The effects of chemical castration with degarelix on bone turnover

Densitometric and biomechanics bone properties of male rats

Research output: Contribution to journalArticle

Abstract

Background: Gonadotropin releasing hormone (GnRH) antagonists may cause chemical castration in males by suppressing the pituitary-gonadal axis, hence reducing testosterone level. There are limited data on the effects of degarelix, a newer series of potent and long acting GnRH antagonist on bone. Objectives: The current study aimed at determining the effects of degarelix on bone turnover, bone densitometry, and bone mechanical strength in male rats. Methods: Eighteen male Sprague-Dawley rats were randomly divided into sham (SHAM), orchidectomized (ORX), and degarelixinduced (DGX) groups. Chemical castration was performed by subcutaneous degarelix injection (2 mg/kg) at the scapular region. The rats were scanned for baseline bone mineral area (BMA), bone mineral content (BMC), and bone mineral density (BMD) using dual-energy x-ray absorptiometry (DXA). Following six weeks of experimental period, BMA, BMC, and BMD were measured again with DXA and blood was collected for testosterone and bone biomarkers (osteocalcin and C-terminal of type I collagen crosslink (CTX-1)) measurements. The rats were euthanized and femora were dissected for bone biomechanical strength analysis. Results: Bilateral orchidectomyanddegarelix administration significantly loweredserumtestosterone level, decreased wholebody BMC, femoral BMA, femoral BMC, and femoralBMD(P < 0.05) compared with theSHAMgroup. However, nosignificant changes were observed in bone biochemical markers and bone mechanical strength in all experimental groups. Conclusions: In conclusion, degarelix administration had comparable effects on bone as bilateral orchidectomy. Administration of degarelix provides an alternative method of inducing testosterone deficient-osteopenia in male rats without need for removing the testes.

Original languageEnglish
Article numbere64038
JournalInternational Journal of Endocrinology and Metabolism
Volume16
Issue number3
DOIs
Publication statusPublished - 1 Jul 2018

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Bone Remodeling
Castration
Biomechanical Phenomena
Bone and Bones
Bone Density
Minerals
Hormone Antagonists
Testosterone
Orchiectomy
Thigh
Gonadotropin-Releasing Hormone
acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide
Biomarkers
X-Rays
Densitometry
Metabolic Bone Diseases
Osteocalcin
Subcutaneous Injections
Collagen Type I
Femur

Keywords

  • Animal model
  • GnRH antagonist
  • Orchidectomy
  • Osteopenia
  • Osteoporosis

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

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title = "The effects of chemical castration with degarelix on bone turnover: Densitometric and biomechanics bone properties of male rats",
abstract = "Background: Gonadotropin releasing hormone (GnRH) antagonists may cause chemical castration in males by suppressing the pituitary-gonadal axis, hence reducing testosterone level. There are limited data on the effects of degarelix, a newer series of potent and long acting GnRH antagonist on bone. Objectives: The current study aimed at determining the effects of degarelix on bone turnover, bone densitometry, and bone mechanical strength in male rats. Methods: Eighteen male Sprague-Dawley rats were randomly divided into sham (SHAM), orchidectomized (ORX), and degarelixinduced (DGX) groups. Chemical castration was performed by subcutaneous degarelix injection (2 mg/kg) at the scapular region. The rats were scanned for baseline bone mineral area (BMA), bone mineral content (BMC), and bone mineral density (BMD) using dual-energy x-ray absorptiometry (DXA). Following six weeks of experimental period, BMA, BMC, and BMD were measured again with DXA and blood was collected for testosterone and bone biomarkers (osteocalcin and C-terminal of type I collagen crosslink (CTX-1)) measurements. The rats were euthanized and femora were dissected for bone biomechanical strength analysis. Results: Bilateral orchidectomyanddegarelix administration significantly loweredserumtestosterone level, decreased wholebody BMC, femoral BMA, femoral BMC, and femoralBMD(P < 0.05) compared with theSHAMgroup. However, nosignificant changes were observed in bone biochemical markers and bone mechanical strength in all experimental groups. Conclusions: In conclusion, degarelix administration had comparable effects on bone as bilateral orchidectomy. Administration of degarelix provides an alternative method of inducing testosterone deficient-osteopenia in male rats without need for removing the testes.",
keywords = "Animal model, GnRH antagonist, Orchidectomy, Osteopenia, Osteoporosis",
author = "Jayusman, {Putri Ayu} and {Naina Mohamed}, Isa and Shuid, {Ahmad Nazrun}",
year = "2018",
month = "7",
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doi = "10.5812/ijem.64038",
language = "English",
volume = "16",
journal = "International Journal of Endocrinology and Metabolism",
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T1 - The effects of chemical castration with degarelix on bone turnover

