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Nmt631 scintigraphy in common bone diseases

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This document discusses various bone diseases and disorders. It begins by describing the different types of cells that make up bone, including osteoprogenitors, osteoblasts, osteoclasts, and osteocytes. It then discusses several specific bone diseases and disorders in more detail, including osteoporosis, Paget's disease, rickets/osteomalacia, hyperparathyroidism, and fractures. It also provides information on osteonecrosis, osteomyelitis, bone tumors, joint diseases like osteoarthritis and rheumatoid arthritis, and other conditions like gout. Throughout, it includes details on pathogenesis, morphology, clinical expression, and imaging findings for many of these diseases.

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Bone Diseases Remo George Ph.D., ABSNM, NMTCB(CNMT)
Cells of Bone • OSTEOPROGENITOR (“STEM”)(TGFβ) • OSTEOBLASTS (surface of spicule), under control of calcitonin to take blood calcium and put it into bone. • OSTEOCYTES (are osteoblasts which are now completely surrounded by bone) • OSTEOCLASTS (macrophage lineage), under control of PTH to chew up the calcium of bone and put it into blood
Classical actions of vitamin D to maintain serum calcium homeostasis • Vitamin D is sole factor that stimulates intestinal calcium absorption • Vitamin D and PTH in concert necessary to mobilize calcium from the bone and conserve calcium from urine.
Ultrastructure and function of osteoclasts. • Multiple nuclei, abundant mitochondria and large number of vacuoles & lysosomes. • Bone-resorbing osteoclasts form ruffled borders and sealing zones • The resorbing area under ruffled border is acidic (vacuolar H+- ATPase are localized) • Enzymes cathepsin K, MMP9 and TRAP secreted into resorption lacuna degrade bone matrix proteins • Degradation products endocytosed, packaged into transcytotic vesicles and secreted from functional secretory domain • Numerous calcitonin receptors and αvβ3 vitronectin receptors • DC-STAMP and OC-STAMP involved in cell–cell fusion of osteoclasts BoneKEy Reports (2014) 3, Article number: 495
Regulation of osteoclast differentiation and function by osteoblastic cells • Bone resorption-stimulating factors act on osteoblastic cells to induce membrane-associated factor RANKL • Osteoblasts constitutively produce M-CSF • Osteoclast precursors express receptors RANK and c-Fms and in the presence of RANKL and M- CSF differentiate into osteoclasts • Osteoblastic cells secrete decoy receptor OPG, which inhibits the RANKL–RANK interaction between osteoblasts and osteoclast precursors • Multinucleated osteoclasts also express RANK, and RANKL induces the bone-resorbing activity of osteoclasts via the interaction with RANK BoneKEy Reports (2014) 3, Article number: 495
Cells of Bone A, Active osteoblasts synthesizing bone matrix proteins. The surrounding spindle cells are osteoprogenitor cells. B, Two osteoclasts resorbing bone. The smaller blue nuclei surrounded by a halo of clearing in the dense pink lamellar bone are osteocytes in their individual lacunae. A B
Cells of the Bone
Bone Diseases • Congenital Disorders of Bone and Cartilage – Osteogenesis Imperfecta – Achondroplasia and Thanatophoric Dwarfism – Osteopetrosis • Acquired Diseases of Bone – Osteoporosis – Paget Disease (Osteitis Deformans) – Rickets and Osteomalacia – Hyperparathyroidism – Fractures – Osteonecrosis (Avascular Necrosis) – Osteomyelitis – Pyogenic Osteomyelitis – Tuberculous Osteomyelitis • Bone Tumors – Bone-Forming Tumors – Cartilage-Forming Tumors – Fibrous and Fibroosseous Tumors – Miscellaneous Bone Tumors • Joints – Arthritis – Osteoarthritis – Rheumatoid Arthritis – Juvenile Rheumatoid Arthritis – Seronegative Spondyloarthropathies – Gout – Pseudogout – Infectious Arthritis – Joint Tumors and Tumor-Like Lesions – Ganglion and Synovial Cysts – Tenosynovial Giant Cell Tumor
