Cancer treatment-induced bone loss (CTIBL): Pathogenesis and clinical implications

D’Oronzo, Stella; Stucci, Luigia Stefania; Tucci, Marco; Silvestris, Franco

doi:10.1016/j.ctrv.2015.09.003

Cited by 87 publications

(73 citation statements)

References 96 publications

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“…However, the positive effects of PTH delivery in a juvenile animal model could potentially occur if bone modeling were attenuated by metabolic bone diseases, chronic disease, immobilization, or following radiotherapy or chemotherapy. 31 Anti-sclerostin antibody, an anabolic drug, has been shown to increase bone mass and strength (but not elastic modulus) in growing wild type and osteogenesis imperfecta mice. 8; 9 A study in juvenile rats found that local bone loss resulting from focal irradiation was attenuated by PTH treatment, 32 possibly due to improved osteoblast/osteocyte survival.…”

Section: Discussionmentioning

confidence: 99%

PTH(1-34) and zoledronic acid have differing longitudinal effects on juvenile mouse femur strength and morphology

et al. 2016

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Treatment of secondary pediatric osteoporosis—particularly that due to chronic diseases, immobilization, and necessary medical treatments—is currently limited by a poor understanding of the long-term efficacy and safety of skeletal metabolism modifying drugs. This study aimed to characterize longitudinal effects of representative anabolic (parathyroid hormone, PTH) and anti-catabolic (zoledronic acid, ZA) drugs on skeletal morphology, mechanical strength, and growth in juvenile mice. BALB/cJ mice aged four weeks were given PTH(1–34) or vehicle (control) daily for eight weeks, or four weekly doses of ZA, and evaluated at time points 0–26 weeks after treatment initiation. There were no enduring differences in body length or mass between treatment groups. ZA increased femur size as early as week 0, including increased distal femur bone volume and diaphyseal cross-sectional area, persisting through week 26. PTH treatment only transiently increased bone size, including distal femur volume at weeks 4–12. ZA decreased diaphyseal cortical tissue mineral density (TMD) at 12–26 weeks vs. controls; PTH decreased TMD only at 2 weeks (vs. controls). ZA increased bending strength at 0–12 weeks and flexural strength at week 4 (vs. controls), but decreased flexural strength and modulus at week 26. PTH treatment increased bending strength only at 4 weeks, and did not affect flexural strength. Overall, ZA rapidly and persistently increased femur strength and size, but compromised bone material quality long-term. In healthy juvenile mice, limited-duration PTH treatment did not exert a strong anabolic effect, and had no adverse effects on femur strength, morphology, or growth.

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Section: Discussionmentioning

confidence: 99%

PTH(1-34) and zoledronic acid have differing longitudinal effects on juvenile mouse femur strength and morphology

et al. 2016

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“…Long‐term sequelae of cancer therapy include an increased risk for developing osteoporosis. Several anticancer therapies (hormonal and nonhormonal) have the potential to promote bone loss through direct dysregulation of bone turnover and indirect mechanisms such as hypogonadism and nephrotoxicity . Such therapies include endocrine therapies for breast cancer, which mitigate the effects of estrogen; androgen deprivation therapy (ADT) for prostate cancer; and antineoplastic drugs such as platinum‐derived compounds (cisplatin), alkylating agents (ifosfamide, cyclophosphamide, doxorubicin), antimetabolites (methotrexate), glucocorticoids, and targeted therapies.…”

Section: Bone Loss In Cancer Patientsmentioning

confidence: 99%

“…Additionally, other interventions for cancer patients such as radiation therapy, gonadal ablation, bilateral orchiectomy, and oophorectomy also result in bone loss . Ultimately, increased bone resorption and turnover can lead to osteopenia, osteoporosis, and resultant increases in fracture risk and mortality …”

