Tourniquet in Orthopaedic Surgery

PART A: Parts / Types / Descriptions of Tourniquet (5 marks)

Definition

Types of Tourniquets Used in Orthopaedics

1. Pneumatic Tourniquet (Most widely used - Gold Standard)

• Cuff - The inflatable bladder that encircles the limb. Available in:
  • Straight cuffs (for cylindrical limbs)
  • Curved/contoured cuffs (for conical thighs - preferred over straight cuffs on conical thighs)
  • Cuffs of varying widths - wider cuffs eliminate blood flow at lower inflation pressures (Moore et al.)
• Pressure gauge / manometer - Displays the inflation pressure in mmHg
• Inflation tubing - Connects the cuff to the pressure source
• Pressure regulator / control unit - Allows setting and maintaining desired pressure
• Timer - Indicates duration of tourniquet inflation; essential for safety

• Applied over cast padding (Webril) - smoothly applied, avoiding wrinkles (wrinkles cause blisters, skin pinching, and necrosis)
• No more than two layers of padding (more padding significantly reduces actual transmitted pressure)
• Applied to the upper arm (near axilla) for upper limb or the thigh (proximal) for lower limb

2. Esmarch Bandage (Rubber Bandage / Elastic Bandage)

• Made of sheet rubber (Martin sheet) or elastic material
• Used primarily for exsanguination of the limb before tourniquet inflation
• Applied from fingertips/toes proximally to within 2.5-5 cm of the tourniquet
• Must NOT be used alone as a tourniquet around the upper arm - risk of nerve damage from uncontrolled local pressure
• Contraindicated in infected cases - elevation alone is used for exsanguination in such cases

3. Sphygmomanometer Cuff

• Used when a formal pneumatic tourniquet is unavailable
• Should be wrapped with gauze bandage to prevent slipping during inflation
• Less reliable than a dedicated pneumatic tourniquet

4. Forearm / Wrist Tourniquet

• Forearm tourniquet is safe and reliable for hand and distal procedures (25 minutes or less, or distal to wrist with regional block)
• Advantages over upper arm tourniquet:
  • Decreased local anesthetic dose required (nearly half)
  • Less tourniquet pain
  • Longer duration of sensory block
  • Prolonged postoperative analgesia

5. Digital (Finger/Toe) Tourniquet

• Examples: Rubber ring tourniquet, ForgetMeNot tourniquet (a beaded bracelet-type device)
• Used for minor finger/toe procedures
• Rubber ring tourniquets should NOT be used on digits as they can be forgotten under dressings - a critical safety hazard
• The ForgetMeNot device has a visible attachment to alert the surgeon

Pressure Guidelines (Campbell's Concepts)

PART B: Complications and Safety Precautions (5 marks)

Complications of Tourniquet Use

1. Tourniquet Paralysis

• Results from:
  • Excessive pressure
  • Insufficient pressure (causes passive venous congestion + hemorrhagic infiltration of nerve)
  • Tourniquet kept inflated too long
  • Application without consideration of local anatomy
• Recommended maximum safe time: 2 hours in a healthy adult
• If a procedure exceeds 2 hours, it is better to complete it rapidly than to deflate for 10 minutes - because 40 minutes is required for tissues to return to normal after prolonged use; a 10-minute break is inadequate

2. Post-Tourniquet Syndrome (Bunnell)

• Characterized by: edema, pallor, joint stiffness, motor weakness, and subjective numbness
• Caused by prolonged ischemia (not the mechanical effect of the cuff itself)
• Increases narcotic requirements and delays early mobilization
• Spontaneously resolves within 1 week

3. Ischemic Complications

• Compartment syndrome
• Rhabdomyolysis
• Pulmonary embolism - asymptomatic emboli can occur within 1 minute of tourniquet release (number of emboli correlates with duration of inflation)

4. Vascular Complications

• Risk in severe arteriosclerosis or patients with prosthetic vascular grafts
• Never apply a tourniquet over a prosthetic vascular graft

5. Skin Complications

• Chemical burns from skin preparation solutions accumulating under the cuff
• Blisters and skin necrosis from wrinkled padding

Safety Rules (Campbell's Key Concepts)

1. Tourniquet time ≤ 2 hours in a healthy adult
2. Use wider cuff (not higher pressure) for larger extremities
3. Avoid straight tourniquets on conical thighs
4. Prepare and drape the limb before applying the tourniquet to prevent cleansing solution running underneath
5. Ensure pneumatic tourniquets are in good working order before use
6. No rubber ring tourniquets on digits - risk of being forgotten under dressings
7. Administer prophylactic antibiotics within 1 hour of tourniquet inflation
8. Do not apply over a prosthetic vascular graft
9. When blood supply to a limb is questionable (peripheral vascular disease), tourniquet is contraindicated

Antibiotic Timing (Clinical Pearl)

Uses of Tourniquet in Orthopaedics

PART A: Surgical Uses (Intraoperative) - 5 marks

1. To Create a Bloodless Operative Field

2. Hand and Upper Limb Surgery

• Tendon repairs (flexor and extensor tendons)
• Nerve repairs and nerve grafting
• Carpal tunnel decompression
• Dupuytren's contracture release
• Wrist arthroplasty and arthroscopy
• Microvascular surgery (anastomosis of vessels)
• The pneumatic tourniquet on the upper arm is the standard; forearm/wrist tourniquet is used for distal procedures

3. Total Knee Arthroplasty (TKA)

4. Foot and Ankle Surgery

• ORIF of ankle fractures
• Calcaneal fractures
• Forefoot and midfoot procedures (bunion correction, metatarsal osteotomies)
• Ankle arthroplasty and arthroscopy
• Thigh or calf/ankle cuff used depending on the procedure level

5. Arthroscopic Surgery

• Knee arthroscopy (thigh tourniquet)
• Ankle and wrist arthroscopy
• Provides clear visualization in the joint fluid medium

6. Bone Tumour and Soft Tissue Tumour Surgery of Limbs

7. Replantation and Microvascular Surgery

8. Intravenous Regional Anaesthesia (Bier's Block)

• The proximal cuff is inflated first to isolate the limb
• Local anaesthetic (lignocaine) is injected IV into the exsanguinated limb
• Once anaesthesia is established, the distal cuff (over anaesthetized skin) is inflated and the proximal cuff released - reduces tourniquet pain
• Used for manipulation of fractures, minor hand surgery, carpal tunnel release

PART B: Emergency / Trauma Uses + Contraindications (5 marks)

9. Haemorrhage Control in Trauma

• Control of life-threatening limb hemorrhage from open fractures, vascular injuries, traumatic amputations
• Military use has shown tourniquet use reduced limb exsanguination deaths from 9% (Vietnam) to 2% (Iraq/Afghanistan)
• Applied when direct pressure fails to control bleeding
• Safe for up to 6 hours in emergency trauma settings

10. Amputation Surgery

• Used during definitive surgical amputation at all levels (below-knee, above-knee, upper limb amputations)
• Allows clean transection through tissues with minimal blood loss

11. Exsanguination Only (Esmarch Bandage Use)

Contraindications (Important for Exam)

Key Exam Points to Remember

• Maximum safe inflation time: 2 hours (average healthy adult)
• Tourniquet pressure: systolic BP + 50-100 mmHg (or 135-255 mmHg upper limb; 175-305 mmHg lower limb - Campbell's)
• Bier's block requires a double-cuff tourniquet specifically
• Tourniquet is NOT used when blood supply to the limb is questionable
• Never apply over a prosthetic vascular graft
• Antibiotic prophylaxis within 1 hour of inflation

Antibiotic Prophylaxis in Orthopaedics

1. Definition

2. Rationale / Why Prophylaxis is Needed

• Most involve implanted foreign material (screws, plates, nails, prostheses) which bacteria can colonize via biofilm formation
• Bone is relatively avascular and has reduced natural resistance to infection
• SSI in orthopaedics carries catastrophic consequences - implant failure, osteomyelitis, periprosthetic joint infection (PJI), need for revision surgery
• Accepted practice for over 30 years; clearly decreases postoperative infection rates (Campbell's Operative Orthopaedics, 15th Ed.)

