Zoledronic Acid Monotherapy Research Articles

Cost-Effectiveness of Sequential Denosumab/Zoledronic Acid Compared With Zoledronic Acid Monotherapy for Postmenopausal Osteoporotic Women in China.

Objective: The primary purpose of this study was to estimate the cost-effectiveness of sequential denosumab/zoledronic acid versus zoledronic acid monotherapy for postmenopausal osteoporotic women in China. Methods: We updated and utilized a previously validated Markov microsimulation model to obtain the cost-effectiveness of two strategies for treating postmenopausal osteoporotic women. We compared the incremental cost-effectiveness ratios (ICERs) (US dollars [$] per quality-adjusted life year [QALY]) of sequential denosumab/zoledronic acid (i.e., biannual subcutaneous denosumab for 3 years followed by annual intravenous zoledronic acid for 3 years) with zoledronic acid monotherapy for 3 years in Chinese women with postmenopausal osteoporosis at ages 65, 70, 75, and 80 from the health care payer perspective. Our study’s willingness-to-pay (WTP) threshold was set to three times the value of China’s per capita GDP in 2020 ($31,512). Results: The ICERs of sequential denosumab/zoledronic acid versus zoledronic acid monotherapy were $59,389/QALY, $23,821/QALY, $22,710/QALY, and $14,027/QALY at age 65, 70, 75, and 80 years, respectively. One-way sensitivity analyses showed that the most impactful parameter was the persistence rate of the medications. If the persistence rate of denosumab or zoledronic acid was increased by 10%, sequential denosumab/zoledronic acid would be cost-effective at age 65. In probabilistic sensitivity analyses, the probabilities of sequential denosumab/zoledronic being cost-effective compared to zoledronic acid monotherapy were approximately 29.3%, 68.7%, 86.1%, and 99.4% for ages 65, 70, 75, and 80 years, respectively, at the WTP threshold of $31,512/QALY. Conclusion: Among Chinese postmenopausal osteoporosis women over 70 years old, sequential denosumab/zoledronic acid was cost-effective compared with zoledronic acid monotherapy at the pre-determined WTP threshold.

Cost-Effectiveness of Sequential Teriparatide/Zoledronic Acid Compared With Zoledronic Acid Monotherapy for Postmenopausal Osteoporotic Women in China.

ObjectiveWe aimed to assess the cost-effectiveness of sequential teriparatide/zoledronic acid relative to zoledronic acid monotherapy for postmenopausal osteoporotic women in China.MethodsA previously validated Markov microsimulation model was updated to examine the cost-effectiveness of daily subcutaneous teriparatide for 2 years followed by annual intravenous zoledronic acid for 3 years (sequential teriparatide/zoledronic acid), compared with zoledronic acid monotherapy for 3 years in Chinese women with postmenopausal osteoporosis at ages 65, 70, 75, and 80 from the health care payer perspective.ResultsThe incremental cost-effectiveness ratios (ICERs) (US dollars [$] per quality-adjusted life-year [QALY]) of sequential teriparatide/zoledronic acid vs. zoledronic acid monotherapy was $173,223/QALY at age 65 years, which was much higher than the pre-determined willingness-to-pay (WTP) threshold of $ 31,512/QALY, and the results were similar at other ages. In one-way sensitivity analyses, the two most impactful parameters were the cost of teriparatide and the residual effects of the medications included in this study. Sequential teriparatide/zoledronic acid became cost-effective at age 80 with the cost of teriparatide reduced by 50%. Without the residual effect, the ICER increased to $257,982/QALY. Probabilistic sensitivity analyses shown that the probabilities of zoledronic acid monotherapy being cost-effective were 100% at a WTP of $31,512/QALY.ConclusionsAmong Chinese women with postmenopausal osteoporosis, sequential teriparatide/zoledronic acid was not cost-effective unless the cost of teriparatide was reduced by 50% only for the participants over 80 years.

Retrospective Study of the Effects of Zoledronic Acid on Muscle Mass in Osteoporosis Patients.

