Update on Osteoporosis

1. Update on Osteoporosis New Data and New Drugs Linkage to Falls Services

2. NICE – GUIDELINES FOR SECONDARY PREVENTION OF FRACTURES, 2005 BISPHOSPHONATES are recommended as treatment for secondary prevention after osteoporosis fractures In women aged 75 and older, without the need for DEXA In women aged between 65 and 75 if the presence of osteoporosis is confirmed by DEXA In women younger than 65 years of age, if they have a very low BMD (t < -3.0), or confirmed osteoporosis with added risk factors

4. A Model Osteoporosis Service Fracture Liaison service (FLS) Osteoporosis nurses see fracture patients as in-patient or out-patient – discuss situation, offer DEXA, etc Direct access DEXA Service (DADS) for GP’s GP’s get back computer-generated treatment suggestions. Complex cases referred to Osteo Clinic Waiting list for Scanning – FLS 8 weeks, DADS 10 weeks

5. RECENT BISPHOSPHONATE EVIDENCE TEN YEAR DATA ON THERAPY DIRECT COMPARISON OF DIFFERENT BISPHOSPHONATES IV BISPHOSPHONATES

6. alendronate 10 mg over 10 years  Treatment with 10 mg of alendronate for 10 years produced mean increases in bone mineral density of 6.7% at the total hip as compared with baseline values (p<0.001).7 Smaller gains occurred in the group given 5 mg daily (p<0.05).7 In the discontinuation group, BMD significantly decreased but remained above baseline values (p<0.001).7Treatment with 10 mg of alendronate for 10 years produced mean increases in bone mineral density of 6.7% at the total hip as compared with baseline values (p<0.001).7 Smaller gains occurred in the group given 5 mg daily (p<0.05).7 In the discontinuation group, BMD significantly decreased but remained above baseline values (p<0.001).7

7. Superior Total Hip BMD with FOSAMAX™ in FACT In a double-blind trial of 1053 postmenopausal women with osteoporosis, at 12 months, FOSAMAX™ Once Weekly 70 mg was 92% more effective in increasing BMD at the total hip than risedronate 35 mg once weekly. At month 12, the mean total hip BMD increased by 2.2% from baseline in the group given FOSAMAX and by 1.2% in the group given risedronate. The treatment difference was 1.1% (95% CI: 0.7%, 1.4%; p<0.001 vs. risedronate).3,38 FOSAMAX thus demonstrated a greater increase in BMD at the total hip than did risedronate.38 FOSAMAX Once Weekly™ (alendronate) is a trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA.In a double-blind trial of 1053 postmenopausal women with osteoporosis, at 12 months, FOSAMAX™ Once Weekly 70 mg was 92% more effective in increasing BMD at the total hip than risedronate 35 mg once weekly. At month 12, the mean total hip BMD increased by 2.2% from baseline in the group given FOSAMAX and by 1.2% in the group given risedronate. The treatment difference was 1.1% (95% CI: 0.7%, 1.4%; p<0.001 vs. risedronate).3,38 FOSAMAX thus demonstrated a greater increase in BMD at the total hip than did risedronate.38 FOSAMAX Once Weekly™ (alendronate) is a trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA.

8. Alendronic Acid and Risedronate – which to use and when? Alendronic Acid is first line in all areas of Scotland. It is generic and price is now £6/month. It causes higher BMD gains than risedronate (£24/month) Alendronate trials excluded all patients with GI history or aspirin/NSAID use. ?Give all patients Alendronic Acid and only consider Risedronate if intolerant? OR Give Risedronate in defined patient groups as first line therapy? Fracture efficacy well proven in elderly and those on aspirin/NSAID

9. Intravenous Bisphosphonates Palmidronate, Ibandronate and Zoledronate

10. Ibandronate DIVA study – Daily Oral v 2 or 3 Monthly IV Ibandronate - (3 min injection) 1395 patient RCT – all osteoporotic BMD improved significantly better with IV Therapy. ?Dose Effect or Adherence effect No fracture data available Similar side-effects, except 5% acute phase response with IV preparation

11. Zolendronate Annual IV preparation – SMC approval 2008 For use in patients intolerant or unable to comply with usual oral bisphosphonates Used extensively in malignant disease and Paget’s Disease. HORIZON (Primary Fracture Trial) HORIZON (Recurrent Fracture Trial, RFT)

