Bisphosphonates Zoledronate and Alendronate for the Management of Postmenopausal Osteoporosis

Bisphosphonates are among the most frequently used antiresorptive drugs for the management of postmenopausal osteoporosis. We review here two of the commonly used bisphosphonates zoledronate and alendronate.

Management of Painful Bone Metastases: The Interaction between Radiation Therapy and Zoledronate

Background: Advanced cancers frequently metastasize to bone, and the presence of bone metastases is the most common cause of cancer-related pain. Pain management requires a multidisciplinary approach that involves the use of analgesics, bisphosphonates, radiotherapy, chemotherapy, surgery. The aim of our study was to evaluate the enhancement of radiotherapy on painful bone metastases in patients treated also with bisphosphonates. Materials and Methods: We analyzed the differences in benefit on pain and on quality of life comparing two groups of treatment. The first group comprised 104 patients treated with Radiotherapy (RT), the second one included 50 patients treated with radiotherapy associated to zoledronic acid (RT + Z). All patients completed before, during and after treatment, a questionnaire that rated the grade of pain, the pharmacological type of analgesic therapy and patient’s performance status. For each patient a total score was calculated, from a minimum value of 0% to a maximum of 20%, then expressed as a percentage. Patients were classified as responder if at the follow-up reported a reduction of over 20% of the initial score, no-change if there was a reduction of between 0% and 20%, progression if there was an increasing of the score. Results: In the group RT + Z we found fewer patients that started radiation therapy with severe pain (16% vs 32%), no patient had pain of grade 10, and a higher proportion of asymptomatic patients (12% vs 4%) was observed. In the RT alone group a higher percentage of patients started treatment assuming strong opioid more than once a day (26% vs 24%) and a reduction in number of these patients was about 14% compared with the reduction of 23.6% observed in the group RT + Z. Furthermore an increased total score was calculated only in the 6% of patient belonged to group RT alone. Finally, in the group RT + Z responder patients are 52%, compared to 36% of the RT group, non-responder were 36% versus 60% in the RT. The risk of adverse events (Pz) in the RT + Z was Pz = 0.36, with an odds (Oz) equal to 0.56, while the risk of adverse events (Pc) in the RT group was Pc = 0.60 with an odds (OC) of 1.5. The odds ratio was OR = 0.37, showing a value in favor of treatment RT + Z. Conclusions: In our retrospective observational study it is relevant a clear potentiation of benefit effects related to palliative radiation therapy in patients receiving also bisphosphonate therapy, so obtaining a better control over pain, a decreased need for pain relief and consequently an improved quality of life.

Bone-seeking nanoplatform co-delivering cisplatin and zoledronate for synergistic therapy of breast cancer bone metastasis and bone resorption

The"vicious cycle"established between tumor growth and osteolysis aggravates the process of breast cancer bone metastasis,leading to life-threatening skeletal-related events that severely reduce survival and quality of life.To effectively interrupt the"vicious cycle",innovative therapeutic strategies that not only reduce osteolysis but also relieve tumor burden are urgently needed.Herein,a bone-seeking moiety,alendronate(ALN),functionalized coordination polymer nanoparticles(DZ@ALN)co-delivering cisplatin prodrug(DSP)and antiresorptive agent zoledronate(ZOL)via Zn2+crosslinking for combination therapy was reported.The versatile DZ@ALN with a diameter of about 40 nm can cross the fissure in the bone marrow sinus capillaries,and possesses an excellent bone-seeking ability both in vitro and in vivo.Additionally,DZ@ALN could synergistically inhibit the proliferation of cancer cells,suppress the formation of osteoclast-like cells and induce the apoptosis of osteoclasts in vitro.Importantly,it could preferentially accumulate in bone affected site,remarkably inhibit the proliferation of tumor cells,relieving bone pain,and significantly inhibit the activation of osteoclasts,protecting the bone from destruction in vivo,eventually leading to the breakdown of"vicious cycle"without inducing obvious systemic toxicity.This innovative nanoagent combines chemotherapy and osteolysis inhibition,exhibiting an inspiring strategy for effective treatment of bone metastasis.

