1 / 39

Osteoporosis – Who to teat and with what? Dr Neil Gittoes Senior Lecturer Endocrinology, University of Birmingham, UK

Osteoporosis – Who to teat and with what? Dr Neil Gittoes Senior Lecturer Endocrinology, University of Birmingham, UK. Key facts about osteoporosis. The clinical relevance of OP is fracture Age is the best predictor of fracture risk

MikeCarlo
Download Presentation

Osteoporosis – Who to teat and with what? Dr Neil Gittoes Senior Lecturer Endocrinology, University of Birmingham, UK

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Osteoporosis – Who to teat and with what? Dr Neil Gittoes Senior Lecturer Endocrinology, University of Birmingham, UK

  2. Key facts about osteoporosis • The clinical relevance of OP is fracture • Age is the best predictor of fracture risk • BMD/DXA is not the be all and end all in fracture assessment • Previous fracture increases risk of subsequent fracture 2-5 fold • Drugs can reduce fracture risk by >60% in high risk patients • Think how a DXA result will change management

  3. Osteoporosis Falls Fracture Falls risk Force of fall Osteoporosis is not a problem if you don’t fracture Fractures Bone fragility

  4. Osteoporosis – the age factor • T score is number of SDs above or below young adult mean BMD

  5. Ageing population – osteoporosis is the “norm”

  6. 10 year risk: age and risk of # with low BMD Kanis et al, 2001

  7. Projected number of hip fractures (000) world wide Number Year Ageing society – osteoporosis a growing problem • Hip fracture • 24% first year mortality • 50% unable to walk without aid • 33% totally dependent

  8. Combined effect of BMD and prior # Ross et al, 1991

  9. What are the current challenges in treatment of osteoporosis? • Which patients to treat? • Where do the new drugs fit? • How do we get patients to take drugs long term? • Treatment guidelines • What is new with calcium and vitamin D? • How long to treat for? • How do we determine if drugs are working? • Depo provera… • Availability of effective drugs is the least concern!

  10. Case finding strategy for prevention -high risk groups • Low trauma fracture (wrist, L-spine, hip, rib, upper humerus) <75 • Prednisolone for >3 months if <65 years • First degree relative with history hip fracture before age 70 years • First degree relative with osteoporosis (T<-2.5) • Premature (<45) menopause not on HRT (iatrogenic/spontaneous) • Radiological evidence of osteopenia • Prolonged amenorrhoea (>6/12) not pregnancy/contraception • Male hypogonadism without testosterone replacement • Anorexia nervosa (BMI < 19kg/m²) • OTHER INDICATIONS FOR BONE MINERAL DENSITY (Secondary care?) • Thyrotoxicosis ·Primary hyperparathyroidism • Cushing’s syndrome · Organ transplantation • Malabsorption · Chronic liver disease Send these patients for BMD measurement

  11. 2 x –1SD Predictors of fracture risk – bone density 35 % patientswith vertebral fractures 30 25 20 15 10 5 0 -5 -4 -3 -2 -1 0 T–score SD – Standard deviation Watts, 2001

  12. Facts about local DXA service • GP direct access • Under utilised • Capacity for further 1000 scans per year • Short wait time • £50 per scan • ‘Budget’ in place • Responds to urgent requests • Clinical reporting/access to outpatient clinics • Excellent quality service

  13. Available therapies to reduce fracture risk • Highly effective in high risk groups • Fractures, older, low BMD (T<-2.5) • 60%+ anti-fracture efficacy • Sustained effect (10 yrs) • Safe • Rapid onset of anti-fracture effect • 6-12 months • Multiple treatment options • Bisphosphonates, raloxifene, teriparatide, strontium ranelate, Ca/D

  14. Which drug for which patient?

  15. FORMATION RESORPTION Sr + Pre-OB Pre-OC REPLICATION Sr - DIFFERENTIATION OB OB OB Sr - OC + BONE FORMING ACTIVITY BONE RESORBING ACTIVITY Bone Strontium ranelate - proposed mode of action In vitro . Marie et al, 2001

  16. Strontium ranelate

  17. GI tolerability strontium ranelate • Diarrhoea higher vs placebo with strontium ranelate • 6.1% vs 3.6% p=0.02 • effect resolved after first 3 months • Constipation slightly lower vs placebo with strontium ranelate • 5.3% vs 7.1% p<0.05 Meunier et al, 2004

  18. Other observations • Overall annual incidence of VTE in strontium studies • 0.7% (0.9% in Sr group / 0.6% in placebo group) • OR 1.42 (Cl [1.02;1.98], p=0.036) • No biological plausible explanation • Caution advised on SPC rather than contraindication Protelos Summary of Product Characteristics. Date of preparation September 2004.