12. Zoledronic Acid Reduced Cumulative 3-Year Risk of Clinical Fractures (Hip, Clinical Vertebral, Non-vertebral) Zoledronic Acid Reduced Cumulative 3-Year Risk of Clinical Fractures (Hip, Clinical Vertebral, Non-vertebral) Zoledronic acid 5 mg consistently reduced the relative risk for fractures in key locations over 3 years : The rate of new hip fractures was 2.49% for placebo and 1.44% for ZOL 5 mg, corresponding to a significant 41% relative risk reduction with active drug (P =.0024) The event rate for clinical vertebral fractures was 2.59% in the placebo group, compared with 0.53% in the ZOL 5-mg group, corresponding to a significant 77% relative risk reduction with active drug (P < .001) The placebo group exhibited a non-vertebral fracture event rate of 10.71% versus 7.97% with ZOL 5 mg, for a significant 25% relative risk reduction (P =.0002). It should be noted that hip fracture was NOT excluded from analysis of non-vertebral fractures. Reference Black DM, Delmas PD, Eastell R, et al, for the HORIZON Pivotal Fracture Trial. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356:1809-1822.Zoledronic Acid Reduced Cumulative 3-Year Risk of Clinical Fractures (Hip, Clinical Vertebral, Non-vertebral) Zoledronic acid 5 mg consistently reduced the relative risk for fractures in key locations over 3 years : The rate of new hip fractures was 2.49% for placebo and 1.44% for ZOL 5 mg, corresponding to a significant 41% relative risk reduction with active drug (P =.0024) The event rate for clinical vertebral fractures was 2.59% in the placebo group, compared with 0.53% in the ZOL 5-mg group, corresponding to a significant 77% relative risk reduction with active drug (P < .001) The placebo group exhibited a non-vertebral fracture event rate of 10.71% versus 7.97% with ZOL 5 mg, for a significant 25% relative risk reduction (P =.0002). It should be noted that hip fracture was NOT excluded from analysis of non-vertebral fractures. Reference Black DM, Delmas PD, Eastell R, et al, for the HORIZON Pivotal Fracture Trial. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356:1809-1822.

13. Zoledronic Acid Reduced Cumulative 3-Year Risk of Clinical Vertebral Fractures (Strata I + II) by 77% Zoledronic Acid Reduced Cumulative 3-Year Risk of Clinical Vertebral Fractures (Strata I + II) by 77% Assessment of number of clinical vertebral fractures (painful fractures that led to an office evaluation) occurring over 3 years revealed that a single annual infusion of ZOL 5 mg reduced the risk of clinical vertebral fractures by 77% compared with placebo over 3 years (P <.001; hazard ratio = 0.23). Reference Black DM, Delmas PD, Eastell R, et al, for the HORIZON Pivotal Fracture Trial. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356:1809-1822. Zoledronic Acid Reduced Cumulative 3-Year Risk of Clinical Vertebral Fractures (Strata I + II) by 77% Assessment of number of clinical vertebral fractures (painful fractures that led to an office evaluation) occurring over 3 years revealed that a single annual infusion of ZOL 5 mg reduced the risk of clinical vertebral fractures by 77% compared with placebo over 3 years (P <.001; hazard ratio = 0.23). Reference Black DM, Delmas PD, Eastell R, et al, for the HORIZON Pivotal Fracture Trial. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356:1809-1822.

