Skip to content

Advertisement

  • Review article
  • Open Access

Diabetes mellitus and bone health: epidemiology, etiology and implications for fracture risk stratification

Clinical Diabetes and Endocrinology20184:9

https://doi.org/10.1186/s40842-018-0060-9

  • Received: 3 January 2018
  • Accepted: 9 April 2018
  • Published:

Abstract

Skeletal fractures can result when there are co-morbid conditions that negatively impact bone strength. Fractures represent an important source of morbidity and mortality, especially in older populations. Diabetes mellitus is a metabolic disorder that has reached worldwide epidemic proportions and is increasingly being recognized as a risk factor for fracture. Type 1 and Type 2 diabetes have different effects on bone mineral density but share common pathways, which lead to bone fragility. In this review, we discuss the available data on diabetes and fractures, bone density and the clinical implications for fracture risk stratification in current practice.

Keywords

  • Diabetes mellitus
  • Type 1 diabetes mellitus
  • Type 2 diabetes mellitus
  • Bone mineral density
  • Fracture
  • Fracture risk stratification
  • Osteoporosis

Background

Osteoporosis is a systemic disease, which confers decreased bone strength and increased fracture risk [13]. Hip fractures especially are a major source of morbidity and mortality in older populations [4] and present an increasing public health burden [5]. Diabetes mellitus type 2 accounts for 90–95% of the incidence of diabetes [6, 7] and its prevalence is increasing worldwide [8]. Type 2 diabetes mellitus (T2DM) is associated with an increased bone mineral density (BMD) but a paradoxically increased risk for skeletal fractures [911]. Type 1 diabetes mellitus (T1DM) is less prevalent, but its incidence is rising, especially in the very young [12] and it has also been associated with increased fracture risk [13]. The causative mechanisms for this association are the subject of study by several groups but have not been completely elucidated. This article aims to evaluate the relationship of diabetes etiology, duration and glucose control with BMD and skeletal fracture. We also discuss potential strategies that increase the accuracy of fracture risk estimates in populations with diabetes mellitus, which could be applied to current clinical practice.

Diabetes and fracture risk

Diabetes mellitus has been associated with increased fracture risk by several groups. The Nurses’ Health Study followed 109,983 women aged 34–59 years old with biennial questionnaires for over 20 years and monitored the occurrence of hip fractures. They found that the risk of hip fracture in women with T1DM was six-fold higher compared with those without diabetes [14]. The Health Improvement Network (THIN) study used longitudinal electronic medical record data in the United Kingdom (UK) to evaluate incident fractures in men and women with T1DM from age 0 to 89 years old, across a median of 4.7 years of follow up. They found that the risk of incident fracture of any type increased in both sexes and in all age groups compared to those without diabetes. When stratified by age, women with T1DM ages 40–49 had the highest risk for fracture at any site, 82% higher than women without diabetes after multivariate adjustment. Men aged 60–69 with T1DM also had double the risk of fracture at any site compared to men without diabetes in the same age group [15]. The same study performed secondary analyses evaluating hip fracture specifically and found that men aged 60–69 with T1DM had 421% increased risk of hip fracture as compared to those without diabetes after adjustment for confounders. Young women with T1DM, in the 30–39 years old group had a 316% increase in the risk of hip fracture compared to those without, the highest magnitude increase in this sex. The authors concluded that fracture risk in T1DM is increased early on in life and that it is maintained throughout. The magnitude of fracture risk seemed to be higher in the lower extremity than at other sites. Others have also identified an association between T1DM and fractures. A cross-sectional case-control study of 82 young eastern European participants (mean age 31.1) with T1DM revealed a 320% increased risk of asymptomatic vertebral fractures compared with controls which was independent of multiple covariates, including lumbar spine bone density [16]. Similarly, a large registry based cohort study from Taiwan age and sex matched 500,868 diabetic patients (identified by diagnosis codes) and found that men and women with diabetes had a 28% and 72% increased risk of hip fracture compared to controls without diabetes. When stratified by age this study revealed that the hazard ratios (HR) for hip fracture were higher for diabetic men and women aged 35 to 44 and were null statistically in men over 74 and women over 84 [17]. It may be that age or menopause related changes overshadow the effect of diabetes on fracture risk, which is why we see disparities between the young and old.

Several studies have found associations between T2DM and skeletal fractures. In the Women’s Health Initiative observational cohort 93,676 generally healthy postmenopausal women were followed for 7 years. Women with T2DM at baseline had a 20% increased risk of fracture at any site after adjusting for multiple covariates, including frequency of falls [9]. The Study of Osteoporotic fractures followed 9654 women 65 years or older for an average of 9.4 years. Radiology reports were used to confirm reported incident fractures. They found that women diagnosed with diabetes after the age of 40 had a 30% increased risk of having any non-vertebral fracture and an 82% increased hip fracture risk compared with those without diabetes. The risk of vertebral fracture was not significantly increased in this analysis [18]. Other studies have specifically evaluated vertebral fractures. A cross-sectional study from Japan ascertained fractures from spinal and thoracic radiographs in participants over 50 years old and found that men and women with T2DM had a 373% and 82% increased risk of having prevalent vertebral fractures respectively after adjustment for lumbar spine bone density [19]. In contrast, a cross-sectional evaluation of the Canadian Multicenter Osteoporosis study did not find that self-reported T1DM nor T2DM was associated with vertebral deformity determined by spinal radiographs among older men and women (mean age 66) [20]. One population-based study evaluated all reported fractures in Denmark and found that T2DM was associated with a 19% increased risk of any fracture while T1DM was associated with 30% increased risk. In this study T1DM was associated with a significantly increased risk of spine fracture while T2DM was not, in contrast both T1DM and T2DM were associated with increased risk for hip fracture when compared to age and sex matched controls [21].

Data from these large well executed studies across multiple populations consistently find that people with T1DM or T2DM have increased fracture risk. Findings for hip fractures seem to be more consistent than those for vertebral fractures, but may depend on the specific populations studied. T1DM may be associated with a lifelong increased risk of fracture. Two meta-analyses evaluating published case-control and cohort studies have found that hip fracture risk was significantly higher for T1DM than T2DM without overlapping confidence intervals [22, 23], suggesting the magnitude of fracture increase is higher in T1DM than in T2DM. It may be that there are different mechanisms of increased fragility for T1DM and T2DM or that disease duration and diabetes control have modulating effects. A summary of fracture risk by diabetes type is presented in Table 1.
Table 1

Association of diabetes mellitus and fracture risk

Type of diabetes

Fracture type

Findings

Study design

Reference

Type 1 diabetes mellitus

Hip fracture

RR 7.10 (CI 95%: 4.4–11.4)

Prospective observational

Janghorbani et al.

