Correlation analysis of LPR-5, SOST and MHR with poor prognosis in patients with type 2 diabetes mellitus complicated with osteoporosis

LPR-5, SOST and MHR for fractures in osteoporosis with type 2 diabetes

  • Xiang Li Department of Orthopedics, Shanghai Fifth People’s Hospital, Fudan University
  • Shiwei Sun Department of Orthopedics, Shanghai Fifth People’s Hospital, Fudan University
  • Tianlong Zhang Department of Orthopedics, Shanghai Fifth People’s Hospital, Fudan University
  • Bohao Li Department of Orthopedics, Shanghai Fifth People’s Hospital, Fudan University
  • Jiarui Zhang Department of Orthopedics, Shanghai Fifth People’s Hospital, Fudan University
  • Yu Zhao Department of Orthopedics, Shanghai Fifth People’s Hospital, Fudan University
  • Yi Xie Endocrinology Department, Zhongshan Hospital Affiliated to Xiamen University
  • Siqi Yang Endocrinology Department, Zhongshan Hospital Affiliated to Xiamen University
  • Minghai Wang Department of Orthopedics, Shanghai Fifth People’s Hospital, Fudan University
DOI: https://doi.org/10.5937/jomb0-62448
Keywords: Type 2 diabetes, Osteoporosis, Fracture, Blood lipids, Hardened protein

Abstract


Objective To evaluate the predictive value of the monocyte/high-density lipoprotein cholesterol ratio (MHR), low-density lipoprotein-associated protein (LRP)-5 and sclerosing protein (SOST) for fractures in patients with osteoporosis due to type 2 diabetes.

Methods For the osteoporosis group, 218 individuals who received a type 2 diabetes diagnosis at this facility between January 2023 and December 2024 were chosen. Moreover, 90 patients with normal bone mass and 130 patients with decreased bone mass due to type 2 diabetes who were diagnosed at this center over the same time period were chosen as the normal bone mass group and the decreased bone mass group. Changes in the MHR, LPR-5 and SOST in each group and their relationships with the severity of fractures were observed. Binary logistic regression was used to analyze the influencing factors of fractures in patients with osteoporosis. Receiver operating characteristic (ROC) curves were used to assess the prediction effectiveness of the MHR, LPR-5, and SOST for fractures iin individuals with type 2 diabetes-related osteoporosis.

Results In the osteoporosis group, the MHR and LPR-5 were substantially higher (P<0.05) than those in the osteopenia group, and in the osteopenia group, they were significantly higher than those in the normal bone mass group.  The MHR and LPR-5 in the fracture group were significantly greater (P<0.05) than in the nonfracture group, and they also significantly increased as the fracture's severity rose (P<0.05). Compared to the groups with osteopenia and normal bone mass, the osteoporosis group's serum SOST level was considerably lower (P<0.05), and that in the osteopenia group was significantly lower than that in the normal bone mass group (P<0.05). The serum SOST level in the fracture group was significantly lower than that in the nonfracture group (P<0.05). Multivariate analysis revealed that BMI, FBG, the MHR, the LPR-5 and the SOST were independent influencing factors for fractures in patients with type 2 diabetes (P<0.05). The MHR, LPR-5, and SOST were significantly more predictive of fractures in patients with osteoporosis and type 2 diabetes than were BMI and FBG (P<0.01). The combined detection of the MHR, LPR-5 and SOST had a sensitivity of 87.5% and a specificity of 83.6% for diagnosing fractures in patients with osteoporosis and type 2 diabetes. While there was no statistically significant difference in the AUC of the individual detections of each index (P>0.05), the area under the curve (AUC) was 0.909, which was significantly greater than the AUC of the individual detections of MHR (Z=3.182, P<0.01), LPR-5 (Z=3.154, P<0.01), and SOST (Z=3.684, P<0.01).