14. Zoledronic Acid 5 mg Reduced Cumulative 3-Year Risk of Clinical Fractures by 35% Over Time Zoledronic Acid 5 mg Reduced Cumulative 3-Year Risk of Clinical Fractures by 35% Over Time As illustrated in this Kaplan-Meier curve, zoledronic acid reduced the cumulative 3-year risk of clinical fractures by 35%. It should be noted that after Month 36 (Day 1080), the changes in the Kaplan-Meier curves become oversensitive to the occurrence of clinical fractures due to the small number of patients who are at risk of clinical fracture after this time point (119 on placebo and 129 on zoledronic acid). As such, every clinical fracture event that occurs has considerable influence on the cumulative incidence of clinical fractures as well as the shape of the Kaplan-Meier curves. Data reliability issues were identified for one center representing a total of 95 patients (48 patients in the zoledronic acid group and 47 in the placebo group). An analysis excluding data from this center was repeated for the ITT population, and the results were similar: hazard ratio of 0.64 (95% CI: 0.49 to 0.84) for the zoledronic acid group vs. the placebo group, representing a 36% reduction in the risk of clinical fractures over time (P=0.0014). Reference Lyles KW, Colón-Emeric CS, Magaziner JS, et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007. [e-publication 10.1056/NEJMoa074941 at www.nejm.org]Zoledronic Acid 5 mg Reduced Cumulative 3-Year Risk of Clinical Fractures by 35% Over Time As illustrated in this Kaplan-Meier curve, zoledronic acid reduced the cumulative 3-year risk of clinical fractures by 35%. It should be noted that after Month 36 (Day 1080), the changes in the Kaplan-Meier curves become oversensitive to the occurrence of clinical fractures due to the small number of patients who are at risk of clinical fracture after this time point (119 on placebo and 129 on zoledronic acid). As such, every clinical fracture event that occurs has considerable influence on the cumulative incidence of clinical fractures as well as the shape of the Kaplan-Meier curves. Data reliability issues were identified for one center representing a total of 95 patients (48 patients in the zoledronic acid group and 47 in the placebo group). An analysis excluding data from this center was repeated for the ITT population, and the results were similar: hazard ratio of 0.64 (95% CI: 0.49 to 0.84) for the zoledronic acid group vs. the placebo group, representing a 36% reduction in the risk of clinical fractures over time (P=0.0014). Reference Lyles KW, Colón-Emeric CS, Magaziner JS, et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007. [e-publication 10.1056/NEJMoa074941 at www.nejm.org]

15. Zoledronic Acid 5 mg Reduced Cumulative 3-Year Risk of Non-vertebral Fractures by 27% Over Time Zoledronic Acid 5 mg Reduced Cumulative 3-Year Risk of Non-vertebral Fractures by 27% Over Time The incidence of non-vertebral fractures was reduced with zoledronic acid relative to placebo. The 2-year event rates based on Kaplan-Meier estimates were 7.57% and 10.72% for the zoledronic acid and placebo groups, respectively. An estimated hazard ratio of 0.73 [95% CI: 0.55 to 0.98, P=0.0338] corresponds to a 27% reduction in the risk of a non-vertebral fracture over time. Reference Lyles KW, Colón-Emeric CS, Magaziner JS, et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007. [e-publication 10.1056/NEJMoa074941 at www.nejm.org] Zoledronic Acid 5 mg Reduced Cumulative 3-Year Risk of Non-vertebral Fractures by 27% Over Time The incidence of non-vertebral fractures was reduced with zoledronic acid relative to placebo. The 2-year event rates based on Kaplan-Meier estimates were 7.57% and 10.72% for the zoledronic acid and placebo groups, respectively. An estimated hazard ratio of 0.73 [95% CI: 0.55 to 0.98, P=0.0338] corresponds to a 27% reduction in the risk of a non-vertebral fracture over time. Reference Lyles KW, Colón-Emeric CS, Magaziner JS, et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007. [e-publication 10.1056/NEJMoa074941 at www.nejm.org]