Type 1 diabetes mellitus Men 60-69yo

Any type

HR 2.00 (CI 95%: 1.63–2.45)

Prospective observational

Weber et al.

Hip fracture

HR 5.21 (CI 95%: 3.2–8.47)

Type 1 diabetes mellitus Men 40-49yo

Any type

HR 1.82 (CI 95%: 1.53–11.43)

Type 1 diabetes mellitus Men 30-39yo

Hip fracture

HR 4.16 (CI 95%: 1.52–11.43)

Type 1 diabetes mellitus

Vertebral fracture

OR 4.20 (CI 95%: 1.40–12.7)

Cross sectional

Zhukouskaya et al.

Type 1 diabetes mellitus men

Hip fracture

HR 1.28 (CI 95%: 1.21–1.34)

Prospective observational

Chen et al.

Type 1 diabetes mellitus women

Hip fracture

HR 1.72 (CI 95%: 1.66–1.78)

Type 1 diabetes mellitus

Hip fracture

RR 6.94 (CI 95%: 3.25–14.78)

Meta-analysis observational studies

Vastergaard et al.

Type 2 diabetes mellitus

Hip fracture

RR 1.38 (CI 95%: 1.25–1.53)

Type 2 diabetes mellitus

Any site

RR 1.20 (CI 95%: 1.11–1.30)

Prospective observational

Bonds et al.

Type 2 diabetes mellitus

Non-vertebral

RR 1.30 (CI 95%: 1.10–1.53)

Prospective observational

Schwartz et al.

Hip fracture

RR 1.82 (CI 95%: 1.24–2.69)

Vertebral

RR 1.12 (CI 95%: 0.69–1.83)

Type 2 diabetes mellitus Men

Vertebral

OR 4.73 (CI 95% 2.19–10.20)

Cross sectional

Yamamoto et al.

Type 2 diabetes mellitus Women

Vertebral

OR 1.86 (CI 95% 1.11–3.12)

Type 2 diabetes mellitus Men

Vertebral

OR 0.77 (CI 95% 0.48–1.22)

Cross sectional

Hanley et al.

Type 2 diabetes mellitus Women

Vertebral

OR 0.92 (CI 95% 0.67–1.26)

Findings in bold letters indicate a significant positive association

RR: relative risk; HR: hazard ratio; OR: odds ratio

Diabetes and bone density

In T1DM, the association of bone mineral density with increased fracture risk is one of the most studied potential mechanisms. Bone density is decreased in T1DM. In a study of premenopausal women, those with T1DM had lower total hip (TH), femoral neck (FN) and whole body BMD after adjusting for multiple covariates, with no difference in lumbar spine (LS) BMD. The bone turnover markers osteocalcin and N-telopeptides of type I collagen were evaluated but did not significantly change the diabetes-BMD association [24]. In one small European study men with T1DM (mean age 43) had similar TH BMD but significantly lower spine BMD z score than age matched controls (Z score − 0.705 vs. -0.099) [25]. In the Fremantle diabetes study in Australia middle aged men with T1DM had significantly lower TH and FN BMD when compared to age and sex matched controls, but women with T1DM and matched controls had similar BMD at each site [26]. Multiple other studies have found lower BMD in T1DM, often associated with the presence of microvascular complications [24, 2730]. The limited sample size in these individual studies preclude wide generalizations, however a systematic review and meta-analysis found that aggregate estimates of published studies showed significantly lower BMD at the spine (Z score − 0.22 ± 0.01) and hip (Z score − 0.37 ± 0.16) in participants with T1DM compared with those without diabetes [22].

In children, low bone density for age may be present early after diagnosis of T1DM. A case control study evaluating children with recently diagnosed T1DM revealed significantly decreased LS BMD and decreased bone formation markers when compared to age, height, and pubertal status matched controls [31]. This study also revealed that LS BMD was significantly lower in those with longer duration since T1DM diagnosis, indicating that diabetes may hamper acquisition of peak bone density during development. Similarly, a cross sectional study conducted in Caucasian children and adolescents with and without T1DM related complications found that duration of diabetes in years was negatively associated with both LS and total body BMD [32]. Bone turnover markers were negatively associated with hemoglobin A1C (HgbA1C) in this study, indicating a potential beneficial role of improved glucose control on bone growth. An additional case control study conducted on 86 younger participants (mean age 27.2) with T1DM, BMD at the total body and LS sites were significantly decreased compared to controls [33]. These findings must be interpreted with caution however, since children with chronic illnesses may have delayed puberty and therefore may not have the same bone size as controls, a factor which could lead to the appearance of significantly lower BMD [34].

In T2DM many studies have not found decreased BMD and some have shown paradoxically increased BMD. In the Women’s Health Initiative women with T2DM had statistically significant increases in BMD at the spine and hip compared to women without diabetes throughout 9 years of follow up [9]. Other studies have shown increased BMD at the lumbar spine and hip in men and women with T2DM who were not using insulin [35], and increased BMD at the hip and forearm in women with T2DM [26]. One meta-analysis found that in T2DM a composite Z score was 0.41 higher at the spine and 0.27 at the hip than in non-diabetic controls. The same study performed a meta-regression analysis and found that BMI was a predictor of bone density in T2DM but not T1DM [22]. Increased BMI has well established associations with development of T2DM [3639] and weight is also associated with increased bone density at weight bearing sites [4042]. However some studies have shown that fracture risk in T2DM is independent of BMI or weight and height [9, 18], and BMD [18, 19, 43] which may indicate that the combined adverse effects of T2DM on bone may overwhelm any of the potential protective benefits from increased bone density.

One analysis of the osteoporotic fractures in men study evaluated volumetric bone mineral density (vBMD) and estimated bone strength using polar strength strain index and section modulus derived from peripheral quantitative computed tomography (pQCT). Older men with T2DM had bone strength that is low despite no difference in cortical vBMD [44], a finding that could imply that normal BMD should not be considered clinically reassuring in diabetes. Other studies have found that the presence of microvascular disease was associated with deficits in microarchitecture of bone, specifically of cortical and trabecular vBMD in T1DM [45] and cortical bone in T2DM [46], which may be driven by high cortical porosity [47]. These structural changes could partly explain the excess fracture risk in these populations.

