Effects of Weight Loss Surgery on Bone Health in Adolescents

Our overall hypothesis is that both Roux-en-Y Gastric Bypass (RYGB) and vertical sleeve
gastrectomy (VSG) in adolescents with morbid obesity will lead to a reduction in areal and
volumetric BMD, and deterioration in bone structure and estimated bone strength, and an
increase in marrow adiposity. We further hypothesize that these effects will be due in part
to a decrease in lean mass, changes in enteric peptide hormones and reduced estrogen levels.

We will enroll 120 participants 13-21 years old for this two-year longitudinal study (36 in
each of the surgical groups and 48 non-surgical controls with obesity). We will screen up to
240 subjects to find these 120 eligibile subjects. Areal bone mineral density (BMD) will be
assessed by dual energy x-ray absorptiometry (DXA), volumetric BMD by quantitative computed
tomography (QCT), bone structure and strength using high resolution peripheral QCT and finite
element analysis, and marrow fat using magnetic resonance spectroscopy. Body composition will
also be assessed.

Adolescence is a critical time for bone accrual and the use of bariatric procedures is
increasing in teenagers. This study will provide novel data needed to establish effects of
RYGB vs. VSG on bone in adolescents and will begin to delineate underlying mechanisms.
Clarifying these mechanisms will identify therapeutic targets to optimize bone accrual in
adolescents undergoing bariatric surgery.

Inclusion Criteria:

1. Adolescents with morbid obesity 13-21yo undergoing RYGB (n=36) or VSG (n=36), or being
followed without surgical intervention (usual care) (n=48).

2. Eligibility criteria for weight loss surgery used at the Weight Center include BMI>40
or BMI>35kg/m2 with major comorbidities. A BMI>35 in adolescents reflects a BMI>99th
percentile. In order to be considered appropriate surgical candidates, children must
have a bone age of ≥14y (F) or ≥16y (M), and ≥1 co-morbidity of obesity. They must
have demonstrated efforts at non-surgical weight loss, and consistent compliance with
appointments and recommendations. Patients must demonstrate sufficient maturity,
psychological stability and cognitive capacity to recognize the significance of the
procedure and implement required post-operative behavioral changes.

Exclusion Criteria:

1. Current pregnancy and breast feeding

2. Medications other than calcium or vitamin D that affect bone, such as glucocorticoids,
phenytoin, phenobarbitone (washout of 3 months prior to enrollment if discontinuation
is medically permissible)

3. Use of antipsychotic medications that cause weight gain if treated for <6 mos, or if
dosage is not stable for >2 mos

4. Untreated thyroid dysfunction or on stable dose for <3 mos

5. HbA1C>8% (to avoid deleterious effects on bone from uncontrolled T2DM)

6. Smoking >10 cigarettes/day; substance abuse per Diagnostic and Statistical Manual
(DSM) V

7. Metal implants, intracranial surgical clips or pacemakers

8. Weight >450 lbs due to limits for MRI and CT.