The Effect of Zoledronic Acid on the Volume of the Fusion-Mass in Lumbar Spinal Fusion

Background

Few studies have explored the effects of bisphosphonates on bony healing in patients undergoing spinal fusion surgery. Most previous studies used animal models and found that bisphosphonate shows negative effects on spinal fusion consolidation. We intended to evaluate the effect of a single-dose of zoledronic acid on the volume of the fusion-mass in lumbar spinal fusion.

Methods

A retrospective review was carried out on 44 patients with symptomatic degenerative lumbar spinal stenosis who underwent one or two-level posterolateral fusion from January 2008 and January 2011. They were divided into 4 groups: group 1, autograft and zoledronic acid; group 2, allograft and zoledronic acid; group 3, autograft alone; and group 4, allograft alone. Functional radiography and three-dimensional computed tomography scans were used to evaluate and quantify the volume of the fusion-mass. The visual analog scale (VAS), the Oswestry disability index (ODI), and the short form 36 (SF-36) were used to evaluate the clinical outcomes.

Results

The mean volume of the fusion-mass per level was 8,814 mm³, 8,035 mm³, 8,383 mm³, and 7,550 mm³ in groups 1, 2, 3, and 4, respectively, but there were no significant differences between the groups (p = 0.829). There were no significant decreases in the volume of the fusion-mass (p = 0.533) in the zoledronic acid groups (groups 1 and 2). The VAS, the ODI, and the SF-36 at the 6-month follow-up after surgery were not significantly different (p > 0.05) among the 4 groups. The VAS, the ODI, and the SF-36 were not correlated with the volume of the fusion-mass (p = 0.120, 0.609, 0.642).

Conclusions

A single dose of zoledronic acid does not decrease the volume of the fusion-mass in patients undergoing spinal fusion with osteoporosis. Therefore, we recommend that zoledronic acid may be used after spinal fusion in osteoporotic patients.     

Zoledronic acid efficacy and safety over five years in postmenopausal osteoporosis

Summary In a 5-year study involving 119 postmenopausal women, zoledronic acid 4 mg given once-yearly for 2, 3 or 5 years was well tolerated with no evidence of excessive bone turnover reduction or any safety signals. BMD increased significantly. Bone turnover markers decreased from baseline and were maintained within premenopausal reference ranges. Introduction After completion of the core study, two consecutive, 2-year, open-label extensions investigated the efficacy and safety of zoledronic acid 4 mg over 5 years in postmenopausal osteoporosis. Methods In the core study, patients received 1 to 4 mg zoledronic acid or placebo. In the first extension, most patients received 4 mg per year and then patients entered the second extension and received 4 mg per year or calcium only. Patients were divided into three subgroups according to years of active treatment received (2, 3 or 5 years). Changes in BMD and bone turnover markers (bone ALP and CTX-I) were assessed. Results All subgroups showed substantial increases in BMD and decreases in bone markers. By the end of the core study, 37.5% of patients revealed a suboptimal reduction (< 30%) of bone ALP levels. After subsequent study drug administration during the extensions, there was no evidence of progressive reduction of bone turnover markers. Furthermore, increased marker levels after treatment discontinuation demonstrates preservation of bone remodelling capacity. Conclusions This study showed that zoledronic acid 4 mg once-yearly was well tolerated and effective in reducing biomarkers over 5 years. Detailed analysis of bone marker changes, however, suggests that this drug regimen causes insufficient reduction of remodelling activity in one third of patients.     

Spontaneous Acetabular Periprosthetic Fracture in a Patient Continuously Having Zoledronic Acid

Zoledronic acid has been used for prevention of osteolytic and osteoblastic bone metastasis. This case report illustrates an undesirable consequence from prolonged usage of zoledronic acid in bone metastasis prevention. Periprosthetic acetabular fracture in a patient treated with zoledronic acid for 7 years was reported. The clinical presentation, radiographic and pathological results were described. This is a rare complication after total hip arthroplasty which should not be ignored especially in patients who received long term bisphosphonate.     

Intravenous vs Intra-Articular Tranexamic Acid in Total Knee Arthroplasty: A Randomized,Double-Blind Trial

Background

Tranexamic acid (TXA) is commonly used in primary total knee arthroplasty (TKA); however, the most appropriate route of administration is still debated. This study was conducted to compare the 2 most commonly used routes of TXA administration, intravenous (IV) and intra-articular (IA).