T1DM and T2DM appear to interact differently with BMD. T1DM may contribute to low BMD, perhaps due to younger age at onset affecting growth of bone and peak bone mass. Increased weight and BMI, a common pathway for both increased BMD and development of T2DM may account for the increased BMD in T2DM. High BMD in T2DM is not entirely protective however, and bone strength may actually be lower than what is predicted for BMD. The microvascular changes of diabetes have been associated with microarchitectural bone defects, which may lead to bone fragility.

Mechanisms for increased fracture risk in diabetes

Shared mechanisms for increased fracture risk in both T1DM and T2DM include accumulation of advanced glycation end-products (AGEs) [4851], chronic hyperglycemia, poor blood glucose control [43, 52], hypercalciuria [53] and high propensity for falls [54, 55]. AGEs are permanently deposited glyco-oxidation products whose formation is thought to be stimulated by intracellular hyperglycemia [56]. AGEs can form cross-links with proteins like collagen that affect their structure and functions [49]. A growing body of evidence indicates that AGEs play a crucial role in the progression of classical diabetes complications [57] and diabetic osteopathy. Collagen is a prominent component of bone and when AGEs such as pentosidine and carboxymethyl lysine are produced in collagen fibers, bone strength deteriorates [5861], which is one potential explanation for why the increased fracture risk in T1DM and T2DM appears to be independent of BMD [51, 62, 63]. Elevated glucose levels accelerate AGE formation [64] and so diabetes control could be an important determinant of bone fragility. Hyperglycemia has direct effects on bone cells as well, inhibiting osteoclastogenesis [65].

Diabetes is associated with decreased bone turnover which could have deleterious effects on bone health. Rodent models of insulin deficiency can have decreased bone growth and turnover driven by decreased osteoblast recruitment. This phenotype can be partially corrected by administration of insulin like growth factor-1 (IGF-1) [66]. In T1DM and in the late stages of T2DM, insulin deficiency could impair bone homeostasis through dysregulation of the growth hormone-IGF-1 axis [53]. Pooled data has shown that bone formation markers such as osteocalcin, procollagen type 1 amino terminal pro-peptide and bone resorption markers such as C-terminal cross-linked telopeptide were significantly lower among those with diabetes and did not necessarily correlate with glucose level [67]. It has been suggested that diabetes mellitus should be considered a state of low bone turnover, perhaps driven by increased serum levels of sclerostin and osteoprotegerin which are known to inhibit osteoblast and osteoclast differentiation respectively [68].

The microvascular complications of diabetes mellitus have been associated with an increased propensity for falls, which could partially explain increases in skeletal fractures. In a cohort of well-functioning older adults, diabetes-related complications of reduced peripheral nerve function, poor vision, and decreased renal function were all associated with increased risk of falls. The study further suggested that even a modest decline of renal function could account for increased fall risk through lower muscle strength and nerve function from lower levels of active vitamin D [54]. The Study of Osteoporotic Fractures revealed an increased risk of falls in women with diabetes, especially in those treated with insulin, who had more than double the risk of having multiple falls than women without diabetes [55] . Poor balance and peripheral neuropathy were found to be important risk factors associated with falls in this study.

Glucose control, length of disease and fracture risk

Given the potential mechanisms described above one would expect that the higher glucose levels from poor diabetes control and longer exposure to diabetes may result in increased fracture risk. This principle has been borne out in several studies. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial randomized participants with T2DM to intensive or standard glycemic control strategies. Those in the intensive glycemia group achieved a median HgbA1C of 6.4% as compared to 7.5% in the standard glycemia group. They found that intensive glycemic control was not significantly associated with fracture or fall risk compared with standard therapy [69]. In the Health in Aging and Body Composition prospective cohort study adults 70–79 years old with T2DM (HgbA1C > 7%) were found to have a 64% increased risk of incident clinical fractures while those with Impaired Fasting Glucose, an intermediate state of abnormal glucose metabolism between normal glucose homeostasis and diabetes, did not have significantly increased risk. In this study participants with T2DM had reduced peripheral sensation, lower lean mass, more falls and lower total hip bone density, highlighting diabetic complications as important considerations in the elderly individuals with T2DM [70]. A community-based prospective cohort study stratified participants with known diabetes by HgbA1C level and compared the risk of hospitalization due to fracture across a median follow up of 20 years. Participants with HgbA1c ≥8% had a 63% higher risk of hospitalization due to fracture compared with those whose HgbA1C was under 8% [71]. Those with unrecognized diabetes prior to study initiation and pre-diabetes did not have increased hospitalization risk compared to those with HgbA1C under 5.7%. Similarly, a prospective population-based cohort in the Netherlands determined that patients with T2DM and HgbA1C over 7.5% had a 62% increased risk of all types of fractures compared to those with HgbA1C under 7.5% after adjustment for covariates including FN BMD [43]. In the United States (US) NHANES database those with diagnosed diabetes or HgbA1C above 6.5% had a significantly increased risk of non-skull fractures compared to non-diabetes controls but those with pre-diabetes did not have a significantly increased fracture risk [72]. Epidemiological data from the National Diabetes Care Program in Taiwan revealed that among 20,025 patients with T2DM aged 65 years or older the risk of hip fracture appeared to increase in a dose-response relationship with each 1% HgbA1C increase above 8%, compared to those with HgbA1C of 6–7%. The increased hip fracture risk was maintained after adjustment for co-variates among patients with HgbA1C levels in the 9–10% range and those with HgbA1C above 10%, suggesting that fracture risk may be increased commensurate to the magnitude of poor glucose control [52]. Similar findings were noted in patients with T1DM in the THIN study where each 1% greater average HgbA1C level was associated with a 5% greater risk of incident fractures in males and 11% greater risk in females [15]. In this study, diabetic neuropathy and retinopathy were found to be risk factors for fracture in males but only diabetic neuropathy was significant in females.

Longer duration of diabetes appears to increase fracture risk as well. In the Nurses’ Health study there was a significant trend for greater fracture risk with increased duration of diabetes. Fracture risk was increased by 200% with diabetes duration over 12 years [14]. In a cohort of 82,094 diabetic adults in Manitoba, Canada diabetes duration of over 5 years increased the risk of combined hip, wrist and spine fractures compared to age and sex matched controls. Interestingly, newly diagnosed diabetes was found to significantly reduce the risk of fracture in this cohort [73]. In a prospective study of the residents of Blue Mountains in Australia diabetes duration over 10 years was also significantly associated with all fractures [74].

