Evaluation of Bone Fragility in Patients with T2DM: History
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Contributor:
José Ignacio Martínez-Montoro
,
Beatriz García-Fontana
,
Cristina García-Fontana
,
Manuel Muñoz-Torres

Bone fragility is a common complication in subjects with type 2 diabetes mellitus (T2DM). However, traditional techniques for the evaluation of bone fragility, such as dual-energy X-ray absorptiometry (DXA), do not perform well in this population. Moreover, the Fracture Risk Assessment Tool (FRAX) usually underestimates fracture risk in T2DM. Importantly, novel technologies for the assessment of one microarchitecture in patients with T2DM, such as the trabecular bone score (TBS), high-resolution peripheral quantitative computed tomography (HR-pQCT), and microindentation, are emerging. Furthermore, different serum and urine bone biomarkers may also be useful for the evaluation of bone quality in T2DM. 

  • type 2 diabetes mellitus
  • bone fragility
  • fracture risk
  • bone structure
  • bone quality

1. Introduction

In the last few decades, type 2 diabetes mellitus (T2DM) has dramatically increased in prevalence worldwide, resulting in significant burdens on patients suffering from this condition and healthcare systems [1]. Of note, the rising prevalence of this disease is associated with the development of a wide range of complications, including retinopathy, nephropathy, neuropathy, and cardiovascular disease [1][2]. These complications often affect the quality of life of patients with T2DM, including their physical and psychological functioning [3]. Although some of these comorbidities have a well-known impact on the quality of life [4][5], others have received less attention [6].
Mounting evidence reveals that bone fragility is common in T2DM [7]. Several studies have shown that T2DM constitutes an independent risk factor for osteoporotic fractures, presenting a particularly strong association with hip fractures [8][9][10][11]. Indeed, a number of meta-analyses have confirmed that T2DM is associated with an increased risk of incident hip, vertebral, and non-vertebral fractures [12][13][14]. Since T2DM has a strong relationship with hip fractures that need replacement surgery using total hip arthroplasty, new techniques have been developed in this field [15][16]. Importantly, increases in the incidence of fractures lead to greater costs and healthcare resource utilization in this population [17]. Moreover, fractures are associated with functional impairment and reduction of health-related quality of life [18][19]. Given the important health and socioeconomic impact of skeletal fragility and fractures, individuals with T2DM, especially those with major diabetes-related determinants and other conventional risk factors for osteoporosis, should be assessed for the presence of bone fragility and their fracture risk [20]. However, traditional imaging techniques and fracture risk assessment tools may not be accurate for this purpose in patients with T2DM [21].

2. Determinants of Skeletal Fragility and Increased Risk of Fracture in T2DM

Several determinants have been identified in the pathogenesis of bone fragility and increased fracture risk in subjects with T2DM [22] (Figure 1). Notably, a longer duration of T2DM was reported to be an independent risk factor for major osteoporotic fractures in women aged ≥40 and with ≥10 years of diabetes duration [23], and a recent meta-analysis showed a greater increase in the risk of both hip and non-vertebral fractures in subjects with longer diabetes duration [13]. Besides this, poor glycemic control is closely linked to fracture risk, as several large-scale population-based cohort studies have demonstrated [24][25][26]. In this regard, the generation of advanced glycation end-products (AGEs) resulting from chronic exposure to hyperglycemia is one of the key mechanisms in the pathophysiology of bone fragility in T2DM [22]. As such, non-enzymatic glycosylation of collagen leads to the formation of collagen-AGEs, which are involved in the development of impaired bone mineralization and quality through different alterations of the extracellular matrix, a reduction of alkaline phosphatase activity in osteoblasts, and an overactivation of the receptor for AGEs (the latter associated with the release of pro-inflammatory cytokines and reactive oxygen species—ROS—by osteoclasts) [22][27]. On the other hand, it is also postulated that the main event related to bone fragility in T2DM is an overall inhibition of bone cells function and decreased bone turnover [22][28]. This effect may be driven in part by insulin resistance [29].
Figure 1. Determinants of bone fragility and increased fracture risk in type 2 diabetes. AGEs, advanced glycation end products.
In addition to chronic hyperglycemia and AGE formation, other mechanisms play a role in bone fragility in T2DM, as previously reviewed [7][22][30]. Among them, a pro-inflammatory state and oxidative stress, along with adipokine dysregulation and marrow adiposity, have a strong influence on bone metabolism [7][30]. Loss of incretin effect has also been implicated in the pathogenesis of skeletal fragility in T2DM [30][31]. Microvascular disease and impaired vascular bone intercommunication determine alterations of bone quality and microarchitecture [7][30]. Ischemic heart disease has also been reported to be associated with an increased risk of vertebral fractures in T2DM [32]. Vitamin D deficiency, commonly found in patients with T2DM, could play a role in both T2DM development and bone fragility [33]. Pathological changes in gut microbiota composition in T2DM may also trigger bone alterations in this population [34].
Further to this, glucose-lowering agents may also be crucial contributors to the reported associations between T2DM and bone fragility [35][36]. The potential benefits of some drugs for bone density and fracture risk (i.e., metformin, glucagon-like peptide 1 receptors agonists and dipeptidyl peptidase-4 inhibitors) [37][38][39] remain to be confirmed in specifically designed studies. Conversely, the long-term use of thiazolidinediones has been independently associated with fracture risk [40], and sodium-glucose cotransporter-2 inhibitors could also have this effect [41][42]. Remarkably, both insulin and sulfonylureas significantly increase fall-related fractures due to episodes of hypoglycemia [43]. In this vein, other prevalent factors in T2DM (i.e., visual impairment, peripheral neuropathy, autonomic dysfunction/postural hypotension, foot ulcers/amputation, and sarcopenia) also lead to an increased risk of fall-related fractures [30][44].

