Obesity is a risk factor for fracture in children but is protective against fracture in adults: A paradox

Abstract

With the rise in obesity worldwide, an important debate has developed as to whether excess fat has a detrimental or protective effect on skeletal health in children and adults. Obese children appear to be over represented in fracture groups and recent evidence suggests that fat may be detrimental to bone accrual in children, although this effect may be confined to adolescence during rapid skeletal growth. Fat induced alterations in hormonal factors and cytokines during growth may play a pivotal role in disturbing bone accrual. In contrast, the widely accepted opinion is that fat appears to be protective of bone in adults and minimises bone loss in postmenopausal women. Recent evidence suggests that in adults, site specific fat depots may exert differing effects on bone (with visceral fat acting as a pathogenic fat depot and subcutaneous fat exerting protective effects), and that the effects of fat mass on bone and fracture risk may vary by skeletal site; obesity protects against hip and vertebral fractures but is a risk factor for fractures of the humerus and ankle. The incidence of fracture during adolescence is rising and osteoporosis remains a considerable health burden in older adults. Understanding the effects of fat mass on bone during growth and early adulthood is vital in informing future health strategies and pharmacotherapies to optimise peak bone mass and prevent fracture.

This article is part of a Special Issue entitled: Interactions Between Bone, Adipose Tissue and Metabolism.

Introduction

Obesity has become a major problem worldwide and the associated co-morbidities have already generated a significant health burden. Much obesity-related co-morbidity acquired during childhood and adolescence, such as type 2 diabetes and hypertension, persists into adulthood with an increased risk of mortality [1], [2]. As obesity has risen in children (BMI SDS > 2.87) and adults (BMI > 30 kg/m²), so has the number of studies examining the relationships between fat and bone. However, despite a considerable body of densitometry-based data there remains controversy as to whether fat has a positive or detrimental effect on bone in both the paediatric and adult populations. Additionally, there is a paucity of longitudinal studies focusing on the effect of excessive fat on bone as children progress through adolescence and peak bone mass accrual into adulthood. Bone mass acquired through childhood and adolescence tracks into adulthood and may ultimately determine future osteoporotic risk [3], [4]. During adolescence, the ratio of cortical to trabecular bone determined by peripheral quantitative computed tomography (pQCT) appears to decrease during mid-puberty in line with a peak in cortical porosity [5]. This may explain the observed peak in the incidence of radial fracture during adolescence [6], [7] (Fig. 1). Therefore, it is vital to understand the changing relationship between fat and bone to help minimise the risk of fracture during adolescence and later osteoporosis, ultimately helping to alleviate significant health burdens at two key stages of life. Understanding factors that alter bone mass during adolescence may help to inform strategies to improve peak bone mass accrual. However, the mechanisms underpinning the relationship between fat and bone from childhood into adulthood remain poorly understood. There is a growing body of evidence suggesting that cytokines and hormones derived from white adipose tissue may play a role in the regulation of bone turnover [8], [9]. Additionally, attention has been drawn to the role of gut-related peptides in the control of bone turnover in relation to nutritional intake [10].