Mg Of Zoledronic Acid Research Articles

Inpatient zoledronic acid in older hip fracture patients is well tolerated and safe.

According to the 2022 Dutch 'Osteoporosis and fracture prevention' guideline, zoledronic acid (ZA) is the preferred osteoporosis treatment for hip fracture patients. Less than 25% of hip fracture patients visit the outpatient fracture liaison service, therefore inpatient administration of ZA during the hip fracture hospitalization is now recommended in patients > 75years. In the OLVG Hospital, inpatient administration of ZA during hospitalization for hip fracture in older patients has been standard of care since 2020. This single center retrospective observational follow-up study included hip fracture patients > 75years admitted to the orthogeriatric ward of the OLVG Hospital, and treated with 5mg of ZA intravenously on the day of hospital discharge between June 2020 and December 2022. Life expectancy estimated < 12months, creatinine clearance < 35ml/min, hypocalcemia, and high risk of osteonecrosis of the jaw were contra-indications. During three months of follow-up (FU) adverse events, emergency room visits, hospital readmissions, and death were recorded. In 161 consecutive hospitalized hip fracture patients (mean age 86 ± 6years, 65% female, 18% nursing home) ZA was administered and no adverse events were recorded. During 3months of FU, 8 patients (5%) visited the emergency room, 19 patients (12%) were re-admitted to the hospital, 3 with a new fracture (2 contralateral hip, 1 radius), and 17 patients (11%) died of reasons unrelated to ZA. This study shows that inpatient administration of zoledronic acid during hip fracture hospitalization is safe and feasible to prevent future fragility fractures in older hip fracture patients.

Effect of Intravenous Zoledronic Acid on Total Knee Replacement in Patients With Symptomatic Knee Osteoarthritis and Without Severe Joint Space Narrowing: A Prespecified Secondary Analysis of a Two-Year, Multicenter, Double-Blind, Placebo-Controlled Clinical Trial.

To determine the effect of zoledronic acid (ZA) on the risk of total knee replacement (TKR) in patients with symptomatic knee osteoarthritis and without severe joint space narrowing (JSN). We included 222 participants (mean age 62 years, 52% female) from the two-year Zoledronic Acid for Osteoarthritis Knee Pain trial (113 received 5 mg of ZA annually and 109 received placebo) conducted between November 2013 and October 2017. Primary TKR were identified until February 22, 2022. The effect of ZA on TKR risk was evaluated using Cox proportional hazard regression models. Because the treatment effect failed the proportional hazards assumption, a time-varying coefficients analysis for treatment was conducted by splitting the study into two periods (ie, within and after two years of randomization). Over a mean follow-up of seven years, 39% and 30% of participants had any TKR in the ZA and placebo groups, and 28% and 18% had TKR in the study knee, respectively. Use of ZA was associated with a higher risk of TKR in any knee (hazard ratio [HR] 4.2, 95% confidence interval [CI] 1.2-14.7) and showed a trend in the study knee (HR 6.8, 95%CI 0.9-53.9) during the trial. In the posttrial period, the risk of TKR was similar in the ZA and the placebo groups for any knee (HR 1.2, 95%CI 0.5-1.8) and the study knee (HR 1.4, 95%CI 0.5-2.2). These results suggest that ZA is not protective against TKR in patients with symptomatic knee osteoarthritis and without severe JSN.

The effect of zoledronic acid on hip geometry in renal transplant recipients: a double-blind placebo-controlled randomized study