COMBINED EFFECTS OF METRONOMIC ZOLEDRONATE WITH CORIOLUS VERSICOLOR IN A METASTATIC BREAST TUMOR MOUSE MODEL

Incidence of breast cancer is high in women worldwide and mortality usually results from tumor metastasis.Adjuvant chemotherapeutic,such as zoledronate(ZOL),has been used in metastatic breast cancer mainly for skeletal protection.Our previous studies demonstrated that Coriolus versicolor(CV)aqueous extract exhibited anti-tumor

Efficacy of intravenous zoledronic acid in the prevention and treatment of osteoporosis:A meta-analysis

Objective:To compare the eflect of zoledronic acid in treatment and prevention of osteoporosis with placebo.Methods:Random control trials regarding zoleilroiiic acid in treatment of osteoporosis were retrieved by selecting Medline.EMbase and Pubmed databases till April 2012. The RevMan software was used for all of the statistical analysis.Results:A total of 9 trials were included in this meta-analysis.The pooled effect shewed that zoledronic acid could increase the bone mineral density by 2.98 times compared with placebo,and reduce the rate of fracture in patients by 32%.The results should the zoledronic acid intervention had significantly less serious adverse events than controls,and the odds ratio was 0.81(0.76-0.87).The longer term intervention, more than 12 months intervention,could gain a better prevention effect for osteoporosis(OR,95% CI for RMD was 3.35.2.77-3.92:for fracture was 0.67.0.54-0.82).Conclusions:This present study shows that zoledronic acid could be effective approach in the prevention of osteoporosis,and could increase the bone mineral density and reduce the risk ol facture.

Sandwich Structure-like Meshes Fabricated via Electrospinning for Controllable Release of Zoledronic Acid

Novel sandwich structure-like nanofiber multilayered meshes were fabricated via electrospinning. The purpose of the present work was to control zoledronic acid release via the novel structure of sandwich structure-like meshes. The in vitro release experiments reveal that the drug release speed and initial burst release were controllable by adjusting the thicknesses of electrospun barrier mesh and drug-loaded mesh. Compared with those of other drug delivery systems, the main advantages of the sandwich structure-like fiber meshes are facile preparation conditions and the generality for hydrophobic and hydrophilic pharmaceuticals.

A Study of Zoledronic Acid as Neo-Adjuvant, Perioperative Therapy in Patients with Resectable Pancreatic Ductal Adenocarcinoma

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by abundant granulocytic myeloid-derived suppressor cells (G-MDSC = CD45+/Lin﹣/CD33+/CD11b+/CD15+), which infiltrate tumors and suppress anti-tumor immunity. We have previously demonstrated in a murine model of PDAC that zoledronic acid (ZA) depletes G-MDSC resulting in decreased tumor growth and improved survival. We report here the results of a phase 1 clinical trial (NCT00892242) using ZA as neo-adjuvant, perioperative therapy in patients with non-metastatic, resectable pancreatic adenocarcinoma. Methods: Eligible PDAC patients received ZA (4 mg) IV 2 weeks prior to surgery. Patients then received 2 additional doses of ZA 4 weeks apart. Blood and bone marrow were obtained from patients prior to treatment with ZA and 3 months after surgery for analysis of G-MDSC by flow cytometry. Results: Twenty-three patients received pre-operative ZA with at least 6 months of follow-up. Only 15 PDAC patients had nonmetastatic PDAC, which was amenable to resection. ZA was well tolerated, and all adverse events were grade 1 or 2. The most common adverse events were fatigue, abdominal pain/discomfort, anorexia, and arthralgia. Of resected PDAC patients treated with ZA, 1- and 2-year overall survival (OS) was 85.7% and 33.3%, respectively, with a median OS of 18 months. This group had a 1- and 2-year progression-free survival (PFS) of 26.9% and 8.9%, respectively, with a median PFS of 12 months. The prevalence of G-MDSC was unchanged in the blood and bone marrow of PDAC patients pre- and post-treatment with ZA. Conclusion: ZA is safe and well tolerated as neo-adjuvant, peri-operative therapy in PDAC patients. In this small study, we did not observe a difference in OS or PFS compared to historical controls. Also, there was no difference in the prevalence of G-MDSC in the blood and bone marrow of PDAC patients pre- and post-treatment with ZA.

