The current address of Dr. Alterations of the endocrine system in patients following Roux-en-Y gastric bypass GBP are poorly described and have prompted us to perform a longitudinal study of the effects of GBP on serum calcium, hydroxy-vitamin-D vitamin Dand parathyroid hormone PTH. Student t test, Fisher exact test, or linear regression was used to determine significance.
When corrected for albumin levels, mean calcium was 9. Alkaline phosphatase levels were elevated in Thus, calcium malabsorption is inherent to gastric bypass. Careful calcium and vitamin D supplementation and long-term screening are necessary to prevent deficiencies and the sequelae of secondary hyperparathyroidism, vitamin d deficiency and elevated pth.
A number of different weight reduction operations are performed throughout the world, but Roux-en-Y gastric bypass GBP is the leading weight reduction operation offered in the United States. It has been well documented that GBP provides long-term weight reduction with prevention or resolution of comorbid conditions, 2—4 but the endocrine side effects of GBP remain incompletely studied.
Until recently, vitamin d deficiency and elevated pth, our bariatric surgery protocol included annual screening of calcium, phosphorus, magnesium, and albumin after GBP. With newer literature, 5 suggesting that patients who undergo GBP are at increased risk for vitamin D deficiency, our screening was updated to include both hydroxyvitamin D vitamin D and parathyroid hormone PTH levels. This is a longitudinal study of prospectively collected data that evaluates the endocrine effects of GBP on vitamin D, calcium and PTH levels.
A total of patients underwent routine laboratory testing after having GBP surgery. The testing included measurement of serum levels of vitamin D, PTH, calcium, and albumin levels. Statistical analysis using Student t test, Fisher exact test, or linear regression was used to determine the correlation of vitamin D levels to PTH levels and also determine whether vitamin D deficiency and hyperparathyroidism correlated to the length of bypass segment and time from initial surgery.
Mean corrected calcium levels were 9. The average vitamin D level for the entire group was Parathormone levels at annual intervals following Roux-en-Y gastric bypass. PTH levels increased in a linear fashion with time. Parathormone levels as a function of hydroxy-vitamin D levels. A significant negative linear correlation is evident. Patients with elevated PTH levels had a higher incidence of elevated alkaline phophatase levels than those with normal PTH levels There was a significant correlation of alkaline phosphatase with PTH levels Fig.
Linear relationship between PTH levels and serum alkaline phosphatase in gastric bypass patients. The relationship suggests active bone loss with secondary hyperparathyroidism, vitamin d deficiency and elevated pth. As the rate of obesity continues to rise in the United States, the demand for weight-reduction surgery will continue to increase. It has been estimated that the number of obesity procedures performed in the United States will topinand may even exceedby When patients undergo GBP, the preferential sites for the absorption of calcium, the duodenum and proximal jejunum are bypassed, vitamin d deficiency and elevated pth, placing them at an increased risk for hypocalcemia.
A necessary component of calcium absorption within the intestines is vitamin D. The decreased intake of vitamin D then leads to a decrease in the absorption of calcium from the intestinal lumen. Furthermore, it has been suggested that the creation of a Roux anastomosis in itself causes malabsorption of fat-soluble vitamins due to poor mixing with bile salts, thus creating a further decrease in the amount of vitamin D available and still less absorption of calcium.
One of the defense mechanisms of the body for the maintenance of normocalcemia, in the setting of decreased absorption of calcium, is the up-regulation of PTH, which directly causes an increased production of 1,dihydroxy vitamin D calcitriol and, more importantly, an increase in calcium reabsorption from the bone.
This is of great concern because, if left neglected over long periods of time, vitamin D deficiency and secondary hyperparathyroidism can result in osteopenia, osteoporosis, and ultimately osteomalacia. As one might anticipate, there was an inverse, linear relationship between PTH levels and serum vitamin D levels such that the lower the vitamin D, the higher the PTH levels Fig.
The longer patients were followed from their original surgery, the more prone they were to deficiencies of vitamin D Fig. Our data underscore the importance of aggressively supplementing, screening, and treating post-GBP patients for vitamin D deficiencies. The fact that a significant number of SL-GBP patients with normal vitamin D levels were also hyperparathyroid suggests that some patients selectively malabsorb calcium after GBP.
Another possibility is that due to a low acid environment after GBP, calcium carbonate may be poorly absorbed; calcium citrate may be a better option in these patients. Since morbidly obese patients have a higher incidence of elevated PTH levels than normal weight individuals, even before surgery, it is apparent that patients should be screened quite early in the therapeutic process and that patients should be educated as to the importance of compliance with vitamin and mineral supplementation.
We currently recommend that all patients be supplemented with at least mg of calcium per day and an additional IU of vitamin D per day following GBP.
Since the paracellular absorptive process in the distal jejunum and ileum is less vitamin D-dependent than the transcellular process in the duodenum and proximal jejunum, there is reason to fear that supplementation may be ineffective. It remains to be seen whether more aggressive therapy with high doses of vitamin D can correct secondary hyperparathyroidism.
