Role of histamine in ovariectomy-induced osteoporosis in rats

ABSTRACT

It has been reported that histamine increases osteoclast activity and number through H1 and H2 receptors, respectively, whereas other studies indicated that the histamine effects on bone resorption were indirect. The present study was designed to assess the possible effect of the H1 receptor antagonist [promethazine] and the H2 receptor antagonist [ranitidine], alone and in combination compared with the bisphosphonate [alendronate], as a standard treatment of osteoporosis, on ovariectomy-induced osteoporosis in rats. The present study was conducted on 60 female albino rats that were divided into 6 groups, each of JO rats. Group I sham-operated, Group II non-treated ovariectomized [OVX] rats, while groups III, 1V V and VI were OVX rats treated with alendronate, promethazine, ranitidine and combination ofpromethazine and ranitidine, respectively. The results of the present study demonstrated that urinary deoxypyridinoline [DPY]/creatinine and serum osteocalcin concentration significantly increased in the OVX non-treated group compared to the sham-operated group, indicating an increased bone turnover. In addition, serum alkaline phosphatase [ALP] activity and serum phosphorus [F] concentration were significantly higher in the OVX non-treated group than in the sham-operated group. Meanwhile, no significant dfference among groups I to VI was observed in the mean serum calcium [Ca] concentration. Treatment of OVX rats with alendronate significantly decreased urinary DPY/creatinine as compared to the OVX non-treated group. Moreover, alendronate significantly decreased serum osteocalcin and F concentrations and serum ALP activity as compared to the OVX non-treated group. Similarly, treatment of OVX rats with promethazine, ranitidine or their combination significantly deceased urinary DPY/creatinine as compared to the OVX non-treated group. Furthermore, the combination of both drugs .reased urinary DPY/creatinine at a higher significant level when compared to each drug alone. In addition, e was no significant difference, regarding this parameter, between the combination, alendronate and shamyrerated groups. Moreover, treatment of OVX rats with promethazine, ranitidine or their combination sigi4ficantly serum osteocalcin and F concentrations and serum ALP activity as compared to the OVX non-treated-group. Furthermore, there was no statistically significant difference, regarding these parameters, between the pnethazine, ranitidine, their combination and alendronate-treated groups. However, there were statistically significant differences, regarding these parameters, between all the drug-treated groups and the sham-operated. It may be concluded from the findings of the present study that the use of the H1 and H2 receptor agonists [promethazine and ranitidine] could be effective in decreasing bone resorption, increasing bone formation and diminishing ovariectomy-induced osteoporotic changes. These findings might be of help in developing therapeutic regimens to protect against postmenopausal osteoporosis in women