U.S. Opportunities in Osteoporosis Management

Companies Covered

ArthroCare Corporation

Biomet, Inc/Interpore Spine, Ltd

Eli Lilly & Company

GE Healthcare

Hologic, Inc

Kyphon, Inc

Ligand Pharmaceuticals, Inc

Merck & Company, Inc

Novartis AG

NPS Pharmaceuticals, Inc

OSI Systems, Inc

Ostex International, Inc

Quidel Corporation

Servier Group

Spineology, Inc

Stryker Corporation

Synthes, Inc

Unigene Laboratories, Inc

Wright Medical Group, Inc

Wyeth

Table of Contents

EXECUTIVE SUMMARY

Overview of Osteoporosis

Diagnosis

Drug Therapy

Fracture Management

Companies

Summary Exhibit 1: U.S. Market for Osteoporosis Products, 2002-2008

Summary Exhibit 2: Patient Forecast for Osteoporosis and Osteopenia Prevalence, 2002-2008

Summary Exhibit 3: U.S. Market for Osteoporosis Diagnostic Products, 2002-2008

Summary Exhibit 4: U.S. Market for Osteoporosis Drugs, 2002-2008

Summary Exhibit 5: U.S. Market for Osteoporosis Fracture Management, 2002-2008

1.0 OVERVIEW OF OSTEOPOROSIS

1.1 Bone Structure

1.2 Bone Metabolism & Remodeling

1.3 Definition of Osteoporosis

1.4 Pathophysiology and Etiology of Osteoporosis

1.5 Risk Factors

1.6 Prevalence

1.7 Clinical Manifestations, Morbidity and Economic Impact

1.8 Diagnosis and Screening

1.9 Treatment

1.10 Male Osteoporosis

Exhibit 1-1: Distribution of Trabecular Bone in the Body

Exhibit 1-2: Structural Elements of Bone & Their Function

Exhibit 1-3: Effect of Select Growth Factors on Bone Formation and Resorption

Exhibit 1-4: Illustration of the Bone Remodeling Process

Exhibit 1-5: Types of Osteoporosis

Exhibit 1-6: Relationship Between Bone Mass and Fracture Risk

Exhibit 1-7: Stages of Bone Mass in The Female Life Cycle

Exhibit 1-8: Risk Factors for Osteoporosis

Exhibit 1-9: Prevalence and Relative Risks of Selected Risk Factors

Exhibit 1-10: Prevalence Data in Females from NHANES III

Exhibit 1-11: Osteopenia and Osteporosis Prevalence in Males from NHANES III

Exhibit 1-12: Osteoporosis Prevalence from the WHO Study

Exhibit 1-13: Patient Forecast for Osteoporosis and Osteopenia Prevalence, 2002-2008.1-21

Exhibit 1-14: Osteoporosis Attribution Probabilities by Fracture Type, Gender and Age in a White Population

Exhibit 1-15: Health Resources Utilized by Osteoporotic Fractures in the U.S., 1995

Exhibit 1-16: Medical Expenditures Attributable to Osteoporotic Fractures in the U.S., 1995

Exhibit 1-17: Osteoporotic Fracture Cost-of-Illness Studies in the U.S., 1995

Exhibit 1-18: Frequency Physicians Recommending Bone Density Testing to Postmenopausal Patients, 2001