Osteogenesis Imperfecta • “Brittle” bone disease, too LITTLE bone • Blue sclerae, Type 1 most common & mildest type • Mutations in genes which code for the alpha-1 and alpha- 2 chains of COLLAGEN 1 • Mutations of COLLAGEN 2,10, 11 manifest themselves as CARTILAGE diseases, ranging from joint cartilage destruction to fatal sequelae
Dwarfism • Achondroplasia, dwarf (non-lethal) • Thanatophoria, dwarf (lethal, FGF-3 mutations) • a point mutation (usually Arg for Gly375) in the gene that codes for FGF receptor 3 (FGFR3), which is located on the short arm of chromosome 4. In the normal growth plate, activation of FGFR3 inhibits cartilage proliferation, hence the term “achondroplastic” • A MUTATION causes FGFR3 to be constantly activated. Achondroplastic “dwarf” Short arms and extra folds of skin Thanatophoric “dwarf”, often lethal J. Nucl. Med. Technol. Sept. 1, 2013 vol. 41 no. 3 234-235
Osteopetrosis • “Marble” bone, increased bone, brittle, sclerotic bone • Carbonic anhydrase deficiency resulting from mutation in encoded CA2 gene, i.e., ↓ acid • ↓ osteoclast resorption • Bone-on-bone appearance on radiographs Medicine (Baltimore). 2015 Jun;94(22)
Osteoporosis • “Peak” bone mass is early adulthood • Normal decline, slow • Osteoporosis is accelerated bone loss • Factors: – AGE – Physical activity – Estrogen withdrawal (menopause) – Nutrition (Ca++) – Genetics Categories of Osteoporosis Nuc Med Rev 2012, 15, 2: 124–131 Patient 60 years old with osteoporosis complicated with vertebral fractures
Paget’s Disease • Matrix madness, Osteoblasts/- cytes gone wild • THREE PHASES: • 1) Increased osteoclast resorption • 2) Increased “hectic” bone formation (osteoblasts) • 3) Osteosclerosis • ELEVATED ALKALINE- PHOSPHATASE • ELEVATED urine HYDROXYPROLINE • CLINICAL: PAIN!!! (MICROFRACTURES) Radionuclide Biphosphonate Imaging
• VITAMIN D deficiency/dysfunction • Rickets: – In children, prior to epiphyseal fusion, vitamin D deficiency results in growth retardation associated with expansion of growth plate known as rickets (cupping, fraying, widening of GP). • Osteomalacia: – In adults, Vit. D deficiency leads to hypocalcemia & hypophosphatemia resulting in poor mineralization of bone matrix proteins Schematic representation of the main steps of the vitamin D biosynthetic pathway, where genetic aberrations may lead to rickets and osteomalacia. The renal defect in pseudo–vitamin D–deficiency rickets (PDDR) is indicated by the break in the 1,25(OH)2D3 arrow arising in the kidney. The mutation leads to insufficient synthesis of 1,25(OH)2D. The left part of the figure represents a target cell where schematic coupling of the ligand to its receptor (VDR) takes place in the cytosol or, more likely, in the nucleus. The VDR then heterodimerizes with the RXR receptor. For ease of representation, the RXR ligand (9-cis retinoic acid) is not depicted. The complex then binds to DNA to regulate gene transcription. Various mutations affecting either of the two VDR domains (DBD, DNA-binding domain; LBD, ligand- binding domain), depicted by the stippled X over the receptor complex, cause hereditary vitamin D–resistant rickets (HVDRR). Rickets & Osteomalacia Osteomalacia. To r/o mets. The unusually large number of rib lesions raised the suspicion of metabolic bone disease rather than metastases.
Hyperparathyroidism • PRIMARY - (PTH adenoma) – Entire skeleton • OSTEITIS FIBROSIS CYSTICA (von Recklinghausen’s disease (of bone) • “Brown” “Tumor” • SECONDARY - (RENAL) (NOT AS SEVERE AS 1º) • TERTIARY - from chronic 20 Overview of the pathogenesis of secondary hyperparathyroidism. PTH, parathyroid hormone; VDR, vitamin D receptors Tertiary Hyperparathyroidism. Diffusely increased uptake in the lungs, stomach, and heart.