3. Bone Density and Fracture Risk Prediction in T2DM

Despite skeletal fragility and fracture risk being greater in subjects with T2DM, this condition is usually associated with normal or even increased BMD measured by DXA [45]. Thus, women with T2DM in the Women’s Health Initiative Observational Study presented higher hip and spine BMD scores compared to those without T2DM [46]. Similarly, in a cross-sectional study including two Swedish cohorts, both men and women exhibited a progressively higher hip BMD according to normal fasting plasma glucose/impaired fasting plasma glucose/T2DM subgroups [47]. In the prospective population-based cohort from the Rotterdam Study, inadequate glycemic control was associated with both higher BMD and increased fracture risk in participants with T2DM [26]. Furthermore, a meta-analysis of 15 observational studies (3473 subjects with T2DM and 19,139 healthy controls) showed that participants with T2DM had significantly higher BMD at the femoral neck, hip, and spine [48].
It is noteworthy that these results contrast with those reported by studies assessing BMD in type 1 diabetes mellitus (T1DM), in which BMD is generally low [49]. Although the mechanisms involved in the association between T2DM and normal/high BMD are not fully understood, some data suggest that these findings might be related to chronic hyperinsulinemia and insulin resistance [50], as well as the effect of some adipokines, such as leptin, on bone metabolism [51]. Excess weight/obesity, which are often encountered in patients with T2DM, could also play a role in increased BMD, although some studies have reported that this relationship remains after adjusting for the body mass index (BMI) [48]. Since T2DM is associated with increased fracture risk, regardless of whether there is a normal/high BMD, a fact known as “the diabetic paradox of bone fragility” [52], the diagnosis of osteoporosis based on BMD measured by DXA, should be cautiously considered [21].
On the other hand, the Fracture Risk Assessment Tool (FRAX), which is widely used to estimate 10-year absolute fracture risk, has been demonstrated to underestimate the risk for both hip and major osteoporotic fractures in patients with T2DM [53]. These results are influenced, in part, by the higher BMD observed in patients with T2DM [48]. Indeed, contrary to T1DM, T2DM is not included in the FRAX tool as a secondary cause of osteoporosis [54]. In this regard, some authors have proposed a correction factor with the use of glycated hemoglobin in order to improve the predictive ability of this algorithm for fracture risk [55]. Recently, adjustment of FRAX for T2DM has been suggested in order to create a useful alternative [56][57], although further research is warranted to confirm these results. Alternatively, certain methods (i.e., inputting rheumatoid arthritis, adjusting FRAX by TBS, reducing the femoral T-score by 0.5, and increasing the age by 10 years) have been proposed to improve the performance of FRAX in T2DM, although no single method appears to be optimal in all settings [58]. In light of the above, new approaches to the evaluation of bone fragility in patients with T2DM are needed.

