Intravenous Zolendronic Acid Research Articles

Estimating Patient Eligibility And Benefit Of Intravenous Zolendronic Acid In Hip Fracture Patients: A Service Evaluation

Abstract Background Low trauma hip fractures are serious and carry an estimated re-fracture rate of 10.6%, leading increased morbidity, mortality and healthcare cost. Intravenous Zolendronic Acid (IVZ) administration following hip fracture reduces re-fracture risk by approximately 23% and is recommended yearly for three years by National Osteoporosis Guidelines Group (NOGG) 2021. However, a significant treatment gap remains with only one-fifth of patients receiving IVZ pre-discharge, due to implementation challenges, such as suboptimal Vitamin D levels and lack of resources for yearly infusions. Recently published consensus guidelines offer practical advice as to how to overcome these barriers. This service evaluation estimates the proportion of hip fracture patients eligible for IVZ; as well as the re-fracture rate, prior to the introduction of a local IVZ pathway. Methods Approval from local Quality and Patient Safety Department was received. Low trauma hip fracture patients were identified from the local Orthogeriatric database (October 2019 to January 2021). Hospital electronic laboratory and radiology software were used to identify renal function on discharge and evidence of further fractures (at six months, 1 year and 3 years). Subjects were deemed potentially eligible for IVZ if they had an estimated glomerular filtration rate (eGFR) of ≥50 mls/min (a proxy for calculated creatinine clearance ≥30mls/min in this patient cohort). Results Of 463 subjects, 384 (82.9%) had an eGFR ≥50. Re-fracture data was collected for 263 eligible subjects. Seventeen (6.5%) re-fractured within six months, 21 (8%) re-fractured within a year and 45 (17.1%) re-fractured at any stage post discharge. Conclusion IVZ treatment is the most efficacious secondary fracture prevention post-hip fracture, and most patients are eligible for this treatment. Implementing IVZ pathways for hip fracture patients may significantly reduce re-fracture rate, however expansion of resources allocated to Orthogeriatrics and Fracture Liaison teams is required to successfully implement inpatient pathways and ongoing care.

Fatal Myocarditis Following Administration of Zoledronic Acid: A Case Report

Myocarditis is a potentially life-threatening condition which occurs due to inflammation of the cardiac muscle. It has a multitude of causes including certain medications. Zoledronic acid is a bisphosphonate given as an intravenous preparation for bone related diseases. Medical literature provides details about only very few cases of Zoledronic acid induced myocarditis and all of them were non-fatal. We report a fatal case of myocarditis due to administration of intravenous Zolendronic acid. A 40-year-old male with a history of multiple joint pain and swelling for one week and right knee joint swelling for three months was administered intravenous Zolendronic acid. One day after administration of Zolendronic acid patient developed dizziness, and eventually became drowsy. His ECG revealed ST depressions in leads I, II, aVF, as well as leads V3 to V5. Highly sensitive Troponin I was elevated to 2195.3 pg/ml (<26.5 pg/ml) and Echocardiogram showed an ejection fraction of 30% with hypokinetic wall segments and regional wall motion abnormalities. He went into cardiogenic shock and was pronounced dead. At the autopsy, macroscopic examination did not reveal any noticeable fatal pathology. however histological examination of the myocardium reveals diffuse infiltration mononuclear cells with myocyte necrosis. This case highlights importance of being vigilant in using this drug.

Analysis of efficacy of intravenous zolendronic acid therapy in osteoporosis with dexa scan

Introduction: Bisphosphonates are one of the commonly used drugs for the treatment and prevention of osteoporosis. Many of the old generation oral bisphosphonates have got lesser affinity to bone mineral matrix and low patient compliance. Newer generation intravenous zolendronic acid has got a better compliance due to once a year dose and it is more effective due to its more affinity towards bone mineral matrix. Hence this study was conducted to evaluate the results of intravenous zolendronic acid in osteoporotic individuals using Dual Energy X ray Absorptiometry. Materials and Methods: The study was conducted in a tertiary centre between January 2012 to January 2016. The sample size was 36. The patient recruitment was done in a consecutive manner. Patients were diagnosed by DEXA scan and Lumbar spine BMD taken as representative and inj. zolendronic acid was given once a year, repeated every year, total for 3 years duration therapy. Student Paired t-test was used to find the statistical significance. Gender, fracture sustained during the study, complication, hypothyroidism and status of improved were expressed as frequency and the percentage. p < 0> Results and Analysis: The mean age of our study population was 67.7 yrs. 12 patients in our study had improvent in BMD (t - score) which was 40% of the whole study group. These 12 patients had an actual percentage rise in BMD by 11.62% on average, detected by DEXA Scan. All these patients were under the age bracket of 65 years. 18 patients did not have any improvement in or worsening of BMD and were above the age bracket of 65 yrs of age. This could be attributed to their medical co - morbid conditions and nutrional status. The incidence of another fracture was 8% among people who had a previous fracture. 10% of the study population had adverse effects like fever and myalgia. There were no other serious adverse effects. Keywords: Osteoporosis, Zolendronic acid, DEXA.