BackgroundIn renal transplant patients, bisphosphonates may prevent bone loss, but little is known about their effects on bone microarchitecture and geometrical hip parameters, as the key factors of bone stability. This study aimed to analyze the effect of zoledronic acid on the mentioned parameters in kidney transplant patients.MethodsIn this double-blind, randomized trial, 33 patients were followed for six months after administering either 4mg of zoledronic acid or a placebo. Bone mineral density (BMD) measurement of the spine, hip, radius, and whole body was obtained, and trabecular bone score (TBS) was evaluated using the software. Geometric assessment at the proximal femur was performed by the HSA program.ResultsEighteen patients in the intervention group and 15 in the control group completed the study. The mean percentages of the changes in the BMD at the lumbar spine and whole body were significantly different between the placebo and intervention groups (-0.23% vs. 4.91% and -2.03% vs. 1.23%) (P < 0.05). Zoledronic acid appeared to enhance the subperiosteal diameter, endocortical diameter, and cross-sectional moment of inertia (CSMI) at the narrow neck in comparison with placebo (P < 0.05); however, no difference in TBS was observed between both groups (P > 0.05).ConclusionsWe concluded that a single administration of zoledronic acid might ameliorate bone loss at the lumbar spine and the whole body and maintain the subperiosteal diameter, endocortical diameter, and CSMI as parameters of bone strength at the narrow neck of the proximal femur after six months in renal-transplant recipients.Trial registrationThis study was registered in IRCT (ID: IRCT20181202041821N1) on 04–05-2019.

The Efficacy of Bisphosphonate in the Treatment of Giant Cell Tumour of the Bone: A Systematic Review and Meta-Analysis.

Anti-osteoclastic mechanism of Bisphosphonate (BP) is crucial to treat Giant Cell Tumour of the Bone (GCTB), however no established guidelines of its use have been published. This systematic review and meta-analysis is the first to summarise recent clinical studies on the subject. A systematic search was performed based on PRISMA guidelines for clinical trials of BP administration in GCTB. Baseline data including BP regimen, dose and timing was summarised. The primary outcomes assessed were recurrence rate, metastases, survival rate, functional outcome, clinical outcome, radiological outcome, and adverse effect. We identified 8 articles from 2008-2020. Most studies administer 4mg of Zoledronic acid post-operatively, with five studies mentioning pre-operative administration and six studies describing post-operative administration. There was a total of 181 GCTB cases analysed in this study. The BP group presented lower recurrence rate than control group (three studies; Odds Ratio [OR] 0.15; 95% Confidence Interval [CI], 0.05 - 0.43; p<0.05; heterogeneity, I2=0%). As for survival rate, BP group is comparable to control group (two studies; OR 1.67; 95% CI, 0.06 - 48.46; p=0.77; heterogeneity, I2=65%). Bisphosphonate therapy offers satisfactory recurrence rate, functional outcome, clinical outcome, radiological outcome, survival rate and metastases rate in patients with GCTB, with minimal adverse effects. Pre- and post-operative administration of bisphosphonates in combination might be the most beneficial in minimalising the recurrence rate.

Familial Mediterranean Fever and Paget’s Disease: Incidental or Associated?

Co-existence of Familial Mediterranean Fever(FMF) and Paget’s disease (PD)is very rare. In this paper, we aimed to present a case of FMF patient presenting with PD. A 62-year old male patient admitted with complaint of chronic low back pain and weight loss. An increased uptake at pelvis which was reported as paget metabolic bone disease was identified in bone scintigraphy. An infusion of 5 mg of zoledronic acid, calcium and Vitamin D treatments were administered. Paget’s disease (PD)is a rare condition in patients with FMF. The co-existence of FMF and PD should not be forgotten.

Asymptomatic active Paget bone disease: a case report

Paget’s disease (osteitis deformans) of bone is a focal skeletal disorder that can be mono- or polyostotic. Paget's disease might be asymptomatic as with normal biomarkers, or it can be symptomatic such as bony enlargement or deformity. The diagnosis can be made by laboratory findings and specific findings in radiology or radionuclide scan, and it is sometimes confirmed by bone biopsy.In this report, we present the case of a 37-year-old man whose initial symptoms indicated sacroiliitis, which led to the suspicion of ankylosing spondylitis. Following other diagnostic evaluations and based on imaging features and bone biopsy, active Paget’s bone disease without abnormal biochemical markers was diagnosed. The laboratory diagnosis tests were normal. Other biomarkers including procollagen type I N-terminal propeptide (PINP), serum C-telopeptide (CTx), urinary N-telopeptide (NTx), and urinary hydroxyproline, are not routinely checked.The patient also showed a coincidence of unilateral idiopathic gynecomastia. A single dose of 5 mg of zoledronic acid intravenously was prescribed, and the patient was followed for six months. Paget's bone disease can occur without any change in biochemical markers. In such cases, the response to treatment can becontrolled by improving the clinical picture or evaluating the correct imaging findings.

