The degree of bone mineralization is maintained with single intravenous bisphosphonates in aged estrogen-deficient rats and is a strong predictor of bone strength

Yao, Wei; Cheng, Zhiqiang; Koester, Kurt J.; Ager, Joel W.; Balooch, M.; Pham, Aaron; Chefo, Solomon; Busse, Cheryl; Ritchie, Robert O.; Lane, Nancy E.

doi:10.1016/j.bone.2007.06.021

Cited by 48 publications

(62 citation statements)

References 31 publications

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“…Both stiffness and ultimate load in the ZOL-treated groups were similar to values in the SHAM-OVX group. Ultimate displacement tended to be lower in both ZOL groups compared to the SHAM-OVX and OVX groups, which could be an indication of a slightly more brittle tissue due to increased mineralization, although in a recent study no effect of ZOL on mineral crystal size was determined in ZOL-treated, OVX rats [14]. In general, we conclude that both early and late ZOL treatment resulted in overall, normal mechanical properties.…”

Section: Discussionmentioning

confidence: 38%

Influence of Early and Late Zoledronic Acid Administration on Vertebral Structure and Strength in Ovariectomized Rats

2008

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An annual infusion of zoledronic acid (ZOL) reduces fracture risk in osteoporotic patients. Previously, we showed that a single ZOL injection inhibited changes in bone microstructure and strength in rat tibiae after ovariectomy. Here, we determined the effects of a single ZOL injection as preventive and restorative treatment on the bone microstructure and strength in lumbar and caudal vertebrae of ovariectomized (OVX) rats. Twenty-nine female 35-weekold Wistar rats were divided into four groups: SHAM-OVX (n = 9), OVX (n = 5), OVX and early ZOL (n = 8), and OVX and late ZOL (n = 7). ZOL was given once (20 lg/kg body weight s.c.) at OVX in the early ZOL group and 8 weeks later in the late ZOL group; rats were killed 16 weeks after OVX. Trabecular and cortical bone microarchitecture were measured in lumbar (L3) and caudal (Cd6) vertebrae using micro-computed tomography, and compressive mechanical properties were determined in L3 vertebrae. Compared to SHAM-OVX, OVX rats had significantly lower BV/TV; SMI, Tb.N, Tb.Sp, and Conn.D tended to be deteriorated in lumbar vertebrae, while both ZOL groups did not differ from the SHAM-OVX group. Both ZOL groups had significantly higher BV/TV than OVX; the early ZOL group also had significantly lower SMI and higher Tb.Th. OVX tended to decrease mechanical properties, while early and late ZOL treatment inhibited OVX-induced degeneration. Neither OVX nor ZOL induced changes in the trabecular microarchitecture of caudal vertebrae. In summary, in adult rats a single ZOL injection inhibited OVX-induced changes in lumbar vertebral bone microarchitecture and strength.Keywords Bisphosphonate Á Bone architecture/ structure Á Osteoporosis Á Animal model Bisphosphonates inhibit bone resorption and are commonly used to treat osteoporotic patients. They slow the process of bone loss and reduce the risk of fracture by maintaining bone mass and microstructure [1][2][3]. Zoledronic acid (ZOL) is a potent bisphosphonate that has recently been shown to significantly reduce fracture risk in osteoporotic patients who received once-yearly doses [4,5]. As the number and depth of in vivo analyses in patients are limited, animal research is ongoing to further elucidate the effects of ZOL on skeletal fragility [6][7][8][9]. Previously, we showed in a longitudinal study of adult rats that a single injection of ZOL at the time of ovariectomy (OVX) inhibited OVX-induced deterioration of bone microstructure and strength in the proximal tibiae for up to 16 weeks [10]. Furthermore, a single injection of ZOL 8 weeks after OVX inhibited further deterioration of the bone microstructure and strength in rat tibiae compared to untreated OVX rats. Other studies have shown that weekly injections of ZOL inhibit changes in bone microstructure and strength in rat vertebrae after OVX [8,9]. However, it is not known to what extent a single dose of ZOL is able to inhibit and restore OVX-induced loss of bone mass, structure, and strength in rat vertebrae.

