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Locomotor > The effect of age on bones and joints: Osteoporosis and Osteoarthritis > Flashcards

The effect of age on bones and joints: Osteoporosis and Osteoarthritis Flashcards

1
Q

What is osteoarthritis?

A
  • Not a single disease
  • Heterogeneous group of disorders with similar pathological and radiological features
  • Characterised by degeneration of articular cartilage, remodelling of subchondral bone and formation of osteophytes
  • Clinical and pathological expression of ‘joint failure’ in response to a variety of aetiological factors
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2
Q

Describe the epidemiology of OA

A
  • Commonest type of arthritis
  • Major cause of musculo-skeletal pain & mobility disability in the elderly
  • Up to 40% of those over 65 years in some communities have symptoms associated with knee or hip OA
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3
Q

What are the primary classifications of OA?

A
  • localised

- generalised (often nodal in post menopausal women)

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4
Q

What are the secondary classifications of OA?

A
  • Developmental (hip dysplasia, slipped epiphysis)
  • Traumatic (intra-articular fracture, menisectomy, occupational, hypermobility)
  • Metabolic (alkaptonuria, haemachromatosis, Paget’s)
  • Endocrine (acromegaly)
  • Inflammatory (RA, gout, haemophilia, joint sepsis)
  • Aseptic necrosis (corticosteroids, sickle-cell disease)
  • Neuropathic (diabetes, syringomyelia, tabes dorsalis)
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5
Q

What are the signs and symptoms of OA?

A
  • Pain- worse on use of joint
  • Stiffness- mild in morning, severe after immobility
  • Loss of movement
  • Pain on movement/ restricted range
  • Tenderness (articular or periarticular)
  • Bony swelling
  • Soft tissue swelling
  • Joint crepitus
  • Heberden’s nodes (distal), Bouchard’s nodes (proximal) in fingers
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6
Q

What are the radiological features of OA?

A
  • Narrowing of joint space
  • Osteophytosis
  • Altered bone contour
  • Bone sclerosis and cysts
  • Periarticular calcification
  • Soft tissue swelling
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7
Q

How do we differentiate OA from RA?

A

OA
-Distribution (DIP and PIP)
-Bony swelling
-Limited stiffness
RA
-Distribution (MCP, PIP, carpal bones, spares DIP)
-Soft tissue swelling
-Stiffness permanent
-Symptoms and signs of systemic inflammation
-Serology
-Erosions, without osteophytes or sclerosis

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8
Q

Describe the pathology of OA affecting all joint tissues

A
  • Thickened capsule
  • Cyst formation and sclerosis in subchondral bone
  • Shelving ‘fibrillated’ cartilage
  • Osteophytic lipping
  • Synovial hypertrophy
  • Altered contour of bone
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9
Q

Which joints develop OA?

A
  • Spine> DIPJ> Knee> Hip
  • Prevalence of OA increases with age at all sites
  • Common: cervical and lumbar spine, hip, knee, distal and proximal interphalangeal, carpometa-carpophalangeal, first metatarsophalangeal
  • Uncommon: temporomandibular, sternoclavicular, shoulder, ankle, midtarsal, talocalcaneal
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10
Q

What risk factors lead to a susceptible joint so an increased risk of incident OA?

A

Modifiable Local Risk Factors

  • Muscle strength
  • Physical activity/ occupation
  • Joint injury
  • Joint alignment
  • Leg length inequality
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11
Q

What are the risk factors that lead to a predisposed individual so an increased risk of incident OA?

A 
Modifiable Systemic Risk Factors:
-Obesity
-Diet
-Bone metabolism
Non-modifiable Systemic Risk Factors:
-Age
-Sex
-Genetics
-Ethnicity
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12
Q

Describe the key pathways that promote pathologic remodelling of cartilage

A
  • Inflammation= changes to subchondral bone + osteophytes, cytokine enzymes= cartilage damage so OA
  • Altered biomechanics= changes to subchondral bone + osteophytes, cartilage damage so OA
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13
Q

Describe the ways to enter the cycle/ key pathways

A
  • Prior inflammatory arthritis, joint injury= inflammation
  • Cytokine enzymes= abnormal lubrication= cartilage damage (+joint injury)
  • Joint injury, dysplasia, malalignment= altered biomechanics
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14
Q

What are catabolic factors?

A 
Increases degradation, decrease synthesis
-IL-1, IL-6
-IL-7, IL-8
-TNFa, TGFa
-Nitric oxide/ ROS
-IL-17, IL-18, LIF
-Oncostatin M
-bGFG
S100 proteins
-Matrix fragments
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15
Q

What are anabolic factors?

A

Increase synthesis, decrease degradation

  • IGF-1
  • OP-1 (BMP-7)
  • TGFb
  • IL-4
  • BMP-2, CDMPs
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16
Q

What are other factors leading to OA?

