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Osteoporosis – detection and treatment

Osteoporosis – detection and treatment. Dr Gill Coombes November 2007. Osteoporosis : Definition (NIH, 2001 ).

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Osteoporosis – detection and treatment

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  1. Osteoporosis –detection and treatment Dr Gill Coombes November 2007

  2. Osteoporosis : Definition (NIH, 2001) A skeletal disorder characterised by compromised bone strength predisposing a person to an increased risk of fracture. Bone strength primarily reflects integration of bone density and bone quality.

  3. Development of osteoporotic bone Rizzoli R ed In Atlas of Postmenopausal Osteoporosis (1st edition) Science Press, 2004

  4. Age and Osteoporotic Fractures 4,000 3,000 2,000 1,000 Men Women Hip Hip Vertebrae Incidence/100,000 person-years Vertebrae Colles' Colles' 35–39 >85 >85 Age group, year Cooper C. Epidemiology of Osteoporosis. Chapter 49:IV. Metabolic Bone Diseases. Am Soc for Bone & Min Research 2003.

  5. Osteoporosis – Some facts and figures • 1 in 2 women and 1 in 5 men aged 50 will suffer a fragility fracture in their remaining lifetime • There are 20 million people aged 50 years and over in the UK. By 2020 this will have increased to 25 million. • The lifetime risk of fracture in women at age 50 is greater than the risk of breast cancer or cardiovascular disease

  6. Annual Incidence of Osteoporotic fractures in England and Wales 180,000 Symptomatic osteoporotic fractures 70,000 Hip fractures 25,000 Vertebral fractures 41,000 Wrist fractures Estimated total cost of treating osteoporotic fractures in postmenopausal women £1.5 to 1.8 billion in 2000 £ 2.1 billion in 2010

  7. Women Men Risk of subsequent fracture after initial vertebral fracture 100 80 60 40 20 0 Cumulative incidence (%) 0 1 2 3 4 5 6 7 8 9 10 Years following vertebral fracture Melton LJ 3rd, et al. Osteoporos Int. 1999; 10(3): 214–21.

  8. Management of Osteoporosis Identifying Risk Factors for Osteoporosis • Previous fragility fracture • Corticosteroid use > 3 months • Family history, especially maternal hip fracture • Medical conditions associated with osteoporosis e.g. RA, coeliac disease, hyperparathyroidism • Premature menopause < 45 years old • Excess alcohol consumption • Low BMI (<19) • Smoking

  9. Bone density referral guidelines • REASON FOR REFERRAL: • Corticosteroid therapy – any dose for more than three months. However, patients of any age who have had a minimal trauma fracture or patients >65 treat without a scan. • Minimal trauma fracture – eg wrist, vertebra, hip, pelvis. If known vertebral fracture, please state which vertebra. • Early menopause – before 45 years, or prolonged amenorrhoea > 1 year – scan when patient reaches 50 years of age. • Other diseases or treatments associated with osteoporosis • Please specify ……………………………….. • Family History of osteoporosis in first degree relative, particularly maternal hip fracture. • Significant radiological osteopenia • Patients with proven osteoporosis who discontinue HRT and who are not on other OP treatment. Scan 12 months after stopping

  10. Prostate cancer Gonadorelin analogues Breast cancer Chemotherapy induced ‘menopause’ Tamoxifen in pre-menopausal women Aromatase inhibitors Osteoporosis and cancer treatments

  11. Osteoporosis and aromatase inhibitors • All aromatase inhibitors cause bone loss (anastrazole, letrozole and exemestane) and are associated with increased fracture risk • Bone loss is most rapid in the first 6-12 months (approx 3%) after changing from tamoxifen • Bone loss then slows eg 4-5% overall at 2 years • Consider DXA scan at time of switching from tamoxifen to aromatase inhibitor especially if other risk factors present

  12. Lumbar Spine DXA Results

  13. DXA Results

  14. Peripheral measurements Forearm DXA Heel DXA Heel ultrasound

  15. Ten year probability of fracture: age and BMD Age (yrs) T-score +1 0 -1 -2 -3 -4 50 2.4 3.8 5.9 9.2 14.1 21.3 60 3.2 5.1 8.2 13.0 20.2 30.6 70 4.3 7.1 11.5 18.3 28.4 42.3 80 4.6 7.7 12.7 20.5 31.8 46.4 Kanis et al. Osteoporosis Int 2001; 12: 989-95.

  16. Kanis JA, Johnell O, Oden A et al. Ten year probabilities of osteoporotic fractures according to BMD and diagnostic thresholds. Osteoporos Int 2001; 12:989–995.

  17. Management of OsteoporosisIdentifying Risk Factors for Falling • Medical conditions e.g. arrhythmias, postural hypotension • Failing vision • Sedative drugs • Physical environment

  18. Osteoporotic vertebral fractures

  19. Investigation of osteoporosis FBC PV Igs / electrophoresis BJP TT glutaminase Biochemical screen including calcium TFTs Testosterone levels in men ? Vitamin D levels

  20. Age-related changes in bone mass Attainment of peak bone mass Consolidation Age-related bone loss Menopause Bone mass Men Fracture threshold Women 0 10 20 30 40 50 60 Age (years) Compston JE. Clin Endocrinol 1990; 33: 653–682.