Fractures • Types – Complete, incomplete – Closed, open (communicating) – Comminuted (splintered, “greenstick”) – Displaced (NON-aligned) – PATHOGENIC, (non-traumatic, 2º to other disease, often metastases) – “STRESS” fracture • Three Phases 1. HEMATOMA, minutes, days 2. SOFT CALLUS (“PRO”-CALLUS), ~1 week 3. HARD CALLUS (BONY CALLUS), several weeks • COMPLICATIONS – PSEUDARTHROSIS (non-union) – INFECTION (especially OPEN [communicating] fractures)
Osteo/Avascular/Aseptic Necrosis • Cause: ISCHEMIA – Trauma – Steroids – Thrombus/Embolism – Alcohol abuse – Vessel injury, e.g., radiation – Sickle cell anemia – INCREASED intra-osseous pressure vascular compression – Venous hypertension
Osteomyelitis • Pyogenic: Staph, E. coli, Pseudom, Kleb, Salmonella – Hematogenous – Contiguous, e.g., from a nearby joint – Direct implantation • TB – Usually blood borne – TB of spine is known as POTTS disease • Syphilis – CONGENITAL – TERTIARY, “SABRE” shins • DX: X-ray, 3-phase bone imaging Sabre Shins
BONE TUMORS • BONE – OSTEOMA (benign, solitary, middle age, skull/face common) – OSTEOID OSTEOMA (benign, >2cm dia, nidus, appendicular skeleton, teens/ 20s, M>>F, painful) – OSTEOBLASTOMA (axial skeleton, no nidus) – OSTEOSARCOMA (late teens, knees, metaphyses, painful) • CARTILAGE – OSTEOCHONDROMA (most common, cartilage & bone present, hereditary, M>>F, pelvis/scapulae/ribs) – CHONDROMA (pure hyaline cartilage) – CHONDROBLASTOMA (rare, teens, M>>F, often knees, epiphyses) – CHONDROMYXOID FIBROMA (Rarest of all, teens, males) – CHONDROSARCOMA (malignant) • FIBROUS – FIBROUS CORTICAL DEFECT/NON-OSSIFYING FIBROMA (most common, < 1cm, children >2, if >5-6cm then called non-ossifying fibroma) – FIBROUS DYSPLASIA (benign, 70% single bone, 27% poly-ostotic, 3% poly-ostotic with café-au-lait, endocrine disorders and precocious puberty – FIBROSARCOMA/MALIGNANT FIBROUS HISTIOCYTOMA (metaphyses of long bones/ pelvis, lytic, fractures) • MISC. – Ewing’s “sarcoma” (neuroendocrine origin, chromosome translocation 11 & 22 with EWS gene rearrangement, 2nd most childhood malignancy, arise in medullary cavity of bone) – Giant Cell Tumor (20s-40s, macrophage lineage) – METASTASES (Prostate (M), breast (F), blastic or lytic?)
Nmt631 scintigraphy in common bone diseases
Joint Diseases • “ARTHRITIS” – DEGENERATIVE (OSTEOARTHRITIS) – RHEUMATOID • “JUVENILE” RHEUMATOID • NON-INFECTIOUS: Ankylosing Spond., Reactive, Psoriasis, IBD • INFECTIOUS: Supp., TB, Lyme, Viral • GOUT (URATE) • PSEUDOGOUT (PYROPHOSPHATE) • Tumors (all are of synovium) – Ganglion (Synovial Cyst), non- neoplastic – Giant Cell Tumor (Pigmented VilloNodular Synovitis[PVNS]), benign – Synovial Sarcoma, malignant
Osteoarthritis • Etiology/Risk Factors: Age, Trauma, Genes • Pathogenesis: Progressive EROSION of articular cartilage • Morphology: X- Ray, “eburnation”, “joint mice”, osteophytes • Clinical Expression: PAIN, Limitation of motion Heberden’s Nodes in DIP
Rheumatoid Arthritis • Chronic systemic inflammatory disorder • Principally attacks the joints • Nonsuppurative proliferative & inflammatory synovitis • Destruction of articular cartilage & ankylosis of joints • May affect many tissues and organs—skin, blood vessels, heart, lungs, & muscles • Morphology: Synovial lymphocytes, macrophages, plasma cells, neutrophils, osteoclasts, “pannus”, hyperemia, rheumatoid “nodules”, vasculitis • Clinical Expression: PAIN, Limitation of motion, malaise, fatigue, rheumatoid factor IgMIgG-Fc, CLINICAL FEATURES : • 1% of population, F>>M • Morning stiffness, mean age 45 yrs • “TYPICAL” hand /x-ray findings, MCP ulnar deviation • Symmetric arthritis • SERUM RHEUMATOID FACTOR ULNAR DEVIATION of MCP joints
RA vs OA
Juvenile Rheumatoid Arthritis • Begins BEFORE age 16, by definition • Unknown etiology, often genetic component • Generally LARGER joints than RA • Often positive antinuclear antibodies Whole body bone scan using technetium-99m shows increased bone uptake in the lesions of a patient with juvenile idiopathic arthritis. J Pediatr. 2010 Nov;53(11):931-935.