Aseptic femur head necrosis revealing Cushing's disease: a rare presentation

Background: Cushing's disease is an endocrine disorder and may be associated with non-traumatic osteonecrosis of the hip. We report the case of avascular necrosis of the femoral heads (AVNFH) as the presenting manifestation of Cushing's disease. Case presentation: A 29-year-old male patient was referred to our department because of non-traumatic bilateral hip pain evolving for two years. The pain was associated with lameness when walking. He noticed a drop in libido since one year with erectile dysfunction. Physical examination revealed facio-truncal obesity, abdominal violaceous striae, dorsal hyper-kyphosis, a pain and limitation of internal rotation of the left hip with a Lequesne index of 16. The standard radiography showed a loss of sphericity of the left femoral head with an aspect of eggshell. The MRI confirmed the diagnosis of a bilateral AVNFH. The baseline cortisol level was 287 ng/ml. AVNFH as the presenting manifestation of Cushing's disease was suspected and confirmed by a pituitary MRI which revealed a pituitary adenoma. A discharge of the hips was indicated. The patient underwent surgical resection of the adenoma and was referred to the endocrinology department. The histopathological examination confirmed the diagnosis of pituitary adenoma (corticotrope adenoma). The patient has also received an intravenous perfusion of 5 mg of Zoledronic acid. The follow up was marked by the regression of the symptoms of Cushing's disease and the hip pain. Conclusion: AVNFH as the presenting manifestation of Cushing's disease is rarely described. Hence, it’s needed to exclude endogenous hypercorticism in any patient with idiopathic osteonecrosis.

Effect of Intravenous Zoledronic Acid on Tibiofemoral Cartilage Volume Among Patients With Knee Osteoarthritis With Bone Marrow Lesions

A proof-of-principle study suggested that intravenous zoledronic acid may reduce knee pain and the size of bone marrow lesions in people with knee osteoarthritis, but data from large trials are lacking. To determine the effects of intravenous zoledronic acid on knee cartilage volume loss in patients with symptomatic knee osteoarthritis and bone marrow lesions. A 24-month multicenter, double-blind placebo-controlled randomized clinical trial conducted at 4 sites in Australia (1 research center and 3 hospitals). Adults aged 50 years or older with symptomatic knee osteoarthritis and subchondral bone marrow lesions detected by magnetic resonance imaging (MRI) were enrolled from November 2013 through September 2015. The final date of follow-up was October 9, 2017. Intravenous infusion with either 5 mg of zoledronic acid in a 100-mL saline solution (n = 113) or a placebo saline solution (n = 110) at baseline and 12 months. The primary outcome was absolute change in tibiofemoral cartilage volume assessed using MRI over 24 months (the minimum clinically important difference [MCID] has not been established). Three prespecified secondary outcomes were change in knee pain assessed by a visual analog scale (0 [no pain] to 100 [unbearable pain]; MCID, 15) and the Western Ontario and McMaster Universities Osteoarthritis Index (0 [no pain] to 500 [unbearable pain]; MCID, 75) over 3, 6, 12, 18, and 24 months and change in bone marrow lesion size over 6 and 24 months (the MCID has not been established). Of 223 participants enrolled (mean age, 62.0 years [SD, 8.0 years]; 52% were female), 190 (85%) completed the trial. Change in tibiofemoral cartilage volume was not significantly different between the zoledronic acid group and the placebo group over 24 months (-878 mm3 vs -919 mm3; between-group difference, 41 mm3 [95% CI, -79 to 161 mm3]; P = .50). No significant between-group differences were found for any of the prespecified secondary outcomes, including changes in knee pain assessed by a visual analog scale (-11.5 in the zoledronic acid group vs -16.8 in the placebo group; between-group difference, 5.2 [95% CI, -2.3 to 12.8]; P = .17), changes in knee pain assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (-37.5 vs -58.0, respectively; between-group difference, 20.5 [95% CI, -11.2 to 52.2]; P = .21), and changes in bone marrow lesion size (-33 mm2 vs -6 mm2; between-group difference, -27 mm2 [95% CI, -127 to 73 mm2]; P = .60) over 24 months. Adverse events were more common with zoledronic acid than with placebo (96% vs 83%, respectively) and consisted mainly of acute reactions (defined as symptoms within 3 days of administration of infusion; 87% vs 56%). Among patients with symptomatic knee osteoarthritis and bone marrow lesions, yearly zoledronic acid infusions, compared with placebo, did not significantly reduce cartilage volume loss over 24 months. These findings do not support the use of zoledronic acid in the treatment of knee osteoarthritis. anzctr.org.au Identifier: ACTRN12613000039785.