Conclusion The MHR, LPR-5, and SOST are independent determinants of fractures and contribute to the onset and progression of osteoporosis in people with type 2 diabetes. The combined detection of the above three indicators has high predictive value for fractures in patients with osteoporosis and type 2 diabetes.

References

1.Martiniakova M, Biro R, Penzes N, Sarocka A, Kovacova V, Mondockova V, Omelka R. Links among Obesity, Type 2 Diabetes Mellitus, and Osteoporosis: Bone as a Target. Int J Mol Sci. 2024 Apr 28;25(9):4827. doi: 10.3390/ijms25094827. PMID: 38732046; PMCID: PMC11084398.
2.Lyu H, Zhao SS, Zhang L, Wei J, Li X, Li H, Liu Y, Yin P, Norvang V, Yoshida K, Tedeschi SK, Zeng C, Lei G, Tang P, Solomon DH. Denosumab and incidence of type 2 diabetes among adults with osteoporosis: population based cohort study. BMJ. 2023 Apr 18;381:e073435. doi: 10.1136/bmj-2022-073435. PMID: 37072150; PMCID: PMC10111187.
3.Li F, Wang Y, Cao J, Chen Q, Gao Y, Li R, Yuan L. Integrated analysis of genes shared between type 2 diabetes mellitus and osteoporosis. Front Pharmacol. 2024 Jun 20;15:1388205. doi: 10.3389/fphar.2024.1388205. PMID: 38966541; PMCID: PMC11222565.
4.Du A, Xu R, Yang Q, Lu Y, Luo X. Exploration of shared gene signatures and molecular mechanisms between type 2 diabetes and osteoporosis. J Cell Mol Med. 2024 May;28(9):e18141. doi: 10.1111/jcmm.18141. PMID: 38742851; PMCID: PMC11092535.
5.Scarpa ES, Antonelli A, Balercia G, Sabatelli S, Maggi F, Caprioli G, Giacchetti G, Micucci M. Antioxidant, Anti-Inflammatory, Anti-Diabetic, and Pro-Osteogenic Activities of Polyphenols for the Treatment of Two Different Chronic Diseases: Type 2 Diabetes Mellitus and Osteoporosis. Biomolecules. 2024 Jul 11;14(7):836. doi: 10.3390/biom14070836. PMID: 39062550; PMCID: PMC11275061.
6.Xu CY, Xu C, Xu YN, Du SQ, Dai ZH, Jin SQ, Zheng G, Xie CL, Fang WL. Poliumoside protects against type 2 diabetes-related osteoporosis by suppressing ferroptosis via activation of the Nrf2/GPX4 pathway. Phytomedicine. 2024 Mar;125:155342. doi: 10.1016/j.phymed.2024.155342. Epub 2024 Jan 7. PMID: 38295665.
7.Cao Y, Dong B, Li Y, Liu Y, Shen L. Association of type 2 diabetes with osteoporosis and fracture risk: A systematic review and meta-analysis. Medicine (Baltimore). 2025 Feb 7;104(6):e41444. doi: 10.1097/MD.0000000000041444. PMID: 39928813; PMCID: PMC11813021.
8.Tan J, Guo A, Zhang K, Jiang Y, Liu H. The effect of empagliflozin (sodium-glucose cotransporter-2 inhibitor) on osteoporosis and glycemic parameters in patients with type 2 diabetes: a quasiexperimental study. BMC Musculoskelet Disord. 2024 Oct 7;25(1):793. doi: 10.1186/s12891-024-07900-5. PMID: 39375646; PMCID: PMC11460138.
9.Mkhize BC, Mosili P, Ngubane PS, Sibiya NH, Khathi A. The Relationship between Renin-Angiotensin-Aldosterone System (RAAS) Activity, Osteoporosis and Estrogen Deficiency in Type 2 Diabetes. Int J Mol Sci. 2023 Jul 26;24(15):11963. doi: 10.3390/ijms241511963. PMID: 37569338; PMCID: PMC10419188.