16. Zoledronic Acid 5 mg Reduced Subsequent Fracture Risk Over Time Zoledronic Acid 5 mg Reduced Subsequent Fracture Risk Over Time With respect to the primary efficacy variable (time to first clinical fracture), 231 patients had at least one adjudicated clinical fracture (92 in zoledronic acid and 139 in placebo). For the primary analysis in the ITT population, the hazard ratio of 0.65 (95% CI: 0.50 to 0.84) for the zoledronic acid group versus the placebo group represents a 35% reduction in the risk of clinical fractures over time (P=0.0012). The level of significance for the two-sided log-rank test was adjusted to 0.0351, to account for the three interim analyses performed for the Data Safety Monitoring Board. As the P-value of 0.0012 is less than the required significance level (0.0351), the superiority of zoledronic acid in reducing the incidence of clinical fractures relative to placebo is concluded. The results of the primary analysis were confirmed and consistent in the per-protocol population. Statistically reductions in favor of zoledronic acid vs. placebo were also observed for non-vertebral fractures (-27%) and vertebral fractures (-46%) The zoledronic acid group had a numerically lower risk in hip fractures compared to the placebo group (30% reduction in risk), but this did not achieve statistical significance. It should be noted that the number of new hip fractures was low since surgical repair of the entry hip often involved arthroplasty, implying that any hip fractures that occurred could only have occurred in the other hip of such patients. Reference Lyles KW, Colón-Emeric CS, Magaziner JS, et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007. [e-publication 10.1056/NEJMoa074941 at www.nejm.org]Zoledronic Acid 5 mg Reduced Subsequent Fracture Risk Over Time With respect to the primary efficacy variable (time to first clinical fracture), 231 patients had at least one adjudicated clinical fracture (92 in zoledronic acid and 139 in placebo). For the primary analysis in the ITT population, the hazard ratio of 0.65 (95% CI: 0.50 to 0.84) for the zoledronic acid group versus the placebo group represents a 35% reduction in the risk of clinical fractures over time (P=0.0012). The level of significance for the two-sided log-rank test was adjusted to 0.0351, to account for the three interim analyses performed for the Data Safety Monitoring Board. As the P-value of 0.0012 is less than the required significance level (0.0351), the superiority of zoledronic acid in reducing the incidence of clinical fractures relative to placebo is concluded. The results of the primary analysis were confirmed and consistent in the per-protocol population. Statistically reductions in favor of zoledronic acid vs. placebo were also observed for non-vertebral fractures (-27%) and vertebral fractures (-46%) The zoledronic acid group had a numerically lower risk in hip fractures compared to the placebo group (30% reduction in risk), but this did not achieve statistical significance. It should be noted that the number of new hip fractures was low since surgical repair of the entry hip often involved arthroplasty, implying that any hip fractures that occurred could only have occurred in the other hip of such patients. Reference Lyles KW, Colón-Emeric CS, Magaziner JS, et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007. [e-publication 10.1056/NEJMoa074941 at www.nejm.org]

17. Zoledronic Acid 5 mg Reduced Risk of All-Cause Mortality by 28% Over Time Zoledronic Acid 5 mg Reduced Risk of All-Cause Mortality by 28% Over Time Analysis confirmed a significant 28% decreased risk of death (Hazard ratio 0.72, 95% CI: 0.56 to 0.93, P=0.0117) with zoledronic acid compared to placebo. The cumulative death rate for both treatment groups over time is shown here. There is a separation of the two treatment groups beginning at approximately Month 16. This is approximately 12 months after the earliest separation of the two treatments groups in time to first clinical fracture (approximately Month 4), after which time the curves for clinical fracture and mortality paralleled each other. It should be noted that after Month 36 (Day 1080), the changes in the Kaplan-Meier curves become oversensitive to the occurrence of death due to the small number of patients who were still being followed up in the study after that time point (149 on placebo and 144 on zoledronic acid). As such, every death that occurs has considerable influence on the cumulative incidence of deaths as well as the shape of the Kaplan-Meier curves. Reference Lyles KW, Colón-Emeric CS, Magaziner JS, et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007. [e-publication 10.1056/NEJMoa074941 at www.nejm.org]Zoledronic Acid 5 mg Reduced Risk of All-Cause Mortality by 28% Over Time Analysis confirmed a significant 28% decreased risk of death (Hazard ratio 0.72, 95% CI: 0.56 to 0.93, P=0.0117) with zoledronic acid compared to placebo. The cumulative death rate for both treatment groups over time is shown here. There is a separation of the two treatment groups beginning at approximately Month 16. This is approximately 12 months after the earliest separation of the two treatments groups in time to first clinical fracture (approximately Month 4), after which time the curves for clinical fracture and mortality paralleled each other. It should be noted that after Month 36 (Day 1080), the changes in the Kaplan-Meier curves become oversensitive to the occurrence of death due to the small number of patients who were still being followed up in the study after that time point (149 on placebo and 144 on zoledronic acid). As such, every death that occurs has considerable influence on the cumulative incidence of deaths as well as the shape of the Kaplan-Meier curves. Reference Lyles KW, Colón-Emeric CS, Magaziner JS, et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007. [e-publication 10.1056/NEJMoa074941 at www.nejm.org]

