Single Dose Of Zoledronic Acid Research Articles

Abstract PO1-12-10: Zoledronic acid to prevent rebound fractures after stopping adjuvant denosumab: a randomized controlled sub-study of the ABCSG-18 trial

Abstract Introduction ABCSG-18 trial showed that 60mg denosumab subcutaneously every 6 months halves fracture risk in postmenopausal patients with early breast cancer, who are treated with adjuvant aromatase inhibitors. However, it has been reported that stopping denosumab may lead to overactivation of osteoclasts resulting in so called rebound vertebral fractures. As shown previously, zoledronic acid (ZA), when given to patients of the ABCSG-18 trial after stopping denosumab prevents a high bone turnover state that can occur in some patients. Here we report the impact of a single ZA dose on bone mineral density (BMD) and fractures after stopping denosumab. Methods ABCSG-18 trial patients, who had received adjuvant denosumab were re-randomized to receive a single dose of ZA 5mg i.v. or not, 8 months +- 4 weeks after their last denosumab dose. DXA scans, lateral spine X-rays and bone turnover markers (CTX and osteocalcin) were assessed at baseline and at 6, 12 and 18 months thereafter. New clinical fractures were assessed until 18 months after randomization. Results 50 patients were randomized to either ZA (24pts) or control (26pts). All patients of the ZA arm and 25 out of 26 patients of the control arm had received 7 doses of denosumab within the ABCSG 18 trial before re-randomization. Baseline bone health factors were well balanced between the 2 arms: Baseline BMD did not differ between the two arms with regard to femoral neck (ZA: 0.817 g/cm2; SOC: 0.816g/cm2), total hip (ZA: 0.918g/cm2; SOC: 0.921g/cm2) and lumbar spine (ZA: 1.128 g/cm2; SOC 1.142 g/cm2), respectively. Relative changes in BMD differed significantly between both arms for femoral neck after 12 months (ZA: 0.5%; control: -4.98%, p 0.004) and for total hip after 6 months (ZA: -0.73%; control: -4.61%, p< 0.001) and after 12 months (ZA: -0.13%; control: -5.62%; p< 0.001). There was a trend towards a greater decline in BMD at lumbar spine after 6 months in the control arm versus the ZA arm (-3.35% vs 0.67%, p=0.052). After randomization, 3 asymptomatic fractures (lumbar vertebral and thoracic vertebral in one patient and thoracic vertebral in a second patient) occurred in the ZA arm, whereas 2 clinical fractures (one radius fracture and one lumbar vertebral fracture) occurred in the SOC arm. Conclusion A single dose of Zoledronic acid prevents high bone turnover state resulting in loss of BMD in some patients after stopping denosumab. ZA may therefore be offered to breast cancer patients with aromatase inhibitor after stopping denosumab. Citation Format: Georg Pfeiler, Christian F. Singer, Dominik Hlauschek, Manfreda Diether, Ferdinand Haslbauer, Paul Sevelda, Kristin Köck, Karl Tamussino, Arno C. Reichenauer, Florian Fitzal, Dietmar Heck, Richard Greil, Claudia Pasterk, Sonja Heibl, Walter Herz, Marija Balic, Daniel Egle, Lidija Sölkner, Michael Gnant. Zoledronic acid to prevent rebound fractures after stopping adjuvant denosumab: a randomized controlled sub-study of the ABCSG-18 trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-12-10.

Depressive Disorder in Primary Hyperparathyroidism and Effects of Surgery in Elderly Patients: Case Series

Background: Patients with primary hyperparathyroidism (PHPT) often present nonspecific symptoms such as major depressive disorder and psychosis. Calcium plays a role in the pathogenesis of psychiatric symptoms by determining changes in monoamine metabolism in the central nervous system, thereby modifying neurotransmission and resulting in mood and cognitive alterations. Case series: This report presents a case series of 3 patients; 70-year-old, 78 year- old and 94 year-old women with PHPT and severe depression symptoms and its response to parathyroidectomy. The patients were a poor historian. Results of preoperative laboratory tests showed an increased serum calcium level (11.15mg/dL, 10.9 mg/dL and 11.4 mg/dL- reference range 8.4-10.2 mg/dL). A repeat serum calcium test confirmed hypercalcemia with concurrent elevated intact parathyroid hormone level. Two patients were undergone at parathyroidectomy. A 94 year-old patient refuse surgical approach and was efficacy treated with a single dose of zoledronic acid. Therefore, the patients underwent parathyroidectomy two months after procedure had a clinical improvement on depressive symptoms. There was any recurrent laryngeal nerve injury or recurrent PHTP. Conclusion: The presence of a long-standing depressive disorder unresponsive to medical therapy may suggest an organic disorder such as chronic hypercalcemia which may be secondary to PHPT. Surgical intervention in these selected cases can assist medical therapy in the improvement of depressive symptoms.