Exhibit 1-19: Overview of Osteoporosis Treatments

2.0 DIAGNOSIS

2.1 Bone Densitometry

2.1.1 Indications

2.1.2 Bone Densitometry Products

2.1.2.1 Central Bone Densitometry Systems

2.1.2.1.1 Hologic

2.1.2.1.2 GE Healthcare

2.1.2.1.3 CooperSurgical

2.1.2.2 Peripheral Bone Densitometry Systems

2.1.2.3 Software-Based Systems

2.1.2.3.1 Central QCT

2.1.2.3.2 X-Ray Systems

2.1.2.4 Reimbursement

2.1.2.5 Procedure Forecast

2.1.2.6 Market Analysis

2.1.2.6.1 Central Systems

2.1.2.6.2 Peripheral Systems

2.1.2.6.3 Supplier Shares

2.1.2.6.4 Software-Based Systems

2.2 Biochemical Markers

2.2.1 Products & Suppliers

2.2.2 Reimbursement

2.2.3 Market Analysis

2.3 Genetic Testing

2.4 Bone-Fragility

2.4.1 Bone Connectivity

2.4.1.1 Histomorphometry

2.4.1.2 Microcomputed Tomography (CT)

2.4.2 Bone Geometry

Exhibit 2-1: WHO-Guided Diagnostic Standards for Osteoporosis

Exhibit 2-2: Comparison of Major Diagnostic Approaches for Osteoporosis

Exhibit 2-3: Imaging Techniques for Osteoporosis Diagnosis, 2004

Exhibit 2-4: Examples of DEXA Systems

Exhibit 2-5: Hologic's Sahara Quantitative Ultrasound System

Exhibit 2-6: Selected Central DEXA Systems, 2004

Exhibit 2-7: Hologic's QDR Systems

Exhibit 2-8: GE Healthcare's Densitometry Products

Exhibit 2-9: CooperSurgical's Densitometry Systems

Exhibit 2-10: Comparison of Selected Peripheral Bone Densitometer Systems, 2004

Exhibit 2-11: Selected Peripheral Bone Densitometer Systems

Exhibit 2-12: CPT Codes for Bone Densitometry, 2004

Exhibit 2-13: U.S. Central DEXA Bone Densitometry Tests, Procedure Forecast, 2002-2008