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Section: Discussionmentioning

confidence: 38%

Influence of Early and Late Zoledronic Acid Administration on Vertebral Structure and Strength in Ovariectomized Rats

2008

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“…In the case of Huang et al, the absence of significant difference is likely a consequence of having a time duration of only 12 weeks between ovariectomy and point of sacrifice, the shortest of any of the studies published [7]. Similarly, the most questionable aspect of the conclusions drawn by Yao et al is the restriction of sample numbers to n = 4 which obviously makes statistical comparison challenging [11].…”

Section: Discussionmentioning

confidence: 99%

“…Noteworthy also are two separate publications in the literature which do not demonstrate significant differences in crystal thickness following ovariectomy [7,11]. Naturally, disparities in reported values can be attributable to a multitude of factors ranging from rat breed, anatomical sites investigated to time-points of ovariectomy and/or sacrifice.…”

Section: Discussionmentioning

confidence: 99%

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Characterising Bone Material Composition and Structure in the Ovariectomized (OVX) Rat Model of Osteoporosis

et al. 2015

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“…The entire lumbar vertebra was scanned and the trabecular bone juxtaposed to both the cranial and caudal growth plates and the cortex was evaluated. The gray-scale images were segmented using a constrained three-dimensional Gaussian filter (sigma, 0.8; support, 1.0; fixed threshold of 240) to extract the structure of the mineralized tissue to obtain trabecular bone volume and thickness [25,42]. For the right midfemur, the scanning was performed at the middle femur continuing proximally 1 mm.…”

Section: Micro-ct Measurements Of Bone Architecture and Mineral Densimentioning

confidence: 99%

β-Ecdysone Augments Peak Bone Mass in Mice of Both Sexes

Dai

Zhang

Zhong

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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Background One of the strongest predictors for osteoporosis is peak bone mass. Interventions to augment peak bone mass have yet to be developed. b-Ecdysone (bEcd), a natural steroid-like compound produced by arthropods to initiate metamorphosis, is believed to have androgenic effects and so may be used to augment bone mass. Questions/purposes The purpose of this study was to use both male and female (1) gonadal-sufficient; and (2) -insufficient mice to investigate sex differences in terms of bone development and structure after bEcd administration.Methods Two-month-old male and female Swiss-Webster mice were randomized to receive either vehicle or bEcd (0.5 mg/kg) for 3 weeks. In a separate experiment to evaluate the effects of bEcd on sex hormone-deficient mice, gonadectomy was performed in male (orchiectomy [ORX]) and female mice (ovariectomy [OVX]). Shamoperated and the ORX/OVX mice were then treated for 3 weeks with bEcd. Primary endpoints for the study were trabecular bone structure and bone strength. Results In male mice, the trabecular bone volume was 0.18 ± 0.02 in the placebo-treated (PL) and 0.23 ± 0.02 in the bEcd-treated group (p \ 0.05 versus PL); and 0.09 ± 0.01 in the ORX group (p \ 0.05 versus PL) and 0.12 ± 0.01 in the ORX + bEcd group. Vertebral bone strength (maximum load) was 43 ± 2 in PL and 51 ± 1 in the bEcd-treated group (p \ 0.05 versus PL); and 30 ± 4 in the ORX group (p \ 0.05 versus PL) and 37 ± 3 in the ORX + bEcd group. In female mice, trabecular bone volume was 0.23 ± 0.02 in PL and 0.26 ± 0.02 in the bEcd-treated group (p \ 0.05 versus PL); and 0.15 ± 0.01 in the OVX group (p \ 0.05 versus PL) and 0.14 ± 0.01 in the OVX + bEcd group. Maximum load of the vertebrae was 45 ± 2 in PL and 48 ± 4 in the bEcd-treated group; and 39 ± 4 in the OVX group (p \ 0.05 versus PL) and 44 ± 4 in the OVX + bEcd group.

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The degree of bone mineralization is maintained with single intravenous bisphosphonates in aged estrogen-deficient rats and is a strong predictor of bone strength

Cited by 48 publications

References 31 publications

Influence of Early and Late Zoledronic Acid Administration on Vertebral Structure and Strength in Ovariectomized Rats

Influence of Early and Late Zoledronic Acid Administration on Vertebral Structure and Strength in Ovariectomized Rats

Characterising Bone Material Composition and Structure in the Ovariectomized (OVX) Rat Model of Osteoporosis

β-Ecdysone Augments Peak Bone Mass in Mice of Both Sexes

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