Curative Effect Analysis of Zoledronic Acid in the Treatment of Postmenopausal Osteoporosis with Different Bone Turnover Rates

Objective: To explore the clinical efficacy of Zoledronic Acid Injection in the treatment of postmenopausal osteoporosis with different bone turnover rates. Methods: A total of 63 patients diagnosed with postmenopausal osteoporosis were included in this study. Each patient was administrated 5 mg/100mL Zoledronic Acid (Aclasta) intravenously once and then given a one-year prescription of 600 mg/d oral Caltrate. The bone turnover parameters (PINP, β-cross, N-MID) were measured prior to the injection of Zoledronic Acid while the bone mineral density (BMD) and the pain scores of each patient were tested before treatment and after the one-year medication. On this basis, the patients were divided into several groups according to their bone turnover rates for intergroup comparison of treatment outcomes. Results: BMD results and pain scores of all participants were significantly improved at different levels after treatment. However, these improvements had no significant differences between the patients with high and low bone turnover rates. Conclusion: Zoledronic Acid Injection can relieve bone pain, enhance the quality of life and increase the BMD in patients with postmenopausal osteoporosis, regardless of the bone turnover status.

The Clinical Effect of Zoledronic Acid Combined with Teriparatide in Perverting Recurrent Fracture of Osteoporotic Vertebral Compressive Fractures in the Elderly after Percutaneous Kyphoplasty

Background: Zoledronic acid and teriparatide have been proved to be effective in improving bone metabolism and preventing fractures, but there is no clear clinical report on the efficacy of their combined application. Purpose: To discuss the clinical effect of zoledronic acid combined with teriparatide in perverting recurrent fracture of osteoporotic vertebral compressive fractures (OVCF) in the elderly after percutaneous kyphoplasty (PKP). Method: A randomized clinical trial was conducted at the First Affiliated Hospital of Hebei North University in China from September 2018 and September 2019. A total of 60 patients with OVCF were enrolled in the study (zoledronic acid: 20 cases;teriparatide: 20 cases;zoledronic acid + teriparatide: 20 cases). Observe and compare the changes of bone mineral density (BMD), pro-collagen type I N-terminal propeptide (PINP) and cross-linked C-terminal telopeptide of type I collagen (β-CTX) before surgery, 6 months and 1 year after surgery. At the same time, secondary fracture events and adverse reaction events were recorded during the follow-up period. Results: After normalized treatment, the bone metabolism indexes of PINP and β-CTX were improved and BMD was increased in three groups. Adverse Reactions: There was no statistical significance in the incidence of fever, gastrointestinal reactions and myalgia among the three groups (P > 0.05). The incidence of recurrent fractures in group A was higher than that in group C (P < 0.05), but there was no significant difference between group B and group C (P > 0.05). Conclusion: Zoledronic acid combined with teriparatide is superior to Zoledronic acid in preventing the risk of recurrent fracture after PKP for old patients with OVCF, but it has no significant advantage over teriparatide.

Efficacy and safety of radiotherapy combined with zoledronic acid in the treatment of lung cancer with bone metastasis: a meta-analysis

