Effect of Alendronate on Bone Formation during Tooth Extraction Wound Healing

Abstract

Alendronate (ALN) is an antiresorptive agent widely used for the treatment of osteoporosis. Its suppressive effect on osteoclasts has been extensively studied. However, the effect of ALN on bone formation is not as clear as its effect on resorption. The objective was to determine the effect of short-term ALN on bone formation and tooth extraction wound healing. Molar tooth extractions were performed in mice. ALN, parathyroid hormone (PTH), or saline (vehicle control) was administered. PTH was used as the bone anabolic control. Mice were euthanized at 3, 5, 7, 10, and 21 d after extractions. Hard tissue healing was determined histomorphometrically. Neutrophils and lymphatic and blood vessels were quantified to evaluate soft tissue healing. Gene expression in the wounds was assessed at the RNA level. Furthermore, the vossicle bone transplant system was used to verify findings from extraction wound analysis. Alkaline phosphatase (ALP) was visualized in the vossicles to assess osteoblast activity. ALN exhibited no negative effect on bone formation. In intact tibiae, ALN increased bone mass significantly more than PTH did. Consistently, significantly elevated osteoblast numbers were noted. In the extraction sockets, bone fill in the ALN-treated mice was equivalent to the control. Genes associated with bone morphogenetic protein signaling, such as bmp2, nog, and dlx5, were activated in the extraction wounds of the ALN-treated animals. Bone formation in vossicles was significantly enhanced in the ALN versus PTH group. In agreement with this, ALN upregulated ALP activity considerably in vossicles. Neutrophil aggregation and suppressed lymphangiogenesis were evident in the soft tissue at 21 d after extraction, although gross healing of extraction wounds was uneventful. Bone formation was not impeded by short-term ALN treatment. Rather, short-term ALN treatment enhanced bone formation. ALN did not alter bone fill in extraction sockets.

Arnica montana effects on gene expression in a human macrophage cell line. Evaluation by quantitative Real-Time PCR

“…49 Also the slight increase inBMP2 gene expression after treatment with A. montana is important because BMP2 is required for the initiation of bone repair 25,50 or other regenerative processes in vitro, 51 and BMP2 gene expression is activated in the wounds caused by tooth extraction in mice treated with alendronate, an antiresorptive agent widely used for the cure of osteoporosis. 52 The extent of differential regulation by A. montana on both types of macrophages was generally low and reached statistical significance only in a minority of the considered genes and dilutions. The slight effect in this in vitro model does not mean that the modulating effect will also be small in vivo, in whole organisms.…”

Clodronate-Loaded Liposome Treatment Has Site-Specific Skeletal Effects

“…Mice were monitored throughout the experiment and euthanized at day 7 or 14 following tooth extraction, and tissues were analyzed in a blinded manner. Time points were selected due to the high presence of macrophages early in oral wound repair and according to previously published studies detailing the typical healing window for rodent extraction sockets (Kuroshima, Entezami, et al 2014; Kuroshima, Mecano, et al 2014; Tanoue et al 2015). These methods are in compliance with the ARRIVE guidelines.…”

Intramedullary injury combined with osteoporosis therapeutics regulates targeted local osteogenesis

“…Injections were initiated at the time of local intramedullary injury. Doses were optimized based on our previous work and the relevant literature 18 , 38 , 39 . The remaining rats were in the fourth group (n = 7), where local intramedullary injury was performed in both tibiae followed by daily administration of PTH for two weeks.…”