Risk factors for loss of bone mineral density after curative esophagectomy
Micronutrient and fat malabsorption and altered enteroendocrine signaling occur after esophagectomy for cancer; however, the impact of malnutrition on bone health in this cohort has not been previously investigated. In this study, the prevalence of osteoporosis increased after curative surgery, associated with disease-specific, treatment-related, and population risk factors.
Improved oncologic outcomes in esophageal cancer (EC) have resulted in increased survivorship and a focus on long-term quality of life. Malnutrition and micronutrient malabsorption are common among patients with EC, but the effect on bone metabolism is not known. The aim of this study was to characterize changes in bone mineral density (BMD) following curative esophagectomy.
Consecutive disease-free patients who underwent esophagectomy with gastric conduit for pathologically node-negative disease from 2000 to 2014 were included. BMD was assessed at vertebral levels T12-L5 by computed tomography using a simple trabecular region-of-interest attenuation technique, and serum markers of nutritional status and bone metabolism were examined. Independent risk factors for osteoporosis were identified by multivariable logistic regression.
Seventy-five consecutive patients were studied. Osteoporosis was present in 25% at diagnosis. BMD declined at 1 and 2 years postoperatively (144.3 ± 45.8 versus 128.6 ± 46.2 and 122.7 ± 43.5 Hounsfield Units (HU), P < 0.0001), with increased osteoporosis prevalence to 38% and 44% (P = 0.049), respectively. No significant postoperative change in vitamin D, calcium, or phosphate was observed, but alkaline phosphatase increased significantly (P < 0.001). While female sex (P = 0.004) and ASA grade (P = 0.043) were independently associated with osteoporosis at diagnosis, age (P = 0.050), female sex (P = 0.023), smoking (P = 0.024), and pathologic T stage (P = 0.023) were independently predictive of osteoporosis at 1 year postoperatively.
Osteoporosis is prevalent among disease-free patients post-esophagectomy for EC, associated with disease-specific, treatment-related, and population risk factors. Strategies which minimize BMD decline should be considered to avoid fragility fractures in this cohort.
KeywordsBone Bone mineral density Esophagectomy Esophageal cancer Malnutrition Malabsorption
Compliance with ethical standards
Conflicts of interest
- 2.Klevebro F, Alexandersson von Dobeln G, Wang N, et al. A randomized clinical trial of neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the oesophagus or gastro-oesophageal junction. Ann Oncol 2016Google Scholar
- 3.Shapiro J, van Lanschot JJ, Hulshof MC, van Hagen P, van Berge Henegouwen M, Wijnhoven BPL, van Laarhoven H, Nieuwenhuijzen GAP, Hospers GAP, Bonenkamp JJ, Cuesta MA, Blaisse RJB, Busch ORC, ten Kate F, Creemers GM, Punt CJA, Plukker JTM, Verheul HMW, Bilgen EJS, van Dekken H, van der Sangen M, Rozema T, Biermann K, Beukema JC, Piet AHM, van Rij C, Reinders JG, Tilanus HW, Steyerberg EW, van der Gaast A, CROSS study group (2015) Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol 16:1090–1098CrossRefGoogle Scholar
- 10.Elliott JA, Docherty NG, Eckhardt HG et al (2016) Weight loss, satiety, and the postprandial gut hormone response after Esophagectomy: a prospective study. Ann SurgGoogle Scholar
