Sex steroids during bone growth: a comparative study between mouse models for hypogonadal and senile osteoporosis.
CONCLUSIONS
In this study, the role of disturbed bone mineral acquisition during puberty in the pathogenesis of osteoporosis was studied. To this end, a mouse model for senile and hypogonadal osteoporosis was used. Longitudinal follow-up showed that bone fragility in both models results from deficient bone build-up during early puberty.


BACKGROUND
Male osteoporosis may result from impaired bone growth. This study characterizes the mechanisms of deficient peak bone mass acquisition in models for senile (SAMP6) and hypogonadal (orchidectomized SAMR1) osteoporosis.


METHODS
Bone mineral acquisition was investigated longitudinally in SAMP6 and orchidectomized SAMR1 mice (eight to ten animals per group) using peripheral quantitative computed tomography and histomorphometry. Additionally, the effects of long-term 5alpha-dihydrotestosterone (DHT) and 17beta-estradiol (E2) replacement were studied. Statistical analysis was performed using ANOVA and Student's t test.


RESULTS
SAMP6 mice showed an early (4 weeks) medullary expansion of the cortex due to impaired endocortical bone formation (-43%). Despite compensatory periosteal bone formation (+47%), cortical thickness was severely reduced in 20-week-old SAMP6 versus SAMR1. Orchidectomy reduced periosteal apposition between 4 and 8 weeks of age and resulted in high bone turnover and less trabecular bone gain in SAMP6 and SAMR1. DHT and E2 stimulated periosteal expansion and trabecular bone in orchidectomized SAMP6 and SAMR1. E2 stimulated endocortical apposition in SAMP6. Moreover, sex steroid action occurred between 4 and 8 weeks of age.


CONCLUSIONS
Bone fragility in both models resulted from deficient bone build-up during early puberty. DHT and E2 improved bone mass acquisition in orchidectomized animals, suggesting a role for AR and ER in male skeletal development.
Ophoff
J
J
Bone Research Unit, Laboratory for Experimental Medicine and Endocrinology, Department of Experimental Medicine, Katholieke Universiteit Leuven, Herestraat 49, 3000, Leuven, Belgium. Jill.Ophoff@med.kuleuven.be
Venken
K
K
Callewaert
F
F
Boonen
S
S
Bouillon
R
R
Vanderschueren
D
D
D015502:Absorptiometry, Photon / Q000379:methods; D000375:Aging / Q000502:physiology; D000596:Amino Acids / Q000652:urine; D000818:Animals; D001846:Bone Development / Q000502:physiology*; D013196:Dihydrotestosterone / Q000627:therapeutic use; D004195:Disease Models, Animal; D004958:Estradiol / Q000627:therapeutic use; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D020249:Hormone Replacement Therapy / Q000379:methods; D007006:Hypogonadism / Q000150:complications* / Q000503:physiopathology; D008297:Male; D051379:Mice; D009919:Orchiectomy; D015675:Osteocalcin / Q000097:blood; D010024:Osteoporosis / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D010641:Phenotype; D014057:Tomography, X-Ray Computed / Q000379:methods
D000596:Amino Acids; D012739:Gonadal Steroid Hormones; D013196:Dihydrotestosterone; D015675:Osteocalcin; D004958:Estradiol; C036020:deoxypyridinoline