A large amount of microdamages in the cortical bone around fracture site in a patient of atypical femoral fracture after long-term bisphosphonate therapy

Iwata, Ken; Mashiba, Tasuku; Hitora, Toshiaki; Yamagami, Yoshiki; Yamamoto, Toshiyuki

doi:10.1016/j.bone.2014.04.012

Cited by 35 publications

(16 citation statements)

References 26 publications

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“…Physiological microdamage formation within the skeleton serves as a stimulant for bone remodeling. Accumulation of unrepaired microdamage in trabecular bone can result from inferior bone quality due to age-related changes or skeletal pathology (Iwata 2014). Despite the importance of microdamage to the mechanical properties of bone, the trabecular stresses and strains experienced at its initiation are not well characterized.…”

Section: Introductionmentioning

confidence: 99%

μFE models can represent microdamaged regions of healthy and metastatically involved whole vertebrae identified through histology and contrast enhanced μCT imaging

Choudhari

Chan

Akens

et al. 2016

Journal of Biomechanics

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Micro-damage formation within the skeleton is an important stimulant for bone remodeling, however abnormal build-up of micro-damage can lead to skeletal fragility. In this study, µCT imaging based micro finite element (μFE) models were used to evaluate tissue level damage criteria in whole healthy and metastatically-involved vertebrae. T13-L2 spinal segments were excised from osteolytic (n=3) and healthy (n=3) female athymic rnu/rnu rats. Osteolytic metastasis was generated by intercardiac injection of HeLa cancer cells. Micro-mechanical axial loading was applied to the spinal motion segments under μCT imaging. Vertebral samples underwent BaSO4 staining and sequential calcein/fuchsin staining to identify load induced micro-damage. μCT imaging was used generate specimen specific μFE models of the healthy and osteolytic whole rat vertebrae. Model boundary conditions were generated through deformable image registration of loaded and unloaded scans. Elevated stresses and strains were detected in regions of micro-damage identified through histological and BaSO4 staining within healthy and osteolytic vertebral models, as compared to undamaged regions. Additionally, damaged regions of metastatic vertebrae experienced significantly higher local stresses and strains than those in the damaged regions of healthy specimens. Areas identified by BaSO4 staining, however, yielded lower levels of stress and strain in damaged and undamaged regions of healthy and metastatic vertebrae as compared to fuschin staining. The multimodal (experimental, image-based and computational) techniques used in this study demonstrated the ability of local stresses and strains computed through µFE analysis to identify trabecular micro-damage, that can be applied to biomechanical analyses of healthy and diseased whole bones.

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Section: Introductionmentioning

confidence: 99%

μFE models can represent microdamaged regions of healthy and metastatically involved whole vertebrae identified through histology and contrast enhanced μCT imaging

Choudhari

Chan

Akens

et al. 2016

Journal of Biomechanics

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“…The matrix susceptibility to microcracking, for example, can contribute to fatigue life and therefore fracture risk, but may not be captured in fracture toughness measurements. Indeed, previous research has clearly shown that tissues from bisphosphonate‐treated preclinical animal studies show an increased microcrack burden and reduced fatigue life following cyclic loading and in human biopsy studies have reported extensive microcracking in regions surrounding atypical femoral fractures . Future work is necessary to determine whether the matrix maturation effects noted in the current study are associated with changes in the fatigue properties of cortical bone.…”

Section: Discussionmentioning

confidence: 76%

“…Indeed, previous research has clearly shown that tissues from bisphosphonate-treated preclinical animal studies show an increased microcrack burden and reduced fatigue life following cyclic loading (38)(39)(40)(41)(42) and in human biopsy studies have reported extensive microcracking in regions surrounding atypical femoral fractures. (43) Future work is necessary to determine whether the matrix maturation effects noted in the current study are associated with changes in the fatigue properties of cortical bone. The current study used a relatively low dose and only a single bisphosphonate.…”