A

Increased:

  • MMPs (matrix metalloproteinases)
  • Aggrecanases, other proteases
  • Hypertrophic phenotype (type X collagen, MMP-13)
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17
Q

What biological processes are enriched for OA-associated genes?

A
  • Transcriptional regulation
  • Hyaluronan and aminoglycan metabolic processes
  • Osteoblast development and differentiation
  • Chondrocyte development and differentiation
  • Cell proliferation and differentiation
  • Regulation of apoptosis
  • Skeletal development and morphogenesis
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18
Q

What are OA GWAS studies?

A
  • Point to genes in a number of biological pathways and to transcriptional regulators
  • Genes for structural proteins not apparently contributing to susceptibility
  • Account for only a small fraction of disease hereditability
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19
Q

Why do genes account for only a small fraction of disease hereditability?

A
  • Poor definition of clinical phenotypes
  • Low penetrance polymorphisms
  • Inheritance of epigenetic modifications
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20
Q

Describe the cycle that leads to OA presentation

A

-Abnormal stress
-Abnormal cartilage
CAUSES
-Chondrocyte apoptosis
-Collagen fibril damage
-Loss of proteoglycans
LEADS TO
-Cartilage fibrillation
-Osteophyte formation
-Subchondral bone sclerosis

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21
Q

What causes abnormal stress?

A
  • Genetic
  • Trauma
  • Dysplasia
  • Obesity
  • Malalignment
  • Muscle weakness
  • Loss of proprioception
22
Q

What causes abnormal cartilage?

A
  • Genetic
  • Ageing
  • Inflammation
  • Metabolic changes
  • Endocrine factors
23
Q

Describe the biochemical cartilage changes in experimental canine OA in weeks 1-4

A
  • Increased hydration
  • Proteoglycans more easily extracted
  • Smaller PG subunits
  • Increase in PG synthesis
  • Increase in collagen synthesis
24
Q

Describe the biochemical cartilage changes in experimental canine OA in weeks 8-16

A
  • Changes in PG structure
  • Longer CS chains
  • Increased expression CS epitopes
  • Loss of PG’s
25
Q

Describe the histological cartilage changes in experimental canine OA in weeks 1-4

A
  • Disruption superficial collagen
  • EM changes in chondrocytes
  • Increase in cellular lipids
  • Angiogenesis
  • Early osteophyte formation
26
Q

Describe the histological cartilage changes in experimental canine OA in weeks 8-16

A
  • Chondrocyte cell division
  • Loss of safranin-O
  • Fibrillation
27
Q

What are the differences in the biochemical properties of normal ageing and osteoarthritic cartilage?

A
  • Keratan sulphate: A= increased, O= decreased
  • Water: A= decreased, O= increased
  • Protein/ uronate: A= increased, O= decreased
  • Extractability of proteoglycans: A= decreased, 0= increased
28
Q

What causes increased stress on cartilage?

A

Insufficiently protected impulsive loading:

  • Cartilage damage= loss of force distribution
  • Bone changes, microfracture stiffening= loss of shock absorption
29
Q

What are the age-related physiological changes contributing to the development of OA?

A
  • Decline in proprioception
  • Decrease in muscle strength (sarcopenia)
  • Changing shape of bones (hip and CMC joint of thumb)
30
Q

What are the cellular and molecular hallmarks of ageing?

A
  • Genomic instability
  • Telomere attrition
  • Epigenetic changes
  • Loss of proteostasis
  • Dysregulated nutrient sensing
  • Mitochondrial dysfunction
  • Cellular senescence
  • Stem cell exhaustion
  • Altered intercellular communication
31
Q

What does ‘infammageing’ lead to?

A
  • Cognitive decline, mental health and well-being
  • Altered body composition and loss of mobility
  • Immune decline and increased susceptibility to infections
  • Cancer
  • Atherosclerosis and vascular disease
  • Insulin resistance and type 2 diabetes
32
Q

What are the age-related changes in matrix molecule metabolism?

A
  • Decreased type 2 collagen turnover
  • Decreased aggrecan turnover
  • Accumulation of glycation end products
  • Cleavage products of matrix molecule (fibronectin)
  • Decreased antioxidant defences
33
Q

What is chondrocyte cellular senescence?

A

-Decreased mitotic activity
-Increased beta galactosidase
-Increased epigenetic hypermethylation
-Decreased telomere length
(Can be reversed experimentally by transfection of human telomere genes)

34
Q

What are the aims of treatment for OA?

A
  • Reducing pain and stiffness
  • Maintaining/ improving joint mobility
  • Reducing physical disability/ handicap
  • Improving health-related quality of life
  • Limiting progression of joint damage
  • Educating about the nature of OA and its management
35
Q

Describe the management of OA

A
  • > 50 modalities non-pharmacological, pharmacological and surgical therapy
  • Few areas of medicine where clinicians have a greater need for balanced, impartial evidence-based advice
36
Q

What are the international treatment recommendations for OA?