  21. Management of Osteoporosis Lifestyle Measures

  22. Antiresorptive drugs HRT Bisphosphonates etidronate alendronate risedronate ibandronate SERMs raloxifene Calcitonin Anabolic drugs PTH (teriparatide) Dual Action Bone Agents (DABAs) Strontium ranelate Treatment Options in Osteoporosis

  23. Antiresorptive drugs HRT Bisphosphonates etidronate alendronate risedronate ibandronate zoledronate SERMs raloxifene Calcitonin Anabolic drugs PTH analogues Forsteo (teriparatide) Preotact Dual Action Bone Agents (DABAs) Strontium ranelate New Treatment Options in Osteoporosis

  24. Bone remodelling cycle Pre-osteoblasts Monocytes Osteoblasts Osteoclasts Osteocytes Servier Medical Art

  25. Alendronate n=1022 Placebo n=1005 Effect of alendronate on risk of fractures RR 0.53 ( 95% Cl 0.41 – 0.68 ) 18 16 14 12 Patients with new fractures after 3 years of treatment (%) 10 8 RR 0.52 ( 95% Cl 0.31 – 0.87 ) 6 RR 0.49 ( 95% Cl 0.23 – 0.99 ) 4 2 0 Vertebral fractures (p=0.001) Wrist fractures (p=0.05) Hip fracture (p=0.05) Adapted from: Rizzoli. R: Atlas of Osteoporosis. (Second Edition). Curr Med Group 2005.

  26. Placebo Risedronate 5 mg/day Effect of risedronate on incidence of new vertebral and non-vertebral fractures RR 0.67 ( 95% Cl 0.44-1.04) RR 0.51 ( 95% Cl 0.36 – 0.73 ) 34 18 32 16 28 14 RR 0.61 ( 95% Cl 0.39 – 0.94 ) RR 0.59 ( 95% Cl 0.43 – 0.82 ) 24 12 20 10 Incidence of new non-vertebral fractures (%) Incidence of new vertebral fractures (%) 16 8 12 6 8 4 4 2 0 0 Vert-MN Years 0-3 P<0.001 Vert-NA Years 0-3 P<0.003 Vert-MN Years 0-3 NS Vert-NA Years 0-3 P=0.02 Vert-MN results adapted from Reginster, J.-Y., Minne, H.W. et al.Osteoporosis International 2000; 11.83-91.Vert-NA results adapted from Harris ST, Watts NB, Genant HK et al. JAMA 1999; 282: 1344–1352.

  27. Daily ibandronate (2.5 mg), n=982 Intermittent ibandronate (20 mg), n=982 Placebo, n=982 Effect of ibandronate on incidence of vertebral fractures 12 RR 0.50 ( 95% Cl 0.34 – 0.74) 10 RR 0.38 ( 95% Cl 0.25 – 0.59) 8 * * RR 0.44 ( 95% Cl 0.26 – 0.73 ) Fracture incidence (%) 6 RR 0.39 ( 95% Cl 0.23 – 0.67 ) * RR 0.42 ( 95% Cl 0.17 – 1.02 ) 4 † 2 0 Year 1 Year 2 Year 3 *p<0.001 versus placbo †p<0.0017 versus placbo Adapted from: Rizzoli. R: Atlas of Osteoporosis. (Second Edition). Curr Med Group 2005.Reproduced with permission from Chestnut CH 3rd, Skag A, Christiansen C; J Bone Miner Res 2004; 19;1241-1249.

  28. Strontium has a dual action FORMATION RESORPTION Strontium + Pre-OB Pre-OC REPLICATION Strontium DIFFERENTIATION OB OB OB Strontium OC + BONE FORMING ACTIVITY BONE RESORBING ACTIVITY Bone Ref 2: Marie PJ et al. Calcif Tissue Int. 2001;69:121-129.

  29. Lumbar BMD1 = +14.4 % Femoral neck BMD1 = +8.3 % over 3 years over 3 years Mean change (%) Mean change (%) 16 8 * Protelos® * * Protelos® 12 * * * * * 4 8 * * * * p<0.001 * 4 placebo 0 placebo 0 - 4 0 6 12 18 24 30 36 Time (mo) 0 6 12 18 24 30 36 Time (mo) Strontium increases bone mineral density * p<0.001 1 mean relative change from baseline versus placebo (p<0.001) Meunier P J et al. N Engl J Med. 2004; 350:459-468.

  30. 35 30 25 Protelos® 2 g/day 20 placebo 15 10 5 RR=0.59, 95%CI [0.48 ; 0.73] * p<0.001 RR=0.51, 95%CI [0.36 ; 0.74] * p<0.001 0 Strontium reduces the risk of vertebral fracture (SOTI) - 41%* Patients (%) NNT = 9 - 49%* 0-3 years First year Meunier P J et al. N Engl J Med. 2004; 350:459-468.

  31. Strontium ranelate reduces non-vertebral fracture risk (TROPOS) 19%* * p=0.031 12 10 8 % patients with OP-related major non-vertebral fractures over 3 years 95% Cl 0.66-0.98 6 4 2 0 Placebo Strontium ranelate n=2537 n=2555 1. Reginster JY, Seeman E, De Vernejoul MC, et al. J Clin Endocrinol Metab 2005; 90(5): 2816-2822. 2. Reginster JY, Hoszowski K, Roces Varela A et al. Bone 2003; 32(5): S94.

  32. Strontium ranelate reduces hip fracture in patients at higher risk (> 74 yr-old and T-score <-2.4) TROPOS 36%* n=1977 8 7 Strontium ranelate 2 g/day n=982 6 Placebo 5 n=995 Patients (%) 4 3 2 1 0 0-3 years ITT, over 3 years: RR = 0.64 95% CI 0.412; 0.997 ] *p = 0.046 1. Reginster JY, Seeman E, De Vernejoul MC, et al. J Clin Endocrinol Metab 2005; 90(5):2816-2822.

  33. NICE guidelines - Teriparatide Secondary prevention of osteoporotic fragility fractures in women aged 65 year and over who have had an unsatisfactory response to bisphosphonates and • Have an extremely low BMD (T score ≤-4) or • Have a very low BMD (T score ≤ -3) with more than 2 fractures plus 1 or more additional age –independent risk factor

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