Bisphosphonate combination therapy for non-femoral avascular necrosis

BackgroundAvascular necrosis at sites other than femoral head (AVNOFH)/Non-Femoral AVN is a rare entity. No standard of treatment still exists for treating early stages of AVNOFH with most of the cases eventually progressing to a late arthritic stage needing surgical intervention. Bisphosphonates have been shown to prevent disease progression, bone collapse, and the requirement for surgery in avascular necrosis of femoral head. The present study is conducted to evaluate the response of bisphosphonates in the non-surgical management of the early stages of AVNOFH.Materials and methodsProspectively collected data of 20 patients diagnosed with an early stage of AVNOFH and treated with the combination of oral alendronate 70 mg weekly and intravenous zolendronic acid (ZA) for 1 year, between Jan 2009 to Dec 2015, was evaluated retrospectively. Clinical evaluation was done using the visual analogue scale (VAS), mean analgesic requirement, and range of motion. Radiographs and magnetic resonance imaging (MRI) were taken to classify the stage of AVN, monitor radiological collapse, and evaluate radiological progression and bone marrow edema changes.ResultsIn our analysis of 18 patients (2 lost to follow-up), 5 patients had AVN of the humeral head, 4 patients of the talus, 3 of the lunate, and 2 each of the scaphoid, medial tibial plateau, and second metatarsal head. Pain relief with the drop in VAS score was seen at a mean duration of 4.3 weeks (range 3–13 weeks) after the start of therapy. A 50% reduction in mean analgesic requirement was achieved in the first 6 weeks (2-11 weeks). MRI showed complete resolution of BME in 13 patients at 6 months and in 17 patients (94.4%) at 1 year. Radiological collapse was seen in 6 out of 18 patients at a mean follow-up of 35.3 months (range 14–56 months). Only one out of 18 patients enrolled required surgery.ConclusionA combination of oral alendronate and intravenous zolendronic acid provides a pragmatic solution to this rare entity of AVNOFH, where no standard treatment exists.

Bisphosphonate Combination Therapy in the Management of Postchemotherapy Avascular Necrosis of the Femoral Head in Adolescents and Young Adults: A Retrospective Study From India.

PurposeWith improved survival after chemotherapy for acute lymphoblastic leukemia (ALL), it is imperative to maintain good quality of life as part of the management of post-therapy adverse effects. Avascular necrosis of the femoral head (AVNFH) is one such adverse effect. A need exists for a therapy that ameliorates discomfort, provides a productive life, is cost effective, and is joint preservative. We conducted the current study to evaluate the response to bisphosphonate in the nonsurgical management of AVNFH in adolescents and young adults (AYA) who receive treatment for ALL.Materials and MethodsThis is a retrospective study of 20 AYA patients—34 affected hips—who received zolendronic acid 5 mg intravenously each year along with oral alendronate 70 mg weekly for 3 years. Clinical evaluation was performed by using the Visual Analog Scale and the Harris Hip Score. Radiographs were used to classify the Ficat-Arlet stage, monitor radiologic collapse, and evaluate the rate of progression.ResultsPain relief with a drop in the Visual Analog Scale score was observed at a mean duration of 5.2 weeks (range, 3 weeks to 11 weeks) after the start of therapy. Radiologic progression by one grade was observed in 12 hips (35.3%), and only one hip (2.94%) showed progression by two grades. At a mean follow-up of 50.3 months, 31 affected hips (91.1%) had a satisfactory clinical outcome and had not required any surgical intervention. The proportion of hips that required total hip arthroplasty were 0%, 5%, and 22.2% in Ficat-Arlet stage I, II, and III, respectively.ConclusionThe combination of intravenous zolendronic acid and oral alendronate provides a pragmatic solution for the management of AVNFH after therapy for ALL in AYA patients. This therapy is safe, effective, and well tolerated.

Headache in patients with Paget’s Disease of Bones

Paget's disease of bone (PDB) is a focal remodeling disorder of unknown origin. Head bones are frequently involved and patients may suffer from deformities and specific symptoms, mainly headache, or neurological deficits, such as deafness. Several pathophysiological entities can give rise to headache in PDB patients. Clinical, laboratory, radiological and scintigraphic findings contribute to distinguish headache related to PDB from other causes of headache. Up to the present, treatment with intravenous zolendronic acid has been reported to improve symptoms of PDB and induce long-standing biochemical and scintigraphic remission. In this review, the main strands of literature about epidemiology, pathophysiology, clinical characteristics and treatment of PDB-related headache are drawn together.

