Efficacy and safety of romosozumab: a meta-analysis of placebo-controlled trials.

INTRODUCTION: We aimed to comprehensively compile placebo-controlled trials on the efficacy and safety of romosozumab (210 mg, subcutaneously, once monthly) in postmenopausal women and men with osteoporosis. MATERIALS AND METHODS: PubMed, Google Scholar, and ClinicalTrials.gov were searched for relevant placebo-controlled trials (as of January 1, 2024). Percent change in bone mineral density (BMD), falls, fractures, and adverse events (AEs) after drug administration were collected. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated. RESULTS: Six trials (7990 patients; follow-up period, 6-12 months) were included. Compared with placebo, romosozumab significantly increased lumbar spine BMD (MD = 12.69; 95% CI 11.10-14.29), total hip BMD (MD = 4.42; 95% CI 3.03-5.80), and femoral neck BMD (MD = 3.99; 95% CI 2.42-5.57) at 12 months. Romosozumab significantly decreased falls (RR = 0.80; 95% CI 0.68-0.93) and major osteoporotic fractures (RR = 0.37; 95% CI 0.25-0.54), but increased injection-site reactions (RR = 1.83; 95% CI 1.46-2.30) within 12 months. No significant differences were observed in other AEs (including cardiovascular AEs) within 12 months. CONCLUSION: Romosozumab treatment resulted in a significant BMD gain, reduced falls and major osteoporotic fractures. It was generally well-tolerated, including the cardiovascular aspects. However, clinicians should consider the occurrence of minor AEs (e.g., injection-site reactions).

Age-adjusted 5-factor modified frailty index as a valuable tool for patient selection in bilateral simultaneous total knee arthroplasty.

Although bilateral simultaneous total knee arthroplasty (BSTKA) is an effective treatment for bilateral knee osteoarthritis, safety concerns and lack of precise patient selection criteria persist. The purpose of this retrospective study was to determine the complication rate and the role of frailty in patient selection for BSTKA. We analyzed data from 434 patients who underwent BSTKA between February 2012 and January 2021, examining demographic factors and preoperative blood test results. Complications occurred in 77 patients (18%), with anemia requiring transfusion being the most common (26 patients, 5.9%). In the univariate analysis, age ≥ 75 years, age-adjusted Charlson Comorbidity Index ≥ 5, age-adjusted 5-factor modified Frailty Index (aamFI-5) ≥ 3, hemoglobin ≤ 11.0 g/dL, albumin ≤ 3.5 g/dL, estimated glomerular filtration rate < 45 ml/dl/1.73 m2, and D-dimer ≥ 2.0 µg/mL contributed to postoperative complications (p < 0.05). Multivariate analysis identified aamFI-5 ≥ 3 as an independent risk factor (p = 0.002). Our findings underscore the practical utility of aamFI-5 in predicting complications after BSTKA, providing valuable guidance to surgeons in the selection of BSTKA candidates and ultimately improving clinical outcomes.

Denosumab vs. bisphosphonates in primary osteoporosis: a meta-analysis of comparative safety in randomized controlled trials.

Denosumab and bisphosphonates for primary osteoporosis are generally well-tolerated, but their comparative safety remains unclear. We aimed to explore the comparative safety of denosumab and bisphosphonates in primary osteoporosis. Databases such as PubMed and Google Scholar were searched for relevant peer-reviewed randomized controlled trials published in English (as of December 2023). Trials comparing adverse events (AE) between denosumab and bisphosphonates in patients with primary osteoporosis were investigated. Data were pooled using a fixed- or random-effects model to determine the risk ratios (RR) and 95% confidence intervals (CIs) for various AEs in patients treated with denosumab in comparison to patients treated with bisphosphonates. Eleven trials (5,545 patients; follow-up period: 12-24 months) were included in this meta-analysis. All trials had a risk of bias (e.g., reporting bias linked to secondary endpoints and selection bias linked to random allocation). In comparison to bisphosphonates, denosumab was significantly associated with less withdrawal due to AEs (RR = 0.49; 95% CI 0.34-0.71), more five-point major adverse cardiovascular events (RR = 2.05; 95% CI 1.03-4.09), more cardiovascular AEs (RR = 1.61; 95% CI 1.07-2.41), more infections (RR = 1.14; 95% CI 1.02-1.27), more upper respiratory tract infections (RR = 1.56; 95% CI 1.08-2.25), less vertebral fractures (RR = 0.54; 95% CI 0.31-0.93), and less abdominal pain (RR = 0.44;95% CI 0.22-0.87). We explored the comparative safety of denosumab and bisphosphonates for primary osteoporosis, some of which could be attributed to their beneficial effects. However, all trials had a risk of bias. Further investigations are required to confirm our results.

Mid-term clinical outcomes and complications of primary total knee arthroplasty in hemodialysis patients: a retrospective comparative cohort study.