10.Chen F, Wang P, Dai F, Zhang Q, Ying R, Ai L, Chen Y. Correlation Between Blood Glucose Fluctuations and Osteoporosis in Type 2 Diabetes Mellitus. Int J Endocrinol. 2025 Jan 23;2025:8889420. doi: 10.1155/ije/8889420. PMID: 39949568; PMCID: PMC11824305.
11.Henney AE, Riley DR, O'Connor B, Hydes TJ, Anson M, Zhao SS, Alam U, Cuthbertson DJ. Denosumab, for osteoporosis, reduces the incidence of type 2 diabetes, risk of foot ulceration and all-cause mortality in adults, compared with bisphosphonates: An analysis of real-world, cohort data, with a systematic review and meta-analysis. Diabetes Obes Metab. 2024 Sep;26(9):3673-3683. doi: 10.1111/dom.15708. Epub 2024 Jun 20. PMID: 38899553.
12.Wu L, Zheng Y, Liu J, Luo R, Wu D, Xu P, Wu D, Li X. Comprehensive evaluation of the efficacy and safety of LPV/r drugs in the treatment of SARS and MERS to provide potential treatment options for COVID-19. Aging (Albany NY). 2021 Apr 20;13(8):10833-10852. doi: 10.18632/aging.202860. Epub 2021 Apr 20. PMID: 33879634; PMCID: PMC8109137.
13.Vilaca T, Eastell R. Antiresorptive Versus Anabolic Therapy in Managing Osteoporosis in People with Type 1 and Type 2 Diabetes. JBMR Plus. 2023 Oct 29;7(11):e10838. doi: 10.1002/jbm4.10838. PMID: 38025034; PMCID: PMC10652175.
14.Yang Q, Wang X, Liu Y, Liu J, Zhu D. Metabolic factors are not the direct mediators of the association between type 2 diabetes and osteoporosis. Front Endocrinol (Lausanne). 2024 Jul 25;15:1404747. doi: 10.3389/fendo.2024.1404747. PMID: 39119008; PMCID: PMC11306037.
15.Jiang L, Song X, Yan L, Liu Y, Qiao X, Zhang W. Molecular insights into the interplay between type 2 diabetes mellitus and osteoporosis: implications for endocrine health. Front Endocrinol (Lausanne). 2025 Jan 17;15:1483512. doi: 10.3389/fendo.2024.1483512. PMID: 39897963; PMCID: PMC11782046.
16.Xu Y, Yan Z, Liu L. Association between advanced lung cancer inflammation index and osteoporosis in patients with type 2 diabetes mellitus: evidence from NHANES. Front Endocrinol (Lausanne). 2024 Nov 25;15:1421696. doi: 10.3389/fendo.2024.1421696. PMID: 39655346; PMCID: PMC11625538.
17.Wu L, Zhong Y, Wu D, Xu P, Ruan X, Yan J, Liu J, Li X. Immunomodulatory Factor TIM3 of Cytolytic Active Genes Affected the Survival and Prognosis of Lung Adenocarcinoma Patients by Multi-Omics Analysis. Biomedicines. 2022 Sep 10;10(9):2248. doi: 10.3390/biomedicines10092248. PMID: 36140350; PMCID: PMC9496572.
18.Li C, Gong H, Shi P, Liu S, Zhang Q. Different Forms of Regulated Cell Death in Type-2-Diabetes-Mellitus-Related Osteoporosis: A Focus on Mechanisms and Therapeutic Strategies. Int J Mol Sci. 2025 May 6;26(9):4417. doi: 10.3390/ijms26094417. PMID: 40362655; PMCID: PMC12072526.
19.Zhao H, Qi C, Zhang Y, Yang L, Ren L, Chen S. Relationship between albumin and osteoporosis in patients with type 2 diabetes mellitus. Front Endocrinol (Lausanne). 2025 Apr 14;16:1449557. doi: 10.3389/fendo.2025.1449557. PMID: 40297171; PMCID: PMC12034542.