Section: Discussionmentioning

confidence: 95%

Osteoporosis Treatments Affect Bone Matrix Maturation in a Rat Model of Induced Cortical Remodeling

et al. 2020

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To test how osteoporosis drugs affect bone matrix maturation during cortical bone remodeling, 72 pregnant rats were switched from a 0.4% to a 0.01% calcium diet at parturition for a 23‐day lactation period. At weaning, eight dams were sacrificed to establish baseline values, while the remaining dams were returned to 0.4% calcium and treated with vehicle (saline), sodium fluoride (NaF), zoledronic acid (ZA), or sclerostin antibody (Scl‐Ab) for either 7 or 28 days (eight animals per group per time point). Femora were examined by μCT, dynamic histomorphometry, Fourier transform infrared imaging, and three‐point bending of notched specimens. Cortical porosity decreased in all groups from baseline to day 28. Intracortical mineralizing surface (MS/BS) and mineral apposition rate (MAR), as well as the mineral‐to‐matrix ratio were unaffected by treatment, but intracortical crystallinity was increased in the ZA group at day 10 compared with vehicle. Cortical area increased in all groups over 28 days mainly because of an addition of bone at the endocortical surface. Endocortical MS/BS did not vary among the groups, but endocortical MAR was suppressed in the NaF group at day 2 and elevated in the Scl‐Ab group at day 4 compared with vehicle. Endocortical mineral‐to‐matrix ratio was increased at days 5 and 10 following NaF treatment and endocortical crystallinity was increased at day 5 following ZA treatment compared with vehicle. Fracture toughness did not differ among the groups. Thus, the treatments affected matrix maturation more strongly at the endocortical then intracortical envelope. In this model of induced remodeling, the bone formation phase is synchronized at multiple sites, facilitating study of the effects of drugs or other bone‐targeting agents on matrix maturation independent of their effects on the initiation of remodeling. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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“…However, because TP is expensive and its allowed duration of administration is limited, the use of TP is problematic in terms of timing [9]. In contrast, several studies have reported osteonecrosis of the jaw or atypical femoral fracture as adverse effects of BP [10][11][12], which are not observed under TP.…”

Section: Introductionmentioning

confidence: 99%

Effect of Bisphosphonates or Teriparatide on Mechanical Complications after Posterior Instrumented Fusion for Osteoporotic Vertebral Fracture: A Multi-center Retrospective Study

Kawabata

Yoshii

Hirai

et al. 2020

Preprint

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Abstract Background: The optimal treatment of osteoporosis after reconstruction surgery for osteoporotic vertebral fractures (OVF) remains unclear. In this multicentre retrospective study, we investigated the effects of typically used agents for osteoporosis, namely, bisphosphonates (BP) and teriparatide (TP), on surgical results in patients with osteoporotic vertebral fractures.Methods: Retrospectively registered data were collected from 27 universities and affiliated hospitals in Japan. We compared the effects of BP vs TP on postoperative mechanical complication rates, implant-related reoperation rates, and clinical outcomes in patients who underwent posterior instrumented fusion for OVF and had been followed up at least for 2 years. Data were analysed according to whether the osteoporosis was primary or glucocorticoid-induced.Results: A total of 165 patients who underwent posterior instrumented fusion for OVF were included. The overall mechanical complication rate was significantly lower in the TP group than in the BP group (BP vs TP: 73.0% vs. 55.7%, p = 0.018). The screw backout rate was significantly lower and the rates of new vertebral fractures and pseudoarthrosis tended to be lower in the TP group than in the BP group. However, there were no significant differences in lumbar functional scores and visual analogue scale pain scores or in implant-related reoperation rates between the two groups. The incidence of pseudoarthrosis was significantly higher in patients with glucocorticoid-induced osteoporosis (GIOP) than in those with primary osteoporosis; however, the pseudoarthrosis rate was reduced by using TP. The use of TP also tended to reduce the overall mechanical complication rate in both primary osteoporosis and GIOP. Conclusions: The overall mechanical complication rate was lower in patients who received TP than in those who received a BP postoperatively, regardless of type of osteoporosis. The incidence of pseudoarthrosis was significantly higher in patients with GIOP, but the use of TP reduced the rate of pseudoarthrosis in GIOP patients.

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A large amount of microdamages in the cortical bone around fracture site in a patient of atypical femoral fracture after long-term bisphosphonate therapy

Cited by 35 publications

References 26 publications

μFE models can represent microdamaged regions of healthy and metastatically involved whole vertebrae identified through histology and contrast enhanced μCT imaging

μFE models can represent microdamaged regions of healthy and metastatically involved whole vertebrae identified through histology and contrast enhanced μCT imaging

Osteoporosis Treatments Affect Bone Matrix Maturation in a Rat Model of Induced Cortical Remodeling

Effect of Bisphosphonates or Teriparatide on Mechanical Complications after Posterior Instrumented Fusion for Osteoporotic Vertebral Fracture: A Multi-center Retrospective Study

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