BONE AND JOINT DISEASES

Osteoblasts: lay down new boneOsteoclasts: resorb (dissolve) boneOsteocytes: help maintain bone Types of bone (structural)Cortical/compact bone (80%)

!"Outer area of bone!"Compact à strength!"Has unique concentric arrangement of Haversian system

Trabecular bone (20%)!"Inner area of bone!"Spongy!"Filled with red or yellow marrow!"Lamellae are arranged in irregular latticework =

trabeculaeHaversian system (osteon) in corticalboneOsteon contains:

!"Haversian canal (contains blood vessels andnerves)

!"Concentric lamellae (concentric arrangement ofcollagen fibres surround Haversian canal)

!"Osteocytes, lacunae (cavity in bone matrix containing osteocyte) and canaliculi (channels that linklacunae)

Volkmann’s canals:!"Connect Haversian canals to periosteum (outer lining of bone)

Interstitial lamellae:!"Lamellae in between Haversian systems (not part of Haversian system)

Circumferential lamellae:!"Parallel to the surface (not part of Haversian system)

Trabecular/spongy bone !"Has a higher surface area to mass ratio!"Softer, weaker, more flexible!"Highly vascular!"Red bone marrow!"Trabeculae aligned towards the mechanical

load distributionWoven bone

!"Immature bone!"Random organisation of collagen fibres!"Mechanically weak!"More osteocytes per unit of volume!"Higher rate of turnover

Found in:!"All foetal bone initially when the bone is laid down!"Initial stage of fractures!"Paget’s disease (abnormal enlargement and weakening of bone)

Bone cellsOsteoblasts

(Fusion of macrophages)

Bone cellsOsteoblasts

!"Bone forming cell!"Produce organic bone matrix (osteoid) which then becomes mineralized (calcium, phosphate)!"Regulate differentiation and activity of osteoclasts!"Arises from stem cell = osteogenic cell

Osteocytes!"90% of the bone!"Terminally differentiated osteoblast!"Initiate mineralisation!"Trapped within mineral deposit!"Located in lacunae!"Regulate and communicate with other cells

and vessels via canaliculi!"Exchange nutrients and waste via canaliculi!"Mediate bone repair!"Mechanosensor

Osteoclast!"Large, multinucleated (fusion of

monocytes/macrophages)!"Attach to bone surface (ruffled border)!"Resorb bone by release of lysosomal

enzymes (break down organic matrix)and acid (H+) release (breaks downinorganic matrix)

!"Resorption bay = H owship’s lacunaeBone remodelling

!"Ongoing replacement of old bone by new bone tissue!"Respond to mechanical loading!"Repair and prevent micro damage (wear and tear)!"Release growth factors and minerals (calcium and phosphate) stored in matrix into circulation!"Ongoing process!"Osteoclasts resorb bone, osteoblast reforms bone

Osteoclast regulation by RANK/RANKL and OPG!"Preosteoclasts express receptor molecules on surface called ‘RANK’!"Ligand (RANKL) binds to RANK, activating osteoclast!"2 forms of RANK ligand = attached to osteoblast or free!"RANKL (ligand) able to bind to RANK and OPG (decoy receptor)!"Binding to OPG inhibits binding to RANK = inhibits osteoclast activation!"OPG binding prevents excessive bone resorption

Factors affecting bone metabolismLocal (autocrine)

!"RANKL binding to RANK receptor à activates osteoclasts!"Osteoprotegerin (OPG) à inhibits osteoclasts!"Sclerostin à inhibit osteoblasts!"Inflammatory cytokines à activate osteoclasts

Systemic!"Hormones

• Parathyroid hormone (PTH) induces osteoclast activity and recruitment à stimulates boneresorption (increases blood calcium)

• Calcitonin à inhibits bone resorption (decreases blood calcium)• Oestrogen à regulates RANKL expression

!"Vitamins and minerals• Vitamin D and C

Bone pathologiesOSTEOPOROSIS

!"Balance of bone formation and bone resorption disrupted!"The loss of bone mass leaves the trabecular bone thinner and porous!"Bones prone to fracture

OSTEOPOROSIS!"Balance of bone formation and bone resorption disrupted!"The loss of bone mass leaves the trabecular bone thinner and porous!"Bones prone to fracture!"Bone mineral density is reduced 35% - 65%!"80% of those affected are women

Primary osteoporosis!"Postmenopausal!"Senile!"Idiopathic (no known cause)

Secondary osteoporosis!"Endocrine disorders!"Rheumatoid arthritis!"Vitamin D deficiency!"Neoplasia!"Immobilization!"Gastrointestinal disorders

Risk factors!"Genetic factors!"Low peak bone mass!"Abnormal bone structure!"Female!"Older age!"Alcohol!"Calcium and vitamin D deficiency!"Hormonal – lack of oestrogen!"Reduced physical activity

Osteoporosis prevention and treatment!"Diet!"Hormone replacement therapy (HRT)!"Bisphosphonates (drug that stops bone resorption)!"Calcium!"Vitamin-D!"Denosumab (RANK inhibitor - stops bone resorption)

OSTEOARTHRITIS!"Most common joint disease!"Progressive erosion of articular cartilage!"Caused by biochemical and metabolic alterations!"Changes in underlying subchondral bone!"Minimal inflammation secondary to cartilage erosion!"Matrix metalloproteinases (MMPs) are primary enzymes responsible for degradation of cartilage!"Common sites: hip, knee, shoulder, spine, foot

