Comparison of Bone and Renal Effects In HIV-infected Adults Switching to Abacavir or Tenofovir Based Therapy in a Randomized Trial

Our objective was to compare the bone and renal effects among HIV-infected patients randomized to abacavir or tenofovir-based combination anti-retroviral therapy.In an open-label randomized trial, HIV-infected patients were randomized to switch from zidovudine/lamivudine (AZT/3TC) to abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC). We measured bone mass density (BMD) and bone turnover biomarkers (osteocalcin, osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), alkaline phosphatase, type I collagen cross-linked C-telopeptide (CTx), and osteoprotegerin). We assessed renal function by estimated creatinine clearance, plasma cystatin C, and urinary levels of creatinine, albumin, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL). The changes from baseline in BMD and renal and bone biomarkers were compared across study arms.Of 40 included patients, 35 completed 48 weeks of randomized therapy and follow up. BMD was measured in 33, 26, and 27 patients at baseline, week 24, and week 48, respectively. In TDF/FTC-treated patients we observed significant reductions from baseline in hip and lumbar spine BMD at week 24 (-1.8% and -2.5%) and week 48 (-2.1% and -2.1%), whereas BMD was stable in patients in the ABC/3TC arm. The changes from baseline in BMD were significantly different between study arms. All bone turnover biomarkers except osteoprotegerin increased in the TDF/FTC arm compared with the ABC/3TC arm, but early changes did not predict subsequent loss of BMD. Renal function parameters were similar between study arms although a small increase in NGAL was detected among TDF-treated patients.Switching to TDF/FTC-based therapy led to decreases in BMD and increases in bone turnover markers compared with ABC/3TC-based treatment. No major difference in renal function was observed.Clinicaltrials.gov NCT00647244

Right drug, right patient, right time: aspiration or future promise for biologics in rheumatoid arthritis?

Individualising biologic disease-modifying anti-rheumatic drugs (bDMARDs) to maximise outcomes and deliver safe and cost-effective care is a key goal in the management of rheumatoid arthritis (RA). Investigation to identify predictive tools of bDMARD response is a highly active and prolific area of research. In addition to clinical phenotyping, cellular and molecular characterisation of synovial tissue and blood in patients with RA, using different technologies, can facilitate predictive testing. This narrative review will summarise the literature for the available bDMARD classes and focus on where progress has been made. We will also look ahead and consider the increasing use of ‘omics’ technologies, the potential they hold as well as the challenges, and what is needed in the future to fully realise our ambition of personalised bDMARD treatment

Gingival crevicular fluid, serum levels of receptor activator of nuclear factor-kappa B ligand, osteoprotegerin, interleukin-17 in rheumatoid arthritis and osteoporosis patients with periodontal disease

Background: This study was performed to evaluate gingival crevicular fluid (GCF) and serum levels of soluble receptor activator of nuclear factor-kappa B ligand (sRANKL), interleukin (IL)-17A, IL-17E, IL-17F, IL-17A/F and osteoprotegerin (OPG) in rheumatoid arthritis (RA), osteoporosis (OPR) and systemically healthy (SH) women all with periodontal disease. Methods: Gingival crevicular fluid (GCF) and serum samples were obtained before any periodontal intervention from 17 RA, 19 OPR patients and 13 SH women with periodontitis. Full-mouth clinical periodontal measurements were recorded. sRANKL, OPG, IL-17 levels were determined by Enzyme-linked Immunosorbent Assay. Results: Clinical periodontal measurements were similar in the three study groups. Although the total amounts of GCF albumin, OPG, IL-17A and IL-17A/F, were similar in the study groups, there were statistically significant differences in GCF concentrations of sRANKL, OPG, IL-17A, IL-17E, IL-17F and IL-17A/F. The sRANKL/OPG ratio were significantly higher in the RA group than in the OPR and SH groups (p<0.05). Serum sRANKL, sRANKL/OPG and IL-17A/IL-17E ratios were significantly higher, while OPG concentrations were significantly lower in the RA group compared with other groups (p<0.05). Serum IL-17A concentrations were significantly higher in the RA and OPR groups than in the SH group (p<0.05). Conclusion: Increased inflammatory mediator levels in RA patients despite the long-term usage of various anti-inflammatory drugs suggest that these patients may have a propensity to overproduce these inflammatory mediators