Biomarkers of Hip Implant Function: Diagnostic Modalities to Prevent Chronic Periprosthetic Joint Infection and Implant Failure

Biomarkers of Hip Implant Function
List of contributors
Copyright
Contents
1 Introduction to hip implants and biomarker testing
	1.1 Overview of the hip joint
		1.1.1 Anatomy of the hip
			1.1.1.1 Cartilage
			1.1.1.2 Joint capsule and synovial fluid
			1.1.1.3 Ligaments
			1.1.1.4 Muscles
			1.1.1.5 Blood supply and innervation
		1.1.2 Hip joint pathologies
			1.1.2.1 Osteoarthritis
			1.1.2.2 Rheumatoid arthritis
			1.1.2.3 Hip dysplasia
			1.1.2.4 Avascular necrosis
			1.1.2.5 Femoroacetabular impingement
			1.1.2.6 Traumatic injuries
	1.2 Overview of hip implants
		1.2.1 Implant biomaterials
			1.2.1.1 Metals
			1.2.1.2 Plastic polymers
			1.2.1.3 Ceramics
		1.2.2 Bone fixation
		1.2.3 Implant classification
		1.2.4 Evolution of a total hip replacement
			1.2.4.1 Implant modularity
		1.2.5 The rise and fall of hip resurfacing
		1.2.6 Implant degradation
		1.2.7 Implant performance
			1.2.7.1 Surgeon factors
			1.2.7.2 Implant factors
			1.2.7.3 Patient factors
	1.3 Introduction to biomarkers
		1.3.1 Biomarker discovery
		1.3.2 Assay validation
		1.3.3 Evaluation of clinical validity
			1.3.3.1 Sensitivity and specificity
			1.3.3.2 Predictive values
			1.3.3.3 Likelihood ratios
			1.3.3.4 Diagnostic accuracy
			1.3.3.5 Receiver operating characteristic curves
			1.3.3.6 Diagnostic odds ratios
		1.3.4 Characteristics of an ideal biomarker
		1.3.5 Biomarkers of hip implant function and toxicity
	References
2 Degradation of metal hip implants
	2.1 Introduction to metallic biomaterials
		2.1.1 Iron-based alloys
		2.1.2 Cobalt-based alloys
		2.1.3 Titanium-based alloys
	2.2 Introduction to tribology
		2.2.1 Contact of surfaces
		2.2.2 Friction
		2.2.3 Wear of materials
			2.2.3.1 Abrasive wear
			2.2.3.2 Adhesive wear
			2.2.3.3 Fretting/fatigue wear
		2.2.4 Lubrication
			2.2.4.1 Boundary lubrication
			2.2.4.2 Fluid-film lubrication
			2.2.4.3 Mixed lubrication
			2.2.4.4 Lubrication in metal hips
	2.3 Introduction to corrosion
		2.3.1 Thermodynamics and electrochemistry
		2.3.2 Passivity of metallic materials
		2.3.3 Types of corrosion
			2.3.3.1 Uniform/general corrosion
			2.3.3.2 Galvanic corrosion
			2.3.3.3 Crevice corrosion
			2.3.3.4 Pitting corrosion
			2.3.3.5 Intergranular corrosion
	2.4 Tribocorrosion
	2.5 Modern hip replacements
		2.5.1 Sources of degradation
			2.5.1.1 Bearing surfaces
			2.5.1.2 Modular tapers
			2.5.1.3 Stem–cement interface
		2.5.2 Adverse reaction to metal debris
		2.5.3 Assessing material loss from metal hip implants
		2.5.4 Studying metal deposits in tissue
			2.5.4.1 Periprosthetic tissue
			2.5.4.2 Organ tissue
	2.6 Summary and future directions
	References
3 Implant metals and their potential toxicity
	3.1 Hip implant metals and the human health
		3.1.1 Cobalt
			3.1.1.1 Toxicokinetics
			3.1.1.2 Systemic toxicity
		3.1.2 Chromium
			3.1.2.1 Toxicokinetics
			3.1.2.2 Systemic toxicity