4. Bone Microstructure in T2DM

As previously discussed, patients with T2DM have normal or elevated BMD; however, bone microarchitecture alterations may be present in this group, resulting in an increased fracture risk [59]. In this context, the trabecular bone score, high-resolution peripheral quantitative computed tomography, and microindentation are useful techniques for the evaluation of the bone microstructure in T2DM.

5. Bone Quality in T2DM: The Role of Biomarkers of Bone Fragility

In addition to bone mineralization and microarchitecture, skeletal material properties are also influenced by bone turnover and the quality of collagen, which may be affected by the accumulation of AGEs, leading to the alteration of collagen crosslinks and function as discussed in previous sections [22]. In this regard, it has been stated that bone turnover is decreased in T2DM, which results in reduced serum levels of bone remodeling markers [22][60][61][62]. However, it remains unknown whether these biochemical markers may be helpful for the diagnosis of bone fragility or the prediction of fracture risk in patients with T2DM. On the one hand, decreased circulating levels of parathyroid hormone (PTH) along with osteocalcin were shown to be associated with a higher risk of vertebral fracture in postmenopausal women with T2DM [63]. On the contrary, in a recent study, Napoli et al. showed that serum bone turnover markers (terminal telopeptide of type 1 collagen-CTX, osteocalcin, and procollagen type 1 N-terminal propeptide-P1NP) were not able to predict fracture risk in T2DM [64].
On the other hand, AGES related to collagen, such as pentosidine and N-carboxymethyl lysine (CML), are increased in bone biopsy specimens from subjects with T2DM [59][65][66]. Therefore, circulating/urinary levels of these AGEs may become attractive surrogate markers of bone quality in subjects with T2DM. Besides this, other novel biomarkers could play a role in the evaluation of bone fragility in T2DM.

