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TC(993).(05).Orthopedics Case No 71.Paget disease of bone

1) Definition — Paget disease of bone কী?

Paget disease of bone / Osteitis deformans হলো chronic focal disorder of bone remodelling, যেখানে osteoclast-mediated bone resorption অস্বাভাবিকভাবে বেড়ে যায়, এরপর osteoblast দিয়ে দ্রুত কিন্তু disorganized new bone তৈরি হয়। ফলে bone বড়, দুর্বল, deform, vascular এবং fracture-prone হয়ে যায়। সাধারণত pelvis, femur/tibia, skull, spine বেশি affected হয়।

2) Cause / Etiology & Pathophysiology — কারণগুলো

Exact cause fully known নয়, তবে কয়েকটি factor গুরুত্বপূর্ণ:

  1. Genetic predisposition
    • Family history থাকতে পারে; Endocrine Society guideline অনুযায়ী family history ৫–৪০% পর্যন্ত report হয়েছে, common estimate ১০–২০%।
    • SQSTM1/p62 mutation familial ও sporadic Paget disease-এর susceptibility বাড়াতে পারে।
  2. Abnormal osteoclast activity
    • মূল pathology হলো osteoclast overactivity → excessive bone resorption → compensatory osteoblast overactivity → disorganized woven/lamellar “mosaic” bone।
    • এই new bone normal bone-এর মতো শক্ত ও organized নয়, তাই deformity/fracture হয়।
  3. Age-related risk
    • সাধারণত ৫০ বছরের পরে বেশি দেখা যায়; elderly population-এ incidental raised ALP বা X-ray finding থেকে ধরা পড়ে।
  4. Environmental factor
    • Environmental trigger suspected, কিন্তু definitive cause প্রমাণিত নয়। MedlinePlus/NIH summary-তে cause uncertain, environmental factor possible বলা হয়েছে।
  5. Viral hypothesis
    • Paramyxovirus/measles-like viral trigger আগে suggest করা হয়েছে, তবে current evidence definitive নয়। Clinical decision সাধারণত genetic + bone turnover abnormality ভিত্তিক।

3) Symptoms — লক্ষণগুলো point আকারে

অনেক patient asymptomatic থাকে; অন্য test করতে গিয়ে ALP high বা X-ray abnormality থেকে ধরা পড়ে। Symptomatic হলে:

  1. Bone pain
    • Deep, dull, constant pain; rest/night pain হতে পারে।
    • Pain disease activity বা adjacent osteoarthritis—দুই কারণেই হতে পারে।
  2. Bone deformity
    • Tibia/femur bowing → হাঁটার ভঙ্গি বদলে যায়।
    • Skull enlargement → hat size বড় হওয়া, frontal bossing।
  3. Skull involvement
    • Headache, hearing loss, tinnitus।
    • Cranial nerve compression হলে visual problem/neurologic symptom হতে পারে।
  4. Spine involvement
    • Back pain, spinal stenosis।
    • Nerve root compression → limb pain, tingling, numbness, weakness।
  5. Pelvis/femur involvement
    • Hip pain, altered gait।
    • Adjacent hip/knee osteoarthritis develop করতে পারে।
  6. Warmth over bone
    • Highly vascular pagetic bone-এর উপর skin warm লাগতে পারে।
  7. Fracture
    • Minimal trauma-তে pathological fracture হতে পারে।

4) Clinically diagnosis — কীভাবে clinically suspect করবেন?

Clinical suspicion করবেন যদি:

  1. Age >50 + unexplained bone pain/deformity।
  2. Incidental isolated raised ALP with normal liver enzymes/GGT।
  3. X-ray-তে typical pagetic change।
  4. Skull involvement হলে headache/hearing loss।
  5. Long bone bowing + joint pain।
  6. Family history of Paget disease।

Typical X-ray signs:

  • Cortical thickening
  • Coarse trabeculae
  • Bone enlargement
  • Mixed lytic–sclerotic lesion
  • Skull: “cotton wool” appearance
  • Vertebra: “picture-frame vertebra”
  • Tibia/femur: bowing, lytic “blade of grass/flame-shaped” lesion

Endocrine Society guideline suspected Paget disease-এ suspicious skeletal region-এর plain radiograph recommend করে।

