Alendronate Inhibits Spine Fusion in a Rat Model

Huang, Russel C.; Khan, Safdar N.; Sandhu, Harvinder S.; Metzl, Joshua A.; Cammisa, Frank P.; Zheng, Fengyu; Sama, Andrew A.; Lane, Joseph M.

doi:10.1097/01.brs.0000186470.28070.7b

Cited by 93 publications

(74 citation statements)

References 29 publications

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“…A 20 kg body weight in humans is approximately equivalent to the weight of a prepubescent rat, which was the growth stage of the rats at the onset of the study. The dose used in our study was calculated using equations performed by other authors (39), who established that a human dose of 1 mg/kg/ wk (70 mg/wk for an average 70 kg human) would be equivalent to 0.35 mg/kg/wk in rats.…”

Section: Discussionmentioning

confidence: 99%

Effect of alendronate on the mandible and long bones: an experimental study in vivo

2015

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Background:Bisphosphonates are anticatabolic agents that inhibit bone resorption and are widely used to treat osteoporosis and bone metastases in adults. They are also used in young patients with diseases like osteogenesis imperfecta or juvenile osteoporosis. Bone modeling/remodeling is elevated in growing subjects, and inhibition of osteoclastic activity has been shown to interfere with growth. Thus, our objective was to evaluate the effect of alendronate (ALN) on growing animals. Methods: Healthy male Wistar rats, aged 1 mo, received ALN or vehicle for 8 wk. Serum levels (calcemia, phosphatemia, and total alkaline phosphatase) were determined. Morphometric (rat: femur and tibia weight and length and hemimandible growth) and histomorphometric parameters (thickness of tibial epiphyseal cartilage and each cartilage zone, interradicular bone volume in the first lower molar, trabeculae volume, percentage of bone and cartilage, and osteoclast number in mandibular condyles) were assessed. results: ALN caused a significant decrease in femur and tibia length, tibial cartilage thickness, and longitudinal growth of hemimandibles. It increased interradicular bone volume and mandibular condyle trabeculae volume, increasing the percentage of cartilage and osteoclast number. conclusion: These findings indicate that administration of ALN to growing animals alters the endochondral ossification process, and thus alters growth.

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Section: Discussionmentioning

confidence: 99%

Effect of alendronate on the mandible and long bones: an experimental study in vivo

2015

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“…RIS is a potent amino-bisphosphonate that is also known to regulate cell proliferation, differentiation and gene expression in osteoblasts 35) . The drug has an affinity for bone tissue and approximately 50% of the systemically absorbed drug is deposited in bone, its presumed site of action 21) . One hypothesis is that RIS prevents bone resorption by altering osteoclasts cytoskeleton's proteins or inhibiting cholesterol synthesis which are necessary for the formation of the ruffled border, interfering directly with the fixation mechanisms of the osteoclasts to bone matrix 7) .…”

Section: Discussionmentioning

confidence: 99%

The Effect of Risedronate on Posterior Lateral Spinal Fusion in a Rat Model

Gezici

Ergün

Gürel

et al. 2009

J Korean Neurosurg Soc

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Objective : To evaluate the potential effects of risedronate (RIS) which shows a higher anti-resorptive effect among bisphosphonates, after a posterolateral lumbar intertransverse process spinal fusion using both autograft and allograft in a rat model. Methods : A totoal of 28 Sprague-Dawley rats were randomized into 2 study groups. A posterolateral lumbar intertransverse process spinal fusion was peformed using both autograft and allograft in a rat model. Group I (control) received 0.1 mL of steril saline (placebo) and Group II (treatment) received risedronate, equivalent to human dose (10 µg/kg/week) for 10-weeks period.Results : The fusion rates as determined by manual palpation were 69% in the group I and 46% in the group II (p = 0.251). According to radiographic score, the spinal segment was considered to be fused radiographically in 7 (53%) of the 13 controls and 9 (69%) of the 13 rats treated with RIS (p = 0.851). The mean histological scores were 5.69 ± 0.13 and 3.84 ± 0.43 for the control and treatment groups, respectively. There was a significant difference between the both groups (p = 0.001). The mean bone density of the fusion masses was 86.9 ± 2.34 in the control group and 106.0 ± 3.54 in the RIS treatment group. There was a statistical difference in mean bone densities of the fusion masses comparing the two groups (p = 0.001). Conclusion : In this study, risedronate appears to delay bone fusion in a rat model. This occurs as a result of uncoupling the balanced osteoclastic and osteoblastic activity inherent to bone healing. These findings suggest that a discontinuation of risedronate postoperatively during acute fusion period may be warranted.

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“…Each received either saline or alendronate (10 μg/100g/wk) subcutaneously for 8 wks and then was sacrificed by CO 2 narcosis. The dose of alendronate used in humans is approximately 1 mg/kg/wk orally (Huang et al, 2005). Our dosage in mice approximated the human dose (Samadfam et al, 2007).…”

Section: Materials and Methods Micementioning

confidence: 99%

Alendronate Affects Osteoblast Functions by Crosstalk through EphrinB1-EphB

2011

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Bisphosphonates are therapeutic agents in the treatment of post-menopausal osteoporosis. Although they have been associated with delayed healing in injured tissues, inappropriate femoral fractures, and osteonecrosis of the jaw (ONJ), the pathophysiological mechanisms involved are not clear. Our hypothesis is that alendronate, a member of the N-containing bisphosphonates, indirectly inhibits osteoblast function through the coupling of osteoclasts to osteoblasts by ephrinB-EphB interaction. We found that alendronate increased gene and protein expression of ephrinB1 and EphB1, as well as B3, in femurs of adult mice injected with alendronate (10 µg/100 g/wk) for 8 weeks. Alendronate suppressed the expression of bone sialoprotein (BSP) and osteonectin in both femurs and bone marrow osteoblastic cells of mice. After elimination of pre-osteoclasts from bone marrow cells, alendronate did not affect osteoblast differentiation, indicating the need for pre-osteoclasts for alendronate’s effects. Alendronate stimulated EphB1 and EphB3 protein expression in osteoblasts, whereas it enhanced ephrinB1 protein in pre-osteoclasts. In addition, a reverse signal by ephrinB1 inhibited osteoblast differentiation and suppressed BSP gene expression. Thus, alendronate, through its direct effects on the pre-osteoclast, appears to regulate expression of ephrinB1, which regulates and acts through the EphB1, B3 receptors on the osteoblast to suppress osteoblast differentiation.

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Alendronate Inhibits Spine Fusion in a Rat Model

Cited by 93 publications

References 29 publications

Effect of alendronate on the mandible and long bones: an experimental study in vivo

Effect of alendronate on the mandible and long bones: an experimental study in vivo

The Effect of Risedronate on Posterior Lateral Spinal Fusion in a Rat Model

Alendronate Affects Osteoblast Functions by Crosstalk through EphrinB1-EphB

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