Diabetes and Risk of Fracture-Related Hospitalization

Schneider, Andrea L.C.; Williams, Emma K.; Brancati, Frederick L.; Blecker, Saul; Coresh, Josef; Selvin, Elizabeth

doi:10.2337/dc12-1168

Cited by 84 publications

(78 citation statements)

References 25 publications

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“…(3) Both diseases are detrimental to the bone resulting in an increased risk for fragility fractures (4) : the lifetime risk to sustain an osteoporotic fracture ranges between 40% to 50% in women (5) and in T2D, the risk of having a fragility fracture lies even higher and varies dependent on the skeletal site between 20% and 160% in elderly women. (6) Given the substantial morbidity, mortality, and costs that emanate from osteoporotic (7) or T2D-related fractures, (8,9) proper recognition of populations at increased fracture risk is indispensable. Areal bone mineral density (aBMD) testing by dual energy X-ray absorptiometry (DXA) and assessment of clinical scores such as the WHO Fracture Risk Assessment Tool (FRAX) are regarded as the international standards for assessment of fracture risk in osteoporosis.…”

Section: Introductionmentioning

confidence: 99%

Serum miRNA Signatures Are Indicative of Skeletal Fractures in Postmenopausal Women With and Without Type 2 Diabetes and Influence Osteogenic and Adipogenic Differentiation of Adipose Tissue–Derived Mesenchymal Stem Cells In Vitro

Heilmeier

Hackl²,

Skalicky

et al. 2016

Journal of Bone and Mineral Research

117

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Standard DXA measurements, including Fracture Risk Assessment Tool (FRAX) scores, have shown limitations in assessing fracture risk in Type 2 Diabetes (T2D), underscoring the need for novel biomarkers and suggesting that other pathomechanisms may drive diabetic bone fragility. MicroRNAs (miRNAs) are secreted into the circulation from cells of various tissues proportional to local disease severity and were recently found to be crucial to bone homeostasis and T2D. Here, we studied, if and which circulating miRNAs or combinations of miRNAs can discriminate best fracture status in a well-characterized study of diabetic bone disease and postmenopausal osteoporosis (n ¼ 80 postmenopausal women). We then tested the most discriminative and most frequent miRNAs in vitro. Using miRNA-qPCR-arrays, we showed that 48 miRNAs can differentiate fracture status in T2D women and that several combinations of four miRNAs can discriminate diabetes-related fractures with high specificity and sensitivity (area under the receiver-operating characteristic curve values [AUCs], 0.92 to 0.96; 95% CI, 0.88 to 0.98). For the osteoporotic study arm, 23 miRNAs were fracture-indicative and potential combinations of four miRNAs showed AUCs from 0.97 to 1.00 (95% CI, 0.93 to 1.00). Because a role in bone homeostasis for those miRNAs that were most discriminative and most present among all miRNA combinations had not been described, we performed in vitro functional studies in human adipose tissue-derived mesenchymal stem cells to investigate the effect of miR-550a-5p, miR-188-3p, and miR-382-3p on osteogenesis, adipogenesis, and cell proliferation. We found that miR-382-3p significantly enhanced osteogenic differentiation (p < 0.001), whereas miR-550a-5p inhibited this process (p < 0.001). Both miRNAs, miR-382-3p and miR-550a-5p, impaired adipogenic differentiation, whereas miR-188-3p did not exert an effect on adipogenesis. None of the miRNAs affected significantly cell proliferation. Our data suggest for the first time that miRNAs are linked to fragility fractures in T2D postmenopausal women and should be further investigated for their diagnostic potential and their detailed function in diabetic bone.

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Section: Introductionmentioning

confidence: 99%

Serum miRNA Signatures Are Indicative of Skeletal Fractures in Postmenopausal Women With and Without Type 2 Diabetes and Influence Osteogenic and Adipogenic Differentiation of Adipose Tissue–Derived Mesenchymal Stem Cells In Vitro

Heilmeier

Hackl²,

Skalicky

et al. 2016

Journal of Bone and Mineral Research

117

View full text Add to dashboard Cite

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“…Individuals with inadequately controlled T2D had a 47-62% higher fracture risk than those without diabetes despite having 1.1-5.6% higher BMD by DXA [ 20 ]. Similarly, those with glycated hemoglobin (HgA1C) >8.0% had a greater risk of fracture than those with HgA1C <8.0%, suggesting fracture risk is a function of the extent to which hyperglycemia is controlled [ 21 ].…”