3. Wound Classification (CDC / Altemeier Classification)

4. Organisms Most Commonly Causing Orthopaedic SSI

5. Drug of Choice

First-Line: Cefazolin (First-generation Cephalosporin)

• Covers S. aureus and most skin flora effectively
• Excellent bone and soft tissue penetration
• Good safety profile, long half-life, cost-effective
• Dose: 1-2 g IV (2 g if patient weight > 80 kg; 3 g if > 120 kg)
• Provides broad-spectrum coverage against Gram-positives and many Gram-negatives

Alternatives:

6. Timing of Administration

• Standard rule: Antibiotics must be given within 60 minutes before skin incision to ensure adequate tissue and bone drug levels at the time of contamination
• Cefazolin specifically: within 1 hour of tourniquet inflation (Campbell's)
• Vancomycin and fluoroquinolones: given within 60-120 minutes before incision (slower infusion required)
• A prospective randomized study showed administration of antibiotics 1 minute after tourniquet inflation achieved cefazolin concentrations in soft tissue and bone at or above minimum inhibitory concentrations - giving antibiotics before tourniquet inflation did not yield better results
• Late administration (>1 hour before incision) is ineffective - the antibiotic window has passed

7. Intraoperative Redosing

• If estimated blood loss exceeds 1500 mL intraoperatively, an additional dose is given regardless of time
• Prolonged surgical duration is independently associated with increased SSI risk

8. Duration of Postoperative Prophylaxis

• Single preoperative dose is adequate for most clean orthopaedic procedures
• Maximum duration: 24 hours postoperatively for clean-contaminated wounds
• No evidence supports continuing antibiotics until drains, catheters, or lines are removed
• Prolonged use increases antibiotic resistance, C. difficile risk, adverse effects, and cost
• Exception: Open fractures require continued antibiotics beyond 24 hours (see below)

9. Specific Situations in Orthopaedics

A. Total Joint Arthroplasty (Hip / Knee)

• Cefazolin 2 g IV within 60 minutes of incision
• Redose every 3-4 hours if procedure prolonged
• Continue for 24 hours postoperatively (some centres: single dose only)
• Preoperative nasal screening for S. aureus with decolonization using mupirocin ointment (nasal) + chlorhexidine baths recommended as adjunct - significantly reduces deep SSI rates
• MRSA-positive patients: switch prophylaxis to Vancomycin

B. Open Fractures (Gustilo-Anderson Classification)

• Antibiotics must be started as early as possible (ideally in Emergency Department) - the "golden period" principle
• Tetanus prophylaxis administered alongside

C. Spinal Surgery with Instrumentation

• Cefazolin standard
• Vancomycin powder applied locally to wound (intrawound) is increasingly used in addition to IV prophylaxis - reduces SSI in high-risk spinal cases
• Some centres use Vancomycin IV for instrumented fusions, especially posterior spine

D. Closed Fractures / Routine Elective Orthopaedic Procedures (without implant)

• Cefazolin single dose preoperatively
• Some debate on need at all for simple procedures (e.g., diagnostic arthroscopy)

E. Hand Surgery

• Cefazolin for clean hand procedures with implants (ORIF, arthroplasty)
• For bites or contaminated hand wounds: amoxicillin-clavulanate or co-amoxiclav to cover polymicrobial flora including anaerobes

10. Contraindications to Standard Prophylaxis

1. Known allergy to cephalosporins or penicillins (modify regimen as above)
2. Pre-existing infection - switch to therapeutic antibiotics (culture-directed)
3. Renal impairment - adjust doses of renally-cleared agents (e.g., vancomycin, gentamicin)
4. MRSA colonization - use vancomycin prophylaxis

11. Additional Measures to Reduce SSI (Adjuncts to Antibiotic Prophylaxis)

1. Preoperative skin preparation - chlorhexidine-alcohol > povidone-iodine for skin decolonization
2. Povidone-iodine irrigation of wound before closure - reduces PJI in arthroplasty (dilute 0.35%)
3. Antibiotic-loaded bone cement (ALBC) - gentamicin or tobramycin cement in total joint arthroplasty; especially for revision cases
4. Antibiotic bead pouches (PMMA beads with antibiotics) - local delivery; more effective than NPWT in reducing bacterial counts in contaminated wounds
5. Nasal decolonization with mupirocin for S. aureus carriers before elective arthroplasty
6. Normothermia maintenance intraoperatively - hypothermia impairs immune function
7. Blood glucose control - hyperglycemia increases SSI risk significantly
8. VTE prophylaxis - concurrent important perioperative measure
9. Wound drains removed early; no antibiotic cover needed until drain removal

12. Summary Table

Antiseptic Agents for Skin Preparation in Orthopaedics

1. Introduction / Definition

2. Need for Skin Preparation in Orthopaedics

• Most involve metallic implants (nails, screws, plates, prostheses) - foreign material dramatically amplifies infection risk
• Bone and joint infections are catastrophic - osteomyelitis, periprosthetic joint infection, implant failure
• Skin harbours both transient flora (easily removed) and resident flora (deeper, harder to eliminate)
• SSIs increase mortality, hospital stay, and cost

3. Classification of Antiseptic Agents

A. Alcohols

B. Iodine and Iodophors

C. Chlorhexidine

D. Hexachlorophene

E. Miscellaneous (hydrogen peroxide, acridines, quaternary ammonium compounds)

4. Individual Agents - Detailed Description

A. ALCOHOLS (Ethyl Alcohol / Isopropyl Alcohol)

• Ethyl alcohol (ethanol): 70-95%
• Isopropyl alcohol: 70%
• 95% ethanol is superior to 70-75% (dilution by moist skin reduces efficacy of lower concentrations)

• Denatures and precipitates bacterial proteins
• Disrupts lipid cell membranes
• Coagulates intracellular proteins
• Rapid action within seconds

• Bactericidal (Gram-positive and Gram-negative)
• Fungicidal
• Virucidal (enveloped viruses)
• NOT sporicidal

• Excellent immediate bactericidal action - fastest onset of all antiseptics
• Inexpensive, widely available
• No residue left on skin

• Short duration of action - dries quickly, no persistent or residual effect
• Not sporicidal
• Flammable - fire risk with diathermy/electrocautery; must be fully dried before use
• Skin irritation with repeated use
• Not effective against spores or some non-enveloped viruses
• Must dry completely before draping to avoid pooling and chemical burns

