EFFECT OF PIOGLITAZONE ON THE BONE HEALTH OF DIABETIC PATIENTS IN JEDDAH, KSA

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. INTRODUCTION AND AIM The insisting importance of therapy of diabetes mellitus is emphasized by the fact that the disease affects a large number of populations and causes many disabling complications. Although traditionally osteoporosis has not been listed as diabetes related complication, increasing evidence suggests that patients with type 1 or type 2 diabetes are at increasing risk of osteoporotic fracture (Brandi, 2010). Therefore, it was proposed that hyperglycemia, a result of insulin deficiency or insulin resistance, is responsible for higher osteoporosis in the population with diabetes (Brandi, 2010). Higher glucose levels in the blood are known to interact with Az. J. Pharm Sci. Vol. 46, September, 2012 2 several proteins to form advanced glycation end (AGE) products that may interact with bone to reduce bone strength, resulting in osteoporosis in patients with diabetes (Yamagishi, et al., 2005; Alikiani, et al., 2007; Munoz, et al., 1996). Another indirect effect of hyperglycemia is glycosuria, which causes hypercalciuria, leading to decreased levels of calcium in the body and poor bone quality. Additionally, several diabetes related complications such as retinopathy, neuropathy, and nephropathy have been linked to decreased BMD (Monami et al., 2008). Thiazolidinediones (TZDs) are class of oral hypoglycemic drugs that have been commonly prescribed throughout the world for the treatment of type 2 diabetes mellitus both as monotherapy and in combination with metformin, sulfonylurea and insulin (Wannakamo, et al., 2012; Priya and Sunder, 2010). Recent evidence from an epidemiological study and an exploratory clinical trial suggests that the use of the insulin-sensitizing agents, TZDs is associated with a decrease in bone density in postmenopausal women (Schwartz, et al., 2006; Grey, et al., 2007). Similar results have been reported by an observational retrospective study exploring variations of bone density in older men with type 2 diabetes (Yaturu, et al., 2007). In vitro and in vivo studies demonstrated that peroxisome proliferator-activated receptor induction in mesenchymal cells leads to increased adipogenesis and decreased osteoblastogenesis (Canalis, et al., 2007). Thiazolidinediones also decrease the expression of insulin-like growth factor I, and this may contribute to decreased bone formation (Giustina, et al., 2008). In addition, thiazolidinediones promote osteoclast differentiation and bone resorption (Wan, et al., 2007; Okazaki, et al., 1999). On the other hand, the insulin-sensitizing effect of TZDs reduces circulating insulin levels and therefore the insulin anabolic effect on the bone is reduced (Thrailkill, et al., 2005). The purpose of this study was to find out if the use of pioglitazone, an oral antidiabetic drug belonging to TZDs class of medications, has any adverse effects on BMD and serum levels of vitamin D, calcium, and creatinine in diabetic patients in Jeddah, KSA. PATIENTS AND METHODS