Objective: To evaluate the efficacy and safety of radiotherapy combined with zoledronic acid fOr the treatment of bone metastases. Methods: Use Pubmed, Cochrane Library, Embase, CBM, CNKI, Wanfang, Weipu tools to search-related databases at home and abroad. From 2013.1 to March 2019, radiotherapy combined with zoledronic acid and radiotherapy alone for bone metastasis of lung cancer were collected. Experimental studies;quality evaluation and data extraction for each of the included studies, and Cochrane risk bias assessment tools for quality evaluation of the literature. Data processing was performed using RevMan 5.3 and Stata 15.0 software, including risk ratio (OR), 95% CI, I2, and P values. Line sensitivity test, publication bias evaluation is using Egger's, Bgge's method quantitative calculation using Revman 5.3 and Stata 15.0 software for statistical analysis. Results: The total of 8 articles was included, and the number of cases was 703. The results of the meta-analysis showed that the radiotherapy, combined with the zoledronic acid group was effective in the treatment of lung cancer with bone metastasis. The meta-analysis was Z = 6.31 (P < 0.00001), OR (95% CI = 3.57, (2.41, 5.30)), the difference was statistically significant. The combined effect of bone metastases was better than that of the single-stage group. The meta-analysis results were Z = 3.18 (P = 0.001) and OR (95% CI = 3.21, (1.57, 6.59)), indicating the therapeutic effect of the two groups in the treatment of bone metastases. The difference is statistically significant. Adverse reactions include: (1) bone marrow suppression, blood toxicity;(2) fever and rash;(3) nausea, vomiting, and fatigue;(4) liver damage and loss of appetite, meta-analysis results are: bone marrow suppression, blood toxicity: Z =0.73 ( P = 0.47), OR (95% CI = 0.58 (0.13, 2.54));fever, rash: Z = 0.36 (P = 0.36), OR (95% CI = 1.3 (0.31, 5.38));nausea, vomiting, Weakness: Z = 0.29 (P = 0.77), OR (95% CI = 0.85 (0.27, 2.62));liver function damage and loss of appetite: Z = 0.00 (P = 1.00), OR (95% CI = 1.00 (0.17, 6.00)). The P values of the four meta-analyses were all greater than 0.05, and the difference was not statistically significant, indicating that the addition of zoledronic acid to the bone metastasis of lung cancer did not aggravate the changes of the above four adverse reactions. Conclusion: Radiotherapy combined with the zoledronic acid group is better than the single radiotherapy group in treating pain caused by bone metastasis. It can effectively treat bone metastasis and will not aggravate the occurrence of adverse reactions.

Anti-proliferation effect of zoledronic acid on human colon cancer line SW480

Objective: To investigate the anti-proliferation effect and mechanism of zoledronic acid(ZOL) on human colon cancer line SW480. Methods: SW480 cells were treated with 0, 12.5, 25, 50, 100 and 200 μmo L/L of ZOL for 48 h, and CCK-8 assay was employed to obtain the survival rate of SW480 cells. SW480 cells were treated with 25 μmo L/L of ZOL for 0, 12, 24, 48 and 72 h, and then the survival rate was obtained. SW480 cells of the ZOL group were treated with 25 μmo L/L of ZOL for 48 h, while cells of the Cs A+ZOL group were pretreated with 10 μmo L/L of Cs A for 0.5 h and then treated with 25 μmo L/L of ZOL for 48 h. Then the survival rates of SW480 cells of the control group, ZOL group and Cs A+ZOL group were determined. Flow cytometry was employed to detect the apoptosis rate and the mitochondrial transmembrane potential(△ψm) of the three groups and Western blot was used to detect the expressions of cyt C in the cytosol of the three groups. Results: ZOL inhibited the proliferation of SW480 cells, and the inhibition rate positively correlated with the concentration of ZOL and the action time(P< 0.01). The cell survival rate and the △ψm of the ZOL group were greatly lower than those of the control group, while the apoptosis rate and the expression of cyt C in the cytosol were obviously higher than those of the control group. All the differences showed distinctly statistical significances(P< 0.01). The cell survival rate and the △ψm of the Cs A+ZOL group were all lower than those of the control group, but substantially higher than those of the ZOL group; while the apoptosis rate and the expression of cyt C in the cytosol were higher than those of the control group, but distinctly lower than those of the ZOL group. All the differences were statistically significant(P < 0.01). Conclusions: ZOL can induce the apoptosis in human colon cancer line SW480 and then inhibit the proliferation of SW480 cells directly by opening the mitochondrial permeability transition pore abnormally, decreasing △ψm, and releasing the cyt C into the cytosol. And the effect enhances with the increases of the concentration of ZOL and the action time.

