Role of Pitavastatin in Prevention of Osteopenic Changes in Ovariectomized Rats.

OBJECTIVE: To determine the effect of pitavastatin, a third generation statin, on development of osteopenia in ovariectomized rats. STUDY DESIGN: Experimental study. PLACE AND DURATION OF STUDY: Department of Pharmacology, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Center, Karachi, from January to July 2013. METHODOLOGY: Forty female Sprague Dawley rats were divided into ovariectomized (OVX), Sham OVX and OVX given pitavastatin 0.4 mg/kg/day, 0.8 mg/kg/day, for 8 weeks. Bone density measurements using CT scan and Archimedes’ principle were made on femora and tibiae. Blood samples were analyzed for acid phosphatase (ACP) and alkaline phosphatase (ALP) levels. RESULTS: Ovariectomy-induced osteopenic changes were indicated by significant decrease in bone densities and Hounsfield (HU) index of distal femoral and proximal tibial metaphyses and elevation of ACP and ALP levels. 0.4 mg/kg pitavastatin did not significantly alter the evaluated parameters. 0.8 mg/kg produced a restoration of HU of lower femur and femoral density comparable to Sham. HU of upper tibia and tibial density following 0.8 mg/kg was significantly higher than OVX but was not approximate to Sham. ALP and ACP with 0.8 mg/kg were comparable to Sham. CONCLUSION: Supra-therapeutic dose of pitavastatin was effective in preventing estrogen deficiency-induced decrease in bone density of ovariectomized rates, over an 8-week period.

Pitavastatin is a potent anti-inflammatory agent in the rat paw model of acute inflammation.

Statins are used extensively as anti-hyperlipidemic agents. In addition to curtailing cholesterol synthesis they have been found to have multiple actions unrelated to cholesterol lowering "the pleiotropic effects," which includes inhibition of inflammation. We aimed at investigating the effect of pitavastatin a 3rd generation statin, in suppressing acute inflammation in rat paw edema model. Male Sprague-Dawley rats were randomly assigned to one of five groups (n=8): Control, indomethacin and pitavastatin (0.2mg/kg, 0.4mg/kg, 0.8mg/kg) treated. 1hour following treatment, inflammation was induced by sub-planter injection of egg albumin into the hind paw. Anti-inflammatory effect was evaluated by measurement of edema formation every half hour for three hours, assessment of polymorphonuclear leukocyte (PMNL) infiltration and measurement of tissue damage in skin biopsies. Ascending doses of pitavastatin were found to attenuate these parameters. The lowest dose of pitavastatin (0.2mg/kg) was found to significantly reduce edema volume, PMNL infiltration and tissue damage. The efficacy of the smallest dose was found comparable to indomethacin.