Poor glucose control and longer exposure to hyperglycemia are known to lead to increased AGEs and the development of the microvascular complications of diabetes including retinopathy, neuropathy and nephropathy [56, 75, 76] which have been associated with microarchitectural changes in bone as previously discussed. These mechanisms may be leading to bone fragility. More data from large prospective cohorts are needed to evaluate the direct effects of microvascular complications on fracture risk. It seems that fracture risk is lower in patients with HgbA1C under 7.5% and may increase as HgbA1C climbs over 8%. However, it appears that improvement beyond reasonable control (HgbA1C around 7.5%) may not lead to additional benefit. While initially T2DM may be protective for fracture, possibly due to hyperinsulinemia through insulin’s homology with IGF-1 causing increased bone strength [53, 77], longer exposure of diabetes is associated with increased fracture risk.

Glucose-lowering medications and fracture risk

Medications used to treat diabetes mellitus can modulate fracture risk. Treatment with thiazolidinediones increased risk of fractures in women with T2DM independent of age and duration of exposure [78, 79]. Thiazolidinediones activate peroxisome proliferator-activated receptors (PPARs) which are factors that promote adipogenesis. Mesenchymal stem cells (MSC) are the common precursors of adipocytes and osteoblasts and PPARγ is an important regulator of MSC differentiation [80]. The increased fracture risk with thiazolidinediones could be due to activation of PPARγ shifting differentiation of MSCs towards adipogenesis and away from osteogenesis through the suppression of key osteogenic transcription factors. Insulin and sulfonylurea use has also been associated with increased fracture risk [81, 82] a finding which could be partially explained by the higher incidence of hypoglycemic events and risk of falls [54, 82]. Metformin has been shown to have a positive or neutral effect on BMD and fracture risk [21]. Sodium glucose co-transporter-2 (SGLT-2) inhibitors such as dapaglifozin did not impact bone turnover markers or BMD [83]. Canaglifozin has been associated with bone loss and increased fracture risk at the hip [84]. More studies are needed to clarify the SGLT-2 class effect on bone fracture risk. Clinical evidence is lacking for dipeptidyl peptidase-4 inhibitors and glucagon like peptide-1 analogs [85].

Fracture risk stratification for diabetes

FRAX is a useful but imperfect tool for fracture risk stratification [86]. Osteoporosis guidelines in the US and UK recommend its use in treatment algorithms [2, 87, 88]. FRAX has been shown to underestimate major osteoporotic fracture and hip fracture risk in patients with diabetes [10, 89]. The University of Manitoba group has made great contributions in determining the effects of diabetes on fracture risk stratification with FRAX. They have shown that the effect of diabetes is independent of other FRAX risk factors, but appears to be more important for hip fracture prediction in younger individuals [90]. Duration of diabetes was associated with hip fracture independent of FRAX scores in a dose dependent fashion, but was associated with increased major osteoporotic fracture risk only at 10 years duration [91]. One strategy to modify FRAX scores to more accurately reflect the estimated fracture risk in diabetes is to include rheumatoid arthritis as a proxy for diabetes since they have similar effects on the FRAX algorithm [92]. Trabecular bone score (TBS) is a technology that when applied to bone density by DXA in the lumbar spine, predicts fractures [93] and identifies a greater proportion of those at risk than BMD in T2DM [94]. TBS can be used with FRAX to improve fracture prediction [95] and may be useful in T2DM, but is not commonly available in many clinical practices.

Conclusions

Type 1 and Type 2 diabetes mellitus both increase the risk of skeletal fracture, particularly at the hip. The etiology of diabetes determines its effects on BMD. Type 1 diabetes is associated with BMD decrease while T2DM is associated with normal to increased BMD. T1DM and T2DM have common mechanisms such as AGEs deposition and bone microarchitectural defects where cortical bone appears to be particularly affected. The increased fracture risk in DM is independent of FRAX and must be considered when risk stratifying patients in clinical practice. Diabetes mellitus should be considered an important fracture risk factor.

Abbreviations

AGEs: 

Advanced glycation end products

BMD: 

Bone mineral density

FN: 

Femoral neck

HgbA1C: 

Hemoglobin A1C

HR: 

Hazard ratio

IGF-1: 

Insulin like growth factor-1

LS: 

Lumbar spine

PPAR: 

Peroxisome proliferator-activated receptors

SGLT-2: 

Sodium glucose co-transporter-2

T1DM: 

Type 1 diabetes mellitus

T2DM: 

Type 2 diabetes mellitus

TH: 

Total hip

THIN: 

The Health Improvement Network

vBMD: 

Volumetric bone mineral density

MSC: 

Mesenchymal stem cells

TBS: 

Trabecular bone score

US: 

United States

UK: 

United Kingdom

Declarations

Authors’ contributions

Conception and design of the article: RJV. Drafted the manuscript: RJV, MIL. Revised it critically for important intellectual content: RJV. Final approval of the version to be published: RJV, MIL.

Ethics approval and consent to participate

Not applicable.

Competing interests

The authors have no financial or non-financial competing interests to report.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
University of Miami Miller School of Medicine, Dominion Tower 1400 NW 10th Ave, Ste. 805A, Miami, FL 33136, USA

