Quantification of Low Amounts of Zoledronic Acid by HPLC-ESI-MS Analysis: Method Development and Validation.

Zoledronic acid (ZA) is used in the treatment of various bone pathologies, but it forms complexes with calcium ions present in body fluids, decreasing ZA bioavailability. Thereby, the study first describes the identification of ZA-calcium complexes that form in calcium-rich environments, in order to establish the bioavailable ZA concentration. Then, a new method for quantification of low ZA amounts in milieus that mimics in vivo conditions by using simulated body fluid and calcium sulfate hemihydrate was described. Almost all analytical methods of ZA quantification described in the literature require compound derivatization. At very low concentrations, derivatization is prone to analyte loss, therefore compromising the analytical results. In our study, we avoided ZA derivatization by using a high-performance liquid chromatography and electrospray ionization mass spectrometry (HPLC-ESI-MS) system, conducting the investigation based on the fragmentation mass extracted ion chromatograms specific to the ZA protonated form. The method was validated by selectivity, precision, accuracy, linearity, signal to noise ratio, and limit of detection and limit of quantification calculation. Experimentally, this method can detect ranges of 0.1-0.5 ng/mL and precisely quantify ZA concentrations as low as 0.1 ng/mL. This method could provide the basis for quantifying low amounts of ZA in the blood during long-term administration.

Randomised controlled trial of triclosan coated vs uncoated sutures in primary hip and knee arthroplasty.

BACKGROUND: Triclosan-coated vicryl plus suture (Ethicon, Inc.) was developed to reduce microbial colonisation during surgical procedures. However, its effect on wound healing and surgical site infections remain unclear after hip and knee arthro-plasty surgery. AIM: To determine the effect of triclosan-coated sutures (TCS) vs non-coated sutures on wound healing, following primary hip and knee arthroplasties. METHODS: A single-centred, double-blind randomised controlled trial (RCT) was undertaken. We randomly allocated patients to receive either the triclosan-coated sutures (TCS vicryl plus) or non-coated sutures (NCS vicryl) during the closure of unilateral primary hip and knee arthroplasties. We utilised the ASEPSIS wound scoring system to evaluate wound healing for the first 6 weeks post-operatively. RESULTS: One hundred and fifty patients undergoing primary total hip or knee arthroplasty over a one-year period were included. Eighty-one were randomised to the TCS group and 69 to the NCS group. Despite no statistically significant difference in the ASEPSIS scores among the study groups (P = 0.75), sensitivity analysis using the Mann Whitney test (P = 0.036) as well as assessment of the wound complications at 6 weeks follow up, demonstrated significantly higher wound complication rates in the TCS group (8 vs 1, P = 0.03). CONCLUSION: No clear advantage was demonstrated for using the TCS. However, larger multi-centred RCTs are required to validate their use in hip and knee arthroplasty surgery.

Total proximal interphalangeal joint arthroplasty for osteoarthritis versus rheumatoid arthritis--a systematic review.

Osteoarthritis (OA) and rheumatoid arthritis (RA) of the proximal interphalangeal joints (PIPJ) can be treated with arthroplasty, although the complicated anatomy of the joint makes surgery challenging. Controversy exists regarding outcomes in relation to disease aetiology. This study aims to compare functional outcomes and re-operation rates in these two conditions. The electronic databases MEDLINE, EMBASE, Cochrane database and Google scholar were searched in accordance with PRISMA. The study quality was assessed using the Methodological Index for Non-Randomised Studies (MINOR). A total of 16 studies were reviewed including 506 cases in the OA and 542 in the RA group. Five studies assessed function and patient satisfaction, demonstrating a non-significant improvement in the OA group. Five studies reported re-operation rate; three showing it to be lower in the OA group and two reporting similar rates. This review suggests that those undergoing PIPJ arthroplasty for OA may have a better functional outcome and lower re-operation rate.

The in vitro and in vivo effects of nicotine on bone, bone cells and fracture repair.

INTRODUCTION: Cigarette smoke has negative effects on bone metabolism and fracture repair. However, no study has reviewed effects of nicotine on bone and fracture repair independent of other constituents of cigarette smoke. The authors review the existing evidence of the effect of nicotine on 'bone' and 'bone cells' and fracture repair, drawing conclusions relevant to clinical practice and future research. AREAS COVERED: A literature review was conducted using PRISMA guidelines and PubMed, Cochrane, MEDLINE/OVID, EMBASE, NHS Evidence and Google scholar databases. Articles were included if they specifically investigated the effects of nicotine on 'bone' or fracture repair in animal or human models or in vitro effects on 'bone cells'. A total of 64 papers were included in this review, of which 15 were human in vitro studies and 49 animal studies wherein 9 were in vitro and 40 in vivo. In vivo studies of the effects of nicotine in animals demonstrated widespread effects on bone including osteoneogenesis, osseointegration, steady-state skeletal bone and genes and cytokines relevant to bone cell physiology and bone homeostasis. In these studies, nicotine's effects are predominately negative, inhibiting bone cell metabolism and fracture repair, whereas most in vitro studies reported biphasic responses in all bone cells except osteoclastic cells. EXPERT OPINION: The review suggests that nicotine has effects on osteoneogenesis, osseointegration and steady-state skeletal bone in animal in vivo models, as well as effects on all 'bone cells', via several mechanisms in both animal and human cell in vitro studies. The effect of nicotine is dose-dependent, with higher concentrations having predominantly negative effects, whereas at low concentrations a stimulatory effect is seen. Stimulatory effects on certain cells may indicate a possible, limited therapeutic role; advice regarding smoking cessation perioperatively should remain due to the other harmful components of cigarette smoke, but there may be scope for allowing the use of nicotine patches instead of complete abstention. Further research into clinical outcomes is required before the exact response of bone and fracture repair in humans to nicotine is known.

In vitro and in vivo effects of antibiotics on bone cell metabolism and fracture healing.

INTRODUCTION: Recent evidence suggests that antibiotics exert direct effects on bone at a cellular level, disrupting mitochondrial function and cell activity. This comprehensive literature review aims to evaluate evidence for the effects of antibiotics and antimicrobials on bone and discuss the clinical implications. AREAS COVERED: A literature search was conducted on electronic databases covering a period from 1969 to 2010. Studies were included if they reported in vivo and in vitro experimental findings regarding the use of antibiotics and synthetic antibacterials in both animals and humans, focusing on bone cell function and especially fracture repair. EXPERT OPINION: Current research suggests that these negative results could be due to direct effects of antibiotics on mitochondrial physiology within mammalian cells. Treatment doses of antibiotics, especially those released from topical delivery systems such as bone cements, result in antibiotic concentrations thousands of times higher than those required to inhibit bacterial growth. Our findings suggest a need to develop current antibiotic delivery systems to elute sufficient doses to inhibit bacterial growth without negative effects on bone physiology and fracture repair processes.