Intermittent minodronic acid treatment with sufficient bone resorption inhibition prevents reduction in bone mass and strength in ovariectomized rats with established osteopenia comparable with daily treatment

Kimoto, Aishi; Tanaka, Makoto; Nozaki, Kazutoshi; Mori, Masamichi; Fukushima, Shinji; Mori, Hiroshi; Shiroya, Tsutomu; Nakamura, Toshio

doi:10.1016/j.bone.2013.02.013

Cited by 12 publications

(5 citation statements)

References 26 publications

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“…Specifically, OVX induced significantly increased MAR which caused further deterioration. However, minodronic acid and dried plum suppressed OVX-induced increases in bone turnover at the tissue level, thereby improving the deterioration of bone quality under osteoporotic disease conditions6566. In our study, we observed that SAL possessed the similar results in vivo .…”

Section: Discussionsupporting

confidence: 66%

Protective effect of salidroside against bone loss via hypoxia-inducible factor-1α pathway-induced angiogenesis

Li¹,

Jin

et al. 2016

Sci Rep

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Hypoxia-inducible factor (HIF)-1α plays a critical role in coupling angiogenesis with osteogenesis during bone development and regeneration. Salidroside (SAL) has shown anti-hypoxic effects in vitro and in vivo. However, the possible roles of SAL in the prevention of hypoxia-induced osteoporosis have remained unknown. Two osteoblast cell lines, MG-63 and ROB, were employed to evaluate the effects of SAL on cell viability, apoptosis, differentiation and mineralization in vitro. Rats subjected to ovariectomy-induced bone loss were treated with SAL in vivo. Our results showed that pre-treatment with SAL markedly attenuated the hypoxia-induced reductions in cell viability, apoptosis, differentiation and mineralization. SAL down-regulated HIF-1α expression and inhibited its translocation; however, SAL increased its transcriptional activity and, consequently, up-regulated vascular endothelial growth factor (VEGF). In vivo studies further demonstrated that SAL caused decreases in the mineral, alkaline phosphatase (ALP), and BGP concentrations in the blood of ovariectomized (OVX) rats. Moreover, SAL improved the trabecular bone microarchitecture and increased bone mineral density in the distal femur. Additionally, SAL administration partially ameliorated this hypoxia via the HIF-1α-VEGF signalling pathway. Our results indicate that SAL prevents bone loss by enhancing angiogenesis and osteogenesis and that these effects are associated with the activation of HIF-1α signalling.

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Section: Discussionsupporting

confidence: 66%

Protective effect of salidroside against bone loss via hypoxia-inducible factor-1α pathway-induced angiogenesis

Li¹,

Jin

et al. 2016

Sci Rep

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“…Asymmetric mechanical load provokes progression of scoliotic deformities according to the Hueter-Volkmann law [ 47 ]. Minodronate can suppress increases in bone turnover and improve bone strength and microarchitecture under osteoporotic disease conditions in monkeys and rats [ 48 , 49 ]. Our results indicated that the administration of minodronate, suppressing accelerated bone resorption and improving bone mass, might protect the vertebral body against the “imbalanced load” and finally reduce the progression of thoracic scoliosis.…”

Section: Discussionmentioning

confidence: 99%

Minodronate treatment improves low bone mass and reduces progressive thoracic scoliosis in a mouse model of adolescent idiopathic scoliosis

Tanabe¹,

Aota²,

Yamaguchi³

et al. 2018

PLoS ONE

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Recent studies have shown an association between osteopenia and adolescent idiopathic scoliosis (AIS) and implied that osteopenia plays a causative role in AIS development. This study aimed to determine if minodronate (MIN) treatment could prevent curve progression by increasing bone mass in a thoracic restraint (TR) mouse model, which develops causes the development of thoracic scoliosis similar to human AIS. A total of 100 young female C57BL6J mice were divided into four groups: (1) control with vehicle (CON/VEH; n = 20), (2) control with MIN (CON/MIN; n = 20), (3) TR with vehicle (TR/VEH; n = 30), or (4) TR with MIN (TR/MIN; n = 30). MIN (0.01 mg/kg/week) and vehicle were administered intraperitoneally to their respective groups. TR was performed at age 4 weeks, and the mice were sacrificed at age 9 weeks. Body weights, spine radiographs, femoral bone mineral density (BMD), serum bone marker levels, and histomorphometry of the cancellous bone of the thoracic vertebrae were analyzed. TR significantly reduced weight gain in the TR/VEH group relative to the CON/VEH group. TR also induced osteoporosis with accelerated bone resorption, as indicated by decreases in femoral BMDs and thoracic cancellous bone volume and increases in serum bone resorption marker levels and histomorphometric resorption parameters in the TR/VEH group. MIN partially improved body weight gain and improved poor bone structure relative to the TR/VEH group by suppressing high bone resorption in the TR/MIN mice. MIN significantly reduced the curve magnitudes, as indicated by a 43% lower curve magnitude in the TR/MIN mice than in the TR/VEH mice (17.9 ± 8.9° vs. 31.5 ± 13.1°; p< 0.001). The administration of MIN increased bone mass and reduced the severity of scoliosis in the TR mice. MIN was suggested as a possible inhibitor of scoliosis development.