5) Investigations — specific workup

A. First-line investigations

  1. Serum total ALP + LFT/GGT
    • Paget disease active হলে ALP বাড়ে।
    • GGT/LFT normal থাকলে raised ALP-এর bone source বেশি suggestive।
    • Guideline radiological diagnosis-এর পরে serum total ALP recommend করে।
  2. Plain X-ray of affected/suspicious bone
    • Diagnosis confirm করার সবচেয়ে practical first imaging।
    • NIAMS-ও X-ray-কে common diagnostic test হিসেবে উল্লেখ করেছে।
  3. Radionuclide bone scan / Tc-99m bone scintigraphy
    • Disease extent দেখতে।
    • Guideline diagnosed Paget disease-এ extent identify করতে bone scan suggest করে।

B. Disease activity ও treatment safety tests

  1. Bone-specific ALP / PINP
    • Liver disease থাকলে total ALP confuse করতে পারে; তখন bone-specific marker useful।
  2. Serum CTX or urinary NTX
    • Bone resorption activity ও response follow-up।
  3. Serum calcium, phosphate, creatinine/eGFR
    • Bisphosphonate দেওয়ার আগে essential।
    • Zoledronic acid CrCl <35 mL/min হলে contraindicated।
  4. 25-OH Vitamin D
    • Vitamin D deficiency থাকলে bisphosphonate-এর পরে hypocalcemia risk বাড়ে।
  5. PTH
    • Hyperparathyroidism exclude করতে।

C. Complication-based tests

  1. MRI spine/brain
    • Spinal cord compression, nerve compression, basilar invagination suspected হলে।
  2. CT scan
  • Complex skull/spine/pelvis involvement, surgical planning, suspected sarcomatous change।
  1. Audiometry
  • Skull involvement + hearing loss থাকলে।
  1. Dental/oral exam
  • IV bisphosphonate-এর আগে ONJ risk কমাতে dental assessment useful; MedEx zoledronic acid page-এ oral exam warning আছে।
  1. Bone biopsy
  • Routine নয়; metastatic bone disease, osteosarcoma, atypical aggressive lesion সন্দেহ হলে।

6) Differential diagnosis

  1. Osteoarthritis
  2. Osteoporosis with fracture
  3. Osteomalacia/Vitamin D deficiency
  4. Bone metastasis
  5. Multiple myeloma
  6. Primary hyperparathyroidism
  7. Fibrous dysplasia
  8. Chronic osteomyelitis
  9. Osteosarcoma
  10. Renal osteodystrophy

7) Complications — সহজভাবে

  1. Pathological fracture
    • Pagetic bone বড় হলেও দুর্বল, তাই minor trauma-তে fracture হতে পারে।
  2. Bone deformity
    • Long bone bowing, skull enlargement, kyphosis।
  3. Secondary osteoarthritis
    • Deformed bone joint-এর উপর abnormal stress দেয় → hip/knee OA হয়।
  4. Hearing loss
    • Skull base involvement হলে auditory nerve/ossicle pathway affected হতে পারে।
  5. Nerve compression
    • Spine/skull involvement → radiculopathy, spinal stenosis, paraplegia rare।
  6. High-output cardiac failure
    • Extensive vascular pagetic bone থাকলে heart বেশি blood pump করতে বাধ্য হয়; severe disease-এ heart failure হতে পারে।
  7. Hypercalcemia
    • Immobilization + high bone turnover থাকলে serum calcium বাড়তে পারে।
  8. Renal stone
    • Excess calcium turnover/immobilization-related hypercalcemia থেকে stone হতে পারে।
  9. Osteosarcoma / giant cell tumor
    • Rare but serious; sudden severe pain, swelling, rapidly enlarging lesion, lytic destruction হলে urgent evaluation।
  10. Surgical bleeding
  • Pagetic bone hypervascular, orthopedic surgery-তে bleeding বেশি হতে পারে।

8) Treatment management — guideline-based

Treatment কাকে দেবেন?