Zoledronic acid combined with androgendeprivation therapy may prolong time to castration-resistant prostate cancer in hormone-naı¨ve metastatic prostate cancer patients e A propensity scoring approach

Objective:To clarify the oncological benefit of zoledronic acid for hormone-naive metastatic prostate cancer,patient outcome of androgen deprivation therapy with zoledronic acid(ADT+Z)and androgen deprivation therapy alone(ADT)was compared.Methods:Fifty-two patients with pathologically confirmed metastatic prostate cancer were prospectively enrolled and treated with combined androgen blockade(goserelin and bicalutamide)with zoledronic acid(4 mg every 4 weeks for 24 months).A propensity score-match with logistic regression analysis was applied to select 50 pair-matched cohorts(both from ADT+Z and from historical control cohorts who had undergone ADT alone),and patient outcomes were compared.Results:Patients with ADT+Z had significantly longer time to progression(TTP)than those with ADT(median TTP;24.2 vs.14.0 months,p=0.0092),while no significant difference of overall survival between two groups(p=0.1502).Multivariate analysis for biochemical recurrence revealed treatment with ADT was the sole independent prognostic factor(HR:1.724,95%CI:1.06-2.86,p=0.0297).Conclusion:Combination of zoledronic acid with ADT may prolong time to castration resistant prostate cancer.

Comparative study of 99Tc-MDP and zoledronic acid in the treatment of osteoporosis

Objective:To compare the efficacy and mechanism of zoledronic acid and Tc-MDP in the treatment of osteoporosis.Methods:From July 2011 to November 2015,232 patients with primary osteoporosis were selected and treated in The First Affiliated Hospital of Hainan Medical College were selected and were divided into the 116 patients in the Tc-MDP group and 116 patients in the zoledronic acid group accorded to the treatment ways.The zoledronic acid group were given zoledronic acid treatment,1 time in one year.The Tc-MDP group were given Tc-MDP treatment,and the treatment were treated for 10 days for 1 course,1 course for 3 months,and a total of 3 years of treatment were observed.The prognosis and the changes of bone mineral density and hematological parameters were recorded.Results:The total effective rates of the zoledronic acid group and Tc-MDP group were 99.1%and 90.0%,respectively,and the zoledronic acid group were significantly higher than the Tc-MDP group(P<0.05).The bone mineral density of lumbar vertebrae and hip after treatment were significantly higher than that of the two groups before treatment,and the zoledronic acid group were also significantly higher than the Tc-MDP group(P<0.05).The joint tenderness scores of the two groups were significantly lower than those before treatment,and the Tc-MDP group were also significantly lower than the zoledronic acid group(P<0.05).There were no significant differences in serum calcium and blood phosphorus levels compared between the two groups(P>0.05),and the erythroeyte sedimentation rate(ESR)levels were lower than before treatment(P<0.05),The ESR levels of the Tc-MDP group were also significantly lower than that of the zoledronic acid group(P<0.05).Conclusion:The zoledronic acid and the application of Tc-MDP in the treatment of osteoporosis can increase bone density,relieve joint tenderness symptoms,reduce ESR content,and will not affect patients'blood calcium and blood phosphorus levels.However,zoledronic acid increases bone density significantly are better than the Yunke,and Yunke relieves joint pain significantly are more than zoledronic acid.

Chemotherapy,transarterial chemoembolization,and nephrectomy combined treated one giant renal cell carcinoma(T3aN1M1)associated with Xp11.2/TFE3:A case report

BACKGROUND Renal cell carcinoma(RCC)with Xp11.2 translocation/TFE3 gene fusion is a rare and distinct subtype of RCC that is classified under tumors with translocation of the microphthalmia-associated transcriptional factor.CASE SUMMARY We report an adult case of Xp11.2 translocation advanced RCC with metastasis(T3a N1M1),after targeted treatment,alcohol ablation,and transarterial chemoembolization,who eventually underwent successful surgical excision.No recurrence or transfer was seen within one year,and the survival period was more than 3 years.A review of the relevant literature was conducted to improve our understanding of the pathogenesis,epidemiology,clinical manifestations,diagnosis,differential diagnosis,treatment,and other aspects of the disease.CONCLUSION Transarterial chemoembolization and ablation did not achieve the desired tumor reduction in this patient,but had a significant effect on reducing intraoperative bleeding and inhibiting tumor activity.