References

  1. Dawson-Hughes B, Committee NOFG. A revised clinician’s guide to the prevention and treatment of osteoporosis. The Journal of Clinical Endocrinology & Metabolism. 2008;93(7):2463–5.View ArticleGoogle Scholar
  2. Compston J, Cooper A, Cooper C, Francis R, Kanis JA, Marsh D, McCloskey EV, Reid DM, Selby P, Wilkins M, et al. Guidelines for the diagnosis and management of osteoporosis in postmenopausal women and men from the age of 50 years in the UK. Maturitas. 2009;62(2):105–8.View ArticlePubMedGoogle Scholar
  3. Adler RA. Osteoporosis in men: a review. Bone Res. 2014;2:14001.View ArticlePubMedPubMed CentralGoogle Scholar
  4. Kiebzak GM, Beinart GA, Perser K, Ambrose CG, Siff SJ, Heggeness MH. Undertreatment of osteoporosis in men with hip fracture. Arch Intern Med. 2002;162(19):2217–22.View ArticlePubMedGoogle Scholar
  5. Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A, Tosteson A. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005–2025. J Bone Miner Res. 2007;22(3):465–75.View ArticlePubMedGoogle Scholar
  6. Zimmet P, Alberti K, Shaw J. Global and societal implications of the diabetes epidemic. Nature. 2001;414(6865):782–7.View ArticlePubMedGoogle Scholar
  7. Cheng D. Prevalence, predisposition and prevention of type II diabetes. Nutrition & metabolism. 2005;2(1):29.View ArticleGoogle Scholar
  8. Chen L, Magliano DJ, Zimmet PZ. The worldwide epidemiology of type 2 diabetes mellitus—present and future perspectives. Nat Rev Endocrinol. 2012;8(4):228–36.View ArticleGoogle Scholar
  9. Bonds DE, Larson JC, Schwartz AV, Strotmeyer ES, Robbins J, Rodriguez BL, Johnson KC, Margolis KL. Risk of fracture in women with type 2 diabetes: the Women’s health initiative observational study. The Journal of clinical endocrinology & metabolism. 2006;91(9):3404–10.View ArticleGoogle Scholar
  10. Schwartz AV, Vittinghoff E, Bauer DC, Hillier TA, Strotmeyer ES, Ensrud KE, Donaldson MG, Cauley JA, Harris TB, Koster A. Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes. JAMA. 2011;305(21):2184–92.View ArticlePubMedPubMed CentralGoogle Scholar
  11. De Liefde I, Van der Klift M, De Laet C, Van Daele P, Hofman A, Pols H. Bone mineral density and fracture risk in type-2 diabetes mellitus: the Rotterdam study. Osteoporos Int. 2005;16(12):1713–20.View ArticlePubMedGoogle Scholar
  12. Patterson CC, Dahlquist GG, Gyürüs E, Green A, Soltész G, Group ES. Incidence trends for childhood type 1 diabetes in Europe during 1989–2003 and predicted new cases 2005–20: a multicentre prospective registration study. Lancet. 2009;373(9680):2027–33.View ArticlePubMedGoogle Scholar
  13. Miao J, Brismar K, Nyrén O, Ugarph-Morawski A, Ye W. Elevated hip fracture risk in type 1 diabetic patients. Diabetes Care. 2005;28(12):2850–5.View ArticlePubMedGoogle Scholar
  14. Janghorbani M, Feskanich D, Willett WC, Hu F. Prospective study of diabetes and risk of hip fracture. Diabetes Care. 2006;29(7):1573–8.View ArticlePubMedGoogle Scholar
  15. Weber DR, Haynes K, Leonard MB, Willi SM, Denburg MR. Type 1 diabetes is associated with an increased risk of fracture across the life span: a population-based cohort study using the health improvement network (THIN). Diabetes Care. 2015;38(10):1913–20.View ArticlePubMedPubMed CentralGoogle Scholar
  16. Zhukouskaya VV, Eller-Vainicher C, Vadzianava VV, Shepelkevich AP, Zhurava IV, Korolenko GG, Salko OB, Cairoli E, Beck-Peccoz P, Chiodini I. Prevalence of morphometric vertebral fractures in patients with type 1 diabetes. Diabetes Care. 2013;36(6):1635–40.View ArticlePubMedPubMed CentralGoogle Scholar
  17. Chen H-F, Ho C-A, Li C-Y. Increased risks of hip fracture in diabetic patients of Taiwan. Diabetes Care. 2008;31(1):75–80.View ArticlePubMedGoogle Scholar
  18. Schwartz AV, Sellmeyer DE, Ensrud KE, Cauley JA, Tabor HK, Schreiner PJ, Jamal SA, Black DM, Cummings SR. Older women with diabetes have an increased risk of fracture: a prospective study. The Journal of clinical endocrinology & metabolism. 2001;86(1):32–8.View ArticleGoogle Scholar
  19. Yamamoto M, Yamaguchi T, Yamauchi M, Kaji H, Sugimoto T. Diabetic patients have an increased risk of vertebral fractures independent of BMD or diabetic complications. J Bone Miner Res. 2009;24(4):702–9.View ArticlePubMedGoogle Scholar
  20. Hanley D, Brown J, Tenenhouse A, Olszynski W, Ioannidis G, Berger C, Prior J, Pickard L, Murray T, Anastassiades T. Associations among disease conditions, bone mineral density, and prevalent vertebral deformities in men and women 50 years of age and older: cross-sectional results from the Canadian multicentre osteoporosis study. J Bone Miner Res. 2003;18(4):784–90.View ArticlePubMedGoogle Scholar
  21. Vestergaard P, Rejnmark L, Mosekilde L. Relative fracture risk in patients with diabetes mellitus, and the impact of insulin and oral antidiabetic medication on relative fracture risk. Diabetologia. 2005;48(7):1292–9.View ArticlePubMedGoogle Scholar
  22. Vestergaard P. Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes—a meta-analysis. Osteoporos Int. 2007;18(4):427–44.View ArticlePubMedGoogle Scholar
  23. Janghorbani M, Van Dam RM, Willett WC, Hu FB. Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol. 2007;166(5):495–505.View ArticlePubMedGoogle Scholar
  24. Strotmeyer ES, Cauley JA, Orchard TJ, Steenkiste AR, Dorman JS. Middle-aged premenopausal women with type 1 diabetes have lower bone mineral density and calcaneal quantitative ultrasound than nondiabetic women. Diabetes Care. 2006;29(2):306–11.View ArticlePubMedGoogle Scholar
  25. Miazgowski T, Pynka S, Noworyta-Ziętara M, Krzyzanowska-Świniarska B, Pikul R. Bone mineral density and hip structural analysis in type 1 diabetic men. Eur J Endocrinol. 2007;156(1):123–7.View ArticlePubMedGoogle Scholar