Section: Bone Loss In Cancer Patientsmentioning

confidence: 99%

Cancer‐ and Chemotherapy‐Induced Musculoskeletal Degradation

et al. 2019

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Mobility in advanced cancer patients is a major health care concern and is often lost in advanced metastatic cancers. Erosion of mobility is a major component in determining quality of life but also starts a process of loss of muscle and bone mass that further devastates patients. In addition, treatment options become limited in these advanced cancer patients. Loss of bone and muscle occurs concomitantly. Advanced cancers that are metastatic to bone often lead to bone loss (osteolytic lesions) but may also lead to abnormal deposition of new bone (osteoblastic lesions). However, in both cases there is a disruption to normal bone remodeling and radiologic evidence of bone loss. Many antitumor therapies can also lead to loss of bone in cancer survivors. Bone loss releases cytokines (TGFβ) stored in the mineralized matrix that can act on skeletal muscle and lead to weakness. Likewise, loss of skeletal muscle mass leads to reduced bone mass and quality via mechanical and endocrine signals. Collectively these interactions are termed bone‐muscle cross‐talk, which has garnered much attention recently as a prime target for musculoskeletal health. Pharmacological approaches as well as nutrition and exercise can improve muscle and bone but have fallen short in the context of advanced cancers and cachexia. This review highlights our current knowledge of these interventions and discusses the difficulties in treating severe musculoskeletal deficits with the emphasis on improving not only bone mass and muscle size but also functional outcomes. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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“…Radiation‐induced bone loss is an important complication in radiotherapy, occupational exposure, and astronauts. They were generally found with reduction in bone mineral density (BMD), deterioration of trabecular microarchitecture and increased risk of fracture, defined as osteopenia and osteoporosis (D'Oronzo, Stucci, Tucci, & Silvestris, ). In population epidemiological studies, it has been reported that patients received radiotherapy for pelvic tumors have increased risk of bone loss induced hip fracture (Baxter, Habermann, Tepper, Durham, & Virnig, ; Ikushima et al, ; Igdem et al, ; Kwon et al, ).…”

Section: Introductionmentioning

confidence: 99%

“…Apart from the already bone loss at direct irradiated bone, bone loss occurs at abscopal tissues as well (Cao et al, ; Van et al, ; Yang et al, ). Thus, radiation induced bone loss is to be a social and economic problem (D'Oronzo et al, ; Williams & Davies, ; Wissing, ), and it is extremely important to reveal the underlying cellular and molecular mechanism of radiation‐induced bone loss.…”

Section: Introductionmentioning

confidence: 99%

Suppressing angiogenesis regulates the irradiation‐induced stimulation on osteoclastogenesis in vitro

Tong

Zhu

Wang

et al. 2017

Journal Cellular Physiology

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Ionizing radiation-induced bone loss is a potential health concern in radiotherapy, occupational exposure, and astronauts. Although impaired bone vasculature and reduced proliferation of bone-forming osteoblasts has been implicated in this process, it has not been clearly characterized that whether radiation affects the growth of bone-resorbing osteoclasts. The molecular crosstalk between different cell populations in the skeletal system has not yet been elucidated in detail, especially between the increased bone resorption at early stage of post-irradiation and bone marrow-derived endothelial progenitor cells (BM-EPCs). In order to further understand the mechanisms involved in radiation-induced bone loss at the cellular level, we assessed the effects of irradiation on angiogenesis of BM-EPCs and osteoclastogenesis of receptor activator for nuclear factor-κB ligand (RANKL)-stimulated RAW 264.7 cells and crosstalk between these cell populations. We herein found significantly dysfunction of BM-EPCs in response to irradiation at a dose of 2 Gy, including inhibited proliferation, migration, tube-forming abilities, and downregulated expression of pro-angiogenesis vascular endothelial growth factors A (VEGF A). Meanwhile, we observed that irradiation promoted osteoclastogenesis of RANKL-stimulated RAW 264.7 cells directly or indirectly. These results provide quantitative evidences of irradiation induced osteoclastogenesis at a cellular level, and strongly suggest the involvement of osteoclastogenesis, angiogenesis and crosstalk between bone marrow cells in the radiation-induced bone loss. This study may provide new insights for the early diagnosis and intervention of bone loss post-irradiation.

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Cancer treatment-induced bone loss (CTIBL): Pathogenesis and clinical implications

Cited by 87 publications

References 96 publications

PTH(1-34) and zoledronic acid have differing longitudinal effects on juvenile mouse femur strength and morphology

PTH(1-34) and zoledronic acid have differing longitudinal effects on juvenile mouse femur strength and morphology

Cancer‐ and Chemotherapy‐Induced Musculoskeletal Degradation

Suppressing angiogenesis regulates the irradiation‐induced stimulation on osteoclastogenesis in vitro

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