Histological and biomechanical effects of zoledronate on fracture healing in an osteoporotic rat tibia model

Türker, Mehmet; Aslan, Arif; Çirpar, Meriç; Kochai, Alauddin; Tulmaç, Özlem Banu; Balcı, Mahi

doi:10.5606/ehc.2016.03

Cited by 15 publications

(7 citation statements)

References 22 publications

(25 reference statements)

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“…BPs in studies of fracture healing produce a larger callus and improved early mechanical fracture properties (Turker et al. 2016 ). In the early fracture-healing phase, a larger callus may explain an increased ability to withstand load.…”

Section: Discussionmentioning

confidence: 99%

Negative effect of zoledronic acid on tendon-to-bone healing

et al. 2018

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Background and purposeOutcome after ligament reconstruction or tendon repair depends on secure tendon-to-bone healing. Increased osteoclastic activity resulting in local bone loss may contribute to delayed healing of the tendon–bone interface. The objective of this study was to evaluate the effect of the bisphosphonate zoledronic acid (ZA) on tendon-to-bone healing.MethodsWistar rats (n = 92) had their right Achilles tendon cut proximally, pulled through a bone tunnel in the distal tibia and sutured anteriorly. After 1 week animals were randomized to receive a single dose of ZA (0.1 mg/kg IV) or control. Healing was evaluated at 3 and 6 weeks by mechanical testing, dual-energy X-ray absorptiometry and histology including immunohistochemical staining of osteoclasts.ResultsZA treatment resulted in 19% (95% CI 5–33%) lower pullout strength and 43% (95% CI 14–72%) lower stiffness of the tendon–bone interface, compared with control (2-way ANOVA; p = 0.009, p = 0.007). Administration of ZA did not affect bone mineral density (BMD) or bone mineral content (BMC). Histological analyses did not reveal differences in callus formation or osteoclasts between the study groups.InterpretationZA reduced pullout strength and stiffness of the tendon–bone interface. The study does not provide support for ZA as adjuvant treatment in tendon-to-bone healing.

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Section: Discussionmentioning

confidence: 99%

Negative effect of zoledronic acid on tendon-to-bone healing

et al. 2018

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“…Osteoporotic models – In rats with a tibial fracture, administration of zoledronic acid resulted in increased biomechanical strength, more callus as well as thicker and more mature bone trabeculae, and in both the zoledronic acid group and the control group there was complete healing [40] . Bisphosphonates in rats with a femoral fracture increased the mechanical strength of the callus [41] and hard callus bone mineral content [25] .…”

Section: Resultsmentioning

confidence: 99%

The effect of osteoporosis and its treatment on fracture healing a systematic review of animal and clinical studies

et al. 2021

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Introduction Osteoporosis is characterised by low bone mass and micro-architectural deterioration of bone structure. Its treatment is directed at the processes of bone formation or resorption, that are of utmost importance in fracture healing. We provide a comprehensive review of the literature aiming to summarize and clarify the effects of osteoporosis and its treatment on fracture healing. Material and methods A literature search was conducted in PubMed and Embase (OVID version). In vivo animal and human studies on long bone fractures were included. A total of 93 articles were included for this review; 23 studies on the effect of osteoporosis (18 animal and 5 clinical studies) and 70 studies on the effect of osteoporosis treatment (41 animal, 26 clinical studies and 3 meta-analyses) on fracture healing. Results In animal fracture models osteoporosis was associated with decreased callus formation and bone growth, bone mineral density, biomechanical strength and delayed cellular and differentiation processes during fracture healing. Two large databases identified osteoporosis as a risk factor for non-union whereas three other studies did not. One of those three studies however found a prolonged healing time in patients with osteoporosis. Anti-osteoporosis medication showed inconsistent effects on fracture healing in both non-osteoporotic and osteoporotic animal models. Only the parathyroid hormone and anti-resorption medication were related to improved fracture healing and delayed remodelling respectively. Clinical studies performed in predominantly hip and distal radius fracture patients showed no effect of bisphosphonates on fracture healing. Parathyroid hormone reduced time to union in several clinical trials performed in mainly hip fracture patients, but this did not result in decreased delayed or non-union rates. Conclusion Evidence that substantiates the negative influence of osteoporosis on fracture healing is predominantly from animal studies and to a lesser extent from clinical studies, since convincing clinical evidence lacks. Bisphosphonates and parathyroid hormone may be used during fracture healing, since no clear negative effect has been shown. Parathyroid hormone might even decrease time to fracture union, without decreasing union rate.

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“…On the other side, biomechanical test was conducted in our research since it was the most direct method to evaluate fracture healing. 26 Specifically, the increase of peak torque indicates the increase of bone mineral content and the improvement of bone microstructure, 27 and torsional stiffness is verified to be a valid variable in the assessment of fracture healing. 28 F I G U R E 5 The expression of osteogenesis-related genes (Runx2, OCN, ALP, COL1A1A1, OSX, and Sox9) (A) and ERK, p38 and JNK-pathway related proteins (B).…”

Section: Discussionmentioning

confidence: 97%

“…On the other side, biomechanical test was conducted in our research since it was the most direct method to evaluate fracture healing . Specifically, the increase of peak torque indicates the increase of bone mineral content and the improvement of bone microstructure, and torsional stiffness is verified to be a valid variable in the assessment of fracture healing . Therefore, we measured the relevant indexes of rat tibia and found that rats in the HMGB1 group had significantly elevated torsional stiffness and peak torque, which suggested that HMGB1 can promote the healing process of rat tibial fractures morphologically and biomechanically.…”

Section: Discussionmentioning

confidence: 99%

HMGB1 promotes bone fracture healing through activation of ERK signaling pathway in a rat tibial fracture model

Chen

Luan

2019

The Kaohsiung J of Med Scie

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This work was to investigate potential roles of HMGB1‐mediated ERK pathway in the healing process of bone fracture. Rat tibial fracture models were established and divided into control (rats with normal saline), HMGB1 (rats with HMGB1), and HMGB1+ PD98059 groups (rats with HMGB1 and 1 mg/kg of ERK1/2 inhibitor PD98059) with 30 rats per each. The healing of rats' fracture was observed by X‐ray films, the morphological changes of bone fractures by HE staining, the callus formation by micro‐CT and biomechanical test, and the expression of osteogenesis‐related genes, HMGB1 and ERK‐related proteins by qRT‐PCR and Western blot. Rats in the HMGB1 group was increased in X‐ray scores, peak torque, torsional stiffness, and the bone volume fraction (bone volume/total volume, BV/TV); meanwhile, those rats presented elevations in osteogenesis‐related genes and HMGB1 expressions, as well as p‐ERK/ERK ratio. However, rats in the HMGB1+ PD98059 group was significantly reduced in X‐ray score, peak torque, torsional stiffness, and BV/TV, as well as the expression of osteogenesis‐related genes and the ratio of p‐ERK/ERK, as compared to those from HMGB1 group. HMGB1 could promote the expressions of osteogenesis‐related genes and accelerate the healing process of fracture via activation of the ERK signaling pathway.

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Histological and biomechanical effects of zoledronate on fracture healing in an osteoporotic rat tibia model

Cited by 15 publications

References 22 publications

Negative effect of zoledronic acid on tendon-to-bone healing

Negative effect of zoledronic acid on tendon-to-bone healing

The effect of osteoporosis and its treatment on fracture healing a systematic review of animal and clinical studies

HMGB1 promotes bone fracture healing through activation of ERK signaling pathway in a rat tibial fracture model

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