Background: Osteoporosis is an important health care issue because the resultant bone fractures cause great deal of morbidity and mortality. Among the important risk factors for the development of osteoporosis is diabetes mellitus.  Objective: Thiazolidinediones (TZDs), group of antidiabetic drugs used to reduce insulin resistance, have been inconsistently shown to be associated with osteoporotic fractures. The purpose of this study was to find out if the use of pioglitazone, an oral antidiabetic medication belonging to TZDs, has any adverse effects on bone health in patients with type-2 diabetes in Jeddah, KSA. Methods: This case control analysis included 56 subjects, 40 to 65 years old (18 diabetic patients under pioglitazone therapy, 18 diabetic patients under metformin-sulfonylurea therapy, and 20 non-diabetic persons) enrolled in osteoporosis center in Jeddah, KSA. Medication information was taken directly from drug containers during in-person interviews. The main outcome measures were the bone mineral density (BMD) and the serum levels of vitamin D, calcium, and creatinine. Results: No significant BMD and biochemical (serum vitamin D, calcium, and creatinine) changes were be detected in the three groups (Pioglitazone users group; metformin-sulfonylurea users group; and the nondiabetic persons group). Conclusion: Pioglitazone does not cause adverse effect on the BMD and biochemical tests. This is in contrast to other studies that showed decreased BMD and increased risk of fracture in patients on TZDs. Some of this contravention may be explained by factors that are included within bone quality, while some may be related to the other non-skeletal factors. In terms of bone quality, there have been suggestions that there are racial differences in bone strength due to genetic, nutritional, lifestyle, and hormonal factors. The possible other non-skeletal factors include the small number of patients studied in the present work as well as the variation of the dose of the drug, and the duration of therapy. Therefore, large prospective, randomized trials are necessary to evaluate the effect of pioglitazone on the bone health of diabetic patients in KSA.