Case 1

Jagdish K

Prof. Dr. A. Gowrishankar’s unit

A 45yrs old lady presented to the opd with the chief complaints of

• Pain in the knee, low backache, pain in the thigh for the past 1yr.

• Breathlessness on & off for 6months.

• Patient was apparently alright 1yr ago following

which patient developed pain in those areas,

insidious in onset, gradually progressive, no specific

character attributed. No specific aggravating /

relieving factors.

• Patient has breathlessness for the past 6months, while

doing her household activity and increases more

during exertion & relieved by rest.

• Patient complains of occasional light headedness

• No h/o Chest painPalpitationSyncopePresyncopeAbdominal painNauseaVomiting/ diarrhoea/ constipation/ bleeding

from orifices.

• No h/oDiplopiaDysphagiaDysarthriaMotor deficitsSensory deficitsUnconsciousness/ altered sensoriumInvoluntary movements

• Attained menopause 2 yrs back, cycles regular during premenstrual period. No gynaec complaints in the post menopausal period

• Vegan by diet,

• Not a k/c/o DM/SHT/TB/Asthma

• Patient has lost 10-15 cm of height in the past 2- 3 yrs.

Examination

• Comfortable at rest, • Conscious, oriented, afebrile• No pallor/ icterus/ cyanosis/ clubbing/

lymphadenopathy/ edema• Pulse: 110/min;• BP: 120/60 mm of hg, rt arm, supine position, SBP

130 mm of hg in lower limb by palpatory method.• JVP not elevated• RR : 16/min

• Patient has fixed flexion deformity of hips

• She has kyphosis, no tenderness of spine

• There is Genu varum / tibia vara.

• Other systems : normal

• Problems:Bone painLoss of heightBreathlessnessLimb deformitiesProbable High output state

Investigations

CBC• Hb: 12.2

• TC : 7,200

• DC : P60 L 40

• ESR : 6/12

• PCV : 36%

• Plt: 1.5

• MCV: 32

• MCH: 29

RFT• RBS: 84

• Urea: 23

• Creatinine: 0.6

Serum electrolytes:• Na+ : 136

• K+ : 4.5

• Cl- : 96

• HCO3- : 24

• Peripheral smear : normocytic normochromic blood picture, adequate RBCs, WBCs & platelets

• ECG : sinus tachycardia

CXR

X ray LS spine

X ray skull

• Serum calcium : 8.8 mg/dl ( total & corrected)

• Phosphate : 4 (N:2.4-4.1mg/dl)

• ALP : 880 (N: 40-140 U/L)

• PTH : 55 pg/ml (N:10-60 pg/ml)

• Vitamin D3: 40 (N: 20-76 pg/ml)

• TFT : T3 : 196 (N: 75 - 220 ng/dL)T4 : 7.2 (N: 4 - 11 μg/dL) TSH : 3.8 (N: 0.5-5.0 mIU/L)

• RBC transketolase: 500 (N:440± 120μg/ml/hr )

• ECHO : EF 66%No RWMANormal LV systolic functionCalcific aortic sclerosis

• ABG : mild respiratory alkalosis

• PFT : normal

• Pelvic bone biopsy:Increase in no & nuclei of osteoclastsJigsaw puzzle pattern appreciatedPicture consistent with Paget’s.

Pagets disease

• Sir James Paget first described it due to an inflammatory process

• Used to be called as osteitis deformans, now called as osteodystrophica deformans.

• A chronic disorder that can present as enlarged & misshapen bones

• Excessive breakdown & formation of bone causes affected bone to weaken, presenting with pain, misshapen bone, fracture & osteoarthritis.

• Disease typically affects one or few bones as opposed to osteopetrosis which affects all bones.

• Rarely diagnosed before 40 yrs

• Prevalence 1.5 – 8% depending on the age & the local prevalence

Etiology

• ViralPaget's disease may be caused by a slow virus

infection (i.e., paramyxoviruses) present for many years before symptoms appear.

Measles though recent evidence has cast some doubt upon the measles association.[4]

Canine distemper virusRespiratory syncytial virus

Genetic

Name OMIM Locus Gene

PDB1 167250 6p ?

PDB2 18q22.1 RANK

PDB3 5q35 SQSTM1

PDB4 606263 5q31 ?

Pathogenesis

• Increased no & size of osteoclasts

• Osteoclasts hypersensitive to Vitamin D3 & RANK ligand

• Marrow stromal cell – increased expression of RANK-Ligand.

Pathogenesis

Phases

• 1 : osteoclastic

• 2 : osteoclastic & osteoblastic

• 3 : exhaustive & burnt out phase

• All three phases may be seen at same time at different sites.

Symptoms

Bone pain is the most common symptom. It can occur in any bone affected by Paget's disease. It often localizes to areas adjacent to the joints.

Headaches and hearing loss may occur when Paget's disease affects the skull.

Pressure on nerves may occur when Paget's disease affects the skull or spine.

Symptoms Hip pain may occur when Paget's disease affects the pelvis or thighbone.

Damage to joint cartilage may lead to arthritis.

Teeth may spread intraorally due to the intraoral force placed on the anterior teeth (especially maxillary central and lateral incisors) by the labial tissues, especially the muscles.

Symptoms Somnolence (drowsiness) may be due to vascular steal

syndrome of the skull.

Paralysis may be due to vascular steal syndrome of the vertebrae.

Increased head size, bowing of limb, or curvature of spine may occur in advanced cases.

Hypercementosis in teeth may occur.

Diagnosis

• Calcium

• Phosphate

• ALP

• Hydroxyproline

• N telopeptide

• C telopeptide

Differential diagnosis

• Fibrogenesis imperfecta ostium

• Osteoblastic mets

• Sickle cell anemia

• Osteopetrosis

• Pyknodysostosis

Treatment

• Decision about treating patients can be complicated because No two people are affected exactly the

same way by the disease Difficulty to predict the progress.

When to treat???

• Bone pain

• Headache

• Nerve related symptoms

• Elevated SAP

• High output state

Drugs

• Oral:Etidronate : 200-400mg OD for

6months Precautions

Alendronate TiledronateRisendronate

Drugs

• IVPamidronate: 30-60 mg iv in NS OD for

3daysZolendronate : 5mg infusion in NS stat.

once a year dose.

• Calcitonin: s/c thrice a week for 18months. Nasal spray not approved for treatment of Paget’s but for osteoporosis.

• Surgery

Calcium levels

• Normal

• Hypo

• Hyper

Diet & Exercise

• 1000-1500 mg of calcium

• Adequate sunshine

• 400 units of Vitamin D3

• Especially when treating with bisphosphonates.

• Administration of calcium & bisphosphonates should be separated by 2 hours.

Prognosis

• The outlook is generally good, particularly if treatment is given earlier.

• Earlier the disease onset,morbidity is more ;

• Disease does not spread to normal bones

• Treatment can control Paget's disease and lessen symptoms, but is not a cure

• Osteogenic sarcoma can occur

• Life expectancy is not altered.

Physician & Paget’s disease

• Headache

• Nerve problems

• Vascular steal phenomenon

• calcific aortic valve sclerosis;

• High output state

Ivory vertebra

Picture frame vertebra

Osteoporosis circumscripta

carry home points • Middle age – elderly ;

• Bone pain,deformity ;nerve compression ;high output state;

• Increased osteoclastic resorption ,compensatory osteoblastic activity ;

• Normal electrolytes ;increased ALP & increased urinary markers ;

• Bisphosphonates are the treatment ;

• Prognosis is usually good ;

• ZOLENDRONATE IS AVAILABLE IN STANLEY