Exhibit 2-14: U.S. Bone Densitometry Market Overview, 2002-2008

Exhibit 2-15: U.S. Market for Central Bone Densitometry Systems, 2002-2008

Exhibit 2-16: U.S. Market for Peripheral Bone Densitometry Systems, 2002-2008

Exhibit 2-17: U.S. Bone Densitometry Market, Supplier Shares, 2003

Exhibit 2-18: Selected Biochemical Markers for Bone Remodeling, 2004

Exhibit 2-19: Selected Biochemical Marker Tests for Bone Remodeling, 2004

Exhibit 2-20: CPT Codes for Bone Turnover Biochemical Marker Assays, 2004

Exhibit 2-21: Biochemical Markers for Bone Turnover, Market Forecast, 2002-2008

Exhibit 2-22: Bone Marker Supplier Shares, 2003

Exhibit 2-23: Comparison of Bone Connectivity in Normal and Osteoporotic Bone

Exhibit 2-24: Example of Microcomputed Tomography Images

Exhibit 2-25: Selected Manufacturers of In Vivo Micro-CT Systems, 2004

Exhibit 2-26: Definition of Hip Geometrical Parameters

3.0 DRUG THERAPY

3.1 Pharmacologic Approaches and Products

3.1.1 Antiresorptive Agents

3.1.1.1 Hormone Replacement Therapy

3.1.1.1.1 Treatment

3.1.1.1.2 Side Effects

3.1.1.1.3 Administration

3.1.1.1.4 Products

3.1.1.1.5 WHI Impact

3.1.1.2 Selective Estrogen Receptor Modulators (SERMs)

3.1.1.2.1 Raloxifene

3.1.1.2.2 Lasofoxifene

3.1.1.2.3 Bazedoxifene

3.1.1.2.4 Arzoxifene

3.1.1.2.5 Ospemifene/Fispemifene

3.1.1.2.6 MDL 103,323

3.1.1.2.7 SERM 3471

3.1.1.3 Selective Tissue Estrogenic Activity Regulator

3.1.1.4 Calcitonin

3.1.1.4.1 Miacalcin

3.1.1.4.2 Fortical

3.1.1.4.3 Nastech’s Calcitonin Nasal Spray

3.1.1.4.4 New Drug Development

3.1.1.5 Bisphosphonates

3.1.1.5.1 Alendronate

3.1.1.5.2 Risedronate

3.1.1.5.3 Ibandronate

3.1.1.5.4 Off-Label Drugs

3.1.1.5.5 New Drug Development

3.1.1.6 Osteoprotegerin/AMG 162

3.1.1.7 Non-antimicrobial Tetracycline Derivatives

3.1.1.8 Cathepsin K Inhibitors

3.1.2 Bone Forming Drugs

3.1.2.1 Sodium Fluoride

3.1.2.2 Recombinant Human Parathyroid Hormone

3.1.2.2.1 Teriparatide (Forteo)

3.1.2.2.2 PREOS

3.1.2.2.3 New Drug Development

3.1.2.3 Selective Androgen Receptor Modulators

3.1.2.3.1 LGD2226

3.1.2.3.2 Ostarine

3.1.2.4 Statin Drugs

3.1.2.5 Calcilytics

3.1.3 Other Emerging Drug Treatments

3.1.3.1 Peptide Growth Factors

3.1.3.2 Strontium Renelate (Protelos)

3.1.3.3 Novel Drug Discovery Platform (Velcura)

3.1.4 Market Analysis

3.1.4.1 By Therapeutic Approach

3.1.4.1.1 HRT

3.1.4.1.2 SERMs

3.1.4.1.3 Bisphosphonates

3.1.4.1.4 Calcitonin

3.1.4.1.5 PTH

3.1.4.2 By Supplier

3.1.4.3 Emerging Therapies

3.1.4.4 Potential Impacting Factors

3.2 Gene Therapy

3.2.1 The Search for Osteoporotic Genes

3.2.1.1 Celltech/Amgen

3.2.1.2 deCODE Genetics/Roche

3.2.1.3 Oscient Pharmaceuticals

3.2.2 Emerging Gene Therapies for Osteoporosis

Exhibit 3-1: Major Pharmacologic Approaches for Managing Osteoporosis

Exhibit 3-2: Current Available Drug Therapy Options for Osteoporosis, 2004

Exhibit 3-3: Selected FDA-Approved Osteoporosis Drugs, 2004

Exhibit 3-4: Emerging Drug Therapy Options for Osteoporosis, 2004

Exhibit 3-5: Selected Pipeline Osteoporosis Drugs, 2004

Exhibit 3-6: Selected Hormone Replacement Therapy Products, 2004

Exhibit 3-7: Current and Emerging SERMs Targeting Osteoporosis, 2004

Exhibit 3-8: Selected Clinical Trials of Current and Emerging SERMs, 2004

Exhibit 3-9: Selected Current and Emerging Bisphosphonates, 2004

Exhibit 3-10: Selected Clinical Trials of Current and Emerging Bisphosphonates, 2004

Exhibit 3-11: Selected Studies of Growth Factors and Their Relationship with Osteoporosis

Exhibit 3-12: U.S. Market for Osteoporosis Drugs, 2002-2008

Exhibit 3-13: U.S. Market for Osteoporosis Drugs, Supplier Shares, 2003

Exhibit 3-14: Estimated Sales Potential for Emerging Therapeutic Drugs

4.0 FRACTURE MANAGEMENT

4.1 Hip Fractures

4.1.1 Internal Fixation

4.1.2 Joint Replacement (Arthroplasty)

4.1.3 Hip Resurfacing

4.1.4 Choice of Treatment

4.1.5 Procedure and Market Forecast

4.2 Vertebral Compression Fractures

4.2.1 Vertebroplasty

4.2.1.1 Technique

4.2.1.2 Setting and Specialties

4.2.1.3 Indications/Contraindications

4.2.1.4 Clinical Experience

4.2.1.5 Product Requirements

4.2.1.6 Procedure Cost and Reimbursement

4.2.2 Kyphoplasty

4.2.2.1 Technique

4.2.2.2 Setting and Specialties

4.2.2.3 Product Requirements

4.2.2.4 Procedure Cost

4.2.2.5 Patient Profile

4.2.2.6 Potential Advantages and Limitations

4.2.2.7 Contraindications

4.2.2.8 Clinical Experience

4.2.2.9 Complications

4.2.2.10 Regulatory Issues

4.2.2.11 Reimbursement

4.2.3 Lordoplasty

4.2.4 Products and Suppliers

4.2.4.1 Bone Cements

4.2.4.1.1 PMMA

4.2.4.1.2 Calcium Phosphate Cements

4.2.4.1.3 Composite Cements (CORTOSS)

4.2.4.1.4 Calcified Triglycerides (Kryptonite)

4.2.4.1.5 Other Biomaterials

4.2.4.1.6 Regulatory Issues

4.2.4.2 Cement Delivery Systems

4.2.4.3 Augmentation Devices

4.2.4.3.1 Kyphon

4.2.4.3.2 ArthroCare Spine

4.2.4.3.3 Disc-O-Tech Medical Technologies

4.2.4.3.4 Spineology

4.2.4.3.5 Spine Wave

4.2.4.3.6 Other Technologies

4.2.4.4 Robotic Systems

4.2.5 Market Analysis

4.2.5.1 Procedure Forecast

4.2.5.2 Market Forecast

4.2.5.2.1 Augmentation Devices

4.2.5.2.2 Cement Delivery

4.2.5.2.3 Bone Cements

4.2.5.3 Supplier Shares

4.3 Other Fractures

Exhibit 4-1: Selected Treatment Approaches for Osteoporotic Fractures

Exhibit 4-2: Anatomy of the Hip Joint

Exhibit 4-3: Types of Fractures of the Proximal Femur (Hip Fractures)