• Almost always used in combination with another antiseptic (chlorhexidine or povidone-iodine) rather than alone
• Rapid pre-injection skin wipe in minor procedures

B. IODINE AND IODOPHORS

i. Iodine (Aqueous and Tincture)

• Tincture of iodine = iodine in alcohol (2% iodine in 70% alcohol) - alcoholic
• Lugol's solution = aqueous iodine (5% iodine + 10% KI in water)

• Free iodine penetrates the cell wall and oxidises key cellular constituents including proteins, nucleic acids, and membrane lipids - results in cell death

• Broad: bactericidal, fungicidal, virucidal, protozoal, sporicidal
• Effective against both Gram-positive and Gram-negative organisms

• Frequent skin irritation (tincture - can be lessened by adding iodine to alcohol)
• True allergic reactions (Lugol's)
• Stains skin and linen
• Inactivated by organic matter (blood, pus) - must clean skin first
• Toxic to open wounds and mucous membranes

ii. Iodophors - Povidone-Iodine (PVP-I / Betadine)

• Iodine complexed with polyvinyl pyrrolidone (PVP) or povidone as carrier
• Available as: 10% solution (= 1% available iodine), 7.5% scrub solution, paint solution

• The povidone acts as a slow-release reservoir of free iodine
• Slower but sustained release of iodine compared to plain iodine
• Same oxidative mechanism as iodine

• Broad: bactericidal (Gram-positive and Gram-negative), fungicidal, virucidal, sporicidal

• Slower, sustained release of iodine - more prolonged action
• Fewer skin reactions than plain iodine
• Less staining
• Lower tissue toxicity
• Covers both Gram-negative and Gram-positive organisms

• Inactivated by organic material (blood, serum, pus) - less effective in contaminated wounds
• May be absorbed systemically through large raw areas (iodine toxicity)
• Contraindicated in thyroid disease (may precipitate thyroid dysfunction)
• Contraindicated in neonates and premature infants (systemic absorption through immature skin)
• Can damage open cartilage surfaces (intra-articular use controversial)
• Allergic reactions possible (true iodine allergy)
• Inferior to chlorhexidine-alcohol for SSI prevention in multiple comparative studies

• Dilute povidone-iodine irrigation (0.35%) of surgical wounds before closure in total joint arthroplasty - shown to significantly reduce periprosthetic joint infection (PJI) rates (Shohat et al., J Arthroplasty 2022 - 31,331 cases)
• Routine skin preparation before incision
• Wound packing/dressings in infected orthopaedic wounds

C. CHLORHEXIDINE GLUCONATE

• 4% aqueous (Hibiscrub) - scrub
• 0.5% in 70% isopropyl alcohol (Hydrex, Chloraprep) - paint
• 2% chlorhexidine + 70% isopropyl alcohol - currently most recommended preparation

• Binds to negatively charged bacterial cell membrane
• Disrupts cell membrane integrity causing leakage of cytoplasmic contents
• At high concentrations: causes coagulation of cytoplasm
• Persistent activity due to binding to stratum corneum proteins

• Bactericidal - Gram-positive > Gram-negative
• Fungistatic
• Some virucidal activity
• NOT sporicidal
• Less effective against Gram-negative organisms than iodine

• Binds to skin proteins and remains active for hours after application (up to 6 hours)
• Repeated washings have a cumulative bactericidal effect - builds up over days of preoperative preparation
• This residual action is chlorhexidine's major advantage over iodine and alcohol

• Best combination of immediate and persistent (residual) antimicrobial activity
• Cumulative effect with repeated use
• Less affected by blood and organic matter than iodine
• Better patient tolerance; less skin irritation
• Current gold standard - multiple studies show superiority over povidone-iodine for SSI prevention
• WHO recommends chlorhexidine-alcohol as first choice for surgical antisepsis (Bailey & Love, 28th Ed.)
• NICE guidelines (2008) confirm: 2% chlorhexidine + 70% isopropyl alcohol is best at preventing SSI
• Sabiston (2024): "It is now standard that chlorhexidine + alcohol preparation be used for surgical site antisepsis unless contraindicated"

• Ototoxic - must not enter the middle ear (contraindicated for head/ear surgery near tympanic membrane)
• Corneal damage - avoid eye contact
• Contraindicated on mucous membranes and open wounds/raw areas
• Not for use on brain or meninges
• Possible anaphylactic reactions (rare but reported; type I hypersensitivity)
• Relatively more expensive than povidone-iodine

• Routine preoperative skin preparation - limb, spine, pelvis surgery
• Preoperative whole-body wash (1-2 days before elective arthroplasty) for S. aureus decolonisation
• Combined with nasal mupirocin for MRSA decolonisation protocol before total joint arthroplasty

D. HEXACHLOROPHENE (pHisoHex)

• 3% hexachlorophene detergent preparation

• Disrupts bacterial cell membrane
• Bacteriostatic at low concentrations; bactericidal at higher concentrations
• Forms a persistent film on skin with retained bacteriostatic properties

• Strong effect against Gram-positive cocci (especially S. aureus, S. pyogenes)
• Little activity against Gram-negative organisms
• Not effective against spores, fungi, or viruses

• Forms a persistent film on skin - prolonged action
• Good anti-staphylococcal activity

• Easily washed off
• Requires multiple applications to be maximally effective
• Neurotoxic in neonates and infants - systemic absorption causes vacuolar encephalopathy
• Must NOT be used on infants, neonates, or large body surface areas
• Poor Gram-negative coverage makes it inadequate as sole agent

E. HYDROGEN PEROXIDE (H₂O₂)

• 3% solution used for wound cleansing
• Mechanism: releases nascent oxygen on contact with tissue catalase - effervescence disrupts biofilm and mechanically loosens debris
• Bactericidal, virucidal, sporicidal (at higher concentrations)
• Not suitable for routine skin prep (tissue-damaging, inhibits wound healing)
• Used for wound irrigation, especially in infected orthopaedic wounds and osteomyelitis debridement

5. Comparative Summary Table

6. Current Recommended Protocol for Orthopaedic Skin Preparation

A. Preoperative (Day before surgery - for elective arthroplasty)

• Whole-body shower or bath with 4% chlorhexidine soap the evening before and morning of surgery
• Decolonises resident skin flora, especially S. aureus

B. Hair removal

• Electric clippers preferred - razor blades increase infection risk (micro-abrasions)
• Hair removed only if it interferes with the surgical site - not routinely

C. Operative skin preparation - Technique

1. Apply 2% chlorhexidine gluconate in 70% isopropyl alcohol (ChloraPrep) - the current gold standard combination
2. Apply using concentric circles starting from the incision site and moving outward (clean to dirty in clean wounds; for contaminated wounds - start periphery and move inward)
3. Allow to dry completely (minimum 3 minutes for alcohol-based solutions) - prevents chemical burns and fire hazard with diathermy
4. Cover tourniquet site with circumferential adhesive drape to prevent antiseptic run-under and chemical burn
5. Apply sterile drapes only after solution is fully dry

D. Special circumstances

7. Ideal Properties of a Skin Antiseptic

1. Broad antimicrobial spectrum
2. Rapid onset of action
3. Prolonged residual / persistent activity
4. Not inactivated by organic matter (blood, pus, proteins)
5. Safe for skin, non-irritant, non-allergenic
6. Non-toxic to tissues, cells, and deeper structures
7. Stable on storage; long shelf life
8. Economical and widely available
9. No systemic absorption / toxicity
10. Should not interfere with wound healing