18. Most Frequent AEs by Preferred Term With =5% Incidence for Any Group Most Frequent AEs by Preferred Term With =5% Incidence for Any Group The most frequently occurring AEs by preferred term (=2.0% for any group) are shown here. Pyrexia, bone pain, musculoskeletal pain, and hyperthermia occurred with a more than twofold higher incidence in the zoledronic acid 5 mg group vs. the placebo group. These types of AEs are consistent with post-dose symptoms and occur most frequently within 3 days following the first intravenous study drug infusion. Osteoporosis, dizziness and chronic obstructive pulmonary disease (not shown in this slide) each occurred with a twofold higher incidence in the placebo group vs. the zoledronic acid group. Reference Lyles KW, Colón-Emeric CS, Magaziner JS, et al. Efficacy and safety of zoledronic acid 5 mg in preventing fractures in men and women with prevalent hip fracture: the HORIZON-Recurrent Fracture Trial. Presented at: 29th Annual Meeting of the American Society for Bone and Mineral Research; September 16-19, 2007; Honolulu, Hawaii. Abstract 1055.Most Frequent AEs by Preferred Term With =5% Incidence for Any Group The most frequently occurring AEs by preferred term (=2.0% for any group) are shown here. Pyrexia, bone pain, musculoskeletal pain, and hyperthermia occurred with a more than twofold higher incidence in the zoledronic acid 5 mg group vs. the placebo group. These types of AEs are consistent with post-dose symptoms and occur most frequently within 3 days following the first intravenous study drug infusion. Osteoporosis, dizziness and chronic obstructive pulmonary disease (not shown in this slide) each occurred with a twofold higher incidence in the placebo group vs. the zoledronic acid group. Reference Lyles KW, Colón-Emeric CS, Magaziner JS, et al. Efficacy and safety of zoledronic acid 5 mg in preventing fractures in men and women with prevalent hip fracture: the HORIZON-Recurrent Fracture Trial. Presented at: 29th Annual Meeting of the American Society for Bone and Mineral Research; September 16-19, 2007; Honolulu, Hawaii. Abstract 1055.

19. Zoledronate Hip Fracture Trial - continued First RCT of secondary prevention after Hip fracture Only followed up for 1.9 years – stopped due to very positive results. Study population had very high absolute fracture risk Zoledronate clearly showed fracture reduction effect Safety data showed no major problems – no increased risk of AF /CVA. No case of ONJ Reduction in Death – unexpected and needs more work Timing of Zoledronate may be crucial - ?after 6 weeks. Sub-analysis underway

20. Osteonecrosis of the Jaw

21. OJN – some facts and figures Incidence – about 0.7 per 100000 patient years Over 90% of cases in patients with malignant disease Over 90% of cases occur in patients given IV bisphosphonates 60% of patients have had recent trauma/dental work. Only 3% of reported cases of OJN have occurred in patients being treated for osteoporosis

22. DRUG THERAPY FOR OSTEOPOROSIS Alternate OPTIONS PTH Strontium Ranelate Calcitonin RANK Ligand antibodies? Lasofoxifene

23. Effects of rhPTH - nonvertebral fractures

24. Lothian Formulary Guidelines for PTH Restricted use (2nd line after bisphosphonate) For woman aged over 65 who: Have severe osteoporosis, T <-2.5 with 2 fractures. Inadequate clinical response to bisphosphonate Occurrence of further fractures after 1 year Intolerant to therapy Are willing to administer daily SC injections. Patients should be off bisphosphonate but be on Ca/VitD Named Consultant use only

25. Strontium Ranelate SMC approval – 2005 Aged over 75 Previous fracture or high risk Bisphosphonate intolerant 2G satchet dissolved in water once daily Poor absorbtion – similar to bisphosphonates Main side-effect – diarrhoea, minor GI symptoms

26. The SOTI study showed that Protelos 2g once daily reduced the vertebral fracture risk as early as the first year of treatment Protelos significantly reduced the risk of vertebral fracture(s) by 49% after one year and by 41% after three years of treatment, in comparison to placebo On the basis of this data, 9 patients would need to be treated for 3 years with Protelos in order to prevent one patient from having a vertebral fracture (95% CI 6-14) ___________________________ Meunier PJ et al. N Engl J Med 2004;350:459-68The SOTI study showed that Protelos 2g once daily reduced the vertebral fracture risk as early as the first year of treatment Protelos significantly reduced the risk of vertebral fracture(s) by 49% after one year and by 41% after three years of treatment, in comparison to placebo On the basis of this data, 9 patients would need to be treated for 3 years with Protelos in order to prevent one patient from having a vertebral fracture (95% CI 6-14) ___________________________ Meunier PJ et al. N Engl J Med 2004;350:459-68

