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Current Osteoporosis Reports
Published in: Current Osteoporosis Reports 1/2021

Open Access 01-02-2021 | Osteoporosis | Bone and Diabetes (A Schwartz and P Vestergaard, Section Editors)

Type 2 Diabetes Mellitus and Vertebral Fracture Risk

Authors: Fjorda Koromani, Samuel Ghatan, Mandy van Hoek, M. Carola Zillikens, Edwin H. G. Oei, Fernando Rivadeneira, Ling Oei

Published in: Current Osteoporosis Reports | Issue 1/2021

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Abstract

Purpose of Review

The purpose of this review is to summarize the recently published evidence concerning vertebral fracture risk in individuals with diabetes mellitus.

Recent Findings

Vertebral fracture risk is increased in individuals with T2DM. The presence of vertebral fractures in T2DM is associated with increased non-vertebral fracture risk and mortality. TBS could be helpful to estimate vertebral fracture risk in individuals with T2DM. An increased amount of bone marrow fat has been implicated in bone fragility in T2DM. Results from two recent studies show that both teriparatide and denosumab are effective in reducing vertebral fracture risk also in individuals with T2DM.

Summary

Individuals with T2DM could benefit from systematic screening in the clinic for presence of vertebral fractures.
Literature
1.
Wild S, et al. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004;27(5):1047–53.PubMedCrossRef
2.
James SL, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1789–858.CrossRef
3.
Johnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int. 2006;17(12):1726–33.PubMedCrossRef
4.
5.
Kanis JA, et al. European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int. 2013;24(1):23–57.PubMedCrossRef
6••.
Koromani F, et al. Vertebral fractures in individuals with type 2 diabetes: more than skeletal complications alone. Diabetes Care. 2020;43(1):137–44 Meta analysis across 852,705 individuals in 15 studies concluding that individuals with T2DM have increased risk of vertebral fractures.PubMedCrossRef
7.
Black DM, et al. Prevalent vertebral deformities predict hip fractures and new vertebral deformities but not wrist fractures. J Bone Miner Res. 1999;14(5):821–8.PubMedCrossRef
8.
Delmas PD, et al. Underdiagnosis of vertebral fractures is a worldwide problem: the IMPACT study. J Bone Miner Res. 2005;20(4):557–63.PubMedCrossRef
9.
Janghorbani M, et al. Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol. 2007;166(5):495–505.PubMedCrossRef
10.
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.PubMedCrossRef
11.
12.
Bonds DE, et al. Risk of fracture in women with type 2 diabetes: the Women’s Health Initiative Observational Study. J Clin Endocrinol Metab. 2006;91(9):3404–10.PubMedCrossRef
13.
Oei L, et al. High bone mineral density and fracture risk in type 2 diabetes as skeletal complications of inadequate glucose control. The Rotterdam Study. 2013;36(6):1619–28.
14.
Jia P, et al. Risk of low-energy fracture in type 2 diabetes patients: a meta-analysis of observational studies. Osteoporos Int. 2017;28(11):3113–21.PubMedCrossRef
15.
Dytfeld J, Michalak M. Type 2 diabetes and risk of low-energy fractures in postmenopausal women: meta-analysis of observational studies. Aging Clin Exp Res. 2017;29(2):301–9.PubMedCrossRef
16.
Wang J, et al. Increased risk of vertebral fracture in patients with diabetes: a meta-analysis of cohort studies. Int Orthop. 2016;40(6):1299–307.PubMedCrossRef
17.
Moayeri A, et al. Fracture risk in patients with type 2 diabetes mellitus and possible risk factors: a systematic review and meta-analysis. Ther Clin Risk Manag. 2017;13:455–68.PubMedPubMedCentralCrossRef
18.
Napoli N, et al. Vertebral fracture risk in diabetic elderly men: the MrOS study. J Bone Miner Res. 2018;33(1):63–9.PubMedCrossRef
19.
20.
