INSULIN RESISTANCE AND PATHOGENESIS OF POSTMENOPAUSAL OSTEOPOROSIS

Abstract

Osteoporosis (OP) is a disease predisposing postmenopausal women to fractures, and often accompanied by insulin resistance (IR) and metabolic syndrome (MetS). Previous studies provided contradictory results concerning prevalence of MetS in postmenopausal OP. To better understand the pathogenesis of IR, we reviewed cellular and molecular aspects and systematically reviewed studies providing homeostasis model assessment (HOMA) index. Bone is an active endocrine organ maintaining its integrity by orchestrated balance between bone formation and resorption. Both osteoblasts and osteoclasts contain receptors for insulin and insulin-like growth factor-1 (IGF-1) operating in skeletal development and in the adult life. Defects in this system generate systemic IR and bone-specific IR, which in turn regulates glucose homeostasis and energy metabolism through osteocalcin. Examination of genetic syndromes of extreme IR revealed intriguing features namely high bone mineral density (BMD) or accelerated growth. Studies of moderate forms of IR in postmenopausal women reveal positive correlations between HOMA index and BMD while correlations with osteocalcin were rather negative. The relation with obesity remains complex involving regulatory factors such as leptin and adiponectin to which the contribution of potential genetic factors and in particular, the correlation with the degree of obesity or body composition should be added.

Keywords: HOMA index; insulin resistance; metabolic syndrome; osteoporosis.

Figure 1

Overview of the relationship between systemic insulin resistance and bone-specific insulin resistance.