Latest News

What underlies post–bariatric surgery bone fragility?



– Charting a healthy path for patients after bariatric surgery can be complicated and addressing bone health is an important part of the endocrinologist’s role in keeping patients safe from postsurgical fractures, according to John Bilezikian, MD.

“Abnormal bone metabolism is a feature of both obesity and gastric bypass surgery,” said Dr. Bilezikian, speaking during a bariatric surgery–focused session at the annual scientific & clinical congress of the American Academy of Clinical Endocrinologists.

It’s not easy to assess bone health, even before surgery, said Dr. Bilezikian. Even objective measures of bone density, such as dual-energy x-ray absorptiometry (DXA), may be skewed: very high fat mass causes artifact that interferes with accurate measurement of bone density, and DXA can’t distinguish between cortical and trabecular bone. The latter is a particular issue in high body mass index patients, since obesity is known to be associated with a more fragile bone microarchitecture, said Dr. Bilezikian, the Dorothy L. and Daniel H. Silberberg Professor of Medicine and director of the metabolic bone diseases unit at Columbia University, New York.

With these caveats in mind, Dr. Bilezikian said, there are some lessons to be learned from existing research to better manage bone health in bariatric patients.

After Roux-en-Y gastric bypass surgery (RYGB), bone turnover soon increases, with bone resorption markers increasing by up to 200% in the first 12-18 months after surgery. Bone formation markers also are elevated but to a lesser extent, said Dr. Bilezikian. Over time, the weight loss from RYGB is associated with a significant drop in bone mineral density (BMD) at weight-bearing sites. Weight loss was associated with bone loss at the total hip (r = 0.70; P less than .0003) and femoral neck (r = 0.47; P = .03 (J Clin Endocrinol Metab. 2013 Feb;98[2] 541-9).

A newer-technology, high-resolution peripheral quantitative CT (HR-pQCT) offers a noninvasive look not just at bone size and density but also at microarchitecture, including cortical thickness and details of trabecular structure. This technology “can help elucidate the structural basis for fragility,” said Dr. Bilezikian.

HR-pQCT was used in a recent study (J Bone Min Res. 2017 Dec. 27. doi: 10.1002/jbmr.3371) that followed 48 patients for 1 year after RYGB. Using HR-pQCT, DXA, and serum markers of bone turnover, the researchers found significant decrease in BMD and estimated decrease in bone strength after RYGB. Bone cortex became increasingly porous as well. Taken together, these changes may indicate an increased fracture risk, concluded the investigators.

A longer study that followed RYGB recipients for 2 years and used similar imaging and serum parameters also found that participants had decreased BMD. Tellingly, these investigators saw more marked increase in cortical porosity in the second year after bypass. Estimated bone strength continued to decline during the study period, even after weight loss had stopped.

All of these findings, said Dr. Bilezikian, point to a pathogenetic process other than weight loss that promotes the deteriorating bone microarchitecture seen years after RYGB. “Loss of bone mass and skeletal deterioration after gastric bypass surgery cannot be explained by weight loss alone,” said Dr. Bilezikian.

Another recent study was able to follow a small cohort of patients for a full 5 years, using DXA, lumbar CT, and Hr-pQCT. Though weight loss stabilized after 2 years and 25-OH D and calcium levels were unchanged from presurgical baseline, bone density continued to drop, and bone microarchitecture further deteriorated, said Dr. Bilezikian (Greenblatt L et al. ASBMR 2017, Abstract 1125).

Initially, post–bariatric surgery weight loss may induce bone changes because of skeletal unloading; further down the road, estrogen production by adipose tissue is decreased with ongoing fat loss, and sarcopenia may have an adverse effect on bone microarchitecture. Postsurgical malabsorption may also be an early mechanism of bone loss.

Other hormonal changes can include secondary hyperparathyroidism. Leptin, adiponectin, and peptide YY levels also may be altered.

Do these changes in BMD and bone architecture result in increased fracture risk? This question is difficult to answer, for the same reasons that other bariatric surgery research can be challenging, said Dr. Bilezikian. There is heterogeneity of procedures and supplement regimens, sample sizes can be small, follow-up times short, and adherence often is not tracked.

However, there are some clues that RYGB may be associated with an increased risk of all fractures and of fragility fractures, with appendicular fractures seen most frequently (Osteoporos Int. 2014 Jan; 25[1]:151-8). A larger study that tracked 12,676 patients receiving bariatric surgery, 38,028 patients with obesity, and 126,760 nonobese participants found that the bariatric patients had a 4.1% risk of fracture at 4 years post surgery, compared with 2.7% and 2.4% fracture rates in the participants with and without obesity, respectively (BMJ. 2016;354:i3794).

Other retrospective studies have found “a time-dependent increase in nonvertebral fractures with Roux-en-Y gastric bypass compared to gastric banding,” said Dr. Bilezikian.

How can these risks be managed after gastric bypass surgery? “Strive for nutritional adequacy” as the first step, said Dr. Bilezikian, meaning that calcium and vitamin D should be prescribed – and adherence encouraged – as indicated. Levels of 25-OH D should be checked regularly, with supplementation managed to keep levels over 30 ng/mL, he said.

All patients should be encouraged to develop and maintain an appropriate exercise regimen, and BMD should be followed over time. Those caring for post–gastric bypass patients can still use a bisphosphonate or other bone-health medication, if indicated using standard parameters. However, “You probably shouldn’t use an oral bisphosphonate in this population,” said Dr. Bilezikian.

Dr. Bilezikian reported that he has consulting or advisory relationships with Amgen, Radius Pharmaceuticals, Shire Pharmaceuticals, and Ultragenyx, and serves on a data safety monitoring board for Regeneron.

Next Article: