Sex steroids during bone growth: a comparative study between mouse models for hypogonadal and senile osteoporosis

Ophoff, Jill; Venken, Katrien; Callewaert, Filip; Boonen, Steven; Bouillon, Roger; Vanderschueren, Dirk

doi:10.1007/s00198-009-0851-z

Cited by 10 publications

(5 citation statements)

References 37 publications

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“…According to previous studies, the bone mass of the laboratory mice with a life-span of 2-3years, reaches its maximum between 4 to 8 months, after which the bone mass decreases with time [19,20]. We purchased 2, 5, 7 and 10 months old C57BL/6 female mice (n = 6) and measured their bone mineral density (BMD) by micro computed tomography (µCT).…”

Section: Mouse Models Of Senile Osteoporosismentioning

confidence: 99%

Lithium chloride enhances osteoblast differentiation and resists senile osteoporosis

Bao

Tang

et al. 2020

Preprint

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Background Lithium chloride (LiCl) is commonly used in the clinic for the treatment of bipolar and other mental disorders. LiCl is an inhibitor of GSK-3β, and has been reported to modulate the balance of adipogenesis and osteogenesis. But, whether LiCl impacts bone formation and homeostasis in senile osteoporosis is still unclear. Methods Analysis of tibia in 2, 5, 7 and 10 months old C57BL/6 male mice were performed by MicroCT (μCT). 7 months old wild-type mice were treated with LiCl orally 0, 100 or 200 mg/kg for 3 months and then tested by μCT. The levels of osteogenesis marker genes and Wnt signaling target genes in bone marrow stromal cells (BMSCs) were detected by reverse transcription quantitative polymerase chain reaction and immunostaining. BMSCs were induced osteoblast differentiation and tested by Alizarin red S staining. Results μCT analyses of C57BL/6 mice showed that bone mineral density (BMD) and trabecular thickness (Tb.Th) increased until the bone mass peaked (5 months) and then began to fall subsequently. LiCl dramatically enhanced bone mass in the senile osteoporotic conditions, represented by increased ratio of bone volume to tissue volume (BV/TV), and decreased in trabeculae separation (Tb.Sp). Moreover, LiCl significantly increased both canonical osteoblastogenesis and Wnt signaling activity without affecting hormones. Conclusion This study uncovered the role of LiCl in canonical Wnt signaling and bone formation and have provided the evidence that LiCl may potentially repress senile osteoporosis.

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Section: Mouse Models Of Senile Osteoporosismentioning

confidence: 99%

Lithium chloride enhances osteoblast differentiation and resists senile osteoporosis

Bao

Tang

et al. 2020

Preprint

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“…Although estrogen is considered by some to exert primarily inhibitory actions on periosteal expansion, there is recent evidence from animals models that many of the actions of estrogen on periosteum may be to stimulate expansion through ERα, but in a dosage sensitive manner, and potentially, in collaboration with androgen actions [76,76,97,113,114] on periosteally located AR [114]. However, recent studies have found that estrogen does not have an independent effect on periosteal expansion and that the action of estrogen and bone loading on bone structure are independent and additive [115].…”

Section: Bone Mineral Density and Architectural Integrity In Humanmentioning

confidence: 99%

“…Specifically, wrist breadth at time of presentation of the hERKO man was greater than normal at 7.2 cm (normal adult males: 6.0 ± 0.5 [mean ± SD]; normal adult females: 5.3 ± 0.3 cm) and the width of the distal femurs were both estimated to be 113 mm (normal adult male 90 ± 7 mm). The skeletal “frame size” as measured at the wrist and knee is distinctly different from the ectomorphic appearing skeleton of longstanding hypogonadism [116] and this phenotype may be due to important actions of androgen in these individuals [79,97,113]. The ArKO subjects have normal to slightly elevated androgen prior to intervention and this may serve to maintain and/or augment bone size.…”

Section: Bone Mineral Density and Architectural Integrity In Humanmentioning

confidence: 99%

Recent experimental and clinical findings in the skeleton associated with loss of estrogen hormone or estrogen receptor activity