27. TROPOS: reduction of non-vertebral fracture risk with Protelos In the TROPOS study, Protelos reduced the risk of non-vertebral fractures by 16% over three years There was also a 19% reduction in Major Osteoporosis Related Non-Vertebral Fractures (pre-defined by an external advisory board as fractures of the humerus, pelvis + sacrum, ribs, proximal femur, clavicle, wrist). Percentage of patients with Major Osteoporotic Fracture (%) for Strontium Ranelate 8.7%, Placebo 10.4%. _________ Reginster JY et al. http://jcem.endojournals.orgIn the TROPOS study, Protelos reduced the risk of non-vertebral fractures by 16% over three years There was also a 19% reduction in Major Osteoporosis Related Non-Vertebral Fractures (pre-defined by an external advisory board as fractures of the humerus, pelvis + sacrum, ribs, proximal femur, clavicle, wrist). Percentage of patients with Major Osteoporotic Fracture (%) for Strontium Ranelate 8.7%, Placebo 10.4%. _________ Reginster JY et al. http://jcem.endojournals.org

28. Strontium Ranelate in Patients over 80 Subanalysis of SOTI and TROPOS 1488 patients over the age of 80 (80-100). 3 year follow-up. Intention to treat analysis – fracture risk reduction was Vertebral 32% and non-vertebral 31% Only drug with 5 year fracture data. Proven AAA evidence in over 80’s Side-effect profile similar to placebo – main issue is GI symptoms

29. Salmon Calcitonin – Nasal Spray Calcitonin – previously available as injection only, but now has a nasal spray. Once daily – 200mcg. Easy to use. Evidence of efficacy in vertebral fracture, but not in non-vertebral fracture Potential role in bisphosphonate-intolerant patients and those with painful vertebral fracture

30. RANK L / OPG SYSTEM - Denosumab A new target in bone metabolism. RANKL stimulates osteoclast activity. OPG inhibits osteoclasts and causes apoptosis Denosumab is a monoclonal antibody which blocks activity of RANKL. Given as SC injection twice per year FREEDOM Trial – 68% reduction in Vertebral, 20% reduction in non-vertebral and 40% reduction in Hip fractures (Sept 2008) Some safety concerns around infections. Likely to get Licence soon. ?Price.

31. LASOFOXIPHENE – a new SERM New SERM to follow Raloxiphene. PEARL study – RCT of 8556 subjects. Mean age 67. Reported Sept 2008 42% reduction in vertebral fractures at 3 years 24% reduction in non-vert at 5 years. No significant hip data. Reduction in incidence of breast cancer and CVS events. VTE risk doubled No licence yet.

32. Refracture rates - Glasgow Fracture Liaison Service – 6137 patients with 6755 fractures over first 5 years Observational data - mean FU - 28 months 8.8% sustained refracture. Background hip fracture rate is 2% Refractures happen quickly - 43% of refractures after hip fracture occur within 6 months Drug therapies are unlikely to influence this – reinforcing the need for falls risk reduction

33. Secondary Prevention after Hip Fracture Observational cohort study – USA databases. 20644 patients over 65 with first Hip Fracture. Mean Age – 80 Primary outcome measure – recurrent hip fracture 6779 were dispensed anti-resorptive therapy. Those dispensed active therapy shown a RR reduction of 25% (CI 0.66-0.87) ASBMR (2006)

34. Mrs MD Age 79 ACUTE ADMISSION TO HOSPITAL PC: “Off Legs” + “Acopia” History Recurrent falls for several months Reducing mobility/lost confidence PMH Hypertension Colles fracture – age 65 CVA – good recovery – age 75 Fractured NOF – age 77 FH Angina and Stroke disease Mother had Hip fracture – aged 70’s

35. Mrs MD - continued SH Lives alone Ex-smoker Package of Care once daily. Drugs Aspirin / Bisoprolol / Simvastatin Bendroflumethazide / Lisinopril This Case History demonstrates a catalogue of MISSED Opportunities 2 previous fragility fractures / history of maternal hip fracture Never had DEXA scan On good cardiovascular therapy, but no bone protection Should have had osteoporosis assessment after both fractures