T2 - Densitometric and biomechanics bone properties of male rats

AU - Jayusman, Putri Ayu

AU - Naina Mohamed, Isa

AU - Shuid, Ahmad Nazrun

PY - 2018/7/1

Y1 - 2018/7/1

N2 - Background: Gonadotropin releasing hormone (GnRH) antagonists may cause chemical castration in males by suppressing the pituitary-gonadal axis, hence reducing testosterone level. There are limited data on the effects of degarelix, a newer series of potent and long acting GnRH antagonist on bone. Objectives: The current study aimed at determining the effects of degarelix on bone turnover, bone densitometry, and bone mechanical strength in male rats. Methods: Eighteen male Sprague-Dawley rats were randomly divided into sham (SHAM), orchidectomized (ORX), and degarelixinduced (DGX) groups. Chemical castration was performed by subcutaneous degarelix injection (2 mg/kg) at the scapular region. The rats were scanned for baseline bone mineral area (BMA), bone mineral content (BMC), and bone mineral density (BMD) using dual-energy x-ray absorptiometry (DXA). Following six weeks of experimental period, BMA, BMC, and BMD were measured again with DXA and blood was collected for testosterone and bone biomarkers (osteocalcin and C-terminal of type I collagen crosslink (CTX-1)) measurements. The rats were euthanized and femora were dissected for bone biomechanical strength analysis. Results: Bilateral orchidectomyanddegarelix administration significantly loweredserumtestosterone level, decreased wholebody BMC, femoral BMA, femoral BMC, and femoralBMD(P < 0.05) compared with theSHAMgroup. However, nosignificant changes were observed in bone biochemical markers and bone mechanical strength in all experimental groups. Conclusions: In conclusion, degarelix administration had comparable effects on bone as bilateral orchidectomy. Administration of degarelix provides an alternative method of inducing testosterone deficient-osteopenia in male rats without need for removing the testes.

AB - Background: Gonadotropin releasing hormone (GnRH) antagonists may cause chemical castration in males by suppressing the pituitary-gonadal axis, hence reducing testosterone level. There are limited data on the effects of degarelix, a newer series of potent and long acting GnRH antagonist on bone. Objectives: The current study aimed at determining the effects of degarelix on bone turnover, bone densitometry, and bone mechanical strength in male rats. Methods: Eighteen male Sprague-Dawley rats were randomly divided into sham (SHAM), orchidectomized (ORX), and degarelixinduced (DGX) groups. Chemical castration was performed by subcutaneous degarelix injection (2 mg/kg) at the scapular region. The rats were scanned for baseline bone mineral area (BMA), bone mineral content (BMC), and bone mineral density (BMD) using dual-energy x-ray absorptiometry (DXA). Following six weeks of experimental period, BMA, BMC, and BMD were measured again with DXA and blood was collected for testosterone and bone biomarkers (osteocalcin and C-terminal of type I collagen crosslink (CTX-1)) measurements. The rats were euthanized and femora were dissected for bone biomechanical strength analysis. Results: Bilateral orchidectomyanddegarelix administration significantly loweredserumtestosterone level, decreased wholebody BMC, femoral BMA, femoral BMC, and femoralBMD(P < 0.05) compared with theSHAMgroup. However, nosignificant changes were observed in bone biochemical markers and bone mechanical strength in all experimental groups. Conclusions: In conclusion, degarelix administration had comparable effects on bone as bilateral orchidectomy. Administration of degarelix provides an alternative method of inducing testosterone deficient-osteopenia in male rats without need for removing the testes.

KW - Animal model

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KW - Orchidectomy

KW - Osteopenia

KW - Osteoporosis

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