Treat করবেন যদি:

  1. Paget-related bone pain থাকে
  2. Active disease: high ALP/bone turnover marker
  3. Skull/spine/weight-bearing bone involvement
  4. Osteolytic lesion বা deformity progression
  5. Fracture risk / planned orthopedic surgery
  6. Neurologic compression
  7. Hypercalcemia due to immobilization
  8. High-output cardiac failure suspected

Endocrine Society most active Paget disease with future complication risk-এ bisphosphonate recommend করে এবং contraindication না থাকলে single 5 mg IV zoledronic acid treatment of choice বলে।

9) Bangladesh prescription-context drug list

MedEx Bangladesh-এ Paget disease indication-এর under-এ listed generics হলো: Alendronic acid, Risedronate sodium, Risedronate sodium + Calcium carbonate, Salmon calcitonin, Zoledronic acid।

A. First-line disease-modifying drug

1) Generic name: Zoledronic acid / Zoledronate

  • Therapeutic category: Bisphosphonate preparation
  • Pharmacological class: Nitrogen-containing bisphosphonate; osteoclast-mediated bone resorption inhibitor
  • Purpose / কেন used হয়: Paget disease-এর high bone turnover suppress করে, bone pain কমায়, ALP normalize করে, long remission দেয়।
  • Dose & duration: 5 mg IV infusion once, infusion time ≥15 minutes। Retreatment usually needed হয় না within several years unless biochemical/clinical relapse। Endocrine Society table: zoledronate 5 mg single infusion over 15 min; retreatment seldom required within 5 years।
  • Before infusion: serum creatinine/eGFR, calcium, phosphate, 25-OH vitamin D check; adequate hydration।
  • Calcium/Vit D: Paget patient-এ zoledronic acid-এর পরে especially first 2 weeks elemental calcium 1500 mg/day + vitamin D 800 IU/day advised।
  • Common side effects: fever, myalgia, headache, arthralgia, limb pain, flu-like illness, nausea/vomiting/diarrhea, eye inflammation।
  • Serious risk: hypocalcemia, renal toxicity, osteonecrosis of jaw, atypical femur fracture, severe musculoskeletal pain।
  • Contraindication: hypocalcemia, CrCl <35 mL/min or acute renal impairment, hypersensitivity।
  • Interaction: aminoglycosides/loop diuretics → hypocalcemia risk; nephrotoxic drugs → renal toxicity; renal-excreted drugs monitor।
  • Bangladesh available brand name with strength:
    • Aclasta — 5 mg/100 mL IV infusion
    • Bonizol — 5 mg/100 mL IV infusion
    • Zandra — 5 mg/100 mL IV infusion
    • Zoldix — 5 mg/100 mL IV infusion
    • Zoledron — 5 mg/100 mL IV infusion
    • Zolenic — 5 mg/100 mL IV infusion
    • Zoltero — 5 mg/100 mL IV infusion
      MedEx lists these 5 mg/100 mL brands in Bangladesh.

Bangladesh doctors commonly use: symptomatic/active Paget disease-এ IV zoledronic acid সবচেয়ে practical first-line, কারণ one-time infusion এবং long remission।

B. Oral bisphosphonate alternatives

2) Generic name: Alendronic acid / Alendronate

  • Therapeutic category: Bisphosphonate preparation
  • Pharmacological class: Osteoclast inhibitor; bone hydroxyapatite binding antiresorptive
  • Purpose / কেন used হয়: Zoledronic acid unavailable/contraindicated/intolerant হলে oral alternative হিসেবে bone turnover কমাতে।
  • Paget dose: 40 mg orally once daily for 6 months। MedEx alendronic acid page-এ Paget dose 40 mg once daily for 6 months উল্লেখ আছে।
  • Administration: সকালে empty stomach, full glass water, 30 মিনিট upright; food/calcium/antacid পরে।
  • Side effects: dyspepsia, esophagitis/esophageal ulcer, dysphagia, abdominal pain, constipation/diarrhea, musculoskeletal pain, headache, rare ONJ/atypical femur fracture।
  • Contraindication: esophageal stricture/achalasia, inability to sit/stand 30 min, hypocalcemia, hypersensitivity, CrCl <35 mL/min not recommended।
  • Interaction: calcium/antacid/iron/magnesium reduce absorption; NSAID/aspirin increases upper GI adverse effects।
  • Bangladesh available brand name with strength:
    • Alendon — 10 mg tablet
    • Alendon — 70 mg tablet
      MedEx lists Alendon 10 mg and 70 mg by Beximco.