Foot and Ankle Insufficiency Fractures in Rheumatoid Arthritis

Objectives: To evaluate causes of foot and ankle insufficiency fractures in patients with rheumatoid arthritis. To conduct a literature review of low dose methotrexate induced osteopathy. Case series: Three patients with rheumatoid arthritis who sustained foot and ankle insufficiency fractures which were only detected on MRI. All three patients were on biologic treatment and methotrexate for RA, and two had evidence of hind-foot deformity. All had evidence of osteoporosis on bone density scan, and two were already on intravenous zolendronic acid. Conclusion: Insufficiency fractures occur in approximately 1% of patients with rheumatoid arthritis [1]. Contributing factors include chronic inflammation; skeletal deformities; biomechanical stresses; use of glucocorticoids; and osteoporosis. An additional pathophysiological mechanism may be low-dose methotrexate induced osteopathy. However, there is currently insufficient evidence to conclude this.

Long-term management of the successful adult liver transplant: 2012 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation

Michael R. Lucey, Norah Terrault, Lolu Ojo, J. Eileen Hay, James Neuberger, Emily Blumberg, and Lewis W. Teperman Division of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI; Gastroenterology Division, Department of Medicine, University of California San Francisco, San Francisco, CA; Division of Nephrology, Department of Medicine, University of Michigan, Ann Arbor, MI; Mayo Clinic, Rochester, MN; Liver Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom; Division of Infectious Diseases, University of Pennsylvania School of Medicine, Philadelphia, PA; and Department of Surgery, NYU Transplant Associates, New York, NY

Intermittent Zolendronic Acid (ZA) for the Prevention of Osteoporosis After Allogeneic Hematopoietic Cell Transplantation (HCT)

AbstractAbstract 1965Bone mineral density (BMD) loss, osteoporosis, and avascular necrosis (AVN) of bone are relatively common in long term survivors of HCT with up to one half of recipients suffering post HCT bone loss. We performed a multi center phase II randomized open label trial of intravenous zolendronic acid (ZA) to prevent BMD loss in recipients of allogeneic HCT with pre-existing osteopenia prior to HCT. Methods:Eligible adult (>18 years) patients had baseline pre-transplant osteopenia defined as a T-score < −1 SD and > −2.5 SD (WHO definifition) at either the lumbar (L) spine and/or the proximal femur at a pre HCT screening evaluation with a dual energy X-Ray absorptiometry (DEXA) scan. Patients were eligible irrespective of donor source, stem cell type, or conditioning regimen intensity. Patients with myeloma, baseline renal dysfunction or concomitant active dental or endocrine issues precluding the use of ZA were excluded. Subjects were allocated by block randomization stratified by center and type of conditioning (myeloablative vs. non-myeloablative) to the treatment or control arms.Both treatment and control groups received 1000 mg of calcium and 400 – 500 IU of vitamin D orally daily and were encouraged to remain active and refrain from tobacco smoking and alcohol. Additionally subjects randomized to the treatment arm received ZA 4 mg iv over 15 minutes within 28 days pre-HCT and at 3 and 6 months (mo) after HCT. Control subjects did not receive ZA or other additional therapy for bone strength. ZA dose was modified for post HCT renal dysfunction.Primary outcome measure was change in BMD from baseline to 12 mo after HCT. Serum osteocalcin, serum bone specific alkaline phophatase (BSAP), and urinary N telopeptide (UNTX) were measured at baseline and at 6 and 12 mo. Results:Between 2006 and 2010, 61 patients were randomized – 32 to the ZA treatment cohort and 29 to the control arm. Cohorts were balanced for age, sex, performance score, donor type, diagnoses and conditioning regimen intensity. HCT co-morbidity index (HCTCI) was significantly worse in the ZA arm (50% with high risk scores > 3). Baseline BMD, T scores at the femoral neck and lumbar spine, urinary NTX, serum osteocalcin and BSAP were similar in both cohorts.Differences between cohorts in bone density and bone specific laboratory parameters at 12 mo post HCT are summarized in Table 1. There was significant increase in BMD at the femoral neck and lumbar Spine; with concomitant decease in bone resorption markers for the treatment group (ZA cohort). Incidences of acute and chronic graft vs. host disease and relapse rates were similar between cohorts. There was significantly higher 1 year mortality in the ZA cohort (15 deaths vs. 6 in the control cohort). Thus overall survival was inferior in the ZA cohort 43% vs. 75% at 2 years post HCT. Grade 3–4 adverse events were similar. Conclusions:We randomized HCT recipients at high risk of post transplant bone loss to receive 3 doses ZA starting prior to HCT. ZA prevented further bone loss and resulted in improvement in BMD and T scores as well the bone resorption marker, urinary NTX. Lower survival was observed in the ZA cohort likely related to baseline imbalance in pretransplant HCTCI scores. ZA was well tolerated and not associated with any cases of osteonecrosis of jaw, renal impairment or other serious adverse events. We conclude that intermittent ZA is effective in preserving long term bone health in HCT recipients at risk for osteoporosis.Table 1ParameterDifference from baseline to 12 moP ValueZA cohortStandard of CareBMD L Spine0.048−0.057<0.01T score L Spine0.55−0.45<0.01Z score L Spine0.50−0.200.06BMD Femoral0.018−0.0540.04T score Femoral0.20−0.400.02Z score Femoral0.30−0.300.03S. Osteocalcin−11−4.10.44S.BSAP−3−30.66Urine NTX−56−90.04 Disclosures:Hari:Novartis: Research Funding. Vesole:Novartis: Research Funding. Burns:Novartis: Research Funding.