A

-Non-pharmacological= education, self-management, weight loss, regular telephone contact, aerobic, muscle strengthening and water based exercises; referral to a physical therapist and use of a stick, shoe insoles and knee braces
-Pharmacological= paracetamol, topical and oral NSAIDs (both non-selective with misoprostol/PPi and selective COX-2), duloxetine, topical capsaicin and IA steroids
-Surgical= joint replacements, osteotomy, knee fusion, knee aspiration and debridement in case of locking
+ combination of non-pharmacological and pharmacological modalities

37
Q

What is the stepwise algorithm for the management of patients with OA?

A

Severity of symptoms= mild to severe

  1. Non-pharmacological management (education, exercise, weight loss, appropriate footwear)
  2. Non-pharmacological management (physiotherapy, braces, and begin pharmacological treatment with simple analgesics; paracetamol)
  3. Pharmacological management (NSAIDs, opioids, if effusion present= aspirate and inject)
  4. Surgery (osteotomy, total joint replacement)
38
Q

What are the current approaches to try to develop a disease-modifying drug (DMOAD) for OA?

A
  • Aggrecanase (ADAMTS 4,5) inhibitors
  • MMP inhibitors
  • Pro-inflammatory cytokine inhibitors
  • Bisphosphonates
  • Calcitonin
  • iNOS inhibitors
  • Strontium ranelate
  • Cathepsin K inhibitors
  • Selective oestrogen-receptor modulators (SERMS)
  • PTH and analogues
  • Bone morphogenetic proteins (BMPs)
  • Sprifermin (recombinant human FGF 18)
39
Q

What is osteoporosis?

A

Systemic skeletal disease, characterised by low bone mass and deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture

40
Q

What are the common osteoporotic fractures?

A
  • Wrist
  • Spine
  • Hip
41
Q

What does osteoporosis present with?

A
  • Back pain
  • Thoracic kyphosis
  • Loss of height
  • Fractures
42
Q

What is the cumulative lifetime risk in 50 year old Caucasian woman?

A

Forearm 15%
Hip 16%
Vertebrae 32%
(1 in 3 women, 1 in 12 men)

43
Q

What are the phases of bone remodelling?

A
  • Resting (lining cell)
  • Resorption (osteoclast)
  • Formation (osteoblast, osteoid)
  • Resting
44
Q

What are the causes of age-related bone loss?

A
  • Decreased bone formation
  • Increased bone resorption
  • Increased sensitivity to PTH and hydroxy vitamin D in the absence of oestrogens
45
Q

What are the modifiable risk factors for osteoporosis?

A
  • Oestrogen deficiency syndromes (premature menopause= idiopathic, surgical oophorectomy, hysterectomy/ amenorrhoea= athletes, anorexia nervosa, prolactinoma)
  • Smoking
  • Alcohol abuse
  • Prolonged immobilisation and inactivity
  • Some drugs like corticosteroids
  • Nutritional factors= low calcium and vitamin D intake
  • Certain diseases= hyperparathyroidism, Cushing’s
  • Low body mass index
  • Susceptibility to falls
46
Q

What are the non-modifiable risk factors for osteoporosis?

A
  • Age
  • Nulliparity
  • Race (Caucasian or Asian)
  • Positive family history
  • Prior fragility fracture
  • Short stature for small bone
47
Q

What does the WHO fracture risk assessment tool measure?

A
  • Country
  • Bone mineral density
  • Age
  • Gender
  • Clinical risk factors= low body mass index, previous fragility fracture, parental history of hip fracture, glucocorticoid treatment, current smoking, alcohol intake (3+ units per day), RA, other secondary causes of osteoporosis
48
Q

What are the approaches to the prevention and treatment of osteoporotic fractures?

A 
-Lifestyle Modification
=Diet, Exercise
=Smoking, Alcohol
=Muscle tone & muscle strength
=Falls prevention
-Drug treatments that affect bone
49
Q

What are the Antiresorptive drug treatments for osteoporosis?

A 
-Bisphosphonates
=Alendronate (Fosamax)
=Risedronate (Actonel)
=Ibandronate (Bonviva)
=Zoledronate (Aclasta)
-HRT
-Calcitonin
-Raloxifene (Evista)
-Strontium (Protelos)
-Denosumab (Prolia)
50
Q

What are the Anabolic drug treatments for osteoporosis?

A 
-Parathyroid Hormone
=Teriparatide (1-34)
=Abaloparatide
=Preotact ( 1-84)
-Strontium?
-Anti sclerostin antibody
=Romosozumab
-Nutritional supplements
=Calcium and Vitamin D

Locomotor (20 decks)

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