SAT253 A Rare Case Of Osteolytic Hypercalcemia Of Malignancy In Acute Myeloid Leukemia

Abstract Disclosure: S. Elahi: None. S. Baim: None. Introduction: Acute myeloid leukemia (AML) and other leukemias do not commonly induce hypercalcemia of malignancy (HCM). Limited previous reports of AML-related HCM have largely attributed cases to inflammatory-cytokine-mediated osteoclast activation, with rare reports of calcitriol-mediated HCM and ectopic parathyroid hormone (PTH) production. We describe an unusual case of AML-induced HCM caused by direct leukemic bone invasion, which responded to bisphosphonate therapy. Case Presentation: A 59-year-old female presented with spontaneous bruising and severe leukocytosis concerning for AML. The diagnosis was confirmed by flow cytometry and bone marrow biopsy. Imaging did not reveal any gross destructive bone lesions, but showed soft tissue nodules in the lumbar region which biopsy revealed to be myeloid sarcoma. Prior to initiation of chemotherapy, the patient developed severe hypercalcemia that was treated with aggressive intravenous hydration and zoledronic acid. Intrathecal chemotherapy and high-dose glucocorticoid therapy were initiated thereafter with normalization of serum calcium levels. PTH levels were suppressed. Calcitriol and PTHrP were below normal and undetectable, respectively. Bone turnover markers (C-telopeptide and bone-specific alkaline phosphatase) were significantly elevated prior to administration of zoledronic acid and normalized post-therapy. Calcium levels did not rebound after several interruptions in chemotherapy. Bone marrow biopsy showed focal areas of erosion in trabecular bone consistent with diffuse microscopic osteolytic disease. The patient developed bisphosphonate-induced hypocalcemia following treatment with zoledronic acid, which normalized with treatment with oral calcium carbonate. Discussion: Hypercalcemia of malignancy is a very unusual consequence of AML. No currently-published reports of this phenomenon have described biopsy-proven diffuse microscopic bone erosion associated with AML. We attribute our patient’s severe HCM to large-scale focal bone erosion by AML, independent of and/or associated with concurrent bone resorption mediated by inflammatory cytokines. A single dose of zoledronic acid, a potent suppressor of bone remodeling, achieved long term control of calcium for our patient despite interruption of chemotherapy. Bisphosphonate therapy should be considered an early treatment of HCM in patients with AML due to several potential mechanisms that result in direct calcium release from the skeleton. Presentation: Saturday, June 17, 2023

Effect of a single dose of zoledronic acid on bone mineral density and trabecular bone score in Indian postmenopausal osteoporotic women with and without type 2 diabetes mellitus - A prospective cohort pilot study.

The objectives were to study the effect of a single dose of intravenous (IV) zoledronic acid (ZA) on changes in bone mineral density (BMD) (lumbar spine (LS), hip, & distal forearm), trabecular bone score (TBS) and bone turnover markers (BTMs) in postmenopausal osteoporotic women with and without diabetes over 12 months. Patients were divided into two groups: type 2 diabetes mellitus (T2DM) (n = 40) and non-DM (n = 40). Both groups received a single dose of 4 mg IV ZA at baseline. The BMD with TBS and BTMs (β-CTX, sclerostin, P1NP) were measured at baseline, six months, and 12 months. At baseline, BMD in all three sites was similar in both groups. T2DM patients were older and had lower BTMs than non-DM patients. The mean increase in LS-BMD (gram/cm2) at 12 months in T2DM and the non-DM group was 3.6 ± 4.7% and 6.2 ± 4.7 %, respectively (P = 0.01). However, the age adjusted mean difference in LS BMD increment between two groups at one year was - 2.86 % (-5.02% to -0.69%), P = 0.01. There was a comparable change in BMD at other two sites, BTMs, and TBS in both the groups over one year follow-up. The gain in the LS-BMD was significantly lower in T2DM group compared to non-DM subjects over 12 months after a single IV infusion of 4 mg ZA. The explanation for this could be low bone turnover in diabetes subjects at baseline.