Comparison of the Effects of Local and Systemic Zoledronic Acid Application on Mandibular Distraction Osteogenesis

Bisphosphonates are antibone resorptive drugs that are used to prevent bone tissue resorption in several skeletal diseases. The aim of this study was to examine the effects of systemic and local applications of zoledronic acid (ZA) on newly regenerated bone in a model of experimental distraction osteogenesis (DO). To do this mandibular DO was applied to 30 adult female Sprague Dawley rats, which were randomly divided into 3 groups: control, DO only, systemic zoledronic acid (SZA), and local zoledronic acid (LZA). In the LZA group, the gap between the bone fragments was filled with a gelatin sponge soaked in 2 mg of ZA and 0.1 mL of sterile saline. In the SZA group, a single dose of 0.1 mg/kg ZA was administered systemically. After the surgery, there was a 5-day latent waiting period and 10-day distraction phase. Following a 28-day consolidation period, the rats were euthanized and their mandibles were collected. The distracted bone area was seen to be filled with newly regenerated bone tissue in all 3 groups, both histologically and histomorphometrically. In addition, amounts of new bone formation, osteoblast cella, osteoclast (OC) cells, osteopontin, and vascular endothelial growth factor in the SZA and LZA groups were found to be higher when compared with the controls. Furthermore, in the SZA group, new bone formation, osteoblast, OC, osteopontin, and vascular endothelial growth factor were detected in significant amounts compared with the LZA group. Osteoclast numbers did not differ in a statistically significant manner in the SZA group with respect to the LZA group. Based on the results of this study, systemic and local applications of ZA could increase the formation of new bone in patients of DO, and systemic application is a more effective method compared with local application.

Cytokines Behavior in Multiple Myeloma Patients during Zoledronic Acid Treatment

Objective: Multiple Myeloma (MM) is characterized by uncoupling of bone resorption from bone formation which leads to the predominance of resorption. Bisphosphonates are chemical compounds that selectively concentrate at the interface of the active osteoclasts and the bone resorption surface where they inhibit osteoclast activity. Aim of this study was to describe cytokines behaviour in MM and to evaluate whether zoledronic acid could have an in vivo anti-angiogenic property in MM as observed in solid tumours.Methods: Serum samples from 29 (16 males and 13 females) consecutive MM patients with lytic bone lesions treated with 4 mg of zoledronic acid were tested for platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), tumor necrosis factor (TNF α) and insulin growth factor (IGF-I). Basal cytokine levels were compared with the values observed after 1, 2, 7 and 21 days of treatment, using the Wilcoxon’s test for nonparametric-dependent continuous variables.Results: A significant increase in IL-6 and TNF α was observed on days 1 and 2. As for VEGF, the levels of this cytokine did not change significantly from basal values during the entire period of observation except for a significant increase day 7 (P=0.0005). Moreover, PDGF significantly decreased (P=0.005) after 2 days from zoledronic acid infusion.Conclusions: From this study appears that in MM, treatment with zoledronic acid induces a transient reduction in PDGF according with previous studies in solid cancer, while the increase of IL-6 and VEGF could be related through a paracrine mechanism. The anti-myeloma effect of this drug could be driven through this mechanism.