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“… 51 , 52 However, optimal doses of minodronate could preserve or even ameliorate bone microarchitecture, as shown in several animal studies. 53 – 55 Microdamage caused by minodronate was less than that caused by alendronate, even though there was stronger suppression of bone remodeling by minodronate for 17 months of treatment for ovariectomized cynomolgus monkeys. 55 In a rat model, minodronate, regardless of the administration regimen (once every 4 weeks or daily), ameliorated worsening bone microarchitectures, including decreased bone mass and trabecular thickness, and increased trabecular separation induced by ovariectomy over 12 months.…”

Section: Bone Quality Assessment For Minodronatementioning

confidence: 97%

“… 55 In a rat model, minodronate, regardless of the administration regimen (once every 4 weeks or daily), ameliorated worsening bone microarchitectures, including decreased bone mass and trabecular thickness, and increased trabecular separation induced by ovariectomy over 12 months. 53 , 56 In a clinical investigation, Ito et al 57 demonstrated that daily minodronate increased BMD, geometry, and bone strength of the proximal femur over 12 months in 103 postmenopausal patients with osteoporosis. They concluded that minodronate reduced age-related endocortical bone resorption, leading to increased cortical thickness and sustained bone strength.…”

Section: Bone Quality Assessment For Minodronatementioning

confidence: 99%

Minodronate for the treatment of osteoporosis

Ohishi¹,

Matsuyama²

2018

TCRM

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Minodronate is a third-generation bisphosphonate that was developed and approved for clinical use in osteoporosis therapy in Japan. The mechanism of action for suppressing bone resorption is the inhibition of farnesyl pyrophosphate synthase, a key enzyme in the mevalonic acid metabolic pathway of osteoclasts, to induce apoptosis of the cells. Minodronate is the strongest inhibitor of bone resorption among the currently available oral bisphosphonates. Large randomized, placebo-controlled, double-blind clinical trials have revealed an increase in bone mineral density of both the lumbar spine and femoral neck over 3 years of daily minodronate therapy and risk reduction in vertebral fractures over 2 years of therapy. The increase in bone mass and the prevention of vertebral fractures are similar to those with alendronate or risedronate. The incidence of adverse events, especially gastrointestinal disturbance, is the same as or less than that with weekly or daily alendronate or risedronate. The unique mechanism of action of minodronate via the inhibition of the P2X(2/3) receptor compared with other bisphosphonates may be an advantage in reducing low back pain in patients with osteoporosis. The monthly regimen of minodronate, introduced in 2011, is expected to have better patient adherence and longer persistence. In experimental animal models, minodronate preserved, or even ameliorated, bone microarchitectures, including microcracks and perforation of the trabeculae in the short term. The lowest incidence of bisphosphonate-related osteonecrosis of the jaw among all bisphosphonates and the lack of atypical femoral fractures attributed to its use to date, however, are partly because only a smaller population used minodronate than those using other bisphosphonates. To date, minodronate is available only in Japan. Hip fracture risk reduction has not been verified yet. More clinical studies on minodronate and its use in osteoporosis treatment, with a large number of subjects, should be conducted to verify hip fracture risk reduction and long-term results.

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Intermittent minodronic acid treatment with sufficient bone resorption inhibition prevents reduction in bone mass and strength in ovariectomized rats with established osteopenia comparable with daily treatment

Cited by 12 publications

References 26 publications

Protective effect of salidroside against bone loss via hypoxia-inducible factor-1α pathway-induced angiogenesis

Protective effect of salidroside against bone loss via hypoxia-inducible factor-1α pathway-induced angiogenesis

Minodronate treatment improves low bone mass and reduces progressive thoracic scoliosis in a mouse model of adolescent idiopathic scoliosis

Minodronate for the treatment of osteoporosis

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