Effects of prior osteoporosis treatment on the treatment response of romosozumab followed by denosumab in patients with postmenopausal osteoporosis.

In patients with postmenopausal osteoporosis, prior osteoporosis treatment affected the bone mineral density increase of following treatment with 12 months of romosozumab, although it did not affect that of following treatment with 12 months of denosumab after romosozumab. PURPOSE: To investigate the effects of prior osteoporosis treatment on the response to treatment with romosozumab (ROMO) followed by denosumab (DMAb) in patients with postmenopausal osteoporosis. METHODS: In this prospective, observational, multicenter study, treatment-naïve patients (Naïve; n = 55) or patients previously treated with bisphosphonates (BP; n = 37), DMAb (DMAb; n = 45) or teriparatide (TPTD; n = 17) (mean age, 74.6 years; T-scores of the lumbar spine [LS] - 3.2 and total hip [TH] - 2.6) were switched to ROMO for 12 months, followed by DMAb for 12 months. Bone mineral density (BMD) and serum bone turnover markers were evaluated for 24 months. RESULTS: A BMD increase was observed at 12 and 24 months in the following patients: Naïve (18.2% and 22.0%), BP (10.2% and 12.1%), DMAb (6.6% and 9.7%), and TPTD (10.8% and 15.0%) (P < 0.001 between the groups at both 12 and 24 months) in LS and Naïve (5.5% and 8.3%), BP (2.9% and 4.1%), DMAb (0.6% and 2.2%), and TPTD (4.3% and 5.4%) (P < 0.01 between the groups at 12 months and P < 0.001 at 24 months) in TH, respectively. The BMD increase in LS from 12 to 24 months was negatively associated with the levels of bone resorption marker at 24 months. Incidences of major fragility fractures for the respective groups were as follows: Naïve (5.5%), BP (16.2%), DMAb (11.1%), and TPTD (5.9%). CONCLUSIONS: Previous treatment affected the BMD increase of following treatment with ROMO, although it did not affect that of following treatment with DMAb after ROMO.

Retention of tocilizumab and anti-tumour necrosis factor drugs in the treatment of rheumatoid arthritis.

OBJECTIVES: The retention of the anti-rheumatic agent tocilizumab (TCZ) has not been well documented in patients with rheumatoid arthritis (RA). We conducted an observational study to compare the retention of TCZ and anti-tumour necrosis factor (TNF) drugs in the treatment of patients with RA. METHOD: We reviewed continuation rates and causes of discontinuation of biological agents (biologics) by assessing medical records of patients with RA who were administered biologics at our institute from September 1999 to April 2012, using the Osaka University Biologics for Rheumatic Diseases (BiRD) registry. RESULTS: A total of 401 patients were included. TCZ, infliximab (IFX), etanercept (ETN), and adalimumab (ADA) were administered to 97, 103, 143, and 58 patients, respectively. There were some differences between the baseline characteristics of the groups. The median duration (range) of TCZ, IFX, ETN, and ADA administration was 2.5 (0.1-12.6), 1.9 (0.0-7.7), 2.9 (0.0-11.3), and 1.3 (0.0-3.4) years, respectively. Continuation rates for TCZ and ETN were significantly higher than those for IFX and ADA. Multivariate analyses showed that discontinuation due to lack or loss of efficacy was significantly less common in the TCZ group than in the other groups. Discontinuation due to overall adverse events was not significantly different between treatment groups. CONCLUSION: TCZ and ETN show better retention than IFX or ADA in the treatment of RA.

A hydrocellular foam dressing versus gauze: effects on the healing of rat excisional wounds.

OBJECTIVE: Hydrocellular foam dressings are characterised by their ability to create a moist wound healing environment and absorb high amounts of exudate. In this study, we examined the effect of a hydrocellular foam dressing on the healing of rat excisional wounds. METHOD: One full-thickness wound was made on the back of rats and wounds were treated with hydrocellular foam dressing or gauze dressing. To examine the histology of the wound, haematoxylin and eosin (HE) staining was performed. Gene expression of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), hepatocyte growth factor (HGF) and hypoxia inducible factor-1 alpha (HIF-1a) in granulation tissue was examined by real-time reverse transcription polymerase chain reaction (real-time RT-PCR). VEGF protein was measured by ELISA. RESULTS: The hydrocellular foam dressing promoted formation of granulation tissue and significantly promoted wound closure. A scab formed on the surface of granulation tissue in the gauze-treated wounds, which disturbed epithelialisation. In addition, the expression of VEGF and mRNA was higher in the gauze-treated wounds. CONCLUSION: These results supports the hypothesis that gauze encourages scab formation, which impairs epithelialisation and increases VEGF expression. In contrast, hydrocellular foam dressing accelerates epithelialisation and new vessel formation in granulation tissue.

NFkappaB decoy oligodeoxynucleotides ameliorates osteoporosis through inhibition of activation and differentiation of osteoclasts.

The transcription factor, nuclear factor-kappa B (NFkappaB), is believed to play a pivotal role in osteoclast formation. In this study, we focused on NFkappaB decoy oligodeoxynucleotides (ODN) as a new therapeutic strategy to attenuate osteoporosis. Tartrate-resistant acid phosphatase (TRAP)-positive multinuclear osteoclasts formed in mononuclear cells including osteoclast precursors from neonatal rabbit bone marrow were increased in the presence of 1,25-dihydroxyvitamin D3, whereas transfection of NFkappaB decoy ODN decreased the number of TRAP-positive cells and attenuated RANKL and M-CSF-induced osteoclast formation. NFkappaB decoy ODN also inhibited the activity of osteoclasts, as assessed by pit formation. In rat ovariectomized model of estrogen deficiency, continuous administration of NFkappaB decoy ODN attenuated the increase of TRAP activity, accompanied by a significant increase in calcium concentration in tibia and femur and decrease in urinary deoxypyridinoline. In additional osteoporosis model using vitamin C-deficient rat, inhibition of NFkappaB by decoy ODN dramatically improved the bone length, weight, density as assessed by dual-energy X-ray absorptiometry. Overall, inhibition of NFkappaB by decoy strategy prevented osteoporosis through the inhibition of bone resorption. Targeting of NFkappaB might be potential therapy in various bone metabolic diseases.

Acceleration of wound healing by combined gene transfer of hepatocyte growth factor and prostacyclin synthase with Shima Jet.

Although skin diseases are one of the target diseases for gene therapy, there has been no practical gene transfer method. First, we examined gene transfer efficiency of the spring-powered jet injector, Shima Jet, which was originally developed as a non-needle jet injector of insulin. Local gene expression was about 100 times higher when the luciferase plasmid was transferred by the Shima Jet than by a needle. Gene transfer of beta-galactosidase revealed gene expression in the epidermis. Based on these results, we then examined the potential of gene therapy using the Shima Jet for wound healing. An increase of cellular proliferation of the epidermis and the number of microvessels in the granulation tissue was observed after hepatocyte growth factor (HGF) gene transfer. An increase in blood flow around the wound was observed after prostacyclin synthase (PGIS) gene transfer. Moreover, promotion on wound healing was observed in HGF gene transferred group, and further promotion was observed in combined gene transferred group as assessed by measuring wound area. These results indicate that co-transfer of HGF and PGIS genes by the Shima Jet could be an effective strategy to wound healing.