MSK

• Bone structure parts


  • Epiphyseal plate- growth plate
  • Spongy bone- honeycomb structure, filled with bone marrow
  • Compact bone- weight baring
• Joint anatomy


  • Synovial- movement
  • Synarthrosis- fused by fibrosis tissue, minimal movement
• Articular Cartlidge (covers end of bone)


  • Smooth
  • Chondrocytes, proteoglycans, collagen, water
  • Deformable but recovers
• Synovial membrane


  • Inner layer of articular capsule, secretes fluid into joint
  • Lubricant
  • Hyaluronic acid
• Inorganic bone components

  • Hydroxyapatite
  • Calcium
• Organic bone components

  • Osteoclasts
  • Osteoblasts
  • Osteocytes
  • Collagen
• Osteoclasts

  • RANKL bind to RANK
  • Bone resorption (break bone down)
• Osteoblasts

  • Reform bone
  • Secretes alkaline phosphatase
• Low Ca2+

  • Stimulates PTH (parathyroid hormone)
  • Increases Ca2+ reabsorption in kidneys and intestine
  • Decreases Pi reabsorption in the kidneys
  • Increases Ca2+ release from the bone (promotes osteoclast differentiation)
• High Ca2+

  • Calcitonin released from thyroid gland
  • Inhibits osteoclasts
  • Increases Ca2+ deposition in bones
• Vitamin D

  Calcitriol (active form)
• Vitamin D2

  Ergocalciferol (plants)
• Vitamin D supplements

  • Alfacalcidol- rapid onset
  • Cholecalciferol (D3)
  • Ergocalciferol (D2)
• Osteoporosis


  • Reduced bone mass
  • Decreased formation and increased reabsorption
• Reduced oestrogen in menopausal women


  Increased risk of osteoporosis
• Reduced oestrogen

  • Increased osteoclast activity
  • Increased RANK & RANKL expression
• Denosumab

  • Humanised monoclonal antibody
  • Binds RANKL (RANK cannot bind)
  • Reduces osteoclast
• Denosumab indications

  • Osteoporosis
  • Bone loss in cancer
• SERMs

  • Selective oestrogen receptor modulators
  • Increase osteoblasts, decrease osteoclasts
  • Reduces risk of vertebral fractures
• Raloxifene

  • Oestrogen receptor agonist in bone
  • Oestrogen receptor antagonist in breast
• Bisphosphonates

  • Alendronate
  • Accumulates in bone
  • Inhibits osteoclasts
  • Inhibits mevalonate pathway
• Osteomalacia

  • Ricketts in children
  • Vitamin D deficiency
  • Causes defects in bone mineralisation and muscle weakness
• Chronic kidney disease


  • Hypocalcaemia caused by decreased synthesis of vitamin D3 in kidney= decreased Ca2+ absorption
  • Causes secondary hyperparathyroidism
• Paget's disease


  • Distortion of bone turnover
  • Increased bone size, shape and weakness
  • Increased osteoblast activity
• Rheumatoid arthritis

  • Alleles HLA-DRI 4&10
  • Autoimmune disease
  • Affects synovial joints
  • Normal synovial membrane= 1-3 cells thick, RA= 10-12 cells (hyperplastic)
• Rheumatoid arthritis signs

  • Increased ESR
  • Increased CRP
  • Increased autoantibodies (anti-CCP & rheumatoid factor)
• Rheumatoid arthritis treatments


  • Pain: NSAIDs, analgesics, corticosteroids
  • Progression and prevention: cDMARDs- methotrexate, hydroxychloroquine, leflunomide (nucleoside synthesis inhibitor)
  • Progression and prevention: bDMARDs- anti-TNF𝛼 = infliximab, adaliminab
  • Progression and prevention: targeted synthetic- filgotimib
  • Joint replacement
• Hyperuricaemia and gout

  • Crystal arthropathy
  • Accumulation of uric acid (product of purine metabolism) = formation of sodium urate crystals in the joint
• Gout symptoms

  • Pain
  • Big toe
  • At night
  • Swollen
  • Inflamed
  • Normally one joint
• Causes of gout

  • Diet: Red meat, beer
  • Overproduction of uric acid
  • Underproduction of uric acid
  • Genetics
• Gout phases

  • Asymptomatic- elevated urate
  • Acute gout- sodium urate induces inflammation
  • Interval gout
  • Chronic tophaceous gout- several joints
• Acute gout treatments

  • 1st line- NSAID, colchicine, short-course corticosteroid
  • 2nd line- I.A./I.M. corticosteroids
  • 3rd line- IL-1 inhibitors
• Colchicine

  • Inhibits microtubule polymerisation
  • Low therapeutic window
• Chronic gout treatments

  • Urate lowering therapy
  • Allopurinol: Xanthine oxidase inhibitor, increases urinary secretion of hypoxanthine and xanthine
  • Febuxostat
  • Colchicine for pain
• Systemic Lupus Erythematosus (SLE)


  • Causes: Genetic, Environment, UV, Decreased vit D, Oestrogen, Drug induced
  • Symptoms: Child bearing age, butterfly facial rash, mouth ulcers, alopecia, photosensitive skin rash, pleuritis, headaches, Raynaud's, depression, anxiety
• Conditions associated with SLE

  • Antiphospholipid syndrome
  • Sjogrens- dry eyes and mouth
• SLE management

  • Mild= hydroxychloroquine, methotrexate, prednisolone
  • Moderate= methotrexate, I.M. trimeinolone, I.M. prednisolone
  • Severe= mycophenolate mofetil, ciclosporin
• COX-1

  • Expressed in all tissues
  • Expression regulated by hormonal signalling involved in maintaining physiological homeostasis
  • Stomach- mucosal defence and repair
• COX-2


  • Responsive to adverse stimuli (inflammation)
  • Has a binding site for steroids
  • Expressed in brain and kidneys
• Selective COX-2 inhibitors

  • Celecoxib
  • Rofecoxib
  • Parecoxib