RESEARCH ARTICLE

Hybrid deep learning model for risk prediction of fracture in patients with diabetes and osteoporosis

  • Yaxin Chen 1,2 ,
  • Tianyi Yang 2 ,
  • Xiaofeng Gao , 2 ,
  • Ajing Xu , 1,3
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  • 1. Department of Pharmacy, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China
  • 2. Shanghai Key Laboratory of Scalable Computing and Systems, Department of Computer Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
  • 3. Clinical Research Unit, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China

Received date: 14 Feb 2020

Accepted date: 17 Sep 2020

Published date: 15 Jun 2022

Copyright

2021 Higher Education Press

Abstract

The fracture risk of patients with diabetes is higher than those of patients without diabetes due to hyperglycemia, usage of diabetes drugs, changes in insulin levels, and excretion, and this risk begins as early as adolescence. Many factors including demographic data (such as age, height, weight, and gender), medical history (such as smoking, drinking, and menopause), and examination (such as bone mineral density, blood routine, and urine routine) may be related to bone metabolism in patients with diabetes. However, most of the existing methods are qualitative assessments and do not consider the interactions of the physiological factors of humans. In addition, the fracture risk of patients with diabetes and osteoporosis has not been further studied previously. In this paper, a hybrid model combining XGBoost with deep neural network is used to predict the fracture risk of patients with diabetes and osteoporosis, and investigate the effect of patients’ physiological factors on fracture risk. A total of 147 raw input features are considered in our model. The presented model is compared with several benchmarks based on various metrics to prove its effectiveness. Moreover, the top 18 influencing factors of fracture risks of patients with diabetes are determined.

Cite this article

Yaxin Chen , Tianyi Yang , Xiaofeng Gao , Ajing Xu . Hybrid deep learning model for risk prediction of fracture in patients with diabetes and osteoporosis[J]. Frontiers of Medicine, 2022 , 16(3) : 496 -506 . DOI: 10.1007/s11684-021-0828-7

Acknowledgements

This work was partially supported by the National Key R&D Program of China (Nos. 2020YFC2005502 and 2018YFB1004700), the National Natural Science Foundation of China (Nos. 61872238 and 61972254), the Science and Technology Commission of Shanghai Municipality (No. 19401900500), the Innovation Program of Shanghai Health Commission (Nos. 201840121 and ZY(2018-2020)-ZWB-1001-CPJS1), the CCF-Huawei Database System Innovation Research Plan (No. CCF-Huawei DBIR2019002A), and the program of Hospital Clinical Research, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (No. 19XHCR11C).

Compliance with ethics guidelines

Yaxin Chen, Tianyi Yang, Xiaofeng Gao, and Ajing Xu declare that they have no conflict of interest. All procedures followed complied with the ethical standards of the responsible committee on human experimentation (institutional and national) and the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients included in the study.
1
Leidig-Bruckner G, Grobholz S, Bruckner T, Scheidt-Nave C, Nawroth P, Schneider JG. Prevalence and determinants of osteoporosis in patients with type 1 and type 2 diabetes mellitus. BMC Endocr Disord 2014; 14(1): 33

DOI PMID

2
Epstein S, Defeudis G, Manfrini S, Napoli N, Pozzilli P; Scientific Committee of the First International Symposium on Diabetes and Bone.Diabetes and disordered bone metabolism (diabetic osteodystrophy): time for recognition. Osteoporos Int 2016; 27(6): 1931–1951

DOI PMID

3
Zhao Z. Correlation analysis of urine proteins and inflammatory cytokines with osteoporosis in patients with diabetic nephropathy. J Musculoskelet Neuronal Interact 2018; 18(3): 348–353

PMID

4
Khazai NB, Beck GR Jr, Umpierrez GE. Diabetes and fractures: an overshadowed association. Curr Opin Endocrinol Diabetes Obes 2009; 16(6): 435–445