This entry is adapted from the peer-reviewed paper 10.3390/jcm11082206

References

  1. Zheng, Y.; Ley, S.H.; Hu, F.B. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat. Rev. Endocrinol. 2018, 14, 88–98.
  2. Dal Canto, E.; Ceriello, A.; Rydén, L.; Ferrini, M.; Hansen, T.B.; Schnell, O.; Standl, E.; Beulens, J.W. Diabetes as a cardiovascular risk factor: An overview of global trends of macro and micro vascular complications. Eur. J. Prev. Cardiol. 2019, 26 (Suppl. 2), 25–32.
  3. Alaofè, H.; Amoussa Hounkpatin, W.; Djrolo, F.; Ehiri, J.; Rosales, C. Factors Associated with Quality of Life in Patients with Type 2 Diabetes of South Benin: A Cross-Sectional Study. Int. J. Environ. Res. Public Health 2022, 19, 2360.
  4. Fenwick, E.K.; Pesudovs, K.; Khadka, J.; Dirani, M.; Rees, G.; Wong, T.Y.; Lamoureux, E.L. The impact of diabetic retinopathy on quality of life: Qualitative findings from an item bank development project. Qual. Life Res. 2012, 21, 1771–1782.
  5. Degu, H.; Wondimagegnehu, A.; Yifru, Y.M.; Belachew, A. Is health related quality of life influenced by diabetic neuropathic pain among type II diabetes mellitus patients in Ethiopia? PLoS ONE 2019, 14, e0211449.
  6. Sinjari, B.; Feragalli, B.; Cornelli, U.; Belcaro, G.; Vitacolonna, E.; Santilli, M.; Rexhepi, I.; D’Addazio, G.; Zuccari, F.; Caputi, S. Artificial Saliva in Diabetic Xerostomia (ASDIX): Double Blind Trial of Aldiamed® Versus Placebo. J. Clin. Med. 2020, 9, 2196.
  7. Khosla, S.; Samakkarnthai, P.; Monroe, D.G.; Farr, J.N. Update on the pathogenesis and treatment of skeletal fragility in type 2 diabetes mellitus. Nat. Rev. Endocrinol. 2021, 17, 685–697.
  8. Schousboe, J.T.; Morin, S.N.; Kline, G.A.; Lix, L.M.; Leslie, W.D. Differential risk of fracture attributable to type 2 diabetes mellitus according to skeletal site. Bone 2021, 154, 116220.
  9. Wang, B.; Wang, Z.; Poundarik, A.A.; Zaki, M.J.; Bockman, R.S.; Glicksberg, B.S.; Nadkarni, G.N.; Vashishth, D. Unmasking Fracture Risk in Type 2 Diabetes: The Association of Longitudinal Glycemic Hemoglobin Level and Medications. J. Clin. Endocrinol. Metab. 2021, 107, e1390–e1401.
  10. Schwartz, A.V. Epidemiology of fractures in type 2 diabetes. Bone 2016, 82, 2–8.
  11. Koromani, F.; Ghatan, S.; van Hoek, M.; Zillikens, M.C.; Oei, E.H.G.; Rivadeneira, F.; Oei, L. Type 2 Diabetes Mellitus and Vertebral Fracture Risk. Curr. Osteoporos. Rep. 2021, 19, 50–57.
  12. Koromani, F.; Oei, L.; Shevroja, E.; Trajanoska, K.; Schoufour, J.; Muka, T.; Franco, O.H.; Ikram, M.A.; Zillikens, M.C.; Uitterlinden, A.G.; et al. Vertebral Fractures in Individuals with Type 2 Diabetes: More Than Skeletal Complications Alone. Diabetes Care 2020, 43, 137–144.
  13. Vilaca, T.; Schini, M.; Harnan, S.; Sutton, A.; Poku, E.; Allen, I.E.; Cummings, S.R.; Eastell, R. The risk of hip and non-vertebral fractures in type 1 and type 2 diabetes: A systematic review and meta-analysis update. Bone 2020, 137, 115457.
  14. Janghorbani, M.; van Dam, R.M.; Willett, W.C.; Hu, F.B. Systematic Review of Type 1 and Type 2 Diabetes Mellitus and Risk of Fracture. Am. J. Epidemiol. 2007, 166, 495–505.
  15. Ammarullah, M.I.; Afif, I.Y.; Maula, M.I.; Winarni, T.I.; Tauviqirrahman, M.; Akbar, I.; Basri, H.; van der Heide, E.; Jamari, J. Tresca Stress Simulation of Metal-on-Metal Total Hip Arthroplasty during Normal Walking Activity. Materials 2021, 14, 7554.
  16. Jamari, J.; Ammarullah, M.; Saad, A.P.M.; Syahrom, A.; Uddin, M.; van der Heide, E.; Basri, H. The Effect of Bottom Profile Dimples on the Femoral Head on Wear in Metal-on-Metal Total Hip Arthroplasty. J. Funct. Biomater. 2021, 12, 38.
