Prevention of Bone Loss in Ovariectomized Rats by Combined Treatment With Risedronate and 1α,25-Dihydroxyvitamin D3

Erben, Reinhold G.; Mosekilde, Lis; Thomsen, Jesper Skovhus; Weber, Karin; Stähr, Kerstin; Leyshon, Alyson; Smith, Susan Y.; Phipps, Roger J.

doi:10.1359/jbmr.2002.17.8.1498

Cited by 65 publications

(50 citation statements)

References 51 publications

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“…A couple of preclinical studies have reported on the efficacy of risedronate for trabecular bone loss using a rat model of postmenopausal osteoporosis: risedronate suppressed bone resorption and prevented trabecular bone loss in ovariectomized rats [5,14]. In the present study, the effect of risedronate on the trabecular and endocortical bone was considered to be suppression of both bone resorption (ES/BS) and bone formation (trabecular BFR/BV and endocortical BFR/BS) in terms of suppression of bone turnover.…”

Section: Discussionmentioning

confidence: 84%

“…However, continuous treatment attenuated trabecular bone loss 6 weeks after OVX despite sufficiently suppressing bone turnover, probably because of the insufficient dosing of risedronate during the 6 weeks after OVX. In fact, high dose risedronate treatment in OVX rats is able to prevent trabecular bone loss [5,14]. Although the effect of continuous treatment on trabecular bone mass was diminished 6 weeks after OVX, two-way factorial ANOVA showed that pre-and post-OVX treatments had an additive effect on trabecular bone mass in both the short-and long-term experiments.…”

Section: Discussionmentioning

confidence: 96%

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Effect of Pre- and Post-Surgery Treatment with Risedronate on Trabecular Bone Loss in Ovariectomized Rats

et al. 2006

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The purposes of the present study were to differentiate the effects of pre-surgery treatment with risedronate and post-surgery treatment with a reduced dosing frequency of risedronate on trabecular bone loss in ovariectomized rats and to determine whether postsurgery treatment with a reduced dosing frequency of risedronate would have a beneficial effect on trabecular bone loss after pre-surgery treatment Materials and Methods Treatment of animalsOne hundred female Sprague-Dawley rats, 3 months of age, were purchased from Charles River Lab (Wilmington, MA, USA). The animals were housed under local vivarium conditions (temperature 23.8°C and 12 h on/off light cycle), and were fed a pelleted standard chow diet (Purina Mills Prolab RMH 2500 Rodent diet #5P14, ON, USA), with free access to water. The rats were used after allowing one-month adaptation to the new environment.The present study included short-term (6 weeks) and long-term (10 weeks) experiments. The short-term experiment was performed on fifty rats. Rats were randomized by the stratified weight method into five groups of 10 rats each (Fig. 1). In detail, 40 rats were divided into two groups with 20 rats in each group. Twenty rats were treated with vehicle for 4 weeks before ovariectomy (OVX) (Vehicle-OVX), and another 20 rats were treated with risedronate for 4 weeks before OVX (Risedronate-OVX). Then, 20 rats in each group were subdivided into two groups of 10 rats each. The 20 rats treated with vehicle before OVX were treated with vehicle (10 rats) or risedronate (10 rats) for 2 weeks following OVX (the Vehicle-OVX-Vehicle [OVX control] and Vehicle-OVX-Risedronate [post-OVX treatment with risedronate] groups, respectively), and the 20 rats treated with risedronate before OVX were treated with vehicle (10 rats) or risedronate (10 rats) for 2 weeks following OVX (the Risedronate-OVX-Vehicle [pre-OVX treatment with risedronate] and Risedronate-OVX-Risedronate [continuous treatment with risedronate] groups, respectively). The remaining 10 rats were treated with vehicle for 6 weeks, with a sham operation performed 4 weeks after the start of the experiment (the Vehicle-Sham-Vehicle [Sham control] group). During the 4 weeks prior to surgery, risedronate (Aventis Pharma, Tokyo, Japan) was dissolved in 0.1

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 96%

Effect of Pre- and Post-Surgery Treatment with Risedronate on Trabecular Bone Loss in Ovariectomized Rats

et al. 2006

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“…A previous study (65) has suggested that calcitriol dose-dependently exhibited inhibitory effects on osteoblastic activity. Thus, although we are unable to rule out an effect of calcitriol in producing the ABD in our animal model, the dose and the actions of 1,25(OH)2D3 in previous studies (57,58,61) suggest that it may not have been the cause of the ABD we observed.…”

