Disease of bones and joints Flashcards
Normal bone
Outer solid cortical bone
Inner trabecular (spongy) bone
Outer surface – periosteum
Inner space (medulla) contains fat or haemopoietic marrow
Constituents
Inorganic - 65%
Organic - 35%
Functions
Mineral homeostasis Houses haemopoietic system -i.e. the bone marrow Mechanical -not a static scaffold - constantly remodelled
Bone diseases
Same stuff that can affect any other organ
-infections
-tumours
-trauma / degeneration
But also :
-specific derangements of bone’s particular specialised processes and function
Specific bone diseases
Disorders of matrix formation
Disorders of mineralisation
Disorders of bone turnover
The bone remodelling cycle - the key to understanding bone disease
Activation of osteoclasts Resorption of bone Death of osteoclasts Formation of new matrix by osteoblasts Mineralisation of new matrix Quiescence
The “Basic Multicellular Unit”
Cartilage
Osteoblasts
Osteoclasts
Bone
The concept of “coupling” of bone remodelling
Osteoblast activity - bone formation
Osteoclast activity - bone resorption
This coupling of bone formation and bone resorption is in normally in balance, except where a local imbalance is required for the purposes of growth
Coupling is lost in osteoporosis, resulting in a loss of bone volume
So what can go wrong with bone?
Defective matrix / matrix formation
Mineralisation problems
Turnover problems
Bone matrix formation diseases - rare
Mutations in collagen -type 1 in particular in bone -->osteogenesis imperfecta -->also affects ears / eyes / skin / teeth Other abnormalities of bone matrix -mucopolysaccharidoses -->Morquio syndrome -->Hurler syndrome
Cartilage matrix formation disorders - uncommon
e.g. Achondroplasia
-autosomal dominant
Failure of cartilage maturation at the growth plate
Caused by a mutation of fibroblast growth receptor receptor 3 which causes it to be continually activated (it is a negative regulator of bone growth)
Diseases of mineralisation - uncommon
Osteomalacia / Ricketts
- caused by deficiency in vitamin D or calcium
- can be dietary or metabolic
- failure to mineralise ->cartilage overgrowth, failure of longitudinal growth
Bone remodelling problems
The big one is : OSTEOPOROSIS > porosity of bone due to a reduction in bone mass -age -hormonal influences (sex steroids) -lifestyle (smoking, alcohol) -activity -genetics (Vit D receptor polymorphisms) -nutrition (including malabsorption)
Osteoporosis - how it happens
“Uncoupling” of bone resorption and formation
-too much bone resorption
-too little bone formation
Loss of trabecular then cortical bone
Osteoporosis - complications
Fragility fractures (vertebrae, femoral neck, distal radius) Kyphosis (dowager’s hump) Loss of height
Osteoporosis - treatment
Inhibit bone resorption (bisphosphonates)
Increase bone formation (experimental treatments)
Disorders of abnormal turnover: Paget’s disease
Aka Osteitis Deformans
Excess turnover - “Collage of matrix madness” (!)
Once thought to hafve a viral cause (paramyxovirus) – link to dog ownership in Lancashire
More recent evidence suggests it is genetic
General pathology affecting bone
Infection
Tumours
Bone infections
Osteomyelitis -complication of compound fractures -also blood borne -necrosis of bone fragments -new bone formation Sinuses drain pus Main organisms: S. aureus, M. tuberculosis
Tumours
Most tumours in bone are metastases
- lung
- breast
- prostate
- thyroid
- kidney
- myeloma
Primary bone tumours
Many are benign
Malignant ones are potentially rapidly fatal
Chondrogenic
60% benign -osteochondroma (many sites) -chondroma (mainly fingers) 40% malignant Chondrosarcoma (femur, pelvis, skull base)
Osteogenic
13% benign
-osteoid osteoma (any site, small tumours in cortex)
-osteoblastoma (larger tumours, typically spinal)
87% malignant
-osteosarcoma (most commonly distal femur)
Malignant bone tumours
Osteosarcoma
Chondrosarcoma
Ewing’s sarcoma
Undifferentiated sarcoma
Malignancies by age/ site
Osteosarcoma: 15-20, metaphyses, most commonly knee (6-%)
Chondrosarcoma: middle aged/ elderly, pelvis, ribs, proximal long bones
Ewing’s sarcoma: <20, diaphyses
Undifferentiated sarcoma: middle aged/ elderly, mainly metaphyses
Joint diseases
Infections Crystal arthropathies Chronic inflammatory arthritis Osteoarthritis Tumours – these are rare so don’t worry about them
Joint infections
Septic arthritis
- can be very trivial causes
- insect bites / small cuts near joints
- ->punching people in teeth
- very painful
- IV antibiotics +/- drainage
Crystal arthropathies
Gout -urate crystals 2nd-ry to raised serum uric acid Pseudogout -calcium pyrophosphate crystals -age related
Chronic inflammatory arthritis
Generally autoimmune
Rheumatoid arthritis is the commonest form
There are a variety of other types
-HLA B27-associated diseases such as ankylosing spondylitis and psoriatic arthritis
-systemic lupus and related conditions
Rheumatoid arthritis
Part of rheumatoid disease Systemic inflammatory disorder Auto-antibodies to immunoglobulins -rheumatoid factor -these are more of a marker of loss of immune self-tolerance than the cause of the disease
Osteoarthritis/ osteoarthrosis
Common Degenerative disease Erosion of cartilage -minimal inflammation -leads to changes in underlying bone Mechanical Predisposed by previous joint damage e.g. inflammation, intra-articular fracture
Features of osteoarthritis
Fragmentation of cartilage (‘fibrillation’)
Osteophyte formation (bony projection associated with the degeneration of cartilage at joints)
Cysts in underlying bone
Represents a final common pathway of joint failure
The only effective treatment is arthoplasty (surgical removal of the joint and replacement with a prosthesis)
Rheumatoid arthritis mechanism
Inflammation of synovium
-lymphocytyes / plasma cells / macrophages
-‘pannus’ formation (inflamed fibrous tissue)
Multiple joints
Extra articular features
Joint destruction caused by a cascade of cytokines driven by tumour necrosis factor-alpha
Anti-TNF-alpha antibodies are an effective treatment of severe rheumatoid disease
