JOINT RECONSTRUCTION AND REPLACEMENT: MATERIALS, TECHNOLOGIES, AND GLOBAL MARKETS. HLC165A July Dr. Ritu Thakur Dangi Project Analyst

Transcription

1 JOINT RECONSTRUCTION AND REPLACEMENT: MATERIALS, TECHNOLOGIES, AND GLOBAL MARKETS HLC165A July 2014 Dr. Ritu Thakur Dangi Project Analyst ISBN: BCC Research 49 Walnut Park, Building 2 Wellesley, MA USA (toll-free within the USA), or (+1) information@bccresearch.com

2 TABLE OF CONTENTS CHAPTER 1 INTRODUCTION 2 JOINT RECONSTRUCTION AND REPLACEMENT 2 STUDY BACKGROUND 2 STUDY GOALS AND OBJECTIVES 3 INTENDED AUDIENCE 4 SCOPE OF THE REPORT 4 METHODOLOGY AND INFORMATION SOURCES 4 ANALYST'S CREDENTIALS 5 RELATED BCC RESEARCH REPORTS 5 BCC RESEARCH WEBSITE 5 DISCLAIMER 6 CHAPTER 2 SUMMARY 8 EXECUTIVE SUMMARY 8 SUMMARY TABLE A GLOBAL MARKET FOR JOINT RECONSTRUCTION AND REPLACEMENT, THROUGH 2018 ($ SUMMARY FIGURE A GLOBAL MARKET FOR JOINT RECONSTRUCTION AND REPLACEMENT, ($ SUMMARY TABLE B GLOBAL JOINT RECONSTRUCTION AND REPLACEMENT MARKET BY SEGMENT TYPE, THROUGH 2018 ($ SUMMARY FIGURE B GLOBAL JOINT RECONSTRUCTION AND REPLACEMENT MARKET BY SEGMENT TYPE, ($ CHAPTER 3 CLINICAL OVERVIEW OF BONES AND JOINTS 12 CLINICAL OVERVIEW AND ROLE OF BONES IN BODY MOVEMENT 12 BONE STRUCTURE 12 CELLULAR STRUCTURE 12 Osteogenic Cells 13 Osteoblasts 13 Osteocytes 13 Osteoclasts 13 Organic Matrix 13 Collagen 13 Cartilage 14 BONE MODELING 14 BONE REMODELING 14 BONE MATERIAL 14 COMPACT BONE 14 SPONGY BONE 15 BONE MARROW 15 LIGAMENTS AND TENDONS 15 JOINT STRUCTURE, FUNCTION AND DEFINITIONS 15 HIP JOINT 16 KNEE JOINT 16 SHOULDER JOINT 16 SMALL JOINTS 16

3 Foot and Ankle 17 Hand and Wrist 17 Elbow 17 Digits 18 CHAPTER 4 JOINT DISORDERS 20 GENERAL OVERVIEW OF JOINT PAIN AND RELATED DISORDERS 20 OSTEOARTHRITIS 20 DISEASE OVERVIEW 20 ETIOLOGY 21 EPIDEMIOLOGY AND MARKET BURDEN 21 TABLE 1 GLOBAL PREVALENCE OF OSTEOARTHRITIS (SYMPTOMATIC) BY GEOGRAPHIC REGION, THROUGH 2018 ( FIGURE 1 GLOBAL PREVALENCE OF OSTEOARTHRITIS (SYMPTOMATIC) BY GEOGRAPHIC REGION, ($ DISEASE SYMPTOMS AND RISK FACTORS 23 Disease Symptoms 23 Risk Factors 23 DIAGNOSIS AND TREATMENT 24 Diagnosis 24 Treatment 24 Non-pharmacological Treatment 24 Pharmacological Treatment 25 Intra-articular Treatment 25 Surgical Treatment 25 Reducing the Risk of Osteoarthritis 26 RHEUMATOID ARTHRITIS 27 OVERVIEW 27 ETIOLOGY 27 EPIDEMIOLOGY AND ECONOMIC BURDEN 28 TABLE 2 GLOBAL PREVALENCE OF RHEUMATOID ARTHRITIS (SYMPTOMATIC) BY REGION, THROUGH 2018 ( FIGURE 2 GLOBAL PREVALENCE OF RHEUMATOID ARTHRITIS (SYMPTOMATIC) BY REGION, ($ DISEASE SYMPTOMS AND RISK FACTORS 29 Disease Symptoms 29 Risk factors 29 DIAGNOSIS AND TREATMENT 30 Diagnosis 30 Treatment 30 Non-pharmacological Treatment 30 Pharmacological Treatment 31 Surgical Treatment 32 REDUCING THE RISK OF RHEUMATOID ARTHRITIS 32 POSTTRAUMATIC ARTHRITIS 33 DISEASE OVERVIEW 33 ETIOLOGY 33 EPIDEMIOLOGY AND MARKET BURDEN