PurposeSeveral osteoporosis drugs can continuously improve bone mass, but the impact on muscle mass is still unknown. This study aims to investigate how zoledronic acid monotherapy affected muscle mass in osteoporosis patients.Patients and MethodsPatients from an osteoporosis database were divided into two groups in this retrospective cohort, case–control study: zoledronic acid-treated patients (n = 113) and a control group without osteoporosis treatment (n = 118). At four years, appendicular skeletal muscle mass (ASM) and appendicular skeletal muscle mass index (ASMI) were calculated using dual-energy X-ray absorptiometry. The differences in muscle mass between the groups were compared.ResultsAt baseline, there was no difference in sex, ASM, ASMI, and bone mineral density between the zoledronic acid treatment group and the control group. The treatment group’s skeletal muscle mass increased by 841 g in ASM and 0.35 kg/m2 in ASMI after three years, while decreased in the control group.ConclusionThis study for the first time demonstrated that that zoledronic acid is beneficial not only to the bone but also to muscle.

Effects of zoledronic acid and ibandronate in the treatment of cancer pain in rats with lung cancer combined with bone metastases.

The aim of the study was to investigate the efficiency and safety of zoledronic acid and ibandronate in the treatment of rats with lung cancer combined with bone metastases. A total of 124 rats with lung cancer bone metastasis were established. Rats were randomly divided into A, B and C groups (n=30). Rats in group A were treated with ibandronate combined with zoledronic acid, rats in group B were treated with zoledronic acid monotherapy, and rats in group C were treated with ibandronate monotherapy. Rats in group A were injected subcutaneously with zoledronic acid 0.1 mg/kg and ibandronate 10 µg/kg, once per week for 12 weeks; rats in group B were injected subcutaneously with zoledronic acid, and rats in group C were injected subcutaneously with ibandronate, the same method as the treatment group. The remaining 34 SD rats were not treated to serve as the control group. Treatment efficacy and physical improvement in 8 weeks were observed, and improvement of pain behavior in rats was evaluated to reflect the effect of drug treatment. Of the 30 rats in group A, 25 showed different degrees of remission, 5 rats showed no improvement and the effective rate was 83.3%. Of the 30 rats in group B, 21 showed different degrees of remission, 9 rats showed no improvement and the effective rate was 70%. Of the 30 rats in group C, 20 showed different degrees of remission, 10 rats showed no improvement and the effective rate was 66.7%. Statistically significant differences in total effective rate were found among three groups, and the combined method showed the highest effective rate (P<0.05). Ibandronate combined with zoledronic acid has a good therapeutic effect on cancer pain caused by bone metastases from lung cancer.

Effects of combined teriparatide and zoledronic acid on posterior lumbar vertebral fusion in an aged ovariectomized rat model of osteopenia.

There has been no study regarding the effect of a combination of teriparatide (TPTD) and zoledronic acid (ZA) on vertebral fusion. In this study, we investigate the effect of single and combined TPTD and ZA treatment on lumbar vertebral fusion in aged ovariectomized (OVX) rats. Sixty two-month-old female Sprague-Dawley rats were ovariectomized and underwent bilateral L4-L5 posterolateral intertransverse fusion after 10 months. The OVX rats received vehicle (control) treatment, or ZA (100 µg/kg, once), or TPTD (60 µg/kg/2 d for 42 d), or ZA + TPTD until they were euthanized at 6 weeks following lumbar vertebral fusion. The lumbar spine was harvested. Bone mineral density (BMD), bone fusion, bone volume (BV), and bone formation rate (BFR)were analyzed by dual-energy X-ray absorptiometry (DXA), radiography, micro-computed tomography, and histomorphometry. Compared with vehicle (control) treatment, ZA and TPTD monotherapy increased bone volume (BV) at fusion site, and ZA + TPTD combined therapy had an additive effect. Treatment with TPTD and ZA + TPTD increased the bone fusion rate when compared with the control group. ZA monotherapy did not alter the rate of bone fusion. The TPTD and ZA + TPTD treatment groups had increased mineral apposition rate (MAR), mineralizing surfaces/bone surface ((MS/BS), and BFR/BS compared with the OVX group. Our experiment confirm that the monotherapy with TPTD and combination therapy with ZA + TPTD in an OVX rat model of osteopenia following lumbar vertebral fusion surgery increased bone fusion mass and bone fusion rate, and ZA + TPTD combined therapy had an additive effect on bone fusion mass. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:937-944, 2018.

Selective efficacy of zoledronic acid on metastasis in a patient-derived orthotopic xenograph (PDOX) nude-mouse model of human pancreatic cancer.

