Sleeve gastrectomy linked to changes in sex steroids, bone markers in adolescents
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Reductions in bone mineral density in adolescents with obesity who undergo sleeve gastrectomy are associated with changes in sex hormones, sclerostin and enteric peptides, according to study findings.
“Given the many metabolic benefits of weight-loss surgery, it is important find therapies for some of the downsides of surgery, such as bone loss,” Madhusmita Misra, MD, MPH, the Talbot Professor of Pediatrics at Harvard Medical School and division chief of pediatric endocrinology at Massachusetts General Hospital for Children, told Healio. “This is particularly important during the adolescent and young adult years, when marked increases in bone mass typically occur toward attainment of peak bone mass in early adult life, a key determinant of future bone health. Reduced bone accrual during this critical period may result in long-standing deficits in bone health that are not completely reversible. Once we know the mechanisms that contribute to bone loss following sleeve gastrectomy, we should be able to develop strategies to prevent or treat this effectively.”
Misra and colleagues conducted a longitudinal observational study of 64 adolescents and young adults aged 13 to 25 years with a BMI of 35 kg/m2 or more with at least one obesity-related comorbidity or a BMI of 40 kg/m2 or more (79.6% female). Of the study cohort, 30 underwent sleeve gastrectomy and 34 were followed with routine weight management without undergoing bariatric surgery. Participants attended study visits at baseline before surgery and 12 months after surgery. The nonsurgical group had study visits at similar intervals. BMI was calculated using height and weight from each visit. DXA was performed at the hip, spine and whole body less head, and high-resolution peripheral quantitative CT was conducted at the distal radius and tibia. Fasting blood samples were collected to measure bone turnover markers.
Changes in sex steroids, bone turnover markers
The group that had surgery had greater decreases in BMI z score and lean mass than the control group at 12 months. The surgery group had larger reductions in areal BMD z scores at the lumbar spine, total hip and femoral neck compared with controls. The surgery group also had a greater decrease in trabecular volumetric BMD at the radius and tibia at 12 months compared with controls.
At 12 months, the surgery group had larger reductions in serum estrone and free androgen index, and greater increases in sclerostin, N-terminal propeptide of type 1 procollagen and C-terminal telopeptide than controls. After stratification by sex, most of the changes were only observed in women. Females who underwent sleeve gastrectomy had a greater reduction in N-terminal propeptide of type 1 procollagen (9.9 µg/L vs. –10.9 µg/L; P = .027), estrone (–21.8 pg/mL vs. –3.2 pg/mL; P = .038), total testosterone (–9.3 ng/dL vs. –0.7 ng/dL; P = .022), and free androgen index (–1.51 vs. 0.18; P = .019); and a greater increase in sex hormone-binding globulin (22.6 nmol/L vs. 0 nmol/L; P = .001) than controls. Greater reduction in ghrelin for those undergoing surgery vs. controls was observed for both females (–181.1 pg/mL vs. 53.9 pg/mL; P = .0001) and males (–89 pg/mL vs. 5.56 pg/mL; P = .023). Females undergoing sleeve gastrectomy also had a greater increase in 25-hydroxyvitamin D levels compared with controls (2 ng/mL vs. 0 ng/mL; P = .047).
Associations between bone loss, sex steroids
After controlling for age and race, among female participants, larger decreases in BMI and lean mass were associated with greater decreases in total hip and femoral neck BMD z scores, radial trabecular volumetric BMD and radial and tibial total volumetric BMD. Decreases in estrone were linked to decreases in total hip and femoral neck BMD z scores. Decreases in free androgen index were associated with decreases in lumbar spine, femoral neck and total hip BMD z score and tibial total volumetric BMD and increases in tibial cortical volumetric BMD. Increases in sclerostin were associated with increases C-terminal telopeptide and in N-terminal propeptide of type 1 procollagen, and decreases in tibial cortical volumetric BMD, and decreases in ghrelin were associated with decreases in femoral neck BMD z score and radial trabecular volumetric BMD and increases in C-terminal telopeptide.
Misra said the findings reveal some potential therapies that may help reverse bone loss in adolescents undergoing sleeve gastrectomy.
“Given that skeletal unloading from weight loss and the associated increase in sclerostin are important contributors to bone loss, bone loading strategies with specific exercise activities and strategies to reduce levels of sclerostin are possible interventions,” Misra said. “Further, therapies could be geared toward replacement of hormones known to have beneficial effects on bone that decrease after sleeve gastrectomy.”
For more information:
Madhusmita Misra, MD, MPH, can be reached at mmisra@mgh.harvard.edu.
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