean Pagetic bone but is usually achieved (Shardlow family (G.S. Kim et al. 1997). Pseudosarcoma, a mass et al. 1999) and there is the risk of immobilisation of non-mineralised pagetic osteoid, may develop in osteolysis after surgery (Oakley and Matheson Paget’s disease, usually in a paracortical location 2003). on a long bone in a lower limb (Tins et al. 2001; Although osteotomy corrects deformity, the McNairn et al. 2001). A pelvic location for this com- indication for femoral osteotomy in Paget’s disease plication has not been described. The MR appear- is usually pain with associated deformity. Average ances can be mixed, with both high and low signal time to union of osteotomy is 6 months in Pagetic areas on T1 weighted imaging (Donáth et al. 2000), bone, with greater delay for diaphyseal osteotomy. consequently differentiation from a true sarcoma Non-union appears commoner in femoral osteotomy can be difficult and biopsy proof is usually required. fixed by intramedullary nail (Parvizi et al. 2003). Another cause of a para-osseous soft tissue mass in Hip arthroplasties may be cemented or unce- Paget’s disease is extramedullary haematopoiesis. mented, both appear satisfactory in patients with This is extremely rare and usually paraspinal in Paget’s disease (Parvizi et al. 2002; Calderoni et location, with only seven cases reported up to 1999 al. 2002; Sochart and Porter 2000). Following hip (Relea et al. 1999). arthroplasty in Paget’s disease, the risk of hetero- 390 R. W. Whitehouse and A. M. Davies topic ossification is moderately raised, but can be References reduced by pre- or immediate post-operative irra- diation (Iorio and Healy 2002). Altman RD (1999) Paget’s disease of bone: rheumatologic Osteomyelitis has been described as a complica- complications. Bone 24 [Suppl 5]:47S–48S Armas JB, Pimentel F, Guyer PB et al (2002) Evidence of geo- tion in Paget’s disease but there is little literature to graphic variation in the occurrence of Paget’s disease. support an increased risk of osteomyelitis in Pagetic Bone 30:649–650 bone after surgical intervention. The loosening or Basaria S, McCarthy EF, Belzberg AJ, Ball DW (2000) Case of an early failure of hip prostheses has been described in ivory vertebra. J Endocrinol Invest 23:533–535 Paget’s disease. Despite these considerations, surgi- Bezza A, Lechevalier D, Monréal M et al (1999) L’atteinte sacro- iliaque au cours de la maladie de Paget. 6 observations. cal management with appropriate prostheses usu- Presse Med 28:1157–1159 ally has a satisfactory outcome. Bonakdarpour A, Maldjian C, Weiss S et al (2000) Hyperphos- phatasemia: report of three cases. Eur J Radiol 35:54–58 Boutin RD, Spitz DJ, Newman JS et al (1998) Complications in Paget disease at MR imaging. Radiology 209:641–651 Calderoni P, Ferruzzi A, Andreoli I, Gualtieri G (2002) Hip 23.7 arthroplasty in coxarthrosis secondary to Paget’s disease. Differential Diagnosis Chir Organi Mov 87:43–48 Choma TJ, Kuklo TR, Islinger RB et al (2004) Paget’s disease The radiographic appearances of Paget’s disease are of bone in patients younger than 40 years. Clin Orthop usually pathognomonic. Where sclerosis is marked 418:202–204 Chrétien J. 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