Patient-derived orthotopic xenograft (PDOX) nude-mouse models replicate the behavior of clinical cancer, including metastasis. The objective of the study was to determine the efficacy of zoledronic acid (ZA) on metastasis of a patient-derived orthotopic xenograft (PDOX) nude-mouse model of pancreatic cancer. In the present study, we examined the efficacy of ZA on pancreatic cancer growth and metastasis in a PDOX nude-mouse model. ZA monotherapy did not significantly suppress primary tumor growth. However, the primary tumor weight of gemcitabine (GEM) and combination GEM + ZA-treated mice was significantly decreased compared to the control group (GEM: P = 0.003; GEM + ZA: P = 0.002). The primary tumor weight of GEM + ZA-treated mice was significantly decreased compared to GEM-treated mice (P = 0.016). The metastasis weight decreased in ZA- or GEM-treated mice compared to the control group (ZA: P = 0.009; GEM: P = 0.007. No metastasis was detected in combination GEM + ZA-treated mice compared to the control group (GEM + ZA; P = 0.005). The results of the present study indicate that ZA can selectively target metastasis in a pancreatic cancer PDOX model and that the combination of ZA and GEM should be evaluated clinically in the near future for this highly treatment-resistant disease.

Polyneuropathic Pain Th erapy with a Patient Suffering from Generalized Castrate- Resistant Prostate Cancer – Clinical Case Report

Tapentadol is a µ -opioid receptors agonist as well as an inhibitor of noradrenaline reuptake. This pharmacologic profile of tapentadol makes it a suitable drug of choice in nociceptive and neuropathic pain control. This clinical report pressents a 65year old man with poorly differentiated prostate cancer - Gleason score 8 (4 + 4) with metastatic bone disease. Besides the initial application of bisphosphonates, the patient had been treated with androgen deprivation therapy (cyproterone acetate + leuprolide acetate) for the period of 18 months. This therapy was terminated due to an increase of PSA levels. Subsequently, the patient underwent palliative docetaxelbased chemotherapy. There were eight cycles applied with positive clinical and laboratory effect. However, the further application was limited by the averse effects, namely the peripheral neuropathy manifested by pain in arms and legs. The peripheral neuropathy had progressive tendency even after the end of chemotherapy, and supportive treatment with gabapentin and amitryptiline failed to succeed. Four months after zoledronic acid monotherapy, the patient was started on tapentadol in 50-mg dose b.i.d., consequently escalated to 100 mg b.i.d. (to this point, 25 µg of transdermal fentanyl were used for pain management). Significant relief from neuropathic discomfort was observed three weeks from the onset of tapentadol therapy. Patients state of health normalized within three months after the initiation of therapy. Consequently, the patient was able to receive docetaxel chemotherapy again, without any neuropathic pain exacerbation on the maintenance dose of tapentadol 50 mg b.i.d. Tapentadol administration resulted in stable and longtime relief from neuropathic pain which is a frequent side effect in the course of castrate-resistant prostate cancer therapy with taxanes.

Abstract LB-105: Radium-223 dichloride monotherapy and combination therapy with zoledronic acid or doxorubicin improve survival in a mouse model of breast cancer bone metastasis.