Clinical Efficacy of Intravenous Lidocaine for Thyroidectomy: A Prospective,Randomized, Double-Blind,Placebo-Controlled Trial

Background

Systemic lidocaine has analgesic and anti-inflammatory effects. The purpose of this prospective, randomized, double-blind study was to evaluate the effects of intravenous lidocaine on pain following thyroidectomy.

Methods

Fifty-eight adult patients scheduled for total thyroidectomy were randomly allocated to receive a 1.5 mg/kg lidocaine bolus followed by a 2 mg/kg/h infusion during surgery, or the same volume of normal saline (control). After thyroidectomy, we evaluated postoperative pain, nausea, fentanyl consumption, frequency of pushing the button (FPB) for patient-controlled analgesia (PCA), High-sensitivity C-reactive protein (hs-CRP) in serum, and patient satisfaction scores regarding the recovery process.

Results

Postoperative pain and nausea scores were significantly lower in the lidocaine group for the first 4 h following thyroidectomy, compared to the control group. Fentanyl consumption and FPB for the PCA were also significantly reduced in the lidocaine group for 4 h following thyroidectomy, and hs-CRP was significantly less in the lidocaine group at postoperative days 1 and 3. Furthermore, satisfaction scores were significantly higher in the lidocaine group compared to the control group.

Conclusions

Intravenous lidocaine effectively reduced postoperative pain and nausea following thyroidectomy as well as improved the quality of recovery. Trial registration number: Clinicaltrials.gov NCT01608360.

     

Zoledronic acid infusion for lumbar interbody fusion in osteoporosis

Background

Clinical outcomes of intravenous (IV) infusion of zoledronic acid (ZOL) for lumbar interbody fusion surgery (LIFS) remain unknown. We investigated the efficacy of IV ZOL on clinical outcome and bone fusion after LIFS.

Materials and methods

We retrospectively analyzed 64 patients with both degenerative lumbar spondylolisthesis and osteoporosis who underwent LIFS from January 2007 to April 2010. All patients were followed up for 2 y. Thirty-two were treated with an IV infusion of ZOL 3 d after surgery and a second injection 1 y later, and the other 32 patients did not receive ZOL. Preoperatively and every 3 mo postoperatively, oswestry disability index questionnaire and visual analog scale (VAS) scores for back and leg were compared. Preoperative and final postoperative follow-up to evaluate for subsequent compression fractures were also performed. Pedicle screw loosening, cage subsidence, and fusion rate were documented 2 y after surgery.

Results

At 2-y follow-up, a solid fusion was achieved in 75% of the ZOL group and only 56% of the control group. At final follow up, the incidence of final subsequent vertebral compression fractures (19% of the ZOL group and 51% of the control group, P = 0.006), pedicle screw loosening (18% of the ZOL group and 45% of the control group, P = 0.03), and cage subsidence >2 mm (28% of the ZOL group and only 54% of the control group, P = 0.04) were significantly lower in the ZOL group than in the control group. The ZOL group demonstrated improvement in VAS (for leg pain VAS, 2/10 for the ZOL group and 5/10 for the control group; for back pain VAS, 2/10 for the ZOL group and 6/10 for the control group) and oswestry disability index scores (7/25 for the ZOL group and 16/25 for the control group).

Conclusions

ZOL treatment has beneficial effects on instrumented LIFS both radiographic and clinically. Thus, ZOL treatment can be recommended for osteoporosis patients undergoing LIFS.     