Section: Discussioncontrasting

confidence: 57%

“…The exact effects of calcitriol on bone are unclear. At low doses, vitamin D metabolites can prevent bone loss in models of osteopenia in rats by an antiresorptive effect, whereas at high doses they also stimulate osteoblast activity and show an anabolic effect (57). Bone histomorphometry in another in vivo study showed that 1,25(OH) 2 D 3 alone exerts a potent proliferative effect on the osteoblasts but depresses their mineralizing capacity in a dose and time dependent manner (58).…”

Section: Discussionmentioning

confidence: 99%

Successful Treatment of an Adynamic Bone Disorder with Bone Morphogenetic Protein-7 in a Renal Ablation Model

Lund¹,

Davies²,

Brown³

et al. 2004

Journal of the American Society of Nephrology

103

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Abstract. An adynamic bone disorder (ABD) is an important complication of chronic kidney disease (CKD) of unknown etiology for which there is no adequate treatment. Reported is an animal model of ablative CKD complicated by an ABD characterized by the absence of secondary hyperparathyroidism and its successful treatment with a skeletal anabolic factor, bone morphogenetic protein-7 (BMP-7). Adult mice were subjected to electrocautery of the right kidney followed by left nephrectomy. Animals were randomized into groups fed normal chow or fed low-phosphate chow supplemented with calcitriol to maintain normophosphatemia in CKD. All groups were maintained on the regimens for 12 wk. Hyperphosphatemia, secondary hyperparathyroidism, and a mild osteodystrophy developed in the CKD/chow-fed group, as expected. When dietary phosphorus was restricted and calcitriol was administered in the CKD low-phosphate/calcitriol group (ABD), Ca, PO 4 , and parathyroid hormone levels were maintained normal. A significant ABD developed in the ABD group characterized by significant depressions in osteoblast number, perimeters, bone formation rates, and mineral apposition rates when compared with the sham-operated, chow-fed group. The abnormal skeletal histomorphometry was reversed by BMP-7 therapy to normal values and significantly improved from the ABD group (P Ͻ 0.05). The sham-operated low-phosphate/ calcitriol-fed control group and the CKD low-phosphate/calcitriol/BMP-7 groups had reduced phosphate levels compared with the other groups (P Ͻ 0.05). ABD produced in mice with CKD in the absence of hyperparathyroidism was successfully reversed with a bone anabolic, BMP-7, associated with a reduction in plasma phosphorus.Renal osteodystrophy is a term used to describe a heterogeneous spectrum of skeletal abnormalities found in patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Renal osteodystrophy ranges from states of high bone turnover to states of low bone turnover (1-3). Predominantly hyperparathyroid bone disease results in a high turnover osteodystrophy (osteitis fibrosa), and it is considered the most prevalent bone disorder in chronic kidney disease and ESKD. Low-turnover osteodystrophy reflects the lack of capacity to produce and mineralize bone matrix and has two main histologic forms: osteomalacia and the adynamic bone disorder (ABD). The ABD is an important complication of CKD associated with high rates of bone fractures (4), impaired growth (5,6), and probably vascular calcification (7,8). There has been an increase in the prevalence of ABD in patients with ESKD on dialysis (9).The pathogenesis of the ABD is unknown. It may occur when parathyroid hormone (PTH) levels are aggressively suppressed (10). As a result, practice standards target maintaining elevated intact PTH levels (about three to five times normal) sufficient to prevent the ABD (11,12). Therapy of the ABD besides adjustment of PTH levels is not available. Because secondary hyperparathyroidism in CKD causes a distinct osteodystrophy, in...

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“…Several preclinical studies have demonstrated the efficacy of risedronate for preventing cancellous bone loss in rat models of osteopenia. Risedronate suppresses bone resorption and prevents cancellous bone loss in ovariectomized rats [8,31], while it prevents loss of cancellous bone mass, bone density and bone strength without affecting cortical bone parameters in sciatic neurectomy rats or hindlimb-immobilized rats [18,30]. The absence of any adverse effect of risedronate on longitudinal and radial bone growth has been confirmed [18].…”

Section: Discussionmentioning

confidence: 82%

Additive Effect of Vitamin K2 and Risedronate on Long Bone Mass in Hypophysectomized Young Rats

et al. 2007

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Prevention of Bone Loss in Ovariectomized Rats by Combined Treatment With Risedronate and 1α,25-Dihydroxyvitamin D3

Cited by 65 publications

References 51 publications

Effect of Pre- and Post-Surgery Treatment with Risedronate on Trabecular Bone Loss in Ovariectomized Rats

Effect of Pre- and Post-Surgery Treatment with Risedronate on Trabecular Bone Loss in Ovariectomized Rats

Successful Treatment of an Adynamic Bone Disorder with Bone Morphogenetic Protein-7 in a Renal Ablation Model

Additive Effect of Vitamin K2 and Risedronate on Long Bone Mass in Hypophysectomized Young Rats

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