Seminiar 30-11-2013 Longziekten en Osteoporosis

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Longziekten en Osteoporosis

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Seminiar 30-11-2013 Longziekten en Osteoporosis

  1. 1. r e . M . t u o W Osteoporosis and COPD E.F.M. Wouters Department of Respiratory Medicine Maastricht University
  2. 2. Disclosures t u o W •  Member Scientific Committee Eclipse (GSK) •  Lectures: Almirall, AstraZeneca, Chiesi, Danone, GSK, Novartis . M . r e •  Advisory board: AstraZeneca, Boehringer Ingelheim, GSK, Pfizer •  Research grants: AstraZeneca, Boehringer Ingelheim, Danone, GSK
  3. 3. Definition of COPD . M . r e t u o W Chronic obstructive pulmonary disease (COPD), a common preventable and treatable disease, is characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients Vestbo et al, Am J Respir Crit Care Med 2013
  4. 4. Background t u o W Muscle weakness Cardiovascular disease . M . COPD Depressive disorder r e Hypertension Osteoporosis Wouters EFM et al, Systemic effects in COPD. Chest 2002;121(5 Suppl):127S-30S. Barnes PJ et al, Systemic manifestations and comorbidities of COPD. ERJ 2009;33(5):1165-85.
  5. 5. 30 24.9 Frequency (%) 25 20 15 10 5 0 . M . 17.8 7.0 2.3 0 1 2 r e t u o W Number of objectively identified comorbidities 19.2 17.8 8.0 2.3 3 4 5 6 7 0.5 8 No. of comorbidities per patient Vanfleteren et al, Am J Respir Crit Care Med 2013
  6. 6. Frequency (%) 60 48 50 40 30 . M . 20 10 0 5 9 14 16 21 r e t u o W Frequencies of objectively identified comorbidities 22 23 28 31 53 54 36 Vanfleteren et al, Am J Respir Crit Care Med 2013
  7. 7. Low  body   weight   Smoking   Age   Gender   Inac7vity     Systemic   inflamma7on     Systemic   Cor7costeroids     Vitamin  D   deficiency   Rib  cage   fractures   . M . Osteoporosis   r e t u o W Pathogenesis of osteoporosis in COPD Exacerba7ons    ↑   Risk  for   fractures  ↑   Morbidity  and   Mortality  ↑   Vertebral   fractures   Decline  of  FEV1   Lehouck et al, Chest 2011
  8. 8. r e . M . t u o W Prevalence of osteoporosis in COPD
  9. 9. r e t u o W Prevalence of osteoporosis in COPD 35   30   25   20   15   10   5   0   Osteoporosis:  Tscores  –2.5   . M . no   mild   male   female   moderate   severe   Sin et al, Am J Med 2003
  10. 10. Osteoporosis in COPD t u o W Odds  ra7o   Normal     Mild  obstruc7on   Moderate  obstruc7on Severe  obstruc7on         . M .         r e          Reference    1.3    2.1    2.4   Airflow  obstruc7on,  independent  of  age,  body  mass  index  and  medica7ons  including   recent  use  of  cor7costeroids,  increased  the  risk  of  osteoporosis  in  a  severity-­‐ dependent  fashion.   Sin et al, Am J Med 2003
  11. 11. osteoporosis osteopenia 100% 41 50 Percentage of subject group 80% 5 18 13 no bone loss 32 . M . 50 60% 40% r e t u o W Osteoporosis in COPD 47 50 55 32 20% 12 0% low BMI-low FFMI n=16 norm al BMI-low FFMI n=17 norm al BMInorm al FFMI n=44 Healthy subjects n=38 Bolton C et al, AJRCCM 2004
  12. 12. . M . r e t u o W Prevalence of osteoporosis in COPD Graat-Verboom et al, ERJ 2009
  13. 13. . M . r e t u o W Prevalence of osteoporosis in COPD Graat-Verboom et al, ERJ 2009
  14. 14. r e t u o W Prevalence of osteoporosis in COPD 18   16   14   12   10   8   6   4   2   0   . M . without  COPD   n=  14,828   P<0.001   with  COPD   n=  995   Schnell et al, BMC Pulmonary Medicine 2012
