Waarde van botmarkers in de dagelijkse praktijk

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Waarde van botmarkers in de dagelijkse praktijk, presentatie van Mw. Dr. E. v.d. Veer op 23/24 november 2012 voor de Stichting IWO.

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Waarde van botmarkers in de dagelijkse praktijk

  1. 1. Botmarkers (BTM) in de dagelijkse praktijkUniversitair Medisch CentrumGroningenDr. E. van der Veer UMCGMaastricht, 23 en 24 november 2012
  2. 2.   Bone volume  Materials properties   Mineralization (adverse effects of fluoride)   Organic matrix composition (mutations in type I collagen gene)  Structure Micro-compression of Bone   Size and shape   Internal architecture   Turnover   Damage accumulation (microcracks)   Connectivity Ralph Müller
  3. 3. PINP BALP CTx Osteocalcine Seeman et al. NEJM 2006UMCG
  4. 4. Naylor K, Eastell R. Bone Turnover Markers: use in osteoporosis. Nat Rev Rheumatol. 2012 Jun 5;8(7):379-389•  BTMs are useful for the management of patients with osteoporosis, –  for initial clinical assessment –  for guiding and monitoring of treatment.
  5. 5. Alendronate 70 mg OW Risedronate 35 mg OW 0 0 –20 –20 Mean change (%) p<0.001 –40 –40% –40 p<0.001 p<0.001 –53% –55% –60 p<0.001 –60 p<0.001 p<0.001 –74% –80 –80 Treatment difference 13% Treatment difference 19% –100 –100 Baseline 3 6 12 months Baseline 3 6 12 monthsAlendronate n = 442 429 414 365 449 443 423 382Risedronate n = 457 449 426 375 459 455 433 387 Urine NTx Serum CTx UMCG
  6. 6. BMD (DXA) wordt uitgedrukt in T-score of Z-score. Maat voor de hoeveelheid botmassaBMD T-Score 3 2 1 0 -1 T-score = -2.5 -2 +1 SD -3 Z-score = -1 0 -1 SD 20 30 40 50 60 70 80 90 Leeftijd (jaren)
  7. 7. Lower half of Upper half of reference interval reference interval Osteoporosis; untreated Osteoporosis; risedronate 0 11 62 27% 7 63 28 2% 80 40 70 Number of patientsNumber of patients 60 30 50 40 20 30 20 10 10 0 0 10 32 100 10 32 100 NTX/Cr (nmol/mmol creatinine) NTX/Cr (nmol/mmol creatinine) UMCG Eastell JBMR 2005
  8. 8. Placebo Calcium + vitamin D Risedronate 5 mg u CTx T-score u NTx T-score 1.  The baseline level of bone resorption is related to subsequent fracture risk, 2.  The reduction in bone resorption explains, in part, the reduction in the risk of fractures with risedronate,UMCG
  9. 9. Eastell R , Barton I , Hannon RA , Chines A , Garnero P , Delmas PD Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate. J Bone Miner Res 2003; 18: 1051– 1056. Eastell R, Hannon RA, Garnero P, Campbell MJ, Delmas PD Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate. Review of statistical analysis.UMCG J Bone Miner Res 2007; 22: 1656– 1660.
  10. 10. CTx T-score <-1.7 -1 0 +1 +2 >+2.4 35 30 25 20 % fractures 15 10 5 0 1 2 3 4 5 6 7 8 9 10 66 patients in each groupe UMCG
  11. 11. BTMs in fracture riskprediction  In the context of fracture risk for groups:The appropiate risk is that of the group above a specified limit compared to the risk of the generalpopulatione.g. Q4/Q1-4In the context of fracture risk assessment for an individual:The most appropiate relative risk (assuming a normal distribution) is the risk of the individualcompared with the risk in the normal population
  12. 12. Rheumatology & Clinical Immunology BTM Healthy reference cohort "   OC: osteocalcin "   PINP: product of collagen formation "   BALP: necessary for start of mineralization "   sCTX: product of collagen degradationUMCG sCTX in males and females of a healthy reference cohort (n=550) "  Z-scores "   (BTM value of individual patient – mean BTM value of the matched 10-year-cohort of reference group) / SD of matched reference cohort
  13. 13. Bisphosphonate calcium & vitamin DUMCG
  14. 14. Follow-up in Z-scores % change after start bisphosphonate LSC LSC = least significant changeUMCG
  15. 15. ???UMCG
  16. 16. UMCG
  17. 17. UMCG