Important Bangladesh note: Paget dose is 40 mg/day, কিন্তু MedEx-listed brand strength 10 mg/70 mg; তাই exact regimen specialist judgement ছাড়া prescribe করা ঠিক নয়।

3) Generic name: Risedronate sodium

  • Therapeutic category: Bisphosphonate preparation
  • Pharmacological class: Osteoclast-mediated bone resorption inhibitor
  • Purpose / কেন used হয়: Oral alternative; Paget disease activity কমাতে।
  • Guideline Paget dose: 30 mg orally once daily for 2 months। Endocrine Society table: risedronate 30 mg/day for 2 months।
  • Administration: সকালে empty stomach, water দিয়ে, 30 মিনিট upright; food/calcium/antacid আলাদা।
  • Side effects: chest pain, dysphagia/odynophagia, heartburn, GI upset, diarrhea/constipation, headache, severe bone/joint/muscle pain, jaw pain/swelling।
  • Contraindication: hypocalcemia, CrCl <30 mL/min, pregnancy/lactation, hypersensitivity।
  • Interaction: calcium/magnesium/aluminum antacid/supplement absorption কমায়; aspirin/NSAID GI irritation বাড়ায়।
  • Bangladesh available brand name with strength:
    • Risedon — 150 mg
    • Risonet — 35 mg, 150 mg
    • Salost — 5 mg, 150 mg
    • Salost DR — 35 mg delayed-release
    • Sedron — 5 mg, 35 mg
      MedEx lists these risedronate brands/strengths.

Important Bangladesh note: Guideline Paget dose 30 mg/day; MedEx-listed strengths 5/35/150 mg বেশি osteoporosis-oriented. তাই active Paget disease-এ exact dose availability না থাকলে IV zoledronic acid preferred।

4) Generic name: Risedronate sodium + Calcium carbonate

  • Therapeutic category: Bisphosphonate preparation
  • Pharmacological class: Bisphosphonate + calcium supplement co-package
  • Purpose / কেন used হয়: Risedronate with calcium support; MedEx Paget indication list-এ আছে, তবে active Paget-এর guideline regimen-এর substitute নয়।
  • Dose form: 1 tablet risedronate 35 mg once weekly + 6 tablets calcium carbonate 500 mg remaining days।
  • Side effects: risedronate-related GI irritation, dysphagia, heartburn, jaw pain; calcium-related constipation/GI upset।
  • Interaction: calcium/antacid risedronate absorption কমায়; separate timing প্রয়োজন।
  • Bangladesh available brand name with strength:
    • Risedon Plus — 35 mg + 500 mg tablet, Square Pharmaceuticals PLC।

C. Second-line / special situation

5) Generic name: Salmon calcitonin

  • Therapeutic category: Hormone in bone formation by inhibiting bone resorption
  • Pharmacological class: Calcitonin hormone analogue; osteoclast inhibition
  • Purpose / কেন used হয়: Bisphosphonate contraindicated/intolerant হলে active Paget disease-এ second-line; hypercalcemia থাকলেও useful হতে পারে। MedEx says active Paget disease when alternative treatments not suitable।
  • Dose: 100 IU SC/IM daily; MedEx range: 50 IU 3 times weekly to 100 IU/day।
  • Duration: Usually 3–6 months or response-guided; ALP follow-up।
  • Side effects: nausea/GI disturbance, dizziness, flushing, tingling, unpleasant taste, rash, abdominal pain, urinary frequency, tremor, injection-site inflammation।
  • Contraindication: hypersensitivity, hypocalcemia।
  • Interaction: digitalis/cardiac glycosides, calcium-channel blockers may need dose adjustment; may decrease lithium concentration।
  • Bangladesh available brand name with strength:
    • Calcitonin — 100 IU/mL injection, City Overseas Ltd।