Seronegative Spondyloarthropathies • ANKYLOSING SPONDYLITIS (aka, “rheumatoid” spondylitis, or Marie-Strumpell Disease [HLA- B27] (M>>F) • “REACTIVE” ARTHRITIS (follows GU or GI infections) – From osteomyelitis – Usually suppurative – GC, staph, strep, H. flu, E. coli, Salmonella, viral – fever, leukocytosis • REITER SYDROME (urethral & conjunctival inflammation too) [HLA-B27] • Arthritis associated with IBD • PSORIATIC ARTHRITIS [HLA-B27] Pathogenesis of ankylosing spondylitis
Bone Scintigraphy in Spondylolysis • (A) Planar images are normal in a 20-year old gymnast with sever low back pain and negative radiographs and MRI • (B) However, transverse and coronal SPECT images show focal abnormal activity in the right posterior element of L5-S1 (arrow) consistent with spondylolysis. Nuclear Medicine: The Requisites, 4th Edn.
Gout • Endpoint of HYPERURICEMIA from ANY cause resulting in JOINT deposition of monosodium urate crystals (TOPHI) • ACUTE • CHRONIC • 10% of population has hyperuricemia (>7 mg/dl), but only 1/20 of these has gout Tophus area predominantly containing crystals. The fanning arrangements of MSU crystals is suggestive of spherulitic crystal formation in a constrained space. Frozen section stained with haematoxylin and eosin, ×400 magnification. Abbreviation: MSU, monosodium urate monohydrate On this image of chronic tophaceous gouty arthritis, extensive bony erosions are noted throughout the carpal bones. Urate depositions may be present in the periarticular areas.
HYPERURICEMIA  GOUT • Age of the individual and duration of the hyperuricemia are factors. Gout rarely appears before 20 to 30 years of hyperuricemia. M>>F • Genetic predisposition is another factor. In addition to the well-defined X- linked abnormalities of HGPRT, primary gout follows multifactorial inheritance and runs in families. • Heavy alcohol consumption predisposes to attacks of gouty arthritis. • Obesity increases the risk of asymptomatic gout. • Certain drugs (e.g., thiazides) predispose to the development of gout. • Lead toxicity increases the tendency to develop gout
Classification of Gout Clinical Category Metabolic Defect Primary Gout (90% of cases) Enzyme defects unknown (85%–90% of primary gout) ■ Overproduction of uric acid Normal excretion (majority) Increased excretion (minority) Underexcretion of uric acid with normal production Known enzyme defects—e.g., partial HGPRT deficiency (rare) ■ Overproduction of uric acid Secondary Gout (10% of cases) Associated with increased nucleic acid turnover—e.g., leukemias ■ Overproduction of uric acid with increased urinary excretion Chronic renal disease ■ Reduced excretion of uric acid with normal production Inborn errors of metabolism—e.g., complete HGPRT deficiency (Lesch- Nyhan syndrome) ■ Overproduction of uric acid with increased urinary excretion HGPRT, hypoxanthine guanine phosphoribosyl transferase.
Pseudogout • Gout: Monosodium Urate • Pseudo-GOUT: Calcium Pyrophosphate • PSEUDOGOUT is also called CHONDROCALCINOSIS, or CPPD (Calcium Phosphate Deposition Disease) • IDIOPATHIC, HEREDITARY, SECONDARY • Secondary joint damage, hyperparathyroidism, hemochromatosis, hypomagnesemia, hypothyroidism, ochronosis, and diabetes
Joint Tumors • BENIGN – GANGLION (SYNOVIAL CYST) – GIANT CELL TUMOR of TENDON SHEATH, aka PVNS, Pigmented VilloNodular Synovitis • MALIGNANT – SYNOVIAL SARCOMA F-18-FDG-PET-CT in a 15-year-old boy with synovial sarcoma in the right shoulder.