		3.1.3 Molybdenum
			3.1.3.1 Toxicokinetics
			3.1.3.2 Systemic toxicity
		3.1.4 Nickel
			3.1.4.1 Toxicokinetics
			3.1.4.2 Systemic toxicity
		3.1.5 Titanium
			3.1.5.1 Toxicokinetics
			3.1.5.2 Systemic toxicity
		3.1.6 Vanadium
			3.1.6.1 Toxicokinetics
			3.1.6.2 Systemic toxicity
		3.1.7 Aluminium
			3.1.7.1 Toxicokinetics
			3.1.7.2 Systemic toxicity
		3.1.8 Reproductive toxicity
		3.1.9 Genotoxicity and carcinogenicity
	3.2 Metal hypersensitivity
	3.3 Local effects of metal debris
	References
4 Markers of hip implant degradation: analytical considerations and clinical interpretation
	4.1 Introduction
	4.2 Mechanisms of implant degradation
		4.2.1 Passive corrosion
		4.2.2 Galvanic corrosion
		4.2.3 Mechanically assisted corrosion
		4.2.4 Bearing wear
		4.2.5 Abnormal component contact
	4.3 Measuring systemic levels of cobalt, chromium, and titanium
		4.3.1 Choice of sample type
			4.3.1.1 Urine
			4.3.1.2 Blood
		4.3.2 Specimen collection and storage
			4.3.2.1 Urine
			4.3.2.2 Blood
		4.3.3 Quantification of metal levels
			4.3.3.1 Sample preparation
			4.3.3.2 Analytical approach
			4.3.3.3 Minimising spectral interferences
			4.3.3.4 Sources of intra- and inter-laboratory variability
			4.3.3.5 The units
	4.4 Using systemic metal levels to assess implant degradation and risk of local adverse reactions
		4.4.1 Cobalt and chromium
		4.4.2 Titanium
	4.5 Summary and future directions
	References
5 Biomarkers of compromised implant fixation
	5.1 Introduction
	5.2 Osseointegration of hip implants
		5.2.1 Implant design
			5.2.1.1 Bioactive coatings
			5.2.1.2 Surface properties
				Wettability
				Chemical composition
				Oxide layer thickness
				Roughness
			5.2.1.3 Porous metals
		5.2.2 Patient-related factors
		5.2.3 Surgeon-related factors
	5.3 Periprosthetic osteolysis and aseptic loosening
	5.4 Postoperative measures to stimulate osseointegration and inhibit osteolysis
		5.4.1 Rehabilitation and postoperative drugs
		5.4.2 Pharmacological inhibition of periprosthetic osteolysis
		5.4.3 Biophysical stimulation
	5.5 Monitoring patients for signs of periprosthetic osteolysis and aseptic loosening
	5.6 Molecular biomarkers of periprosthetic osteolysis and aseptic loosening
		5.6.1 Inflammatory markers
		5.6.2 Markers of bone turnover
		5.6.3 Markers of oxidative stress
		5.6.4 Single-nucleotide polymorphisms
			5.6.4.1 Cytokines
			5.6.4.2 Proteins, receptors, and intracellular mediators
			5.6.4.3 Enzymes
	5.7 Summary and future directions
	References
6 Biomarkers of periprosthetic joint infection
	6.1 Introduction
	6.2 Periprosthetic joint infection
		6.2.1 Pathogenesis and bacterial aetiology
		6.2.2 Clinical presentation
		6.2.3 Treatment
	6.3 Clinical definition of periprosthetic joint infection
	6.4 Diagnostic categories
		6.4.1 Clinical symptoms
		6.4.2 Imaging studies
		6.4.3 Blood biomarkers
			6.4.3.1 C-reactive protein and erythrocyte sedimentation rate
			6.4.3.2 D-dimer
			6.4.3.3 Interleukin-6
			6.4.3.4 Procalcitonin
			6.4.3.5 Fibrinogen