  15. 15. . M . r e t u o W Prevalence of osteoporosis in COPD Miller et al, Respir Med 2013
  16. 16. Comorbidity in COPD Stage II Heart trouble 26% Heart attack 10% Stroke 4% Heart failure Arrhythmia Osteoporosis Diabetes . M . 7% 12% 13% 11% Inflamm. Bowel Dis. 6% Peptic ulcer 11% r e t u o W Stage III Stage IV p-value 25% 25% 0.992 8% 8% 0.457 3% 3% 0.327 6% 9% 0.287 12% 10% 0.721 14% 12% 0.785 9% 11% 0.118 3% 6% 0.045 11% 8% 0.206 Reflux/heartburn 31% 23% 21% <0.001 Depression requring tx. 16% 17% 15% 0.516 Agusti A et al, Respir Res 2010
  17. 17. r e t u o W Prevalence of osteoporosis in COPD DXA-scan 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% . M . GOLD I GOLD II Normal BMD Osteopenia Osteoporosis GOLD III GOLD IV Graat et al, J Bone Miner Res 2011
  18. 18. r e t u o W Definitions of 13 comorbidities Underweight: BMI < 21 kg·m-2 (Celli et al., N Engl J Med 2004) Muscle wasting: FFMI < 16 kg·m-2 for men or < 15 kg·m-2 for women (Schols et al., Am J Clin Nutr 2005) Obesity: BMI ≥ 30 kg·m-2 (WHO) Renal failure: Osteoporosis: Anemia: . M . eGFR (Cockroft and Gault) < 60 ml·min-1 (KDOQI, Am J Kidney Dis 2007) T-score < -2,5 on the local sites hip and lumbal spine or whole body (Graat-Verboom et al., J. Osteoporos 2010) Hemoglobin level <13 g·dL-1 (8,1 mmol/L) in men and <12 g·dL-1 (7,5 mmol/L) in women (WHO) Vanfleteren et al, Am J Respir Crit Care Med 2013
  19. 19. Frequency (%) 60 48 50 40 30 . M . 20 10 0 5 9 14 16 21 r e t u o W Frequencies of objectively identified comorbidities 22 23 28 31 53 54 36 Vanfleteren et al, Am J Respir Crit Care Med 2013
  20. 20. Cardiovascular Metabolic . M . Less comorbidity r e t u o W Identification of five comorbidity clusters Cachectic Psychological Vanfleteren et al, Am J Respir Crit Care Med 2013
  21. 21. r e t u o W Characteristics of comorbidity clusters ‘less comorbidity’ ‘cardiovascular’ CLUSTER 2 CLUSTER 3 CLUSTER 4 CLUSTER 5 67 49 44 33 20 2.5 ± 1.4 3.8 ± 1.7 4.2 ± 1.4 4.4 ± 1.1 4.1 ± 1.8 Renal impairment 16 24 45 9 5 Anaemia, % 9 4 2 3 5 3 98 43 100 5 30 14 0 61 15 0 0 66 3 0 12 10 98 0 20 52 14 43 91 60 42 16 25 67 40 27 37 52 0 35 5 28 26 0 84 6 23 7 6 68 56 67 12 81 53 2 11 7 13 32 Clinical characteristics n No. of comorbidiites Hypertension, % Obesity, % Underweight, % Muscle wasting, % Hyperglycaemia, % Dyslipidaemia, % Osteoporosis, % Anxiety, % Depression, % Atherosclerosis, % CLUSTER 1 . M . Myocardial infarction, % ‘cachectic’ ‘metabolic’ ‘psychologic’ Vanfleteren et al, Am J Respir Crit Care Med 2013
  22. 22. Osteoporosis in COPD . M . t u o W r e
  23. 23. r e . M . t u o W
  24. 24. . M . r e t u o W Pulmonary emphysema and osteoporosis in COPD Ohara et al, Chest 2008
  25. 25. Corticosteroids: inhaled . M . r e t u o W Risk factors for osteoporosis in COPD Vit D deficiency Systemic inflammation Emphysema
  26. 26. . M . r e t u o W Pathophysiology of glucocorticoid-induced effects on bone cells Den Uyl et al, Curr Rheumatol Rep 2011
  27. 27. . M . r e t u o W Inhaled steroids and osteoporosis Ferguson et al, Chest 2009
  28. 28. . M . r e t u o W Inhaled steroids and osteoporosis: Change in hip BMD Ferguson et al, Chest 2009
  29. 29. . M . r e t u o W Inhaled steroids and osteoporosis: spine BMD Ferguson et al, Chest 2009