4 TABLE 3 POST-TRAUMATIC ARTHRITIS AND INCIDENCE OF KNEE FRACTURES BY GEOGRAPHIC REGION, THROUGH 2018 (ACTUAL) ( FIGURE 3 POST-TRAUMATIC ARTHRITIS AND GLOBAL INCIDENCE OF KNEE FRACTURES BY REGION, ($ DISEASE SYMPTOMS AND RISK FACTORS 34 DIAGNOSIS AND TREATMENT 35 Diagnosis 35 Treatment 35 REDUCING THE RISK OF POST-TRAUMATIC ARTHRITIS 35 OSTEOPOROSIS 36 DISEASE OVERVIEW 36 ETIOLOGY 37 EPIDEMIOLOGY AND ECONOMIC BURDEN 37 TABLE 4 GLOBAL PREVALENCE OF OSTEOPOROSIS BY REGION, THROUGH 2018 ( FIGURE 4 GLOBAL PREVALENCE OF OSTEOPOROSIS BY REGION, ($ DISEASE SYMPTOMS AND RISK FACTORS 39 Disease Symptoms 39 Fractures 39 Spinal Deformities 39 Pain 39 Risk Factors 39 DIAGNOSIS AND TREATMENT 41 Diagnosis 41 Treatment 41 REDUCING THE RISK OF OSTEOPOROSIS 42 JOINT DISORDERS AND ECONOMIC BURDEN ON THE U.S. HEALTHCARE SYSTEM 43 HISTORICAL BACKGROUND OF ORTHOPEDIC MARKET CHAPTER 5 JOINT IMPLANTS, MATERIALS AND ASSOCIATED ISSUES 46 JOINT IMPLANTS 46 HIP IMPLANTS 46 KNEE IMPLANTS 46 SHOULDER IMPLANTS 46 SMALL JOINT IMPLANTS 46 Elbow Implants 46 Foot and Ankle Implants 46 Hand Wrist Implants 47 Digit Implants 47 IMPLANT MATERIALS 47 HISTORICAL BACKGROUND 47 CURRENT MATERIALS 48 Titanium 48 Cobalt-Chrome 48 Tantalum 48 Foam Metal Implants 48 Polyetheretherketone 48

5 Allograft Prosthesis 49 Innovative Ceramics 49 ISSUES ASSOCIATED WITH CURRENT MATERIALS 49 JOINT REPLACEMENT PROCEDURES 50 OPEN PROCEDURE 50 MINIMALLY INVASIVE PROCEDURE 50 IMPLANT FIXATION 50 IMPLANTS BY BEARING TYPE 51 FIXED BEARING IMPLANTS 51 MOBILE BEARING IMPLANTS 51 CHAPTER 6 HIP REPLACEMENT 54 OVERVIEW OF HIP REPLACEMENT 54 HIP FRACTURES 55 TABLE 5 GLOBAL INCIDENCE OF HIP FRACTURES BY REGION, THROUGH 2018 FIGURE 5 GLOBAL INCIDENCE OF HIP FRACTURES BY REGION, HIP IMPLANT TYPES 56 MODULAR VS NON-MODULAR IMPLANTS 56 CEMENTED VERSUS PRESS-FIT (CEMENTLESS) IMPLANTS 57 BEARING SURFACES 57 Metal-on-Polyethylene 57 Ceramic-on-Ceramic 57 Metal-on-Metal 58 CROSS-LINKED POLYETHYLENE 58 BIPOLAR IMPLANTS 59 GENDER SPECIFIC HIP IMPLANTS 59 HIP REPLACEMENT BY TYPE 59 PRIMARY/TOTAL HIP REPLACEMENT 59 Indications for Total Hip Replacement 59 Cemented Hip Implants 60 Cementless Hip Implants (Press-Fit) 60 Hybrid Hip Implants 61 HIP RESURFACING 61 Birmingham Hip Resurfacing (BHR) 61 Indications for Hip Resurfacing 62 REVISION HIP REPLACEMENT 62 HEMIARTHROPLASTY 62 MINIMALLY INVASIVE HIP ARTHROPLASTY 63 Anterior Hip Replacement Surgery 63 NAVIGATION SYSTEMS 63 Robotic Hip Surgery 64 HIP REPLACEMENT PROCEDURES BY REGION 64 TABLE 6 GLOBAL HIP REPLACEMENT PROCEDURES VS TOTAL JOINT RECONSTRUCTION PROCEDURES, THROUGH 2018 FIGURE 6 GLOBAL HIP REPLACEMENT PROCEDURES VS TOTAL JOINT RECONSTRUCTION PROCEDURES,

6 TABLE 7 GLOBAL HIP REPLACEMENT PROCEDURES BY REGION, THROUGH 2018 FIGURE 7 GLOBAL HIP REPLACEMENT PROCEDURES BY REGION, BENEFITS, RISK FACTORS AND COMPLICATIONS ASSOCIATED WITH HIP REPLACEMENT CHAPTER 7 KNEE REPLACEMENT 69 OVERVIEW OF KNEE REPLACEMENT 69 KNEE IMPLANT TYPES 70 FIXED BEARING KNEE IMPLANT 70 MOBILE BEARING KNEE IMPLANT 70 MEDIAL PIVOT KNEE IMPLANT 71 GENDER SPECIFIC KNEE IMPLANTS 71 PATIENT-SPECIFIC/CUSTOMIZED IMPLANTS 71 KNEE REPLACEMENT TYPES 72 PRIMARY/TOTAL KNEE REPLACEMENT 72 Indications for Total Knee Replacement 72 Posterior Stabilized/Cruciate Retaining 72 Cemented Knee Prostheses 73 Cementless Knee Prostheses 73 Hybrid Knee Fixation 73 KNEE RESURFACING 74 REVISION KNEE REPLACEMENT 74 Indications for Revision Knee 74 UNICONDYLAR KNEE REPLACEMENT 74 NAVIGATION SYSTEMS 75 Robotic Knee Surgery 75 NAVIGATION SYSTEMS 76 Computer-Guided Robotic Shoulder Replacement Surgery 76 MINIMALLY INVASIVE SURGERY 76 KNEE REPLACEMENT PROCEDURES BY REGION 76 TABLE 8 GLOBAL KNEE REPLACEMENT PROCEDURES VS TOTAL JOINT RECONSTRUCTION PROCEDURES, THROUGH 2018 FIGURE 8 GLOBAL KNEE REPLACEMENT PROCEDURES VS TOTAL JOINT RECONSTRUCTION PROCEDURES, TABLE 9 GLOBAL KNEE REPLACEMENT PROCEDURES BY REGION, THROUGH 2018 FIGURE 9 GLOBAL KNEE REPLACEMENT PROCEDURES BY REGION, BENEFITS, RISK FACTORS AND COMPLICATIONS OF KNEE REPLACEMENT PROCEDURES CHAPTER 8 SHOULDER REPLACEMENT 81 OVERVIEW OF SHOULDER REPLACEMENT 81 SHOULDER IMPLANT MATERIALS AND TYPES 81 SHOULDER REPLACEMENT TYPES 82 PRIMARY/TOTAL SHOULDER REPLACEMENT 82 REVERSE SHOULDER ARTHROPLASTY 83