  17. Sato, M.; Ye, W.; Sugihara, T.; Isaka, Y. Fracture risk and healthcare resource utilization and costs among osteoporosis patients with type 2 diabetes mellitus and without diabetes mellitus in Japan: Retrospective analysis of a hospital claims database. BMC Musculoskelet. Disord. 2016, 17, 489.
  18. Shah, A.; Wu, F.; Jones, G.; Cicuttini, F.; Toh, L.S.; Laslett, L.L. The association between incident vertebral deformities, health-related quality of life and functional impairment: A 10.7-year cohort study. Osteoporos. Int. 2021, 32, 2247–2255.
  19. Peeters, C.M.M.; Visser, E.; Van de Ree, C.L.P.; Gosens, T.; Den Oudsten, B.L.; De Vries, J. Quality of life after hip fracture in the elderly: A systematic literature review. Injury 2016, 47, 1369–1382.
  20. Ferrari, S.L.; Abrahamsen, B.; Napoli, N.; Akesson, K.; Chandran, M.; Eastell, R.; El-Hajj Fuleihan, G.; Josse, R.; Kendler, D.L.; Kraenzlin, M.; et al. Diagnosis and management of bone fragility in diabetes: An emerging challenge. Osteoporos. Int. 2018, 29, 2585–2596.
  21. de Waard, E.A.C.; van Geel, T.A.C.M.; Savelberg, H.H.C.M.; Koster, A.; Geusens, P.P.M.M.; van den Bergh, J.P.W. Increased fracture risk in patients with type 2 diabetes mellitus: An overview of the underlying mechanisms and the usefulness of imaging modalities and fracture risk assessment tools. Maturitas 2014, 79, 265–274.
  22. Hofbauer, L.C.; Busse, B.; Eastell, R.; Ferrari, S.; Frost, M.; Müller, R.; Burden, A.M.; Rivadeneira, F.; Napoli, N.; Rauner, M. Bone fragility in diabetes: Novel concepts and clinical implications. Lancet Diabetes Endocrinol. 2022, 10, 207–220.
  23. Majumdar, S.R.; Leslie, W.D.; Lix, L.M.; Morin, S.N.; Johansson, H.; Oden, A.; McCloskey, E.V.; Kanis, J.A. Longer Duration of Diabetes Strongly Impacts Fracture Risk Assessment: The Manitoba BMD Cohort. J. Clin. Endocrinol. Metab. 2016, 101, 4489–4496.
  24. Dufour, A.B.; Kiel, D.P.; Williams, S.A.; Weiss, R.J.; Samelson, E.J. Risk Factors for Incident Fracture in Older Adults with Type 2 Diabetes: The Framingham Heart Study. Diabetes Care 2021, 44, 1547–1555.
  25. Li, C.-I.; Liu, C.-S.; Lin, W.-Y.; Meng, N.-H.; Chen, C.-C.; Yang, S.-Y.; Chen, H.-J.; Lin, C.-C.; Li, T.-C. 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, 1338–1346.
  26. Oei, L.; Zillikens, M.C.; Dehghan, A.; Buitendijk, G.H.S.; Castaño-Betancourt, M.C.; Estrada, K.; Stolk, L.; Oei, E.H.G.; van Meurs, J.B.J.; Janssen, J.A.M.J.L.; et al. High Bone Mineral Density and Fracture Risk in Type 2 Diabetes as Skeletal Complications of Inadequate Glucose Control: The Rotterdam Study. Diabetes Care 2013, 36, 1619–1628.
  27. Romero-Díaz, C.; Duarte-Montero, D.; Gutiérrez-Romero, S.A.; Mendivil, C.O. Diabetes and Bone Fragility. Diabetes Ther. 2020, 12, 71–86.
  28. Starup-Linde, J.; Vestergaard, P. Biochemical bone turnover markers in diabetes mellitus—A systematic review. Bone 2016, 82, 69–78.
  29. Tonks, K.T.; White, C.; Center, J.R.; Samocha-Bonet, D.; Greenfield, J. Bone Turnover Is Suppressed in Insulin Resistance, Independent of Adiposity. J. Clin. Endocrinol. Metab. 2017, 102, 1112–1121.
  30. Napoli, N.; Chandran, M.; Pierroz, D.D.; Abrahamsen, B.; Schwartz, A.V.; Ferrari, S.L. Mechanisms of diabetes mellitus-induced bone fragility. Nat. Rev. Endocrinol. 2017, 13, 208–219.
  31. Nuche-Berenguer, B.; Portal-Núñez, S.; Moreno, P.; González, N.; Acitores, A.; López-Herradón, A.; Esbrit, P.; Valverde, I.; Villanueva-Peñacarrillo, M.L. Presence of a functional receptor for GLP-1 in osteoblastic cells, independent of the cAMP-linked GLP-1 receptor. J. Cell. Physiol. 2010, 225, 585–592.
  32. Muñoz-Torres, M.; Reyes-García, R.; García-Martin, A.; Jiménez-Moleón, J.J.; Gonzalez-Ramírez, A.R.; Lara-Villoslada, M.J.; Moreno, P.R. Ischemic heart disease is associated with vertebral fractures in patients with type 2 diabetes mellitus. J. Diabetes Investig. 2013, 4, 310–315.
