Bisphosphonates in the Treatment of Patients With Metastatic Breast, Lung, and Prostate Cancer

Liu, Jing; Huang, Wenhui; Zhou, Ruoyu; Jia, Shuting; Tang, Wenru; Luo, Ying; Zhang, Jihong

doi:10.1097/md.0000000000002014

Cited by 27 publications

(17 citation statements)

References 38 publications

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“…This study has several limitations. We did not evaluate every bisphosphonate that is used in clinical practice because most injectable bisphosphonates are used to treat metastatic cancer and are not practical for patients needing rotator cuff repair [33]. We focused on alendronate, a lower-potency bisphosphonate commonly used to treat osteoporosis, giving this study clinical significance for rotator cuff surgery [34,35].…”

Section: Discussionmentioning

confidence: 99%

In vitro effects of alendronate on fibroblasts of the human rotator cuff tendon

Sung

Kim

Hah

et al. 2020

BMC Musculoskelet Disord

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Background: Bone mineral density of the humeral head is an independent determining factor for postoperative rotator cuff tendon healing. Bisphosphonates, which are commonly used to treat osteoporosis, have raised concerns regarding their relationships to osteonecrosis of the jaw and to atypical fracture of the femur. In view of the prevalence of rotator cuff tear in osteoporotic elderly people, it is important to determine whether bisphosphonates affect rotator cuff tendon healing. However, no studies have investigated bisphosphonates' cytotoxicity to human rotator cuff tendon fibroblasts (HRFs) or bisphosphonates' effects on rotator cuff tendon healing. The purpose of this study was to evaluate the cytotoxicity of alendronate (Ald), a bisphosphonate, and its effects on HRF wound healing. Methods: HRFs were obtained from human supraspinatus tendons, using primary cell cultures. The experimental groups were control, 0.1 μM Ald, 1 μM Ald, 10 μM Ald, and 100 μM Ald. Alendronate exposure was for 48 h, except during a cell viability analysis with durations from 1 day to 6 days. The experimental groups were evaluated for cell viability, cell cycle and cell proliferation, type of cell death, caspase activity, and wound-healing ability. Results: The following findings regarding the 100 μM Ald group contrasted with those for all the other experimental groups: a significantly lower rate of live cells (p < 0.01), a higher rate of subG1 population, a lower rate of Ki-67 positive cells, higher rates of apoptosis and necrosis, a higher number of cells with DNA fragmentation, higher caspase-3/7 activity (p < 0.001), and a higher number of caspase-3 positive staining cells. In scratch-wound healing analyses of all the experimental groups, all the wounds healed within 48 h, except in the 100 μM Ald group (p < 0.001). Conclusions: Low concentrations of alendronate appear to have little effect on HRF viability, proliferation, migration, and wound healing. However, high concentrations are significantly cytotoxic, impairing cellular proliferation, cellular migration, and wound healing in vitro.

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Section: Discussionmentioning

confidence: 99%

In vitro effects of alendronate on fibroblasts of the human rotator cuff tendon

Sung

Kim

Hah

et al. 2020

BMC Musculoskelet Disord

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“…In a super-aging society, the increasing number of patients with bone-resorption diseases (e.g., osteoporosis) has become an important issue of societal concern. Bone resorption inhibitors, such as bisphosphonates (BP), have been widely used for not only the treatment of osteoporosis but also suppression of bone metastatic cancer [ 1 , 2 , 3 , 4 ]. Rarely, however, individuals taking bone resorption inhibitors present with medication-related osteonecrosis of the jaw (MRONJ), particularly those who have suffered invasive dental treatments, such as tooth extraction.…”