7 SHOULDER HEMIARTHROPLASTY/PARTIAL SHOULDER REPLACEMENT 83 SHOULDER RESURFACING 84 REVISION SHOULDER REPLACEMENT 84 MINIMALLY INVASIVE SHOULDER REPLACEMENT 84 SHOULDER REPLACEMENT PROCEDURES BY REGION 85 TABLE 10 GLOBAL SHOULDER REPLACEMENT PROCEDURES VS TOTAL JOINT RECONSTRUCTION PROCEDURES, THROUGH 2018 FIGURE 10 GLOBAL SHOULDER REPLACEMENT PROCEDURES VS TOTAL JOINT RECONSTRUCTION PROCEDURES, TABLE 11 GLOBAL SHOULDER REPLACEMENT PROCEDURES BY REGION, THROUGH 2018 FIGURE 11 GLOBAL SHOULDER REPLACEMENT PROCEDURES BY REGION, BENEFITS, RISK FACTORS AND COMPLICATIONS OF SHOULDER REPLACEMENT PROCEDURES CHAPTER 9 SMALL JOINT REPLACEMENT 89 OVERVIEW OF SMALL JOINT REPLACEMENT 89 SMALL JOINT REPLACEMENT TYPES 90 ANKLE REPLACEMENT 90 Mobile Bearing 91 Fixed Bearing 91 ELBOW REPLACEMENT 91 Total Elbow Arthroplasty 91 Constrained Arthroplasty 92 Semiconstrained Arthroplasty 92 Unconstrained Arthroplasty 92 Radial Head Arthroplasty 92 Metal and Pyrocarbon 93 Silicone 93 HAND WRIST REPLACEMENT 93 DIGITS REPLACEMENT 93 Finger Replacement 94 Toe Replacement 94 Thumb Replacement 94 ARTHROSCOPIC (MINIMALLY INVASIVE) SMALL JOINT SURGERY 94 Ankle Arthroscopy 95 Elbow Arthroscopy 95 Wrist Arthroscopy 95 SMALL JOINT REPLACEMENT PROCEDURES BY REGION 95 TABLE 12 GLOBAL SMALL JOINT REPLACEMENT PROCEDURES VS TOTAL JOINT RECONSTRUCTION PROCEDURES, THROUGH 2018 FIGURE 12 GLOBAL SMALL JOINT REPLACEMENT PROCEDURES VS TOTAL JOINT RECONSTRUCTION PROCEDURES, TABLE 13 GLOBAL SMALL JOINT REPLACEMENT PROCEDURES BY REGION, THROUGH 2018 FIGURE 13 GLOBAL SMALL JOINT REPLACEMENT PROCEDURES BY REGION,

8 BENEFITS, RISK FACTORS AND COMPLICATIONS OF SMALL JOINT REPLACEMENT PROCEDURES 97 CHAPTER 10 JOINT RECONSTRUCTION AND REPLACEMENT MARKET ASSESSMENT 100 JOINT RECONSTRUCTION AND REPLACEMENT MARKET 100 GLOBAL MARKET 100 Global Market by Region 100 TABLE 14 GLOBAL JOINT RECONSTRUCTION AND REPLACEMENT MARKET BY REGION, THROUGH 2018 ($ FIGURE 14 GLOBAL JOINT RECONSTRUCTION AND REPLACEMENT MARKET BY REGION, ($ BILLIONS) Global Market by Segments 101 TABLE 15 GLOBAL JOINT RECONSTRUCTION AND REPLACEMENT MARKET BY SEGMENT, THROUGH 2018 ($ FIGURE 15 GLOBAL JOINT RECONSTRUCTION AND REPLACEMENT MARKET BY SEGMENT, ($ FIGURE 16 JOINT RECONSTRUCTION AND REPLACEMENT MARKET BY SEGMENT TYPE, 2013 (% OF TOTAL MARKET) JOINT RECONSTRUCTION AND REPLACEMENT MARKET BY SEGMENTS 103 HIP REPLACEMENT 103 Hip Replacement by Region 103 TABLE 16 GLOBAL HIP REPLACEMENT MARKET BY REGION, THROUGH 2018 ($ FIGURE 17 GLOBAL HIP REPLACEMENT MARKET BY REGION, ($ Hip Replacement by Type 104 TABLE 17 GLOBAL HIP REPLACEMENT MARKET BY PROCEDURE, THROUGH 2018 ($ FIGURE 18 GLOBAL HIP REPLACEMENT MARKET BY PROCEDURE, ($ KNEE REPLACEMENT 106 Knee Replacement by Region 106 TABLE 18 GLOBAL KNEE REPLACEMENT MARKET BY REGION, THROUGH 2018 ($ FIGURE 19 GLOBAL KNEE REPLACEMENT MARKET BY REGION, ($ Knee Replacement by Type 107 TABLE 19 GLOBAL KNEE REPLACEMENT MARKET BY PROCEDURE, THROUGH 2018 ($ FIGURE 20 GLOBAL KNEE REPLACEMENT MARKET BY PROCEDURE, ($ SHOULDER REPLACEMENT 108 TABLE 20 GLOBAL SHOULDER REPLACEMENT MARKET BY REGION, THROUGH 2018 ($ FIGURE 21 GLOBAL SHOULDER REPLACEMENT MARKET BY REGION, ($ SMALL JOINT REPLACEMENT 109 TABLE 21 GLOBAL SMALL JOINT REPLACEMENT MARKET BY REGION, THROUGH 2018 ($ FIGURE 22 GLOBAL SMALL JOINT REPLACEMENT MARKET BY REGION, ($

