Beschermt overgewicht tegen fracturen?, Presentatie van prof.dr J.C Netelenbos op 3 oktober 2012 voor de Stichting IWO.

1. Beschermt overgewicht tegen
fracturen?
IWO 3 Oktober 2012 te Utrecht
em.prof.dr J.C Netelenbos VUmc

2. Conflict of Interest
I receive research grants, speaker’s and/or consulting fees
from the following companies:
• Achmea
• Amgen
• E. Lilly
• GSK
• Novartis
• Nycomed
• Roche Diagnostics
• Sanofi-Aventis
• Will Farma
•
J. Coen Netelenbos, MD

3. ITEMS
- Obesitas, fracturen en gevolgen 4 slides
- BMD en DXA meting bij obesitas 5 slides
- Botstructuur en vetweefsel 2 slides
- Effect vetzucht op botombouw 3 slides
- Spier en vet 1 slide
- Rol voor vitamine D? 3 slides
- Geeft afvallen botverlies? 2 slides
- Conclusies 1slide

4. More ankle and upper leg fractures and less hip,
spine, wrist and rib fractures in obese older women
Obese women with fracture differed from non-obese by:
• early menopause
• 2 or more falls past 2 years
• use of arms to assist standing from sitting position
They also experienced more astma, emphysema, and diabetes
Compston JE et al . AJM 2011;124:1043-1050 (GLOW study)

5. Obesity and fracture
Upper leg
Modified after Shapses SA et al Annu Rev Nutr 2012;32:287-309
• Mechanical instability ?
• Site-specific bone loss ?

6. Older diabetic women have especially fractures at
humerus, femur and distal lower leg
Representative HRpQCT of tibia in diabetic woman with
fracture showing major cortical porosity
Patsch JM et al. J Bone Miner Res. 2012 Sep 18 [Epub ahead of print]

7. Lower percentage of obese women who were on
treatment with Anti Osteoporosis Medication
before and after fracture
Compston JE et al (GLOW study)

8. Vetzucht: BMD en DXA meting

9. Total body fat most consistent predictor of BMD is
in cross-sectional study in normal postmenopausal
women in 1992
Reid IR et al. J Clin Endocrinol Metab. 1992 Jul;75(1):45-51.

10. Most consistent predictor of BMD still is total body
fat after 10 years of follow up
Wu Fet al. Clin Endocrinol (Oxf). 2002 Jun;56(6):703-11

11. Obesity increases precision errors in DXA
Percentage coefficient of variation (CV) of two duplicate DXA
scans with repositioning in 100 women
BMI<25 BMI 25-30 BMI>30
(n=48) (n=26) (n=26)
LS BMD 0.99 1,30 1,68*
FN BMD 1,32 1,37 2,00*
Total Hip BMD 0,85 0,88 1,06
Total Body BMD 0,66 0,73 0,91*
Caution with serial measurements in obesity
Knapp KM et al. J Clin Densitometry 2012;(Sept)315-319

12. Simulated Increases in Body Fat and Errors in Bone
Mineral Density Measurements by DXA and QCT
YU EW et al. JBMR 2012;27:119–124

13. In obesity greater measurement error of
lumbar spine DXA leading to overestimation
• excess abdominal fat,
• greater risk op spinal osteoarthritis and
osteophytes
• addditional concern about difficulty of positioning
when measuring TBBMD

14. Botstructuur en vetweefsel

15. HR-pQCT of distal radius in two obese 34-yrs old men both with
BMI of 32kg/m2,with high (A) and low (B) visceral fat
Subject A with lower trabecular and cortical density and area and also lower cortical
thickness and impaired mechanical properties (decreased stiffness and failure load)
By secretion of inflammatory cytokines as TNFα, IL-1 and IL-6 stimulating osteoclasts.
Bredella MA et al. J Clin Endocrinol Metab, November 2012, 97(11):0000–0000

16. Lifetime changes in marrow fat content and lumbar spine
BMD for male subjects
in vivo proton (1H) MR spectroscopy of L3
BMD
Males
BMD
marrow fat
Females
Griffith JF et al . J Magn Reson Imaging. 2012 Jul;36(1):225-30

