Opioid use in the management of chronic pain is widespread. However, it is a recognized risk factor for the development of osteoporosis. The hypothesis of this study was to evaluate the effect of various analgesic drugs; morphine, fentanyl and tramadol, on the bone of adult female rats. Forty rats were divided into 4 groups; Control, morphine (8 mg/kg), fentanyl (32 μg/kg) and tramadol (10 mg/kg) groups. After 90 days of treatment, the serum calcium, alkaline phosphatase, osteocalcin and estradiol were assayed and the bones were prepared for histomorphometric study. In comparison to the control group, morphine and fentanyl groups showed a significant biochemical and histological osteoporotic changes while treatment with tramadol leads to non-significant osteoporotic effect. In conclusion, tramadol had the least osteoporotic effect as compared to morphine or fentanyl on chronic administration suggesting the safety use of tramadol in the treatment of patients with chronic pain particularly in association with osteoporosis.