Osteonecrosis maxilar asociada a bisfosfonatos e infección por Actinomyces

Bisphosphonate related osteonecrosis of the jaw (BRONJ) has raised considerable interest since its recent description. Its pathogenesis is not yet clarified; formerly it has been considered a non-infectious complication, but recent studies seem to implicate bacteria of the genus Actinomyces. The objective of this study is to analyze the cases of BRONJ in our institution. Review of medical records of patients diagnosed of BRONJ in the Maxillofacial Surgery Unit of our hospital. We have found 11 cases of BRONJ in our hospital: 4 women taking oral alendronate or risendronate for osteoporosis and 7 cancer patients treated with intravenous zolendronic acid. All of them showed bone invasion by bacteria of the genus Actinomyces. Nine patients underwent prolonged treatment with amoxicillin with favourable clinical outcome in all of them, but 3 died of their malignancy. By contrast, one patient with beta-lactamic allergy and irregular treatment with erythromycin and tetracycline had a chronic evolution of the lesions. There was no information for other patient. Actinomyces play an important role in the development of BRONJ and specific antibiotic treatment improves the prognosis of this process.

The early metabolic effect of zolendronic acid on FDG-PET scans in patients with bone metastasis.

e21168 Background: 18-fluorodeoxyglucose (FDG) positron emission tomography combined with computerized tomography (FDG-PET/CT) is widely used in staging of several cancers. Any agent that can cause a decreased uptake of FDG by tumor cells can lead to inaccurate staging of the cancer. Bisphosphonates are routinely administered to patients with bone metastasis to reduce the morbidity related to skeletal events. Recently, it was shown that zolendronic acid (ZA) has also antitumor effects due to several potential mechanisms, including the induction of tumor cell apoptosis, inhibition of tumor cell invasion/migration, activation of anticancer tumor responses and anti-angiogenic effects. Although we know that the interval between the last dose of chemotherapy and the PET/CT study is important for reliable interpretation, the effect of ZA on maximum standardized uptake values (SUVmax) on FDG-PET scans in cancer pts with bone metastasis is not identified. Methods: The primary aim for this trial was to assess the change in maximum SUVs of tumor lesions on PET/CT, 72 hour after the administration of ZA therapy in pts with bone metastasis. Twelve pts (6 male, 6 female) with newly diagnosed cancer having bone metastasis on FDG-PET/CT were prospectively enrolled to this trial. Pts were chemotherapy-naïve. No prior or concurrent use of bisphosphonates was allowed. Pts received 4 mg of intravenous ZA and PET/CT was done 72 hours later. Results: The median age of pts was 59 years (38-70). The primary tumors were non-small cell lung cancer (n=7), breast cancer (n=3), renal cell carcinoma (n=1) and gastric neuroendocrine tumor (n=1). When baseline PET/CT was compared with the PET/CT that was done 72 hours after ZA administration, no significant change was detected in the SUVmax of the bone lesions and SUVmax of the primary lesion. In 3 pts, some bone lesions became metabolically unrecognizable after ZA administration, but the stage did not change in these pts. These lesions had a relatively low SUVmax on baseline PET/CT. Conclusions: Our results suggest that administration of ZA prior to staging with PET/CT does not seem to affect the FDG-uptake level of tumor lesions in PET/CT.

The effect of intravenous zolendronic acid (ZOL) 5mgs once yearly in the treatment of postmenopausal osteoporosis. A peripheral quantitative computed tomography (PQCT) study

The effect of intravenous zolendronic acid (ZOL) 5mgs once yearly in the treatment of postmenopausal osteoporosis. A peripheral quantitative computed tomography (PQCT) study

Intravenous Zolendronic Acid for the Patients Treated Operatively after Hip Fracture: A Short-Term Safety Prospective Cohort Study

Intravenous Zolendronic Acid for the Patients Treated Operatively after Hip Fracture: A Short-Term Safety Prospective Cohort Study