The association between fracture and obesity is site-dependent: A population-based study in postmenopausal women

Prieto-Alhambra, Daniel; Premaor, Melissa Orlandin; Avilés, Francesc Fina; Hermosilla, Eduard; Martínez-Laguna, D; Carbonell-Abella, C; Nogués, Xavier; Compston, Juliet; Díez-Pérez, Adolfo

doi:10.1002/jbmr.1466

Cited by 293 publications

(251 citation statements)

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“…Several studies have demonstrated that the relationship between BMI and fracture is site-specific (8,11,12,14,16,21,22). While obesity is protective against hip fracture in women, it is associated with higher risk of fractures at some other sites.…”

Section: Site Of Fracturementioning

confidence: 99%

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Obesity and fractures

Premaor

Comim

Compston³

2014

Arq Bras Endocrinol Metab

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Until recently obesity was believed to be protective against fractures. However, a report from a Fracture Liaison Clinic in the UK (2010) reported a surprisingly high proportion of obese postmenopausal women attending the clinic with fractures, and in the GLOW study (2011), a similar prevalence and incidence of fractures in obese and non-obese postmenopausal women was observed. Subsequently, other studies have demonstrated the importance of obesity in the epidemiology of fractures. Obese women are at increased risk of fracture in ankle, leg, humerus, and vertebral column and at lower risk of wrist, hip and pelvis fracture when compared to non-obese women. In men, it has been reported that multiple rib fractures are associated with obesity. Furthermore, falls appear to play an important role in the pathogenesis of fractures in obese subjects. Regarding hip fracture and major fractures, the FRAX algorithm has proven to be a useful predictor in obese individuals. Obese people are less likely to receive bone protective treatment; they have a longer hospital stay and a lower quality of life both before and after fracture. Moreover, the efficacy of antiresorptive therapies is not well established in obese people. The latter is a field for future research. Arq Bras Endocrinol Metab. 2014;58(5):470-7 Keywords Obesity; fractures; osteoporosis; osteopenia ReSumo Acreditava-se que pessoas obesas estavam protegidas contra fraturas. No entanto, um estudo realizado no Reino Unido (2010) encontrou uma proporção surpreendentemente alta de obesidade entre as mulheres na pós-menopausa que se consultaram em uma Clínica de Fraturas Ósseas. Da mesma maneira, o estudo GLOW (2011) observou prevalência e incidência semelhantes de fraturas em mulheres na pós-menopausa obesas e não obesas. Posteriormente, vários outros estudos têm demonstrado a importância da obesidade na epidemiologia de fraturas. Mulheres obesas têm maior risco de fratura no tornozelo, na perna, no úmero e na coluna vertebral e têm menor risco de fratura de punho, quadril e pelve quando comparadas às mulheres não obesas. A associação entre fraturas múltiplas de costelas e obesidade foi descrita em homens. Além disso, as quedas parecem desempenhar um papel importante na patogênese de fraturas em pacientes obesos. O algoritmo FRAX parece ser uma ferramenta útil na predição do risco de fraturas em indivíduos obesos. Indivíduos obesos são menos propensos a receber tratamento preventivo para as fraturas ósseas e, quando sofrem uma fratura óssea, sua internação costuma ser mais longa do que a internação de indivíduos magros. A qualidade de vida dos indivíduos obesos é menor antes e depois da fratura. Não obstante, a eficácia de terapias antirreabsorção não está bem estabelecida em pessoas obesas. Este último é um campo para pesquisas futuras. Arq Bras Endocrinol Metab. 2014;58(5):470-7 Descritores Obesidade; fraturas ósseas; osteoporose, osteopenia

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Section: Site Of Fracturementioning

confidence: 99%

“…Subsequently, other investigators have studied the impact of obesity on bone mass and the risk of fracture (9)(10)(11)(12)(13)(14). The present review focuses on the epidemiology, risk factors, diagnosis, and management of fractures in obese postmenopausal women and older men.…”

mentioning

confidence: 99%

Obesity and fractures

Premaor

Comim

Compston³

2014

Arq Bras Endocrinol Metab

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“…A number of previous studies have revealed that obesity stimulates bone formation by inhibiting apoptosis. A recent study demonstrated that high BMI prevents normal bone fracture and osteoporotic fracture in various age groups and genders (7). By contrast, it has also been reported that osteoporosis occurs in obese individuals (8).…”

