The association between insulin levels and cortical bone: Findings from a cross-sectional analysis of pQCT parameters in adolescents

Abstract

Recent studies suggest that patients with type 2 diabetes mellitus are at increased risk of fracture, possibly because hyperinsulinemia is a risk factor for low bone mineral density, which may in turn be a consequence of a lipotoxic effect of visceral and/or intramuscular fat on bone. In the current study, we investigated whether insulin plays a role in cortical bone development by performing a cross-sectional study based on the Avon Longitudinal Study of Parents and Children (ALSPAC), where we examined associations between fasting insulin levels and peripheral quantitative computed tomography (pQCT) parameters as assessed at the mid-tibia in 2784 boys and girls with a mean age 15.5 years. In particular, we wished to examine whether associations that we observed were independent of body composition, including intramuscular fat. We found that insulin was inversely related to cortical bone mineral density (BMDC) after adjustment for age and after further adjustment for height, muscle cross-sectional area (MCSA), subcutaneous fat (SAT), and muscle density (MD), which is inversely related to intramuscular fat (−0.018, 95% confidence interval [CI] −0.030, −0.006, p < 0.0001). Insulin was positively related to periosteal circumference (PC) after adjusting for age (0.015, 95% CI 0.003, 0.027, p = 0.015; beta = change per 50% increase in insulin), but this changed to an inverse association after additional adjustment for height and body composition (−0.013, 95% CI −0.022, −0.003, p = 0.008). Path analyses revealed inverse associations between insulin and PC via a direct pathway (−0.012, 95% CI −0.022, −0.003, p = 0.01) and via MD (−0.002, 95% CI −0.004, −0.001, p = 0.0004), and positive associations between insulin and PC via SAT (0.013, 95% CI 0.009, 0.016, p < 0.0001) and MCSA (0.015, 95% CI 0.010, 0.020, p < 0.0001). In conclusion, we found an inverse relationship between insulin and PC via intramuscular fat, suggesting a lipotoxic effect on bone. However, an inverse association between insulin and both PC and BMDC persisted after adjusting for all body composition variables, suggesting insulin also acts to inhibit bone development via additional pathways yet to be elucidated. © 2012 American Society for Bone and Mineral Research

Obese Versus Normal-Weight Late-Adolescent Females have Inferior Trabecular Bone Microarchitecture: A Pilot Case-Control Study

“…Greater visceral adiposity was also accompanied by higher values of insulin resistance, which may have in turn influenced bone metabolism [34, 35]. That the obesity-related trabecular bone deficits were consistently attenuated following adjustment for HOMA-IR supports an intermediary role of insulin resistance in the fat-bone connection [36]. However, the manner in which insulin resistance influences skeletal tissue is relatively uncertain.…”

Insulin Resistance Is Associated With Smaller Cortical Bone Size in Nondiabetic Men at the Age of Peak Bone Mass

“…Inverse associations of HOMA-IR with periosteal and endosteal circumferences at the ultradistal radius and tibia have been reported in nondiabetic postmenopausal women (14), whereas fasting insulin levels were inversely associated with midtibial periosteal circumference and SSI in adolescents (13), and with midtibial total and cortical bone area and SSI in older adult men (22). Our findings are moreover largely in agreement with the existing literature on bone geometry in T2DM, with 2 pQCT studies reporting a smaller bone area at the distal and midshaft radius and tibia in individuals with vs without T2DM (5, 6).…”

“…Alternatively, decreased bone strength may develop early as a consequence of the pathophysiology underlying T2DM, which is characterized by insulin resistance. Indeed, an inverse association of fasting insulin levels with periosteal circumference at the tibia has been reported in healthy adolescents (13), whereas insulin resistance [expressed as the homeostasis model assessment of insulin resistance (HOMA-IR)] correlated inversely with periosteal and endosteal circumference but positively with cortical thickness and trabecular microarchitecture at the ultradistal radius and tibia in nondiabetic postmenopausal women (14). Until now, our understanding of the mechanisms underlying these findings remains limited, and no studies have investigated this in adult men.…”

Skeletal muscle and pediatric bone development

“…Sayers et al [44] suggested that the negative relationship between insulin resistance and cortical bone may be, at least in part, attributed to muscle fat. Although Janz et al [45 & ] showed that the relationships between muscle function and cortical bone outcomes were mediated by muscle size, it has also been shown in older and younger adults that muscle adiposity may impede muscular function [46,47].…”

“…Muscle adipose tissue infiltration is associated with metabolic disturbances, such as insulin resistance, which may adversely influence cortical bone geometry in adolescents [43,44]. Sayers et al [44] suggested that the negative relationship between insulin resistance and cortical bone may be, at least in part, attributed to muscle fat.…”