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Nmt631 scintigraphy in common bone diseases

  • 1. Bone Diseases Remo George Ph.D., ABSNM, NMTCB(CNMT)
  • 2. Cells of Bone • OSTEOPROGENITOR (“STEM”)(TGFβ) • OSTEOBLASTS (surface of spicule), under control of calcitonin to take blood calcium and put it into bone. • OSTEOCYTES (are osteoblasts which are now completely surrounded by bone) • OSTEOCLASTS (macrophage lineage), under control of PTH to chew up the calcium of bone and put it into blood
  • 3. Classical actions of vitamin D to maintain serum calcium homeostasis • Vitamin D is sole factor that stimulates intestinal calcium absorption • Vitamin D and PTH in concert necessary to mobilize calcium from the bone and conserve calcium from urine.
  • 4. Ultrastructure and function of osteoclasts. • Multiple nuclei, abundant mitochondria and large number of vacuoles & lysosomes. • Bone-resorbing osteoclasts form ruffled borders and sealing zones • The resorbing area under ruffled border is acidic (vacuolar H+- ATPase are localized) • Enzymes cathepsin K, MMP9 and TRAP secreted into resorption lacuna degrade bone matrix proteins • Degradation products endocytosed, packaged into transcytotic vesicles and secreted from functional secretory domain • Numerous calcitonin receptors and αvβ3 vitronectin receptors • DC-STAMP and OC-STAMP involved in cell–cell fusion of osteoclasts BoneKEy Reports (2014) 3, Article number: 495
  • 5. Regulation of osteoclast differentiation and function by osteoblastic cells • Bone resorption-stimulating factors act on osteoblastic cells to induce membrane-associated factor RANKL • Osteoblasts constitutively produce M-CSF • Osteoclast precursors express receptors RANK and c-Fms and in the presence of RANKL and M- CSF differentiate into osteoclasts • Osteoblastic cells secrete decoy receptor OPG, which inhibits the RANKL–RANK interaction between osteoblasts and osteoclast precursors • Multinucleated osteoclasts also express RANK, and RANKL induces the bone-resorbing activity of osteoclasts via the interaction with RANK BoneKEy Reports (2014) 3, Article number: 495
  • 6. Cells of Bone A, Active osteoblasts synthesizing bone matrix proteins. The surrounding spindle cells are osteoprogenitor cells. B, Two osteoclasts resorbing bone. The smaller blue nuclei surrounded by a halo of clearing in the dense pink lamellar bone are osteocytes in their individual lacunae. A B
  • 8. Bone Diseases • Congenital Disorders of Bone and Cartilage – Osteogenesis Imperfecta – Achondroplasia and Thanatophoric Dwarfism – Osteopetrosis • Acquired Diseases of Bone – Osteoporosis – Paget Disease (Osteitis Deformans) – Rickets and Osteomalacia – Hyperparathyroidism – Fractures – Osteonecrosis (Avascular Necrosis) – Osteomyelitis – Pyogenic Osteomyelitis – Tuberculous Osteomyelitis • Bone Tumors – Bone-Forming Tumors – Cartilage-Forming Tumors – Fibrous and Fibroosseous Tumors – Miscellaneous Bone Tumors • Joints – Arthritis – Osteoarthritis – Rheumatoid Arthritis – Juvenile Rheumatoid Arthritis – Seronegative Spondyloarthropathies – Gout – Pseudogout – Infectious Arthritis – Joint Tumors and Tumor-Like Lesions – Ganglion and Synovial Cysts – Tenosynovial Giant Cell Tumor
  • 9. Osteogenesis Imperfecta • “Brittle” bone disease, too LITTLE bone • Blue sclerae, Type 1 most common & mildest type • Mutations in genes which code for the alpha-1 and alpha- 2 chains of COLLAGEN 1 • Mutations of COLLAGEN 2,10, 11 manifest themselves as CARTILAGE diseases, ranging from joint cartilage destruction to fatal sequelae
