Relationships between Obesity and Incidence of Fractures in a Middle‐Aged Population: A Study from the CARTaGENE Cohort

Abstract

The association between obesity and fracture risk is complex and may vary by definition of obesity, skeletal site, and sex. We aimed to evaluate the relationships between obesity, defined using body mass index (BMI) or waist circumference (WC), and fracture incidence at any site and by skeletal site (i.e., major osteoporotic fractures [MOFs], distal lower limb fractures [tibia, ankle, feet], and distal upper limb fractures [forearm/elbow, wrist]). The secondary aim was to assess the aforementioned relationships by sex. We used CARTaGENE, a large population‐based cohort of individuals aged 40–70 years from Quebec, Canada, who were assessed in 2009–2010. Incident fractures were identified via linkage with healthcare administrative databases over a 7‐year period. Cox proportional hazard models adjusted for several potential confounders were used to estimate the relationships, with exposures treated as continuous variables. Results are reported as adjusted hazard ratios (aHRs) and 95% confidence intervals. We identified 19 357 individuals (mean ± standard deviation: age 54 ± 8 years, BMI 27 ± 5 kg/m2, WC 94 ± 14 cm; 51.6% women). During follow‐up, 497 women and 323 men sustained a fracture. There was a linear relationship between fracture incidence and WC, while cubic splines best fitted the relationship for BMI. Greater WC was associated with an increased risk of fracture at the distal lower limbs in the whole cohort and in the subgroup of women: aHR for each 10 cm increased in WC of 1.12 (1.03, 1.21) and 1.12 (1.01, 1.24), respectively. In men, WC was not significantly associated with any fracture outcome. Higher BMI was also significantly associated with distal lower limb fracture risk in the whole cohort (p = 0.018). No significant relationships were found between either WC or BMI and the risk of any fracture, MOFs, and distal upper limb fractures. In middle‐aged individuals, obesity, and mainly abdominal obesity, was associated with distal lower limb fracture risk. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Effect of BMI-Discordant Abdominal Tissue Thickness on Fracture Probability: A Registry-Based Study

“…(21) Most recently, a population-based study of 18,236 men and women aged 40-70 years from Canada reported that greater BMI-adjusted waist circumference (adjusted for multiple covariates but not BMD) was associated with increased risk of distal lower limb fractures (but only for BMI within the normal and overweight ranges) and distal upper limb fractures (only for BMI in the overweight range) and was not significantly associated with risk for all fractures or MOF. (20,22) The biological mechanism underlying this association is unclear but may in part relate to associations of visceral adiposity with diabetes and systemic inflammation. (7)(8)(9) Waist circumference is positively correlated with the inflammatory markers interleukin-6 and tumor necrosis factor-α, consistent with the hypothesis that central obesity is a biomarker from the inflammatory state.…”

“…(10)(11)(12) However, the effects of abdominal obesity on BMD and fracture risk have been inconsistent. (13)(14)(15)(16)(17)(18)(19)(20)(21)(22) Importantly, none of the previous studies specifically examined clinical implications for FRAX or adjusted for competing mortality, which is increased by central obesity in both women and men even after adjusting for BMI. (23) The current analysis was performed to evaluate the effect of abdominal tissue thickness that deviates from BMI-predicted abdominal tissue thickness on performance of FRAX for MOF and hip fracture prediction.…”

“…( 10‐12 ) However, the effects of abdominal obesity on BMD and fracture risk have been inconsistent. ( 13‐22 ) Importantly, none of the previous studies specifically examined clinical implications for FRAX or adjusted for competing mortality, which is increased by central obesity in both women and men even after adjusting for BMI. ( 23 )…”

Diet-Stimulated Marrow Adiposity Fails to Worsen Early, Age-Related Bone Loss

“…Studies point to adverse bone outcomes in sarcopenic obesity, as opposed to obesity alone, which implicates additional factors such as exercise/physical activity as potential mediators [5]. Obesity associates with more distal limb fractures and less hip fractures [6][7][8]; however, clinical impact of this and mechanistic underpinnings are unclear.…”