Case Report
Paget’s Disease of the Bone : A Report of Three Cases
K Bhatt*, C Balakrishnan*, G Mangat*, K Bajan**, T Ashavaid***, VR Joshi*

Abstract

Paget’s disease is uncommon in Asians. We present 3 patients with varying manifestations. A 50 years oldlady was detected to have raised alkaline phosphatase at a routine health check-up. Isoenzyme studiesconfirmed its bony origin. Bone scan revealed polyostotic disease. A 65 years old male patient with knownPaget’s disease of 6 years duration presented with pelvic girdle pain, progressive increase in alkalinephosphatase levels and worsening bone scan. A 45 years old male was admitted with chest pain. Cardiacevaluation was normal. Bone scan picked up a cough fracture in the left 7th rib and an incidental Paget’sdisease of the skull. All three had elevated markers of bone metabolism in the serum and urine. With monthlyintravenous pamidronate there was significant improvement in the bone markers and follow-up bonescans. ©
INTRODUCTION
Paget’s disease is uncommon in Asians.1 There areonly stray case reports from India.2,3 We describe ourexperience with three patients and, review the relevantliterature.
CASE 1
Mrs KI, a 50 years old lady was referred to us inOctober 2002. She had well-controlled hypertension anddiabetes for the past 10 years. In September 2002 sheunderwent a routine health check. Clinical examinationthen was normal and baseline investigations were allnormal except an elevated alkaline phosphatase (310u/l). Vitamin D and PTH levels were normal. She wasreferred to a gastroenterologist who suspectedsubclinical primary biliary cirrhosis. The alkalinephosphatase isoenzymes ( liver component 44 u/l andbone component 266 u/l) revealed that the elevation wasmainly due to the heat stable bone fraction and hencethe referral to us. She complained of mechanical backand knee pains of a few years duration but, there wereno bony pains.
On examination general examination was normal.There was mild restriction of the lumbosacral spinemovement. There was patellofemoral crepitus. There wasno bone tenderness. Systemic examination was normal
Radiographs of the lumbosacral spine and kneesshowed mild degenerative joint disease. Bone scan (Fig. 1) showed intense uptake in the skull, left ilium andright femur. A diagnosis of polyostotic Paget’s diseasewas made. In view of the intense calvarial involvement,CT scan of the base of the skull was done, and it ruledout cranial nerve involvement at the exit foramina.
*Rheumatology; **Internal Medicine; ***Biochemistry Divisions,
PD Hinduja Hospital and MRC, Veer Savarkar Marg,
Mumbai 400 016.
Received : 14.2.2004; Accepted : 30.6.2005
Although she was asymptomatic, in view of thepolyostotic disease and skull base involvement she hasbeen started on monthly intravenous pamidronateinfusions.
There was significant improvement in the symptoms,serum alkaline phosphatase (Table 1) and bone scan(Fig. 2) after 3 intravenous pamidronate (60mg per dose)infusions.
CASE 2
Mr TS, a 65 years old male patient, was seen in therheumatology clinic in May 2001 for bilateral hip painsof 6 months duration. In 1990, upper gastrointestinalendoscopy confirmed reflux oesophagitis. Appropriatetreatment led to complete resolution of the refluxsymptoms and repeat endoscopy in 1995 was normal.In 1997 he underwent trans-urethral prostatic resectionfor benign hypertrophy of the prostate. Laboratoryreports revealed progressive increase in the serumalkaline phosphatase from 1995. Recent alkalinephosphatase was 950 u/l. Bone scan in 2000 hadrevealed multiple hot spots (Fig. 3). Urosurgeon had ruledout prostatic metastasis. A diagnosis of Paget’s diseasewas made and symptomatic treatment given. He wasreviewed in March 2003. His symptoms had worsenedand the serum alkaline phosphatase had increased to1720 u/l.
Clinical examination was normal. Repeat bone scanhad shown increased uptake (Fig. 4). Bone specific alkaline phosphatase and urinary pyridine and deoxypyridine cross links were elevated (Table 1). He wastreated with 6 monthly intravenous infusions ofpamidronate (60mg per dose). There was significantimprovement in biochemical parameters (Table 1) andbone scan (Fig. 5).