  • 10. Dwarfism • Achondroplasia, dwarf (non-lethal) • Thanatophoria, dwarf (lethal, FGF-3 mutations) • a point mutation (usually Arg for Gly375) in the gene that codes for FGF receptor 3 (FGFR3), which is located on the short arm of chromosome 4. In the normal growth plate, activation of FGFR3 inhibits cartilage proliferation, hence the term “achondroplastic” • A MUTATION causes FGFR3 to be constantly activated. Achondroplastic “dwarf” Short arms and extra folds of skin Thanatophoric “dwarf”, often lethal J. Nucl. Med. Technol. Sept. 1, 2013 vol. 41 no. 3 234-235
  • 11. Osteopetrosis • “Marble” bone, increased bone, brittle, sclerotic bone • Carbonic anhydrase deficiency resulting from mutation in encoded CA2 gene, i.e., ↓ acid • ↓ osteoclast resorption • Bone-on-bone appearance on radiographs Medicine (Baltimore). 2015 Jun;94(22)
  • 12. Osteoporosis • “Peak” bone mass is early adulthood • Normal decline, slow • Osteoporosis is accelerated bone loss • Factors: – AGE – Physical activity – Estrogen withdrawal (menopause) – Nutrition (Ca++) – Genetics Categories of Osteoporosis Nuc Med Rev 2012, 15, 2: 124–131 Patient 60 years old with osteoporosis complicated with vertebral fractures
  • 13. Paget’s Disease • Matrix madness, Osteoblasts/- cytes gone wild • THREE PHASES: • 1) Increased osteoclast resorption • 2) Increased “hectic” bone formation (osteoblasts) • 3) Osteosclerosis • ELEVATED ALKALINE- PHOSPHATASE • ELEVATED urine HYDROXYPROLINE • CLINICAL: PAIN!!! (MICROFRACTURES) Radionuclide Biphosphonate Imaging
  • 14. • VITAMIN D deficiency/dysfunction • Rickets: – In children, prior to epiphyseal fusion, vitamin D deficiency results in growth retardation associated with expansion of growth plate known as rickets (cupping, fraying, widening of GP). • Osteomalacia: – In adults, Vit. D deficiency leads to hypocalcemia & hypophosphatemia resulting in poor mineralization of bone matrix proteins Schematic representation of the main steps of the vitamin D biosynthetic pathway, where genetic aberrations may lead to rickets and osteomalacia. The renal defect in pseudo–vitamin D–deficiency rickets (PDDR) is indicated by the break in the 1,25(OH)2D3 arrow arising in the kidney. The mutation leads to insufficient synthesis of 1,25(OH)2D. The left part of the figure represents a target cell where schematic coupling of the ligand to its receptor (VDR) takes place in the cytosol or, more likely, in the nucleus. The VDR then heterodimerizes with the RXR receptor. For ease of representation, the RXR ligand (9-cis retinoic acid) is not depicted. The complex then binds to DNA to regulate gene transcription. Various mutations affecting either of the two VDR domains (DBD, DNA-binding domain; LBD, ligand- binding domain), depicted by the stippled X over the receptor complex, cause hereditary vitamin D–resistant rickets (HVDRR). Rickets & Osteomalacia Osteomalacia. To r/o mets. The unusually large number of rib lesions raised the suspicion of metabolic bone disease rather than metastases.
  • 15. Hyperparathyroidism • PRIMARY - (PTH adenoma) – Entire skeleton • OSTEITIS FIBROSIS CYSTICA (von Recklinghausen’s disease (of bone) • “Brown” “Tumor” • SECONDARY - (RENAL) (NOT AS SEVERE AS 1º) • TERTIARY - from chronic 20 Overview of the pathogenesis of secondary hyperparathyroidism. PTH, parathyroid hormone; VDR, vitamin D receptors Tertiary Hyperparathyroidism. Diffusely increased uptake in the lungs, stomach, and heart.