  18. 18. Osteoporose25OHvitD en Botmarkers metenStart behandeling3 – 6 mnd botmarkers herhalen Daling tot onder gemiddelde waarde gezonde vrouwen, 25OHvitD en botmarkers jaarlijks metenGeen goede daling, Na 5 jaar evaluatie behandeling compliantie navragen evt dosering aanpassen? ander geneesmiddel overwegen? Behandeling stoppen Behandeling voortzetten UMCG Botmarkers meten Botmarkers jaarlijks meten
  19. 19. Ca+D # # # 6* p<0.05 from baselineUMCG # p<0.05 from placebo Watts et al, OI, 2007
  20. 20. Ca+D # # # #* p<0.05 from baselineUMCG # p<0.05 from placebo Watts et al, OI, 2007
  21. 21. AlendronateUrine NTxMean Percentage Change Bone NEJM 2004UMCG
  22. 22. AlendronateBALPMean PercentageChange Bone NEJM 2004UMCG
  23. 23. Naylor K, Eastell R. Bone turnover markers: use in osteoporosis. Nat Rev Rheumatol. 2012 Jun 5;8(7):379-389•  BTMs are useful for the management of patients with osteoporosis, –  for initial clinical assessment –  for guiding and monitoring of treatment.•  BTM levels respond rapidly to both anabolic and antiresorptive treatments
  24. 24. BTMs in monitoring of osteoporosis treatment Vasikaran 2011
  25. 25. BTMs in monitoring of osteoporosis treatment
  26. 26. Naylor K, Eastell R. Bone turnover markers: use in osteoporosis. Nat Rev Rheumatol. 2012 Jun 5;8(7):379-389•  BTMs are useful for the management of patients with osteoporosis, –  for initial clinical assessment –  for guiding and monitoring of treatment.•  BTM levels respond rapidly to both anabolic and antiresorptive treatments•  BTMs  are  also  poten.ally  useful  as  surrogate  biomarkers  for  fracture.    
  27. 27. CTx T-score <-1.7 -1 0 +1 +2 >+2.4 35 30 25 20 % fractures 15 10 5 0 1 2 3 4 5 6 7 8 9 10 66 patients in each groupe UMCG
  28. 28. BTMs in fracture riskprediction   uCTX T-score > 2.0 SD BMD T-score < -2.5 SD
  29. 29. Naylor K, Eastell R. Bone turnover markers: use in osteoporosis. Nat Rev Rheumatol. 2012 Jun 5;8(7):379-389•  BTMs are useful for the management of patients with osteoporosis, –  for initial clinical assessment –  for guiding and monitoring of treatment.•  BTM levels respond rapidly to both anabolic and antiresorptive treatments•  BTMs are also potentially useful as surrogate biomarkers for fracture.•  BTMs can indentify patients with high bone turnover and rapid bone loss –  to determine possible causes of secondary osteoporosis
  30. 30. BTM in secondary osteoporosis  Disease Specific BTM findingsPrimary Hyperparathyroidism increased BTM (depend disease severity)Thyroid diseaseDiabetesPaget disease of bone high BTMMyeloma high BTMRheum Arthritis increased BTM (depend disease severity)Bechterew disease increased BTM (depend disease severity) Malabsorption vit D and Ca2+ , increasedCrohns disease BTMChronic Kidney disease impaired renal function, increased BTM
  31. 31. Rheumatology & Clinical Immunology Ankylosing Spondylitis "   Increased bone formation "   Syndesmophytes "   Joint ankylosis NORMAL "   Increased bone resorptionUMCG "   Osteoporosis "   Vertebral fractures OSTEOPOROSIS
  32. 32. Rheumatology & Clinical Immunology Ankylosing Spondylitis "   AS "   bone formation "   bone resorption "   Detection of osteoporosis is difficult in patients with advanced AS "   overestimation of lumbar spine BMD by the presence of syndesmophytes, ligamentUMCG calcifications, and fusion of facet joints
  33. 33. Naylor K, Eastell R. Bone turnover markers: use in osteoporosis. Nat Rev Rheumatol. 2012 Jun 5;8(7):379-389•  BTMs are useful for the management of patients with osteoporosis, –  for initial clinical assessment –  for guiding and monitoring of treatment.•  BTM levels respond rapidly to both anabolic and antiresorptive treatments•  BTMs are also potentially useful as surrogate biomarkers for fracture.•  BTMs can indentify patients with high bone turnover and rapid bone loss –  to determine possible causes of secondary osteoporosis•  BTM changes can also be used for understanding the mechanism of action of drugs in development and identifying the correct dose.•  Appropriate reference intervals should be used for the optimum interpretation of results.

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