D. Supportive drugs doctors often add

6) Generic name: Calcium carbonate + Vitamin D3

  • Therapeutic category: Specific mineral & vitamin combined preparation
  • Pharmacological class: Calcium supplement + cholecalciferol
  • Purpose / কেন used হয়: Zoledronic acid/bisphosphonate-এর পরে hypocalcemia prevent; bone health support; vitamin D deficiency correction।
  • Dose: Paget patient receiving zoledronic acid: elemental calcium 1500 mg/day divided + vitamin D 800 IU/day, especially first 2 weeks।
  • Common Bangladesh dosing forms: Calcium 500 mg + D3 200 IU, or Calcium 500/600 mg + D3 400 IU; MedEx usual dosing 1 tab twice daily depending strength।
  • Side effects: constipation, nausea, vomiting, stomach cramps, dry mouth, increased thirst/urination if excess।
  • Contraindication: hypercalcemia, renal calculi/nephrolithiasis, hyperthyroidism, Zollinger–Ellison syndrome।
  • Interaction: tetracycline/doxycycline/minocycline absorption কমায়; digoxin toxicity risk; other calcium/vit D/calcitriol excess hypercalcemia risk।
  • Bangladesh available brand examples with strength:
    • A-Cal D — 500 mg + 200 IU
    • A-Cal DX — 500 mg + 400 IU
    • Acical-D — 500 mg + 200 IU
    • Acical-DX — 600 mg + 400 IU
    • Calbo-D — 500 mg + 200 IU
    • Calcin-D — 500 mg + 200 IU
    • Calcin-DX — 600 mg + 400 IU
    • Calvimax D — 500 mg + 200 IU
    • Ipical-D — 500 mg + 200 IU
    • Ipical DX — 600 mg + 400 IU
      MedEx lists many brands; examples above are from the listed Bangladesh brands.

7) Generic name: Paracetamol / Acetaminophen

  • Therapeutic category: Non-opioid analgesic
  • Pharmacological class: Analgesic–antipyretic
  • Purpose / কেন used হয়: Bone pain/joint pain control; zoledronic acid infusion-এর acute-phase fever/myalgia কমাতে। MedEx zoledronic acid page also notes acetaminophen after infusion may reduce acute-phase reaction।
  • Adult dose: 500–1000 mg every 6–8 hours PRN; usual max 3–4 g/day, liver disease/alcohol use/low body weight হলে lower max।
  • Side effects: usually safe; overdose → severe hepatotoxicity।
  • Interaction: alcohol, warfarin chronic high dose, other paracetamol-containing combination।
  • Bangladesh available brand examples:
    • Napa — 500 mg
    • Ace — 500 mg
    • Fast — 500 mg
    • Xcel — 500 mg
    • Napa One/Fast One — 1000 mg
      MedEx lists common 500 mg brands including Ace, Fast, Napa.

8) Generic name: Aceclofenac / Etoricoxib — short-course pain control

  • Therapeutic category: NSAID / COX-2 selective NSAID
  • Pharmacological class: Anti-inflammatory analgesic
  • Purpose / কেন used হয়: Paget-related adjacent osteoarthritis বা inflammatory musculoskeletal pain-এ short-term pain relief; disease-modifying নয়।
  • Aceclofenac dose: 100 mg orally twice daily after food, short course।
  • Etoricoxib dose: 60–90 mg once daily short course, patient risk অনুযায়ী।
  • Side effects: gastritis/ulcer/bleeding, renal dysfunction, fluid retention, BP rise; etoricoxib-এ CV risk caution।
  • Interaction: anticoagulant/antiplatelet, steroid, ACEi/ARB/diuretic, CKD, peptic ulcer disease।
  • Bangladesh available brand examples:
    • Aceclofenac: Avenac 100 mg, Biofenac 100 mg, Reservix 100 mg, Vaxtin 100 mg, Aceclofenac 100 mg। MedEx lists many 100 mg brands.
    • Etoricoxib: Etorix 60/90/120 mg, Recox 60/90 mg, Etoshine 60/90 mg, X Dol 60/90/120 mg।

10) Practical prescription pattern in Bangladesh

Common doctor-used list:

  1. Zoledronic acid 5 mg/100 mL IV infusion — single dose
    • First-line for symptomatic/active Paget disease.
    • Used because one dose gives long biochemical remission and good pain response.
  2. Calcium carbonate + Vitamin D3
    • Given around bisphosphonate therapy to prevent hypocalcemia and correct deficiency.
  3. Paracetamol 500–1000 mg PRN
    • Pain/fever/myalgia control; especially after zoledronic infusion.
  4. NSAID short course
    • If adjacent osteoarthritis/joint pain prominent and renal/GI/CV risk acceptable.
  5. Alendronate / Risedronate
    • Oral alternative when IV zoledronic acid unsuitable; but Bangladesh strength availability may not match classic Paget regimen.
  6. Salmon calcitonin injection
    • Rarely used now; mainly if bisphosphonate contraindicated or not tolerated.

