Treatment of bone loss in proximal femurs of postmenopausal osteoporotic women with AGN1 local osteo-enhancement procedure (LOEP) increases hip bone mineral density and hip strength: a long-term prospective cohort study.

This first-in-human study of AGN1 LOEP demonstrated that this minimally-invasive treatment durably increased aBMD in femurs of osteoporotic postmenopausal women. AGN1 resorption was coupled with new bone formation by 12 weeks and that new bone was maintained for at least 5-7 years resulting in substantially increased FEA-estimated femoral strength. INTRODUCTION: This first-in-human study evaluated feasibility, safety, and in vivo response to treating proximal femurs of postmenopausal osteoporotic women with a minimally-invasive local osteo-enhancement procedure (LOEP) to inject a resorbable triphasic osteoconductive implant material (AGN1). METHODS: This prospective cohort study enrolled 12 postmenopausal osteoporotic (femoral neck T-score ≤ - 2.5) women aged 56 to 89 years. AGN1 LOEP was performed on left femurs; right femurs were untreated controls. Subjects were followed-up for 5-7 years. Outcomes included adverse events, proximal femur areal bone mineral density (aBMD), AGN1 resorption, and replacement with bone by X-ray and CT, and finite element analysis (FEA) estimated hip strength. RESULTS: Baseline treated and control femoral neck aBMD was equivalent. Treated femoral neck aBMD increased by 68 ± 22%, 59 ± 24%, and 58 ± 27% over control at 12 and 24 weeks and 5-7 years, respectively (p < 0.001, all time points). Using conservative assumptions, FEA-estimated femoral strength increased by 41%, 37%, and 22% at 12 and 24 weeks and 5-7 years, respectively (p < 0.01, all time points). Qualitative analysis of X-ray and CT scans demonstrated that AGN1 resorption and replacement with bone was nearly complete by 24 weeks. By 5-7 years, AGN1 appeared to be fully resorbed and replaced with bone integrated with surrounding trabecular and cortical bone. No procedure- or device-related serious adverse events (SAEs) occurred. CONCLUSIONS: Treating femurs of postmenopausal osteoporotic women with AGN1 LOEP results in a rapid, durable increase in aBMD and femoral strength. These results support the use and further clinical study of this approach in osteoporotic patients at high risk of hip fracture.

Investigation of the levels of free purine and pyrimidine bases and metabolites in mechanically recovered meats.

Levels of free purine and pyrimidine bases and metabolites, in particular xanthine, have been investigated in poultry meat and MRM as potential qualitative or quantitative markers for the presence of MRM in meat products. Only xanthine was found to exhibit significantly different levels between the source meat and MRM product where, for example, it was found to be present at approximately 100 µg/g in turkey MRM but only 57, 33 and 14 µg/g in the neck, leg and breast meat respectively. The wide variation in levels within a cut, together with the overlap between figures for source meat and MRM, preclude the use of xanthine as a robust qualitative or quantitative marker. Processing of turkey meat by subjecting it to an increasing level of comminution does not appear to elevate the indigenous level of free xanthine.

Investigation of the levels of N(τ)-methylhistidine in a range of pork and chicken meats.

Protein bound N(τ)-methylhistidine (N-MeHis) has been suggested as an index for the estimation of muscle (meat) protein in meat and meat products. This paper examines the level of N-MeHis in a range of five pork and two chicken prime cuts together with five other pork and one chicken manufacturing cuts of meat. It is shown that whilst similar levels are present in the prime cuts there is a considerable variation in those found in the other cuts. The average N-MeHis level, expressed as µg/g fat-free connective tissue-free (FFCF) meat, was 116 for pork, 116 for chicken breast and 129 for chicken leg. From the other pork cuts investigated, only two gave levels similar to that for prime pork whilst the rest were all considerably lower. Chicken MRM gave an N-MeHis level 75% of that for (combined) leg and breast meat. Since all these meat cuts are regarded as legitimate meat materials in the UK, there would appear to be serious drawbacks to the use of N-MeHis as a quantitative index of lean meat.

High-performance liquid chromatographic column switching method for the determination of hydroxyproline in meat and meat products.

A method is described for the determination of 4-hydroxyproline in meat and meat products. The amino acid is converted to a sensitive fluorescent derivative with 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole. Chromatography of other (unwanted) amino acid derivatives is avoided by column switching, thereby shortening analysis time. The method is suitable for routine analysis and is applicable to the entire range of 4-hydroxyproline levels normally encountered in meat and meat products (0.05-12.5%).

Investigation of the levels of N(τ)-Methylhistidine in a range of beef cuts and offals.

Protein-bound N(τ)-methylhistidine (N-MeHis) has been suggested as an index for the estimation of muscle (meat) protein in meat and meat products. This paper examines the levels of N-MeHis in a range of six prime beef cuts together with beef flank, cheek, mechanically recovered meat (MRM) and offals. The study was undertaken by two separate laboratories using a previously reported HPLC procedure involving the conversion of N-MeHis to a fluorescent derivative. It is shown that, whilst similar N-MeHis levels are present in the prime cuts, there is considerable variation in those found in the other cuts and offals. The average N-MeHis level in six prime cuts observed at both laboratories is 122 µg/g fat-free connective tissue-free (FFCF) meat; however, flank exhibits apparently high N-MeHis levels, whilst cheek and MRM contain only approximately 70% of the level found in the prime cuts. The offals contain between 0 and 65% of the N-MeHis level found in prime cuts. The greater variability and the often lower value of the N-MeHis content of these legitimate meat materials preclude the establishment of a single realistic index for FFCF beef, and present fundamental problems for the assessment of the lean meat content of manufactured beef products by N-MeHis determination.