Effectiveness and Safety of Zoledronic Acid in the Treatment of Osteoporosis.

The effectiveness of current treatments for osteoporosis is limited by poor patient compliance. However, a favorable dosing regimen of zoledronic acid (ZA) has the potential to improve patient compliance and thus clinical outcomes. The author conducted a retrospective analysis to examine adherence to and the antiosteoporotic effects of a once-yearly infusion of 5 mg of ZA in Taiwanese patients with osteoporosis for up to 48 months. Five men and 149 postmenopausal women (mean age, 77.1 years) were included. Prior to ZA treatment, 66.2% of patients had fractures; most patients discontinued previous treatments due to compliance or convenience issues. Approximately 85% of patients received at least 2 infusions of ZA. Following ZA treatment, bone mineral density improved from baseline at 12 months (11% from baseline; P=.01) and 48 months (20.7% from baseline; P=.009). In addition there was a significant reduction in mean beta-C-telopeptide at all time points from 12 (P<.001) to 36 months (P=.010). New clinical fractures occurred in 16 (10.4%) patients, of which 12 patients experienced a single fracture. Zoledronic acid had an acceptable safety profile; no adverse events were considered to be drug related. Treatment with ZA improved bone health by enhancing bone mineral density and reducing bone turnover, even in high-risk patients. Low fracture rates and high adherence further elucidate the benefits of ZA in the treatment of osteoporosis.

Role of intravenous dosage regimens of bisphosphonates in relation to other aetiological factors in the development of osteonecrosis of the jaws in patients with myeloma

The aim of this case-control study was to identify possible explanatory risk factors for the development of bisphosphonate-related osteonecrosis of the jaws (BRONJ) by estimating the effects of intravenous dosage regimens of bisphosphonates, coexisting diseases, and other drugs on 201 patients with multiple myeloma, with or without BRONJ. We compared sex, treatment with bisphosphonates, incidence of diabetes, and the taking of drugs such as corticosteroids and chemotherapy in patients who had BRONJ (n=44) and patients who did not (n=157). Among the bisphosphonates given intravenously zoledronic acid showed a stronger correlation with BRONJ than pamidronic acid. The risk of developing BRONJ increased dramatically at cumulative intravenous doses of more than 78mg of zoledronic acid or 600mg of pamidronic acid, which corresponds to treatment for 18 months or longer. Diabetes mellitus correlated significantly with the development of BRONJ (p=0.01) while there was no correlation with sex, simultaneous treatment with corticosteroids, or chemotherapy. In conclusion, treatment with zoledronic acid, high doses of pamidronic acid, and the coexistence of diabetes mellitus seem to be associated with the development of BRONJ.

Bilateral Typical Femoral Fractures in a Patient with Metastatic Breast Cancer on Long-Term Bisphosphonate Therapy: A Case Report

