+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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+

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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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+

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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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+

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+

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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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+

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+

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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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