Effects of bisphosphonate treatment on bone repair under immunosuppression using cyclosporine A in adult rats

Matsunaga, Takaharu; Shigetomi, Mitsunori; Hashimoto, Takahiro; Suzuki, Haruko; Gondo, Toshikazu; Tanaka, Hiroshi; Sugiyama, Toshihiro; Taguchi, Toshihiko

doi:10.1007/s00198-007-0387-z

Cited by 7 publications

(2 citation statements)

References 44 publications

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“…[7][8][9] Other treatments are now in use or in trial, such as WNT pathway regulators, parathyroid hormone, statins, and prostaglandin agonists. [10][11][12][13][14] In parallel, the demand for new cell-based therapies is growing. The need for additional sources of cells is particularly evident for severe trauma cases, cancer treatment, and maxillofacial reconstructive surgery when large bone defects cannot be filled solely with artificial scaffolds or autografts.…”

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confidence: 99%

Cell Sources for Bone Tissue Engineering: Insights from Basic Science

Colnot

2011

Tissue Engineering Part B: Reviews

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One of the goals of bone tissue engineering is to design delivery methods for skeletal stem/progenitor cells to repair or replace bone. Although the materials used to retain cells play a central role in the quality of the constructs, the source of cells is key for bone regeneration. Bone marrow is the most common cell source, but other tissues are now being explored, such as the periosteum, fat, muscle, cord blood, and embryonic or induced pluripotent stem cells. The therapeutic effect of exogenous stem/progenitor cells is accepted, yet their contribution to bone repair is not well defined. The in vitro osteo- and/or chondrogenic potential of these skeletal progenitors do not necessarily predict their differentiation potential in vivo and their function may be affected by their ability to home correctly to bone. This review provides an overview of animal models used to test the efficacy of cell-based approaches. We examine the mechanisms of endogenous cell recruitment during bone repair and compare the role of local versus systemic cell recruitment. We discuss how the normal repair process can help define efficacious cell sources for bone tissue engineering and improve their methods of delivery.

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confidence: 99%

Cell Sources for Bone Tissue Engineering: Insights from Basic Science

Colnot

2011

Tissue Engineering Part B: Reviews

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“…Only a few studies have examined the effects of anti-osteoporosis drugs on tacrolimus-induced bone loss. The clinical studies (30,31) and animal studies (32,33) found significant protective effects of bisphosphonate on calcineurin inhibitor-induced bone loss. However, long-term administration of bisphosphonate increases microdamage accumulation in the bone (15)(16)(17) and is involved in the development of atypical femoral fractures (18)(19)(20)(21).…”

Section: Bone Strength Propertiesmentioning

confidence: 99%

Effects of the combined administration of risedronate and menatetrenone on bone loss induced by tacrolimus in rats

Kanda

Furukawa

Izumo

et al. 2020

DD&T

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Bisphosphonate, menatetrenone, combined administration, bone loss, tacrolimus Tacrolimus, a calcineurin inhibitor, affects bone metabolism and increases the risk of fracture due to marked bone loss. Bisphosphonates increase the bone mineral density (BMD) in osteoporosis patients. Menatetrenone has less positive effects on BMD but reduces the risk of fracture by improving bone quality. In this study, we investigated the effectiveness of the combined administration of risedronate and menatetrenone against bone loss induced by tacrolimus. Wistar rats were divided into four groups: [1] control, [2] tacrolimus at 1.5 mg/kg, [3] tacrolimus + risedronate at 1.0 mg/kg, and [4] tacrolimus + risedronate + menatetrenone at 20 mg/kg. After the drugs were administered for 4 weeks, bone histomorphometric analysis was performed and bone strength was evaluated using a threepoint bending method. BMD was measured using quantitative computed tomography. Tacrolimus significantly reduced the BMD and strength properties of the lower limb bones. These tacrolimusinduced decreases were suppressed by risedronate treatment. The combined administration of risedronate and menatetrenone more significantly improved bone strength properties than risedronate alone. Bone histomorphometric analysis revealed a significant increase in bone resorption with tacrolimus. Risedronate alone significantly suppressed the tacrolimus-induced increase in bone resorption but simultaneously reduced bone formation. On the other hand, the combined administration of risedronate and menatetrenone suppressed the tacrolimus-induced increase in bone resorption, in addition to the significant risedronate-induced decrease in bone formation. This study suggests that the combined administration of risedronate and menatetrenone improves bone strength in tacrolimustreated rats by preventing and ameliorating the risedronate-induced suppression of bone formation.

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Sequential Treatment with Intermittent Low-Dose Human Parathyroid Hormone (1-34) and Bisphosphonate Enhances Large-Size Skeletal Reconstruction by Vascularized Bone Transplantation

et al. 2007

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Vascularized bone transplantation enables reconstruction of large skeletal defects, but this process needs a long time. Since short-term intermittent parathyroid hormone (PTH) enhances rat fracture healing, we investigated the effects of 4-week intermittent low-dose (10 microg/kg/day) or high-dose (100 microg/kg/day) PTH followed by 4-week vehicle, low-dose or high-dose intermittent PTH, or zoledronic acid (ZOL, 2 micro/kg/week), a potent bisphosphonate, on large skeletal reconstruction by vascularized tibial grafting in rats. Compared to 8-week vehicle, 8-week low-dose PTH did not significantly increase the serum osteocalcin level as well as the urinary deoxypyridinoline level, while 4-week low-dose or high-dose PTH followed by 4-week ZOL decreased both of these levels. Eight-week PTH increased the bone mass of the graft and strength of the reconstructed skeleton in a dose-dependent manner; notably, the reconstructed skeleton showed an obviously higher response to PTH compared to the contralateral nonoperated femur. In contrast, 4-week PTH followed by 4-week vehicle reduced these effects and caused local bone loss at the host-graft junctions. Four-week PTH followed by 4-week ZOL did not induce such bone loss; however, 4-week high-dose PTH followed by 4-week ZOL caused a large callus in the distal cortical junction. Four-week PTH followed by 4-week ZOL increased the bone mass and strength similarly to 8-week PTH. These preliminary findings suggest, for the first time, that sequential treatment with short-term intermittent low-dose PTH and bisphosphonate as well as long-term intermittent low-dose PTH treatment enhance large skeletal reconstruction by vascularized bone transplantation, though early timing of sequential antiresorptive treatment could result in delay of bone repair.

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Effects of bisphosphonate treatment on bone repair under immunosuppression using cyclosporine A in adult rats

Abstract: In this rat model, long-term CsA administration increases bone turnover, at least partly, through hyperparathyroidism and high-dose zoledronic acid treatment does not impair the union of CsA-administered bone.

Cited by 7 publications

References 44 publications

Cell Sources for Bone Tissue Engineering: Insights from Basic Science

Cell Sources for Bone Tissue Engineering: Insights from Basic Science

Effects of the combined administration of risedronate and menatetrenone on bone loss induced by tacrolimus in rats

Sequential Treatment with Intermittent Low-Dose Human Parathyroid Hormone (1-34) and Bisphosphonate Enhances Large-Size Skeletal Reconstruction by Vascularized Bone Transplantation

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