Increased Bone Turnover Markers in Patients with Type 2 Diabetes Randomized to Bariatric Surgery Vs. Intensive Medical Therapy at 5 Years

Presentation Number: OR06-5
Date of Presentation: April 4th, 2017

Megan Crawford*1, Nathan Hubert Pham2, Leila Zeinab Khan1, James Bena3, Philip Schauer1 and Sangeeta Rao Kashyap1
1Cleveland Clinic, Cleveland, OH, 2Case Western Reserve University, Cleveland, OH, 3Cleveland Clinic Foundation, Cleveland, OH

Abstract

Abstract: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) lead to impaired bone metabolism, and recent data support increased fracture risk in patients undergoing certain bariatric procedures (1). Bone turnover markers are known to increase after significant weight loss, however data beyond 3 years post-intervention is lacking, especially when compared to age and gender matched controls. Thus, we studied 95 subjects (63F, 75% Caucasian, mean BMI: 36.5 ± 3.6 kg/m2, mean age: 48.5 ± 8.2 years) with type 2 diabetes (T2DM) (mean HbA1C: 9.3 ± 1.6%) who were randomized to intensive medical therapy (IMT) (n= 25), RYGB (n= 37) or SG (n=33) in a randomized controlled trial. Subjects had measurements of 25-hydroxyvitamin D (25(OH)D), calcium, PTH, bone formation marker osteocalcin (OC) and bone resorption marker serum C-telopeptide of type 1 collagen (CTX) at baseline and 5 years post-intervention. At 5 years, mean weight loss was lower in IMT (7.3 ± 11.8%) vs. RYGB (22.3 ± 8.5%) and SG (19.0 ± 6.8%) (p <0.001). The percent change in CTX at 5 years increased markedly from baseline in both surgical groups by 137± 108.2% in RYGB (p<0.001), 61.1 ± 90.7% in SG (p<0.001) and 29.8 ± 93.5% in IMT (p=0.12), with RYGB having the greatest incremental increase in CTX of the three groups (p=0.017). OC also increased from baseline in the surgical cohorts by 138 ± 19.0% in RYGB (p<0.001) and 71 ± 68.8% in SG (p<0.001), compared to 43.8 ± 121.1% in IMT (p = 0.83). In the surgical cohorts, significant negative associations were observed between increase in CTX and changes in BMI and weight (p<0.01) and similar negative associations were seen with percent OC change and these same parameters (p<0.04). A significant positive association was seen between changes in both CTX and OC with PTH (p<0.001 for both). No significant differences in calcium or 25(OH)D were noted when comparing the three groups at 5 years, and there were no significant differences in these measures between baseline and 5 years for any group. Men had significantly greater increases in PTH from baseline compared with women (p<0.05), indicating possibly less adherence with or higher requirement of calcium and vitamin D supplementation than female counterparts.

Conclusion: Bone turnover remains elevated at 5 years post-bariatric surgery in patients with T2DM, long after initial significant weight loss has occurred. These changes in bone markers are most pronounced in RYGB, but are also present after SG. We suspect that absorption issues leading to metabolic bone disease as well as complex alterations in adipokines and insulin sensitivity are likely culprits for increased long term bone turnover in post-surgical patients with type 2 diabetes. Evaluating intra-individual bone turnover marker changes may lead to identification of those at increased risk for metabolic bone disease and possibly fracture in the long term following bariatric surgery.

 

Disclosure: PS: Clinical Researcher, Ethicon EndoSurgery, Clinical Researcher, Bard-Davol, Clinical Researcher, Stryker Endoscopy, Clinical Researcher, Baxter, Clinical Researcher, Gore, Clinical Researcher, Covidian, Clinical Researcher, Allergan, Board Member, Ethicon EndoSurgery. SRK: Clinical Researcher, Jansen Pharmaceuticals, Clinical Researcher, Johnson &Johnson. Nothing to Disclose: MC, NHP, LZK, JB