Adipose Tissue Dysfunction: Impact on Bone and Osseointegration

Abstract

Bone metabolism may be adversely affected in metabolic diseases such as obesity and metabolic syndrome, which are characterised by weight gain, due to the expansion of adipose tissue deposits. As an important regulator of energy metabolism, adipose tissues synthesise and secrete several key regulatory adipokines that influence a range of metabolic functions. This narrative review outlines the evidence for the mechanisms by which adipose tissue dysfunction may alter bone metabolism prior to the development of frank hyperglycaemia and presents the emerging evidence for the impact of diet-induced expansion of adipose tissue on implant osseointegration. Successful osseointegration requires normal bone cell function, and the expansion of adipose tissue deposits results in dysregulated adipokine production favouring an increase in pro-inflammatory adipokines, contributing to the development of a chronic inflammatory state and insulin resistance. The increase in inflammatory cytokines promotes the growth and differentiation of osteoclasts indirectly through the modulation of osteoblastic RANKL production and directly by reducing osteoclast apoptosis and increased osteoclastic expression of RANK. Conversely, the suppression of osteoblastic regulatory genes results in reduced osteoblast numbers and function contributing to compromised bone turnover. Compromised osseointegration has been established in hyperglycaemia; however, as discussed in this review, it may not be the only driver of altered bone metabolism. The incidence of metabolic disease in the community is rising, patients may present for implant treatment with undiagnosed, underlying changes to bone cell metabolism due to adipose tissue dysmetabolism.

Keywords: Adipokines; Adipose tissue dysfunction; Bone; Insulin resistance; Osseointegration; Pro-inflammatory cytokines.