Xun-Zi Cai

Comparison of clinical efficacy and safety between denosumab and alendronate in postmenopausal women with osteoporosis: a meta-analysis

The aim of this study was to perform a head‐to‐head comparison of efficacy and safety profile between 60 mg denosumab (Den) subcutaneously (SC) per 6 months (Q6M) and 70 mg alendronate (Aln) orally per week (QW) for postmenopausal women with low bone mineral density. We searched electronic databases comparing efficacy and safety of Den SC Q6M and Aln QW in postmenopausal women. The primary outcomes of efficacy evaluation in included trials were incidence of clinical fracture in both groups and bone mineral density (BMD) at different skeletal sites. And adverse events (AEs), including incidence of neoplasms and infections, were considered as secondary outcomes. Following the instructions of ‘Cochrane Handbook for systematic Reviews of Interventions 5.0.2’, we identified eligible studies, evaluated the methodological quality and abstracted relevant data. Four heterogeneous randomised controlled trials (RCTs) involving 1942 women were identified. The results of review showed low evidence quality that supported the hypothesis the denosumab vs. alendronate could reduce risk of fracture [OR (95% CI) 1.42 (0.84 to 2.40), 11 more women per 1000 (from 4 fewer to 36 more), p = 0.19] but the moderate to high quality evidence suggesting treatment with 60 mg Den SC Q6M was more effective for postmenopausal women in increasing BMD [at distal radius (DR), total hip (TH), lumbar spine (LS), and femoral neck (FN)]. Hazards of neoplasms [OR (95% CI) 1.10 (0.65 to 1.86), 3 more per 1000 (from 10 fewer to 24 more), p = 0.62] or infections [OR (95% CI) 0.95 (0.79 to 1.15), 12 fewer per 1000 (from 53 fewer to 33 more,), p = 0.62] were appeared to be similar.Our review suggested within 1 year 60 mg Den SC Q6M treatment was more effective in increasing bone mass but could not reduce the fracture risk to a greater extent than 70 mg Aln QW therapy. Also the Den SC Q6M therapy did not increase the risks of neoplasms and infections compared with Aln QW.

Effect of Delayed Pulsed-Wave Ultrasound on Local Pharmacokinetics and Pharmacodynamics of Vancomycin-Loaded Acrylic Bone Cement In Vivo

ABSTRACT This study sought to investigate the effect of delayed pulsed-wave ultrasound with low frequency on drug release from and the antimicrobial efficacy of vancomycin-loaded acrylic bone cement in vivo and the possible mechanism of this effect. After the implantation of cement and the inoculation of Staphylococcus aureus into the bilateral hips of rabbits, ultrasound (average intensity, 300 mW/cm2; frequency, 46.5 kHz; on/off ratio, 20 min/10 min) was applied to animals in the normal ultrasound group (UG0-12) from 0 through 12 h after surgery and to those in the delayed-ultrasound group (UG12-24) from 12 through 24 h after surgery. The control group (CG) was not exposed to ultrasound. Based on vancomycin concentrations in left hip cavities at projected time intervals, the amount of time during which the local drug concentration exceeded the MIC (T>MIC) in UG12-24 was significantly prolonged compared with that in either CG or UG0-12, and the ratios between the areas under the concentration-time curves over 24 h and the MIC for UG0-12 and UG12-24 were both increased compared with that for CG. The greatest reductions in bacterial densities in both right hip aspirates and right femoral tissues at 48 h were achieved with UG12-24. Local hemorrhage in rabbits of UG0-12 during the 12-h insonation was more severe than that in rabbits of UG12-24. Of four variables, the T>MIC and the bioacoustic effect were both identified as parameters predictive of the enhancement of the antimicrobial efficacy of cement by ultrasound. Sustained concentrations above the MIC replaced early high maximum concentrations and long-term subtherapeutic release of the drug, provided that ultrasound was not applied until local hemorrhage was relieved. The enhancement of the antimicrobial efficacy of cement by ultrasound may be attributed to the prolonged T>MIC and the bioacoustic effect caused by ultrasound.

