Endocrinol Metab.  2024 Aug;39(4):632-640. 10.3803/EnM.2024.1956.

Differential Impact of Subcutaneous and Visceral Fat on Bone Changes after Gastrectomy

• Cho S
• Shin S
• Lee S
• Rhee Y
• Kim HI
• Hong N

• KMID: 2558947
• DOI: http://doi.org/10.3803/EnM.2024.1956

Abstract

Background
Osteoporosis and fragility fractures are crucial musculoskeletal complications in long-term survivors of gastric cancer. However, the relationship between changes in body composition after gastrectomy and bone loss has not been investigated. Therefore, this study aimed to explore whether computed tomography (CT)-derived body composition parameters are associated with bone loss after gastrectomy in patients with gastric cancer.
Methods
We retrospectively reviewed medical records and abdomen CT scans of patients who underwent gastrectomy at Yonsei University Severance Hospital between 2009 and 2018. Patients with non-metastatic gastric adenocarcinoma and preoperative and postoperative non-contrast CT scans were analyzed. Section area of skeletal muscle (SMA), visceral fat (VFA), and subcutaneous fat (SFA) were assessed using semi-automatic segmentation software. Changes in trabecular bone attenuation of L1 mid-vertebra level (L1 Hounsfield units [HU]) were measured.
Results
Fifty-seven patients (mean age, 65.5±10.6; 70.2% males) were analyzed, and the median duration was 31 months. Fortyseven patients (82.5%) lost weight after gastrectomy. Baseline SMA and VFA did not differ between the bone loss and preserved groups; however, baseline SFA was significantly higher in the bone preserved group than in the bone loss group (P=0.020). In a multivariable linear regression model adjusted for confounding factors, one standard deviation higher VFA at baseline was associated with greater annualized L1 HU loss (%) (P=0.034). However, higher preoperative SFA was associated with protection against bone loss after gastrectomy (P=0.025).
Conclusion
Higher preoperative SFA exhibited a protective effect against bone loss after gastrectomy in patients with non-metastatic gastric cancer, whereas VFA exhibited a negative effect.

Keyword

Body composition; Subcutaneous fat; Gastrectomy; Stomach neoplasms

Figure

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  Fig. 1. Study flow. CT, computed tomography.

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  Fig. 2. Comparison of body composition including (A) skeletal muscle area, (B) visceral fat area, and (C) subcutaneous fat area between the bone loss and preserved groups. Bone loss and preserved groups are stratified by the median of annualized trabecular bone loss. Pre, preoperative; Post, postoperative. aP<0.05 vs. Pre value; bP=0.020.

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Reference

1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021; 71:209–49.

2. Oh HJ, Yoon BH, Ha YC, Suh DC, Lee SM, Koo KH, et al. The change of bone mineral density and bone metabolism after gastrectomy for gastric cancer: a meta-analysis. Osteoporos Int. 2020; 31:267–75.

3. Oh HJ, Lim CH, Yoon BH, Yoon SB, Baeg MK, Kim WC, et al. Fracture after gastrectomy for gastric cancer: a longterm follow-up observational study. Eur J Cancer. 2017; 72:28–36.

4. Park C, Ha YC, Jang S, Jang S, Yoon HK, Lee YK. The incidence and residual lifetime risk of osteoporosis-related fractures in Korea. J Bone Miner Metab. 2011; 29:744–51.

5. Langlois JA, Visser M, Davidovic LS, Maggi S, Li G, Harris TB. Hip fracture risk in older white men is associated with change in body weight from age 50 years to old age. Arch Intern Med. 1998; 158:990–6.

6. Langlois JA, Harris T, Looker AC, Madans J. Weight change between age 50 years and old age is associated with risk of hip fracture in white women aged 67 years and older. Arch Intern Med. 1996; 156:989–94.

7. Davis JL, Selby LV, Chou JF, Schattner M, Ilson DH, Capanu M, et al. Patterns and predictors of weight loss after gastrectomy for cancer. Ann Surg Oncol. 2016; 23:1639–45.

8. Aoyama T, Kawabe T, Hirohito F, Hayashi T, Yamada T, Tsuchida K, et al. Body composition analysis within 1 month after gastrectomy for gastric cancer. Gastric Cancer. 2016; 19:645–50.

9. Baek KH, Jeon HM, Lee SS, Lim DJ, Oh KW, Lee WY, et al. Short-term changes in bone and mineral metabolism following gastrectomy in gastric cancer patients. Bone. 2008; 42:61–7.

10. Zillikens MC, Uitterlinden AG, van Leeuwen JP, Berends AL, Henneman P, van Dijk KW, et al. The role of body mass index, insulin, and adiponectin in the relation between fat distribution and bone mineral density. Calcif Tissue Int. 2010; 86:116–25.

11. Kim JH, Choi HJ, Ku EJ, Hong AR, Kim KM, Kim SW, et al. Regional body fat depots differently affect bone microarchitecture in postmenopausal Korean women. Osteoporos Int. 2016; 27:1161–8.

12. Yip C, Dinkel C, Mahajan A, Siddique M, Cook GJ, Goh V. Imaging body composition in cancer patients: visceral obesity, sarcopenia and sarcopenic obesity may impact on clinical outcome. Insights Imaging. 2015; 6:489–97.

13. Gilsanz V, Chalfant J, Mo AO, Lee DC, Dorey FJ, Mittelman SD. Reciprocal relations of subcutaneous and visceral fat to bone structure and strength. J Clin Endocrinol Metab. 2009; 94:3387–93.

14. Choi MH, Kim KA, Hwang SS, Byun JY. CT-quantified muscle and fat change in patients after surgery or endoscopic resection for early gastric cancer and its impact on longterm outcomes. Medicine (Baltimore). 2018; 97:e13878.