CASE 3
A 52 years old male patient was admitted in November2002 with a week's history of chest pain. This pain wasworse on lying on the left and on coughing.
Clinical examination revealed localised tendernessof the left 7th rib. Rest of the examination was normal.
Baseline haemogram was normal. ECG and 2-D Echowere normal. Bone scan revealed a stress fracture of therib and Paget’s disease of the skull (Fig. 6). Serumalkaline phosphatase was elevated at 223 u/l (bonefraction 219 u/l). Serum PTH was normal. Urinarypyridine and pyridine-D cross links were elevated (Table 1).
A diagnosis of Paget’s disease was made and he wasgiven 3, monthly pulse of IV pamidronate (60mg/perdose). There was significant improvement in both theclinical features and biochemical parameters (Table 1).
DISCUSSION
Paget's disease is common in the Caucasianpopulation.1 The reason for this could be geneticsusceptibility. It is commoner in males and tends toincrease in prevalence with age. Although viral aetiologyhas been proposed, the exact cause is unknown.1Majority (~ 95%) are asymptomatic and are detectedincidentally due a raised alkaline phosphatase or when radiographs are done for other reasons.4 Pain, (80%)deformity (15%), fractures (9%), and malignancy (< 1%)occur in those with symptoms.4 Pelvis, thoracolumbarspine, femur, and skull are the usual bones affected.Majority, are polyostotic. When skull is involved, hearing loss, cranial nerve palsies, hydrocephalus, headaches,and mental dysfunction can occur.
Bone profile may show raised alkaline phosphatase.Isoenzyme studies reveal that it is the bone component(BALP), which is elevated. BALP is not influenced byfood intake and hence is a specific marker for boneformation.5 X rays may appear to be normal in the earlystages but bone scan is more sensitive and helps todocument polyostotic disease.4 Urinary pyridiniumcollagen cross-links (CCLs) - pyridinoline (PYD) anddeoxy pyridinoline (DPYD) represent one of the finalsteps in the maturation and stabilisation of collagenwithin the bone matrix. They are released into thecirculation during bone resorption and are excreted inthe urine. They are not influenced by diet or metabolisedor reused for collagen synthesis, hence are consideredto be the best markers of bone turnover.6 Serial monitoringof urinary CCLs helps to assess the disease activity.
Parenteral calcitonin was first used in 1960. But theshort half-life, frequent relapses after stoppage of therapyand resistance to treatment has limited its use.Bisphosphonates are now the drugs of choice.4 Theyreduce osteoclast-induced resorption and osteoclasticmaturation. Further relapses are uncommon due to theirlong tissue half-life. Oral risndronate and intravenouspulses of pamidronate have both been used with goodefficacy.
Pain relief, reduction in urinary pyridinoline anddeoxypyridinoline cross-links and reduction /normalization of alkaline phosphatase occur withadequate therapy. After this the treatment can be stoppedand the patient followed closely with 3-6 monthly bonemarkers.7 A 25% increase in these markers when compared to the previous lowest point is an indicationto restart treatment.7 Further, on treatment osteolyticlesions especially those in the skull may show sclerosis.Quantitative bone scan assessment shows animprovement but up to 20 % residual uptake may persistin spite of adequate disease control.
To conclude, we described three patients with Paget'sdisease of the bone. Two of these were asymptomatic.Even if asymptomatic these patients often need treatmentto prevent fractures or development of osteosarcoma.Parenteral pamidronate is effective in reducing thedisease activity. Apart from repeat bone scan, bonealkaline phosphatase and urinary pyridinoline/de-oxypyridinoline levels when monitored, act as a guide to therapy.

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