Intermittent watt‐level ultrasonication facilitates vancomycin release from therapeutic acrylic bone cement

Ultrasound holds promise for enhancing the vancomycin release from cement though the length of time when local drug level exceeded the minimum inhibitory concentration (T(>MIC)) was not prolonged by the previous protocol of milliwatt-level ultrasonication. Here vancomycin-loaded cements were subjected to continuous watt-level ultrasonication (CUG), intermittent watt-level ultrasonication (IUG) or no ultrasonication (NUG) for 14 d during immersion in 40-ml phosphate buffered saline (PBS) for 28 d. The T(>MIC) for IUG was more than three times that for NUG. In contrast, T(>MIC) for CUG was slightly shortened. The subtherapeutic release of vancomycin between 15 d and 28 d for IUG was one-ninth that for NUG. The fitting equations indicated a significant enhancement on the burst release and the slow release for IUG; however, the continuous ultrasonication hampered the slow release. SEM images exhibited denser craters and pores with larger diameters and less residual drug in specimens from IUG relative to those from both CUG and NUG. Intermittent watt-level ultrasonication improved the ultrasound-enhanced vancomycin release from cement in view of the prolonged T(>MIC) and the inhibited subtherapeutic release compared with continuous ultrasonication. The mechanisms may be associated with the distinctive effects of detaching forces and pushing forces by acoustic microstreams.

CORR Insights®: Addition of Vancomycin to Cefazolin Prophylaxis Is Associated with Acute Kidney Injury After Primary Joint Arthroplasty

I nfection after total joint arthroplasty (TJA) is a devastating complication that causes tremendous morbidity and accounts for a substantial proportion of orthopaedic healthcare expenditures. The treatment of periprosthetic infection also can be a source of considerable unease and confusion for arthroplasty surgeons. The proportion of patients who develop infection after TJA is low, at approximately 1% to 2% [8, 10]. Surgeons can help keep the risk of infection low by using appropriate perioperative antimicrobial prophylaxis, laminar airflow, antibiotic-impregnated cement, and decreased traffic in the operating room. Although patients, and to some degree even the healthcare system in theUnited States, seem to have an expectation that this complication should never occur, the reality is that prosthetic infection is unlikely to be eliminated in the next few years. The choice of antimicrobial regimen is currently based on the results of experimental studies and clinical experience, but we still lack randomized clinical trials (RCTs) [2–4]. It has been suggested that in some settings, particularly those in which the local antibiogram includes a high proportion of infections with methicillin-resistant Staphyloccus aureus (MRSA), vancomycin may be appropriate for prophylactic antibiotic regimens [1, 7]. However, researchers have observed complications in patients with routine administration of vancomycin including resistant bacteria, acute kidney injury, and hearing loss. Moreover, Vancomycin needs to be combined with traditional prophylactic agents in order to provide coverage against Gram-negative bacteria. The benefits to adding vancomycin to prophylactic regimens is still hotly debated [5–7]. In this study, Courtney and colleagues retrospectively evaluated a series of 1828 patients undergoing primary hip and knee arthroplasty during a 2-year period. These patients received either cefazolin (n = 500) or cefazolin and vancomycin (n = 1328) as prophylactic perioperative antibiotics. The patient characteristics, case mix, and preoperative renal function and baseline creatinine clearance were This CORR Insights is a commentary on the article ‘‘Addition of Vancomycin to Cefazolin Prophylaxis Is Associated with Acute Kidney Injury After Primary Joint Arthroplasty’’ by Courtney and colleagues available at: DOI: 10.1007/s11999-0144062-3. The authors certify that they, or any members of their immediate families, have no funding or commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research editors and board members are on file with the publication and can be viewed on request. The opinions expressed are those of the writers, and do not reflect the opinion or policy of CORR or the Association of Bone and Joint Surgeons. This CORR Insights comment refers to the article available at DOI: 10.1007/s11999014-4062-3. H.-X. Zhu MD, X.-Z. Cai MD (&) Department of Orthopedic Surgery, Second Affiliated Hospital’s Campus in Binjiang District, School of Medicine, Zhejiang University, No. 1511 Jianghong Road, Hangzhou 310009, People’s Republic of China e-mail: emilcai@hotmail.com CORR Insights Published online: 6 January 2015 The Association of Bone and Joint Surgeons1 2015