17. Effect vetzucht op botombouw

18. Effect vetzucht op botombouw
• Cytokinen uit vetcel met direct effect op botcellen
m.n. viscerale vetcel: inflammatie cytokinen als TNFα, IL-1, IL-6, resistin
verhogen botresorptie of remmen botvorming
• Adipokines uit vetcel leptine, adiponectine die via
hypothalamus en sympaticus effect hebben op
botcellen:remmen osteoblast en stimuleren osteoclast differentiatie
• Paracriene en endocriene regulatie in beenmerg
differentiatie mesenchymale stamcel in adipocyt of osteoblast o.a. PPARγ, E2,IGF-1

19. Schematic model of bone–fat connections
Kawai M et al. J Intern Med. 2012 Oct;272(4):317-29

20. Schematic model of bone–fat connections
Aging
Lower E2
Elevated aromatase
Less response to IGF1
Kawai M et al. J Intern Med. 2012 Oct;272(4):317-29

21. Irisin: A new potential hormonal target for the
treatment of obesity The myocyte-adipocyte
connection
Kelly DP. Science 2012;336:42-43; Boström P et al. Nature. 2012 Jan 11;481(7382):463-8

22. Rol vitamine D?

23. Vitamine D spiegels van deelnemers aan de
Hoorn studie (538 mannen en vrouwen 60-87
jaar) zijn lager bij toename lichaamsvet
RM van Dam et al. Am J Clin Nutr 2007;85:755–61

24. Adjusted relationship between 25(OH)D and
probabilities of metabolic syndrome at 5 years in
Australian cohort (AusDiab)
Contribution of 25(OH)D explained
about 1% of the variance of risk
metabolic syndrome
Cagnon C et al. JCEM 2012;97:1953-1961

25. Calcium and vitamin D supplementation is associated
with decreased visceral adipose tissue (VAT) in
overweight and obese (2 RCT)
During 16 weeks:
3x240 ml glass daily:
Orange Juice (OJ)
Regular or Light
with or without
350mgCa+100 IUvitD
Rosenblum JL et al. Am J Clin Nutr. 2012 Jan;95(1):101-8

26. Geeft afvallen botverlies?

27. Weight Loss in Obese Older Adults Increases
Serum CTX and Decreases Hip BMD
Both Are Prevented by Exercise Training
Armamento-Villareal R et al.J Bone Miner Res.2011 Dec;26(12):2851-9 2012

28. A Losing Battle:
Weight regain does not
restore weight loss-
induced bone loss in 0- 6 months
postmenopausal
women
6- 18 months
Villalon KL et al. Obesity (Silver Spring). 2011 Dec;19(12):2345-50

29. Conclusie

30. Lifestyle-paradox: Vetzucht is risicofactor voor
fractuur bij kind maar werkt beschermend tegen
fractuur bij volwassene, maar niet bij ouderen
Dimitri P et al. Bone. 2012 Feb;50(2):457-66

31. Dank voor uw
aandacht
Vragen?

32. Reserve dia’s

33. Diabetes and Fractures

34. Insuline regulates skeletal homeostasis
OPG
RANKL
Bone resorption
Modified JCN
Kawai M et al. J Intern Med. 2012 Oct;272(4):317-29

35. Adjusted RRs for fracture among older women with
diabetes, stratified by insulin use, compared with
nondiabetic women (SOF study)
Schwartz AV et al. Diabetes Care. 2002 Oct;25(10):1749-54

36. Cortical porosit and
pathophysiology of fragility in
type 2 diabetes

37. Changes in anthropometric measurements, bone mineral density and
HbA1c in new diagnosed type 2 diabetes of postmenopausal women
• Bone markers did not change
• Lower adiponectin did not change and was inversely correlated with BMD
Miazgwoski T et al. Diab.Med 2012;29:62-69

38. Review effect vitamin D supplementation on HbA1c, a
marker of longer-term glycaemic control: no change in
patients with impaired glucose tolerance or type 2 diabetes
P. S. George et al. Diabet Med. 2012 Aug;29(8):e142-50

39. Risk of fracture after bariatric surgery: population
based, retrospective cohort study (UK)
Lalmohamed A et al. BMJ. 2012 Aug 3;345:e5085. doi: 10.1136/bmj.e5085.