Exhibit 4-4: Garden Classification of Femoral Neck Fractures

Exhibit 4-5: General Classification of Hip (Proximal Femur) Fractures

Exhibit 4-6: Risk Factors for Hip Fractures and Their Relative Risks

Exhibit 4-7: Annual Risk of Hip Fracture by Number of Risk Factors and Age-Specific Calcaneal Bone Density

Exhibit 4-8: Comparison of Surgical Options for Hip Fracture Management

Exhibit 4-9: Selected Products and Suppliers of Internal Fixation Devices for Hip Fracture

Exhibit 4-10: Selected Internal Fixation Products for Hip Fracture

Exhibit 4-11: Hip Arthroplasty Approaches and Related Product Types

Exhibit 4-12: Selected Hip Reconstruction Products and Suppliers, 2004

Exhibit 4-13: Selected Hip Replacement Products

Exhibit 4-14: Prospective Clinical Studies Comparing Hemi-Arthroplasty and Internal Fixation for Displaced Femoral Fractures

Exhibit 4-15: Cost-Effectiveness of Interventions for Displaced Femoral Neck Fractures in the Elderly

Exhibit 4-16: Surgical Management of Hip Fractures, Procedure Forecast by Fracture Type and Treatment Modality, 2002-2008

Exhibit 4-17: Hip Fixation Products, Supplier Shares, 2003

Exhibit 4-18: Market Forecast for Hip Fracture Products by Segment, 2002-2008

Exhibit 4-19: Structure of the Vertebrae

Exhibit 4-20: The Spine

Exhibit 4-21: Comparison of Vertebral Fracture Management Approaches

Exhibit 4-22: Approaches to the Spine for Vertebroplasty

Exhibit 4-23: Vertebral Compression Fracture, Pre- and Post-Treatment

Exhibit 4-24: Indications and Contraindications for Vertebroplasty

Exhibit 4-25: Selected Pain Outcomes Following Vertebroplasty

Exhibit 4-26: Overview of Recent Vertebroplasty Clinical Studies in Osteoporotic Patients

Exhibit 4-27: Suggested Thresholds for Selected Vertebroplasty Complications

Exhibit 4-28: Selected Reimbursement Codes for Vertebroplasty

Exhibit 4-29: ICD-9 Codes that Support Medical Necessity for Vertebroplasty

Exhibit 4-30: Kyphoplasty Procedure

Exhibit 4-31: Comparison of Cement Leakage with Kyphoplasty and Vertebroplasty

Exhibit 4-32: Selected Pain Outcomes Following Kyphoplasty

Exhibit 4-33: Overview of Selected Recent Kyphoplasty Clinical Studies

Exhibit 4-34: Comparison of Bone Cement Types

Exhibit 4-35: Selected Bone Cements for Percutaneous Vertebral Augmentation, 2004

Exhibit 4-36: Selected Cement Delivery Systems for Percutaneous Vertebral Augmentation, 2004

Exhibit 4-37: Selected Vertebral Augmentation Devices, 2004

Exhibit 4-38: Kyphon's KyphX System

Exhibit 4-39: Disc-O-Tech's Kyphoplasty Products

Exhibit 4-40: Spineology's OptiMesh System

Exhibit 4-41: Spine Wave's Stackable Wafer Vertebral Fracture Reduction System

Exhibit 4-42: Robotic Systems for Percutaneous Vertebral Augmentation

Exhibit 4-43: Mazor Surgical Technologies' SpineAssist

Exhibit 4-44: Percutaneous Vertebral Augmentation, Procedure Forecast, 2002-2008

Exhibit 4-45: Percutaneous Vertebral Augmentation, Market Forecast, 2002-2008

Exhibit 4-46: Percutaneous Vertebral Augmentation, Supplier Shares, 2003

5.0 COMPANY PROFILES

5.1 ArthroCare Corporation

5.2 Biomet, Inc/Interpore Spine, Ltd

5.3 GE Healthcare

5.4 Hologic, Inc

5.5 Kyphon, Inc

5.6 Ligand Pharmaceuticals, Inc

5.7 Eli Lilly & Company

5.8 Merck & Company, Inc

5.9 Novartis AG

5.10 NPS Pharmaceuticals, Inc

5.11 OSI Systems, Inc

5.12 Ostex International, Inc

5.13 Quidel Corporation

5.14 Servier Group

5.15 Spineology, Inc

5.16 Stryker Corporation

5.17 Synthes, Inc

5.18 Unigene Laboratories, Inc

5.19 Wright Medical Group, Inc

5.20 Wyeth

APPENDIX: COMPANY LIST