Section: Introductionmentioning

confidence: 99%

BMP-2/β-TCP Local Delivery for Bone Regeneration in MRONJ-Like Mouse Model

Mikai

Ono

Tosa

et al. 2020

IJMS

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Medication-related osteonecrosis of the jaw (MRONJ) is a severe pathological condition associated mainly with the long-term administration of bone resorption inhibitors, which are known to induce suppression of osteoclast activity and bone remodeling. Bone Morphogenetic Protein (BMP)-2 is known to be a strong inducer of bone remodeling, by directly regulating osteoblast differentiation and osteoclast activity. This study aimed to evaluate the effects of BMP-2 adsorbed onto beta-tricalcium phosphate (β-TCP), which is an osteoinductive bioceramic material and allows space retention, on the prevention and treatment of MRONJ in mice. Tooth extraction was performed after 3 weeks of zoledronate (ZA) and cyclophosphamide (CY) administration. For prevention studies, BMP-2/β-TCP was transplanted immediately after tooth extraction, and the mice were administered ZA and CY for an additional 4 weeks. The results showed that while the tooth extraction socket was mainly filled with a sparse tissue in the control group, bone formation was observed at the apex of the tooth extraction socket and was filled with a dense connective tissue rich in cellular components in the BMP-2/β-TCP transplanted group. For treatment studies, BMP-2/β-TCP was transplanted 2 weeks after tooth extraction, and bone formation was followed up for the subsequent 4 weeks under ZA and CY suspension. The results showed that although the tooth extraction socket was mainly filled with soft tissue in the control group, transplantation of BMP-2/β-TCP could significantly accelerate bone formation, as shown by immunohistochemical analysis for osteopontin, and reduce the bone necrosis in tooth extraction sockets. These data suggest that the combination of BMP-2/β-TCP could become a suitable therapy for the management of MRONJ.

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“…Bisphosphonates therapy can prevent the occurrence of osteolytic lesions and SREs caused by BM, which has become an effective treatment for bone pain and hypercalcemia (21,22). Commonly used bisphosphonates such as pamidronate, zoledronic acid and ibandronate can be treated for BM patients in combination with conventional anti-tumor drugs.…”

Section: Discussionmentioning

confidence: 99%

The Distinction of Clinicopathological Characteristics, Treatment Strategy and Outcome in Colorectal Cancer Patients With Synchronous vs. Metachronous Bone Metastasis

Guan

Wei

et al. 2020

Front. Oncol.

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Background: The impact of the timing of bone metastasis (BM) diagnosis on colorectal cancer (CRC) patients is unclear. Our study aimed to explore the differences in clinicopathological characteristics, treatments and prognosis between synchronous BM (SBM) and metachronous BM (MBM) from CRC. Methods: We retrospectively investigated clinical data of CRC patients with SBM or MBM from 2008 to 2017 at Chinese National Cancer Center. Cancer specific survival (CSS) after BM diagnosis was estimated using the Kaplan-Meier method. The multivariable COX regression model identified the prognostic factors of CSS. Results: Finally, 63 CRC patients with SBM and 138 CRC patients with MBM were identified. Compared to SBM from CRC, MBM significantly was more involving multiple bone lesions (63.0 vs. 7.9%; p < 0.001), and more frequently originated from rectal cancer (60.9 vs. 41.3%; p = 0.033). The therapeutic strategies in SBM and MBM group were contrasted including systemic treatment, bisphosphonates, radiotherapy and metastasectomy for BM. 85.5% of patients in MBM group and 25.4% of patients in SBM group underwent primary tumor resection at initial diagnosis (p < 0.001). The median CSS was 11 months in both SBM and MBM group (p = 0.556), yet MBM patients developed from CRC in early AJCC stage presented obviously longer survival than those from advanced stage. Furthermore, patients could have improved CSS from primary tumor resection while there might be no survival benefit from targeted therapy in both SBM and MBM groups. Bisphosphonates was associated with a better CSS for patients with SBM, while radiotherapy for BM was related to a better CSS for patients with MBM. Conclusion: The CRC patients in SBM and MBM group represented different clinicopathological characteristics and treatment modalities, which affected the prognosis in different ways. Distinct consideration for CRC patients with SBM and MBM in clinical decision making is required.

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Bisphosphonates in the Treatment of Patients With Metastatic Breast, Lung, and Prostate Cancer

Cited by 27 publications

References 38 publications

In vitro effects of alendronate on fibroblasts of the human rotator cuff tendon

In vitro effects of alendronate on fibroblasts of the human rotator cuff tendon

BMP-2/β-TCP Local Delivery for Bone Regeneration in MRONJ-Like Mouse Model

The Distinction of Clinicopathological Characteristics, Treatment Strategy and Outcome in Colorectal Cancer Patients With Synchronous vs. Metachronous Bone Metastasis

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