An atypical femoral fracture may be one of the devastating side effects of bisphosphonate. We present a patient who obliged to multiple surgeries for atypical femoral fracture of the femur after bisphosphonate therapy. A 63-yearold woman had been on anti-estrogen therapy for skeletal metastasis of the breast cancer. She received 90 mg of pamidronate disodium for 2 years and 4 mg of zoledronic acid for 4 years. Four month after she developed spontaneous left thigh pain, she fell from a standing height. X-ray films showed a subtrochanteric fracture of the left femur. The patient underwent surgery with an intramedullary nail, and radiation therapy was delivered to the fracture site because the possibility of a pathological fracture was unable to be excluded. Radiographs showed some evidence of callus formation, but the fracture line persisted. Two years later, the intramedullary nail broke at a screw hole in radiographs. Bipolar hip arthroplasty was performed and bone chips were grafted at the fracture site. Ten weeks after the operation, callus formation was satisfactory and she was able to walk without pain. One year after the first operation on the left femur, she complained of spontaneous pain in the right thigh and radiographs showed a lateral cortical beak sign with no evident fracture line. The patient underwent intramedullary nailing to prevent subsequent fracture. The radiological fracture sign were improved one year after the operation. The prophylactic intramedullary nailing is effective for the patients with lateral cortical thickening and/or a medial spike on X-ray.

Early Inhibitory Effects of Zoledronic Acid in Tooth Extraction Sockets in Dogs Are Negated by Recombinant Human Bone Morphogenetic Protein

This study was conducted with 2 purposes. The first was to determine the effect of a single dose of zoledronic acid (ZA) on the healing of a tooth extraction socket in dogs. The second was to determine if placement of recombinant human bone morphogenetic protein-2 (rhBMP-2)/absorbable collagen sponge (ACS) - INFUSE, (Medtronic, Memphis, TN) into these extraction sockets would inhibit the inhibition on bone healing and remodeling by ZA. Nine adult female beagle dogs (2 to 3 yr old) were placed into 3 groups of 3 dogs each. Group I received 15 mL of sterile saline intravenously; group II received 2.5 mg of ZA intravenously; and group III received 5 mg of ZA intravenously. Forty-five days after treatment, all dogs underwent extraction of noncontiguous right and left mandibular first molars and second premolars. In group I, the right mandibular extraction sockets had nothing placed in them, whereas the left mandibular sockets had only ACS placed in them. In groups II and III, the right mandibular sockets had rhBMP-2/ACS placed in them, whereas the left mandibular sockets had only ACS placed. All extraction sockets were surgically closed. Tetracycline was given intravenously 5 and 12 days later, and all animals were euthanized 15 days after tooth extraction. The extraction sockets and rib and femur samples were harvested immediately after euthanasia, processed, and studied microscopically. A single dose of ZA significantly inhibited healing and bone remodeling in the area of the tooth extractions. The combination of rhBMP-2/ACS appeared to over-ride some of the bone remodeling inhibition of the ZA and increased bone fill in the extraction sites, and remodeling activity in the area was noted. The effects of rhBMP-2/ACS were confined to the area of the extraction sockets because bone activity at distant sites was not influenced. A single dose of ZA administered intravenously inhibits early healing of tooth extraction sockets and bone remodeling in this animal model. The combination of rhBMP-2/ACS significantly increased bone fill and bone remodeling in these areas, negating much of the effect of the ZA.

Short-term effect of zoledronic acid upon fracture resistance of the mandibular condyle and femoral head in an animal model

Objective: The aim of this study was to compare the effects in terms of resistance to fracture of the mandibular condyle and femoral head following different doses of zoledronic acid in an animal model. Study design: A total of 80 adult male Sprague-Dawley rats were included in a prospective randomized study. The animals were randomly divided into four groups of 20 rats each. Group 1 (control) received sterile saline solution, while groups 2, 3 and 4 received a accumulated dose of 0.2 mg, 0.4 mg and 0.6 mg of zoledronic acid, respectively. The animals were sacrificed 28 days after the last dose, and the right hemimandible and the right femur were removed. The fracture strength was measured (in Newtons) with a universal test machine using a 1 kN load connected to a metal rod with one end angled at 30 degrees. The cross-head speed was 1 mm/min. Later, the specimens were observed under a scanning electron microscope with backscattered electron imaging (SEM-BSE). At last, chemical analysis and elemental mapping of the mineral bone composition were generated using a microanalytical system based on energy-dispersive and X-ray spectrometry (EDX). Results: A total of 160 fracture tests were performed. The fracture resistance increased in mandible and femur with a higher accumulated dose of zoledronic acid. Statistically significant differences were recorded versus the controls with all the studies groups. The chemical analysis in mandible showed a significantly increased of calcium and phosphorous to compare the control with all of the study groups; however, in femur no statistically significant differences between the four study groups were observed. Conclusions: The administration of bisphosphonates increases the fracture resistance in mandible and femur. Key words:Zoledronic acid, bisphosphonates, animal experimentation, fracture test.

