Reduced Intestinal Calcium Absorption Correlates With Bone Loss After Sleeve Gastrectomy: Implications for Clinical Care

Obesity is a worldwide epidemic that shows no sign of abating. By 2030, if the trend continues, half of the population will be obese and 10% will suffer from severe obesity (1). For people living with severe obesity, bariatric surgery provides an unmet need to attain sufficient and sustainable weight loss, and to revert obesity-related complications. However, the undisputed health benefits of bariatric surgery come at a cost. It is now clear that the malabsorptive bariatric procedures, such as the Roux-in-Y gastric bypass (RYGB) and biliopancreatic diversion with duodenal switch (BPD), lead to clinically significant bone loss, deteriorated bone microarchitecture, and increased fracture risk (2). Multiple factors contribute to the adverse skeletal effects of malabsorptive bariatric procedures, including reduced intestinal absorption of calcium. RYGB and BPD bypass the duodenum and proximal jejunum, which are the primary sites of active transcellular 1,25-dihydroxyvitamin D–mediated intestinal calcium absorption. While paracellular intestinal calcium absorption also occurs throughout the intestine, active transcellular intestinal calcium absorption is particularly solicited when calcium intake is low (3). Using the dual stable isotope technique, Schafer et al have previously reported that fractional excretion of calcium (FCA) decreases by as much as 73% at 6 months after RYGB despite ensuring adequate vitamin D status and supplementing with the recommended calcium citrate dose (4). As expected, as FCA declined, 24-hour urinary calcium decreased, while serum parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D levels increased. Moreover, those with lower FCA had a greater rise in the serum bone resorption marker C-telopeptide. These results suggest that patients undergoing RYGB require higher calcium intake to maintain calcium homeostasis, and to mitigate adverse skeletal health consequences. Laparoscopic sleeve gastrectomy (LSG) has surpassed RYGB and is nowadays the most performed bariatric procedure. While the available data on the impact of LSG on fracture risk are reassuring—at least in the short to medium term—LSG leads to bone loss that has been reported to be lesser than or similar to RYGB (5). In contrast to RYGB and BPD, LSG is a restrictive procedure that limits food intake by reducing stomach size. As the intestinal tract remains intact, it is not predicted to affect calcium absorption per se. Nonetheless, insufficient overall nutrient intake (including calcium), reduced gastric acidity, and accelerated gastric emptying and intestinal motility might interfere with calcium balance after LSG (6). To determine the impact of LSG on calcium homeostasis, a carefully designed study that assesses rigorously calcium absorption in vitamin D–replete individuals with recommended calcium intake is essential. Indeed, adequate calcium intake is a potentially actionable factor to minimize bone resorption and skeletal deterioration after bariatric surgery. Such an elegant clinical study was performed by Wu et al (7). Using the dual stable isotope technique, they measured FCA before and at 6 months after LSG in 35 individuals meeting the criteria for bariatric surgery and aged 24-70 years (mean age 45.6 years; mean body mass index 43.7 kg/m2; 86% women of whom 37% were postmenopausal; 77% White, 20% Black, 3% more than 1 race). Despite meticulous attention to ensuring serum 25-hydroxyvitamin D levels ≥30 ng/mL and achieving recommended daily calcium intake of 1200 mg from diet and calcium citrate supplements over the study period, FCA dropped substantially by half, from a mean of 31.4% at baseline to 16.1% at 6 months after LSG. In parallel, serum 1,25-dihydroxyvitamin D and bone turnover markers rose while areal bone mineral density at the total hip and femoral neck declined significantly. Noteworthy, lower postoperative FCA levels were associated with greater total hip areal bone mineral density loss. We now need studies on the impact of reduced FCA on long-term skeletal outcomes after LSG. Other findings deserve discussion. While most participants experienced FCA decline after LSG, there was interindividual variability among the participants. In fact, FCA variation was larger after LSG than what had been reported for RYGB (4). A better understanding of the factors affecting FCA after LSG could pave the way to intervention strategies. Yet, they remain largely unknown. The authors explored several potential determinants but none of them were found to be associated with postoperative FCA or FCA change after LSG, including age, sex, menopausal status, proton pump inhibitor use, changes in weight, dietary macronutrient or fiber intakes, calciotropic hormones, estradiol levels, or adipokines. Of interest, however, they did find that participants with greater postoperative increases in serum insulin-like growth factor 1 (IGF-1) levels had higher postoperative FCA and a lower magnitude of hip bone loss. This is in line with previous work supporting a role of serum IGF-1 in calcium balance, especially when there is higher calcium demand or reduced calcium availability (8). It is also worth mentioning that despite markedly reduced FCA after LSG, serum PTH and 24-hour urinary calcium levels did not change significantly. The reason behind the unexpected lack of serum parathyroid hormone increase and 24-hour urinary calcium decrease in the context of FCA decline is unclear. The authors speculate that it might be related to non-PTH–mediated increases in bone resorption. This finding is however surprising and warrants further study. It also means that PTH and 24-hour urinary calcium cannot be used in clinical practice to monitor calcium intake after LSG. This study has implications for clinical practice. The most recent position statement on metabolic bone changes after bariatric surgery from the American Society for Metabolic and Bariatric Surgery recommends 1200 to 1500 mg of calcium daily from diet and calcium citrate supplements following LSG. Wu et al have calculated that to maintain the same net calcium input that the participants had preoperatively, they would need to consume 2340 mg of calcium daily, which is substantially higher than the current recommendations. This would translate into a lifelong commitment to consume several calcium tablets daily, which is challenging for the patients. There is thus a need for identifying innovative strategies to enhance calcium bioavailability after LSG, for instance via hormonal (eg, increased IGF-1), diet, or gut microbiota modulation. This opens a whole new exciting field of research that could ultimately increase the benefit–risk ratio of bariatric procedures by mitigating their deleterious effects on skeletal health. The author would like to thank Dr. Suzanne N. Morin for critically reviewing the manuscript. C.G. is a research scholar from the Fonds de recherche du Québec-Santé. None. biliopancreatic diversion with duodenal switch fractional excretion of calcium insulin-like growth factor 1 laparoscopic sleeve gastrectomy parathyroid hormone Roux-in-Y gastric bypass

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