A randomised clinical trial (RCT) that investigated the effects of zoledronic acid (ZA) for the prevention of bone loss after Roux-en-Y gastric bypass or sleeve gastrectomy, has found ZA compared with placebo, increases bone mass in the spine and prevents bone loss in the hip after bariatric and metabolic surgery (BMS).
The study’s authors from Esbjerg Hospital, University Hospital of Southern Denmark, Esbjerg, Denmark, noted that previous research has found BMS can results in negative effects on bone metabolism, whilst increasing the risk of fractures. The causes are believed to be multifactorial including mechanical unloading, hormonal changes, malnutrition and changes in body composition.
Current treatments aimed at preventing post-BMS bone loss include calcium and vitamin D supplements and exercise intervention (resistance exercise and/or high-impact activities) however, the results are limited and patient adherence can be low.
Bisphosphonates, such as Zoledronate (ZA), have been found to inhibit osteoclast activity, reduce the risk of fractures in patients with osteoporosis and normalise bone resorption in high bone turnover diseases. As a result, the researchers designed an RCT to assess whether ZA can prevent bone loss in patients undergoing BMS. We hypothesized that zoledronic acid will prevent excessive bone resorption and reduce bone loss after bariatric surgery.
In total, 59 patients were enrolled in the study – 31 received zoledronic acid (intervention [INT]) and 28 received placebo (control [CON]) 180 to 7 days prior to surgery, and follow-up assessment was performed 12 months after surgery. Patients received a single dose of zoledronic acid 5mg or placebo administered in a solution containing 100 mL of saline water (0.9% sodium chloride) and slowly infused intravenously (≥15 min).
To ensure sufficient levels of calcium and vitamin D, all participants were advised supplements with calcium (citrate or carbonate) 400mg twice daily and vitamin D 38μg daily starting from inclusion and throughout the study. A loading dose of 100,000IU of vitamin D3 was given orally if serum 25(OH)-vitamin D level was less than 25nmol/L.
The primary outcome was changes in spinal trabecular volumetric bone mineral density (vBMD; milligrams per centimeters cubed) of the lumbar spine (L1-L2) and secondary outcomes were total hip and femoral neck vBMD.
Outcomes
Fifty-three patients completed the 12-month visit. Baseline characteristics revealed that the groups were well balanced for age, weight, surgery type and time of administration of the study drug, as well as bone outcomes, although a higher number of male individuals was allocated to INT compared with CON.
At the 12-month follow-up, both INT and CON experienced a reduction in body weight: 31.2kg (p<0.001) and 30.4kg (p<0.001), respectively, and there was no difference between the groups (p=0.79).
For trabecular spine vBMD and spine areal BMD (aBMD), there were significant differences in favour of INT: 6.8mg/cm3 (p=0.003) and 0.053g/cm2 (p=0.002), respectively. Compared with baseline, INT had an increase in spine vBMD (2.6%; p=0.028) and preserved aBMD (1.1%; p=0.19), whereas CON had unchanged vBMD (−2.0%; p=0.14) and a 3.3% reduction in aBMD (p<0.004).
For trabecular total hip vBMD and total hip aBMD, there were significant differences in favour of INT: 5.0mg/cm3 (p=0.006) and 0.040g/cm2 (p=0.003), respectively. vBMD was preserved in INT (−0.6%; p=0.46), compared with CON that had a 3.6% reduction (p<0.001). Both groups experienced significant aBMD losses vs. baseline, although losses were larger in CON than INT (aBMD: −3.4% vs. −7.0%; p=0.003).
For femoral neck aBMD, there was also a significant difference in favour of INT: 0.043 mg/cm2 (p=0.018). CON had a reduction of 2.7% in vBMD (p=0.019) and 5.7% in aBMD (p<0.001), whereas INT had unchanged vBMD (0.0%; p=0.99) and aBMD (−1.0%; p=0.46) vs. baseline.
For P1NP, there was a significant difference of −34.7μg/L observed (p<0.001). In INT, P1NP remained stable (9.6%; p=0.29), whereas CON had marked increases of 73.4% vs. baseline (p<0.001). Regarding CTX-1, they observed a difference of −0.18μg/L (p=0.013), with INT having less pronounced increases of 85.4% (p<0.001) vs. 165.6% (p < 0.001) in CON.
For serum calcium, there were no differences observed one and 12 months after surgery. One month after surgery, INT had increased PTH levels of 2.61pmol/L (p=0.039) compared with CON. By 12 months, no differences were observed between the groups (p=0.76), with similar PTH levels vs. baseline (p=0.15 and 0.11, respectively).
For CON, they reported that the postoperative absolute weight loss was correlated with the absolute declines in total hip aBMD (p<0.001) and femoral neck aBMD (p=0.002), whereas such correlations were not present in INT. In both groups, weight loss was not correlated with changes in spine vBMD or aBMD. For CTX-1, they reported an inverse correlation with change in spine aBMD (p=0.017) in INT and CON (p=0.017), and additionally in CON, CTX-1 was also inversely correlated with the changes in total hip (p=0.017) and femoral neck (p=0.02).
“In this randomised, placebo-controlled study investigating the effects of zoledronic acid after bariatric surgery, we found that a single infusion of zoledronic acid increased spine bone mass and prevented bone loss in the hip region, whereas those receiving placebo had significant bone loss in the hip region,” the researchers wrote. “These results confirm our hypothesis that ZA can prevent bone loss after bariatric surgery. Furthermore, our safety data were reassuring, indicating that treating patients undergoing bariatric surgery with ZA is safe.”
The findings were reported in the paper, ‘Zoledronic acid increases spine bone mass and prevents hip bone loss after bariatric surgery: a randomized placebo-controlled study’, published in Obesity. To access this paper, please click here
Comments