Lip Ulceration Associated with Intravenous Administration of Zoledronic Acid: Report of a Case

Although osteonecrosis of the jaw is a well-known adverse reaction of bisphosphonates (BPs), random cases of oral mucosal ulceration after per os administration of BP-aledronate have been attributed to prolonged mucosal irritation. This report, for the first time, describes the mucosal ulceration related to intravenous use of zoledronic acid (ZA). A 52-year-old female patient presented with painful ulcers on both cutaneous/mucosal surfaces of the lower lip and a 2-month history of osteonecrosis of the mandible beside the right lower canine. Her medical record included intravenous administration of ZA for 10 months for primary breast cancer metastatic to bone. Examination of the peripheral blood showed severe anemia and a slightly increased white blood cell count, due to urinary tract infection by E. coli, but no evidence of a viral infection. The treatment of anemia and E. coli infection did not improve the labial ulcers. Biopsy from the mucosal lesion revealed a non-specific ulceration with moderate inflammatory infiltration. There was no evidence of infection or malignancy. ZA administration was discontinued and within 3 months the lesions were resolved after treatment with systemic antibiotics (amoxicillin), vitamins A and E, chlorexidine and H₂O₂ (hydrogen peroxide) solutions and local pantothenic acid/vitamin A creams. Recurrence was detected a month after ZA re-administration. Nevertheless, after new treatment, the patient was free of oral/skin lesions 18 months later. This case, which is the first report of ulceration associated with intravenous administration of bisphosphonates, suggests that systemic mechanisms may be implicated in BP-induced oral mucosal ulceration. Furthermore, ZA appears to cause the same oral mucosal manifestations as alendronate. This emphasizes the need for oral examination in all cases of BP therapy, whether per os or intravenously administrated.     

Intravenous Acetaminophen in Multimodal Pain Management for Patients Undergoing Total Knee Arthroplasty: A Randomized,Double-Blind,Placebo-Controlled Trial

Background

Although multimodal pain management including periarticular multidrug injection can provide excellent pain relief in the early postoperative period after total knee arthroplasty (TKA), rebounding pain remains an important challenge. A randomized, double-blind, placebo-controlled trial was performed to investigate the efficacy of adding intravenous acetaminophen to multimodal pain management for TKA.

A Randomized,Double-Blind,Placebo-Controlled Trial of Intravenous Acetaminophen on Hospital Length of Stay in Obese Individuals Undergoing Sleeve Gastrectomy

Background

Retrospective studies indicate that acetaminophen iv administration reduces hospital length of stay (LoS) and opiate consumption in patients undergoing bariatric surgery.

Objective

This study sought to determine whether using acetaminophen iv in morbidly obese subjects undergoing sleeve gastrectomy decreased LoS and total hospital charges as compared to patients receiving saline placebo.

Setting

Single-center university hospital

Methods

Using a randomized, double-blind, placebo-controlled design, subjects were assigned to receive either acetaminophen iv (group A) or saline placebo iv (group P). Data were collected between Jan 1 and Dec 31, 2016. Group A received acetaminophen every 6 h for a total of four doses. The first dose was administered following the induction of general anesthesia; group P received saline iv on the same schedule. Anesthetic management and prophylactic antiemetic regimen were standardized in all subjects. Postoperative pain management consisted of hydromorphone via patient-controlled infusion pump. Primary outcomes include hospital LoS and associated hospital costs. Secondary outcomes include patient satisfaction and postoperative nausea and pain scores.

Results

Subject demographics (n?=?127) and intraoperative management were similar in the two groups. Across all subjects, median hospital LoS in group A (n?=?63) was 1.87 vs. 1.97 days in group P (n?=?64) (p?=?0.03, Wilcoxon rank-sum test). Postoperatively, daily quality-of-recovery (QoR-15) scores, narcotic consumption, and the use of rescue antiemetics were not significantly different between groups. Median hospital costs were as follows: group A, $12,885 vs. group P, $12,977 (n?=?64).

Conclusions

Acetaminophen iv may reduce hospital LoS in subjects undergoing sleeve gastrectomy.

     

Efficacy of Zoledronic Acid in the Treatment of Nonmalignant Painful Bone Marrow Lesions: A Triple-Blind,Randomized, Placebo-Controlled Phase III Clinical Trial (ZoMARS)

