Beschermt overgewicht tegen fracturen?

em.prof.dr J.C Netelenbos VUmc

IWO 3 Oktober 2012 te Utrecht

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

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

More ankle and upper leg fractures and less hip,

spine, wrist and rib fractures in obese older women

Compston JE et al . AJM 2011;124:1043-1050 (GLOW study)

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

Obesity and fracture

Modified after Shapses SA et al Annu Rev Nutr 2012;32:287-309

Upper leg

•  Mechanical instability ? •  Site-specific bone loss ?

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]

Lower percentage of obese women who were on treatment with Anti Osteoporosis Medication

before and after fracture

Compston JE et al (GLOW study)

Vetzucht: BMD en DXA meting

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.

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

Obesity increases precision errors in DXA

BMI<25 (n=48)

BMI 25-30 (n=26)

BMI>30 (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*

Percentage coefficient of variation (CV) of two duplicate DXA scans with repositioning in 100 women

Caution with serial measurements in obesity

Knapp KM et al. J Clin Densitometry 2012;(Sept)315-319

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

In obesity greater measurement error of lumbar spine DXA leading to overestimation

•  addditional concern about difficulty of positioning when measuring TBBMD

•  excess abdominal fat, •  greater risk op spinal osteoarthritis and

osteophytes

Botstructuur en vetweefsel

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

Bredella MA et al. J Clin Endocrinol Metab, November 2012, 97(11):0000–0000

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.

Lifetime changes in marrow fat content and lumbar spine

BMD for male subjects

Griffith JF et al . J Magn Reson Imaging. 2012 Jul;36(1):225-30

in vivo proton (1H) MR spectroscopy of L3

Males

Females

BMD

marrow fat

BMD

Effect vetzucht op botombouw

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

Schematic model of bone–fat connections

Kawai M et al. J Intern Med. 2012 Oct;272(4):317-29

Schematic model of bone–fat connections

Kawai M et al. J Intern Med. 2012 Oct;272(4):317-29

Aging Lower E2 Elevated aromatase Less response to IGF1

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

Rol vitamine D?

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

Adjusted relationship between 25(OH)D and probabilities of metabolic syndrome at 5 years in

Australian cohort (AusDiab)

Cagnon C et al. JCEM 2012;97:1953-1961

Contribution of 25(OH)D explained about 1% of the variance of risk metabolic syndrome

Calcium and vitamin D supplementation is associated with decreased visceral adipose tissue (VAT) in

overweight and obese (2 RCT)

Rosenblum JL et al. Am J Clin Nutr. 2012 Jan;95(1):101-8

During 16 weeks: 3x240 ml glass daily: Orange Juice (OJ) Regular or Light with or without 350mgCa+100 IUvitD

Geeft afvallen botverlies?

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

A Losing Battle: Weight regain does not

restore weight loss-induced bone loss in

postmenopausal women

Villalon KL et al. Obesity (Silver Spring). 2011 Dec;19(12):2345-50

6- 18 months

0- 6 months

Conclusie

Dimitri P et al. Bone. 2012 Feb;50(2):457-66

Lifestyle-paradox: Vetzucht is risicofactor voor fractuur bij kind maar werkt beschermend tegen

fractuur bij volwassene, maar niet bij ouderen

Dank voor uw aandacht

Vragen?

Reserve dia’s

Diabetes and Fractures

Insuline regulates skeletal homeostasis

Kawai M et al. J Intern Med. 2012 Oct;272(4):317-29

OPG

RANKL

Bone resorption

Modified JCN

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

Cortical porosit and pathophysiology of fragility in

type 2 diabetes

Changes in anthropometric measurements, bone mineral density and HbA1c in new diagnosed type 2 diabetes of postmenopausal women

Miazgwoski T et al. Diab.Med 2012;29:62-69

•  Bone markers did not change •  Lower adiponectin did not change and was inversely correlated with BMD

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

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.