  26. Rakic V, Davis W, Chubb S, Islam F, Prince R, Davis T. Bone mineral density and its determinants in diabetes: the Fremantle diabetes study. Diabetologia. 2006;49(5):863.View ArticlePubMedGoogle Scholar
  27. Kayath MJ, Dib SA, Vieira JH. Prevalence and magnitude of osteopenia associated with insulin-dependent diabetes mellitus. J Diabetes Complicat. 1994;8(2):97–104.View ArticlePubMedGoogle Scholar
  28. Rix M, Andreassen H, Eskildsen P. Impact of peripheral neuropathy on bone density in patients with type 1 diabetes. Diabetes Care. 1999;22(5):827–31.View ArticlePubMedGoogle Scholar
  29. Clausen P, Feldt-Rasmussen B, Jacobsen P, Rossing K, Parving HH, Nielsen P, Feldt-Rasmussen U, Olgaard K. Microalbuminuria as an early indicator of osteopenia in male insulin-dependent diabetic patients. Diabet Med. 1997;14(12):1038–43.View ArticlePubMedGoogle Scholar
  30. Eller-Vainicher C, Zhukouskaya VV, Tolkachev YV, Koritko SS, Cairoli E, Grossi E, Beck-Peccoz P, Chiodini I, Shepelkevich AP. Low bone mineral density and its predictors in type 1 diabetic patients evaluated by the classic statistics and artificial neural network analysis. Diabetes Care. 2011;34(10):2186–91.View ArticlePubMedPubMed CentralGoogle Scholar
  31. Gunczler P, Lanes R, Paoli M, Martinis R, Villaroel O, Weisinger J. Decreased bone mineral density and bone formation markers shortly after diagnosis of clinical type 1 diabetes mellitus. J Pediatr Endocrinol Metab. 2001;14(5):525–8.View ArticlePubMedGoogle Scholar
  32. Tsentidis C, Gourgiotis D, Kossiva L, Doulgeraki A, Marmarinos A, Galli-Tsinopoulou A, Karavanaki K. Higher levels of s-RANKL and osteoprotegerin in children and adolescents with type 1 diabetes mellitus may indicate increased osteoclast signaling and predisposition to lower bone mass: a multivariate cross-sectional analysis. Osteoporos Int. 2016;27(4):1631–43.View ArticlePubMedGoogle Scholar
  33. Bhagwat N. A study of bone mineral density and its determinants in type 1 diabetes mellitus. J Osteoporos. 2013;Google Scholar
  34. Bachrach LK, Sills IN. Bone densitometry in children and adolescents. Pediatrics. 2011;127(1):189–94.View ArticlePubMedGoogle Scholar
  35. van Daele PL, Stolk RP, Burger H, Algra D, Grobbee DE, Hofman A, Birkenhager JC, Pols HA. Bone density in non-insulin-dependent diabetes mellitus: the Rotterdam study. Ann Intern Med. 1995;122(6):409–14.View ArticlePubMedGoogle Scholar
  36. Narayan KV, Boyle JP, Thompson TJ, Gregg EW, Williamson DF. Effect of BMI on lifetime risk for diabetes in the US. Diabetes Care. 2007;30(6):1562–6.View ArticlePubMedGoogle Scholar
  37. Kodama S, Horikawa C, Fujihara K, Heianza Y, Hirasawa R, Yachi Y, Sugawara A, Tanaka S, Shimano H, Iida KT. Comparisons of the strength of associations with future type 2 diabetes risk among anthropometric obesity indicators, including waist-to-height ratio: a meta-analysis. Am J Epidemiol. 2012;176(11):959–69.View ArticlePubMedGoogle Scholar
  38. Ganz ML, Wintfeld N, Li Q, Alas V, Langer J, Hammer M. The association of body mass index with the risk of type 2 diabetes: a case–control study nested in an electronic health records system in the United States. Diabetology & metabolic syndrome. 2014;6(1):50.View ArticleGoogle Scholar
  39. Schienkiewitz A, Schulze MB, Hoffmann K, Kroke A, Boeing H. Body mass index history and risk of type 2 diabetes: results from the European prospective investigation into Cancer and nutrition (EPIC)–Potsdam study. Am J Clin Nutr. 2006;84(2):427–33.PubMedGoogle Scholar
  40. Felson DT, Zhang Y, Hannan MT, Anderson JJ. Effects of weight and body mass index on bone mineral density in men and women: the Framingham study. J Bone Miner Res. 1993;8(5):567–73.View ArticlePubMedGoogle Scholar
  41. Edelstein SL, Barrett-Connor E. Relation between body size and bone mineral density in elderly men and women. Am J Epidemiol. 1993;138(3):160–9.View ArticlePubMedGoogle Scholar
  42. Morin S, Tsang J, Leslie W. Weight and body mass index predict bone mineral density and fractures in women aged 40 to 59 years. Osteoporos Int. 2009;20(3):363–70.View ArticlePubMedGoogle Scholar
  43. Oei L, Zillikens MC, Dehghan A, Buitendijk GH, Castaño-Betancourt MC, Estrada K, Stolk L, Oei EH, van Meurs JB, Janssen JA. High bone mineral density and fracture risk in type 2 diabetes as skeletal complications of inadequate glucose control. Diabetes Care. 2013;36(6):1619–28.View ArticlePubMedPubMed CentralGoogle Scholar
  44. Petit MA, Paudel ML, Taylor BC, Hughes JM, Strotmeyer ES, Schwartz AV, Cauley JA, Zmuda JM, Hoffman AR, Ensrud KE. Bone mass and strength in older men with type 2 diabetes: the osteoporotic fractures in men study. J Bone Miner Res. 2010;25(2):285–91.View ArticlePubMedGoogle Scholar
  45. Shanbhogue VV, Hansen S, Frost M, Jorgensen NR, Hermann AP, Henriksen JE, Brixen K. Bone geometry, volumetric density, microarchitecture, and estimated bone strength assessed by HR-pQCT in adult patients with type 1 diabetes mellitus. J Bone Miner Res. 2015;30(12):2188–99.View ArticlePubMedGoogle Scholar
  46. Burghardt AJ, Issever AS, Schwartz AV, Davis KA, Masharani U, Majumdar S, Link TM. High-resolution peripheral quantitative computed tomographic imaging of cortical and trabecular bone microarchitecture in patients with type 2 diabetes mellitus. The Journal of Clinical Endocrinology & Metabolism. 2010;95(11):5045–55.View ArticleGoogle Scholar
  47. Shanbhogue VV, Hansen S, Frost M, Jørgensen NR, Hermann AP, Henriksen JE, Brixen K. Compromised cortical bone compartment in type 2 diabetes mellitus patients with microvascular disease. Eur J Endocrinol. 2016;174(2):115–24.View ArticlePubMedGoogle Scholar