Bone marrow lesions (BML) represent areas of deteriorated bone structure and metabolism characterized by pronounced water-equivalent signaling within the trabecular bone on magnetic resonance imaging (MRI). BML are associated with repair mechanisms subsequent to various clinical conditions associated with inflammatory and non-inflammatory injury to the bone. There is no approved treatment for this condition. Bisphosphonates are known to improve bone stability in osteoporosis and other bone disorders and have been used off-label to treat BML. A randomized, triple-blind, placebo-controlled phase III trial was conducted to assess efficacy and safety of single-dose zoledronic acid (ZOL) 5 mg iv with vitamin D 1000 IU/d as opposed to placebo with vitamin D 1000 IU/d in 48 patients (randomized 2:1) with BML. Primary efficacy endpoint was reduction of edema volume 6 weeks after treatment as assessed by MRI. After treatment, mean BML volume decreased by 64.53% (±41.92%) in patients receiving zoledronic acid and increased by 14.43% (±150.46%) in the placebo group (p = 0.007). A decrease in BML volume was observed in 76.5% of patients receiving ZOL and in 50% of the patients receiving placebo. Pain level (visual analogue scale [VAS]) and all categories of the pain disability index (PDI) improved with ZOL versus placebo after 6 weeks but reconciled after 6 additional weeks of follow-up. Six serious adverse events occurred in 5 patients, none of which were classified as related to the study drug. No cases of osteonecrosis or fractures occurred. Therefore, single-dose zoledronic acid 5 mg iv together with vitamin D may enhance resolution of bone marrow lesions over 6 weeks along with reduction of pain compared with vitamin D supplementation only. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Intravenous Dexamethasone Injection Reduces Pain From 12 to 21 Hours After Total Knee Arthroplasty: A Double-Blind,Randomized, Placebo-Controlled Trial

BackgroundPain after total knee arthroplasty (TKA) affects postoperative recovery and patient satisfaction. The analgesic benefits of corticosteroids have not been well studied. We, therefore, investigated the analgesic effects of intravenous (IV) dexamethasone (DEX) in patients undergoing a TKA.MethodsThis was a randomized, double-blind, placebo-controlled trial of 0.15 mg/kg of IV DEX vs saline placebo in unilateral TKA. Fifty patients/arm were recruited. Primary outcomes were pain level, determined by a visual analog scale, and the amount of morphine consumption (mg) ≤48 hours post-TKA. Secondary outcomes were rates of nausea and vomiting, C-reactive protein concentrations, and functional outcomes.ResultsThe DEX group had a significantly lower mean visual analog scale score both at rest and during motion at 12, 15, 18, and 21 hours (P < .05). At 21 hours, the mean difference (Δ) in pain at rest was −11 points (95% confidence interval [CI], −21 to −2 points; P = .02) while the mean difference in pain during motion was −15 points (95% CI, −25 to −5 points; P = .004). The DEX group also had lower rates of nausea and vomiting: 29/50 (58%) vs 42/50 (84%) (P = .008) and lower mean C-reactive protein level: 89 vs 167, Δ = −78 mg/L (95% CI, −100 to −58 mg/L, P < .0001). There were no significant differences in mean morphine consumption by 48 hours, modified Western Ontario and McMaster University Osteoarthritis Index scores, and range of motion of the knee at 3-month follow-up (P > .05).ConclusionIV DEX relieves postoperative pain between 12 to 21 hours after TKA and may be a useful adjunct for controlling pain in patients undergoing TKA.     

A Randomized Double-Blind Placebo-Controlled First-In-Human Phase 1 Trial of TransCon PTH in Healthy Adults

TransCon PTH is a sustained-release, essentially inactive prodrug transiently bound to an inert carrier, designed to release PTH(1-34), and in development for hypoparathyroidism (HP). This phase 1, randomized, placebo-controlled, single and multiple ascending dose (SAD and MAD, respectively) trial evaluated safety, tolerability, pharmacodynamics (PD), and pharmacokinetics (PK) of TransCon PTH in healthy adults. SAD and MAD cohorts consisted of 10 subjects (eight active, two placebo) who received up to seven single or six multiple ascending doses of TransCon PTH, respectively. TransCon PTH doses ranged from 3.5 to 124 μg PTH(1-34) for the SAD cohorts and 3.5 to 24 μg PTH(1-34)/day for the MAD cohorts. The primary PK endpoint was Free PTH. The PD endpoints included albumin adjusted serum calcium (sCa), fractional excretion of calcium (FECa), intact endogenous PTH(1-84), bone turnover markers, renal tubular maximum reabsorption of phosphate/glomerular filtration rate (TMP/GFR), serum phosphate (sP) and magnesium, and 1,25 dihydroxyvitamin D. TransCon PTH was generally well tolerated; there were no drug-related serious adverse events (SAEs), and all AEs were transient in nature. Free PTH demonstrated an effective half-life of approximately 60 hours and a dose-dependent, sustained exposure with an infusion-like profile within the calculated physiologic range for active PTH at steady-state. Albumin-adjusted sCa demonstrated a dose-dependent, sustained response with complete control of FECa despite modest hypercalcemia at higher doses. Renal tubular maximum reabsorption of phosphate/glomerular filtration rate (TMP/GFR) showed a dose-dependent decrease, resulting in a dose-dependent decrease in sP. TransCon PTH administered daily for 10 days showed no increase in the osteoblastic bone formation markers, serum bone-specific alkaline phosphatase (BSAP) or P1NP, or the osteoclastic bone resorption marker, urine NTx, but modestly and transiently increased the osteoclast marker, serum CTx. These phase 1 data support TransCon PTH as a daily replacement therapy for HP providing physiological levels of PTH 24 hours per day and advancement into phase 2 clinical development. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