DOI PMID

5
Pecina JL, Romanovsky L, Merry SP, Kennel KA, Thacher TD. Comparison of clinical risk tools for predicting osteoporosis in women ages 50–64. J Am Board Fam Med 2016; 29(2): 233–239

DOI PMID

6
Liu JM, Zhu DL, Mu YM, Xia WB; Chinese Society of Osteoporosis and Bone Mineral Research, the Chinese Society of Endocrinology, Chinese Diabetes Society, Chinese Medical Association; Chinese Endocrinologist Association, Chinese Medical Doctor Association.Management of fracture risk in patients with diabetes—Chinese Expert Consensus. J Diabetes 2019; 11(11): 906–919

DOI PMID

7
Roux S, Cabana F, Carrier N, Beaulieu M, April PM, Beaulieu MC, Boire G. The World Health Organization Fracture Risk Assessment Tool (FRAX) underestimates incident and recurrent fractures in consecutive patients with fragility fractures. J Clin Endocrinol Metab 2014; 99(7): 2400–2408

DOI PMID

8
Esteva A, Kuprel B, Novoa RA, Ko J, Swetter SM, Blau HM, Thrun S. Dermatologist-level classification of skin cancer with deep neural networks. Nature 2017; 542(7639): 115–118

DOI PMID

9
Haenssle HA, Fink C, Schneiderbauer R, Toberer F, Buhl T, Blum A, Kalloo A, Hassen ABH, Thomas L, Enk A, Uhlmann L, Reader study level-I and level-II Groups; Alt C, Arenbergerova M, Bakos R, Baltzer A, Bertlich I, Blum A, Bokor-Billmann T, Bowling J, Braghiroli N, Braun R, Buder-Bakhaya K, Buhl T, Cabo H, Cabrijan L, Cevic N, Classen A, Deltgen D, Fink C, Georgieva I, Hakim-Meibodi LE, Hanner S, Hartmann F, Hartmann J, Haus G, Hoxha E, Karls R, Koga H, Kreusch J, Lallas A, Majenka P, Marghoob A, Massone C, Mekokishvili L, Mestel D, Meyer V, Neuberger A, Nielsen K, Oliviero M, Pampena R, Paoli J, Pawlik E, Rao B, Rendon A, Russo T, Sadek A, Samhaber K, Schneiderbauer R, Schweizer A, Toberer F, Trennheuser L, Vlahova L, Wald A, Winkler J, Wölbing P, Zalaudek I. Man against machine: diagnostic performance of a deep learning convolutional neural network for dermoscopic melanoma recognition in comparison to 58 dermatologists. Ann Oncol 2018; 29(8): 1836–1842

DOI PMID

10
Cheng JZ, Ni D, Chou YH, Qin J, Tiu CM, Chang YC, Huang CS, Shen D, Chen CM. Computer-aided diagnosis with deep learning architecture: applications to breast lesions in US images and pulmonary nodules in CT scans. Sci Rep 2016; 6(1): 24454

DOI PMID

11
Cicero M, Bilbily A, Colak E, Dowdell T, Gray B, Perampaladas K, Barfett J. Training and validating a deep convolutional neural network for computer-aided detection and classification of abnormalities on frontal chest radiographs. Invest Radiol 2017; 52(5): 281–287

DOI PMID

12
Kooi T, Litjens G, van Ginneken B, Gubern-Mérida A, Sánchez CI, Mann R, den Heeten A, Karssemeijer N. Large scale deep learning for computer aided detection of mammographic lesions. Med Image Anal 2017; 35: 303–312

DOI PMID

13
Barreira CM, Bouslama M, Haussen DC, Grossberg JA, Baxter B, Devlin T, Frankel M, Nogueira RG. Abstract WP61: automated large artery occlusion detection IN stroke imaging-ALADIN study. Stroke 2018; 49(Suppl_1): AWP61

14
Gulshan V, Peng L, Coram M, Stumpe MC, Wu D, Narayanaswamy A, Venugopalan S, Widner K, Madams T, Cuadros J, Kim R, Raman R, Nelson PC, Mega JL, Webster DR. Development and validation of a deep learning algorithm for detection of diabetic retinopathy in retinal fundus photographs. JAMA 2016; 316(22): 2402–2410

