CSB520 Lecture Notes - Lecture 9: Osteophyte, Sarcoma, Synovial Joint
Week 9 - Bone and Joint Pathology
Sunday, 5 June 2016 10:55 PM
Bone Normal Structure - Hard MatrixBone Normal Structure - Hard Matrix
•Matrix proteins:
○Type 1 collagen - main framework
○Many others, including growth factors, signalling proteins etc.
•Part of what makes a good place for secondary cancers
○Proteoglycans - not as critical to bone structure, more so cartilage
•Minerals - for structural resilience
○Calcium phosphate complex 'hydroxyapatite'
•Gives bone their strength
○Osteoblast enzyme alkaline phosphatase & vitamin D metabolites important for
mineralisation
•2 cell types:
○OsteoclastsOsteoclasts - a completely different family
○Osteoblast familyOsteoblast family
•Osteoblasts
•Osteocytes
•Lining cells
Osteoclasts - bone resorbing cellsOsteoclasts - bone resorbing cells
•Specialised members of the monocyte-macrophage family
•Mono- or multi-nucleated
•Short lived
•Recruited to sites of remodelling
•Forms a seal and secretes H+ & proteolytic enzymes that destroy the bone matrix
○Like a toilet plunger, actually
•The constituents are then released back into blood
○Can be done when calcium is needed to donate into blood
Osteoblast FamilyOsteoblast Family
•Unrelated to osteoclasts
•Related to fibroblasts, chondrocytes & adipocytes
•OsteoblastsOsteoblasts - bone forming cells
○Can sense how much strain is placed on bone and can encourage more bone
development
•OsteocytesOsteocytes - mechanosensory cells that form an interconnecting network throughout
the bone matrix
•Lining cells - cover metabolically inactive bone surfaces
The CycleThe Cycle
•Very well orchestrated (otherwise it will be out of balance)
2 Types of Mature Bones2 Types of Mature Bones
•Cortical
○Dense, load-bearing bone
○Forms diaphysis of long bones and outer surfaces of trabecular bones
•Trabecular (cancellous)
○Some structural function, but predominantly metabolic
○Very metabolically active - good blood supply (common site for metastases)
○Prone to disease associated with increased remodelling (e.g. osteoporosis) and
the common site for metastatic cancers
Bone RemodellingBone Remodelling
•3 functions:
○Continually release minerals to maintain appropriate serum levels
○Maintain structural integrity of bone
○Allow changes in bone structure in response to growth and altered load bearing
•Normally, formation & reabsorption are coupled - except when extra matrix is needed
(growth)
•Pathology - formation/reabsorption are uncoupled
Bone DevelopmentBone Development
•Endochondral ossification
○'Growth plates' - cartilaginous template converted to bone at ossification
centres
○Epiphyseal cartilage persists into adolescence/early adulthood
•Usually matures at puberty
•Intramembrane ossification
○Bone formed in CT in loose, disorganised arrangement (woven bone)
•Matures into organised compact lamellar bone
•Most bones formed as cartilaginous matrix "anlage" - ~8weeks
•Dystoses - embryonic cells don't migrate to location
•Dysplasias - abnormal skeletal growth (in terms of bone, not pre-cancerous change)
Osteogensis ImperfectaOsteogensis Imperfecta
•Autosomal dominant congenital disease
•Mutation in type 1 collagen - short stature, blue sclera, multiple bone fractures, early
hearing loss
Bone development after birthBone development after birth
•Shape & size changes during growth & adulthood
•Fat - leptin (which actually secretes a lot of hormones. Correlates with subcutaneous
levels, research shown it can trigger puberty)
•Puberty - oestrogen and testosterone
•Growth hormone
•Thyroid hormones
Main Clinical Signs of of Bone DiseaseMain Clinical Signs of of Bone Disease
•Pain
•Fractures
•Deformity
•Disturbed mineral homeostasis (usually hypercalcaemia)
Pain Stimulation of Nerve Ending By:Pain Stimulation of Nerve Ending By:
•Inflammation (bone takes longer to heal)
•Trauma
•Tumour (tends to be very painful, as tumour puts pressure on surrouding cells)
•Increased resorption (e.g. Paget's disease'
WeakeningWeakening
•Congenital disorders
•Metabolic bone disease
•Erosion by tumours
Abnormal growth/remodelling & DeformityAbnormal growth/remodelling & Deformity
•Congenital disorders
•Metabolic bone disease
•Malunion of a fracture (when a bone breaks and the 2 ends are not aligned)
•Extensive erosion by tumour
•Excess PTH (parathyroid hormone)
•Excess PTH-related peoptide
Causes of FractureCauses of Fracture
•Fracture of a normal one:
○Significant trauma
○Unexpected fall
•Repeated minor trauma - stress fracture (associated with high intensity sports)
•Pathologic fracture - occurs in bones already weakened by diseasePathologic fracture - occurs in bones already weakened by disease
○Can be anything - cancers, osteoporosis, etc.
Types of FracturesTypes of Fractures
•Partial
•Straight through bone
•Penetrates skin
○Bone is meant to be a sterile site, and since the skin has bacteria on it, the
shards can become necrotic (as it has to be pinned)
•Bits of bone
Fracture Healing ProcessFracture Healing Process
•Haematoma at fracture site
•Callus at fracture site - collagen holds it together
•CT scar tissue becomes mineralised hard bone, bigger than before
○Over time it will become remodelled
Impaired HealingImpaired Healing
•What disrupts the process of healing? (above)
○Movement
○Interposed soft tissue (between the 2nds of the bone)
○Gross misalignment
○Infection (e.g. osteomyelitis)
○Pre-existing bone disease
Pre-existing Bone DiseasePre-existing Bone Disease
•Osteoporosis
•Osteomalacia/rickets
•Paget's disease (involving too much resorption & secretion - uncouple cycle)
•Osteomyelitis
•Primary malignancies
•Secondary malignancies (more common than primary)
OsteoporosisOsteoporosis
•1:2 Women
•1:3 Men
○More common in females
•30-40 years - see notable changes in skeleton
•0.7% bone loss per year in men & women
○Rate of loss influenced by peak bone mass, diet, activity, hormones, growth
Document Summary
Bone normal structure - hard matrix: matrix proteins: Many others, including growth factors, signalling proteins etc: part of what makes a good place for secondary cancers. Proteoglycans - not as critical to bone structure, more so cartilage: minerals - for structural resilience. Calcium phosphate complex "hydroxyapatite: gives bone their strength. Osteoblast enzyme alkaline phosphatase & vitamin d metabolites important for mineralisation: 2 cell types: Osteoclasts - bone resorbing cells: specialised members of the monocyte-macrophage family, mono- or multi-nucleated, short lived, recruited to sites of remodelling, forms a seal and secretes h+ & proteolytic enzymes that destroy the bone matrix. Like a toilet plunger, actually: the constituents are then released back into blood. Can be done when calcium is needed to donate into blood. Osteoblast family: unrelated to osteoclasts, related to fibroblasts, chondrocytes & adipocytes, osteoblasts. Can sense how much strain is placed on bone and can encourage more bone development: osteocytes.