- 12.Healy LA, Ryan A, Doyle SL, Ní Bhuachalla ÉB, Cushen S, Segurado R, Murphy T, Ravi N, Donohoe CL, Reynolds JV (2017) Does prolonged enteral feeding with supplemental Omega-3 fatty acids impact on recovery post-Esophagectomy: results of a randomized double-blind trial. Ann Surg 266:720–728CrossRefGoogle Scholar
- 14.Elliott JA, Doyle SL, Murphy CF, et al. Sarcopenia: Prevalence, and Impact on Operative and Oncologic Outcomes in the Multimodal Management of Locally Advanced Esophageal Cancer. Ann Surg 2017Google Scholar
- 19.Frederiksen KD, Hanson S, Hansen S, et al. Bone Structural Changes and Estimated Strength After Gastric Bypass Surgery Evaluated by HR-pQCT. Calcif Tissue Int 2015Google Scholar
- 20.Yu EW, Wewalka M, Ding SA, et al. Effects of Gastric Bypass and Gastric Banding on Bone Remodeling in Obese Patients with Type 2 Diabetes. J Clin Endocrinol Metab 2015:jc20153437Google Scholar
- 22.Chambers AP, Smith EP, Begg DP, Grayson BE, Sisley S, Greer T, Sorrell J, Lemmen L, LaSance K, Woods SC, Seeley RJ, D'Alessio DA, Sandoval DA (2014) Regulation of gastric emptying rate and its role in nutrient-induced GLP-1 secretion in rats after vertical sleeve gastrectomy. Am J Physiol Endocrinol Metab 306:E424–E432CrossRefGoogle Scholar
- 26.Cunningham D, Allum WH, Stenning SP, Thompson JN, van de Velde C, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, MAGIC Trial Participants (2006) Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 355:11–20CrossRefGoogle Scholar
- 28.van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen M, Wijnhoven BP, Richel DJ, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, Cuesta MA, Blaisse RJ, Busch OR, ten Kate F, Creemers GJ, Punt CJ, Plukker JT, Verheul HM, Spillenaar Bilgen EJ, van Dekken H, van der Sangen M, Rozema T, Biermann K, Beukema JC, Piet AH, van Rij C, Reinders JG, Tilanus HW, van der Gaast A, CROSS Group (2012) Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 366:2074–2084CrossRefGoogle Scholar
- 29.Keegan N, Keane F, Cuffe S et al (2014) ICORG 10-14: neo-AEGIS: a randomized clinical trial of neoadjuvant and adjuvant chemotherapy (modified MAGIC regimen) versus neoadjuvant chemoradiation (CROSS protocol) in adenocarcinoma of the esophagus and esophagogastric junction. J Clin Oncol 32:TPS4145CrossRefGoogle Scholar
- 36.Gepp H, Koch M, Schwille PO, Erben RG, Rümenapf G, Schmiedl A, Fries W (2000) Vagus-sparing gastric fundectomy in the rat: development of osteopenia, relationship to urinary phosphate and net acid excretion, serum gastrin and vitamin D. Res Exp Med (Berl) 200:1–16Google Scholar
- 40.Schafer AL, Weaver CM, Black DM, Wheeler AL, Chang H, Szefc GV, Stewart L, Rogers SJ, Carter JT, Posselt AM, Shoback DM, Sellmeyer DE (2015) Intestinal calcium absorption decreases dramatically after gastric bypass surgery despite optimization of vitamin D status. J Bone Miner Res 30:1377–1385CrossRefGoogle Scholar
- 42.Elias E, Casselbrant A, Werling M, Abegg K, Vincent RP, Alaghband-Zadeh J, Olbers T, le Roux CW, Fändriks L, Wallenius V (2014) Bone mineral density and expression of vitamin D receptor-dependent calcium uptake mechanisms in the proximal small intestine after bariatric surgery. Br J Surg 101:1566–1575CrossRefGoogle Scholar
- 47.Muschitz C, Kocijan R, Haschka J et al (2015) The impact of vitamin D, calcium, protein supplementation, and physical exercise on bone metabolism after bariatric surgery: the BABS study. J Bone Miner ResGoogle Scholar
- 50.Haas S, Krins S, Knauerhase A, Löhr M (2015) Altered bone metabolism and bone density in patients with chronic pancreatitis and pancreatic exocrine insufficiency. JOP: J Pancreas 16:58–62Google Scholar