Muscle-Specific Micro-Ribonucleic Acids miR-1-3p, miR-133a-3p, and miR-133b Reflect Muscle Regeneration After Single-Dose Zoledronic Acid Following Rotator Cuff Repair in a Rodent Chronic Defect Model

Background: Zoledronic acid improves bone microarchitecture and biomechanical properties after chronic rotator cuff repair (RCR) in rats. Besides the positive effects of zoledronic acid on bone mineral density and bone microarchitecture, bisphosphonates have positive effects on skeletal muscle function. Purposes/Hypothesis: The purposes of this study were to (1) longitudinally evaluate circulating bone- and muscle-specific serum micro-ribonucleic acids (miRNAs) and (2) investigate supraspinatus muscle tissue after tenotomy and delayed RCR in a rat model. It was hypothesized that zoledronic acid would improve muscle regeneration after chronic RCR in rats. Study design: Controlled laboratory study. Methods: A total of 34 male Sprague-Dawley rats underwent unilateral (left) supraspinatus tenotomy (time point 1) with delayed transosseous RCR after 3 weeks (time point 2). All rats were sacrificed 8 weeks after RCR (time point 3). Animals were randomly assigned to 2 groups. One day after RCR, the control group was given 1 mL of subcutaneous saline solution, and the intervention group was treated with a subcutaneous single-dose of 100 µg/kg body weight of zoledronic acid. All 34 study animals underwent miRNA analysis at all 3 time points. In 4 animals of each group, histological analyses as well as gene expression analyses were conducted. Results: Circulating miRNAs showed significantly different expressions between both study groups. In the control group, a significant downregulation was observed for muscle-specific miR-1-3p (P = .004), miR-133a-3p (P < .001), and miR-133b (P < .001). Histological analyses showed significantly higher rates of regenerating myofibers on the operated side (left) of both study groups compared with the nonoperated side (right; P = .002). On the nonoperated side, significantly higher rates of regenerating myofibers were observed in the intervention group compared with the control group (P = .031). The myofiber cross-sectional area revealed significantly smaller myofibers on both sides within the intervention group compared with both sides of the control group (P < .001). Within the intervention group, significantly higher expression levels of muscle development/regeneration marker genes embryonal Myosin heavy chain (P = .017) and neonatal Myosin heavy chain (P = .016) were observed on the nonoperated side compared with the operated side. Conclusion: An adjuvant single-dose of zoledronic acid after RCR in a chronic defect model in rats led to significant differences in bone- and muscle-specific miRNA levels. Therefore, miR-1-3p, miR-133a-3p, and miR-133b might be used as biomarkers for muscle regeneration after RCR. Clinical Relevance: Adjuvant treatment with zoledronic acid may improve muscle regeneration after chronic RCR in humans, thus counteracting fatty muscle infiltration and atrophy.

Orchestrated delivery of PTH [1-34] followed by zoledronic acid prevents radiotherapy-induced bone loss but does not abrogate marrow damage.

Postradiotherapy bone fragility fractures are a frequent late-onset complication in cancer survivors. There is a critical need to develop preventative interventions, and the use of Food and Drug Administration-approved drugs remains an attractive option. Prior data from our lab and others have shown that parathyroid hormone [1-34] mitigates radiotherapy-induced bone loss, but only for the duration of drug delivery. Utilizing a murine hindlimb radiotherapy model, we investigated whether orchestrated delivery of single-dose zoledronic acid could extend these anabolic benefits after cessation of parathyroid hormone delivery. We then explored the potential use of parathyroid hormone as a bone marrow radioprotectant. While the addition of zoledronic acid to parathyroid hormone increased irradiated bone mass, there was no increase in femur bending strength. In this model, the parathyroid hormone was not effective as a marrow radioprotectant, although this could be due to the short course of parathyroid hormone treatment. Marrow repopulation kinetics differed from those in total body irradiation, with hematopoietic stem cell repopulation occurring relatively early at four weeks postirradiation. Furthermore, we found radiation induced a loss of marrow stromal cells and an increase in inflammatory monocytes. Statement of Clinical Significance: Staged delivery of parathyroid hormone and zoledronic acid shows promise as an off-the-shelf intervention to mitigate post-radiotherapy bone damage in cancer patients, but parathyroid hormone is unlikely to function as a broad-spectrum marrow radioprotectant.

