SUN-785 - The Weight Loss Caused by GLP-1 and Dual GLP-1/GIP Receptor Agonists is Accompanied by Cortical Bone Loss at the Proximal Femur and Loss of Volume in Key Locomotor Muscles in Obese Diabetic Patients.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and the dual GLP-1/Glucose-dependent Insulinotropic Polypeptide (GIP) RA, tirzepatide, improve glycemia and cause weight loss. In obese individuals, voluntary weight loss of ~7-10% is associated with bone loss at the hip, predominantly in the cortical compartment, increased fractures, and loss of muscle mass. We performed two retrospective studies to evaluate the musculoskeletal impact of the weight loss-induced by GLP-1 RAs or Tirzepatide in obese diabetic patients treated for at least one year. First, we analyzed 48 participants: 36 post-menopausal women and 12 males, with a mean age of 64.8±10.2 (SD) years who had two BMD measurements by DXA at least 1 year apart while on treatment. The average weight loss between the two DXA measurements was 4.6 ± 8.6 %. The average loss of BMD at the total femur was 2.3±3.5%/year. Using linear regression analysis, we calculated the R2 and multiple comparison adjusted p-value between the % weight change between DXAs with the % change in BMD and delta T-score. The weight loss was positively correlated with bone loss at the total femur [R2 0.25, p=0.0129 for BMD and R2 0.16, p=0.0317 for T score], and femoral trochanter [R2 0.16, p=0.0317 for BMD and R2 0.14, p=0.0331 for T score]. These associations remained significant after adjusting for the use of steroids, bisphosphonates, estrogen or androgen receptor inhibitors. No significant association was found between weight loss and BMD at the spine and femoral neck. In the second study, we analyzed 54 participants, 36 women (34 post-menopausal) and 18 males, with a mean age of 59.1±10.4 years, and evaluated the relationship between weight loss and cancellous and cortical volumetric BMD (vBMD) measured on opportunistic CT scans obtained at least 1 year apart. To measure vBMD of the femur and lumbar spine, we used an automated machine learning model for bone segmentation (Skellytour).The average weight loss between the two CT measurements was 4.8 ± 7.5 %. Weight loss was positively correlated with bone loss at the femur cortical bone [R2 0.2127, p=0.027] but not at femoral cancellous bone [R2 0.0415, p=0.59]. No significant association was found between weight loss and vBMD at the lumbar spine. Another machine model called multi-organ objective segmentation (MOOSE) was used to segment and calculate the volume of key locomotor muscles. The amount of weight loss was positively correlated with muscle loss at the iliopsoas [R2 0.5376, p=0.0000235], gluteus maximus [R2 0.635, p=0.0000235], and gluteus medius [R2 0.1197, p=0.0257]. These findings suggest that, in elderly diabetic patients, GLP-1 RA–associated weight loss preferentially affects femoral cortical bone and also affects key locomotor muscles. Therefore, bone mass and muscle mass should be evaluated in patients treated with those drugs and protective management should be considered.

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