  • 16. Fractures • Types – Complete, incomplete – Closed, open (communicating) – Comminuted (splintered, “greenstick”) – Displaced (NON-aligned) – PATHOGENIC, (non-traumatic, 2º to other disease, often metastases) – “STRESS” fracture • Three Phases 1. HEMATOMA, minutes, days 2. SOFT CALLUS (“PRO”-CALLUS), ~1 week 3. HARD CALLUS (BONY CALLUS), several weeks • COMPLICATIONS – PSEUDARTHROSIS (non-union) – INFECTION (especially OPEN [communicating] fractures)
  • 17. Osteo/Avascular/Aseptic Necrosis • Cause: ISCHEMIA – Trauma – Steroids – Thrombus/Embolism – Alcohol abuse – Vessel injury, e.g., radiation – Sickle cell anemia – INCREASED intra-osseous pressure vascular compression – Venous hypertension
  • 18. Osteomyelitis • Pyogenic: Staph, E. coli, Pseudom, Kleb, Salmonella – Hematogenous – Contiguous, e.g., from a nearby joint – Direct implantation • TB – Usually blood borne – TB of spine is known as POTTS disease • Syphilis – CONGENITAL – TERTIARY, “SABRE” shins • DX: X-ray, 3-phase bone imaging Sabre Shins
  • 19. BONE TUMORS • BONE – OSTEOMA (benign, solitary, middle age, skull/face common) – OSTEOID OSTEOMA (benign, >2cm dia, nidus, appendicular skeleton, teens/ 20s, M>>F, painful) – OSTEOBLASTOMA (axial skeleton, no nidus) – OSTEOSARCOMA (late teens, knees, metaphyses, painful) • CARTILAGE – OSTEOCHONDROMA (most common, cartilage & bone present, hereditary, M>>F, pelvis/scapulae/ribs) – CHONDROMA (pure hyaline cartilage) – CHONDROBLASTOMA (rare, teens, M>>F, often knees, epiphyses) – CHONDROMYXOID FIBROMA (Rarest of all, teens, males) – CHONDROSARCOMA (malignant) • FIBROUS – FIBROUS CORTICAL DEFECT/NON-OSSIFYING FIBROMA (most common, < 1cm, children >2, if >5-6cm then called non-ossifying fibroma) – FIBROUS DYSPLASIA (benign, 70% single bone, 27% poly-ostotic, 3% poly-ostotic with café-au-lait, endocrine disorders and precocious puberty – FIBROSARCOMA/MALIGNANT FIBROUS HISTIOCYTOMA (metaphyses of long bones/ pelvis, lytic, fractures) • MISC. – Ewing’s “sarcoma” (neuroendocrine origin, chromosome translocation 11 & 22 with EWS gene rearrangement, 2nd most childhood malignancy, arise in medullary cavity of bone) – Giant Cell Tumor (20s-40s, macrophage lineage) – METASTASES (Prostate (M), breast (F), blastic or lytic?)
  • 21. Joint Diseases • “ARTHRITIS” – DEGENERATIVE (OSTEOARTHRITIS) – RHEUMATOID • “JUVENILE” RHEUMATOID • NON-INFECTIOUS: Ankylosing Spond., Reactive, Psoriasis, IBD • INFECTIOUS: Supp., TB, Lyme, Viral • GOUT (URATE) • PSEUDOGOUT (PYROPHOSPHATE) • Tumors (all are of synovium) – Ganglion (Synovial Cyst), non- neoplastic – Giant Cell Tumor (Pigmented VilloNodular Synovitis[PVNS]), benign – Synovial Sarcoma, malignant
  • 22. Osteoarthritis • Etiology/Risk Factors: Age, Trauma, Genes • Pathogenesis: Progressive EROSION of articular cartilage • Morphology: X- Ray, “eburnation”, “joint mice”, osteophytes • Clinical Expression: PAIN, Limitation of motion Heberden’s Nodes in DIP
  • 23. Rheumatoid Arthritis • Chronic systemic inflammatory disorder • Principally attacks the joints • Nonsuppurative proliferative & inflammatory synovitis • Destruction of articular cartilage & ankylosis of joints • May affect many tissues and organs—skin, blood vessels, heart, lungs, & muscles • Morphology: Synovial lymphocytes, macrophages, plasma cells, neutrophils, osteoclasts, “pannus”, hyperemia, rheumatoid “nodules”, vasculitis • Clinical Expression: PAIN, Limitation of motion, malaise, fatigue, rheumatoid factor IgMIgG-Fc, CLINICAL FEATURES : • 1% of population, F>>M • Morning stiffness, mean age 45 yrs • “TYPICAL” hand /x-ray findings, MCP ulnar deviation • Symmetric arthritis • SERUM RHEUMATOID FACTOR ULNAR DEVIATION of MCP joints
  • 25. Juvenile Rheumatoid Arthritis • Begins BEFORE age 16, by definition • Unknown etiology, often genetic component • Generally LARGER joints than RA • Often positive antinuclear antibodies Whole body bone scan using technetium-99m shows increased bone uptake in the lesions of a patient with juvenile idiopathic arthritis. J Pediatr. 2010 Nov;53(11):931-935.