15. Park HS, Kim HS, Beom SH, Rha SY, Chung HC, Kim JH, et al. Marked loss of muscle, visceral fat, or subcutaneous fat after gastrectomy predicts poor survival in advanced gastric cancer: single-center study from the CLASSIC trial. Ann Surg Oncol. 2018; 25:3222–30.

16. Yoon DY, Kim HK, Kim JA, Choi CS, Yun EJ, Chang SK, et al. Changes in the abdominal fat distribution after gastrectomy: computed tomography assessment. ANZ J Surg. 2007; 77:121–5.

17. Japanese Gastric Cancer Association. Japanese Gastric Cancer Treatment Guidelines 2021 (6th edition). Gastric Cancer. 2023; 26:1–25.

18. Kim TH, Kim IH, Kang SJ, Choi M, Kim BH, Eom BW, et al. Korean Practice Guidelines for Gastric Cancer 2022: an evidence-based, multidisciplinary approach. J Gastric Cancer. 2023; 23:3–106.

19. Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, et al. The eighth edition AJCC Cancer Staging Manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin. 2017; 67:93–9.

20. Lee YS, Hong N, Witanto JN, Choi YR, Park J, Decazes P, et al. Deep neural network for automatic volumetric segmentation of whole-body CT images for body composition assessment. Clin Nutr. 2021; 40:5038–46.

21. Jang S, Graffy PM, Ziemlewicz TJ, Lee SJ, Summers RM, Pickhardt PJ. Opportunistic osteoporosis screening at routine abdominal and thoracic CT: normative L1 trabecular attenuation values in more than 20 000 adults. Radiology. 2019; 291:360–7.

22. Pickhardt PJ, Pooler BD, Lauder T, del Rio AM, Bruce RJ, Binkley N. Opportunistic screening for osteoporosis using abdominal computed tomography scans obtained for other indications. Ann Intern Med. 2013; 158:588–95.

23. Gimble JM, Robinson CE, Wu X, Kelly KA. The function of adipocytes in the bone marrow stroma: an update. Bone. 1996; 19:421–8.

24. Rosen CJ, Bouxsein ML. Mechanisms of disease: is osteoporosis the obesity of bone? Nat Clin Pract Rheumatol. 2006; 2:35–43.

25. Yamauchi M, Sugimoto T, Yamaguchi T, Nakaoka D, Kanzawa M, Yano S, et al. Plasma leptin concentrations are associated with bone mineral density and the presence of vertebral fractures in postmenopausal women. Clin Endocrinol (Oxf). 2001; 55:341–7.

26. Morley JE, Baumgartner RN. Cytokine-related aging process. J Gerontol A Biol Sci Med Sci. 2004; 59:M924–9.

27. Stein EM, Carrelli A, Young P, Bucovsky M, Zhang C, Schrope B, et al. Bariatric surgery results in cortical bone loss. J Clin Endocrinol Metab. 2013; 98:541–9.

28. Lindeman KG, Rushin CC, Cheney MC, Bouxsein ML, Hutter MM, Yu EW. Bone density and trabecular morphology at least 10 years after gastric bypass and gastric banding. J Bone Miner Res. 2020; 35:2132–42.

29. Yoo SH, Lee JA, Kang SY, Kim YS, Sunwoo S, Kim BS, et al. Risk of osteoporosis after gastrectomy in long-term gastric cancer survivors. Gastric Cancer. 2018; 21:720–7.

30. Kang KY, Hong YS, Park SH, Ju JH. Increased serum alkaline phosphatase levels correlate with high disease activity and low bone mineral density in patients with axial spondyloarthritis. Semin Arthritis Rheum. 2015; 45:202–7.

31. Ciecko C, Okut H, Lancaster B, Schwasinger-Schmidt T. Prevalence of elevated alkaline phosphatase levels among post-bariatric surgery patients. Langenbecks Arch Surg. 2023; 408:285.

32. Mihmanli M, Isil RG, Isil CT, Omeroglu S, Sayin P, Oba S, et al. Effects of laparoscopic sleeve gastrectomy on parathyroid hormone, vitamin D, calcium, phosphorus, and albumin levels. Obes Surg. 2017; 27:3149–55.

33. Lim SM, Kim YN, Park KH, Kang B, Chon HJ, Kim C, et al. Bone alkaline phosphatase as a surrogate marker of bone metastasis in gastric cancer patients. BMC Cancer. 2016; 16:385.

34. Wu YJ, Wang Y, Qin R, Cao ZY, Zhao HZ, Du XH, et al. Serum alkaline phosphatase predicts poor disease-free survival in patients receiving radical gastrectomy. Med Sci Monit. 2018; 24:9073–80.

35. Choi MK, Kim SM, Lim JK. Diagnostic efficacy of Hounsfield units in spine CT for the assessment of real bone mineral density of degenerative spine: correlation study between T-scores determined by DEXA scan and Hounsfield units from CT. Acta Neurochir (Wien). 2016; 158:1421–7.

36. Lee SJ, Anderson PA, Pickhardt PJ. Predicting future hip fractures on routine abdominal CT using opportunistic osteoporosis screening measures: a matched case-control study. AJR Am J Roentgenol. 2017; 209:395–402.

37. Zou D, Ye K, Tian Y, Li W, Zhou F, Zhang Z, et al. Characteristics of vertebral CT Hounsfield units in elderly patients with acute vertebral fragility fractures. Eur Spine J. 2020; 29:1092–7.

38. Pickhardt PJ, Graffy PM, Zea R, Lee SJ, Liu J, Sandfort V, et al. Automated abdominal CT imaging biomarkers for opportunistic prediction of future major osteoporotic fractures in asymptomatic adults. Radiology. 2020; 297:64–72.