8. Key Exam Points

• Gold standard: 2% chlorhexidine + 70% isopropyl alcohol
• Residual activity: Chlorhexidine > Iodophors > Alcohol (none)
• Sporicidal: Only iodine/iodophors
• Ototoxic: Chlorhexidine
• Neurotoxic in neonates: Hexachlorophene
• Inactivated by organic matter: Iodine/Iodophors
• Fire hazard: Alcohols - must dry completely before diathermy
• Wound irrigation (PJI prevention): Dilute povidone-iodine 0.35%
• Never apply antiseptic under tourniquet - causes chemical burns

Calcium Homeostasis and the Calcium-Brain Axis

PART A: CALCIUM HOMEOSTASIS (10 marks)

1. Introduction

• 99% is stored in bone (as hydroxyapatite - Ca₁₀(PO₄)₆(OH)₂)
• 1% is in extracellular fluid (ECF), intracellular fluid, and soft tissues

2. Physiological Roles of Calcium

1. Bone and tooth mineralisation (structural)
2. Neuromuscular transmission and excitability
3. Cardiac action potential (plateau phase) and cardiac contractility
4. Intracellular signalling - second messenger (IP₃/Ca²⁺ pathway)
5. Blood coagulation (Factor IV in coagulation cascade)
6. Enzyme activation (lipase, ATPase)
7. Hormone secretion (exocytosis of secretory granules)
8. Smooth muscle contraction

3. Organs Involved in Calcium Homeostasis

4. Hormonal Regulators - The Three Key Hormones

A. Parathyroid Hormone (PTH)

• Decrease in ionised serum Ca²⁺ is the primary stimulus
• Sensed by Calcium-Sensing Receptors (CaSR) on chief cell membranes, linked via Gq protein to phospholipase C
• When ECF Ca²⁺ falls → decreased CaSR activation → decreased IP₃/Ca²⁺ → stimulates PTH secretion
• Response is rapid - within seconds
• Chronic hypocalcaemia causes parathyroid gland hyperplasia (long-term)

B. Vitamin D (Calcitriol / 1,25-Dihydroxycholecalciferol)

Skin (UV light): 7-dehydrocholesterol → Cholecalciferol (Vitamin D₃)
↓
Liver: 25-hydroxylase → 25-hydroxycholecalciferol (Calcidiol)
↓
Kidney: 1-α hydroxylase (stimulated by PTH, low Ca²⁺, low PO₄³⁻) → 1,25-(OH)₂D₃ (CALCITRIOL - active form)

• Children: Rickets (soft bones, bowing of legs)
• Adults: Osteomalacia (defective bone mineralisation)

C. Calcitonin

• Inhibits osteoclastic bone resorption → lowers plasma Ca²⁺
• Inhibits renal tubular reabsorption of Ca²⁺ and PO₄³⁻ (minor)

5. Calcium Balance - Daily Flux

• Gross GI absorption: 350 mg
• GI secretion (into gut fluids): 150 mg
• Net absorption: 200 mg/day
• Fecal excretion: 800 mg/day
• Renal excretion: 200 mg/day (to maintain balance)
• Renal filtration: 10,000 mg/day; 98% reabsorbed (Costanzo Physiology)

6. Integrated Feedback Loop

↓Serum Ca²⁺
    ↓
PTH secreted (parathyroid glands)
    ↓
① Bone resorption ↑ → Ca²⁺ released
② Renal Ca²⁺ reabsorption ↑
③ Renal PO₄³⁻ reabsorption ↓ (phosphaturia)
④ Renal 1-α hydroxylase activated → Calcitriol ↑
    ↓
Intestinal Ca²⁺ absorption ↑
    ↓
↑Serum Ca²⁺ → inhibits PTH secretion (negative feedback)

7. Disorders of Calcium Homeostasis (Brief)

PART B: CALCIUM-BRAIN AXIS (5 marks)

1. Concept

• Brain → Bone (central regulation of bone/calcium metabolism)
• Bone → Brain (skeletal hormones influencing brain function)

2. Brain to Bone Direction: Central Regulation of Calcium Homeostasis

A. Sympathetic Nervous System (SNS) - Adrenergic Pathway

• The hypothalamus regulates bone metabolism through the sympathetic nervous system
• Osteoblasts express β2-adrenergic receptors
• SNS activation → β2 receptor stimulation on osteoblasts → inhibits bone formation and stimulates bone resorption (via RANKL upregulation)
• This is a major pathway by which stress, autonomic dysfunction, and central neurological disorders cause bone loss

B. Leptin - Hypothalamic Relay

• Leptin (adipokine from fat cells) crosses the blood-brain barrier (BBB) and acts on the arcuate nucleus (ARC) of the hypothalamus
• Acts via two pathways:
  1. Direct: Leptin receptors on osteoblasts → inhibits bone formation (anti-osteogenic)
  2. Central/indirect: Leptin activates hypothalamic neurons → increases sympathetic outflow to bone → inhibits bone formation and increases resorption
• Leptin thus paradoxically inhibits bone mass despite being a satiety hormone (Ducy et al., Cell 2000 - Karsenty group)

C. Serotonin (5-HT) - Brain-Gut-Bone Connection

• Central 5-HT (brain serotonin): inhibits sympathetic nervous system activity → indirectly promotes bone formation and prevents bone resorption
• Peripheral 5-HT (gut-derived): directly inhibits bone formation (opposite effect)
• Leptin suppresses central 5-HT → increases SNS activity → reduces bone formation
• Clinical implication: SSRIs (serotonin reuptake inhibitors) are associated with reduced bone mineral density and increased fracture risk - by reducing peripheral 5-HT effects and altering central circuits

D. Hypothalamic Neuropeptides

• Neuropeptide Y (NPY): Acts via Y1 and Y2 receptors in hypothalamus; high NPY → inhibits osteoblast activity → reduces bone formation
• CART (Cocaine- and Amphetamine-Regulated Transcript): Mediates leptin's inhibitory effects on bone resorption
• CRH, VIP, substance P and other neuropeptides act on bone cells via autonomic terminals in periosteum and bone marrow

E. Calcium-Sensing Receptors (CaSR) in the Brain

• CaSR is expressed not only in parathyroid glands but also in hypothalamus, pituitary, and other brain regions
• Changes in systemic ionised Ca²⁺ can directly modulate neuronal excitability and brain function via these receptors
• Hypocalcaemia → increased neuronal excitability → tetany, seizures, anxiety, paraesthesiae

3. Bone to Brain Direction: Skeletal Hormones Influencing Brain Function

A. Osteocalcin (OC) - The Bone Hormone

• Osteocalcin is a small protein (49 amino acids) secreted by osteoblasts - the most abundant non-collagenous protein in bone
• Traditionally considered only a bone mineralisation marker
• Gerard Karsenty's group (Columbia University) demonstrated that decarboxylated (undercarboxylated) osteocalcin acts as a circulating hormone with significant brain effects

• Stimulates insulin secretion from pancreatic β-cells (↑ energy metabolism)
• Promotes testosterone synthesis in testes
• Reduces fat accumulation (visceral fat)

