Arotinoid Ethylester

Palmoplantar pustulosis (PPP) is a chronic recurring and refractory pustular dermatosis. To investigate the efficacy and safety of arotinoid ethylester in patients with PPP, sixteen adult subjects with PPP, who had taken no systemic medications for three months, were enrolled. All the subjects received 0.03 mg of arotinoid ethylester once daily as initial dosage. The number of pustules and lesion area index (LAI) were measured pre- and post-treatment. Repeated measures of one factor ANOVA was used to statistically analyze the data. After 3 months of treatment, pustules disappeared completely in all patients (F = 15.04; p < .0001); LAI decreased significantly (F = 24.54; p < .0001). Complete clearance (100% reduction of LAI and complete disappear of pustules) and near complete clearance (75%-99%) occurred in 6 and 8 patients, respectively; the other two patients exhibited partial clearance (50%-74%). Side effects were observed in 10 patients, but were mild to moderate and well tolerated. Our study suggested that arotinoid ethylester is an effective therapy for PPP with minimal side effects.

Excess of Vitamin A (retinol) and related compounds (retinoids) induces bone fragility and is associated with increased hip fracture incidence in humans. Yet, their impact on the adult skeleton has been studied in relatively little detail. It is assumed that they induce generalized bone loss and decrease long-bone thickness due to reduction of radial bone growth. Here we characterized early skeletal responses of adult rodents to retinoid treatment, revealing novel aspects of retinoid action on the mature skeleton. The retinoid Ro 13-6298, given subcutaneously for 4 days, induced bone loss in the hind limbs of 12- and 56-week-old rats and of 15-week-old mice. In vivo monitoring of bone mass and geometry changes by peripheral quantitative computed tomography demonstrated that bone mass decline was due to subperiosteal cortical bone loss, which induced a shrinkage of bone diameter, whilst cancellous bone mass was preserved. We observed that the native retinoic acid isomer all-trans RA induced an identical pattern of bone loss. Histomorphometric evaluation revealed that increased subperiosteal osteoclastic bone resorption caused the cortical bone destruction. Interestingly, bone resorption was suppressed in cancellous bone, which was in agreement with reduced in vitro formation of osteoclasts from bone marrow cells that were derived from the proximity of cancellous bone. The retinoid-induced increase in subperiosteal bone resorption could be blocked by bisphosphonate as direct potent inhibitor of osteoclast action, but not by estradiol. Retinoid treatment induced a reduction of bone-forming surfaces at the subperiosteal site, but not in cancellous bone. In vitro osteoblast performance was also reduced or unchanged, depending on the cellular system used and assay type/duration. In conclusion, our studies revealed that the impact of retinoids on bone is highly bone-compartment-specific at early treatment phases. Furthermore, we showed that bone diameter shrinks in the adult skeleton after retinoid treatment due to subperiosteal osteoclastic bone resorption. Thus, retinoid-induced bone thinning is not only due to reduced radial bone growth as previously assumed. Our findings might explain why high intake of retinol is associated with increased hip fracture risk in the elderly and suggest a therapy to prevent such potential negative effects.