A First Prospective,Randomized, Double-Blind,Placebo-Controlled Clinical Trial Evaluating Extracorporeal Shock Wave Therapy for the Treatment of Peyronie's Disease

Background

Extracorporeal shock wave therapy (ESWT) is a conservative therapy for patients with Peyronie's disease (PD).

Objective

To investigate the effects of ESWT in patients with PD.

Design, setting, and participants

One hundred patients with a history of PD not >12 mo who had not had previous PD-related treatments were enrolled in a prospective, randomized, double-blind, placebo-controlled study. Patients were randomly allocated to either ESWT (n = 50) or placebo (n = 50). Erectile function (EF), pain during erection, plaque size, penile curvature, and quality of life (QoL) were assessed at baseline, at 12 wk, and at 24 wk follow-up.

Intervention

Four weekly treatment sessions were administered. Each ESWT session consisted of 2000 focused shock waves. For the placebo group, a nonfunctioning transducer was employed.

Measurements

EF was evaluated with the shortened version of the International Index of Erectile Function (IIEF-5), pain was evaluated with a visual analog scale (VAS; 0–10), plaque size was measured in cm², and penile curvature was measured in degrees.

Results and limitations

After 12 wk, mean VAS score, mean IIEF-5 score, and mean QoL score ameliorated significantly in patients receiving ESWT. Mean plaque size and mean curvature degree were unchanged in the ESWT group, while a slight increase was reported in the placebo group (p-value not significant vs baseline). After 24 wk, mean IIEF-5 score and mean QoL score were stable in the ESWT group, while mean VAS score was significantly lower when compared with baseline in both groups. Interestingly, after 24 wk, mean plaque size and mean curvature degree were significantly higher in the placebo group when compared with both baseline and ESWT values. The main limitations were that the QoL questionnaire was not validated, ED was not etiologically characterized, and inclusion criteria were restricted.

Conclusions

In patients with PD, ESWT leads to pain resolution and ameliorates both EF and QoL.     

二膦酸盐联合维生素D治疗糖皮质激素性骨质疏松和骨量减少的初步观察

目的：观察联合维生素D和第三代二膦酸盐对糖皮质激素长期应用所造成的骨量丢失肾炎患者的疗效。方法：15例来自本院经定量CT（QCT）诊断为糖皮质激素性骨质疏松和骨量减少病情稳定肾炎患者,服用钙尔奇1片/d和福善美70mg/周,观察入选时及治疗6月后临床症状和空腹血钙、磷、甲状旁腺激素、碱性磷酸酶、24h尿钙、磷和定量CT腰椎骨密度值变化。结果：疼痛症状改善总有效率（显效加有效）为53.3%。治疗6个月前后血钙、磷、甲状旁腺激素、碱性磷酸酶、24h尿钙、磷变化,无统计学意义（P〉0.05）,腰椎骨密度差值为（11.8±5.3）mg/cm^3,经检验有统计学意义（P〈0.01）。结论：维生素D联合二膦酸盐能有效改善糖皮质激素长期应用所造成的骨量丢失,增加骨密度,改善疼痛,有利于最大程度的预防骨质疏松骨折,但是否优于传统单纯钙和维生素D治疗有待进一步对照研究。