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Bones of Contention – HIV and Bone Disease Dr Paddy Mallon MB BCh BAO FRACP FRCPI PhD

Bones of Contention – HIV and Bone Disease Dr Paddy Mallon MB BCh BAO FRACP FRCPI PhD School of Medicine and Medical Sciences Mater Misericordiae University Hospital University College Dublin Ireland paddy.mallon@ucd.ie. UCD School of Medicine & Medical Science. Scoil an Leighis agus

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Bones of Contention – HIV and Bone Disease Dr Paddy Mallon MB BCh BAO FRACP FRCPI PhD

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  1. Bones of Contention – HIV and Bone Disease Dr Paddy Mallon MB BCh BAO FRACP FRCPI PhD School of Medicine and Medical Sciences Mater Misericordiae University Hospital University College Dublin Ireland paddy.mallon@ucd.ie UCD School of Medicine & Medical Science Scoil an Leighis agus Eolaíocht An Leighis UCD

  2. What are the ‘bones of contention’? • Is low BMD more common in HIV? • Are fractures more common in HIV? • What’s the best measure – the ‘T’ score or the ‘Z’ score? • Is it ARV, BMI or vitamin D? • Which patients should I screen?

  3. What are the ‘bones of contention’? • Is low BMD more common in HIV? • Are fractures more common in HIV? • What’s the best measure – the ‘T’ score or the ‘Z’ score? • Is it ARV, BMI or vitamin D? • Which patients should I screen?

  4. Low BMD is common in HIV+ patients Adapted from Brown TT & Qaqish RB. AIDS 2006; 20:2165-2174

  5. Progression of BMD is common Spain. N=391. 49% osteopenic, 22% osteoporosis. Progression after 2.5 years: - 12.5% to osteopenia - 15.6% to osteoporosis Aquitaine cohort. N=255. 68% men. Age 44 yrs. All on ART. 72% osteopenic (osteoporosis excluded) Progression after 2.3 years: - 7.8% to osteopenia - 11.4% to osteoporosis Cazanave C et al. 17th CROI 2010. Abstract 747. Bonjoch A et al. 18th IAC 2010. Abstract THPDB104.

  6. What are the ‘bones of contention’? • Is low BMD more common in HIV? • Are fractures more common in HIV? • What’s the best measure – the ‘T’ score or the ‘Z’ score? • Is it ARV, BMI or vitamin D? • Which patients should I screen?

  7. Fractures are more common in HIV+ patients Healthcare Registry study 8,525 HIV-infected patients 2,208,792 non HIV-infected patients Fracture rates in women demonstrated HIV+ HIV- 7 6 Overall comparison p=0.002 5 4 Fracture prevalence in women /100 persons 3 2 1 0 40-49 70-79 50-59 60-69 30-39 Years Triant VA et al, JCEM 2008;93:3499-3504

  8. What are the ‘bones of contention’? • Is low BMD more common in HIV? • Are fractures more common in HIV? • What’s the best measure – the ‘T’ score or the ‘Z’ score? • Is it ARV, BMI or vitamin D? • Which patients should I screen?

  9. Osteoporosis / osteopenia T score = standard deviation (SD) difference from BMD of white women at peak bone density (aged 30 years)1,2 Z score = SD difference from BMD of individuals of the same age, race and gender 2 <50 yrs – Z score >50 yrs – T score 1. World Health Organ Tech Rep Ser 1994; 843:1–129 2. NIH consensus development panel on osteoporosis prevention, diagnosis and therapy. JAMA 2001; 285:785–795

  10. What are the ‘bones of contention’? • Is low BMD more common in HIV? • Are fractures more common in HIV? • What’s the best measure – the ‘T’ score or the ‘Z’ score? • Is it ARV, BMI or vitamin D? • Which patients should I screen?

  11. # * # ART initiation is associated with bone loss Greater loss in BMD with ART containing NRTI -0.2 Within group and between-group differences all P<0.05 Lumbar spine Z score -0.3 ZDV/3TC/LPV/r NVP/LPV/r -0.4 -0.5 -0.6 -0.7 -0.8 -0.9 0 3 12 24 month • Changes in BMD accompanied by increases in markers of bone turnover von Voderen M. et al. AIDS 2009; 23(11): 1367-1376

  12. ART and bone Loss -ABC/3TC vs TDF/FTC Hip Lumbar Spine 0 0 P<0.001 P=0.036 -1  -1   % change in BMD - 2 - 2 % change in BMD    - 3 - 3   - 4 - 4 48 24 0 24 48 0 week week Subjects ABC/3TC: 176 134 117 182 141 125 TDF/FTC: 180 156 138 183 165 143 ABC/3TC: -1.90% TDF/FTC: -3.55% D = -1.68 ; 95% CI (-2.26, -1.09) ABC/3TC: -1.59% TDF/FTC: -2.41% D = -0.84 ; 95% CI (-1.61, -0.06) Stellbrink HJ et al., EACS 2009