Relationship Between Changes in Serum Levels of Intact Parathyroid Hormone and Sclerostin After a Single Dose of Zoledronic Acid: Results of a Phase 1 Pharmacokinetic Study

Although changes in serum sclerostin levels at 12 months after infusion of zoledronic acid have been reported, the changes in sclerostin levels at earlier time points are poorly understood. We reanalyzed the study data of a previous phase 1 pharmacokinetic study and investigated the correlation between changes in sclerostin levels and relevant factors in calcium metabolism. A total of 24 Japanese female subjects with primary postmenopausal osteoporosis were administered a single 4- or 5-mg dose of zoledronic acid. Serum and urine samples were collected on days 15, 29, 90, 180, and 365 after administration. Serum levels of calcium, phosphate, intact parathyroid hormone (iPTH), and sclerostin were measured. Levels of serum sclerostin were unchanged from baseline on days 15 and 29, but increased significantly on day 90, subsequently decreased significantly on day 180, and returned to baseline levels on day 365. A significant negative correlation was observed between changes in iPTH levels at early time points and sclerostin levels at later time points. This suggests that sclerostin was negatively regulated by iPTH, and the decrease in sclerostin may indicate the start of bone formation during later time points after zoledronic acid injection.

Zoledronic acid and bone health in older adults with cognitive impairment.

Osteoporosis has detrimental consequences for frail older adults. The effects on those with both osteoporosis and cognitive impairment are compounded due to increased risk of falls and changes in mobility, both of which can lead to fracture. However, there are limited data on treatment benefits for osteoporotic individuals with cognitive impairment. This post hoc, secondary analysis of data from a randomized, double-blind, placebo-controlled clinical trial of single-dose zoledronic acid included 179 women age ≥ 65 years residing in assisted living facilities or nursing homes, 43 of whom had mild to severe cognitive impairment. We assessed bone mineral density (BMD) of the total hip, femoral neck, and lumbar spine by dual-energy x-ray absorptiometry and serum bone turnover markers (C-terminal telopeptide of type I collagen and procollagen type I N propeptide) at 6 and 12 months. In participants with cognitive impairment, those who received zoledronic acid had 4.3% greater BMD at the total hip (p=.005) and 5.3% greater BMD at the femoral neck (p<.001) after 12 months compared to those in the placebo group. Bone turnover markers demonstrated significant decreases at 6 months in those with cognitive impairment who received active treatment compared to the placebo group. Improvements in bone health measures with zoledronic acid were similar to those seen in participants without cognitive impairment. Zoledronic acid improves bone health in frail older women with cognitive impairment similar to those without impairment. Further studies are warranted to assess the benefit for fracture reduction in this undertreated population.

Single-Dose Therapy of Zoledronic Acid for the Treatment of Primary Bone Marrow Edema Syndrome.

ObjectiveTo review the patients diagnosed with bone marrow edema syndrome who had been treated with one single dose of zoledronic acid.MethodsThe data of 54 patients with bone marrow edema syndrome treated with a single dose of intravenous zoledronic acid and partial weight-bearing were included in the study. The diagnosis was based on clinical examination, the existence of prolonged pain, the presence of bone marrow edema on magnetic resonance imaging, and the patient’s medical history. The efficacy was assessed using changes in symptoms, visual analogue scale, and changes in magnetic resonance imaging.ResultsOverall, 54 patients (35.2% male) were included with bone marrow edema syndrome, with a mean age of 52.7 ± 9.77 years (range: 35 - 74 years). The most commonly affected joint was the knee in 32 patients (59.2%), followed by the foot/ankle in 13 patients (24.1%), and the hip in nine patients (16.7%). Improved mobility was reported by 29 patients (53.7%) among the total number of the patients at the six-month follow-up visit. The mean visual analogue scale was 6.77 ± 0.83, 7.25 ± 1.19, and 7.46 ± 0.96 at baseline and 5.11 ± 2.14, 4.25 ± 1.84 and 5.15 ± 2.03 at the six-month follow-up for the hip, knee and foot/ankle, respectively (p = 0.098, p < 0.001, p = 0.002). At the six-month follow-up, the MRI showed resolution of the edema in 20 out of 54 patients (approximately 37%). Only 7.4% of the patients reported minor adverse events which were resolved through a single administration of paracetamol.ConclusionOur data show that the combination treatment of a single dose of zoledronic acid and partial weight-bearing for one month improves mobility and reduces edema in patients with bone marrow edema syndrome in the primary weight-bearing joints.

