Major Pancreatic Resection Increases Bone Mineral Density Loss, Osteoporosis, and Fractures

Objective: To assess whether long-term survivors of pancreatic surgery show increased risk to develop impaired bone mineral density, osteoporosis, and vitamin D deficiency. Background: Pancreatic resection poses a risk for malabsorption of fat-soluble vitamins and other micronutrients essential for bone mineralization. Here, we evaluated the long-term effects of pancreatic resection on bone mineral density (BMD) and its clinical sequelae. Methods: This was a two-pronged analysis of post-pancreatectomy patients with a follow-up period greater than 3 years comprising (1) a large, propensity score-matched, cohort study based on a multinational federated research network (FRN) and (2) a retrospective single institution review of clinical and radiographic patient data. In the FRN analysis, an initial cohort of 8,423 post-pancreatectomy patients were identified and propensity score-matched with normal controls. The primary endpoint was the 10-year risk of developing osteoporotic pathological fractures and secondary endpoints included diagnosis of osteoporosis, vitamin-D deficiency, and related therapies. The single institution retrospective analysis identified 224 patients who underwent pancreatic resection between 2005 and 2019. BMD was quantified in CT images acquired before and after surgery. BMD trends and related factors were assessed in a time-series mixed effect linear regression model. Results: A total of 8,080 propensity score-matched pairs were included in the FRN analysis. The analysis revealed a 2.4-fold increase in pathological fractures ( P <0.0001) and 1.4-1.5 fold increase in osteoporosis/osteomalacia ( P <0.0001) and vitamin-D deficiency ( P <0.0001) in post-pancreatectomy patients. Vitamin-D supplements were more common in the pancreatectomy group (OR 1.4, 95% CI 1.28-1.53, P <0.0001), as were specific osteoporosis/osteomalacia treatments such as calcitonin, denosumab, romosozumab, abaloparatide, and teriparatide (OR 2.24, 95%CI 1.69-2.95, P <0.0001). Retrospective analysis of CT imaging revealed that BMD declined more rapidly following pancreatic resection compared to normal historical controls ( P =0.015). Older age, pancreatic cancer, and pancreaticoduodenectomy were associated with increased rates of BMD loss ( P <0.05, each). Conclusions: After pancreatic resection, patients are at higher risk for BMD loss and subsequent fractures. As the cohort of pancreatic resection survivorship grows, attention will need to be paid to focused prevention efforts to reduce BMD loss, osteoporosis, and fractures in these vulnerable patients, with specific attention to the pancreatic cancer population.