Sequential Treatment Reduces the Acute Phases of Adverse Effect of Zoledronic Acid in First Time Users

Objective: To investigate whether sequential regimen such as traditional anti-reabsorption medications followed by zoledronic acid could reduce the side effects after initiation of zoledronic acid in postmenopausal osteoporosis patients. Methods: A total of 156 postmenopausal osteoporosis patients who presented at our osteoporosis outpatient clinic were enrolled in this study. They were randomly divided into four groups: the control group, alendronate group, calcitonin group, and raloxifene group. All participants were treated with Caltrate 600 mg per day and calcitriol 0.25 ug per day as a baseline treatment, followed by administrating 5 mg/100 mL of zoledronic acid intravenously for one single time three months afterwards. During the abovementioned course of three months, the alendronate group received 70 mg of alendronate sodium orally once a week, the calcitonin group received nasal spray form of salmon calcitonin 10iu daily, the raloxifene group received 60mg of raloxifene orally daily, and the control group received nothing but only the baseline treatment. We tested parameters such as β-cross, blood calcium level, renal function both pre and post zoledronic acid treatment. We also documented those side effects that typically occurred within one week of treatment initiation, which included the proportion, severity, onset time, and duration of the fever, demand for pain medication, severity of bone and joint pain, flu-like symptoms, arrhythmia, blood calcium level, and kidney function impairment. We also evaluated how willing the patients were to receive a second dose of zoledronic acid. Then we did comparative analysis between control group and sequential group. Results: The side effects such as fever, bone and joint pain, flu-like symptoms after zoledronic acid treatment in alendronate group and calcitonin group were all significantly lower than that in control group, while raloxifene group showed no significant difference compared to that in the control group. The proportions of patients who needed NSAIDs in the alendronate group and the calcitonin group were significantly lower than that in control group. However, the raloxifene group showed no significant difference in the NSAIDs demand from that of the control group. The percentages of patients who consented to a second dose of zoledronate therapy in the alendronate, calcitonin and raloxifene groups were significantly higher than that in the control group. Conclusions: Sequential treatment with alendronate sodium or calcitonin can significantly reduce the side effects such as fever, bone/joint pain, flu-like symptoms caused by first-time zoledronic acid therapy. Raloxifene sequential treatment does not seem to have decreased or increased the side effects of zoledronic acid treatment. Also, sequential treatment can improve the patient compliance with a second dose of zoledronic acid.

The Role of Health Education in Improving Patient Compliance with Zoledronic Acid

Objective: To define the role of health education in improving patient compliance with Zoledronic Acid for osteoporosis treatment and management and draw closer attention of patients and physicians to the importance of health education. Methods: A total of 198 postmenopausal patients with osteoporosis who were admitted by the osteoporosis outpatient clinic of our hospital and had the first administration of Zoledronic Acid in 2015 were invited to participate in the follow-up visit that involved questions concerning the frequency of health education and the questionnaire survey on osteoporosis in 2015 and the administration of Zoledronic Acid during the past three years. The patients were divided into five groups according to the frequency of health education to compare the survey results of each group in 2015 and 2018 and investigate the differences in the scores and frequency of administration among the five groups. Results: Among the 198 patients, there were 182 attending the follow-up visit. In terms of the frequency of health education (FREQ = 0, 1, 2, 3, 4), these patients were divided into five groups of 47, 63, 35, 18 and 19 members respectively. After three years of treatment, the questionnaire score of each group was higher than the pre-treatment level and the difference showed statistical significance (p Conclusion: Health education is an effective approach to influence a patient’s knowledge connected to relevant diseases in a positive way and improve patient compliance with Zoledronic Acid treatment. An enhanced health education program can be developed to assist the patients in chronic disease management.

