1. Case Study: Metabolic bone disease H.R. vd Berg Dept Radiology Kimberley Hospital 25/5/2012

2. 74 y old female Refered from Springbok (Originally from Port Nolloth) to Orthopaedics KH HT, DM-2 Pathological right midshaft humerus fracture ? Primary bone malignancy Mrs X

4. Events: 10 July – Fractured arm 11 July – Seen in Springbok & referred to Kimberley 15 July – Admitted by Ortho – Xrays done – Bloods: s-ALP 482(↑), CRP 16.7(↑), Normal FBC, UEC, LFT, CMP. 18 July ?Paget’s 21 July - Intern Med consult 22 July – Radiology consult 1 Aug – Bone scan 12 Aug – ORIF 15 Aug – D/c

7. Bone Scintogram:

8. Paget’s disease: (Osteitis deformans) Sir James Paget 1877 Multifocal chronic skeletal disease characterized by disordered & exaggerated bone remodelling leading to weak & deformed bone Disease of osteoclasts – too many with lots of nucleoli Etiology: – Genetic (20%): Autosomal dominant Earlier onset, more bones involved, more deformities & fractures – Viral: Based on clusters of disease in people exposed to unvaccinated animals & nuclear material resembling Paramyxo viral RNA found in osteoclasts ? Role of viral infection in genetically susceptible people Average onset: 45-55y (Unusual < 40y); 3M:2F More prevalent in Northern Europe, North America & Australia

9. Clinical manifestations: Asymptomatic (1/5) Fatigue Pain + tenderness Primary process Pathological fractures Malign transformation Deg joint disease ↑Hat size Deformity of long bones Warm involved extremity Peripheral nerve compression Neurological (Brainstem compression) Hearing loss, blindness, facial palsy (Neural foramina narrowing) High output CCF (↑Metabol & perfusion) LAB: ↑s-ALP / bone specific ALP: Osteoblastic act ↑u-Hydroxyproline: Osteoclastic act Normal Ca & PO (Ca may ↑ if immobilized/fracture) Usually polyostotic and asymmetrical: pelvis, 75% > femur > skull > tibia > vertebra > clavicle > humerus > ribs

10. Stages: 1.Early/ Osteolytic/ “Hot” phase: Active bone resorption Lytic lesions with sharp borders destroying cortex and advance along the shaft (candle flame, blade of grass) Start at one end of bone and slowly extend along the shaft. Bone marrow is replaced by fibrous tissue and disorganized trabecular “mosaic” pattern Flat bones showing lytic lesions = Osteoporosis circumscripta

11. 2. Intermediate/ Mixed phase: Mixed lytic & sclerotic Thickened cortex Trabecular coarsening Bowing Cortical thickening Sclerosis of iliopectineal & ischiopubic lines Dense sclerotic periphery & lucent centre = Picture frame Partial replacement of end plates by coarse trabecular bone Focal patchy densities = Cotton wool

12. 3. Inactive/ Cool/ Sclerotic phase: Decreased bone turnover with diffuse sclerosis, cortical thickening & blurred cortical- medullary borders

13. Different phases may coexist in same bone:

14. Malignant transformation(<1%): Cortical disruption, Extension into soft tissue, Periosteal reactions, Expansile intramedullary mass Biopsy indicated in monostotic lesions not which does not have the characteristics of Pagets/ young pt/ demography not usually seen – Osteosarcoma(22-90%) – Malignant fibrous histiocytoma/ Fibrosarcoma(29-51%) – Chondrosarcoma(1-15%)

16. Other complications: Stress fractures (banana fractures) Pathological fractures Osteoarthritis & Acetabular protrusio

17. Collapse with spinal stenosis Ivory vertebrae: Metastases, Lymphoma, Paget's disease, Infection

18. Basilar invagination(PF ROACH): Paget disease Fibrous dysplasia Rickets Osteogenesis imperfecta, Osteomalacia Achondroplasia Cleidocranial dysplasia Hyperparathyroidism, Hurler syndrome

19. Bone scintogram: Sensitivity 94% Symptomatic lesions have increased uptake due to bloodflow & blastic activity Normal scan in sclerotic burned-out areas Marginal uptake in lytic areas Used to establish extend & localization (sites rarely change over lifetime) as baseline

20. MR findings: For imaging of complications (spinal stenosis, basilar impression, tumour staging) Cortical thickening & Coarse trabeculations (↓T1&2) Decreased medullary cavity(↓T1&2) Cyst-like fat filled marrow spaces(↑T1&2) Bone widening

21. Cortical thickening Coarse trabeculae

22. Treatment of Paget’s disease: Pain relief Calcitonin/ Bisphosphonates – Inh osteoclast activity Surgical – Fractures, deformaties, compression, etc

23. Differential: Metastases Fibrous dysplasia Multiple myeloma Lymphoma Haemangioma Hyperparathyroidism

24. Metastases: Multiple bone lesions in pt >50y usually mets Mostly axial & proximal skeleton Lytic: Kidney, breast, thyroid, GI Blastic: Prostate, Breast, Cervix, Ovary, Bladder Mixed: Any, mostly Breast & Lung Usually widespread Cortical destruction & periosteal new bone formation Extension into soft tissue ↑Uptake on bonescan Paget’s: Thickened cortex & trabeculae Marrow replacement not mass like No cortical destruction Usually unilateral

26. Fibrous dysplasia Inability of bone forming tissue to produce mature lamellar bone Peak age: 10-20y Expansile marrow lesion Groundglass No soft tissue involvement Thin cortex Skull: greater involvement of outer table Usually ↑uptake on bone scan

27. Multiple myeloma: Monoclonal neoplastic proliferation of plasma cells involving bone marrow Peak age: 64y Multiple well-defined intramedullary lytic lesions (“Punched out”) Sclerosis rare (usually after treatment) Endosteal scalloping of cortex Soft tissue mass adjacent to bone destruction Cold on bone scan

28. Lymphoma: Peak age: 35-45y Mottled permeative bone destruction 70% Associated soft tissue component Cortical destruction late Mixed lytic & sclerotic (“Ivory bone”) ↑Uptake on bone scan

29. Hemangioma: Lytic with radiating trabecular thickening “Honeycomb”, “corduroy” in vertebrae Vertical/ radial striations (“Spoke wheel”) in skull Small punctated sclerosis(“Polka dot”) May have periosteal reaction/ soft tissue mass Usually spine & calvarium Vertebral bodies not enlarged & endplates well defined Moderate uptake on bone scan

30. Hyperparathyroidism: ↑s-Ca (↑s-ALP in 50%) Thin cortices with subperiosteal and subchondral bone resorption Spotty deossification with coarse trabecular pattern – “Salt & Pepper skull” Weak bone – basilar invagination, bowing, vertebral deformaties, fractures Brown tumour (bony replacement by vascularized fibrous tissue) Osteosclerosis – “rugger jersey spine” Periosteal new born formation (sometimes cortical thickening) Normal bone scan 80%

32. References: Diagnosis and Management of Paget’s Disease of the bone, www.uptodate.com, 2012 Diagnostic Imaging: Orthopaedics, Stoller DW, 2 nd ed, 2004 Orthopedic Imaging: A Practical Approach, Greenspan A, 4 th ed, 2004 Radiology Review Manual, Dahnert W, 6 th ed, 2007 Primer of Diagnostic Imaging, Weissleder R, et al, 2007