Smith

Specker

Korach

2010

The Journal of Steroid Biochemistry and Molecular Biology

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Studies on rodent models and rare human disorders of estrogen production or response have revealed an increased complexity of the actions of estrogen on bone. ERα disruption in human males results in delayed epiphyseal maturation, tall stature, trabecular thinning, marked cortical thinning, genu valgum and significantly reduced cortical vBMD, but trabecular number is preserved and there is normal to increased periosteal expansion. Aromatase deficiency results overall in a similar phenotype, although less is known about skeletal architecture. Importantly, estrogen replacement in these individuals, even if provided late in the third decade, may normalize aBMD. Less certain is whether there is complete recovery of normal skeletal architecture and strength. Rodent models, in general, are consistent with the human phenotype but are confounded by inherent differences between mouse and human physiology and issues regarding the completeness of the different knock-out lines. Both human and rodent studies suggest that residual effects of estrogen through ERβ, truncated ERα forms or nonclassical estrogen receptors might account for different phenotypes in the hERKO man, aromatase deficient subjects and rodents. Importantly, androgen, particularly by preserving trabecular number and augmenting both periosteal and epiphyseal growth, also has significant actions on bone.

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“…Besonders die Effekte auf den Knochenstoffwechsel sind im Hinblick auf die Behandlung der Osteoporose interessant. Dass Androgene wie Testosteron und DHT auf den Knochen wirken, konnte unter anderem an männlichen orchiektomierten Nagern (Ophoff et al 2009, Vandenput et al 2002, Vanderschueren et al 1992) sowie an Männern aufgezeigt werden (Anderson et al 1997). In der männlichen Adoleszenz führen Androgene zu einer starken periostalen Apposition und folglich zu einer dickeren Kortikalis (Seeman 2001a, Seeman 2001b.…”

Section: öStrogenmangel Führt Zu Einemunclassified

Die Wirkung von Sexual- und Phytohormonen auf das Remodelling des osteoporotischen Knochens der orchiektomierten Ratte nach Trepanation und Vibration

Thole¹

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Einleitung 1 1 Einleitung "Osteoporose?! Frag doch lieber deine Mutter!" H. Thole Ähnlich werden wahrscheinlich die meisten deutschen Männer reagieren, wenn man sie zum Thema Osteoporose befragen möchte. Diese Aussage zeigt, dass in weiten Kreisen der Bevölkerung die Osteoporose als Erkrankung der Frau angesehen wird. Dabei betrifft diese Krankheit nicht nur Frauen. Insgesamt sind in Deutschland etwa 6 Millionen Menschen an Osteoporose erkrankt, davon ist jeder Fünfte ein Mann (Bartl 2011). Im Alter verlieren Männer im Durchschnitt jährlich 1 % ihrer Knochenmineraldichte (Hannan et al. 2000). Auch wird davon ausgegangen, dass die im Alter häufig auftretenden Oberschenkelhalsbrüche schätzungsweise bei 20-30 % der Männer durch Osteoporose verursacht werden (Bartl 2011, Johnell und Kanis 2006). Das Auftreten einer Fraktur bedeutet aber gleichzeitig auch ein erhöhtes Risiko für das Vorkommen einer weiteren Fraktur (Klotzbuecher et al. 2000). So besitzen Patienten mit einer Wirbelkörperfraktur ein 2,3-fach erhöhtes Risiko für eine Hüftfraktur und ein 1,4-faches Risiko für eine Unterarmfraktur (Sambrook und Cooper 2006). In der älteren Bevölkerung ist das Auftreten einer Fraktur, besonders an der Hüfte, mit einer höheren Folgemortalität vergesellschaftet, wobei das Risiko für Männer grundsätzlich größer ist als für Frauen (Center et al. 1999). Infektionen im Krankenhaus oder postoperative Komplikationen stellen dabei weitere Folgegefahren dar. Mit dem demographischen Wandel der Bevölkerung wächst der Anteil der älteren Gesellschaft und folglich wird die Inzidenz von Frakturen sowohl für Frauen als auch für Männer weiter zunehmen (European Prospective Osteoporosis Study (EPOS)

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Sex steroids during bone growth: a comparative study between mouse models for hypogonadal and senile osteoporosis

Abstract: 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.

Cited by 10 publications

References 37 publications

Lithium chloride enhances osteoblast differentiation and resists senile osteoporosis

Lithium chloride enhances osteoblast differentiation and resists senile osteoporosis

Recent experimental and clinical findings in the skeleton associated with loss of estrogen hormone or estrogen receptor activity

Die Wirkung von Sexual- und Phytohormonen auf das Remodelling des osteoporotischen Knochens der orchiektomierten Ratte nach Trepanation und Vibration

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