  48. Paul R, Bailey A. Glycation of collagen: the basis of its central role in the late complications of ageing and diabetes. Int J Biochem Cell Biol. 1996;28(12):1297–310.View ArticlePubMedGoogle Scholar
  49. Bos DC, de Ranitz-Greven WL, de Valk HW. Advanced glycation end products, measured as skin autofluorescence and diabetes complications: a systematic review. Diabetes Technol Ther. 2011;13(7):773–9.View ArticlePubMedGoogle Scholar
  50. Furst JR, Bandeira LC, Fan W-W, Agarwal S, Nishiyama KK, McMahon DJ, Dworakowski E, Jiang H, Silverberg SJ, Rubin MR. Advanced glycation endproducts and bone material strength in type 2 diabetes. The Journal of Clinical Endocrinology & Metabolism. 2016;101(6):2502–10.View ArticleGoogle Scholar
  51. Neumann T, Lodes S, Kästner B, Franke S, Kiehntopf M, Lehmann T, Müller U, Wolf G, Sämann A. High serum pentosidine but not esRAGE is associated with prevalent fractures in type 1 diabetes independent of bone mineral density and glycaemic control. Osteoporos Int. 2014;25(5):1527–33.View ArticlePubMedGoogle Scholar
  52. Li CI, Liu CS, Lin WY, Meng NH, Chen CC, Yang SY, Chen HJ, Lin CC, Li TC. Glycated hemoglobin level and risk of hip fracture in older people with type 2 diabetes: a competing risk analysis of Taiwan diabetes cohort study. J Bone Miner Res. 2015;30(7):1338–46.View ArticlePubMedGoogle Scholar
  53. Thrailkill KM, Lumpkin CK, Bunn RC, Kemp SF, Fowlkes JL. Is insulin an anabolic agent in bone? Dissecting the diabetic bone for clues. American journal of physiology-endocrinology and metabolism. 2005;289(5):E735–45.View ArticlePubMedPubMed CentralGoogle Scholar
  54. Schwartz AV, Vittinghoff E, Sellmeyer DE, Feingold KR, De Rekeneire N, Strotmeyer ES, Shorr RI, Vinik AI, Odden MC, Park SW. Diabetes-related complications, glycemic control, and falls in older adults. Diabetes Care. 2008;31(3):391–6.View ArticlePubMedGoogle Scholar
  55. Schwartz AV, Hillier TA, Sellmeyer DE, Resnick HE, Gregg E, Ensrud KE, Schreiner PJ, Margolis KL, Cauley JA, Nevitt MC. Older women with diabetes have a higher risk of falls. Diabetes Care. 2002;25(10):1749–54.View ArticlePubMedGoogle Scholar
  56. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414(6865):813–20.View ArticlePubMedGoogle Scholar
  57. Goh S-Y, Cooper ME. The role of advanced glycation end products in progression and complications of diabetes. The Journal of Clinical Endocrinology & Metabolism. 2008;93(4):1143–52.View ArticleGoogle Scholar
  58. Karim L, Vashishth D. Heterogeneous glycation of cancellous bone and its association with bone quality and fragility. PLoS One. 2012;7(4):e35047.View ArticlePubMedPubMed CentralGoogle Scholar
  59. Hernandez CJ, Tang SY, Baumbach BM, Hwu PB, Sakkee AN, van der Ham F, DeGroot J, Bank RA, Keaveny TM. Trabecular microfracture and the influence of pyridinium and non-enzymatic glycation-mediated collagen cross-links. Bone. 2005;37(6):825–32.View ArticlePubMedPubMed CentralGoogle Scholar
  60. Saito M, Fujii K, Marumo K. Degree of mineralization-related collagen crosslinking in the femoral neck cancellous bone in cases of hip fracture and controls. Calcif Tissue Int. 2006;79(3):160–8.View ArticlePubMedGoogle Scholar
  61. Yamamoto M, Yamaguchi T, Yamauchi M, Yano S, Sugimoto T. Serum pentosidine levels are positively associated with the presence of vertebral fractures in postmenopausal women with type 2 diabetes. The Journal of Clinical Endocrinology & Metabolism. 2008;93(3):1013–9.View ArticleGoogle Scholar
  62. Yamamoto M, Yamaguchi T, Yamauchi M, Sugimoto T. Low serum level of the endogenous secretory receptor for advanced glycation end products (esRAGE) is a risk factor for prevalent vertebral fractures independent of bone mineral density in patients with type 2 diabetes. Diabetes Care. 2009;32(12):2263–8.View ArticlePubMedPubMed CentralGoogle Scholar
  63. Schwartz AV, Garnero P, Hillier TA, Sellmeyer DE, Strotmeyer ES, Feingold KR, Resnick HE, Tylavsky FA, Black DM, Cummings SR. Pentosidine and increased fracture risk in older adults with type 2 diabetes. The Journal of Clinical Endocrinology & Metabolism. 2009;94(7):2380–6.View ArticleGoogle Scholar
  64. Yan SF, Ramasamy R, Schmidt AM. Mechanisms of disease: advanced glycation end-products and their receptor in inflammation and diabetes complications. Nat Rev Endocrinol. 2008;4(5):285–93.View ArticleGoogle Scholar
  65. Wittrant Y, Gorin Y, Woodruff K, Horn D, Abboud H, Mohan S, Abboud-Werner S. High d (+) glucose concentration inhibits RANKL-induced osteoclastogenesis. Bone. 2008;42(6):1122–30.View ArticlePubMedPubMed CentralGoogle Scholar
  66. Verhaeghe J, Suiker A, Visser W, Van Herck E, Van Bree R, Bouillon R. The effects of systemic insulin, insulin-like growth factor-I and growth hormone on bone growth and turnover in spontaneously diabetic BB rats. J Endocrinol. 1992;134(3):485–92.View ArticlePubMedGoogle Scholar
  67. Starup-Linde J, Eriksen S, Lykkeboe S, Handberg A, Vestergaard P. Biochemical markers of bone turnover in diabetes patients—a meta-analysis, and a methodological study on the effects of glucose on bone markers. Osteoporos Int. 2014;25(6):1697–708.View ArticlePubMedGoogle Scholar
  68. Hygum K, Starup-Linde J, Harsløf T, Vestergaard P, Langdahl BL. Mechanisms in endocrinology: diabetes mellitus, a state of low bone turnover–a systematic review and meta-analysis. Eur J Endocrinol. 2017;176(3):R137–57.View ArticlePubMedGoogle Scholar
  69. Schwartz AV, Margolis KL, Sellmeyer DE, Vittinghoff E, Ambrosius WT, Bonds DE, Josse RG, Schnall AM, Simmons DL, Hue TF. Intensive glycemic control is not associated with fractures or falls in the ACCORD randomized trial. Diabetes Care. 2012;35(7):1525–31.View ArticlePubMedPubMed CentralGoogle Scholar