  33. Mitri, J.; Pittas, A.G. Vitamin D and Diabetes. Endocrinol. Metab. Clin. N. Am. 2014, 43, 205–232.
  34. Knudsen, J.K.; Leutscher, P.; Sørensen, S. Gut Microbiota in Bone Health and Diabetes. Curr. Osteoporos. Rep. 2021, 19, 462–479.
  35. Shanbhogue, V.V.; Mitchell, D.M.; Rosen, C.J.; Bouxsein, M.L. Type 2 diabetes and the skeleton: New insights into sweet bones. Lancet Diabetes Endocrinol. 2016, 4, 159–173.
  36. Rozas-Moreno, P.; Reyes-García, R.; Jódar-Gimeno, E.; Varsavsky, M.; Luque-Fernández, I.; Cortés-Berdonces, M.; Muñoz-Torres, M. Recomendaciones sobre el efecto de los fármacos antidiabéticos en el hueso. Endocrinol. Diabetes Nutr. 2017, 64, 1–6.
  37. Molinuevo, M.S.; Schurman, L.; McCarthy, A.D.; Cortizo, A.M.; Tolosa, M.J.; Gangoiti, M.V.; Arnol, V.; Sedlinsky, C. Effect of metformin on bone marrow progenitor cell differentiation: In vivo and in vitro studies. J. Bone Miner. Res. 2010, 25, 211–221.
  38. Monami, M.; Dicembrini, I.; Antenore, A.; Mannucci, E. Dipeptidyl Peptidase-4 Inhibitors and Bone Fractures: A meta-analysis of randomized clinical trials. Diabetes Care 2011, 34, 2474–2476.
  39. Su, B.; Sheng, H.; Zhang, M.; Bu, L.; Yang, P.; Li, L.; Li, F.; Sheng, C.; Han, Y.; Qu, S.; et al. Risk of bone fractures associated with glucagon-like peptide-1 receptor agonists’ treatment: A meta-analysis of randomized controlled trials. Endocrine 2014, 48, 107–115.
  40. Zhu, Z.-N.; Jiang, Y.-F.; Ding, T. Risk of fracture with thiazolidinediones: An updated meta-analysis of randomized clinical trials. Bone 2014, 68, 115–123.
  41. Kohan, D.E.; Fioretto, P.; Tang, W.; List, J.F. Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control. Kidney Int. 2014, 85, 962–971.
  42. Neal, B.; Perkovic, V.; Mahaffey, K.W.; de Zeeuw, D.; Fulcher, G.; Erondu, N.; Shaw, W.; Law, G.; Desai, M.; Matthews, D.R.; et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N. Engl. J. Med. 2017, 377, 644–657.
  43. Johnston, S.S.; Conner, C.; Aagren, M.; Ruiz, K.; Bouchard, J. Association between hypoglycaemic events and fall-related fractures in Medicare-covered patients with type 2 diabetes. Diabetes Obes. Metab. 2012, 14, 634–643.
  44. Mayne, D.; Stout, N.R.; Aspray, T.J. Diabetes, falls and fractures. Age Ageing 2010, 39, 522–525.
  45. Dennison, E.M.; Syddall, H.E.; Aihie Sayer, A.; Craighead, S.; Phillips, D.I.W.; Cooper, C. Type 2 diabetes mellitus is associated with increased axial bone density in men and women from the Hertfordshire Cohort Study: Evidence for an indirect effect of insulin resistance? Diabetologia 2004, 47, 1963–1968.
  46. Bonds, D.E.; Larson, J.C.; Schwartz, A.V.; Strotmeyer, E.S.; Robbins, J.; Rodriguez, B.L.; Johnson, K.C.; Margolis, K. Risk of Fracture in Women with Type 2 Diabetes: The Women’s Health Initiative Observational Study. J. Clin. Endocrinol. Metab. 2006, 91, 3404–3410.
  47. Mitchell, A.; Fall, T.; Melhus, H.; Wolk, A.; Michaëlsson, K.; Byberg, L. Type 2 Diabetes in Relation to Hip Bone Density, Area, and Bone Turnover in Swedish Men and Women: A Cross-Sectional Study. Calcif. Tissue Int. 2018, 103, 501–511.
  48. Ma, L.; Oei, L.; Jiang, L.; Estrada, K.; Chen, H.; Wang, Z.; Yu, Q.; Zillikens, M.C.; Gao, X.; Rivadeneira, F. Association between bone mineral density and type 2 diabetes mellitus: A meta-analysis of observational studies. Eur. J. Epidemiol. 2012, 27, 319–332.
  49. Pan, H.; Wu, N.; Yang, T.; He, W. Association between bone mineral density and type 1 diabetes mellitus: A meta-analysis of cross-sectional studies. Diabetes Metab. Res. Rev. 2014, 30, 531–542.
  50. Srikanthan, P.; Crandall, C.J.; Miller-Martinez, D.; Seeman, T.E.; Greendale, G.A.; Binkley, N.; Karlamangla, A.S. Insulin Resistance and Bone Strength: Findings From the Study of Midlife in the United States. J. Bone Miner. Res. 2014, 29, 796–803.