  30. 30. Bone fractures in COPD t u o W Rate  of  fracture  per  1,000  treatment  years   22   . M . 21   20   19   18   17   Placebo  Group   n=1,544   r e SAL  Group   n=1,542   FP  Group   n=1,552   SFC  Group   n=1,546   Ferguson et al, Chest 2009
  31. 31. Bone fractures in COPD t u o W Probability  of  fracture  by  3  yr,  %   7   6   . M . 5   4   3   2   1   0   Placebo  Group   n=1,544   r e SAL  Group   n=1,542   FP  Group   n=1,552   SFC  Group   n=1,546   Ferguson et al, Chest 2009
  32. 32. Corticosteroids: inhaled . M . r e t u o W Risk factors for osteoporosis in COPD Vit D deficiency Systemic inflammation Emphysema
  33. 33. r e . M . t u o W Vitamin D metabolism
  34. 34. . M . r e t u o W Vitamin D synthesis pathways
  35. 35. Vit D deficiency in COPD r e t u o W 25-­‐OHD  levels  >  30  ng/ml   25-­‐OHD  levels  20  -­‐  30  ng/ml   . M . 25-­‐OHD  levels  <  20  ng/ml   Janssens et al, Thorax 2010
  36. 36. Vit D status in COPD . M . r e t u o W Romme et al, Ann Med 2013
  37. 37. . M . 25-­‐OHD  levels  <  30  ng/ml:  69  %   25-­‐OHD  levels  <  20  ng/ml:  39  %   25-­‐OHD  levels  <  10  ng/ml:  8.7  %   r e t u o W Vit D and lung function in COPD r  =  0.116   p  <  0.01   Berg et al, Respir Med 2013
  38. 38. . M . r e t u o W Vit D and lung structure in COPD r  =  0.141   p  <  0.01   Berg et al, Respir Med 2013
  39. 39. Vit D and GOLD severity <   . M . >   r e t u o W Berg et al, Respir Med 2013
  40. 40. . M . r e t u o W Risk factors for osteoporosis in COPD Graat-Verboom, Bone 2012
  41. 41. r e t u o W Bone mineral density and Vit D BMI   Age     . M . 25  (OH)D     R2=0.22   Romme et al, Ann Med 2013
  42. 42. . M . r e t u o W Vitamin D beyond bones in COPD Janssens et al, AJRCCM 2009
  43. 43. Corticosteroids: inhaled . M . r e t u o W Risk factors for osteoporosis in COPD Vit D deficiency Systemic inflammation Emphysema
  44. 44. . M . r e t u o W Pathogenesis of osteoporosis in COPD Lehouck et al, Chest 2011
  45. 45. . M . r e t u o W OPG/RANK/RANKL system in COPD with osteoporosis Zhang et al, COPD 2013
  46. 46. . M . r e t u o W OPG/RANK/RANKL system in COPD with osteoporosis Zhang et al, COPD 2013
  47. 47. . M . r e t u o W OPG/RANK/RANKL pathway in COPD with osteoporosis Bai et al, Respir Research 2011
  48. 48. . M . r e t u o W OPG/RANK/RANKL pathway in COPD with osteoporosis Bai et al, Respir Research 2011
  49. 49. . M . r e t u o W OPG/RANK/RANKL pathway in COPD with osteoporosis Bai et al, Respir Research 2011
  50. 50. Inflammatory  markers   YES   N   283   CRP,  mg/L   2.6  +  5   Fibrogen,  mg/dL   462  +  135   IL-­‐6,  pg/mL   1.4  +  2   IL-­‐8,  pg/mL   5.4  +  8.3   TNF-­‐alpha,  pg/mL   2.4  +  4   SPD,  ng/mL   117  +  89   CCL-­‐18,  ng/mL   CC-­‐16,  ng/mL   r e t u o W Inflammation data and osteoporosis in COPD NO   P-­‐value   1730   3.3  +  6   0.035   446  +  126.5   0.310   1.5  +  2   0.371   7.3  +  10.2   0.272   2.4  +  10   0.994   119  +  87   0.971   108  +  57   105  +  53   0.954   4.8  +  3.6   5.0  +  3.5   0.947   . M . Miller J et al, Respir Med 2013
  51. 51. . M . r e t u o W Biomarkers  in  COPD   Agus7  et  al,  Plos  One  2012  
  52. 52. Conclusions t u o W 1.  Osteoporosis is highly prevalent in COPD 2.  The pathogenesis of bone abnormalities in COPD is multifactorial . M . r e 3.  Growing evidence of a link between emphysema and osteoporosis: The implosive COPD phenotype?

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