Dataset Information

Zoledronic acid for prevention of bone loss in patients receiving bariatric surgery.

ABSTRACT:

Purpose

Bariatric surgery is an effective treatment for severe obesity but causes substantial bone loss and increased risk of fractures. To date, there have been no studies examining whether pharmacologic treatments can prevent bone loss after bariatric surgery. We performed an exploratory study to examine the preliminary safety and efficacy of zoledronic acid (ZOL), a potent anti-resorptive bisphosphonate, to suppress bone turnover markers (BTM) and prevent declines in bone mineral density (BMD) after Roux-en-Y gastric bypass (RYGB) surgery.

Methods

We performed an open-label pilot study of pre-operative ZOL in postmenopausal women with obesity who were planning RYGB (n = 4). A single dose of zoledronic acid 5 mg was given intravenously prior to RYGB. Serum bone biochemistries including C-telopeptide (CTX) and procollagen type 1 N-terminal propeptide (P1NP) were measured at multiple timepoints throughout the 24-week study. BMD was also obtained at the spine and hip by dual-energy x-ray absorptiometry (DXA) and at the trabecular spine by quantitative computed tomography (QCT) at pre-operative baseline and 24 weeks. Results were compared against pre-operative baseline and against changes among RYGB historical controls (n = 10).

Results

At 2 weeks after RYGB, there was a nonsignificant trend for CTX and P1NP levels to be lower than baseline levels in the ZOL group. By 24 weeks after RYGB, however, participants who received ZOL had a significant increase in CTX above pre-operative baseline (+0.228 ± 0.117 ng/dL, p = 0.030) but this CTX rise was less than that observed in the controls (+0.601 ± 0.307 ng/dL, p = 0.042 between groups). Despite ZOL use, participants had significant areal BMD loss at the total hip as compared to pre-operative baseline (-4.2 ± 1.5%, p = 0.012) that was similar in magnitude to total hip BMD loss in the controls (-5.5 ± 3.9%, p = 0.005). There was a suggestion that the ZOL group might be protected against trabecular spine volumetric bone loss as compared to the control group (+4.8 ± 8.0% vs. -5.9 ± 7.0%, p = 0.075 between groups). Serum calcium, 25-hydroxyvitamin D, and parathyroid hormone did not change in either group. No hypocalcemia or serious adverse events were reported after ZOL.

Conclusion

In this proof of concept study, a single dose of ZOL prior to RYGB appeared to transiently mitigate but not fully prevent high bone turnover in the acute postoperative period. At 24 weeks after RYGB, our preliminary data suggest that ZOL was not sufficient to prevent bone loss at the hip, although it may preserve bone density at the trabecular spine. Further prospective, controlled studies are needed to confirm our findings and to identify the best strategies for preventing bone loss in bariatric patients receiving RYGB.

SUBMITTER: Liu Y

PROVIDER: S-EPMC8005765 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Obesity is a global health challenge that warrants effective treatments to avoid its multiple comorbidities. Bariatric surgery, a cornerstone treatment to control bodyweight excess and relieve the health-related burdens of obesity, can promote accelerated bone loss and affect skeletal strength, particularly after malabsorptive and mixed surgical procedures, and probably after restrictive surgeries. The increase in bone resorption markers occurs early and persist for up to 12 months or longer after bariatric surgery, while bone formation markers increase but to a lesser extent, suggesting a potential uncoupling process between resorption and formation. The skeletal response to bariatric surgery, as investigated by dual-energy X-ray absorptiometry (DXA), has shown significant loss in bone mineral density (BMD) at the hip with less consistent results for the lumbar spine. Supporting DXA studies, analyses by high-resolution peripheral quantitative computed tomography (HR-pQCT) showed lower cortical density and thickness, higher cortical porosity, and lower trabecular density and number for up to 5 years after bariatric surgery. These alterations translate into an increased risk of fall injury, which contributes to increase the fracture risk in patients who have been subjected to bariatric surgery procedures. As bone deterioration continues for years following bariatric surgery, the fracture risk does not seem to be dependent on acute weight loss but, rather, is a chronic condition with an increasing impact over time. Among the post-bariatric surgery mechanisms that have been claimed to act globally on bone health, there is evidence that micro- and macro-nutrient malabsorptive factors, mechanical unloading and changes in molecules partaking in the crosstalk between adipose tissue, bone and muscle may play a determining role. Given these circumstances, it is conceivable that bone health should be adequately investigated in candidates to bariatric surgery through bone-specific work-up and dedicated postsurgical follow-up. Specific protocols of nutrients supplementation, motor activity, structured rehabilitative programs and, when needed, targeted therapeutic strategies should be deemed as an integral part of post-bariatric surgery clinical support.

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