  • 26. Seronegative Spondyloarthropathies • ANKYLOSING SPONDYLITIS (aka, “rheumatoid” spondylitis, or Marie-Strumpell Disease [HLA- B27] (M>>F) • “REACTIVE” ARTHRITIS (follows GU or GI infections) – From osteomyelitis – Usually suppurative – GC, staph, strep, H. flu, E. coli, Salmonella, viral – fever, leukocytosis • REITER SYDROME (urethral & conjunctival inflammation too) [HLA-B27] • Arthritis associated with IBD • PSORIATIC ARTHRITIS [HLA-B27] Pathogenesis of ankylosing spondylitis
  • 27. Bone Scintigraphy in Spondylolysis • (A) Planar images are normal in a 20-year old gymnast with sever low back pain and negative radiographs and MRI • (B) However, transverse and coronal SPECT images show focal abnormal activity in the right posterior element of L5-S1 (arrow) consistent with spondylolysis. Nuclear Medicine: The Requisites, 4th Edn.
  • 28. Gout • Endpoint of HYPERURICEMIA from ANY cause resulting in JOINT deposition of monosodium urate crystals (TOPHI) • ACUTE • CHRONIC • 10% of population has hyperuricemia (>7 mg/dl), but only 1/20 of these has gout Tophus area predominantly containing crystals. The fanning arrangements of MSU crystals is suggestive of spherulitic crystal formation in a constrained space. Frozen section stained with haematoxylin and eosin, ×400 magnification. Abbreviation: MSU, monosodium urate monohydrate On this image of chronic tophaceous gouty arthritis, extensive bony erosions are noted throughout the carpal bones. Urate depositions may be present in the periarticular areas.
  • 29. HYPERURICEMIA  GOUT • Age of the individual and duration of the hyperuricemia are factors. Gout rarely appears before 20 to 30 years of hyperuricemia. M>>F • Genetic predisposition is another factor. In addition to the well-defined X- linked abnormalities of HGPRT, primary gout follows multifactorial inheritance and runs in families. • Heavy alcohol consumption predisposes to attacks of gouty arthritis. • Obesity increases the risk of asymptomatic gout. • Certain drugs (e.g., thiazides) predispose to the development of gout. • Lead toxicity increases the tendency to develop gout
  • 30. Classification of Gout Clinical Category Metabolic Defect Primary Gout (90% of cases) Enzyme defects unknown (85%–90% of primary gout) ■ Overproduction of uric acid Normal excretion (majority) Increased excretion (minority) Underexcretion of uric acid with normal production Known enzyme defects—e.g., partial HGPRT deficiency (rare) ■ Overproduction of uric acid Secondary Gout (10% of cases) Associated with increased nucleic acid turnover—e.g., leukemias ■ Overproduction of uric acid with increased urinary excretion Chronic renal disease ■ Reduced excretion of uric acid with normal production Inborn errors of metabolism—e.g., complete HGPRT deficiency (Lesch- Nyhan syndrome) ■ Overproduction of uric acid with increased urinary excretion HGPRT, hypoxanthine guanine phosphoribosyl transferase.
  • 31. Pseudogout • Gout: Monosodium Urate • Pseudo-GOUT: Calcium Pyrophosphate • PSEUDOGOUT is also called CHONDROCALCINOSIS, or CPPD (Calcium Phosphate Deposition Disease) • IDIOPATHIC, HEREDITARY, SECONDARY • Secondary joint damage, hyperparathyroidism, hemochromatosis, hypomagnesemia, hypothyroidism, ochronosis, and diabetes
  • 32. Joint Tumors • BENIGN – GANGLION (SYNOVIAL CYST) – GIANT CELL TUMOR of TENDON SHEATH, aka PVNS, Pigmented VilloNodular Synovitis • MALIGNANT – SYNOVIAL SARCOMA F-18-FDG-PET-CT in a 15-year-old boy with synovial sarcoma in the right shoulder.