Nancy A Melville

September 18, 2017

DENVER — The bone loss known to occur along with significant weight reduction following gastric-bypass surgery continues even after weight stabilizes, with deterioration seen up to 5 years postsurgery.

"Based on these results as well as those of other studies documenting increased fracture risk after gastric-bypass surgery, we recommend skeletal health should be assessed and actively managed for gastric-bypass patients," senior author Elaine W Yu, MD, of the endocrine unit at Massachusetts General Hospital and assistant professor at Harvard Medical School, Boston, told attendees at the American Society for Bone and Mineral Research (ASBMR) 2017 Annual Meeting, in presenting the findings here.

While gastric-bypass surgery is associated with a host of important metabolic improvements, the surgery is also known to be linked to bone loss.

Previous research from Dr Yu's team has shown Roux-en-Y gastric bypass to be associated with bone-density declines of 7% to 10% in the initial 2 years following bypass surgery and as much as a 40% to 50% increased risk of hip and wrist fractures.

Research is lacking, however, on the longer-term trajectory of bone loss after weight loss stabilizes, which typically occurs within 2 years of gastric-bypass surgery.

In commenting on the study, Anne Schafer, MD, an assistant professor of medicine and epidemiology and biostatistics at the University of California, San Francisco, said the research offers important new insights.

"The 5-year data are very important for the characterization of the skeletal effects of gastric-bypass surgery," she told Medscape Medical News

The new study adds to the understanding of what those mechanisms may be, she said.

"The findings of continued BMD decreases and detrimental changes in bone microstructure, even after weight stabilizes, suggest that there is indeed a cause for concern."

Trial Findings

To better understand the changes, Dr Yu and colleagues conducted a longitudinal study involving 21 Roux-en-Y gastric-bypass (RYGB) patients, including 17 female and four male patients, with bone measures available for up to 5 years after their gastric-bypass surgery.

The patients, who had a mean age of 51, had a mean baseline body mass index (BMI) of 45 kg/m2 and after 5 years, the mean weight loss was 33 kg, with the weight stabilizing in all patients after 2 years and remaining stable until year 5.

The patients maintained normal calcium, vitamin D, and parathyroid (PTH) levels in the first 2 years with supplementation, in which they essentially double their calcium intake and triple their vitamin D intake to compensate for reduced absorption related to the bypass surgery.

Bone-mineral density (BMD) assessments of the patients at 5 years postsurgery using dual-energy x-ray absorptiometry (DXA) showed significant cumulative bone loss compared with levels at 2 years: total hip areal BMD decreased by 12% at 2 years and further to 15% at 5 years, compared with baseline, while femoral neck BMD dropped by 11% at 2 years, reaching 14% by 5 years (both P < .05 compared with 2 years).

In the spine, areal BMD declines were 6% at 2 years and 8% at 5 years.

In assessments using quantitative computed tomography (QCT), the most significant bone loss was seen in the trabecular spine and hip: declining from 8% to 12% from 2 to 5 years in the trabecular spine and from 9% to as much as 20% in the trabecular hip (both P < .05 for both compared with 2 years).

Assessments using high-resolution peripheral QCT (HR-pQCT), also showed significant declines from 2 to 5 years postsurgery in both trabecular and cortical bone.

"Large cumulative declines in BMD and microarchitecture occur after RYGB, with continued worsening between years 2 and 5 at multiple skeletal sites and in both cortical and trabecular bone," the researchers conclude.

"This persistent deterioration raises concerns about the long-term skeletal consequences of RYGB and indicates that active management of bone health in these patients is warranted."

Serum CTX, a marker of bone resorption, increased by as much as 196% at 2 years and declined slightly at 5 years, but remained high at 150%, compared with baseline.

Importantly, no correlations were found between changes in any of the BMD assessments and changes in weight, lean mass, or parathyroid (PTH) levels.

Calcium? Hormones? Mechanisms Pondered

Dr Yu said she is aware of only one other published study reporting on 5-year longitudinal bone-density changes after gastric bypass, a study published last year (Obes Surg. 2016;26:1141–1145).

While the DXA-reported bone loss in that study was even greater (20%–25%), Dr Yu noted that patients in that study had minimal supplementation with calcium or vitamin D, whereas the current standard of care is to provide supplements to all patients after bypass.

"It's difficult to know whether the significant calcium/D deficiency in that study may have contributed to the more severe skeletal outcome than seen in our study," she told Medscape Medical News.

In terms of mechanisms, she said the lack of a correlation between bone loss and weight loss or changes in lean mass suggests that something other than skeletal unloading may contribute to the bone loss seen after gastric bypass.

"When a person loses weight, some decline in BMD may be a natural, physiologically appropriate adaptation, as the skeleton has less body mass to support. However, recent studies documenting increased fracture risk after gastric bypass have indicated that there may be something more —something pathologic — happening in this patient population."

"Calcium/vitamin D malabsorption may contribute, but I don't think it's the primary mechanism, since the most rapid bone loss occurs within the first 2 years, a time period where our patients were aggressively supplemented with calcium/D and maintained normal PTH levels without secondary hyperparathyroidism.

"I believe that there are likely hormonal changes that are directly disturbing bone homeostasis," she explained.

For example, gastric-bypass surgery induces changes in gastrointestinal hormones, including GLP-1 and PYY, and adipocytic hormones, including leptin and adiponectin, as well as changes in the gut microbiome, Dr Yu said.

"Many of these factors have also been found to have a direct effect on bone.

"It's possible that the same factors that are helping patients to lose weight and put diabetes in remission may also have the unintended consequence of causing bone loss."

Clinical Implications: Keep Up Supplementation Post-RYGB and More Research

While a proven intervention to prevent the bone loss associated with gastric-bypass surgery remains elusive, emerging evidence points to some key potential strategies to help minimize the effects, Dr Yu noted.

For example, "it's clear that poor adherence with calcium and vitamin D supplements leads to even worse bone loss," she said.

"Also, one or two studies have found that exercise interventions may mitigate (but not eliminate) the magnitude of RYGB-induced bone loss; this needs to be confirmed in larger and longer studies.

"Finally, high-risk patients, such as older patients, those with history of fractures, or those that start with lower bone density, might additionally need pharmacologic medications to prevent bone loss after surgery, but we don't yet have clinical trials to demonstrate the efficacy or safety of such treatments."

Dr Yu and Dr Schafer had relevant financial relationships.

American Society for Bone and Mineral Research 2017 Annual Meeting. September 11, 2017, Denver, Colorado. Abstract 1125.

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