Nonx

Non-Neoplastic Bone Disease Renal Osteodystrophy (CKD-MBD) • Can be one or many of: o Osteitis cystica fibrosa o Osteomalacia o Osteoporosis • Pathogenesis o ↓Phosphate excretion  ↑Serum phosphate combined with ↓vitD conversion to active form  ↑PTH  ↑Osteoclastic activity and bone resorption  metabolic acidosis to increase bone resorption and demineralisation Osteoporosis • Porous bone  low bone mass • Senile/post-menopausal/disease/ageing • Pathogenesis o ↓Osteoblastic activity  bone loss at turnover sites o Inactivity  lack of mechanical stimulation  ↓stimulation of bone formation o Genes: osteoclast regulators: RANK, RANKL, OPG o Calcium nutritional status o Hormonal influence: ↓Oestrogen  ↑inflammatory cytokines  ↑osteoclast activity Paget’s Disease (Osteitis Deformans) • Disease of high bone turnover activity  large bone mass but structurally unsound • Pathogenesis o Inflammation of bones secondary to paramyxomavirus o Genetic factors (7x relative risk in 1st degree relative) o SQSTM1 gene mutation  ↑RANK signalling  ↑osteoclast activity • Multifocal heterogeneity • Mosaic lamellar bone formation o Osteolytic stage: ↑Osteoclast activity o Mixed stage: osteoblast and osteoclast activity o End stage/osteosclerotic: thick, coarse, easily fractured cortical bone • Controlled with calcitonin (inhibit PTH) and bisphosphonates • Affects axial skeletal, proximal femur • Pain secondary to microfractures, overgrowth of bones compress nerves • Craniofacial enlargement, skull base invagination, long bone bowing, secondary osteoarthritis • AV-shunt  high output cardiac failure • Secondary lesions: GCT, osteosarcoma Achondroplasia • Disease of epiphyseal plate • Cause of dwarfism • Autosomal dominant • Activating mutation of FGFR3: unchecked inhibition of cartilage production • Short proximal limbs  Normal trunk length • Enlarged head • Depression of nose root • Normal intelligence, longevity, reproductive ability Osteogenesis Imperfecta • Brittle bone disease • Type 1 collagen deficiency (found in osteoid) • Autosomal dominant • Clinically varying severity o Fatal: death in utero due to extraordinary bone fragility o Mild: childhood fractures • Blue sclerae, hearing loss, irregular teeth Osteopetrosis • Marble bone/Albers-Schonberg disease • Reduced bone resorption and diffuse skeletal sclerosis • Impaired osteoclast function • Mutations impairing acidification of resorption pits  poor Ca dissolution • Bones hard, brittle, prone to fracture • AR and AD subtypes • Clinically mild to severe groups • Bones lack medulla, with bulbous, misshapen ends • No remodelling • Compression of neural foramina  Severe forms in utero/infancy: o Fractures o Anaemia o Hydrocephaly o Cranial nerve defects o Early death • Mild forms o Recurrent fractures • Lack of haematopoiesis o Lack of marrow space o Infections, hepatosplenomegaly • 1st genetic disease to be treated with bone marrow transplantation Osteonecrosis (Avascular Necrosis) • Bone infarction  Risk Factors: o Fractures o Idiopathic o Corticosteroid use o Infection • Usually limited to medulla or subchondral bone • Cartilage survives from synovial fluid nutrients • Necrotic fat cells in marrow  release fatty acids and dystrophic calcification • Creeping substitution of dead bone • Clinical symptoms depending on severity and location o Subchondral: chronic progressive pain, collapse with secondary osteoarthritis o Medullary is silent Osteomyelitis • Bone inflammation  Sources: o Systemic/septicaemia o Localised o Pyogenic bacteria and mycobacteria o Exotic infections in 3rd world immigrants o Opportunistic infections in immunocompromised  E.g. o Pyogenic o Tuberculosis o Syphilitic Pyogenic Osteomyelitis • Bacterial bone infection • Haematogenous spread o Children: can be from minor cuts in mucosa and skin o Adults: surgery, DM foot nephropathy, IV drugs use • Extension from adjacent soft tissue or direct implantation from open fracture • Majority are S aureus o Receptors for bone matrix proteins e.g. collagen • In children: metaphysis • In adults: subchondral bone • Bone necrosis in 48hrs  sequestrum • Infection spreads along bone shafts • Permeation to subperiosteal plane  abscess  rupture  sinus  sequestrum discharge • Periosteal lifting  ischaemia • Extends to joint  septic arthritis • > 1 week o Peripheral reactive new bone  involucrum o Eponyms-Brodie abscess, sclerosing osteomyelitis of Garre • Acute onset fever, pain • Radiology: bone destruction (lysis) surrounding by reactive new bone (sclerosis) • Positive blood culture for pathogens • Treatment: antibiotics and surgical drainage Tuberculosis Osteomyelitis • Migrations from regions with endemic TB • Immunocompromised patients • Spine, knees, hip most common • More destructible than pyogenic osteomyelitis • Pott disease (spine involvement  infection through multiple vertebrae, IV discs, soft tissues  abscess) with spinal deformities and neurological defects Skeletal Syphilis • Treponema Pallidum (Spirochetes)  Congenital forms: o Bone destruction and deformity especially nose, palate, skull and limbs o Infection localises to areas of endochondral ossification and periosteum