  13. ART and bone loss - ABC/3TC vs TDF/FTC ACTG A5224s Hip Lumbar Spine McComsey GA et al. CROI 2010

  14. ART and bone loss - PI vs NNRTI Hip Lumbar Spine PI/ NNRTI PI/ NRTI NNRTI/ NRTI PI/ NNRTI PI/ NRTI NNRTI/ NRTI PI: LPV/r (40-74%) NNRTI: EFV (55-60%) NRTIs: AZT/3TC (85%) IDV/r (25-47%)NVP (37-45%) Duvivier, et al., AIDS 2009; 27:817-24

  15. ART and bone loss - PI vs NNRTI ACTG A5224s Hip Lumbar Spine McComsey GA et al. CROI 2010

  16. Body Mass Index and BMD…. • Consistently associated with low BMD in HIV1-7 • In one meta-analysis, low BMI explained much of the difference in BMD between HIV+ and HIV- 8 • Association between weight loss and BMD loss observed in HIV- male populations9 • Usually associated with negative health implications • Lower BMI in HIV+ patients associated with greater loss of BMD in prospective studies10 • Low BMI does not explain loss of BMD with ARV initiation 1. Mondy K, et al. CID 2003; 36:482–490 2. Fausto A et al.Bone 2006;38:893-7 3. Carr A et al. AIDS 2001;15:703-9 4. Nolan D et al. AIDS 2001;15:1275-80 5. Arnsten JH et al. AIDS 2007;21:617-23 6. Arnsten JH et al. CID 2006;42:1014-20 7. Dolan SE et al. JCEM 2006;91:2938-45 8. Bolland MJ et al. JCEM 2007;92:4522-8. 9. Shen Y et al. J Bone Mineral Res 2009;24:1290-1298. 10. Bonjoch A et al. 18th IAC 2010. Abstract THPDB104.

  17. Vitamin D….. • High prevalence of low vitamin D in HIV+ patients1-3 • High prevalence of low vitamin D in general population4 • Associations with EFV exposure and low 25-OH vitamin D (but not 1,25-OH vitamin D)2,5 • N=33. PHI. 45% osteopenia, 6% osteoporosis but none had vitamin D deficiency (25-OH and 1,25-OH)6 • Seasonal variation important4 • EFV use not associated with accelerated bone loss7 • High bone turnover state in HIV+ patients8 1. Jacobson D, et al. JAIDS 2008; 49:298–308, 2. Dao, CN et al, CROI 2010 #750. 3. 2. Fux et al. CROI 2010t #749. 4. Stephensen CB, et al. Am J Clin Nutr 2006; 83:1135–41. 5. Muller N. et al. CROI 2010 #752. 6. Grijsen ML et al. AIDS 2010;24 7. McComsey GA et al. CROI 2010. 8. Stellbrink HJ et al., EACS 2009

  18. Biomarkers and ART initiation… 97% 100 92% 81% 80% 75% 80 72% 60 ABC/3TC Unadjusted % change from baseline 44% 44% TDF/FTC 40 20 0 P1NP Osteocalcin BSAP CTX N= 114 134 112 130 114 134 113 134 In a multivariate analysis, differences between arms were statistically significant for P1NP, Osteocalcin and BSAP Stellbrink HJ et al., EACS 2009

  19. What are the ‘bones of contention’? • Is low BMD more common in HIV? • Are fractures more common in HIV? • What’s the best measure – the ‘T’ score or the ‘Z’ score? • Is it ARV, BMI or vitamin D? • Which patients should I screen?

  20. Who should be screened? EVERYBODY! >40 years old use FRAX (www.shef.ac.uk/FRAX) Or Consider DXA if ≥ 1 of following: History of low-impact fractures High falls risk Post-menopausal women Men >50 yrs Hypogonadism Steroid Exposure http://www.europeanaidsclinicalsociety.org/guidelines.asp

  21. BMD and the ‘Double Edged Sword’ ‘Main Entry: double–edged sword Function: noun Date: 15th century : something that has or can have both favorable and unfavorable consequences’

  22. Patient age in Brighton cohort: 1996-2009 HIV+ patients are getting older Personal communication, M. Fisher

  23. HIV+ patients are getting older Most of the age increase is in the 50-60 age group Patient age in Brighton cohort: 1996-2009 The increase in the over 50s is greater than the overall cohort Personal communication, M. Fisher

  24. Acknowledgements Grants / research support: Science Foundation Ireland, Molecular Medicine Ireland, European Union (NEAT), Irish Lung Foundation, Mater College, GlaxoSmithKline, Pfizer Speaker Bureau / Honoraria: GlaxoSmithKline, ViiV Healthcare, Merck, Gilead, Abbott, Tibotec, BMS

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