Contents:

Chapter 1 EXECUTIVE SUMMARY 3 Scope of the analysis 3 Insight into the osteoporosis market 5 Osteoporosis is severely underdiagnosed and undertreated. Our primary research suggests that just 10% of the prevalent population across the seven major markets is diagnosed with osteoporotic bone loss and only just over half of those receive drug treatment. Growth in this market depends on driving patient identification and diagnosis, yet this is an area fraught with unmet needs including disease awareness and access to and utilization diagnostic tools. 6 Datamonitor primary research has identified strong variances in class and brand prescribing preferences among physicians, according to both disease severity and geography. Combination therapy is prescribed in the US, Japan, the UK, France and Spain, though not in Italy and Germany. The practice varies significantly in the extent of physician participation and use in the patient population 8 Trends in monotherapy 8 Combination therapy in osteoporosis 9 Three trends in osteoporosis R&D have the potential to radically change treatment and expand the market: SERMs in additional indications; PTH/anabolic drugs in fracture patients and novel bisphosphonates in flexible dosing and delivery formulations. However, our primary research suggests that prescribers will vary widely in how receptive they are to these innovations. 10 SERMs – gaining on HRT and growing its patient population? 10 PTH – a much needed weapon against osteoporosis fractures, but how best to use it? 12 Long-interval bisphosphonates – ibandronate and zoledronate are the likely lads but have much to prove to beat the gold-standard 13 Key metrics 14 Chapter 2 INTRODUCTION AND SCOPE 27 Coverage of the Stakeholder Insight survey 27 Supporting data sets 29 WHO Study Group on Osteoporosis 29 National Osteoporosis Risk Assessment (NORA) program 30 National Health and Nutrition Examination Survey (NHANES III) 31 European Vertebral Osteoporosis Study (EVOS) and European Prospective Osteoporosis Study (EPOS) 31 Japanese Population-based Osteoporosis Study (JPOS) 31 The Study of Osteoporotic Fractures (SOF) 32 Chapter 3 COUNTRY TREATMENT TREES 33 US 33 Japan 35 France 36 Germany 38 Italy 40 Spain 41 UK 43 Chapter 4 EPIDEMIOLOGY AND PATIENT SEGMENTATION 45 Osteoporosis definition and classification 45 Introduction 45 Classification of osteoporosis 45 WHO Classification 46 Disease stage classification 47 Mayo Clinic classification 47 Etiology of osteoporosis 48 Epidemiology of osteoporosis 49 Methodological difficulties in assessing prevalence 49 Prevalence of osteoporosis and osteopenia in postmenopausal women 50 Overview of the prevalence of osteoporosis/osteopenia in women 50 US 52 Japan 53 France 54 Germany 54 Italy 55 Spain 56 UK 57 Prevalence of osteoporosis and osteopenia in men 57 Introduction 57 Overview of the prevalence of osteoporosis/osteopenia in men 58 US 61 Japan 61 France 62 Germany 62 Spain 63 UK 63 Comparative physician-based patient population data 64 Osteoporosis population forecast 64 Fractures, their implications and minor risk groups 65 Introduction 65 Overview of fracture prevalence 67 US 68 Japan 69 France 69 Germany 70 Italy 70 Spain 71 UK 72 Chapter 5 DIAGNOSIS AND TREATMENT OPTIONS 73 Presentation and diagnosis 73 The problem of patient identification in osteoporosis 75 Screening – who, how and when? 75 Severe osteoporosis slips through the cracks 77 Patient referrals in osteoporosis 78 Diagnosis – techniques and patient population 79 Diagnosis rates 80 Treatment rates 81 Treatment options 85 Treatment guidelines 86 Chapter 6 PRESCRIBING TRENDS AND INFLUENCING FACTORS 89 Prescribing trends 89 Drug therapy – an overview 89 Bisphosphonates 89 SERMs 90 Hormones – calcitonin, and HRT 90 Geographical trends in osteoporosis drug prescriptions 91 Bisphosphonate prescribing across the major markets 93 Non-pharmacological interventions 95 HRT in osteoporosis – not fade away? 97 Recent controversies… 97 …and repercussions 98 Changes in therapy 99 Case study: SERMs vs. HRT in osteoporosis 100 Patient switching to Evista since the WHI 102 Potential of future SERM use 104 Combination therapy in osteoporosis 106 Non-compliance with therapy 110 Chapter 7 IMPROVING TREATMENT OUTCOMES 114 Treatment outcomes 114 What influences the choice of drug prescribed? 115 New product development 118 Bisphosphonates in development 119 Awareness 119 Perception of dosing developments 122 Critical success factors for novel bisphosphonates 124 Parathyroid hormone – teriparatide (Forteo) 125 Awareness of Forteo 126 Impact of Forteo on prescribing behavior 127 Unmet needs 128 Physician/patient education 128 The need for greater awareness and education among physicians, specialists in particular 128 Need for disease management 131 Need for prioritisation of osteoporosis 132 Diagnostic unmet needs 133 Need for improved sensitivity of disgnostic and disease monitoring tools 133 Access to diagnostic equipment and treatment 135 Need for nationally supported diagnosis and treatment guidelines 137 Misappropriate use of DXA? Time for a rethink 138 Therapeutic unmet needs 138 Efficacy – a fractured approach 138 Reducing side-effects 139 Chapter 8 OTHER STAKEHOLDER INFLUENCES 141 Regulatory perspectives 143 Clinical trial endpoints in osteoporosis 143 Fracture risk reduction 144 Bone turnover markers 145 Bone microarchitecture and bone quality 145 Clinical trial design in osteoporosis 146 Prevention and treatment: implications for endpoint selection 146 Trial design and patient selection 147 Payer/provider perspectives 148 Cost-effectiveness in preventive therapy 148 Implications for reimbursement 148 Chapter 9 OPINION LEADER AND STAKEHOLDER TRANSCRIPTS 150 Key Opinion Leader 1 – Belgium 150 Key Opinion Leader 2 - UK 158 Key opinion Leader 3 – UK 167 Key Opinion Leader 4 - Germany 175 APPENDIX A BIBLIOGRAPHY 183 Epidemiology 183 United States 184 Japan 184 France 185 Germany 185 Italy 186 Spain 186 UK 187 Clinical trial data 188 APPENDIX B 190 Physician research methodology 190 Physician Sample breakdown 190 US 190 Japan 190 France 191 Germany 191 Italy 192 Spain 192 UK 193 Contributing experts 193 Stakeholder Insight: Osteoporosis QUESTIONNAIRE 194 1. Epidemiology 194 2. Screening and Diagnosis 199 3. Treatment patterns 202 OSTEOPENIA (Combination therapy) 206 b) COMBINATION Therapy 206 Dose (in mg or ml) per unit 206 Delivery method 206 Percentage of treated osteopenia population (%) 206 OSTEOPOROSIS (Combination therapy) 208 b) COMBINATION Therapy 208 Dose (in mg or ml) per unit 208 Delivery method 208 Percentage of treated osteopenia population (%) 208 SEVERE OSTEOPOROSIS (Combination therapy) 210 b) COMBINATION Therapy 210 Dose (in mg or ml) per unit 210 Delivery method 210 Percentage of treated osteopenia population (%) 210 4. Patient compliance 214 5. Specific Drug Classifications: HRT, SERMs and bisphosphonates 215 6. Recent developments: Forteo and its potential 220 The opinion leader discussion guide 224 Opinion leader interview guide 224 Screening and diagnosis 224 Treatment rates 224 Treatment outcomes and practice 225 Current issues in osteoporosis 226 Research methodology 228