seminar 22-11-2014 - mw. drs. n.m. appelman-dijkstra - groeihormoon en het bot
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Groeihormoon en het botTRANSCRIPT
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+Groeihormoon
en Bot
IWO Osteoporose dag Lage Landen 2014
Natasha Appelman-Dijkstra Internist-endocrinoloog LUMC
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Femur
Trabecular bone Cortical bone
Periosteum
Vertebrae: ≥75% trabecular bone
Cor$cal and trabecular bone
Aangepast van Dempster DW. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 6th ed. 2006:7-11.
Long bones: >75% cortical bone
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+Normal Bone Remodeling
Seeman E and Delmas PD. N Engl J Med 2006; 354:2250–2261
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Growth Hormone exerts is function on bone through IGF-1
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+Normal physiology of growth hormone
n Growth hormone increases in childhood
n After puberty a gradual decline
n Further decline of IGF-1 in aging
IGF
-1 le
vel
Age mw. N
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+IGF-1 as biomarker for nutritional status
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+Serum IGF-1 goes up with protein intake
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GH
IGF-1 IGF-1
GHR GHR
0 week 8 weeks 16 weeks Normal skeletal growth
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GH
IGF-1 IGF-1
GHR GHR
GHR GHR
0 week 8 weeks 16 weeks Normal skeletal growth
Altered skeletal growth
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GH
IGF-1 IGF-1
GHR GHR
GHR GHR
GH
IGF-1
GHR GHR
0 week 8 weeks 16 weeks Normal skeletal growth
Catch-up skeletal growth
Altered skeletal growth
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+IGF-1 is related to bone and muscle mass
n In men IGF-1 is positivly related to BMD
n In women IGF-1 is positivly related to BMC
n In elderly women a low IGF-1 is associated with a greater bone loss at the Femoral Neck
n However serum IGF-1 is not related with osteoporosis mw. N.A
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+Serum IGF-1 and fracture risk
Ohlsson JBMR Vol. 26, No. 4, April 2011, pp 865–872
N=3014
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+Growth hormone as a treatment for osteoporosis
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+Ongoing increase of bone mass after discontinuation
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+Growth hormone ideal treatment for osteoporosis?
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+Growth hormone ideal treatment for osteoporosis?
NO mw. N
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+Abnormal growth hormone production
n Increases in growth hormone secretion
n Decreases in growth hormone secretion mw. N
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+High IGF-1
n Cortical bone proliferation: increased bone volume produced per time unit
n Longer and bigger bones
n Puberty: fast skeletal growth
n Acromegaly
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+
Claessen KMJA et al JCEM 2013
Acromegaly
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+Acromegaly
High baseline VF prevalence of 63% Mean VF number per pa$ent 2.3±1.4 Wedge type
Claessen KMJA et al JCEM 2013
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+ Resorp$on Cavi$es are Mechanical Stress Concentrators
The deeper resorption cavities in postmenopausal bone act to concentrate mechanical stress. Bone will tend to fracture at such sites, as will the cane at right.
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+Effect of crossconnections on buckling strength
Horizontal Trabecula
Effective Length Buckling Strength
0 L S
1 ½ L 4xS
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+Acromegaly
n Ac8ve acromegaly:
n Cor$cal bone prolifera$on: increased bone volume produced per $me unit
n Loss of architecture: decreased mechanical loading strength, despite trabecle thickening
n Normal BMD, but diminished bone strength à high fracture risk, since vertebrae consist mostly of trabecular bone
n A<er disease cure:
n Sustained trabecular widening, decrease in cor$cal bone
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+Growth Hormone Deficiency
n Congenital Hypopituitarism
n Acquired Hypopituitarism
n Growth hormone insensitivity
n Diabetes
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+Diabetes
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+ GH deficiency
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Elbornson EJE (2012) 166 787–795
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+
Lumbar (L1-L4) spine BMD
Baseline 5yr 10yr 15yr0.8
0.9
1.0
1.1
1.2MalesFemales
**
*
BM
D L
WK
(g/c
m2)
GHD therapy
Appelman-Dijkstra NM, Clin Endo 2014
Lumbar (L1-L4) spine BMD - Males
Baseline 5yr 10yr 15yr0.6
0.8
1.0
1.2
1.4* *
*
*
* *BM
D L
WK
(g/
cm2)
Left femoral neck BMD - Males
Baseline 5yr 10yr 15yr0.0
0.5
1.0
1.5No bisphosphonate useBisphosphonate use
BM
D L
eft
fem
oral
nec
k (g
/cm
2)
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+GH therapy and bisphosphonates
Biermasz NR JCEM 2001
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+Conclusion
n IGF-1/GH is an important regulator for bone remodeling
n Abnormalities in Gh production are associated with a decrease in bone quality and an increase in fracture risk
n GH replacement therapy has a biphasic effect on bone turnover. Although associated with inreases in bone mass , its effect on fracture risk has not been fully investigated
n The use of GH for the treatment of osteoporosis has been superseded by the use of more bone specific anabolic agensts such as recombinant PTH and antisclerostin antibodies
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+
Gius$na et al. End Rev 2008; Canalis et al. NEJM 2007; Bonadonna et al. JBMR 2005; Ohlsson et al. End Rev 1998
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