Site-specific differential effects of once-yearly zoledronic acid on the hip assessed with quantitative computed tomography: results from the HORIZON Pivotal Fracture Trial

We used new approaches to the analysis of diagnostic scans to detect changes in bone density in different regions of the hip after 3years of treatment with the zoledronic acid. We showed that the drug significantly increases hip bone density compared to placebo at regions where hip fractures usually occur. This study aims to identify whether treatment with zoledronic acid exerts site-specific differential effects on volumetric bone mineral density (vBMD) at the hip. We analysed quantitative computed tomography scans of the hip obtained at baseline and 36months in 179 women participating in the HORIZON Pivotal Fracture Trial. Cortical, trabecular and integral BMDs were determined at three main regions of interest-the femoral neck (FN), trochanter (TR) and total hip (TH)-and several sub-regions of interest, namely the proximal, middle, distal, anterior, posterior, inferomedial and superolateral FN, and the middle and distal TR. Volumetric BMD increased significantly (p < 0.05) from baseline with zoledronic acid compared to placebo. Trabecular vBMD increased as follows: FN, 5.4%; FN sub-regions, 6.0% (proximal), 4.4% (middle), 5.6% (distal), 7.5% (anterior), 7.0% (superolateral) and 5.4% (posterior); TR, 6.5% and TH, 5.7%. Cortical vBMD increased as follows: FN sub-regions, 5.0% (proximal FN) and 2.3% (anterior); TR, 4.6%; middle TR, 2.7% and TH, 3.8%. The effects on vBMD of annual infusion of 5mg of zoledronic acid are site-specific and dominated by trabecular changes.

1580P - Pain Interference Outcomes in a Randomized Phase 3 Clinical Trial of Denosumab vs Zoledronic Acid (ZA) in Patients with Solid Tumors and Bone Metastases

ABSTRACT Background In patients with advanced cancer, bone metastases cause pain and may lead to skeletal-related events (SREs). Subcutaneous (SC) denosumab prevented SREs more effectively than intravenous (IV) ZA in patients with solid tumors and bone metastases in a phase 3 clinical trial (n = 1597; Henry D, J Clin Oncol. 2010. Abstr 9133). We now describe pain interference outcomes for patients with solid tumors in this trial (ClinicalTrials.gov NCT00330759; May 25, 2006; sponsor Amgen Inc.). Methods Patients received 120 mg of denosumab SC or 4 mg of ZA IV every 4 weeks in a randomized, multinational, double-blind, double-dummy trial. Patient-reported pain interference (overall, activity, and affect) was assessed by the Brief Pain Inventory (0: does not interfere-10: completely interferes) at baseline (BL) and upon each monthly visit. Analyses included time to clinically meaningful (≥2-point increase or decrease from BL) worsening or improvement in pain interference, and percentage of patients reporting clinically meaningful worsening in pain interference by visit. Analyses were conducted for patients with no/mild pain (worst pain 0-4) at BL and all patients at risk. Results In patients with no/mild pain at BL, denosumab delayed the median time to clinically meaningful worsening in pain interference compared with ZA (overall 3.4 months, P = 0.0213; activity 1.8 months, P = 0.0124; affect 0.9 months, P = 0.0518). Similarly, fewer of these patients treated with denosumab vs ZA reported clinically meaningful worsening in pain interference over all visits (average relative difference: overall 13%; activity 16%; affect 10% fewer). Time to clinically meaningful improvement in pain interference was similar between treatment groups. Pain interference outcomes were similar among all patients at risk compared to those with no/mild pain at BL. Conclusion In patients with solid tumors, denosumab delayed time to worsening of pain interference, and fewer patients reported worsening in pain interference over time, compared with ZA. Greater effects on pain interference were seen for patients with no/mild pain at BL, suggesting the benefit of early intervention with denosumab. Disclosure C. Cleeland: Advisory board member for Amgen, Genentech, Merck, and Exelixis, L. Fallowfield: Consultancy honoraria for serving on an advisory board for Amgen Inc., R. von Moos: Advisory board member for Amgen, Roche, & Novartis and unrestricted research grants from Amgen and Roche, D. Patrick: Research funding from Amgen Inc., D.H. Henry: Advisory board member, served on the speakers bureau, and received research funding from Amgen Inc., V. Hirsh: Advisory board member for Amgen Inc., A. Feng: Employed by and owns stock/stock options in Amgen Inc., Z. Cong: Employed by and owns stock/stock options in Amgen Inc., A. Braun: Employed by and owns stock/stock options in Amgen Inc., All other authors have declared no conflicts of interest.