9 BONE CEMENT 110 TABLE 22 GLOBAL BONE CEMENT MARKET BY REGION, THROUGH 2018 ($ FIGURE 23 GLOBAL BONE CEMENT SMALL JOINT REPLACEMENT MARKET BY REGION, ($ MARKET GROWTH DRIVERS AND RESTRAINTS 112 GROWTH DRIVERS 112 Growing Aged Population 112 Baby Boom Population Reaching Retirement 112 Increasing Awareness 112 Active Younger Patients Seeking Surgery 112 Increasing Demand for Joint Replacement Surgery 112 Development and Adoption of Newer Implant Materials and Techniques Constant Innovations in Implant Design 113 Increased Adoption of Minimally Invasive Surgery 113 Increased Adoption of Computer Guided (Robotic) Surgery 113 Direct-to-Customer Marketing 113 Favorable Reimbursement for Procedure Growth 114 Medical Tourism 114 GROWTH RESTRAINTS 114 Downward Pricing Pressure and Increasing Material Cost 114 Increasing Competition and Decreasing Profit Margins 114 Risk of Failure Rates of Newer Implant Materials 114 Increasing Research and Development Costs 115 Regulatory Hurdles and Product Recalls 115 Shorter Product Life Cycles 115 Risk and Complications 115 Alternative Treatment Options CHAPTER 11 COMPETITION AND MARKET SHARES 117 COMPETITIVE LANDSCAPE 117 TABLE 23 GLOBAL JOINT RECONSTRUCTION AND REPLACEMENT MARKET SHARES, 2013 ($ MILLIONS/%) FIGURE 24 GLOBAL JOINT RECONSTRUCTION AND REPLACEMENT MARKET LEADERS, 2012 (% OF TOTAL MARKET) MARKET SEGMENT COVERAGE BY COMPANY 119 TABLE 24 ORTHOPEDIC COMPANIES JOINT RECONSTRUCTION PRODUCT SEGMENT COVERAGE MATRIX CHAPTER 12 MARKET STRATEGY 122 JOINT RECONSTRUCTION AND REPLACEMENT MARKET STRATEGY 122 KEY STRATEGIC EVENTS IN LAST 10 YEARS 122 TABLE 25 JOINT RECONSTRUCTION AND REPLACEMENT MARKET, KEY MERGERS/ACQUISITIONS MICROPORT SCIENTIFIC'S ACQUISITION OF ORTHORECON BUSINESS OF WRIGHT MEDICAL STRYKER'S ACQUISITION OF MAKO SURGICAL 124 ZIMMER'S ACQUISITION OF NORMED MEDIZIN-TECHNIK

10 SMITH & NEPHEW'S ACQUISITION OF SUSHRUT SURGICALS 124 ZIMMER'S ACQUISITION OF KNEE CREATIONS 125 STRYKER'S ACQUISITION OF TRAUSON 125 JOHNSON & JOHNSON'S ACQUISITION OF SYNTHES 125 MEDTRONIC'S ACQUISITION OF CHINA KANGHUI HOLDINGS 126 TORNIER'S ACQUISITION OF ORTHOHELIX SURGICAL DESIGNS 126 INTEGRA LIFESCIENCES' ACQUISITION OF ASCENSION ORTHOPEDICS 126 STRYKER'S ACQUISITION OF ORTHOVITA 126 EXACTECH'S ACQUISITION OF BRIGHTON PARTNERS 126 ZIMMER HOLDINGS' ACQUISITION OF BEIJING MONTAGNE MEDICAL DEVICE 126 ORTHOPEDIC SYNERGY'S ACQUISITION OF PRAXIM 127 SMALL BONE INNOVATIONS' ACQUISITION OF LINK AMERICA 127 DEPUY ORTHOPEDICS' ACQUISITION OF FINSBURY ORTHOPAEDICS 127 WRIGHT MEDICAL'S ACQUISITION OF INBONE TECHNOLOGIES 127 SMITH & NEPHEW'S ACQUISITION OF PLUS ORTHOPAEDICS 128 TORNIER'S ACQUISITION OF NEXA ORTHOPAEDICS 128 SMITH & NEPHEW'S ACQUISITION OF OSTEOBIOLOGICS 128 SMALL BONE INNOVATIONS ACQUISITION OF AVANTA ORTHOPAEDICS 128 ZIMMER'S ACQUISITION OF IMPLEX 128 ZIMMER'S ACQUISITION OF CENTERPULSE 129 CHAPTER 13 MARKETED AND PIPELINE PRODUCTS 131 MARKETED PRODUCTS 131 HIP RECONSTRUCTION AND REPLACEMENT 131 Key Products from Leading Companies 131 DePuy Synthes (Johnson & Johnson) 131 Zimmer 132 Stryker 132 Biomet 133 Smith & Nephew 133 Exactech 133 Key Device Approvals by the FDA 134 TABLE 26 HIP RECONSTRUCTION AND REPLACEMENT: LIST OF KEY DEVICE APPROVALS BY THE FDA, Key Premarket Approvals in the U.S. 137 DePuy Ceramax Ceramic Total Hip System (P070026) 137 Pinnacle CoMplete Acetabular Hip System (P090002) 137 KNEE RECONSTRUCTION AND REPLACEMENT 137 Key Products from Leading Companies 137 DePuy Synthes (Johnson & Johnson) 137 Zimmer 138 Stryker 138 Biomet 139 Smith & Nephew 139 Exactech 139 Key Device Approvals by the FDA 140 TABLE 27 KNEE RECONSTRUCTION AND REPLACEMENT, LIST OF KEY DEVICE APPROVALS BY THE FDA,