36. Mrs MD - continued Previous fractures were both the result of Falls and had history of multiple falls prior to hospital admission No apparent Falls assessments done No referral for Falls work-up in Geriatric Day Hospital No documented assessment of visual acuity No apparent review of medications Environmental assessment completed by OT’s at time of CVA

37. The Future - Risk Scores for Osteoporosis? Increasing efforts to calculate risk – similar to cardiovascular risk scoring. FRAX score – WHO and IOF approved tool, Launched February 2008 – www.shef.ac.uk Calculates 10 year risk of a major osteoporotic fracture or of hip fracture BMD is not essential to generate a risk score

41. National Clinical Audit of Falls and Bone Health in Older People – Healthcare Commission (Nov 2007) 91% of PCO’s in England and Wales took part Each provided data from 40 non-hip and 20 hip fracture patients Audit comprised 5642 non-hip and 3184 hip fractures. Non-hip: mean age 79, and 86% women Hip: mean age 83, and 80% women

42. National Audit – Nov 2007 – Key Points 31% of operations for Hip fracture were delayed beyond the 48 hour target. Most patients returning home from A+E after a fragility fracture were not offered falls risk assessment and only 22% were referred for exercise to reduce falls risk. After 3 months, only 20% were on appropriate treatment for osteoporosis Less than 50% of hip fracture patients were on appropriate bone therapy at 3 months The 5% who attended Falls Clinics received better falls and bone assessments and treatments

43. Scottish Government - NHS HDL (2007) 13 Delivery Framework for Adult Rehabilitation and Prevention of Falls in Older People “Health Boards are asked to take the lead in developing with all relevant partners, a combined falls prevention and bone health strategy, by the end of 2007-8”

44. Falls Prevention and Risk Minimisation – a Mapping ExerciseScott Porter Research – commissioned by NHS QIS, June 2007 Definition for a Progressive service Designated Falls Lead Established and integrated strategy across Health and social services Combined Falls and Bone Health service in place. A Multi-disciplinary Falls assessment facility is available – using standardised tools and interventions

45. Results of Mapping Exercise, 2007 Only 2 of 14 Scottish Health Boards met the criteria for a “progressive service” Another 4 were defined as “Focused” or “Evolving” services Five Health Boards were “exploring” options with patchy services – but with obvious gaps Three were felt to have no significant service

46. Falls and Bone Health – the Vision - Part 1 Each CHP will have a Falls Coordinator with links to community rehab / rapid response teams. Primary care and A+E refer fallers to a central contact point. Elderly fallers will be assessed by a member of this team and appropriate action taken. If required – refer for full work-up Falls work-up will include – Strength and balance training Home hazard assessment and intervention Visual assessment and referral Medication review and modification Basic Osteoporosis assessment will be done by Falls team – looking for risk factors. ?Use of FRAX risk tool. Onward referral if necessary

47. Falls and Bone Health – the Vision – Part 2 Direct access DEXA scanning available for “at risk” patients – referral could come from falls service Fracture Liaison Service sees patients with fragility fractures – provides information and organises DEXA scans. DEXA scans advise Primary Care on therapy – taking local Drug formulary into account. Fracture Liaison assesses patient for falls risk – and refers to Falls Coordinator in CHP if required Osteoporosis Clinics are available in secondary care to see more complex patients.

48. Mrs JM Age 72 History Fall at home Colles Fracture – treated in A+E FU at Fracture Clinic At Clinic - Reviewed by Orthopods – satisfactory reduction. Seen by Fracture Liaison Nurse who sees patient and - Information sheet on Osteoporosis Offered DEXA scan and agrees Slow “Timed get up and go” test Mrs JM agrees to referral to Falls Coordinator of local CHP DEXA Score shows Hip and Spine t-score of -3.1 and -2.7 respectively. Commenced on Bisphosphonate and Ca/VitD

49. Mrs JM - continued Falls Coordinator Organises Home Assessment by member of team Visit leads to provision of new safety equipment in house and removal of falls hazards Mrs JM referred to local geriatric Day Hospital No need for package of care identified Day Hospital 8 week individualised balance and exercise programme Visual acuity satisfactory Postural Hypotension identified – medication review leads to withdrawal of diuretic Mrs JM discharged after 10 weeks Advised to contact Health Centre if further falls