DOI PMID

15
Poplin R, Varadarajan AV, Blumer K, Liu Y, McConnell MV, Corrado GS, Peng L, Webster DR. Prediction of cardiovascular risk factors from retinal fundus photographs via deep learning. Nat Biomed Eng 2018; 2(3): 158–164

DOI PMID

16
De Fauw J, Ledsam JR, Romera-Paredes B, Nikolov S, Tomasev N, Blackwell S, Askham H, Glorot X, O’Donoghue B, Visentin D, van den Driessche G, Lakshminarayanan B, Meyer C, Mackinder F, Bouton S, Ayoub K, Chopra R, King D, Karthikesalingam A, Hughes CO, Raine R, Hughes J, Sim DA, Egan C, Tufail A, Montgomery H, Hassabis D, Rees G, Back T, Khaw PT, Suleyman M, Cornebise J, Keane PA, Ronneberger O. Clinically applicable deep learning for diagnosis and referral in retinal disease. Nat Med 2018; 24(9): 1342–1350

DOI PMID

17
Cireşan DC, Giusti A, Gambardella LM, Schmidhuber J. Mitosis detection in breast cancer histology images with deep neural networks. International Conference on Medical Image Computing and Computer-assisted Intervention 2013: 411–418

18
Liu Y, Gadepalli K, Norouzi M, Dahl GE, Kohlberger T, Boyko A, Venugopalan S, Timofeev A, Nelson PQ, Corrado GS. Detecting cancer metastases on gigapixel pathology images. 2017. arXiv:1703.02442

19
Charoentong P, Finotello F, Angelova M, Mayer C, Efremova M, Rieder D, Hackl H, Trajanoski Z. Pan-cancer immunogenomic analyses reveal genotype-immunophenotype relationships and predictors of response to checkpoint blockade. Cell Rep 2017; 18(1): 248–262

DOI PMID

20
Beck AH, Sangoi AR, Leung S, Marinelli RJ, Nielsen TO, Van De Vijver MJ, West RB, Van De Rijn M, Koller D. Systematic analysis of breast cancer morphology uncovers stromal features associated with survival. Sci Transl Med 2011; 3(108): 108ra113 PMID: 22072638

DOI

21
Shickel B, Tighe PJ, Bihorac A, Rashidi P. Deep EHR: a survey of recent advances in deep learning techniques for electronic health record (EHR) analysis. IEEE J Biomed Health Inform 2018; 22(5): 1589–1604

DOI PMID

22
Rajkomar A, Oren E, Chen K, Dai AM, Hajaj N, Hardt M, Liu PJ, Liu X, Marcus J, Sun M, Sundberg P, Yee H, Zhang K, Zhang Y, Flores G, Duggan GE, Irvine J, Le Q, Litsch K, Mossin A, Tansuwan J, Wang D, Wexler J, Wilson J, Ludwig D, Volchenboum SL, Chou K, Pearson M, Madabushi S, Shah NH, Butte AJ, Howell MD, Cui C, Corrado GS, Dean J. Scalable and accurate deep learning with electronic health records. NPJ Digit Med 2018; 1(1): 18

DOI PMID

23
Liu V, Kipnis P, Gould MK, Escobar GJ. Length of stay predictions: improvements through the use of automated laboratory and comorbidity variables. Med Care 2010; 48(8): 739–744

DOI PMID

24
Choi Ed, Bahadori MT, Schuetz A, Stewart WF, Sun J. Doctor AI: predicting clinical events via recurrent neural networks. Machine Learning for Healthcare Conference 2016: 301–318

25
Che Z, Purushotham S, Cho K, Sontag D, Liu Y. Recurrent neural networks for multivariate time series with missing values. Sci Rep 2018; 8(1): 6085