11 SHOULDER RECONSTRUCTION AND REPLACEMENT 143 Key Products from Leading Companies 143 DePuy Synthes (Johnson & Johnson) 143 Zimmer 144 Stryker 144 Biomet 144 Exactech 145 Key Device Approvals by the FDA 145 TABLE 28 SHOULDER RECONSTRUCTION AND REPLACEMENT, LIST OF KEY DEVICE APPROVALS BY FDA, SMALL JOINT RECONSTRUCTION AND REPLACEMENT 147 Key Products from Leading Companies 147 DePuy Synthes (Johnson & Johnson) 147 Zimmer 147 Stryker 147 Biomet 147 Wright Medical 148 Key Device Approvals by the FDA 148 TABLE 29 SMALL JOINT RECONSTRUCTION AND REPLACEMENT, LIST OF KEY DEVICE APPROVALS BY THE FDA, KEY PIPELINE PRODUCTS 149 HIP RECONSTRUCTION AND REPLACEMENT 149 ReCap Total Hip Resurfacing System 149 TABLE 30 HIP RECONSTRUCTION AND REPLACEMENT, LIST OF KEY PIPELINE DEVICES Trinity BIOLOX delta Ceramic-on-Ceramic Total Hip System 150 Element Proportional Neck Stems 150 NovoHip: Total Hip System 151 DePuy Silent Hip 151 Reflection FSO V Total Hip Replacement 151 KNEE RECONSTRUCTION AND REPLACEMENT 152 TABLE 31 KNEE RECONSTRUCTION AND REPLACEMENT, LIST OF KEY PIPELINE DEVICES Alpina Unicompartmental Knee 152 Uniglide Mobile Bearing Unicondylar Knee System 152 NovoKnee Total Knee System 153 BiPhasic Cartilage Repair Implant 153 GEM Total Knee System 153 HemiCAP Femoral Condyle 153 Exactech GPS Guided Personalized Surgery 154 Optetrak Logic RBK 154 SHOULDER AND OTHER SMALL JOINT RECONSTRUCTION AND REPLACEMENT TABLE 32 SHOULDER AND OTHER SMALL JOINT RECONSTRUCTION AND REPLACEMENT, LIST OF KEY PIPELINE DEVICES Simpliciti Shoulder 155 aspire Total Shoulder Arthroplasty System 155 Luna Stemless Humeral Prosthesis 155 AFT Proximal Humerus Fracture Prosthesis

12 Reverse Shoulder Implant 156 Reverse Shoulder Implant 156 Pyrohemi Implant 156 Akilos Total Ankle System 156 CHAPTER 14 REGULATORY STRUCTURE 158 REGULATORY STRUCTURE 158 U.S. 158 EUROPEAN UNION 160 TABLE 33 DIFFERENCES IN REGULATORY APPROVALS: U.S. VS EUROPE 162 JAPAN 162 OTHER ASIA 163 China 163 Hong Kong 164 Taiwan 164 India 164 CHAPTER 15 PRICING AND REIMBURSEMENT 166 REIMBURSEMENT STRUCTURE 166 U.S. 166 ICD-9-CM 167 TABLE 34 HIP AND KNEE REPLACEMENT, INTERNATIONAL CLASSIFICATION OF DISEASES, NINTH REVISION (ICD-9) CODES ICD Insurance and Reimbursement 169 TABLE 35 CENTERS FOR MEDICARE & MEDICAID SERVICES, MEDPAR INPATIENT HOSPITAL NATIONAL DATA FOR FISCAL YEAR 2011 ($) EUROPE 171 JAPAN 172 OTHER ASIA 172 MEDICAL DEVICE PRICING TRENDS CHAPTER 16 CONCLUSIONS: OUTLOOK FOR JOINT RECONSTRUCTION AND REPLACEMENT MAJOR DEVELOPMENTS TO INFLUENCE JOINT RECONSTRUCTION AND REPLACEMENT MARKET TECHNOLOGICAL DEVELOPMENTS 175 Adaptation of Minimally Invasive Techniques to New Types of Surgical Procedures Future Materials and Implants Technologies 175 DEMOGRAPHIC AND ECONOMIC TRENDS 176 Increasing Aging Population 176 TABLE 36 ESTIMATED WORLD POPULATION AND ANNUAL GROWTH BY SELECTED AGE GROUP AND SELECTED YEARS, THROUGH 2030 ( FIGURE 25 ESTIMATED WORLD POPULATION BY SELECTED AGE GROUP AND SELECTED YEARS, ( TABLE 37 WORLD POPULATION BY SELECTED GEOGRAPHIC REGIONS, THROUGH 2020 ( FIGURE 26 WORLD POPULATION BY SELECTED COUNTRIES, (