B. FGF-23 (Fibroblast Growth Factor 23)

• Secreted by osteocytes in bone
• Primarily regulates phosphate excretion by kidney (phosphatonin)
• Crosses BBB; influences brain neuroinflammation
• Elevated FGF-23 in chronic kidney disease is associated with cognitive decline and neurological dysfunction

C. Bone Morphogenetic Proteins (BMPs)

• Secreted by bone matrix and osteoblasts
• BMPs (especially BMP-2, BMP-4, BMP-7) play roles in neural development, differentiation of neurons, and neuronal survival
• BMP signalling is active in the brain (choroid plexus, hippocampus) and modulates neurogenesis

4. Clinical Implications of the Calcium-Brain Axis

5. Summary of the Calcium-Brain Axis

BRAIN (CNS)
    ↓ SNS (β2-adrenergic) ↓ bone formation ↑ resorption
    ↓ Leptin → hypothalamic relay → ↑ SNS → ↓ bone mass
    ↓ 5-HT (central) → ↓ SNS → ↑ bone formation
    ↓ NPY, CART → hypothalamic neuropeptides → modulate remodelling
         ↕ BIDIRECTIONAL
BONE (Skeleton)
    ↑ Osteocalcin → crosses BBB → improves memory, cognition, reduces anxiety
    ↑ FGF-23 → phosphate regulation + brain neuroinflammation
    ↑ BMPs → neuronal differentiation, neurogenesis
    ↑↓ Calcium → directly affects neuronal excitability via CaSR in brain

Key Exam Points to Remember

1. Normal serum Ca²⁺: 8.5-10.5 mg/dL; ionised fraction is physiologically active
2. Three hormones: PTH (↑Ca²⁺), Vitamin D (↑Ca²⁺), Calcitonin (↓Ca²⁺)
3. PTH: 84 amino acids, active in N-terminal 34 AA; secreted in response to ↓Ca²⁺
4. PTH raises Ca²⁺ + lowers PO₄³⁻; Vitamin D raises both Ca²⁺ and PO₄³⁻
5. Active Vitamin D = 1,25-(OH)₂D₃ formed in kidney by 1-α hydroxylase (stimulated by PTH)
6. Calcitonin - uncertain physiological role in humans; inhibits osteoclasts
7. Brain-Bone axis is bidirectional - brain regulates bone via SNS/leptin/5-HT; bone regulates brain via osteocalcin/FGF-23/BMPs
8. Osteocalcin is the key bone hormone influencing brain - memory, cognition, anxiety via GPR158
9. Hypocalcaemia → neurological excitability (tetany, seizures, Chvostek's and Trousseau's signs)
10. Hypercalcaemia → neurological depression ("psychic moans") + confusion + coma

RANK / RANK Ligand (RANKL) Concept

1. Introduction

2. The Three Key Players

3. Mechanism of Action

Step 1 - Osteoclastogenesis (RANKL stimulates RANK)

Osteoblast/Stromal cell → secretes RANKL
           ↓
RANKL binds RANK on osteoclast precursor
           ↓
Intracellular signalling: NF-κB activation
           ↓
Differentiation of monocyte/macrophage precursors into mature multinucleated osteoclasts
           ↓
Osteoclast activation → bone resorption (acid secretion + cathepsin K release)

Step 2 - OPG blocks RANKL (inhibitory)

Osteoblast → secretes OPG (decoy receptor)
           ↓
OPG binds RANKL → RANKL cannot bind RANK
           ↓
Osteoclast differentiation inhibited → bone resorption reduced

4. The RANKL:OPG Ratio - The Master Switch

5. Wnt Signalling and the RANKL Axis

• Wnt proteins from osteoprogenitor cells bind LRP5/6 + Frizzled receptors on osteoblasts
• Activates β-catenin → promotes osteoblast differentiation and OPG secretion
• Osteocytes secrete Sclerostin (SOST) which inhibits Wnt/β-catenin → reduces bone formation
• Dickkopf-1 (Dkk1) and sFRPs also antagonise Wnt signalling

6. Coupling: How Osteoclasts Talk to Osteoblasts

• During osteoclastic resorption, bone matrix releases sequestered growth factors (BMPs, TGF-β, IGF-1)
• These liberated factors stimulate osteoblast recruitment and new bone formation
• This coupling ensures that resorption is normally followed by formation in the same remodelling unit (BMU)

7. Clinical Significance in Orthopaedics

A. Osteoporosis

• Post-menopausal: Oestrogen loss → OPG ↓, RANKL ↑ → osteoclast overactivity → bone loss
• Glucocorticoid-induced: Direct ↑ RANKL, ↓ OPG + reduced osteoblast lifespan

B. Rheumatoid Arthritis

• Activated T-lymphocytes and synoviocytes secrete RANKL → osteoclast activation in pannus → periarticular erosions, subchondral bone destruction

C. Periprosthetic Osteolysis (Implant Loosening)

• Wear particles (polyethylene, metal) from implants activate macrophages → produce IL-1, IL-6, TNF-α → ↑ RANKL expression → osteoclast activation → bone resorption around implant → loosening

D. Bone Metastases

• Tumour cells (breast, prostate, lung, myeloma) secrete PTHrP, IL-6, RANKL → osteoclast activation → "vicious cycle" of lytic metastases

E. Giant Cell Tumour (GCT) of Bone

• Stromal cells of GCT overexpress RANKL → recruits and activates osteoclast-like giant cells → aggressive bone destruction
• Basis for using denosumab in GCT treatment

F. Paget's Disease

• Osteoclasts are hyperactive due to dysregulated RANKL signalling (viral/genetic trigger)
• Uncontrolled resorption followed by disorganised formation → pagetic bone

8. Therapeutic Applications

9. Summary Diagram

Osteoblast/Stromal Cell
    │
    ├── RANKL (membrane-bound) ──────────────→ RANK (on osteoclast precursor)
    │                                              │
    │                                    NF-κB activation
    │                                              │
    │                              Osteoclast differentiation + activation
    │                                              │
    └── OPG (decoy) ────X───────── RANKL blocked       Bone resorption
    
RANKL:OPG ratio determines net bone balance
↑ Oestrogen, Wnt → ↑ OPG → bone protection
↓ Oestrogen, inflammation, glucocorticoids, PTH → ↑ RANKL → bone loss

Key Exam Points

1. RANK = receptor on osteoclasts; RANKL = ligand on osteoblasts - the cross-talk between these two cell types is the basis of coupled remodelling
2. OPG = decoy receptor (not a cell receptor) - secreted, binds and neutralises RANKL
3. RANKL:OPG ratio determines bone balance
4. NF-κB is the critical intracellular mediator
5. Oestrogen deficiency → ↑ RANKL:OPG → bone loss (postmenopausal osteoporosis)
6. Denosumab mimics OPG - it is an anti-RANKL monoclonal antibody
7. M-CSF is needed alongside RANKL for complete osteoclastogenesis
8. GCT uses denosumab because stromal cells overexpress RANKL
9. The concept explains periprosthetic osteolysis, RA erosions, and bone metastases

