Cisplatin chemotherapy impairs the peri‐implant bone repair around titanium implants: An in vivo study in rats

Matheus, Henrique Rinaldi; Ervolino, Edílson; Faleiros, Paula Lazilha; Novaes, Vivian Cristina Noronha; Theodoro, Letícia Helena; Garcia, Valdir Gouveia; Almeida, Juliano Milanezi de

doi:10.1111/jcpe.12824

Cited by 20 publications

(36 citation statements)

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“…Methotrexate increases osteocyte apoptosis in the metaphysis of long bones and also increases osteoclast number in trabecular bone of rats . Cisplatin inhibits bone healing in mice and rats . Cytokines and growth factors in bone serve both an autocrine and paracrine function to facilitate normal bone turnover and remodeling .…”

Section: Discussionmentioning

confidence: 99%

Zoledronic Acid Improves Muscle Function in Healthy Mice Treated with Chemotherapy

Hain

Jude

et al. 2019

Journal of Bone and Mineral Research

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Carboplatin is a chemotherapy drug used to treat solid tumors but also causes bone loss and muscle atrophy and weakness. Bone loss contributes to muscle weakness through bone-muscle crosstalk, which is prevented with the bisphosphonate zoledronic acid (ZA). We treated mice with carboplatin in the presence or absence of ZA to assess the impact of bone resorption on muscle. Carboplatin caused loss of body weight, muscle mass, and bone mass, and also led to muscle weakness as early as 7 days after treatment. Mice treated with carboplatin and ZA lost body weight and muscle mass but did not lose bone mass. In addition, muscle function in mice treated with ZA was similar to control animals. We also used the anti-TGFβ antibody (1D11) to prevent carboplatin-induced bone loss and showed similar results to ZA-treated mice. We found that atrogin-1 mRNA expression was increased in muscle from mice treated with carboplatin, which explained muscle atrophy. In mice treated with carboplatin for 1 or 3 days, we did not observe any bone or muscle loss, or muscle weakness. In addition, reduced caloric intake in the carboplatin treated mice did not cause loss of bone or muscle mass, or muscle weakness. Our results show that blocking carboplatin-induced bone resorption is sufficient to prevent skeletal muscle weakness and suggests another benefit to bone therapy beyond bone in patients receiving chemotherapy.n 368 HAIN ET AL. TissueMice were euthanized and the tibialis anterior (TA), soleus, and gastrocnemius were dissected. The extensor digitorum longus (EDL) muscle was dissected for muscle contractility. Muscles were either snap frozen in liquid nitrogen for biochemical analysis or embedded in optimum cutting temperature (O.C.T., Tissue Tek, Torrance, CA, USA) compound in cryomolds and frozen in liquid nitrogencooled 2-methylbutane (isopentane) for histological analysis. (38) Journal of Bone and Mineral Research ZA IMPROVES MUSCLE FUNCTION IN HEALTHY MICE TREATED WITH CHEMOTHERAPY 369 n 40. Wen Y, Murach KA, Vechetti IJ Jr, et al. MyoVision: software for automated high-content analysis of skeletal muscle immunohistochemistry. J Appl Physiol. 2018;124(1):40-51. 41. Edwards JR, Nyman JS, Lwin ST, et al. Inhibition of TGF-beta signaling by 1D11 antibody treatment increases bone mass and quality in vivo.

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Section: Discussionmentioning

confidence: 99%

Zoledronic Acid Improves Muscle Function in Healthy Mice Treated with Chemotherapy

Hain

Jude

et al. 2019

Journal of Bone and Mineral Research

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“…Among the most recently used chemotherapeutic drugs, Cisplatin stands out because it has a marked antitumor activity against various types of cancer (Almeida et al, ; Mitin et al, ). However, one of its side effects is a reduction in bone remodeling (Al‐Mahalawy et al, ; Kovács, ; Matheus et al, ; Stine et al, ; Young, Shih, et al, ; Young, Virolainen, et al, ), which may hamper the patients' bone metabolism and, consequently, impair their rehabilitation with osseointegratable implants. Thus, this study assessed the bone quality and the osseointegration of dental implants after exposure to the chemotherapeutic drug Cisplatin.…”