  51. Upadhyay, J.; Farr, O.M.; Mantzoros, C.S. The role of leptin in regulating bone metabolism. Metabolism 2015, 64, 105–113.
  52. Botella Martínez, S.; Varo Cenarruzabeitia, N.; Escalada San Martin, J.; Calleja Canelas, A. The diabetic paradox: Bone mineral density and fracture in type 2 diabetes. Endocrinol. Nutr. 2016, 63, 495–501.
  53. Giangregorio, L.M.; Leslie, W.D.; Lix, L.M.; Johansson, H.; Oden, A.; McCloskey, E.; Kanis, J.A. FRAX underestimates fracture risk in patients with diabetes. J. Bone Miner. Res. 2012, 27, 301–308.
  54. El Miedany, Y. FRAX: Re-adjust or re-think. Arch. Osteoporos. 2020, 15, 150.
  55. Valentini, A.; Cianfarani, M.A.; De Meo, L.; Morabito, P.; Romanello, D.; Tarantino, U.; Federici, M.; Bertoli, A. FRAX tool in type 2 diabetic subjects: The use of HbA1c in estimating fracture risk. Acta Diabetol. 2018, 55, 1043–1050.
  56. Wen, Z.; Ding, N.; Chen, R.; Liu, S.; Wang, Q.; Sheng, Z.; Liu, H. Comparison of methods to improve fracture risk assessment in chinese diabetic postmenopausal women: A case-control study. Endocrine 2021, 73, 209–216.
  57. Hu, L.; Li, T.; Zou, Y.; Yin, X.-L.; Gan, H. The Clinical Value of the RA-Adjusted Fracture Risk Assessment Tool in the Fracture Risk Prediction of Patients with Type 2 Diabetes Mellitus in China. Int. J. Gen. Med. 2021, 14, 327–333.
  58. Leslie, W.D.; Johansson, H.; McCloskey, E.V.; Harvey, N.C.; Kanis, J.A.; Hans, D. Comparison of Methods for Improving Fracture Risk Assessment in Diabetes: The Manitoba BMD Registry. J. Bone Miner. Res. 2018, 33, 1923–1930.
  59. Hunt, H.B.; Torres, A.M.; Palomino, P.M.; Marty, E.; Saiyed, R.; Cohn, M.; Jo, J.; Warner, S.; Sroga, G.E.; King, K.B.; et al. Altered Tissue Composition, Microarchitecture, and Mechanical Performance in Cancellous Bone From Men With Type 2 Diabetes Mellitus. J. Bone Miner. Res. 2019, 34, 1191–1206.
  60. Starup-Linde, J.; Lykkeboe, S.; Handberg, A.; Vestergaard, P.; Høyem, P.; Fleischer, J.; Hansen, T.K.; Poulsen, P.L.; Laugesen, E. Glucose variability and low bone turnover in people with type 2 diabetes. Bone 2021, 153, 116159.
  61. Starup-Linde, J.; Eriksen, S.A.; 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, 1697–1708.
  62. Reyes-Garcia, R.; Rozas-Moreno, P.; López-Gallardo, G.; Garcia-Martin, A.; Varsavsky, M.; Avilés-Pérez, M.D.; Muñoz-Torres, M. Serum levels of bone resorption markers are decreased in patients with type 2 diabetes. Acta Diabetol. 2013, 50, 47–52.
  63. Yamamoto, M.; Yamaguchi, T.; Nawata, K.; Yamauchi, M.; Sugimoto, T. Decreased PTH Levels Accompanied by Low Bone Formation Are Associated with Vertebral Fractures in Postmenopausal Women with Type 2 Diabetes. J. Clin. Endocrinol. Metab. 2012, 97, 1277–1284.
  64. Napoli, N.; Conte, C.; Eastell, R.; Ewing, S.K.; Bauer, D.C.; Strotmeyer, E.S.; Black, D.M.; Samelson, E.J.; Vittinghoff, E.; Schwartz, A.V. Bone Turnover Markers Do Not Predict Fracture Risk in Type 2 Diabetes. J. Bone Miner. Res. 2020, 35, 2363–2371.
  65. Karim, L.; Moulton, J.; Van Vliet, M.; Velie, K.; Robbins, A.; Malekipour, F.; Abdeen, A.; Ayres, D.; Bouxsein, M.L. Bone microarchitecture, biomechanical properties, and advanced glycation end-products in the proximal femur of adults with type 2 diabetes. Bone 2018, 114, 32–39.
  66. Wölfel, E.M.; Jähn-Rickert, K.; Schmidt, F.N.; Wulff, B.; Mushumba, H.; Sroga, G.E.; Püschel, K.; Milovanovic, P.; Amling, M.; Campbell, G.M.; et al. Individuals with type 2 diabetes mellitus show dimorphic and heterogeneous patterns of loss in femoral bone quality. Bone 2020, 140, 115556.
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