Examining zoledronic acid for the prevention of bone loss in patients receiving bariatric surgery

PurposeBariatric surgery is an effective treatment for severe obesity but causes substantial bone loss and increased risk of fractures. To date, there have been no studies examining whether pharmacologic treatments can prevent bone loss after bariatric surgery. We performed an exploratory study to examine the preliminary safety and efficacy of zoledronic acid (ZOL), a potent anti-resorptive bisphosphonate, to suppress bone turnover markers (BTM) and prevent declines in bone mineral density (BMD) after Roux-en-Y gastric bypass (RYGB) surgery. MethodsWe performed an open-label pilot study of pre-operative ZOL in postmenopausal women with obesity who were planning RYGB (n = 4). A single dose of zoledronic acid 5 mg was given intravenously prior to RYGB. Serum bone biochemistries including C-telopeptide (CTX) and procollagen type 1 N-terminal propeptide (P1NP) were measured at multiple timepoints throughout the 24-week study. BMD was also obtained at the spine and hip by dual-energy x-ray absorptiometry (DXA) and at the trabecular spine by quantitative computed tomography (QCT) at pre-operative baseline and 24 weeks. Results were compared against pre-operative baseline and against changes among RYGB historical controls (n = 10). ResultsAt 2 weeks after RYGB, there was a nonsignificant trend for CTX and P1NP levels to be lower than baseline levels in the ZOL group. By 24 weeks after RYGB, however, participants who received ZOL had a significant increase in CTX above pre-operative baseline (+0.228 ± 0.117 ng/dL, p = 0.030) but this CTX rise was less than that observed in the controls (+0.601 ± 0.307 ng/dL, p = 0.042 between groups). Despite ZOL use, participants had significant areal BMD loss at the total hip as compared to pre-operative baseline (−4.2 ± 1.5%, p = 0.012) that was similar in magnitude to total hip BMD loss in the controls (−5.5 ± 3.9%, p = 0.005). There was a suggestion that the ZOL group might be protected against trabecular spine volumetric bone loss as compared to the control group (+4.8 ± 8.0% vs. -5.9 ± 7.0%, p = 0.075 between groups). Serum calcium, 25-hydroxyvitamin D, and parathyroid hormone did not change in either group. No hypocalcemia or serious adverse events were reported after ZOL. ConclusionIn this proof of concept study, a single dose of ZOL prior to RYGB appeared to transiently mitigate but not fully prevent high bone turnover in the acute postoperative period. At 24 weeks after RYGB, our preliminary data suggest that ZOL was not sufficient to prevent bone loss at the hip, although it may preserve bone density at the trabecular spine. Further prospective, controlled studies are needed to confirm our findings and to identify the best strategies for preventing bone loss in bariatric patients receiving RYGB.

Zoledronic acid does not affect insulin resistance in men receiving androgen deprivation therapy: a prespecified secondary analysis of a randomised controlled trial.

Background:Animal studies suggest that undercarboxylated osteocalcin may improve insulin sensitivity via its effect on testicular testosterone production. Human studies have been conflicting. Men undergoing androgen deprivation therapy (ADT) for prostate cancer experience profound hypogonadism resulting in increased insulin resistance. In a randomised controlled trial (RCT) of zoledronic acid versus placebo in men commencing extended-duration ADT, we aimed to examine the effects on fat mass and glucose metabolism. We hypothesised that zoledronic acid, which reduces osteocalcin concentrations, would worsen ADT-induced insulin resistance.Methods:This was a prespecified secondary analysis of an RCT designed to evaluate the effects of zoledronic acid on bone microarchitecture in 76 men with non-metastatic prostate cancer undergoing curative radiotherapy combined with adjuvant ADT (n = 39 randomised to a single dose of zoledronic acid 5 mg, n = 37 randomised to matching placebo). Oral glucose tolerance tests to determine Matsuda Index were performed at 0, 3, 12 and 24 months. Using a mixed model, mean adjusted differences [MAD (95% confidence interval)] between the groups over time are reported.Results:Over 24 months of ADT, fat mass increased and lean mass decreased for both groups, with no significant between group difference [MAD 401 g (−1307; 2103), p = 0.23 and −184 g (−1325; 955), p = 0.36 respectively]. Bone remodelling markers C-telopeptide [MAD −176 ng/l (−275; −76), p < 0.001 and P1NP −18 mg/l (−32; −5), p < 0.001] as a surrogate for osteocalcin, remained significantly lower in the zoledronic acid group, compared with placebo. There was no mean adjusted between-group difference for homeostatic model assessment 2 insulin resistance (HOMA2-IR) [−0.2 (−0.6; 0.2), p = 0.45], HbA1c [−0.1% (−0.3; 0.1), p = 0.64] or Matsuda Index [0.8 (−1.1; 2.7), p = 0.38]. The Matsuda Index decreased in both groups consistent with worsening insulin resistance with ADT.Conclusion:A single dose of zoledronic acid does not appear to influence glucose metabolism in men newly commencing ADT. Further study to evaluate the endocrine relationship between bisphosphonates, bone and glucose metabolism is required.Trial Registration Number:[ClinicalTrials.gov identifier: NCT01006395].

