Background: Obesity suppresses bone turnover markers (BTMs) in circulation, and weight loss after metabolic and bariatric surgery (MBS) increases BTM levels. However, the relationship between regional fat distribution and BTMs has not been thoroughly investigated. This study aimed to determine which specific fat compartments - namely abdominal and femoral subcutaneous fat (SF), intraperitoneal fat, extraperitoneal fat, and total visceral fat (VF) - have the greatest impact on circulating BTM levels following weight loss induced by MBS.

Methods: The study comprised a cohort of individuals with severe obesity (n = 46) studied before and 6 months after MBS, either sleeve gastrectomy (SG, n = 25) or Roux-en-Y gastric bypass (RYGB, n = 21). Healthy individuals without obesity (n = 25) served as controls. Regional fat depots were quantified with magnetic resonance imaging. The BTMs included Tartrate-Resistant Acid Phosphatase 5b, C-terminal Telopeptide of Type I Collagen (CTX), Procollagen Type I N-terminal Propeptide (PINP), and Total (TotalOC), Carboxylated (cOC), and Undercarboxylated (ucOC) osteocalcin.

Results: In the pooled baseline analysis, no significant associations were observed between fat depots and BTMs (all p > 0.05). Postoperatively, distinct patterns emerged between surgical groups. In the SG cohort, femoral SF was inversely associated with cOC levels (p < 0.05) compared to the RYGB group. Following RYGB, extraperitoneal, intraperitoneal, and total VF were significantly associated with TotalOC, while intraperitoneal and total VF were also negatively associated with ucOC (all p < 0.05) compared to SG. All p-values were adjusted for false discovery rate to correct for multiple comparisons.

Conclusions: The findings suggest a specific interaction between intraperitoneal, extraperitoneal, and total visceral compartments and bone metabolism following RYGB. These observed relationships highlight the need for clinicians to consider regional fat distribution when assessing bone health in post-MBS patients.