Abstract Breast cancer metastasis to bone results in significant morbidity and poor prognosis. Radium-223 dichloride is an alpha-emitting calcium mimetic that localizes to bone and provides targeted radiation therapy. A phase III clinical study on prostate cancer patients with bone metastases showed that radium-223 dichloride improved overall survival (ALSYMPCA, Parker et al. ECCO/ESMO 2011). We have previously reported that radium-223 decreases osteolysis and tumor burden in bone in a mouse model of breast cancer bone metastasis in preventive and micro-metastatic settings (Suominen et al. AACR Annual Meeting 2012), as well as, in mice with established bone metastases (Suominen et al. AACR Annual Meeting 2011). Here, we investigated the effects of radium-223 dichloride monotherapy compared to and in combination with either doxorubicin or zoledronic acid on survival in a mouse model of established breast cancer bone metastasis. Human MDA-MB-231(SA)/GFP cells were inoculated intracardially into nude mice, and 15 days later, a single dose of vehicle, radium-223 dichloride (300 kBq/kg, iv injection) and/or zoledronic acid (0.1 mg/kg, sc injection) was administered. Doxorubicin (5 mg/kg, ip injection) was administered once weekly. Radium-223 dichloride monotherapy extended time to sacrifice (P = 0.039), unlike doxorubicin or zoledronic acid monotherapy which did not improve survival as compared to the vehicle group. Radium-223 dichloride in combination with zoledronic acid (P = 0.004) or doxorubicin (P &amp;lt; 0.001) also extended time to sacrifice as compared to the vehicle but did not provide additional survival benefit as compared to the radium-223 dichloride monotherapy. Histological examination revealed that radium-223 dichloride treatment induced tumor cell necrosis in bone metastases. Therefore, the effect of radium-223 dichloride in inducing double-strand breaks in cancer cells was evaluated by immunohistochemical staining of γ-H2AX molecules. A 3-fold increase in the number of tumor cells with double-strand breaks in the radium-223 dichloride-treated as compared to the vehicle control mice was observed (P &amp;lt; 0.001). This finding supports our previous observations that radium-223 dichloride has an effect on both tumor cells and osteoclasts. In conclusion, radium-223 dichloride therapy alone or in combination with doxorubicin or zoledronic acid increases survival in breast cancer bone metastasis mouse model via dual action by targeting tumor growth and osteolysis, both important players in the destructive vicious cycle of bone metastasis. Our findings strongly support the development of radium-223 dichloride for the treatment of patients with bone metastatic breast cancer. Citation Format: Mari I. Suominen, Jukka P. Rissanen, Rami Kakonen, Katja M. Fagerlund, Esa Alhoniemi, Dominik Mumberg, Karl Ziegelbauer, Jussi M. Halleen, Sanna-Maria Kakonen, Arne Scholz. Radium-223 dichloride monotherapy and combination therapy with zoledronic acid or doxorubicin improve survival in a mouse model of breast cancer bone metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-105. doi:10.1158/1538-7445.AM2013-LB-105

A Case of Bone, Lung, Pleural and Liver Metastases from Renal Cell Carcinoma Which Responded Remarkably Well to Zoledronic Acid Monotherapy

Herein, we report a rare case in which bisphosphonate zoledronic acid (ZA) effectively treated not only multiple bone metastases but also lung, pleural and liver metastases from renal cell carcinoma (RCC). Recently, ZA is used to treat skeletal-related events (SREs) such as bone pain caused by bone metastasis from many kinds of cancer. The patient in the present report had multiple bone metastases from RCC. Remarkable improvement of the bone metastasis was observed following treatment with ZA at a dosage of 4 mg administered once every 4 weeks. Moreover, lung, pleural and liver metastases also diminished markedly in size in response to the treatment. The metastases have shown no progression for 20 months since starting the ZA treatment. We believe that the present report is the first of its kind announcing that ZA monotherapy has been effective for lung, pleural and liver metastases from RCC.

Death receptor 5 agonist TRA8 in combination with the bisphosphonate zoledronic acid attenuated the growth of breast cancer metastasis

Bone metastasis affects the majority of patients with advanced breast cancer and no adequate therapy exists. Bisphosphonates, like zoledronic acid, inhibit the osteolytic component of tumor growth in osseous tissues, but these drugs are not curative. The current study evaluated the combination of zoledronic acid with death receptor 5 agonists in an animal model of breast cancer bone metastasis. Materials and Methods. Female athymic nude mice (age 4-6 weeks, n=35) were inoculated with 200,000 luciferase-positive MDA- MB-435 cells by injection into the left ventricle. Animals were immediately imaged by bioluminescence technique and placed into one of the following therapy groups: Saline, hTRA8, hTRA8 + zoledronic acid, mTRA8, mTRA8 + zoledronic Acid, or zoledronic acid monotherapy. DR5 agonists were given at 200 µg/dose and zoledronic acid 5 µg /dose, with mice treated biweekly for 4.5 weeks and imaged weekly. Results. Combination therapy containing either hTRA8 or mTRA8 with zoledronic acid significantly reduced the number of secondary lesions (7.67+2.2 and 7.5+1.7 lesions/mouse, respectively) compared to saline treated controls (12.1+/-1.56 lesions/mouse) as assessed by bioluminescence imaging (p