		6.4.4 Synovial biomarkers
			6.4.4.1 White blood cell count and polymorphonuclear leukocyte percentage
			6.4.4.2 Leukocyte esterase
			6.4.4.3 Alpha-defensin
			6.4.4.4 Calprotectin
			6.4.4.5 Synovial C-reactive protein
			6.4.4.6 Synovial interleukin-6
			6.4.4.7 Synovial interleukin-8
		6.4.5 Microbiology
			6.4.5.1 Joint aspiration culture
			6.4.5.2 Preoperative periprosthetic biopsy culture
			6.4.5.3 Intraoperative periprosthetic tissue culture
			6.4.5.4 Sonication fluid culture
		6.4.6 Histology
			6.4.6.1 Gram stain
		6.4.7 Molecular techniques
			6.4.7.1 Polymerase chain reaction
			6.4.7.2 Next-generation sequencing
	6.5 Confounding factors
		6.5.1 Adverse reaction to metal debris
		6.5.2 Inflammatory arthritis
		6.5.3 Crystal-induced arthritis
	6.6 Summary and future directions
	References
7 Hip implants and systemic cobalt toxicity: a comprehensive review with case studies
	7.1 Introduction
	7.2 Arthroprosthetic cobaltism
		7.2.1 Case studies
			7.2.1.1 Case study 1
			7.2.1.2 Case study 2
			7.2.1.3 Case study 3
			7.2.1.4 Case study 4
			7.2.1.5 Case study 5
			7.2.1.6 Case study 6
			7.2.1.7 Case study 7
			7.2.1.8 Case study 8
			7.2.1.9 Case study 9
			7.2.1.10 Case study 10
			7.2.1.11 Case study 11
			7.2.1.12 Case study 12
			7.2.1.13 Case study 13
			7.2.1.14 Case study 14
			7.2.1.15 Case study 15
			7.2.1.16 Case study 16
			7.2.1.17 Case study 17
			7.2.1.18 Case study 18
		7.2.2 Mechanisms of cobalt toxicity
			7.2.2.1 Induction of oxidative stress
			7.2.2.2 Disruption of mitochondrial function
			7.2.2.3 Simulation of cellular hypoxia
			7.2.2.4 Interference with calcium signalling
			7.2.2.5 Displacement of divalent metal cations from metalloproteins
			7.2.2.6 Inhibition of iodine uptake
		7.2.3 Differential diagnosis
			7.2.3.1 Cardiomyopathy
			7.2.3.2 Neurotoxic and psychiatric symptoms
			7.2.3.3 Thyroid abnormalities
		7.2.4 Treatment
			7.2.4.1 Revision surgery
			7.2.4.2 Chelation therapy
			7.2.4.3 Therapeutic plasma exchange
		7.2.5 Individual susceptibility to systemic cobalt toxicity
			7.2.5.1 Decreased albumin–cobalt binding capacity
			7.2.5.2 Kidney disease
			7.2.5.3 Nutritional and hormonal deficiencies
		7.2.6 Systemic toxicity and free cobalt ion levels
	7.3 Summary and future directions
	References
8 Clinical guidelines on the use of biomarkers for surveillance of hip replacements
	8.1 Introduction
	8.2 Evaluating implant wear and risk of local adverse reactions to metal debris in patients with metal-on-metal hips
		8.2.1 Circulating cobalt and chromium levels
		8.2.2 The decision to revise
		8.2.3 Conclusion
	8.3 Investigation for systemic toxicity
		8.3.1 Circulating cobalt levels
		8.3.2 The decision to revise
		8.3.3 Conclusion
	8.4 Monitoring of patients with titanium-based hip implants
		8.4.1 Circulating titanium levels
		8.4.2 The decision to revise
		8.4.3 Conclusion
	8.5 Investigation for periprosthetic infection
		8.5.1 Conclusion
	8.6 Summary and future directions
	References
Index