Ma L, et al. Association between bone mineral density and type 2 diabetes mellitus: a meta-analysis of observational studies. Eur J Epidemiol. 2012;27(5):319–32.PubMedPubMedCentralCrossRef
21•.
Giangregorio LM, et al. FRAX underestimates fracture risk in patients with diabetes. J Bone Miner Res. 2012;27(2):301–8 Important study documenting that the fracture risk in individuals with T2DM have an increased risk of fracture that is independent of BMD and underestimated by FRAX.PubMedCrossRef
22.
23.
Hans D, Stenova E, Lamy O. The trabecular bone score (TBS) complements DXA and the FRAX as a fracture risk assessment tool in routine clinical practice. Curr Osteoporos Rep. 2017;15(6):521–31.PubMedCrossRef
24.
Schacter GI, Leslie WD. DXA-based measurements in diabetes: can they predict fracture risk? Calcif Tissue Int. 2017;100(2):150–64.PubMedCrossRef
25.
Silva BC, Leslie WD. Trabecular bone score: a new DXA-derived measurement for fracture risk assessment. Endocrinol Metab Clin N Am. 2017;46(1):153–80.CrossRef
26•.
Martineau P, et al. In which patients does lumbar spine trabecular bone score (TBS) have the largest effect? Bone. 2018;113:161–8 Intersting study evaluating the strenth of association between TBS and several fracture risk factors, including diabetes.PubMedPubMedCentralCrossRef
27.
Yamamoto M, Yamauchi M, Sugimoto T. Prevalent vertebral fracture is dominantly associated with spinal microstructural deterioration rather than bone mineral density in patients with type 2 diabetes mellitus. PLoS One. 2019;14(9):e0222571.PubMedPubMedCentralCrossRef
28.
Choi YJ, Ock SY, Chung YS. Trabecular bone score (TBS) and TBS-adjusted fracture risk assessment tool are potential supplementary tools for the discrimination of morphometric vertebral fractures in postmenopausal women with type 2 diabetes. J Clin Densitom. 2016;19(4):507–14.PubMedCrossRef
29.
Zhukouskaya VV, et al. The utility of lumbar spine trabecular bone score and femoral neck bone mineral density for identifying asymptomatic vertebral fractures in well-compensated type 2 diabetic patients. Osteoporos Int. 2016;27(1):49–56.PubMedCrossRef
30.
Chen FP, et al. Status of bone strength and factors associated with vertebral fracture in postmenopausal women with type 2 diabetes. Menopause. 2019;26(2):182–8.PubMedCrossRef
31.
32.
Kanazawa I, et al. Overweight and underweight are risk factors for vertebral fractures in patients with type 2 diabetes mellitus. J Bone Miner Metab. 2019;37(4):703–10.PubMedCrossRef
33.
Bianchi L, Volpato S. Muscle dysfunction in type 2 diabetes: a major threat to patient's mobility and independence. Acta Diabetol. 2016;53(6):879–89.PubMedCrossRef
34.
Li G, et al. Frailty and risk of fractures in patients with type 2 diabetes. Diabetes Care. 2019;42(4):507–13.PubMedCrossRef
35.
Szulc P, Feyt C, Chapurlat R. High risk of fall, poor physical function, and low grip strength in men with fracture-the STRAMBO study. J Cachexia Sarcopenia Muscle. 2016;7(3):299–311.PubMedCrossRef
36.
Yokomoto-Umakoshi M, et al. Association between the risk of falls and osteoporotic fractures in patients with type 2 diabetes mellitus. Endocr J. 2017;64(7):727–34.PubMedCrossRef
37.
Schousboe JT, et al. Prevalent vertebral fracture on bone density lateral spine (VFA) images in routine clinical practice predict incident fractures. Bone. 2019;121:72–9.PubMedCrossRef
38.
Hygum K, et al. 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.PubMedCrossRef
39.
Farr JN, Khosla S. Determinants of bone strength and quality in diabetes mellitus in humans. Bone. 2016;82:28–34.PubMedCrossRef
40.
Napoli N, et al. Mechanisms of diabetes mellitus-induced bone fragility. Nat Rev Endocrinol. 2017;13(4):208–19.PubMedCrossRef
41.
Saito M, Marumo K. Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus. Osteoporos Int. 2010;21(2):195–214.PubMedCrossRef
42.
Waqas K, et al. Skin autofluorescence, a noninvasive biomarker for advanced glycation end-products, is associated with prevalent vertebral and major osteoporotic fractures: the Rotterdam study. J Bone Miner Res. 2020.