Efficacy of Zoledronic Acid in Maintaining Areal and Volumetric Bone Density After Combined Denosumab and Teriparatide Administration: DATA-HD Study Extension.

Combined teriparatide and denosumab rapidly and substantially increases bone mineral density (BMD) at all anatomic sites. Discontinuation of denosumab however, results in high-turnover bone loss and increased fracture risk. The optimal way to prevent this bone loss remains undefined. This study is a preplanned extension of the DATA-HD study, where postmenopausal women with osteoporosis were randomized to receive 9 months of either 20 μg or 40 μg of teriparatide daily overlapping with denosumab (60 mg administered at months 3 and 9). At the completion of this 15-month study, women were invited to enroll in the DATA-HD Extension where they received a single dose of zoledronic acid (5 mg) 24 to 35 weeks after the last denosumab dose. Areal BMD and bone turnover markers were measured at month 27 and 42 (12 and 27 months after zoledronic acid, respectively) and spine and hip volumetric bone density by quantitative CT was measured at month 42. Fifty-three women enrolled in the DATA-HD Extension. At the femoral neck and total hip, the mean 5.6% and 5.1% gains in BMD achieved from month 0 to 15 were maintained both 12 and 27 months after zoledronic acid administration. At the spine, the mean 13.6% gain in BMD achieved from month 0 to 15 was maintained for the first 12 months but modestly decreased thereafter, resulting in a 3.0% reduction (95% CI, -4.0% to -2.0%, p < .0001) 27 months after zoledronic acid. The pattern of BMD changes between months 15 and 42 were qualitatively similar in the 20-μg and 40-μg groups. A single dose of zoledronic acid effectively maintains the large and rapid total hip and femoral neck BMD increases achieved with combination teriparatide/denosumab therapy for at least 27 months following the transition. Spine BMD was also largely, though not fully, maintained during this period. These data suggest that the DATA-HD Extension regimen may be an effective strategy in the long-term management of patients at high risk of fragility fracture. © 2021 American Society for Bone and Mineral Research (ASBMR).

Differing Effects of Zoledronic Acid on Bone Microarchitecture and Bone Mineral Density in Men Receiving Androgen Deprivation Therapy: A Randomized Controlled Trial.

Androgen deprivation therapy (ADT) given to men with prostate cancer causes rapid and severe sex steroid deficiency, leading to increased bone remodeling and accelerated bone loss. To examine the effects of a single dose of zoledronic acid on bone microarchitecture, we conducted a 2-year randomized placebo controlled trial in 76 men, mean age (interquartile range [IQR]) 67.8 years (63.8 to 73.9) with non-metastatic prostate cancer commencing adjuvant ADT; 39 were randomized to zoledronic acid and 37 to matching placebo. Bone microarchitecture was measured using high-resolution peripheral quantitative computed tomography (HR-pQCT). Using a mixed model, mean adjusted differences (MAD; 95% confidence interval [95% CI]) between the groups are reported as the treatment effect at several time points. Over 24 months, zoledronic acid showed no appreciable treatment effect on the primary outcomes for total volumetric bone mineral density (vBMD); radius (6.7 mg HA/cm3 [-2.0 to 15.4], p = 0.21) and tibia (1.9 mg HA/cm3 [-3.3 to 7.0], p = 0.87). Similarly, there were no between-group differences in other measures of microarchitecture, with the exception of a modest effect of zoledronic acid over placebo in total cortical vBMD at the radius over 12 months (17.3 mgHA/cm3 [5.1 to 29.5]). In contrast, zoledronic acid showed a treatment effect over 24 months on areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) at all sites, including lumbar spine (0.10 g/cm2 [0.07 to 0.13]), p < 0.001), and total hip (0.04 g/cm2 [0.03 to 0.05], p < 0.001). Bone remodeling markers were initially suppressed in the treatment group then increased but remained lower relative to placebo (MADs at 24 months CTX -176 ng/L [-275 to -76], p < 0.001; P1NP -18 mg/L [-32 to -5], p < 0.001). These findings suggest that a single dose of zoledronic acid over 2 years is ineffective in preventing the unbalanced bone remodeling and severe microstructural deterioration associated with ADT therapy. © 2020 American Society for Bone and Mineral Research.