BACKGROUND: Numerous patients who receive hemodialysis (HD) undergo total knee arthroplasty (TKA) due to advanced knee joint arthritis. However, there are few studies that describe the clinical outcomes and complications of TKA in HD patients. This study investigated the mid-term results of TKA in patients undergoing HD. METHODS: This single-center retrospective study compared clinical and surgical outcomes following TKA in patients who were receiving HD with those who were not. We used propensity scores to match 21 knees of 18 patients who received HD to 706 knees of 569 patients who had not received HD, from a total of 727 knees (587 patients) that underwent primary unilateral TKA. The clinical outcomes were evaluated using the American Knee Society Score-knee (AKSS-knee) and AKSS-function scores. The primary surgical outcome measure was the number of knees with postoperative complications. RESULTS: In both the HD and non-HD groups, postoperative AKSS-knee and function scores significantly improved when compared to preoperative values. Postoperative AKSS-knee and function scores were not significantly different between the groups. The number of knees with postoperative complications was larger in the HD group than the non-HD group within the first postoperative month, 0-12 months, 12-24 months, 0-24 months, and two years after surgery. Additionally, in the HD group, more complications occurred in the first month than any subsequent month in the two years after surgery. CONCLUSIONS: TKA improves AKSS-knee and function scores equivalently for HD patients and non-HD patients. However, HD patients develop more complications after TKA, especially within the first month. Therefore, surgeons who perform TKA for HD patients should obtain informed consent after explaining the possible complications, and HD patients should be carefully observed following TKA.

Failure analysis of alumina on alumina total hip arthroplasty with a layered acetabular component: minimum ten-year follow-up study.

This prospective study reports the outcome of total hip arthroplasty (THA) performed in a consecutive series of patients using an alumina ceramic on a ceramic-layered component (Alumina-Bearing-Surface system). The cohort consisted of 270 hips in 229 patients. The study evaluated the clinical and radiological results over a mean follow-up of 11.4 years. Revision THA was performed on 58 hips, including alumina alternative failure in 50 hips, loosening in 4 hips, recurrent dislocation in 2 hips, stem neck fracture in 1 hip and hematoma in 1 hip. The survival rate was 68% with revision for any reason as the end point. The risk factors of implant failure are the preoperative range of motion of the hip joint and postoperative dislocation.

Effect of bacterial media on the evaluation of the antibacterial activity of a biomaterial containing inorganic antibacterial reagents or antibiotics.

Several studies have been performed to assess the effectivesness of the antibacterial coating of a biomaterial to reduce surgical site infection. However, evaluations of these materials are inconsistent, and therefore it is difficult to compare their antibacterial performance. In this study, we evaluated the influence of different media such as nutrient broth (NB), Mueller-Hinton broth (MHB) and fetal bovine serum (FBS) on the antibacterial activity of AgNO3- or gentamicin-added bone cement using a modified ISO 22196 standard to devise a method to evaluate the antibacterial activity of biomaterials in vitro. The antibacterial activity results against Staphylococcus aureus and Escherichia coil were different in each medium. The antibacterial activity of AgNO3 in FBS was lower than the other media, whereas the antibacterial activity of gentamicin in FBS was higher than in the other media. It was assumed that the fluctuating antibacterial activity was influenced by serum components. The results showed that the ISO 22196 antibacterial evaluation method is suitable to evaluate antibacterial biomaterials after modifying the medium to FBS.

In vivo antibacterial and silver-releasing properties of novel thermal sprayed silver-containing hydroxyapatite coating.

One of the serious postoperative complications associated with joint replacement is bacterial infection. In addressing this problem, we have previously described the development of a novel thermal spraying technology combining silver (Ag) showing antibacterial activity with hydroxyapatite (HA) displaying good biocompatibility and osteoconductivity, and reported the in vitro properties. This study evaluated serum Ag ion concentrations and antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) using a subcutaneous rat model. HA loaded with 3 wt % of silver oxide (Ag-HA) and plain HA were sprayed on the surface of titanium disks. Ag-HA- or HA-coated samples were implanted into the back subcutaneous pockets of male Sprague-Dawley rats. Mean serum Ag ion concentration in the Ag-HA group increased to more than 50 ppb by 48 h after implantation, then decreased gradually to baseline levels. Mean (+/- standard error of the mean) number of viable MRSA on HA coating was (1.5 +/- 0.5) x 10(5), which is significantly more than the (1.1 +/- 0.4) x 10(4) on Ag-HA coating (p < 0.001). Ag-HA coating offers good abilities to release Ag ions and kill MRSA in vivo.

Development of novel thermal sprayed antibacterial coating and evaluation of release properties of silver ions.

Several studies have addressed the use of antibacterial coating to reduce implant-associated infections. In this study, novel silver (Ag)-containing calcium-phosphate (CP) coating technology based on the thermal spraying method was developed. The coating's physical and chemical properties, in vitro antibacterial activity, hydroxyapatite (HA)-forming ability, and release of Ag ions were evaluated. An amorphous structure of the coating was confirmed by X-ray diffraction, and Ag residue in the coating was determined by elementary analysis. The coating showed strong antibacterial activity to methicillin-resistant Staphylococcus aureus in fetal bovine serum (FBS) along with HA-forming ability in simulated body fluid. Therefore, it is expected that the coating would confer antibacterial and bone bonding abilities to the implant surface. Time course release testing of Ag ions from the coating on immersion in FBS showed pronounced Ag release for up to 24 h after immersion, with consistent strong antibacterial activity at the early postoperative stage. In repeated testing, the amount of released Ag ions was about 6500 parts per billion (ppb, microg/L) for the first release test, after which it gradually decreased. However, retention of significant release of Ag ions after a sixth repeat implies that Ag release from the coating is slow in FBS.