  19. Key points - strontium ranelate • Significant reduction in • Vertebral fractures (clinical and radiographic) • Non-vertebral fractures • Hip fractures in a high risk elderly population • Anti-fracture efficacy demonstrated in over 80s • Side effects (diarrhoea) mild and transient • Positioning • First line alternative to bisphosphonate • Particularly in elderly • Concerns regarding upper GI complications • Women with intolerance/inadequate response to other Rx

  20. Proportion with hip # > 60 years (n = 553) with vitamin D inadequacy, according to six different thresholds Gallacher et al, 2005 Combination bisphosphonate + vitamin D • Fosavance – ALN 70 mg + 2800 iU D • BPs don’t work in setting of vit D deficiency • Vitamin D deficiency is common • Adherence/compliance big problem

  21. Vitamin D inadequacy worldwide 81% 90 N=1285 80 63% 70 59% 59% 52% 51% 60 50 Prevalence (%) 40 30 20 10 0 All Australia LatinAmerica Asia Middle East Europe Regions Vitamin D inadequacy defined as serum 25(OH)D <30 ng/ml 1285 community-dwelling women with osteoporosis from 18 countries to evaluate serum 25(OH)D distribution. Lim S-K et al, 2005

  22. Liver Intestine Bone formation Vitamin D action UVB Sun ProD3  PreD3  Vitamin D3 Skin DietVitamin D3 Vitamin D2 25(OH)D Kidney Increase calcium and phosphorus absorption 1,25(OH)2D Maintain serum calcium and phosphorus Metabolic functions Bone health Neuromuscular functions

  23. Consequences of vitamin D insufficiency Calcium absorption Parathyroidhormone Bone mineraldensity Appropriateneuromuscularfunction Risk of fracture Falls

  24. Probable reasons for prevalence of vitamin D inadequacy • Lack of sunlight exposure (with age) • Vitamin D is not common in the diet • Ability to synthesize vitamin D in the skin decreases with age • Lack of compliance taking daily supplements • Growing use of sun screens • All clinical trials have had supplemental Ca/D • 500mg Ca + 400iU vitamin D • Evidence based practice

  25. Fosavance • Supersedes Fosamax/ALN • Deals with potential vitamin D deficiency • One weekly tablet • Adherence/compliance • Pricing • Ca/D supplementations • Some may need further vitamin D (calcium?) supplementation

  26. Bisphosphonates

  27. Ibandronate vertebral fracture incidence over 3 years 10 8 6 4 2 0 62% fracture risk reduction 9.6% Incidence new vertebralfractures at year 3 (%) 4.7% Placebo 2.5 mg daily ibandronate †p=0.0001 vs placebo Chesnut et al, 2004

  28. MOBILE study – monthly non inferiorityLumbar spine BMD Year 2 Year 1 7 6 5 4 3 2 1 0 6.6%† 5.0% 4.9%* 3.9% Mean change from baseline (%) 2.5mg 150mg 2.5mg 150mg daily monthly daily monthly *p=0.002 vs daily ibandronate (2.5mg) †p<0.001 vs daily ibandronate (2.5mg) Delmas et al, 2005

  29. MOBILE study – non inferiorityHip BMD 2.5mg daily 150mg monthly 7 6 5 4 3 2 1 0 * 6.2 * 4.2 4.0 * 3.1 Mean change from baseline (%) 2.5 1.9 Total hip Femoral neck Trochanter *p<0.05 vs daily ibandronate (2.5mg) Delmas et al 2005

  30. MOBILE study – Adverse events Lewiecki et al, 2004

  31. Conclusions - monthly ibandronate • Prevents vertebral fractures • No conclusive supporting evidence that prevents non-spine and hip fractures • Is well tolerated • Offers potential for improved compliance • Does well in persistence studies • Is supported by a patient support programme

  32. So how do we use these drugs? NICE tell us how to manage patients with fragility fracturesSecondary prevention of osteoporotic fractures – NICE technology appraisal 87, January 2005

  33. NICE – HTA 87 – some background • Low trauma/fragility fracture • # as result of fall from standing height or less • Fractures other than skull are included • Minority of vertebral # present clinically • Coincidental vertebral # on XR • Clinical diagnosis of OP if no history of significant trauma • Consider underlying conditions predisposing to # • Check T in men

  34. Secondary prevention of osteoporosis(after fracture) - NICE Treat (BP) Treat (BP) Treat (BP) Low BMI, unRx menop, FH hip #, GC, infl, immob T-score Age

  35. Limitations of NICE guidelines • Deals with populations rather than individuals • Treat patients with no evidence base • Made all BPs ‘equal’ • Concept of ‘treatment failure’ is difficult • Did not deal with men • Strontium ranelate to follow • Primary prevention to follow

  36. What do I do with a • 53 year old F with recent Colle’s #? • DXA • Dependent on T-score treat with BP + Ca/D • 77 year old F with recent # ankle? • Empirical treatment with BP + Ca/D • 75 year old M with 2 T-spine wedge # on XR? • Consider secondary causes (measure T, etc) • T replacement if appropriate • Empirical treatment with ALN

  37. Assess suitability Assess suitability Consider long term BP if OP Consider long term BP if OP 1 stop DXA 1 g Ca + 800U vit D 1 g Ca + 800U vit D OP – antiresorptive + Ca/D Non-OP Lifestyle advice A fracture liaison service for S Bham? Clinical #, age >50 Fracture clinic Orthopaedic wards

  38. 40 30 20 10 Vertebrae Annual incidence per 1000 women Hip Wrist 50 60 70 80 Age (Years) Age stratified approach to managing osteoporosis IBN HRT PTH Strontium SERM Weekly BP Ca/D

More Related