43.
Oei L, et al. Osteoporotic vertebral fracture prevalence varies widely between qualitative and quantitative radiological assessment methods: the Rotterdam study. J Bone Miner Res. 2018;33(4):560–8.PubMedCrossRef
44.
Dong X, et al. FFAs-ROS-ERK/P38 pathway plays a key role in adipocyte lipotoxicity on osteoblasts in co-culture. Biochimie. 2014;101:123–31.PubMedCrossRef
45.
Zhu L, et al. Marrow adiposity as an indicator for insulin resistance in postmenopausal women with newly diagnosed type 2 diabetes - an investigation by chemical shift-encoded water-fat MRI. Eur J Radiol. 2019;113:158–64.PubMedCrossRef
46.
Woods GN, et al. Greater bone marrow adiposity predicts bone loss in older women. J Bone Miner Res. 2020;35(2):326–32.PubMedCrossRef
47.
48.
Martinez-Laguna D, et al. Excess of all-cause mortality after a fracture in type 2 diabetic patients: a population-based cohort study. Osteoporos Int. 2017;28(9):2573–81.PubMedCrossRef
49.
Miyake H, Kanazawa I, Sugimoto T. Association of bone mineral density, bone turnover markers, and vertebral fractures with all-cause mortality in type 2 diabetes mellitus. Calcif Tissue Int. 2018;102(1):1–13.PubMedCrossRef
50.
Schwartz AV. Diabetes, bone and glucose-lowering agents: clinical outcomes. Diabetologia. 2017;60(7):1170–9.PubMedCrossRef
51.
Choi HJ, et al. Risk of fractures and diabetes medications: a nationwide cohort study. Osteoporos Int. 2016;27(9):2709–15.PubMedCrossRef
52.
Notsu M, et al. Serum dipeptidyl peptidase-4 is associated with multiple vertebral fractures in type 2 diabetes mellitus. Clin Endocrinol. 2016;84(3):332–7.CrossRef
53.
Lin F, et al. The effect of metformin on vertebral marrow fat in postmenopausal women with newly diagnosed type 2 diabetes mellitus. Menopause. 2019.
54.
Mai QG, et al. Metformin stimulates osteoprotegerin and reduces RANKL expression in osteoblasts and ovariectomized rats. J Cell Biochem. 2011;112(10):2902–9.PubMedCrossRef
55.
Zhang Y, et al. Insulin use and fracture risk in patients with type 2 diabetes: a meta-analysis of 138,690 patients. Exp Ther Med. 2019;17(5):3957–64.PubMedPubMedCentral
56.
Corrao G, et al. Is switching from oral antidiabetic therapy to insulin associated with an increased fracture risk? Clin Orthop Relat Res. 2019.
57.
Hygum K, et al. Bone resorption is unchanged by liraglutide in type 2 diabetes patients: a randomised controlled trial. Bone. 2020;132:115197.PubMedCrossRef
58.
Schwartz AV. Efficacy of osteoporosis therapies in diabetic patients. Calcif Tissue Int. 2017;100(2):165–73.PubMedCrossRef
59.
Anagnostis P, et al. Efficacy of anti-osteoporotic medications in patients with type 1 and 2 diabetes mellitus: a systematic review. Endocrine. 2018;60(3):373–83.PubMedCrossRef
60.
Langdahl BL, et al. Real-world effectiveness of teriparatide on fracture reduction in patients with osteoporosis and comorbidities or risk factors for fractures: integrated analysis of 4 prospective observational studies. Bone. 2018;116:58–66.PubMedCrossRef
61.
Ferrari S, et al. Denosumab in postmenopausal women with osteoporosis and diabetes: subgroup analysis of FREEDOM and FREEDOM extension. Bone. 2020;134:115268.PubMedCrossRef
62.
Malik AT, et al. Declining trend in osteoporosis management and screening following vertebral compression fractures - a national analysis of commercial insurance and Medicare advantage beneficiaries. Spine J. 2019.
63.
64.
Metadata
Title
Type 2 Diabetes Mellitus and Vertebral Fracture Risk
Authors
Fjorda Koromani
Samuel Ghatan
Mandy van Hoek
M. Carola Zillikens
Edwin H. G. Oei
Fernando Rivadeneira
Ling Oei
Publication date
01-02-2021
Publisher
Springer US
Published in
Current Osteoporosis Reports / Issue 1/2021
Print ISSN: 1544-1873
Electronic ISSN: 1544-2241
DOI
https://doi.org/10.1007/s11914-020-00646-8

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