Bisphosphonate tiludronate increases bone strength by improving mass and structure in established osteopenia after ovariectomy in rats

Ohnishi, Hideo; Nakamura, Toshio; Narusawa, Kenichiro; Murakami, Hiroshi; Abe, Mitsuhiro; Barbier, A.; Suzuki, Koji

doi:10.1016/s8756-3282(97)00145-2

Cited by 50 publications

(49 citation statements)

References 33 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 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%

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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“…Random loss of trabecula seems to be more detrimental to the ultimate strength of bone compared to a thinning of trabecula [31,32]. The number of trabecula aligned in the loading direction is important in the maintenance of the mechanical properties of trabecular bone [33]. In the current study, "catchup" growth seemed to be directed in the 0° orientation which is more able to resist the loading placed on the proximal tibia.…”

Section: Discussionmentioning

confidence: 56%

The effect of a short-term delay of puberty on trabecular bone mass and structure in female rats: A texture-based and histomorphometric analysis

Yingling

Xiang

Raphan

et al. 2007

Bone

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Accrual of bone mass and strength during development is imperative in order to reduce the risk of fracture later in life. Although delayed pubertal onset is associated with an increased incidence of stress fracture, evidence supports the concept of "catch up" growth. It remains unclear if deficits in bone mass associated with delayed puberty have long term effects on trabecular bone structure and strength. The purpose of this study was to use texture-based analysis and histomorphometry to investigate the effect of a delay in puberty on trabecular bone mass and structure immediately postpuberty and at maturity in female rats. Forty-eight female Sprague Dawley rats (25 days) were randomly assigned to one of four groups; 1) short-term control (C-ST), 2) long-term control (C-LT), 3) short-term GnRH antagonist (G-ST) and 4) long-term GnRH antagonist (G-LT). Injections of either saline or gonadotropin-releasing hormone antagonist (GnRH-a) (100 μg/day) (Cetrotide™, Serono, Inc) were given intraperitoneally for 18 days (day 35-42) to both ST and LT. The ST groups were sacrificed after the last injection (day 43) and the LT groups at 6 months of age. Pubertal and gonadal development was retarded by the GnRA antagonist injections as indicated by a delay in vaginal opening, lower ovarian and uterine weights and suppressed estradiol levels in the short-term Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptBone. Author manuscript; available in PMC 2007 April 10. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript experimental animals (G-ST). Delayed puberty caused a transient reduction in trabecular bone area as assessed by histomorphometry. Specifically, the significant deficit in bone area resulted from a decreased number of trabecula and an increase in trabecular separation. Texture analysis, a new method to assess bone density and structural anisotropy, correlated well with the standard histomorphometry and measured significant deficits in the density measure (M Density ) in the G-ST group that remained at maturity (6 months). The texture energy deficit in the G-ST group was primarily in the 0° orientation (−13.2 %), which measures the longitudinal trabeculae in the proximal tibia. However, the deficit in the G-LT group was in the 45° and 135° orientations. These results suggest that any "catch-up" growth following the cessation of the GnRH-antagonist injection protocol may be directed in trabeculae oriented perpendicular to 0° at the expense of trabeculae in other orientations.

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“…A three-point bending test was done as previously described 10,19) using a load tester (Rheoner, Model RE-33005, Yamaden, Co., Ltd., Tokyo). Each specimen of a left femur was placed on a holding device with supports located at a distance of 12 mm, with the lesser trochanter proximal to, and in contact with, the proximal transverse bar.…”

Section: Methodsmentioning

confidence: 99%

Effects of Voluntary Resistance Exercise and High-protein Snack on Bone Mass, Composition, and Strength in Rats Given Glucocorticoid Injections

Matsuo

Nozaki

Okamura

et al. 2003

Bioscience, Biotechnology, and Biochemistry

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Bisphosphonate tiludronate increases bone strength by improving mass and structure in established osteopenia after ovariectomy in rats

Cited by 50 publications

References 33 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

The effect of a short-term delay of puberty on trabecular bone mass and structure in female rats: A texture-based and histomorphometric analysis

Effects of Voluntary Resistance Exercise and High-protein Snack on Bone Mass, Composition, and Strength in Rats Given Glucocorticoid Injections

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