Tendon Suturing Techniques and Principles of Tendon Transfer

PART A: TENDON SUTURING TECHNIQUES

1. Introduction and Biological Background

Tendon Nutrition

1. Synovial fluid within the tenosynovial sheath (diffusion)
2. Vincular circulation - longitudinal blood vessels along the tendon
3. Paratenon vessels - longitudinal vessels in peritendinous tissue
4. Intraosseous vessels at tendon insertion

• FDS: beneath the A2 pulley (proximal phalanx)
• FDP: beneath A2 and A4 pulleys

Tendon Healing - Three Phases

Extrinsic vs Intrinsic Healing

• Extrinsic healing: Peripheral fibroblasts from surrounding tissue invade → dominant mechanism for adhesion formation (bad)
• Intrinsic healing: Fibroblasts from within the tendon substance → ideal, scar-free healing (good)

2. Properties of an Ideal Tendon Suture

1. Easy to handle and tie
2. Secure knot - no slipping
3. Does not gap at repair site (gap >3 mm at repair site leads to failure)
4. Sufficient tensile strength to allow early active mobilisation
5. Smooth - does not create obstruction to gliding through the sheath
6. Minimal bulk within the sheath
7. Good biocompatibility, minimal tissue reaction
8. Resorbable or non-resorbable as appropriate

• Core suture: 3-0 or 4-0 non-absorbable (polypropylene, nylon, polyester, braided polyester)
• Peripheral/epitendinous: 5-0 or 6-0 monofilament nylon or braided polyester (cross-stitch/Silfverskiöld)

3. Classification of Tendon Suture Techniques

1. Core suture - provides the bulk of tensile strength (primary repair)
2. Peripheral/Epitendinous suture - smooth surface, augments strength by 10-50%, reduces gap formation

A. Core Suture Techniques

i. Bunnell's Suture (Criss-Cross / Figure-of-8)

• Originally described by Sterling Bunnell
• Suture passes in a criss-cross (zig-zag) pattern through both tendon ends
• Disadvantage: Strangulates tendon blood supply within suture loops → ischaemia, poor healing, adhesions
• Largely historical; not recommended for primary flexor tendon repair

ii. Modified Kessler (Kessler-Tajima) Suture

• Most widely used two-strand core suture
• Two transverse grasping loops on each tendon end, with a longitudinal component
• The knot is buried within the repair (Tajima modification)
• Advantages: Simple, less constriction of blood supply, good strength for 2-strand repair
• Disadvantage: Only 2 strands cross the repair - strength limited, may not withstand early active motion protocols

iii. Tsuge Suture (Locking Loop)

• Uses a locking loop configuration - suture loops lock around tendon fibres
• Provides more secure purchase than standard grasping
• Available as single (2-strand) or double (4-strand) Tsuge

iv. Savage Suture (6-Strand)

• Three pairs of sutures cross the repair site in a complex interlocking pattern
• 6 strands cross the repair - significantly stronger than 2-strand techniques
• Designed for active rehabilitation protocols
• More technically demanding; more suture bulk

v. Cruciate Four-Strand Repair

• Two separate sutures placed to create 4 strands across the repair
• Cadaver studies show better resistance to gap formation and greater ultimate tensile strength than 2-strand techniques
• Can withstand early active mobilisation

vi. Lee / Adelaide Four-Strand Repair

• Modification providing 4 strands across repair with good strength
• More practical to perform than Savage

vii. Eight-Strand Repair

• Higher strand count = stronger repair
• Allows full active mobilisation but technically very demanding

B. Peripheral / Epitendinous Suture Techniques

• Smooth the repair site (reduces impingement in sheath)
• Resist gap formation at repair edge
• Augments core suture strength by 10-50%

i. Simple Running Suture

• Continuous over-and-over suture circumferentially

ii. Silfverskiöld Cross-Stitch (Modified Halsted)

• Running cross-stitch (X pattern) circumferentially
• Stronger than simple running; resists gap

iii. Peripheral Locking Suture

• Locks around outer tendon fibres at each pass

iv. "Cross-Stitch" (6-0 Braided Polyester)

• 6-0 braided polyester cross-stitch found to be 117% stronger than modified Kessler alone (Campbell's 2026)
• Widely recommended as the epitendinous suture of choice

4. Zones of Flexor Tendon Injury

5. General Principles of Tendon Repair

1. Atraumatic technique - use of fine instruments, minimal handling
2. Primary repair preferred within the first 12-24 hours (golden period) if wound is clean
3. Delayed primary (within 2 weeks) if contaminated wound
4. Core + peripheral suture combined for all zone II repairs
5. Tension: Repair without undue tension; don't shorten musculotendinous unit
6. Preserve pulleys (especially A2 and A4 in finger) - critical for bowstringing prevention
7. Post-repair early mobilisation (Kleinert passive or Duran protocols) reduces adhesions
8. Suture material: Non-absorbable for core, fine monofilament/braided for peripheral

PART B: PRINCIPLES OF TENDON TRANSFER

1. Definition

• Tendon graft (bridging a defect in the same tendon using donor tissue)
• Tenodesis (passive tendon fixation to bone)

2. Indications

• Irreparable peripheral nerve injuries (radial, ulnar, median nerve palsy)
• Poliomyelitis sequelae
• Spastic conditions (cerebral palsy, stroke)
• Rupture of irreparable tendons (e.g., extensor pollicis longus rupture after distal radius fracture)
• Congenital anomalies with absent muscles

3. Campbell's Key Principles of Tendon Transfer (SESEISIT Mnemonic)

1. Expendability

• The donor muscle must be expendable - its removal should not create a significant deficit
• Restoring one major function is contraindicated if it sacrifices another major function
• Example: PT (pronator teres) can be transferred without significant loss of pronation because PQ takes over

2. Strength

• Donor muscle must have grade 4 or 5 (Good or Normal) strength
• Reason: A muscle loses one grade of strength when transferred (due to changed line of pull, altered length-tension relationship)
• A grade 3 or below muscle will be nonfunctional after transfer

3. Soft-Tissue Equilibrium

• The tissue bed must be soft, pliable, and free of scar
• Scarred, fibrotic tissue prevents tendon gliding → transfer fails
• Transfer is contraindicated in the presence of active infection or severe soft-tissue scarring
• May require skin grafting, flap coverage, or scar release before transfer

4. Supple Joints / Passive Range of Motion

• All joints across which the tendon will act must have full passive range of motion before transfer
• A transferred tendon cannot overcome a contracted or stiff joint
• Contractures must be corrected before (or at the time of) transfer
• This is the most common reason for transfer failure

5. Excursion / Amplitude

• The donor tendon must have sufficient amplitude (excursion) to perform the required function
• Ideally, the donor and recipient tendon have similar amplitudes
• Amplitude can be augmented by:
  • Extensive proximal dissection of the muscle belly
  • Performing a tenodesis effect to augment passive excursion
• Reference amplitudes (Curtis, 1974):
  • Wrist tendons: 33 mm
  • FDP: 70 mm
  • FDS: 64 mm
  • EDC: 50 mm
  • EPL: 58 mm
  • Brachioradialis: short excursion (limited by musculotendinous junction anatomy); can be extended by proximal dissection

6. Integrity / One Function

• Each transferred tendon should ideally perform only one function
• When a split tendon is transferred to two insertions, the muscle acts primarily on the slip under greatest tension (unpredictable)
• A single transfer to a single insertion is more reliable and retrainable

