title: Gastric bypass in obese rats causes bone loss, vitamin D deficiency, metabolic acidosis, and elevated peptide YY.
abstract: BACKGROUND
  Metabolic bone disease and bariatric surgery have long been interconnected. The objective of this study is to better understand the mechanisms of bone mass loss after Roux-en-Y gastric bypass (RYGB) surgery. We evaluated mineral homeostasis and bone mass in diet-induced obese (DIO) rats after RYGB or sham surgery.
  
  
  METHODS
  Twelve DIO male Sprague Dawley rats underwent RYGB (n = 8) or sham (n = 4) surgery at 21 weeks of age. Postoperatively, animals ate an ad libitum 40% fat, normal calcium diet and were euthanized 22 weeks later. Serum and urine chemistries, insulin, leptin, bone turnover markers (BTM), and calciotropic and gut hormones were measured before and 22 weeks after surgery. Femurs were analyzed using microcomputed tomography (µCT).
  
  
  RESULTS
  Compared to sham, RYGB animals had lower serum bicarbonate, calcium, 25-hydroxyvitamin D, insulin, and leptin levels with higher serum parathyroid hormone, peptide YY, and urinary calcium at 43 weeks of age. Sham control rats gained weight and had coupled decreases in formation (P1NP and OC) and unchanged resorption (CTX) BTMs. Comparatively, RYGB animals had higher serum CTX and OC but even lower P1NP levels than controls. µCT revealed lower trabecular bone volume, number, and thickness and lower cortical bone volume, thickness, and moment of inertia relative to controls.
  
  
  CONCLUSIONS
  In rats with DIO, long-term RYGB-associated bone resorption appears to be driven in part by vitamin D malabsorption and secondary hyperparathyroidism. Other mechanisms, such as chronic acidosis, changes in fat-secreted hormones, and persistently elevated gut-derived hormone peptide YY, may also contribute to observed bone mass differences. Further investigation of these potential contributors to bone loss may lead to new targets for skeletal maintenance after RYGB.
authors: Department of Urology, North Florida/South Georgia Veterans Affairs Medical Center and University of Florida, Gainesville, Florida. Electronic address: benjamin.canales@urology.ufl.edu.
authors: Benjamin K
authors: BK
authors: Canales
authors: Endocrine Research Unit, San Francisco Veterans Affairs Medical Center and University of California, San Francisco, California.
authors: Anne L
authors: AL
authors: Schafer
authors: Endocrine Research Unit, San Francisco Veterans Affairs Medical Center and University of California, San Francisco, California.
authors: Dolores M
authors: DM
authors: Shoback
authors: Department of Pediatrics (Endocrinology), Yale University School of Medicine, New Haven, Connecticut.
authors: Thomas O
authors: TO
authors: Carpenter
mesh_terms: D000138:Acidosis / Q000209:etiology*; D000818:Animals; D018488:Bone Demineralization, Pathologic / Q000209:etiology*; D015519:Bone Density / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D015390:Gastric Bypass / Q000009:adverse effects*; D006706:Homeostasis / Q000502:physiology; D020738:Leptin / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000601:surgery; D010281:Parathyroid Hormone / Q000378:metabolism; D019894:Peptide YY / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D014807:Vitamin D / Q000031:analogs & derivatives / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000209:etiology*; D015431:Weight Loss / Q000502:physiology
chemical_list: D020738:Leptin; D010281:Parathyroid Hormone; D019894:Peptide YY; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D002118:Calcium
keywords: Bone resorption; Bone turnover markers; Gastric bypass surgery; Metabolic acidosis; Metabolic bone disease; Morbid obesity; Peptide YY