Efficacy of zoledronic acid infusion on bone mineral density among adult population

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Osteoporosis is a skeletal disease characterised by impaired bone strength due to reduced bone mineral density. As a consequence, patients with osteoporosis are at increased risk of fractures. Zoledronic acid is an anti-resorptive agent that acts by slowing down osteoclast medicated bone resorption, thereby increasing bone density. This study was carried out to evaluate the efficacy of Zoledronic acid on bone mineral density.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; This study was carried out as a record based cross sectional study among 30 symptomatic adult patients who visited the outpatient department of Orthopedics for a period of two years. Bone mineral density (BMD) parameters assessed using dual-energy X-ray absorptiometry (DEXA) scan were documented for initial period and after six months of intervention. Documentation of intervention with single dose of zoledronic acid 5 mg by intravenous infusion was verified and noted.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; There was a significant difference in the mean scores for both femoral neck and lumbar spine with respect to BMD values and T-score values between baseline parameters and values measured after 6 months of Zoledronic acid infusion. The difference was statistically significant (p&amp;lt;0.05).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Single dose of zoledronic acid 5 mg by intravenous infusion was found to be effective in increasing the BMD among individuals suffering from osteopenia and osteoporosis.&lt;/p&gt;

Long term effects on biochemical bone markers of a single infusion of zoledronic acid in Paget disease of bone

BackgroundThe aim of the present study is to evaluate long term biochemical response to a single dose of zoledronic acid in patients with Paget disease of bone, as well as evaluating the value of bone turnover markers in diagnosis and follow-up. MethodsThis is an observational, descriptive and prospective study. Included patients received a single-dose intravenous infusion of 5 mg zoledronic acid. Bone turnover markers were measured at baseline, and in every follow up visit. ResultsThirty-nine patients with a mean follow-up of 56.49 months were included. At the time Paget disease was diagnosed, all of the patients (100%) had high serum procollagen type 1 amino-terminal propeptide values, but not all patients had high serum C-terminal telopeptide and alkaline phosphatase values (85% and 89% respectively). Biochemical response to therapy occurred in 38 out of 39 patients (97%). Two patients had partial response at 6 months but complete response thereafter. Only one patient relapsed (nadir procollagen type 1 amino-terminal propeptide 35.06 μg/l, value at relapse 75.2 μg/l) 4.5 years after treatment. Values of serum C-terminal telopeptide and alkaline phosphatase of this patient were normal despite P1NP relapse. ConclusionsWe hence conclude that zoledronic acid is effective in inducing and maintaining biochemical remission and that procollagen type 1 amino-terminal propeptide is a better diagnostic and prognostic marker in PDB when compared to C-terminal telopeptide and alkaline phosphatase.

Antiretroviral Therapy-Induced Bone Loss Is Durably Suppressed by a Single Dose of Zoledronic Acid in Treatment-Naive Persons with Human Immunodeficiency Virus Infection: A Phase IIB Trial.

Human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) are associated with bone loss leading to increased fracture rate among persons with HIV (PWH). We previously showed long-acting antiresorptive zoledronic acid (ZOL) prevented ART-induced bone loss through 48 weeks of therapy and here investigate whether protection persisted. We randomized 63 nonosteoporotic, treatment-naive adult PWH initiating ART to ZOL (5 mg) versus placebo in a double-blinded, placebo-controlled, phase IIb trial. Here we analyzed the long-term outcome data (144 weeks). Plasma bone turnover markers and bone mineral density (BMD) were quantified at weeks 0, 12, 24, 48, 96, and 144. Primary outcome was change in bone resorption marker C-terminal telopeptide of collagen (CTx). Repeated-measures analyses using mixed linear models were used to estimate and compare study endpoints. At 96 weeks, mean CTx was 62% lower with ZOL relative to placebo (n = 46; CTx = 0.123 vs 0.324 ng/mL; P < .001); at 144 weeks a 25% difference between arms was not statistically significant. At 48 weeks, lumbar spine BMD with ZOL was 11% higher than placebo (n = 60; P < .001) and remained 9-11% higher at 96 (n = 46) and 144 (n = 41; P < .001) weeks. 144 weeks after ZOL infusion, BMD did not change at the lumbar spine (P = .22) but declined at the hip (P = .04) and femoral neck (P = .02). A single dose of ZOL administered at ART initiation blunts bone resorption and BMD loss at key fracture-prone anatomical sites in treatment-naive PWH for 3 years. A multicenter randomized phase III clinical trial validating these results in a larger population is needed. NCT01228318.