Section: Incidence and Contributing Factorsmentioning

confidence: 87%

The Effects of Diabetes and Obesity on the Skeleton

Furst

Bilezikian

Rubin

2015

Preventive Nutrition

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• Osteoporosis is a disorder of compromised bone strength that increases fracture risk. It is a disease that has reached epidemic proportions affecting 200 million women worldwide.• Type 2 diabetes (T2D) and obesity have emerged as newly recognized risk factors for osteoporosis.• Mechanisms for bone loss in T2D include reduced bone formation, abnormal skeletal microstructure, and abnormal bone material properties. • Many medications for the treatment of osteoporosis have shown effi cacy in preserving or improving the bone health of those with T2D.• Mechanisms for increased fracture risk in obesity include altered distribution of fat depots in the body, some locations of which can be associated with reduced bone quality.

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“…Interestingly, the bone density scan was normal. Cross-sectional epidemiological studies have found that patients with type 2 diabetes mellitus have a higher incidence of fragility fractures despite normal or elevated BMD [3,[8][9][10]. This is likely to be explained by the fact that type 2 diabetes induces deterioration of bone microarchitecture leading to a porous skeleton susceptible to fracture.…”

Section: Discussionmentioning

confidence: 99%

“…Poor diabetes control is also associated with high risk of bone fracture. For instance, the Atherosclerosis Risk in Communities (ARIC) Study showed that type 2 diabetes was significantly and independently associated with increased risk of fracture especially those treated with insulin or those with HbA1c ≥ 8% (64 mmol/L) as compared to those individuals with HbA1c below 8% [9]. Furthermore, the Rotterdam Study data showed that poor glycemic control based on an HbA1c cut-off of 7.5%…”

Section: Introductionmentioning

confidence: 99%

Fracture of Femur in a Young Obese Individual With Type 2 Diabetes, Hypogonadism and Low Vitamin D: As in the Titanic We Are Only Seeing the Tip of the Iceberg?

2016

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We report a case of a 42-year-old male with poorly controlled type 2 diabetes and body mass index (BMI) of 35 kg/m 2 who was admitted with fracture of right head of the femur after small fall from stepladder. Imaging of the pelvis in the form of an X-ray showed multi-fragmented fracture through trochanteric region of the right femur. His fracture was fixed with an intramedullary device. However, subsequent tests revealed low testosterone (4.2 nmol/L and reference range 10 -35 nmol/L) and low vitamin D (13.2 nmol/L and reference range > 50). His bone densitometry scan showed no evidence of osteoporosis. Furthermore, his diabetes control was poor with an average HbA1c of 11% and he was also known to have background diabetic retinopathy. The combination of poor diabetes control, obesity, hypogonadism and low vitamin D may all have contributed to an increase in risk of fracture in association with simple fall in this young man. Obesity and type 2 diabetes are associated with hypogonadism and low vitamin D. In view of the high epidemic of diabetes and obesity, it is possible to suggest that there are large numbers of these individuals with high risk for fracture likely to be induced upon any mild degree of trauma. Furthermore, it is possible to suggest that obesity-induced fracture will increase the burden in orthopedic department and the current numbers of fractures related to obesity may represent the tip of iceberg. Our case report is unique as the fracture occurred in a young individual with all these metabolic disorders. Therefore, our case report illustrates the needs for close collaboration between orthopedic surgeons, general practioners and endocrinologists and importantly the need for robust methods for screening and risk stratifications.

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Diabetes and Risk of Fracture-Related Hospitalization

Cited by 84 publications

References 25 publications

Serum miRNA Signatures Are Indicative of Skeletal Fractures in Postmenopausal Women With and Without Type 2 Diabetes and Influence Osteogenic and Adipogenic Differentiation of Adipose Tissue–Derived Mesenchymal Stem Cells In Vitro

Serum miRNA Signatures Are Indicative of Skeletal Fractures in Postmenopausal Women With and Without Type 2 Diabetes and Influence Osteogenic and Adipogenic Differentiation of Adipose Tissue–Derived Mesenchymal Stem Cells In Vitro

The Effects of Diabetes and Obesity on the Skeleton

Fracture of Femur in a Young Obese Individual With Type 2 Diabetes, Hypogonadism and Low Vitamin D: As in the Titanic We Are Only Seeing the Tip of the Iceberg?

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