Zoledronic Acid Cut Older Men's Fractures

Zoledronic Acid Cut Older Men's Fractures

Prophylactic use of zoledronic acid to prevent early bone loss is safe and feasible in patients with acute myeloid leukemia undergoing allogeneic stem cell transplantation

Osteopenia and osteoporosis are well-known consequences of allogeneic stem cell transplantation (allo-SCT). The role of prophylactic zoledronic acid on bone turnover following allo-SCT has not been well characterized. We prospectively studied the role of prophylactic use of zoledronic acid on bone metabolism in 17 patients with acute myeloid leukemia (AML) undergoing allo-SCT over a period of three yr (2006-2009). We measured bone mineral density using dual energy X-ray absorptiometry (DXA) scanning and the markers of bone turnover by urinary N-terminal telopeptide (uNTX) and serum osteocalcin levels prior to and serially following transplantation. All patients received 4 mg of zoledronic acid (Zometa, Novartis Pharmaceuticals Corp., Basel, Switzerland) intravenously prior to starting conditioning regimen and at six months after SCT. DXA scores did not change significantly in any patient over time (p > 0.05). uNTX progressively decreased over time (p < 0.001) and serum osteocalcin stabilized after six months. No patient developed osteonecrosis of the jaw. In conclusion, in this prospective pilot study, prophylactic use of zoledronic acid to prevent early bone loss was found to be safe and feasible in patients with AML undergoing allo-SCT during the immediate post-transplantation period.

Locally Administered Zoledronic Acid Therapy for Giant Cell Tumor of Bone

Giant cell tumor of bone is locally aggressive and occurs in the meta-epiphyseal region of long bones. Because of its high recurrence rate, local adjuvant therapies such as phenol or liquid nitrogen have been recommended. In the present study, zoledronic acid, a nitrogen-containing bisphosphonate, was administered locally as an adjuvant during a biopsy. An otherwise healthy 43-year-old man presented with pain and swelling in the right knee. Plain radiographs showed an osteolytic lesion of the right proximal tibia. An open biopsy was performed and the intraoperative pathologic diagnosis was giant cell tumor of bone. Following biopsy, the defect was filled with betatricalcium phosphate, and 4 mg of zoledronic acid was locally administered into the tumor lesion. Two months after the biopsy, curettage and bone grafting were performed. Sections were obtained during the curettage for histology to evaluate the response to bisphosphonate treatment. Histologic examination revealed massive tumor cell death in the lesion in which both stromal cells and osteoclast-like giant cells were necrotic. Curettage was performed and the defect was filled with a commercial preshaped hydroxyapatitetricalcium phosphate bone substitute. Eighteen months after curettage, the patient had regained full range of motion and good function of the knee, and radiographs at 18 months after curettage revealed no recurrence of giant cell tumor of bone.