13 U.S. Demographics 179 TABLE 38 U.S. POPULATION ESTIMATES AND PROJECTIONS BY AGE GROUP, THROUGH 2030 ( FIGURE 27 U.S. POPULATION ESTIMATES AND PROJECTIONS BY AGE GROUP, ( FIGURE 28 DISTRIBUTION OF TYPES OF JOINT SURGERIES PERFORMED GLOBALLY AMONG THE TOTAL GENERAL POPULATION, AGED 65 YEARS AND ABOVE, 2013 (%) U.S: Gender, Age and Life Expectancy 181 TABLE 39 ESTIMATES OF ANTICIPATED U.S. LIFE EXPECTANCY AT BIRTH AND PROJECTIONS BY GENDER, (YEARS) FIGURE 29 ESTIMATES OF ANTICIPATED U.S. LIFE EXPECTANCY AT BIRTH AND PROJECTIONS BY GENDER, (YEARS) European Demographics 182 TABLE 40 EUROPEAN POPULATION ESTIMATES AND PROJECTIONS BY AGE GROUP, THROUGH 2030 ( FIGURE 30 EUROPEAN POPULATION ESTIMATES AND PROJECTIONS BY AGE GROUP, Japanese Demographics 183 TABLE 41 JAPANESE POPULATION ESTIMATES AND PROJECTIONS BY AGE GROUP, THROUGH 2030 ( FIGURE 31 JAPANESE POPULATION ESTIMATES AND PROJECTIONS BY AGE GROUP, ( Income Growth in Developing Markets 184 TABLE 42 PROJECTED TRENDS IN PER CAPITA REAL GDP GROWTH BY REGION, (ANNUAL AVERAGE PERCENTAGE CHANGE) CHANGING STRUCTURE OF THE HEALTHCARE INDUSTRY 185 Hospital Consolidation 185 Medical Tourism 185 Health Insurance Developments 186 FUTURE OUTLOOK 186 CONSISTENT GROWTH TO CONTINUE IN A MATURE MARKET 186 MARKET GROWTH WILL BE DRIVEN BY PROCEDURE VOLUME RATHER THAN THE PRICE OF IMPLANTS YOUNGER AND BROADENING PATIENT BASE TO DRIVE SHORT- AND MEDIUM-TERM GROWTH "BABY BOOM" POPULATION SET TO DRIVE LONG-TERM GROWTH 187 REVISION AND PARTIAL REPLACEMENT TO DRIVE MARKET SEGMENT GROWTH MINIMALLY INVASIVE SURGERY 188 DEVELOPMENT BIOLOGICAL IMPLANTS CHAPTER 17 APPENDIX A: ACRONYMS 190 CHAPTER 18 APPENDIX B: VENDOR PROFILES 194 AESCULAP INC. 194 ALLOSOURCE 194 ALPHATEC SPINE INC. 195 ANIKA THERAPEUTICS INC. 195 ARISTOTECH IMPLANT TECHNOLOGIES GMBH 196 ARTHREX INC. 196

14 ARTHROCARE CORP. 197 ARTHROSURFACE 197 ASCENSION ORTHOPEDIC 197 B. BRAUN MELSUNGEN AG 198 BIOMET INC. 199 BIOMIMEDICA INC. 199 BONOVO ORTHOPEDICS INC. 200 BRAINLAB AG 200 CERAVER 201 CONFORMIS INC. 201 CONSENSUS ORTHOPEDICS 201 CORENTEC CO. LTD. 202 CORIN GROUP 202 DEPUY (SUBSIDIARY OF JOHNSON & JOHNSON) 203 DJO INC. 203 ENCORE MEDICAL LP 204 ENZTEC LTD. 204 EXACTECH INC. 205 FH ORTHOPAEDICS 205 GLOBUS MEDICAL INC. 206 HOWMEDICA OSTEONICS 206 ICONACY ORTHOPEDIC IMPLANTS LLC 206 IMPLANTS INTERNATIONAL 207 INGEN ORTHOPEDICS 207 INTEGRA LIFE SCIENCES CORP. 207 JAPAN MEDICAL DYNAMIC MARKETING INC. 208 JRI ORTHOPEDICS LTD. 208 KINAMED INC. 208 LAFITT 209 LIMACORPORATE SPA 209 MAKO SURGICAL CORP. 209 MEDACTA INTERNATIONAL SA 210 MEDARTIS AG 210 MEDIN 211 MEDSHAPE INC. 211 MERETE MEDICAL GMBH 211 METRIMED 212 MICROPORT SCIENTIFIC CORP. 212 MOXIMED INC. 212 NOVOSOURCE INC. 213 NUVASIVE INC. 213 OMNI LIFE SCIENCE INC. 214 ORTHEON MEDICAL 214 ORTHO DEVELOPMENT CORP. 214 ORTHO SOLUTIONS 215 ORTHODYNAMICS PTY LTD. 215 ORTHOFIX INTERNATIONAL 215

15 ORTHOPAEDIC SYNERGY INC. 216 ORTHOPEDIC INNOVATION LTD. 216 ORTHOVITA INC. 217 OSTEOMED 217 PERMEDICA SPA 217 PIPELINE BIOMEDICAL 218 PIVOT MEDICAL 218 Q-MED 219 RENOVIS SURGICAL TECHNOLOGIES 219 RTI SURGICAL 219 SEIKAGAKU CORP. 220 SERF DEDIENNE SANTE 220 SHOULDER OPTIONS INC. 220 SIGNATURE ORTHOPAEDICS PTY LTD. 221 SKELETAL DYNAMICS 221 SMALL BONE INNOVATIONS 221 SMITH & NEPHEW 222 STANMORE IMPLANTS 223 STELKAST 223 STRYKER 224 SYNOVIS 225 SYNTHES INC. 225 TENDON TECHNOLOGY LTD. 226 THE ORTHOPAEDIC IMPLANT CO. 226 TORNIER INC. 226 TOTAL JOINT ORTHOPEDICS INC. 226 U&I CORP. 227 WALDEMAR LINK 227 WRIGHT MEDICAL TECHNOLOGY INC. 227 ZIMMER HOLDINGS 228 CHAPTER 19 APPENDIX C: INDUSTRY AND PROFESSIONAL ORGANIZATIONS 231 AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS 231 AMERICAN ASSOCIATION OF HIP AND KNEE SURGEONS 231 AMERICAN JOINT REPLACEMENT REGISTRY 231 AMERICAN ORTHOPAEDIC ASSOCIATION 232 CENTERS FOR MEDICARE & MEDICAID SERVICES 232 CHINA'S MINISTRY OF SCIENCE AND TECHNOLOGY 232 DEPARTMENT OF HEALTH AND HUMAN SERVICES 233 EUROPEAN DATABANK ON MEDICAL DEVICES (EUDAMED) 233 FOOD AND DRUG ADMINISTRATION 233 HEALTHCARE COST AND UTILIZATION PROJECT 234 INTERNATIONAL FEDERATION OF PHARMACEUTICAL MANUFACTURERS AND ASSOCIATIONS INTERNATIONAL OSTEOPOROSIS FOUNDATION 234 NATIONAL CENTER FOR BIOTECHNOLOGY INFORMATION 235 NATIONAL INSTITUTE ON AGING (NIA) 235 NATIONAL JOINT REGISTRY