Section: Introductionmentioning

confidence: 99%

Adipocytes regulate the bone marrow microenvironment in a mouse model of obesity

Hang

et al. 2013

Molecular Medicine Reports

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Abstract. Obesity is markedly associated with abnormal bone density indicating the importance of adipocytes in bone metabolism. However, the specific function of adipocytes remains unclear, with marked discrepancies in observations of previous studies. In the present study, the effect of adipocytes on osteoblasts/osteoclasts was analyzed. A mouse model of obesity was established and an in vitro co-culture system was utilized containing adipocyte and MC3T3/RAW 264.7 cells in a Transwell plate. Compared with control mice, obese mice exhibited low body weight and bone mineral density of the tibia and fat cells were observed to accumulate in bone marrow. MC3T3/RAW 264.7 cells were co-cultured with adipocytes and the mRNA and protein expression of alkaline phosphatase and osteocalcin was found to be decreased in MC3T3-E1 cells and mRNA and protein expression of tartrate-resistant acid phosphatase and cathepsin K was significantly increased in RAW 264.7 cells. In addition, the effect of adipocytes on the osteoprotegerin (OPG)/receptor activator of nuclear factor κB ligand (RANKL)/RANK system indicated that the RANKL/OPG ratio secreted by osteoblasts increased and RANK expression by osteoclasts increased, leading to increased osteoclastogenesis. These results indicate that bone metabolism is impaired in obese mice leading to decreased osteoblastogenesis and marked increases in osteoclastogenesis and low bone mass. IntroductionObesity is becoming increasingly prevalent, leading to reduced life expectancy and increased health problems (1). High body mass index (BMI) is associated with various diseases, including cardiovascular, obstructive sleep apnea, diabetes mellitus type 2, specific types of cancer and osteoarthritis (2). Bone metabolism is also abnormal in obesity (3) and positive and negative factors have been identified to be associated with bone health status (4-6). A number of previous studies have revealed that obesity stimulates bone formation by inhibiting apoptosis. A recent study demonstrated that high BMI prevents normal bone fracture and osteoporotic fracture in various age groups and genders (7). By contrast, it has also been reported that osteoporosis occurs in obese individuals (8). These inconsistencies may be due to the use of different animal models in each study.Adipose tissue, a large endocrine organ, secretes a number of hormones that affect bone metabolism. Adipocytes in the bone marrow microenvironment differentiate from bone marrow mesenchymal cells and secrete cytokines which affect osteoblast and osteoclast levels in bone marrow. The effect of adipocytes on osteoblasts/osteoclasts remains controversial.The aim of the present study was to identify the function of adipocytes in the bone marrow microenvironment. To analyze the biological foundations of bone metastasis in obesity, a high-fat diet was selected to establish a mouse model of obesity (9). The results indicate that adipocytes accumulate in the bone marrow environment and affect bone turnover and osteoblast/osteoclast differentiation....

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“…However, fracture risk in obesity is not lower at all skeletal sites; the risk of some non-spine fractures including proximal humerus (RR 1.28), upper leg (OR 1.7) and ankle fracture (OR 1.5) is higher [4,5]. A large number of low-trauma fractures occur in overweight and obese men and women, and the prevalence of low-trauma fractures is similar in obese and non-obese women [6].…”

Section: Obesity Fracture and Bmdmentioning

confidence: 99%

Comparison of Metabolic Risk Factors and Physical Fitness according to Femur Osteoporotic Status in Elderly Women

cho¹,

Lee²,

Kang³

2017

Exerc Sci

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clinicians. However, the limited available evidence suggests that osteoporosis treatment does reduce fracture risk in obesity and T2DM with generally similar efficacy to other patients.Keywords Bone · Obesity · Diabetes · Fat · Fracture Obesity, Type 2 Diabetes and BoneObesity is a major and growing public health problem; for example, in the UK, 40% of adults will be obese by 2025 [1]. Obesity is the most important risk factor for type 2 diabetes (T2DM), and the global prevalence of T2DM is likely to be 592 million by 2035 [2]. As the population ages, the burden of osteoporosis and fragility fracture also increases. Obesity and T2DM have effects on fracture risk, and fractures in T2DM are associated with greater morbidity than in the general population. Understanding how to assess and treat fracture risk in these groups is important for health care planning and individual patients. Additionally, the study of the mechanisms of action of obesity and T2DM on bone has already offered insights that may be applicable in the broader study of osteoporosis, such as the effects of adipokines on bone cells and the effects of collagen glycation on material properties of bone. There are some similarities in the effect of obesity and T2DM on bone, but some important differences such as cortical porosity and collagen glycation.In this review, we describe the effects of obesity and T2DM on fracture risk and discuss possible mechanisms of their effects. We also consider the validity of existing fracture risk prediction tools and efficacy of osteoporosis treatment in these patient groups. AbstractIn an increasingly obese and ageing population, type 2 diabetes (T2DM) and osteoporotic fracture are major public health concerns. Understanding how obesity and type 2 diabetes modulate fracture risk is important to identify and treat people at risk of fracture. Additionally, the study of the mechanisms of action of obesity and T2DM on bone has already offered insights that may be applicable to osteoporosis in the general population. Most available evidence indicates lower risk of proximal femur and vertebral fracture in obese adults. However the risk of some fractures (proximal humerus, femur and ankle) is higher, and a significant number fractures occur in obese people. BMI is positively associated with BMD and the mechanisms of this association in vivo may include increased loading, adipokines such as leptin, and higher aromatase activity. However, some fat depots could have negative effects on bone; cytokines from visceral fat are pro-resorptive and high intramuscular fat content is associated with poorer muscle function, attenuating loading effects and increasing falls risk. T2DM is also associated with higher bone mineral density (BMD), but increased overall and hip fracture risk. There are some similarities between bone in obesity and T2DM, but T2DM seems to have additional harmful effects and emerging evidence suggests that glycation of collagen may be an important factor. Higher BMD but higher fracture risk presents challenges i...

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The association between fracture and obesity is site-dependent: A population-based study in postmenopausal women

Cited by 293 publications

References 25 publications

Obesity and fractures

Obesity and fractures

Adipocytes regulate the bone marrow microenvironment in a mouse model of obesity

Comparison of Metabolic Risk Factors and Physical Fitness according to Femur Osteoporotic Status in Elderly Women

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