Section: Discussionmentioning

confidence: 99%

“…One of the parameters of direct assessment of this osseointegration is the removal torque. To our knowledge, none of the studies that assessed the effect of Cisplatin on osseointegration of implants (Al‐Mahalawy et al, ; Kovács, ; Matheus et al, ) performed the measurement of this parameter. In the present study, the implants of the animals in the CIS groups required less torque for their removal in relation to those placed in the animals of the CTL groups, in both time points.…”

Section: Discussionmentioning

confidence: 99%

“…A possible reason for the reduction in removal torque may be related to a change in the inflammatory response of the animals exposed to Cisplatin. A recent study that assessed the effect of this drug on the osseointegration of implants reported that the animals treated had an exacerbated and persistent inflammatory response up to 60 days after implant installation (Matheus et al, ). During the surgical procedure for implant installation, the perforated cavity of the bone is comparable to a common bone wound.…”

Section: Discussionmentioning

confidence: 99%

“…This effect may induce a state similar to osteoporosis, leading to a possible reduction in the survival rates of dental implants, even when hormone replacement is performed (Minsk & Polson, ). Another side effect resulting from chemotherapy, specifically with Cisplatin, is a reduction in bone remodeling (Al‐Mahalawy et al, ; Kovács, ; Matheus et al, ; Monsell, Barnes, Bellemore, Biston, & Goodship, ; Young, Shih, et al, ; Young, Virolainen, Inoue, Frassica, & Chao, ). In vivo experiments in dogs found that, when this drug was administered after orthopedic surgery, there was a smaller amount of new bone formation (Young, Shih, et al, ).…”

Section: Introductionmentioning

confidence: 99%

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The influence of Cisplatin‐based chemotherapy on the osseointegration of dental implants: An in vivo mechanical and histometrical study

Dantas

Verzola

Sanitá³

et al. 2019

Clinical Oral Implants Res

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Objectives To evaluate the effect of Cisplatin on bone repair and mineralization around implants and on the mechanical properties of bone tissue. Materials and methods Forty‐three Wistar rats were randomly divided into two groups: Cisplatin (CIS, medication) and control (CTL, placebo solution), administered once a week for 4 weeks. After 4 weeks, implants were installed in both tibiae metaphysis. After 30 and 60 days, the animals were sacrificed and their femurs and tibiae were removed. Femurs were subjected to mechanical tests and tibiae for removal torque, arrangement and distribution of collagen fibers, morphometrical analyses (bone tissue in contact with the implant surface [BIC] and areal fraction between implant threads occupied by bone tissue [BAFO]) and scanning electron microscopy to calcium and calcium/phosphorus analysis. Data were analyzed by ANOVA or MANOVA, and Tukey or Games–Howell post hoc tests, respectively (α = 0.05). Results The CTL specimens had significantly higher values (0.0001 ≤ p≤0.036) of strength (N), removal torque (N/cm2), %BIC, and %BAFO than CIS specimens, being their best results at day 60. No significant differences were found among the groups regarding the values of deformation, percentage of calcium, and calcium/phosphorus ratio. In CIS groups, there was a reduction in the organization of collagen at the bone/implant interface, resulting in a trabecular bone with thin trabeculae and birefringent collagen and irregular arrangement. Conclusions and clinical implications Cisplatin interfered negatively in the repair and mineralization around dental implants, as well as on the quality of the bone tissue, mainly in the period of 30 days after the implant placement.

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Bone Biology

2022

Essential Techniques of Alveolar Bone Augmentation in Implant Dentistry

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Cisplatin chemotherapy impairs the peri‐implant bone repair around titanium implants: An in vivo study in rats

Abstract: Within the limits of this study, it was concluded that the chemotherapeutic CIS negatively affects the bone repair at peri-implant areas, jeopardizing the osseointegration of titanium implants.

Cited by 20 publications

References 56 publications

Zoledronic Acid Improves Muscle Function in Healthy Mice Treated with Chemotherapy

Zoledronic Acid Improves Muscle Function in Healthy Mice Treated with Chemotherapy

The influence of Cisplatin‐based chemotherapy on the osseointegration of dental implants: An in vivo mechanical and histometrical study

Bone Biology

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