  70. Strotmeyer ES, Cauley JA, Schwartz AV, Nevitt MC, Resnick HE, Bauer DC, Tylavsky FA, de Rekeneire N, Harris TB, Newman AB. Nontraumatic fracture risk with diabetes mellitus and impaired fasting glucose in older white and black adults: the health, aging, and body composition study. Arch Intern Med. 2005;165(14):1612–7.View ArticlePubMedGoogle Scholar
  71. Schneider AL, Williams EK, Brancati FL, Blecker S, Coresh J, Selvin E. Diabetes and risk of fracture-related hospitalization. Diabetes Care. 2013;36(5):1153–8.View ArticlePubMedPubMed CentralGoogle Scholar
  72. Looker AC, Eberhardt MS, Saydah SH. Diabetes and fracture risk in older US adults. Bone. 2016;82:9–15.View ArticlePubMedGoogle Scholar
  73. Leslie WD, Lix LM, Prior HJ, Derksen S, Metge C, O'Neil J. Biphasic fracture risk in diabetes: a population-based study. Bone. 2007;40(6):1595–601.View ArticlePubMedGoogle Scholar
  74. Ivers RQ, Cumming RG, Mitchell P, Peduto AJ. Diabetes and risk of fracture. Diabetes Care. 2001;24(7):1198–203.View ArticlePubMedGoogle Scholar
  75. Fowler MJ. Microvascular and macrovascular complications of diabetes. Clinical diabetes. 2008;26(2):77–82.View ArticleGoogle Scholar
  76. Forbes JM, Cooper ME. Mechanisms of diabetic complications. Physiol Rev. 2013;93(1):137–88.View ArticlePubMedGoogle Scholar
  77. Fukunaga Y, Minamikawa J, Inoue D, Koshiyama H. Does insulin use increase bone mineral density in patients with non—insulin-dependent diabetes mellitus? Arch Intern Med. 1997;157(22):2668–9.View ArticlePubMedGoogle Scholar
  78. Zhu Z-N, Jiang Y-F, Ding T. Risk of fracture with thiazolidinediones: an updated meta-analysis of randomized clinical trials. Bone. 2014;68:115–23.View ArticlePubMedGoogle Scholar
  79. Loke YK, Singh S, Furberg CD. Long-term use of thiazolidinediones and fractures in type 2 diabetes: a meta-analysis. Can Med Assoc J. 2009;180(1):32–9.View ArticleGoogle Scholar
  80. Kawai M, Rosen CJ. PPARγ: a circadian transcription factor in adipogenesis and osteogenesis. Nat Rev Endocrinol. 2010;6(11):629.View ArticlePubMedPubMed CentralGoogle Scholar
  81. Monami M, Cresci B, Colombini A, Pala L, Balzi D, Gori F, Chiasserini V, Marchionni N, Rotella CM, Mannucci E. Bone fractures and hypoglycemic treatment in type 2 diabetic patients. Diabetes Care. 2008;31(2):199–203.View ArticlePubMedGoogle Scholar
  82. Lapane KL, Yang S, Brown MJ, Jawahar R, Pagliasotti C, Rajpathak S. Sulfonylureas and risk of falls and fractures: a systematic review. Drugs Aging. 2013;30(7):527–47.View ArticlePubMedGoogle Scholar
  83. Ljunggren Ö, Bolinder J, Johansson L, Wilding J, Langkilde A, Sjöström C, Sugg J, Parikh S. Dapagliflozin has no effect on markers of bone formation and resorption or bone mineral density in patients with inadequately controlled type 2 diabetes mellitus on metformin. Diabetes Obes Metab. 2012;14(11):990–9.View ArticlePubMedGoogle Scholar
  84. Watts NB, Bilezikian JP, Usiskin K, Edwards R, Desai M, Law G, Meininger G. Effects of canagliflozin on fracture risk in patients with type 2 diabetes mellitus. J Clin Endocrinol. 2016;101(1):157–66.View ArticleGoogle Scholar
  85. Mosenzon O, Wei C, Davidson J, Scirica BM, Yanuv I, Rozenberg A, Hirshberg B, Cahn A, Stahre C, Strojek K. Incidence of fractures in patients with type 2 diabetes in the SAVOR-TIMI 53 trial. Diabetes Care. 2015;38(11):2142–50.View ArticlePubMedGoogle Scholar
  86. Kanis JA, Hans D, Cooper C, Baim S, Bilezikian JP, Binkley N, Cauley JA, Compston JE, Dawson-Hughes B, Fuleihan GE-H. Interpretation and use of FRAX in clinical practice. Osteoporos Int. 2011;22(9):2395.View ArticlePubMedGoogle Scholar
  87. Dawson-Hughes B, Tosteson A. Melton Lr, Baim S, Favus M, Khosla S, Lindsay R: implications of absolute fracture risk assessment for osteoporosis practice guidelines in the USA. Osteoporos Int. 2008;19(4):449–58.View ArticlePubMedGoogle Scholar
  88. Cosman F, De Beur S, LeBoff M, Lewiecki E, Tanner B, Randall S, Lindsay R. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int. 2014;25(10):2359–81.View ArticlePubMedPubMed CentralGoogle Scholar
  89. Giangregorio LM, Leslie WD, Lix LM, Johansson H, Oden A, McCloskey E, Kanis JA. FRAX underestimates fracture risk in patients with diabetes. J Bone Miner Res. 2012;27(2):301–8.View ArticlePubMedGoogle Scholar
  90. Leslie W, Morin S, Lix L, Majumdar S. Does diabetes modify the effect of FRAX risk factors for predicting major osteoporotic and hip fracture? Osteoporos Int. 2014;25(12):2817–24.View ArticlePubMedGoogle Scholar
  91. Majumdar SR, Leslie WD, Lix LM, Morin SN, Johansson H, Oden A, McCloskey EV, Kanis JA. Longer duration of diabetes strongly impacts fracture risk assessment: the Manitoba BMD cohort. The Journal of Clinical Endocrinology & Metabolism. 2016;101(11):4489–96.View ArticleGoogle Scholar
  92. Schacter GI, Leslie WD. DXA-based measurements in diabetes: can they predict fracture risk? Calcif Tissue Int. 2017;100(2):150–64.View ArticlePubMedGoogle Scholar
  93. Hans D, Goertzen AL, Krieg MA, Leslie WD. Bone microarchitecture assessed by TBS predicts osteoporotic fractures independent of bone density: the Manitoba study. J Bone Miner Res. 2011;26(11):2762–9.View ArticlePubMedGoogle Scholar
  94. Leslie WD, Aubry-Rozier B, Lamy O, Hans D. TBS (trabecular bone score) and diabetes-related fracture risk. The Journal of Clinical Endocrinology & Metabolism. 2013;98(2):602–9.View ArticleGoogle Scholar
  95. McCloskey EV, Odén A, Harvey NC, Leslie WD, Hans D, Johansson H, Barkmann R, Boutroy S, Brown J, Chapurlat R. A meta-analysis of trabecular bone score in fracture risk prediction and its relationship to FRAX. J Bone Miner Res. 2016;31(5):940–8.View ArticlePubMedGoogle Scholar

Copyright

© The Author(s). 2018

Advertisement