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

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.

Bone Density and Trabecular Morphology at Least 10 Years After Gastric Bypass and Gastric Banding.

Roux-en-Y gastric bypass (RYGB) instigates high-turnover bone loss in the initial 5 years after surgery, whereas skeletal changes after adjustable gastric banding (AGB) are less pronounced. Long-term skeletal data are scarce, and the mechanisms of bone loss remain unclear. We sought to examine bone density and microarchitecture in RYGB and AGB patients a decade after surgery and to determine whether prior published reports of bone loss represent an appropriate adaptation to new postsurgical weight. In this cross-sectional study, 25 RYGB and 25 AGB subjects who had bariatric surgery ≥10 years ago were matched 1:1 with nonsurgical controls for age, sex, and current body mass index (BMI). We obtained bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA), volumetric BMD and microarchitecture by high-resolution peripheral quantitative computed tomography (HR-pQCT), trabecular morphology by individual trabecular segmentation, and metabolic bone laboratory results. As compared with BMI-matched controls, RYGB subjects had significantly lower hip BMD, and lower total volumetric BMD at the distal radius and tibia. Substantial deficits in cortical and trabecular microarchitecture were observed in the RYGB group compared to controls, with reduced trabecular plate bone volume fraction and estimated failure load at both the radius and tibia, respectively. Bone turnover markers CTX and P1NP were 99% and 77% higher in the RYGB group than controls, respectively, with no differences in serum calcium, 25-hydroxyvitamin D, or parathyroid hormone. In contrast, the AGB group did not differ from their BMI-matched controls in any measured bone density, microarchitecture, or laboratory parameter. Thus, RYGB, but not AGB, is associated with lower than expected hip and peripheral BMD for the new weight setpoint, as well as deleterious changes in bone microarchitecture. These findings suggest that pathophysiologic processes other than mechanical unloading or secondary hyperparathyroidism contribute to bone loss after RYGB, and have important clinical implications for the long-term care of RYGB patients. © 2020 American Society for Bone and Mineral Research.