MacDonald Greenville, North Carolina: Many of the findings in this paper have been confirmed by other reports, although there is not complete unanimity of the results, and there remain some unanswered questions that I would like to ask of the authors, although I am not sure there are definite answers. A possible explanation is the increased uptake and clearance of calcidiol by adipose tissue, which we all know is a pretty active metabolic organ. If this is the case, though, should not the bioavailability of vitamin D increase with the decrease in adiposity after surgery?
That is question 1. Do you have vitamin d deficiency and elevated pth data on preoperative vitamin D and PTH levels in your patients and do you have any thoughts about this issue of vitamin D bioavailability versus changes in the gut absorption after gastric bypass? My second question is: Question 3, just to further confuse the picture, I have read articles about the purely restrictive laparoscopic banding operation that report no increase in PTH levels, which might make some sense, although bone marker studies still show increased bone resorption.
You reported a progressive, essentially linear increase in PTH levels with time after surgery, but the data on the graph out to 10 years show few data points that are widely scattered. Do you think there is enough long-term data to show the PTH levels continue to increase with time? Or, perhaps, because of increased food intake which occurs with all of these people and the decreased adiposity increasing bioavailability, is there a chance that perhaps there is increased calcidiol available and perhaps PTH levels will be moderated in the future?
Finally, vitamin d deficiency and elevated pth, my last question, do you have any evidence from your studies that oral supplementation of vitamin D and calcium citrate at the doses you recommended effectively prevent bone disease? You discussed this very briefly in the conclusion of your manuscript, but I want to know if you can elaborate any further.
This study proceeded from studies of my patients at Iowa where we had looked at serial bone densities in patients undergoing laparoscopic gastric bypass and showed a significant decrease in bone density at 1 and 2 years.
Now, that varied a little bit depending on where the site was. The lumbosacral spine and the hip seemed to be most affected, the radius and forearm less affected. And we saw a significant but small augmentation of parathormone in those patients. The purpose of this study was really to get a snapshot of what we were dealing with. And we were really astonished at the magnitude of what we saw here. I think that is something that is going to require clinical studies in the future to determine the nature of this problem.
Our purpose was really to bring this to the attention of the sort of bariatric surgical community as a potential problem. I think, as with most studies, this opens up new questions that are going to have to be answered in future studies. And I think that goes to the essence of your last question: We are planning right now in conjunction with our endocrinologists to do a clinical research center study where we take some of these patients and see whether this regimen of vitamin D supplementation is effective, and those will be coming in the near future.
As far as your question about whether or not 30 is a proper goal for vitamin D levels in these patients, this is derived from the endocrinology literature. I think it is a place to start. As far as your question about laparoscopic gastric banding as well as the secondary hyperparathyroidism that is seen in obese patients before surgery, in fact, that is the case. So that is another unknown sort of confounding variable in here that we have to dissect in the future, vitamin d deficiency and elevated pth.
These are really areas vitamin d deficiency and elevated pth surgical gastroenterologists that are beyond our usual level of knowledge, and we are having to acquire this expertise as we go along. There have been studies in the past on a small level, almost anecdotal level in some cases, of all these factors before.
But this was sort of a snapshot of patients over a year and a half, and I think it gives us a good baseline of what we are dealing with in that it increases over time. So it is a base for new studies in the future. The study is a snapshot of patients at one point in time and not a longitudinal study. So my first question would be: I was also struck that after 6 years I counted up the little dots on the scanograms and it seemed to me that there were many more patients who had normal PTH levels than had abnormal PTH levels.
When he did a biliopancreatic procedure in his Italian patients, he studied their calcium metabolism in over patients. He did find that the patients showed transient hypocalcemia followed by normalization of calcium levels. Then he did bone densitometry vitamin d deficiency and elevated pth these patients.
He did not find that they had substantial losses of bone density. They were in the normal range. Now, heavy patients, vitamin d deficiency and elevated pth, in my opinion, probably have different bone densitometer readings than patients who are not heavy.
That may explain why your lumbosacral patients lost density where the radial arm did not. It may be vitamin d deficiency and elevated pth matter of which bones were exposed to less stress.
Xylene antabuse you look at bone densitometer in your patients? Did you document any parathyroid disease? In other words, did you find any adenomas or masses in the neck? As far as your question about the longitudinal nature of this study, it is not of a longitudinal nature. The patients that I studied at the University vitamin d deficiency and elevated pth Iowa started invitamin d deficiency and elevated pth, and that was a longitudinal study; we looked at all of these measurements in those patients.
But frankly, at the time I left, about a year and a half ago, we really only had 3-year data on about vitamin d deficiency and elevated pth patients at that point in time.
We did see the same sort of things. The augmentations in parathormone were of a lesser magnitude than we have seen in these patients followed longer periods of time out. And actually the studies on the patients at Iowa are continuing in a longitudinal fashion.
They are attempting to get bone density studies every year. You would think an insurance company would be interested in that sort of information even if it does cost them a bit of money. But that, of course, is not the case. It very well may not be. Scopinaro has really studied his patients extraordinarily well.