Effects of 16 weeks of treatment with tibolone on bone mass and bone mechanical and histomorphometric indices in mature ovariectomized rats with established osteopenia on a low-calcium diet

Yoshitake, Kazusada; Yokota, Kazuaki; Kasugai, Yumiko; Kagawa, Mai; Sukamoto, Takayuki; Nakamura, Toshio

doi:10.1016/s8756-3282(99)00172-6

Cited by 45 publications

(28 citation statements)

References 57 publications

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“…OVX also causes a reduction in BMD, bending strength of the femur and compressive strength of the vertebral bodies. Our results concerning biochemical markers of bone turnover, bone strength and histomorphometry in the OVX rats are therefore consistent with published studies of this model [23][24][25][26][27][28][29][30]. Administration of SCH 57068 to the OVX-treated animals in our experiment appeared to markedly reduce the increase in overall bone turnover induced by OVX.…”

Section: Discussionsupporting

confidence: 92%

“…The OVX rat model mimics changes in bone metabolism observed in human postmenopausal osteoporosis. Biochemical markers of bone resorption and formation reflecting bone turnover are elevated after OVX and return to low levels after estrogen repletion or after treatment with antiresorptive agents [23][24][25][26]. OVX also causes a reduction in BMD, bending strength of the femur and compressive strength of the vertebral bodies.…”

Section: Discussionmentioning

confidence: 99%

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The selective estrogen receptor modulator SCH 57068 prevents bone loss, reduces serum cholesterol and blocks estrogen-induced uterine hypertrophy in ovariectomized rats

Goss

Cheung

et al. 2004

The Journal of Steroid Biochemistry and Molecular Biology

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Our objective was to determine the effects of SCH 57068 alone and with 17β-estradiol (E 2 ) on bone, lipids and uteri in ovariectomized (OVX) rats. In OVX animals lumbar vertebral and femoral bone mineral density (BMD) were significantly higher after 12 weeks of treatment with SCH 57068 than in untreated OVX controls. Similarly BMD was superior in OVX + E 2 + SCH 57068 treated animals than in OVX + E 2 controls. SCH 57068 also significantly reduced the increase in bone turnover markers, serum pyridinoline and serum osteocalcin levels, induced by OVX, and increased mechanical bone strength. SCH 57068 also significantly reduced the rise in serum cholesterol and low-density lipoprotein cholesterol induced by OVX. SCH 57068 had no stimulatory effect on uterine epithelium when given alone in OVX rats. SCH 57068 (1 and 2.5 mg/kg) reduced uterine weight and blocked endometrial stimulation induced by E 2 . In summary, SCH 57068 adds to the positive effects of E 2 on bone and lipid metabolism but blocks the stimulatory effects of E 2 on the uterus. Potentially, E 2 + SCH 57068 could be combined for the treatment and prevention of breast cancer or as a novel hormone replacement therapy.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

The selective estrogen receptor modulator SCH 57068 prevents bone loss, reduces serum cholesterol and blocks estrogen-induced uterine hypertrophy in ovariectomized rats

Goss

Cheung

et al. 2004

The Journal of Steroid Biochemistry and Molecular Biology

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“…Esse dado se torna ainda mais relevante se analisarmos apenas os trabalhos com osso, os quais variam de quatro (19,35) a 16 semanas (46) . Apenas um trabalho relata o uso de tibolona durante 16 meses, em ratas ooforectomizadas, em que foram testadas diversas doses, sendo a maior de 0,5 mg/dia (18) .…”

Section: Discussionunclassified

“…Contudo, considerando o menor percentual de porosidade óssea nos côndilos femorais no grupo OVX + T, pode-se presumir que a atuação benéfica da tibolona ocorre principalmente no osso trabecular. Isto pode ser explicado pelo fato de que o osso trabecular é considerado mais responsivo aos hormônios, assim como a intervenções farmacológicas, se comparado com o osso cortical (1,46) .…”