16 NATIONAL OSTEOPOROSIS FOUNDATION 236 NATIONAL RHEUMATOID ARTHRITIS SOCIETY 236 ORGANIZATION FOR ECONOMIC CO-OPERATION AND DEVELOPMENT 236 PHARMACEUTICAL AND MEDICAL DEVICE AGENCY (PMDA) 237

17 LIST OF TABLES TABLE HEADING SUMMARY TABLE A GLOBAL MARKET FOR JOINT RECONSTRUCTION AND REPLACEMENT, THROUGH 2018 ($ SUMMARY TABLE B GLOBAL JOINT RECONSTRUCTION AND REPLACEMENT MARKET BY SEGMENT TYPE, THROUGH 2018 ($ TABLE 1 GLOBAL PREVALENCE OF OSTEOARTHRITIS (SYMPTOMATIC) BY GEOGRAPHIC REGION, THROUGH 2018 ( TABLE 2 GLOBAL PREVALENCE OF RHEUMATOID ARTHRITIS (SYMPTOMATIC) BY REGION, THROUGH 2018 ( TABLE 3 POST-TRAUMATIC ARTHRITIS AND INCIDENCE OF KNEE FRACTURES BY GEOGRAPHIC REGION, THROUGH 2018 (ACTUAL) ( TABLE 4 GLOBAL PREVALENCE OF OSTEOPOROSIS BY REGION, THROUGH 2018 ( TABLE 5 GLOBAL INCIDENCE OF HIP FRACTURES BY REGION, THROUGH 2018 TABLE 6 GLOBAL HIP REPLACEMENT PROCEDURES VS TOTAL JOINT RECONSTRUCTION PROCEDURES, THROUGH 2018 TABLE 7 GLOBAL HIP REPLACEMENT PROCEDURES BY REGION, THROUGH 2018 TABLE 8 GLOBAL KNEE REPLACEMENT PROCEDURES VS TOTAL JOINT RECONSTRUCTION PROCEDURES, THROUGH 2018 TABLE 9 GLOBAL KNEE REPLACEMENT PROCEDURES BY REGION, THROUGH 2018 TABLE 10 GLOBAL SHOULDER REPLACEMENT PROCEDURES VS TOTAL JOINT RECONSTRUCTION PROCEDURES, THROUGH 2018 TABLE 11 GLOBAL SHOULDER REPLACEMENT PROCEDURES BY REGION, THROUGH 2018 TABLE 12 GLOBAL SMALL JOINT REPLACEMENT PROCEDURES VS TOTAL JOINT RECONSTRUCTION PROCEDURES, THROUGH 2018 TABLE 13 GLOBAL SMALL JOINT REPLACEMENT PROCEDURES BY REGION, THROUGH 2018 TABLE 14 GLOBAL JOINT RECONSTRUCTION AND REPLACEMENT MARKET BY REGION, THROUGH 2018 ($ TABLE 15 GLOBAL JOINT RECONSTRUCTION AND REPLACEMENT MARKET BY SEGMENT, THROUGH 2018 ($ TABLE 16 GLOBAL HIP REPLACEMENT MARKET BY REGION, THROUGH 2018 ($ TABLE 17 GLOBAL HIP REPLACEMENT MARKET BY PROCEDURE, THROUGH 2018 ($ TABLE 18 GLOBAL KNEE REPLACEMENT MARKET BY REGION, THROUGH 2018 ($ TABLE 19 GLOBAL KNEE REPLACEMENT MARKET BY PROCEDURE, THROUGH 2018 ($ TABLE 20 GLOBAL SHOULDER REPLACEMENT MARKET BY REGION, THROUGH 2018 ($ TABLE 21 GLOBAL SMALL JOINT REPLACEMENT MARKET BY REGION, THROUGH 2018 ($ TABLE 22 GLOBAL BONE CEMENT MARKET BY REGION, THROUGH 2018 ($ 111 TABLE 23 GLOBAL JOINT RECONSTRUCTION AND REPLACEMENT MARKET SHARES, 2013 ($ MILLIONS/%) TABLE 24 ORTHOPEDIC COMPANIES JOINT RECONSTRUCTION PRODUCT SEGMENT COVERAGE MATRIX

