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.

Keywords: Bariatric surgery; Bisphosphonates; Bone loss; Bone turnover marker; Gastric bypass; Zoledronic acid.

Fig. 1

Bone turnover markers in the 24 weeks after RYGB in zoledronic acid (ZOL) and control groups. Panels show serum CTX (A) and P1NP (B) at pre-operative baseline and serial timepoints up to 24 weeks. Individual results are shown for each participant in the ZOL (black circles) and control groups (gray triangles).

Fig. 2

Laboratory parameters in the 24 weeks after RYGB in zoledronic acid (ZOL) and control groups. Panels show serum calcium (A), 25-hydroxyvitamin D (B), and PTH (C) at pre-operative baseline and serial timepoints up to 24 weeks. Individual results are shown for each participant in the ZOL (black circles) and control groups (gray triangles).

Fig. 3

Changes in bone density in the 24 weeks after RYGB in zoledronic acid (ZOL) and control groups. Percent change in bone mineral density (BMD) and volumetric BMD (vBMD) were assessed by DXA and QCT, and are shown at the total hip (A), femoral neck (B), posterior-anterior spine (C), and trabecular spine (D). Mean and standard deviation for each group are depicted with black bars (ZOL) and gray bars (controls). There were no statistically significant differences between groups at any skeletal site (p > 0.05).