Section: Discussionunclassified

Histomorfometria do tecido ósseo em ratas castradas tratadas com tibolona

Carvalho¹,

Henriques²,

Pantaleão³

et al. 2010

J. Bras. Patol. Med. Lab.

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Introdução e objetivo: O efeito da tibolona utilizada em alta dose e por tempo prolongado foi analisado mediante estudo histomorfométrico de tíbias e fêmures de ratas castradas. Métodos: O experimento utilizou 20 ratas Wistar, com peso médio de 250 g. Os animais foram distribuídos aleatoriamente em três grupos: ooforectomizado recebendo tibolona (OVX + T) (n = 9), ooforectomizado (OVX) (n = 6) e grupo controle não ooforectomizado (C) (n = 5). Deu-se início ao protocolo experimental 30 dias após a ooforectomia, perdurando por 20 semanas, com administração de tibolona (1 mg/dia) a OVX + T e carboximetilcelulose a OVX. O grupo C não foi submetido a qualquer tratamento. Tíbias e fêmures direitos foram fixados em formol a 10% tamponado, descalcificados e processados para inclusão em parafina. Os cortes histológicos foram corados mediante hematoxilina-eosina para análise histomorfométrica. Mediram-se a espessura cortical e a cavidade medular em cortes transversais de tíbia e fêmur e percentual de porosidade e densidade trabecular em cortes longitudinais de fêmur. Resultados e discussão: Não houve diferença estatística entre OVX e OVX + T nas diversas análises. Os resultados demonstram que a tibolona não melhorou de forma significativa a qualidade óssea, porém preservou a massa óssea cortical, nas diáfises femoral e tibial, e o osso trabecular, nos côndilos femorais. O uso prolongado de tibolona em concomitância com alta dose pode ter influenciado tais efeitos, já que estudos recentes têm preconizado a utilização de doses mais baixas na prevenção da osteoporose. Conclusão: A ooforectomia ocasionou perda óssea nas regiões analisadas; a tibolona, apesar de não ter aumentado a massa óssea, manteve-a em níveis satisfatórios. . The animals were randomly divided into three groups: oophorectomized receiving tibolone (OVX + T) (n = 9), oophorectomized (OVX) (n = 6) and non-oophorectomized as control group (C) (n = 5). The experimental protocol was initiated 30 days after oophorectomy and lasted 20 weeks. Tibolone (1 mg/day) was administered to OVX + T rats and carboxymethyl cellulose to OVX. C rats did not go through any treatment. Right side tibias and femurs

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“…Preclinical studies indicate that tibolone prevents bone loss (axial and appendicular), caused by oophorectomy or low calcium intake in both young and mature rats and in rats with established osteopenia (Yoshitake et al, 1999). Experimental data conclude that tibolone is as effective as estrogen to prevent bone loss secondary to the decline of ovarian function, observed even in osteopenic rats an increase in BMD and femoral and vertebral bone strength, similar to estrogen (Berning et al, 2001).…”

Section: Effects On Bonementioning

confidence: 92%

The Role of Hormone Replacement Therapy (HRT) and Tibolone in the Prevention and Treatment of Postmenopausal Osteoporosis

Lamarca¹

2012

Osteoporosis

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Effects of 16 weeks of treatment with tibolone on bone mass and bone mechanical and histomorphometric indices in mature ovariectomized rats with established osteopenia on a low-calcium diet

Cited by 45 publications

References 57 publications

The selective estrogen receptor modulator SCH 57068 prevents bone loss, reduces serum cholesterol and blocks estrogen-induced uterine hypertrophy in ovariectomized rats

The selective estrogen receptor modulator SCH 57068 prevents bone loss, reduces serum cholesterol and blocks estrogen-induced uterine hypertrophy in ovariectomized rats

Histomorfometria do tecido ósseo em ratas castradas tratadas com tibolona

The Role of Hormone Replacement Therapy (HRT) and Tibolone in the Prevention and Treatment of Postmenopausal Osteoporosis

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