11) Monitoring follow-up

  1. Baseline: ALP, LFT/GGT, calcium, phosphate, creatinine/eGFR, 25-OH vitamin D।
  2. Treat vitamin D deficiency and hypocalcemia before bisphosphonate।
  3. After zoledronic acid: check calcium if symptomatic or high-risk।
  4. Serum ALP at 3–6 months; then 6–12 monthly if active/high-risk।
  5. Bone scan/X-ray not routinely repeated unless symptoms persist, ALP rises, or lytic lesion monitoring needed।
  6. New severe focal pain/swelling → urgent X-ray/MRI to exclude fracture/sarcoma।

12) Prevention — কীভাবে complication prevent করবেন?

Primary prevention নিশ্চিতভাবে নেই, কারণ exact cause unknown। তবে complication prevention করা যায়:

  1. Family history থাকলে age >50 থেকে serum ALP + targeted X-ray consider।
  2. Unexplained isolated raised ALP হলে liver source exclude করে bone evaluation।
  3. Adequate vitamin D/calcium intake, especially before/after bisphosphonate।
  4. Fall prevention: walking aid, home safety, vision correction।
  5. High-impact exercise avoid if weight-bearing pagetic bone involved; physiotherapy-guided low-impact exercise।
  6. Hearing symptom থাকলে early audiometry।
  7. Dental assessment before IV bisphosphonate; invasive dental procedure আগে plan।
  8. Persistent new severe bone pain, swelling, deformity progression হলে urgent evaluation।
  9. Surgery planned on pagetic bone হলে pre-operative bisphosphonate specialist plan; bleeding risk কমাতে পারে।

Overview / Summary

Paget disease of bone হলো focal high-turnover bone remodelling disorder, যেখানে bone বড় কিন্তু structurally weak হয়। Diagnosis সাধারণত X-ray + raised ALP + bone scan for extent দিয়ে হয়। Symptomatic/active disease-এর first-line treatment হলো bisphosphonate, বিশেষ করে Zoledronic acid 5 mg IV single infusion। Bangladesh MedEx অনুযায়ী disease-specific available generics হলো alendronic acid, risedronate, risedronate+calcium, salmon calcitonin, zoledronic acid।

Actionable Plan / Steps

  1. Suspect করলে: ALP + LFT/GGT + X-ray affected bone।
  2. Confirm হলে: bone scan দিয়ে extent map করুন।
  3. Before treatment: Ca, phosphate, creatinine/eGFR, 25-OH vitamin D, dental review।
  4. Symptomatic/active/high-risk হলে: Zoledronic acid 5 mg IV once if CrCl ≥35 and calcium normal।
  5. Calcium 1500 mg elemental/day + Vit D 800 IU/day at least first 2 weeks after infusion।
  6. Follow-up ALP at 3–6 months, then 6–12 monthly।
  7. Red flags: sudden severe pain, swelling, fracture, neurologic deficit, hearing loss → urgent imaging/specialist referral।

Reference List — Textbook + Guideline + DOI

  1. Harrison’s Principles of Internal Medicine, 21st ed. Chapter: Disorders of Bone and Mineral Metabolism / Paget Disease of Bone.
  2. Davidson’s Principles and Practice of Medicine, 24th ed. Chapter: Metabolic Bone Disease.
  3. Robbins & Cotran Pathologic Basis of Disease, 10th ed. Chapter: Bones, Joints, and Soft Tissue Tumors—Paget disease / osteitis deformans.
  4. Singer FR, Bone HG, Hosking DJ, et al. Paget’s Disease of Bone: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2014;99(12):4408–4422. DOI: 10.1210/jc.2014-2910.
  5. Ralston SH, Corral-Gudino L, Cooper C, et al. Diagnosis and Management of Paget’s Disease of Bone in Adults: A Clinical Guideline. Journal of Bone and Mineral Research. 2019;34(4):579–604. DOI: 10.1002/jbmr.3657.
  6. Ralston SH, Langston AL, Reid IR. Pathogenesis and management of Paget’s disease of bone. The Lancet. 2008;372:155–163. DOI: 10.1016/S0140-6736(08)61035-1.

Md.Rafiqul Islam Lipu,Date:-13-06-2026 Saturday Time:-02-57-33 Pm

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