7. Synergy

• A synergistic transfer is one where the donor muscle normally contracts at the same time as the lost function
• Example: Wrist flexors (ECR) are synergistic to finger extension → transfer is easier to retrain
• Non-synergistic transfers require intensive retraining (phase conversion) - patient must learn to fire the muscle in a new phase
• Example: FCU (wrist flexor) → EDC (finger extensor) - synergistic
• Example: Brachioradialis → FPL - non-synergistic (elbow flexion to thumb flexion)

8. Straight Line of Pull

• The transferred tendon should have the straightest possible line of pull from origin to new insertion
• Acute angles reduce mechanical efficiency and cause friction
• If an acute angle is unavoidable, a pulley must be created (e.g., using bone, fibrous ring)
• Every pulley = reduction in mechanical efficiency due to friction

9. Neurovascular Bundle Preservation

• The neurovascular bundle typically enters the muscle at its proximal third
• Excessive proximal dissection to gain excursion risks devascularising and denervating the muscle
• Dissection must respect this anatomy

10. Correct Tension Setting

• This is one of the most technically demanding aspects of tendon transfer
• Too tight: transferred tendon overpowers, cannot be elongated by antagonist
• Too loose: insufficient power, poor functional result
• General rule: set tension slightly tighter than expected (it will relax over time)
• A muscle detached from insertion for some time will have developed contracture and should be anchored under more tension (it will stretch back)

11. Timing

• Perform only after achieving:
  • Stable, well-healed, pliable soft tissues
  • Full passive joint ROM
  • Maximal neurological recovery (if nerve injured - wait 18 months before labelling as permanent)
  • Patient cooperation and readiness for rehabilitation

4. Common Tendon Transfers in Orthopaedics

5. Methods of Tendon Attachment (Fixation at Insertion)

6. Post-Transfer Rehabilitation

• Immobilisation for 3-4 weeks in a position that relaxes the repair
• Followed by graded active physiotherapy
• Synergistic transfers retrain more quickly (weeks)
• Non-synergistic transfers may require months of phase-conversion retraining with biofeedback

Summary - Key Exam Points

• Tendon heals in 3 phases: inflammatory → fibroblastic → remodelling (up to 3.5 months)
• Modified Kessler = most common 2-strand core suture
• Strength ∝ number of strands crossing the repair
• Always add peripheral (epitendinous) suture - adds 10-50% strength
• Adhesions = tendon injury + sheath injury + immobilisation
• Early mobilisation reduces adhesions and stimulates intrinsic healing

• Loses one grade of strength after transfer - must be grade 4+ preoperatively
• Seven principles: Expendability, Strength, Soft-tissue equilibrium, Supple joints, Excursion, Integrity, Synergy (ESSEEIS)
• Soft tissue must be pliable; joints must have full passive ROM
• Straight line of pull; one function per transfer
• Synergistic transfers easier to retrain

Radionuclides in Orthopaedics

1. Introduction

2. Radionuclides Used in Orthopaedics

3. Technetium-99m Bone Scan - The Workhorse

Mechanism of Uptake

• ⁹⁹ᵐTc is chelated to MDP (methylene diphosphonate) or HMDP
• After IV injection, ⁹⁹ᵐTc-MDP is adsorbed onto hydroxyapatite crystals in bone mineral matrix
• Uptake depends on two main factors:
  1. Blood flow to the area
  2. Osteoblastic activity (bone turnover/metabolic rate)
• By 2-6 hours post-injection, ~50% of the injected dose is in the skeleton
• Remainder is excreted via kidneys → patient should drink plenty of water and void frequently to reduce renal/bladder dose

Three-Phase Bone Scan

Interpretation

• Increased uptake ("hot spot") = increased osteoblastic activity (infection, fracture, tumour, Paget's, healing)
• Decreased uptake ("cold spot") = reduced blood flow or osteoblastic activity (avascular necrosis early, radiation necrosis, aggressive lytic tumour, myeloma)
• Negative scan (all three phases) = essentially excludes osteomyelitis (high negative predictive value)

4. Applications / Indications in Orthopaedics

A. Infection and Osteomyelitis

• Osteomyelitis: All 3 phases positive (increased flow, blood pool, and delayed)
• Cellulitis: Phases 1 and 2 positive but phase 3 (bone) normal
• Sensitivity high (85-95%), specificity low (70%) - falsely positive in fractures, trauma, surgery
• If all 3 phases negative → infection reliably excluded
• Combined SPECT-CT increases sensitivity and localisation accuracy

• Cannot reliably differentiate infection from other causes of bone turnover
• False positives in: recent fractures, diabetic arthropathy, gout, post-surgical changes
• Neonatal osteomyelitis - may be cold (photopenic) due to vascular occlusion

B. Bone Metastases (Staging)

• Most important single indication for whole-body bone scan in orthopaedics
• Detects metastases 4-6 months before plain radiographs (30-40% bone destruction needed for X-ray changes)
• Used for staging of carcinoma breast, prostate, lung, kidney, thyroid
• Characteristic pattern: multiple "hot spots" scattered through axial skeleton
• Limitation: Purely lytic metastases (myeloma, renal cell carcinoma) may appear as "cold spots" or even normal (poor osteoblastic response)
• Superscan: diffuse symmetric uptake throughout skeleton with absent renal uptake = widespread metastatic disease

C. Stress Fractures and Occult Fractures

• Plain X-rays are negative for first 2-3 weeks after stress fracture
• Bone scan becomes positive within 24-72 hours of injury
• Shows focal fusiform intense uptake at the fracture site
• Useful in: athletes, military recruits, march fractures (metatarsal), tibial stress fractures, navicular stress fractures, femoral neck stress fractures
• MRI has largely replaced bone scan for this indication in resource-rich settings (better specificity, no radiation)

D. Avascular Necrosis (AVN / Osteonecrosis)

• Early AVN: "Cold spot" (photopenic area) due to reduced blood flow to the necrotic segment
• Later AVN: "Hot spot" surrounded by cold = "doughnut sign" (reactive hyperaemia at margins)
• MRI is now the gold standard for AVN - more sensitive and specific than bone scan
• Bone scan still useful when MRI is unavailable or contraindicated

E. Paget's Disease of Bone

• Bone scan is the most sensitive test for Paget's disease
• Shows markedly increased uptake in affected bones due to intense osteoblastic activity
• Used for:
  • Initial staging to document extent of disease
  • Monitoring response to treatment (bisphosphonates reduce uptake)
  • Identifying monostotic vs polyostotic involvement
• Characteristic patterns: enlargement of bone + intense uniform uptake ("tiger jersey spine," expanded calvarium)

F. Reflex Sympathetic Dystrophy (CRPS - Complex Regional Pain Syndrome)

• Three-phase bone scan in CRPS:
  • Phases 1 and 2: increased uptake (hyperaemia)
  • Phase 3: increased periarticular uptake in affected limb
• Useful for confirmation and monitoring
• Pattern typically diffuse periarticular (not focal)

G. Periprosthetic Infection / Loosening

• Differentiating infection from mechanical loosening of prostheses
• Bone scan alone: limited (both infection and loosening show increased uptake for up to 2 years post-arthroplasty normally)
• Combined WBC scan + bone scan (dual-tracer) is the nuclear medicine standard:
  • Infection: WBC scan positive + bone scan positive = discordant
  • Mechanical loosening: bone scan positive + WBC scan negative = concordant
• FDG-PET increasingly used for periprosthetic infection assessment

