Seminar 22-11-2014 - Mw. Drs. N.M. Appelman-Dijkstra - Groeihormoon en het bot
-
Upload
stichting-interdisciplinaire-werkgroep-osteoporose -
Category
Healthcare
-
view
101 -
download
3
description
Transcript of Seminar 22-11-2014 - Mw. Drs. N.M. Appelman-Dijkstra - Groeihormoon en het bot
+Groeihormoon
en Bot
IWO Osteoporose dag Lage Landen 2014
Natasha Appelman-Dijkstra Internist-endocrinoloog LUMC
mw. N.A
ppelm
an-D
ijkstr
a
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
mw. N.A
ppelm
an-D
ijkstr
a
+
mw. N.A
ppelm
an-D
ijkstr
a
+Normal Bone Remodeling
Seeman E and Delmas PD. N Engl J Med 2006; 354:2250–2261
mw. N.A
ppelm
an-D
ijkstr
a
+
Growth Hormone exerts is function on bone through IGF-1
mw. N.A
ppelm
an-D
ijkstr
a
+
mw. N.A
ppelm
an-D
ijkstr
a
+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
.App
elman
-Dijk
stra
+IGF-1 as biomarker for nutritional status
mw. N.A
ppelm
an-D
ijkstr
a
+Serum IGF-1 goes up with protein intake
mw. N.A
ppelm
an-D
ijkstr
a
GH
IGF-1 IGF-1
GHR GHR
0 week 8 weeks 16 weeks Normal skeletal growth
mw. N.A
ppelm
an-D
ijkstr
a
GH
IGF-1 IGF-1
GHR GHR
GHR GHR
0 week 8 weeks 16 weeks Normal skeletal growth
Altered skeletal growth
mw. N.A
ppelm
an-D
ijkstr
a
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
mw. N.A
ppelm
an-D
ijkstr
a
+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
ppelm
an-D
ijkstr
a
+Serum IGF-1 and fracture risk
Ohlsson JBMR Vol. 26, No. 4, April 2011, pp 865–872
N=3014
mw. N.A
ppelm
an-D
ijkstr
a
+Growth hormone as a treatment for osteoporosis
mw. N.A
ppelm
an-D
ijkstr
a
+Ongoing increase of bone mass after discontinuation
mw. N.A
ppelm
an-D
ijkstr
a
+Growth hormone ideal treatment for osteoporosis?
mw. N.A
ppelm
an-D
ijkstr
a
+Growth hormone ideal treatment for osteoporosis?
NO mw. N
.App
elman
-Dijk
stra
+Abnormal growth hormone production
n Increases in growth hormone secretion
n Decreases in growth hormone secretion mw. N
.App
elman
-Dijk
stra
+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
mw. N.A
ppelm
an-D
ijkstr
a
+
mw. N.A
ppelm
an-D
ijkstr
a
+
mw. N.A
ppelm
an-D
ijkstr
a
+
Claessen KMJA et al JCEM 2013
Acromegaly
mw. N.A
ppelm
an-D
ijkstr
a
+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
mw. N.A
ppelm
an-D
ijkstr
a
+ 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.
mw. N.A
ppelm
an-D
ijkstr
a
+Effect of crossconnections on buckling strength
Horizontal Trabecula
Effective Length Buckling Strength
0 L S
1 ½ L 4xS
mw. N.A
ppelm
an-D
ijkstr
a
+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
mw. N.A
ppelm
an-D
ijkstr
a
+Growth Hormone Deficiency
n Congenital Hypopituitarism
n Acquired Hypopituitarism
n Growth hormone insensitivity
n Diabetes
mw. N.A
ppelm
an-D
ijkstr
a
+Diabetes
mw. N.A
ppelm
an-D
ijkstr
a
+ GH deficiency
mw. N.A
ppelm
an-D
ijkstr
a
+
Elbornson EJE (2012) 166 787–795
mw. N.A
ppelm
an-D
ijkstr
a
+
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)
mw. N.A
ppelm
an-D
ijkstr
a
+GH therapy and bisphosphonates
Biermasz NR JCEM 2001
mw. N.A
ppelm
an-D
ijkstr
a
+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
mw. N.A
ppelm
an-D
ijkstr
a
+
mw. N.A
ppelm
an-D
ijkstr
a
+
mw. N.A
ppelm
an-D
ijkstr
a
+
mw. N.A
ppelm
an-D
ijkstr
a
+
mw. N.A
ppelm
an-D
ijkstr
a
+
Gius$na et al. End Rev 2008; Canalis et al. NEJM 2007; Bonadonna et al. JBMR 2005; Ohlsson et al. End Rev 1998
mw. N.A
ppelm
an-D
ijkstr
a