Bone Scan Index Is a Prognostic Factor for Breast Cancer Patients with Bone Metastasis Being Treated with Zoledronic Acid

Bone scan index (BSI) has been used to quantify the spread of bone metastasis and be a prognostic indicator in prostate cancer with bone metastases. However, the utility of BSI in breast cancer patients with bone metastasis has not been yet established. We retrospectively reviewed 57 female breast cancer patients with osteoblastic/lytic combined type bone metastases and treated with zoledronic acid after bone metastasis was identified. Serial bone scintigrams were taken at the time of bone metastasis detection and during the 6- and 12-month follow-ups. The scintigrams were analyzed by BONE NAVITM version 1 and the BSI value was calculated. Additionally, serum cancer antigen 15-3 (CA15-3) and carcinoembryonic antigen (CEA) were measured. The patients were divided in 2 distinct groups—group A representing all follow-up BSI values ≤ initial BSI values and group B representing all follow-up BSI values ≥ initial BSI values. The interval changes of CA15-3 and CEA were divided in the same fashion. Kaplan-Meier method and log-rank test revealed that the overall survival rate was significantly greater in group A than those of group B after 6 months (p = 0.011) and 12 months (p = 0.016). Univariate analysis revealed that the overall survival rate was significantly greater in group A than those of group B, after a 6 month period (Hazard Ratio [HR] 5.841;95% confidence interval [CI] 1.248 - 27.34;p = 0.025) and 12 month period (HR: 4.22;95% CI 1.17615.15;p = 0.027). Multivariate analysis demonstrated that BSI changes after 6 and 12 months trended toward significance regarding parameters affecting survival rate (age and CA15-3) with a HR = 12.760 (95%CI 1.8110 - 89.850) at 6 months with a p = 0.010 and a HR = 5.0640 (95%CI 1.0590 - 24.220) at 12 months with a p = 0.042. BSI changes after 6 and 12 months appear to be a prognostic factor in breast cancer patients with bone metastasis treated with zoledronic acid.

Severe and Prolonged Hypocalcaemia Post Zoledronic Acid Infusion in a Patent with Sleeve Gastrectomy

Background: Zoledronic acid is commonly used to treat hypercalcaemia and osteoporosis, as well as to prevent skeletal complications from haematological and solid organ malignancies. Case presentation: We report the case of a 38 year old lady who presented with severe hypocalcaemia following the administration of zoledronic acid. Her significant background history included vitamin D deficiency and sleeve gastrectomy three years ago. She had prolonged hypocalcaemia requiring IV calcium replacement for two months. Her prolonged hypocalcaemia was attributed to her vitamin D deficiency at the time of zoledronic acid infusion as well as her history of bariatric surgery. Conclusion: This case emphasises the importance of ensuring vitamin D levels are replete prior to zoledronic acid infusion and ensuring the calcium levels are checked frequently in patients with a history of bariatric surgery obtaining zoledronic acid.

Osteonecrosis of the jaw in a patient taking once-yearly infusion of zoledronic acid for osteopenia

Osteonecrosis of the jaw (ONJ) is an adverse effect of nitrogen-containing bisphosphonates. Advancing age, intravenous administration of zoledronic acid (ZOL), history of dento-alveolar surgery, and concomitant systemic diseases such as diabetes are known as risk factors for developing ONJ. However, despite numerous studies, the exact pathophysiology remains unclear and management strategies are largely anecdotal. Once-yearly intravenously administered 5 mg ZOL was approved by the US Food and Drug Administration in 2007 for the treatment of osteoporosis and its efficacy with 3 year-regimen had been recently proven in preventing new clinical fracture. Although occurrences of ONJ have been reported to be rare with this drug administration, available data is very limited and long-term outcomes are lacking. We present a case of ONJ identified in an osteopenic patient with an intermittent but long standing sore mouth related to exposed mandibular bone. Once-yearly infusion of zoledronic acid used in the treatment of osteopenia may contribute to the spontaneous development of ONJ, especially in those presenting with multiple comorbidity factors. This report suggests the importance of health care professionals keeping abreast of new developments in this area and providing appropriate information to their patients.