20.Chen X, Jia X, Lan J, Wu W, Ni X, Wei Y, Zheng X, Liu J. Association between risk factors and bone mineral density and the development of a self-assessment tool for early osteoporosis screening in postmenopausal women with type 2 diabetes. PeerJ. 2024 Oct 11;12:e18283. doi: 10.7717/peerj.18283. PMID: 39403190; PMCID: PMC11472793.
21.Chen Y, Zhang Y, Qin S, Yu F, Ni Y, Zhong J. The correlation between TyG-BMI and the risk of osteoporosis in middle-aged and elderly patients with type 2 diabetes mellitus. Front Nutr. 2025 Mar 11;12:1525105. doi: 10.3389/fnut.2025.1525105. PMID: 40135223; PMCID: PMC11932904.
22.Wu L, Liu Q, Ruan X, Luan X, Zhong Y, Liu J, Yan J, Li X. Multiple Omics Analysis of the Role of RBM10 Gene Instability in Immune Regulation and Drug Sensitivity in Patients with Lung Adenocarcinoma (LUAD). Biomedicines. 2023 Jun 29;11(7):1861. doi: 10.3390/biomedicines11071861. PMID: 37509501; PMCID: PMC10377220.
23.Son O. Comparison of the effect of Dapagliflozin and Pioglitazone on the risk of osteoporosis in postmenopausal women with Type-2 diabetes. Pak J Med Sci. 2023 Sep-Oct;39(5):1238-1242. doi: 10.12669/pjms.39.5.7580. PMID: 37680820; PMCID: PMC10480740.
24.Al-Janabi AAHS. ROLE OF TYPE 2 DIABETES AND BODY MASS IN PROGRESSIVE OSTEOPENIA AND OSTEOPOROSIS. Acta Endocrinol (Buchar). 2024 Oct-Dec;20(4):544-550. doi: 10.4183/aeb.2024.544. Epub 2025 Oct 3. PMID: 41069533; PMCID: PMC12506882.
25.Tan YQ, Ng DX, Gunasekaran K, Lim WL, Tan NC. Clinical characteristics and risk factors for osteoporosis among older Asian men with type-2 diabetes mellitus, hypertension, or hyperlipidemia. Arch Osteoporos. 2024 Sep 5;19(1):83. doi: 10.1007/s11657-024-01442-y. PMID: 39235564; PMCID: PMC11377474.
Wu L, Zheng Y, Ruan X, Wu D, Xu P, Liu J, Wu D, Li X. Long-chain noncoding ribonucleic acids affect the survival and prognosis of patients with esophageal adenocarcinoma through the autophagy pathway: construction of a prognostic model. Anticancer Drugs. 2022 Jan 1;33(1):e590-e603. doi: 10.1097/CAD.0000000000001189. PMID: 34338240; PMCID: PMC8670349.
26.Lu CH, Lee CH, Wu LW, Liao CC, Su SC, Liu JS, Li PF, Huang CL, Ho LJ, Lin CM, Lin MH, Chang CY, Liu YC, Lin CP, Cheng AC, Kuo FC. Gender-specific impacts of thigh skinfold thickness and grip strength for predicting osteoporosis in type 2 diabetes. Diabetol Metab Syndr. 2023 May 18;15(1):103. doi: 10.1186/s13098-023-01087-w. PMID: 37198661; PMCID: PMC10193705.
27.Cheng L, Wang S, Tang H. Type 2 diabetes mellitus plays a protective role against osteoporosis --mendelian randomization analysis. BMC Musculoskelet Disord. 2023 Jun 2;24(1):444. doi: 10.1186/s12891-023-06528-1. PMID: 37268885; PMCID: PMC10236750.
28.Vilaca T, Eastell R. Efficacy of Osteoporosis Medications in Patients with Type 2 Diabetes. Curr Osteoporos Rep. 2024 Feb;22(1):1-10. doi: 10.1007/s11914-023-00833-3. Epub 2023 Dec 14. PMID: 38093031; PMCID: PMC10912145.