Efficacy of single dose of zoledronic acid in treating post-menopausal osteoporosis

 The purpose of this study is to analyse the effect of single dose of zoledronic acid in treating post-menopausal osteoporosis.Aim of the study To show the significance increase in bmd with zoledronic acid infusion in single dose. Materials Study design - prospective study. Study population - patients attending opd in department of orthopaedics with osteoporosis evaluated by bone mineral density (bmd) scan in govt. kilpaukmedical college hospital. Duration of study – 1 year  After patients were screened with peripheral BMD densitometry patient were selected then they were subjected to do bmd dexa scan to confirm osteoporosis. Those who were in osteoporotic group were included in our study. Method After patient is evaluated, they were instructed to drink 500ml-1000ml of water for hydration.  Then single dose of Zoledronic acid in 100 ml of Normal saline was infused intravenously over 15 mins.  Patient were observed for two hours then were discharged with prophylactic Paracetamol tablets.

Primena zoledroni^ne kiseline unapre\uje zarastanje osteoporoti^nih fraktura kod ovarijektomisanih ze^eva

Objectives: To evaluate the radiological, histological and mechanical effects on osteoporotic fracture healing of single-dose zoledronic acid (ZA) applied to an animal model with an experimentally created osteoporotic bone fracture. Methods: A total of 14 adult, female New Zealand rabbits, aged 5-6 months were used in the study. Bone mineral density (BMD) values were calculated from bone densitometry measurements and recorded. Bilateral ovariectomy was then applied to all the rabbits. At 10 weeks after ovariectomy, bone densitometry was again performed on all the animals and the BMD values were compared. Osteoporosis was accepted as having developed in animals determined with a reduction of 28% in BMD values. After the placement of a K-wire intramedullarly in the femurs of the rabbits, a closed fracture was created with the standard method. The animals were then randomly separated into 2 groups as the zoledronic acid group (ZAG) and the control group (CG). An infusion of 0.1 mg/kg ZAwas administered to the ZAG animals from the ear vein. With visualisation of bone union rabbits were sacrificed by decapitation. Radiological, mechanical and histological assesments were then applied. Results: In the histological evaluation, the mean histological score was determined as 5.00 in the ZAG and 3.00 in the CG. The difference between the groups was found to be statistically significant (p &lt; 0.001). In the radiological evaluation, the mean score was 7.00 in the ZAG and 6.25 in the CG. Even though higher points were obtained by the ZAG in the inter-observer evaluations, the difference between the groups was not statistically significant (p = 0.073). In the mechanical evaluation, the elasticity collapse in negative proportion to rigidity was measured as 2.91 mm in the ZAG and 3.96 mm in the CG (p = 0.686). The rigidity data of the ZAG were higher in the mechanical tests but the difference between the groups was not statistically significant (p = 0.086). Conclusion: As the results of the study showed that the ZAG had higher values than those of the CG in all the histological, mechanical and radiological evaluations, the application of a single dose of ZA can be considered to increase the healing of osteoporotic fractures.

Cost-effectiveness of single-dose zoledronic acid for nursing home residents with osteoporosis in the USA

ObjectiveTo evaluate the cost-effectiveness of routine administration of single-dose zoledronic acid for nursing home residents with osteoporosis in the USA.DesignMarkov cohort simulation model based on published literature from a healthcare...

Combined effects of neoadjuvant letrozole and zoledronic acid on γδT cells in postmenopausal women with early-stage breast cancer

IntroductionAdjuvant bisphosphonates lead to better prognosis in postmenopausal breast cancer. However, the association between clinical outcomes and immune modulation by them is still unclear. MethodsIn this prospective, open-label phase II study, postmenopausal women with estrogen receptor-positive and human epidermal growth factor receptor 2-negative early-stage breast cancer received neoadjuvant letrozole (LET) for one month, followed by treatment with a single dose of zoledronic acid. The patients underwent an additional 5 months of treatment with LET prior to surgery. The primary endpoint was the tumor objective response rate (ORR) determined by diameter via MRI. The association between the ORR and γδT cell frequencies was assessed as a secondary endpoint. ResultsOut of sixty patients, 55 patients were evaluable for response by MRI. The ORR for LET with zoledronic acid was 38.2% (21/55), which was comparable to that of historical controls (45%). A decrease in the frequency of the Vδ2 T cell subset was observed throughout treatment, and Vδ2 T cells were activated for 6 months. In planned subgroup analyses, patients with low frequencies of Vδ2 T cells prior to zoledronic acid infusion experienced a favorable tumor response compared to those with high frequencies (59.3% [16/27] vs 17.9% [5/28], p = .002). There were no serious adverse events with this treatment regimen. ConclusionThese results showed that neoadjuvant LET with zoledronic acid could not achieve overall effect for local tumor response. However, patients with a low frequency of γδ T cells would benefit from the treatment including zoledronic acid. (UMIN 000008701).