DOI PMID

26
Suresh H, Hunt N, Johnson A, Celi LA, Szolovits P, Ghassemi M. Clinical intervention prediction and understanding with deep neural networks. Machine Learning for Healthcare Conference 2017: 322–337

27
Abbeel P, Ng AY. Apprenticeship learning via inverse reinforcement learning. Proceedings of the 21st International Conference on Machine Learning 2004: 1

28
Ratliff ND, Silver D, Bagnell JA. Learning to search: Functional gradient techniques for imitation learning. Auton Robots 2009; 27(1): 25–53

DOI

29
Schulman J, Gupta A, Venkatesan S, Tayson-Frederick M, Abbeel P. A case study of trajectory transfer through non-rigid registration for a simplified suturing scenario. IEEE/RSJ International Conference on Intelligent Robots and Systems 2013: 4111–4117

30
He X, Pan J, Jin O, Xu T, Liu B, Xu T, Shi Y, Atallah A, Herbrich R, Bowers S, Candela JQ. Practical lessons from predicting clicks on Ads at Facebook. Proceedings of the ACM SIGKDD International Conference on Knowledge Discovery and Data Mining 2014: 1–9

31
Chen T, Guestrin C. XGBoost: a scalable tree boosting system. KDD '16: Proceedings of the 22nd ACM SIGKDD International Conference on Knowledge Discovery and Data Mining 2016: 785–794

32
Kingma DP, Ba J. Adam: a method for stochastic optimization. 2014. arXiv:1412.6980

33
Defeudis G, Mazzilli R, Gianfrilli D, Lenzi A, Isidori AM. The CATCH checklist to investigate adult–onset hypogonadism. Andrology 2018; 6(5):665–679PMID: 29888533

DOI

34
Poiana C, Capatina C. Fracture risk assessment in patients with diabetes mellitus. J Clin Densitom 2017; 20(3): 432–443

DOI PMID

35
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): 1338–1346

DOI PMID

36
Lee YY, Kim HB, Lee JW, Lee GM, Kim SY, Hur JA, Cho HC. The association between urine albumin to creatinine ratio and osteoporosis in postmenopausal women with type 2 diabetes. J Bone Metab 2016; 23(1): 1–7

DOI PMID

37
Jassal SK, von Muhlen D, Barrett-Connor E. Measures of renal function, BMD, bone loss, and osteoporotic fracture in older adults: the Rancho Bernardo study. J Bone Miner Res 2007; 22(2): 203–210

DOI PMID

38
Liu C, Li H. Correlation of the severity of chronic kidney disease with serum inflammation, osteoporosis and vitamin D deficiency. Exp Ther Med 2019; 17(1): 368–372

PMID

39
Afshinnia F, Pennathur S. Association of hypoalbuminemia with osteoporosis: analysis of the National Health and Nutrition Examination Survey. J Clin Endocrinol Metab 2016; 101(6): 2468–2474

DOI PMID

40
Xiu S, Chhetri JK, Sun L, Mu Z, Wang L. Association of serum prealbumin with risk of osteoporosis in older adults with type 2 diabetes mellitus: a cross-sectional study. Ther Adv Chronic Dis 2019; 10: 2040622319857361

DOI PMID

41
Do HJ, Shin JS, Lee J, Lee YJ, Kim MR, Nam D, Kim EJ, Park Y, Suhr K, Ha IH. Association between liver enzymes and bone mineral density in Koreans: a cross-sectional study. BMC Musculoskelet Disord 2018; 19(1): 410

DOI PMID

42
Noguchi T, Ebina K, Hirao M, Otsuru S, Guess AJ, Kawase R, Ohama T, Yamashita S, Etani Y, Okamura G, Yoshikawa H. Apolipoprotein E plays crucial roles in maintaining bone mass by promoting osteoblast differentiation via ERK1/2 pathway and by suppressing osteoclast differentiation via c-Fos, NFATc1, and NF-kB pathway. Biochem Biophys Res Commun 2018; 503(2): 644–650

DOI PMID

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