Primary osteoarthritis: absence of any known underlying diseases (wear and tear damage)Secondary osteoarthritis: due to some underlying disease (diabetes, obesity, trauma)Risk factors:

!"Age!"Obesity!"Joint injury!"Long-term overuse!"Malformed joints

Management of osteoarthritis!"No treatments available to prevent development and progression!"Managing symptoms such as pain, stiffness and swelling!"Maintaining healthy weight!"Improving joint mobility and flexibility, surgery

RHEUMATOID ARTHRITIS!"Chronic inflammatory!"Autoimmune disease!"Approx. 1% of global population!"Female > male!"Destruction of the joint!"Extra-articular manifestations: skin, blood vessels, heart, lung, muscles!"Unknown cause!"Rehumatological = autoimmune!"Antibodies produced against articular cartilage in joints à causes autoimmune response

!"Unknown cause!"Rehumatological = autoimmune!"Antibodies produced against articular cartilage in joints à causes autoimmune response

Pathologies of rheumatoid arthritis joints!"Hyperplasia à thickening!"Accumulation of inflammatory cells!"Increased vascularity!"Cartilage and bone erosion

Current RA treatments!"Anti-inflammatory medications!"Immunosuppressive therapy!"Disease modifying anti rheumatic drugs (DMARDs)!"Surgical treatments (arthroplasty – joint replacement, synovectomy – removal of cartilage)

CHRONIC PERIDONTITIS!"Chronic inflammatory disease of periodontium (tooth supporting structures)!"Results in erosion of alveolar bone à loss of teeth!"Affects over 65% of adults above 65

Common characteristics!"Onset: any age, most common in adults!"Plaque initiates condition!"Subgingival calculus (calcification of bacterial plaque) common finding!"Slow progression!"Modified by local factors/systemic factors/stress/smoking

Risk factors!"Prior history!"Local factors:

• Plaque• Microbiological factors• Trauma

!"Systemic factors:• Smoking• Diabetes• Nutritional factors• Osteoporosis

!"Environmental and behavioural factorsTreatmentsNon-surgical procedures

!"Scaling!"Root planning!"Antimicrobial therapy!"Improvement in oral hygiene

Surgical procedures!"Pocket reduction surgery!"Correction of morphological/anatomical defects

FORENSIC PATHOLOGY What is forensic pathology?Pathology: Study of injury and diseaseForensic pathology: how this applies to the law

!"Autopsies ordered by the state coroner• 50% natural disease• 20% suicides• 15% motor vehicle accidents• 5% homocides

Disaster victim identification!"Formal process of identifying victims in cases of multiple deaths (pathologists examine bodies in

mortuaries)!"Antemortem data: before death!"Postmortem data: after death – pathology, DNA, fingerprints, dental

!"Formal process of identifying victims in cases of multiple deaths (pathologists examine bodies inmortuaries)

!"Antemortem data: before death!"Postmortem data: after death – pathology, DNA, fingerprints, dental

Problems!"Heat (affects body preservation)!"Dehydration!"Smell!"Flies

What is death?Full cessation of the functions in a biological organismSomatic death: death of the bodyBrain death: cessation of brain activityCell death: death of individual cells and tissuesForensic problems

!"When does death occur?!"Can cellular metabolism continue after somatic death? (yes)!"How does this affect dating of wounds, injuries and disease?

Steps in assessment!"Scene examination!"Autopsy!"Report/synthesis!"Court (if required)

The reason for a pathologist at the scene!"Nature of death (homicide, natural?)!"Time of death!"Discussion of other issues (unusual markings etc.)

Time of death!"Temperature: body temp falls after death!"Lividity (pooling of blood)!"Rigor mortis (stiffening of muscles

Temperature!"Undisturbed scene with core and environmental temperature!"Charts!"“rule of thumb”!"Great variation

Lividity!"Post-mortem settling of blood (e.g. lying on back = blood pools at back, settles after 8hrs)!"Can be used to tell if body has been moved!"Commences after 0.5 hrs, fixes at 8 hrs

Rigor mortis!"Stiffening of muscles – commences at 1-2 hours, passes off at 24-48 hrs!"Jaw, arms legs

Putrefaction!"Part of decomposition process!"Green stained skin!"Skin slippage!"Blisters!"Purging (reddish fluid comes out of mouth and nose)

Identification of bodies!"Visual: notoriously inaccurate!"Dental: very accurate!"Finger prints: very accurate!"DNA: very accurate!"Circumstantial: inaccurate

Marine predator attacks!"Injuries not well categorized!"Bodies not recovered!"Incomplete or decomposed!"Wounds not well preserved

Types of cases!"Those with bites to limbs who exsanguinate (loose blood)!"Those not recovered or fragmented!"Differences in species/type of attack

Characteristics of bite marks!"Major wounds in cases often consist of circular incisions 20-25cm across

!"Those not recovered or fragmented!"Differences in species/type of attack

Characteristics of bite marks!"Major wounds in cases often consist of circular incisions 20-25cm across!"Sharply defined margins with minor scalloping, highly characteristic of damage produced by

separated edges of teeth of great white shark