H. Primary Bone Tumours

• Used for:
  • Initial assessment of primary bone tumours (extent of disease)
  • Detection of skip lesions (especially osteosarcoma, Ewing's sarcoma)
  • Detection of distant bone metastases
  • Monitoring response to chemotherapy
• Osteosarcoma shows intense uptake; chondroblastoma, GCT show variable uptake
• Bone scan cannot diagnose tumour type - only shows hypermetabolic bone

I. Metabolic Bone Disease

• Osteomalacia: may show diffuse increased uptake with pseudofractures (Looser's zones appearing as focal hot spots)
• Hyperparathyroidism: diffuse increased uptake with "superscan"
• Renal osteodystrophy: increased overall skeletal uptake

J. Bone Viability Assessment

• Assessment of bone fragment viability before replantation or free bone grafts
• Vascularity of vascularised bone grafts post-transfer

K. Spondylosis / Discitis / Sacroiliitis

• Discitis: increased uptake at affected disc level
• Sacroiliitis: early detection of sacroiliac joint inflammation in seronegative spondyloarthropathies
• Bone scan may detect sacroiliitis before MRI in some cases

5. Specialist Nuclear Medicine Scans in Orthopaedics

A. Gallium-67 (⁶⁷Ga Citrate) Scan

• Gallium mimics iron - binds to lactoferrin, transferrin, and accumulates in inflammatory cells (neutrophils, macrophages)
• Preferred agent for spinal infection (discitis, vertebral osteomyelitis) because ¹¹¹In-WBC scan is unreliable in the spine (abundant physiological marrow)
• Imaging at 24-72 hours post-injection (slow clearance)
• Also used for fever of unknown origin, soft tissue infections
• Limitation: Higher radiation dose; longer imaging time; less specific than WBC scan

B. Indium-111 (¹¹¹In) or ⁹⁹ᵐTc-HMPAO Labelled White Cell Scan

• Autologous WBCs are extracted, labelled with ¹¹¹In-oxyquinoline or ⁹⁹ᵐTc-HMPAO in the laboratory, then reinjected
• Labelled WBCs migrate to sites of active infection
• Gold standard nuclear medicine test for peripheral skeleton infection (osteomyelitis, PJI)
• At least two imaging time points: 3-4 hours and 20-24 hours
• Increase in uptake with time = infection; decrease = inflammation/marrow activity
• Requires ≥2000 circulating WBCs/μL for adequate labelling
• Combined with ⁹⁹ᵐTc-sulphur colloid marrow scan (to exclude physiological marrow uptake)
• Limitation: Less accurate in axial skeleton (spine, sacrum)

C. FDG-PET (¹⁸F-Fluorodeoxyglucose PET)

• FDG enters the glucose cycle and concentrates in high metabolic activity cells - activated leukocytes, macrophages, tumour cells
• Fasting 4-6 hours + resting 1 hour before scan to minimise background
• Highest diagnostic accuracy for chronic osteomyelitis, especially axial skeleton
• Also used for: bone tumour staging, detection of metastases, monitoring chemotherapy response
• PET-CT hybrid: anatomical and metabolic correlation simultaneously
• Limitations: Higher cost, lower availability; false positives in post-surgical granulation tissue, fractures, implants, atherosclerosis, neuro-osteoarthropathy

D. SPECT-CT (Single Photon Emission CT)

• Hybrid system combining nuclear medicine (SPECT) with CT
• The CT provides precise anatomical localisation of radionuclide uptake
• Significantly improves sensitivity and specificity of standard ⁹⁹ᵐTc bone scan
• Reduces need for additional imaging investigations (cost-effective)
• Particularly useful for:
  • Spinal pathology (facet arthropathy vs disc vs sacroiliitis)
  • Periprosthetic infection localisation
  • Complex foot and ankle pathology

6. Therapeutic Radionuclides in Orthopaedics

A. Strontium-89 (⁸⁹Sr) Chloride

• Strontium is a calcium analogue → selectively concentrates in areas of osteoblastic bone metastases
• Emits beta particles → localised irradiation of metastatic sites
• Used for palliative treatment of pain from multiple bone metastases in prostate and breast cancer
• Response rate: 60-80% pain relief; onset 1-3 weeks
• Duration: 3-6 months
• Main adverse effect: bone marrow suppression (thrombocytopenia, leucopenia)
• Dose: 150 MBq (4 mCi) IV single dose

B. Samarium-153-EDTMP (¹⁵³Sm)

• Localises to areas of increased bone turnover (osteoblastic metastases)
• Emits beta radiation (therapeutic) + gamma radiation (imaging simultaneously)
• Used for palliative bone pain relief in multiple metastases
• Advantage over ⁸⁹Sr: shorter half-life (46 hours vs 50 days) → faster marrow recovery
• Can image distribution with gamma camera after injection

C. Radium-223 (²²³Ra) Dichloride - Xofigo

• Calcium mimetic → targeted alpha emitter to osteoblastic metastases
• Alpha radiation has high linear energy transfer → potent cell killing with short range (< 100 μm)
• FDA approved for castration-resistant prostate cancer with bone metastases (no visceral metastases)
• Shown to improve overall survival (ALSYMPCA trial)
• Advantage: alpha particles cause minimal marrow suppression vs beta emitters

7. Comparison Summary

8. Advantages and Limitations

Advantages

• Whole-body survey in one scan (can detect multifocal disease)
• Detects pathology months before plain radiograph changes
• Functional/metabolic information (not just anatomical)
• Relatively low cost vs MRI; widely available
• High sensitivity for detecting bone metastases

Limitations

• Low specificity - many causes of "hot spots" (fracture, infection, tumour, Paget's all look similar)
• Poor spatial/anatomical resolution on its own (improved with SPECT-CT or PET-CT)
• Radiation exposure (3-6 mSv for standard ⁹⁹ᵐTc scan)
• Cannot determine tumour type
• Pure lytic lesions (myeloma, RCC) may be occult/cold
• Physiological uptake at growth plates in children can mask pathology

Key Exam Points

1. ⁹⁹ᵐTc-MDP is the most commonly used radionuclide in orthopaedics - adsorbs to hydroxyapatite, reflects osteoblastic activity
2. Three phases: Flow → Blood pool → Delayed (3 hours) - all positive in osteomyelitis; phase 3 only positive in low-grade infection
3. If all 3 phases negative → infection excluded (high NPV)
4. Bone scan detects metastases 4-6 months before X-ray
5. Early AVN = cold spot; late AVN = hot-in-cold (doughnut sign)
6. Paget's disease: most sensitive = bone scan (intense uniform uptake in affected bones)
7. ¹¹¹In-WBC scan = gold standard nuclear medicine for peripheral skeleton PJI
8. ⁶⁷Ga scan preferred for spinal infection
9. FDG-PET has highest sensitivity and specificity overall; best for chronic osteomyelitis
10. Therapeutic use: ⁸⁹Sr, ¹⁵³Sm = palliative bone pain; ²²³Ra = survival benefit in prostate Ca
11. SPECT-CT: combines nuclear medicine with CT anatomy → increased specificity