29.Wu L, Zhong Y, Yu X, Wu D, Xu P, Lv L, Ruan X, Liu Q, Feng Y, Liu J, Li X. Selective poly adenylation predicts the efficacy of immunotherapy in patients with lung adenocarcinoma by multiple omics research. Anticancer Drugs. 2022 Oct 1;33(9):943-959. doi: 10.1097/CAD.0000000000001319. Epub 2022 Aug 9. PMID: 35946526; PMCID: PMC9481295.
30.Yang T, Feng X, Wang N, Zhang T, Zheng Z, Wang G. Association between lncRNA H19 and osteoporosis in postmenopausal patients with type 2 diabetes mellitus. J Orthop Surg Res. 2025 Aug 7;20(1):737. doi: 10.1186/s13018-025-06153-9. PMID: 40775721; PMCID: PMC12330039.
31.Pan B, Zhao Y, Chen C, Cai J, Li K, Wang Y, Liu J. The relationship between advanced liver fibrosis and osteoporosis in type 2 diabetes patients with MAFLD. Endocrine. 2024 Jul;85(1):206-221. doi: 10.1007/s12020-024-03724-4. Epub 2024 Feb 17. PMID: 38367145.
32.Wu L, Li H, Liu Y, Fan Z, Xu J, Li N, Qian X, Lin Z, Li X, Yan J. Research progress of 3D-bioprinted functional pancreas and in vitro tumor models. International Journal of Bioprinting. 2024, 10(1), 1256. doi: 10.36922/ijb.1256.
33.Ni J, Zhang Q, Lei F. Noninvasive diagnostic potential of salivary miR-25-3p for periodontal disease and osteoporosis among a cohort of elderly patients with type 2 diabetes mellitus. BMC Oral Health. 2023 May 23;23(1):318. doi: 10.1186/s12903-023-02992-2. PMID: 37221590; PMCID: PMC10204676.
34.Chen M, Lyu Y, Zhao J, Han X, Huang T, Yang T, Zhou Y. Use of GLP-1 receptor agonist and risk of osteoporosis among patients with type 2 diabetes: a real-world study. Front Endocrinol (Lausanne). 2025 May 21;16:1586589. doi: 10.3389/fendo.2025.1586589. PMID: 40469447; PMCID: PMC12133453.
35.Tan J, Zhang Z, He Y, Xu X, Yang Y, Xu Q, Yuan Y, Wu X, Niu J, Tang S, Wu X, Hu Y. Development and validation of a risk prediction model for osteoporosis in elderly patients with type 2 diabetes mellitus: a retrospective and multicenter study. BMC Geriatr. 2023 Oct 27;23(1):698. doi: 10.1186/s12877-023-04306-1. PMID: 37891456; PMCID: PMC10604807.
Published
2025/12/21
Issue
Ahead of print
Section
Original paper

Copyright (c) 2025 Xiang Li, Shiwei Sun, Tianlong Zhang, Bohao Li, Jiarui Zhang, Yu Zhao, Yi Xie, Siqi Yang, Minghai Wang

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

The published articles will be distributed under the Creative Commons Attribution 4.0 International License (CC BY). It is allowed to copy and redistribute the material in any medium or format, and remix, transform, and build upon it for any purpose, even commercially, as long as appropriate credit is given to the original author(s), a link to the license is provided and it is indicated if changes were made. Users are required to provide full bibliographic description of the original publication (authors, article title, journal title, volume, issue, pages), as well as its DOI code. In electronic publishing, users are also required to link the content with both the original article published in Journal of Medical Biochemistry and the licence used.

Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.