18 TABLE HEADING TABLE 25 JOINT RECONSTRUCTION AND REPLACEMENT MARKET, KEY MERGERS/ACQUISITIONS TABLE 26 HIP RECONSTRUCTION AND REPLACEMENT: LIST OF KEY DEVICE APPROVALS BY THE FDA, TABLE 27 KNEE RECONSTRUCTION AND REPLACEMENT, LIST OF KEY DEVICE APPROVALS BY THE FDA, TABLE 28 SHOULDER RECONSTRUCTION AND REPLACEMENT, LIST OF KEY DEVICE APPROVALS BY FDA, TABLE 29 SMALL JOINT RECONSTRUCTION AND REPLACEMENT, LIST OF KEY DEVICE APPROVALS BY THE FDA, TABLE 30 HIP RECONSTRUCTION AND REPLACEMENT, LIST OF KEY PIPELINE DEVICES TABLE 31 KNEE RECONSTRUCTION AND REPLACEMENT, LIST OF KEY PIPELINE DEVICES TABLE 32 SHOULDER AND OTHER SMALL JOINT RECONSTRUCTION AND REPLACEMENT, LIST OF KEY PIPELINE DEVICES TABLE 33 DIFFERENCES IN REGULATORY APPROVALS: U.S. VS EUROPE 162 TABLE 34 HIP AND KNEE REPLACEMENT, INTERNATIONAL CLASSIFICATION OF DISEASES, NINTH REVISION (ICD-9) CODES TABLE 35 CENTERS FOR MEDICARE & MEDICAID SERVICES, MEDPAR INPATIENT HOSPITAL NATIONAL DATA FOR FISCAL YEAR 2011 ($) TABLE 36 ESTIMATED WORLD POPULATION AND ANNUAL GROWTH BY SELECTED AGE GROUP AND SELECTED YEARS, THROUGH 2030 ( TABLE 37 WORLD POPULATION BY SELECTED GEOGRAPHIC REGIONS, THROUGH 2020 ( TABLE 38 U.S. POPULATION ESTIMATES AND PROJECTIONS BY AGE GROUP, THROUGH 2030 ( TABLE 39 ESTIMATES OF ANTICIPATED U.S. LIFE EXPECTANCY AT BIRTH AND PROJECTIONS BY GENDER, (YEARS) TABLE 40 EUROPEAN POPULATION ESTIMATES AND PROJECTIONS BY AGE GROUP, THROUGH 2030 ( TABLE 41 JAPANESE POPULATION ESTIMATES AND PROJECTIONS BY AGE GROUP, THROUGH 2030 ( TABLE 42 PROJECTED TRENDS IN PER CAPITA REAL GDP GROWTH BY REGION, (ANNUAL AVERAGE PERCENTAGE CHANGE)

19 LIST OF FIGURES FIGURE TITLE SUMMARY FIGURE A GLOBAL MARKET FOR JOINT RECONSTRUCTION AND REPLACEMENT, ($ SUMMARY FIGURE B GLOBAL JOINT RECONSTRUCTION AND REPLACEMENT MARKET BY SEGMENT TYPE, ($ FIGURE 1 GLOBAL PREVALENCE OF OSTEOARTHRITIS (SYMPTOMATIC) BY GEOGRAPHIC REGION, ($ FIGURE 2 GLOBAL PREVALENCE OF RHEUMATOID ARTHRITIS (SYMPTOMATIC) BY REGION, ($ FIGURE 3 POST-TRAUMATIC ARTHRITIS AND GLOBAL INCIDENCE OF KNEE FRACTURES BY REGION, ($ FIGURE 4 GLOBAL PREVALENCE OF OSTEOPOROSIS BY REGION, ($ FIGURE 5 GLOBAL INCIDENCE OF HIP FRACTURES BY REGION, FIGURE 6 GLOBAL HIP REPLACEMENT PROCEDURES VS TOTAL JOINT RECONSTRUCTION PROCEDURES, FIGURE 7 GLOBAL HIP REPLACEMENT PROCEDURES BY REGION, FIGURE 8 GLOBAL KNEE REPLACEMENT PROCEDURES VS TOTAL JOINT RECONSTRUCTION PROCEDURES, FIGURE 9 GLOBAL KNEE REPLACEMENT PROCEDURES BY REGION, FIGURE 10 GLOBAL SHOULDER REPLACEMENT PROCEDURES VS TOTAL JOINT RECONSTRUCTION PROCEDURES, FIGURE 11 GLOBAL SHOULDER REPLACEMENT PROCEDURES BY REGION, FIGURE 12 GLOBAL SMALL JOINT REPLACEMENT PROCEDURES VS TOTAL JOINT RECONSTRUCTION PROCEDURES, FIGURE 13 GLOBAL SMALL JOINT REPLACEMENT PROCEDURES BY REGION, FIGURE 14 GLOBAL JOINT RECONSTRUCTION AND REPLACEMENT MARKET BY REGION, ($ BILLIONS) FIGURE 15 GLOBAL JOINT RECONSTRUCTION AND REPLACEMENT MARKET BY SEGMENT, ($ FIGURE 16 JOINT RECONSTRUCTION AND REPLACEMENT MARKET BY SEGMENT TYPE, 2013 (% OF TOTAL MARKET) FIGURE 17 GLOBAL HIP REPLACEMENT MARKET BY REGION, ($ 104 FIGURE 18 GLOBAL HIP REPLACEMENT MARKET BY PROCEDURE, ($ FIGURE 19 GLOBAL KNEE REPLACEMENT MARKET BY REGION, ($ FIGURE 20 GLOBAL KNEE REPLACEMENT MARKET BY PROCEDURE, ($ FIGURE 21 GLOBAL SHOULDER REPLACEMENT MARKET BY REGION, ($ FIGURE 22 GLOBAL SMALL JOINT REPLACEMENT MARKET BY REGION, ($ FIGURE 23 GLOBAL BONE CEMENT SMALL JOINT REPLACEMENT MARKET BY REGION, ($ FIGURE 24 GLOBAL JOINT RECONSTRUCTION AND REPLACEMENT MARKET LEADERS, 2012 (% OF TOTAL MARKET)

20 FIGURE TITLE FIGURE 25 ESTIMATED WORLD POPULATION BY SELECTED AGE GROUP AND SELECTED YEARS, ( FIGURE 26 WORLD POPULATION BY SELECTED COUNTRIES, ( 178 FIGURE 27 U.S. POPULATION ESTIMATES AND PROJECTIONS BY AGE GROUP, ( FIGURE 28 DISTRIBUTION OF TYPES OF JOINT SURGERIES PERFORMED GLOBALLY AMONG THE TOTAL GENERAL POPULATION, AGED 65 YEARS AND ABOVE, 2013 (%) FIGURE 29 ESTIMATES OF ANTICIPATED U.S. LIFE EXPECTANCY AT BIRTH AND PROJECTIONS BY GENDER, (YEARS) FIGURE 30 EUROPEAN POPULATION ESTIMATES AND PROJECTIONS BY AGE GROUP, FIGURE 31 JAPANESE POPULATION ESTIMATES AND PROJECTIONS BY AGE GROUP, (