title: Regional fat depots and their relationship to bone density and microarchitecture in young oligo-amenorrheic athletes.
abstract: BACKGROUND
  Various fat depots have differential effects on bone. Visceral adipose tissue (VAT) is deleterious to bone, whereas subcutaneous adipose tissue (SAT) has positive effects. Also, marrow adipose tissue (MAT), a relatively newly recognized fat depot is inversely associated with bone mineral density (BMD). Bone mass in athletes depends on many factors including gonadal steroids and muscle mass. Exercise increases muscle mass and BMD, whereas, estrogen deficiency decreases BMD. Thus, the beneficial effects of weight-bearing exercise on areal and volumetric BMD (aBMD and vBMD) in regularly menstruating (eumenorrheic) athletes (EA) are attenuated in oligo-amenorrheic athletes (OA). Of note, data regarding VAT, SAT, MAT and regional muscle mass in OA compared with EA and non-athletes (C), and their impact on bone are lacking.
  
  
  METHODS
  We used (i) MRI to assess VAT and SAT at the L4 vertebra level, and cross-sectional muscle area (CSA) of the mid-thigh, (ii) 1H-MRS to assess MAT at L4, the proximal femoral metaphysis and mid-diaphysis, (iii) DXA to assess spine and hip aBMD, and (iv) HRpQCT to assess vBMD at the distal radius (non-weight-bearing bone) and tibia (weight-bearing bone) in 41 young women (20 OA, 10 EA and 11 C 18-25 years). All athletes engaged in weight-bearing sports for ≥ 4 h/week or ran ≥ 20 miles/week.
  
  
  METHODS
  VAT, SAT and MAT at L4; CSA of the mid-thigh; MAT at the proximal femoral metaphysis and mid-diaphysis; aBMD, vBMD and bone microarchitecture.
  
  
  RESULTS
  Groups had comparable age, menarchal age, BMI, VAT, VAT/SAT and spine BMD Z-scores. EA had higher femoral neck BMD Z-scores than OA and C. Fat mass was lowest in OA. SAT was lowest in OA (p = 0.048); L4 MAT was higher in OA than EA (p = 0.03). We found inverse associations of (i) VAT/SAT with spine BMD Z-scores (r = -0.42, p = 0.01), (ii) L4 MAT with spine and hip BMD Z-scores (r = -0.44, p = 0.01; r = -0.36, p = 0.02), and vBMD of the radius and tibia (r = -0.49, p = 0.002; r = -0.41, p = 0.01), and (iii) diaphyseal and metaphyseal MAT with vBMD of the radius (r ≤ -0.42, p ≤ 0.01) and tibia (r ≤ -0.34, p ≤ 0.04). In a multivariate model including VAT/SAT, L4 MAT and thigh CSA, spine and hip BMD Z-scores were predicted inversely by L4 MAT and positively by thigh CSA, and total and cortical radius and total tibial vBMD were predicted inversely by L4 MAT. VAT/SAT did not predict radius or tibia total vBMD in this model, but inversely predicted spine BMD Z-scores. When L4 MAT was replaced with diaphyseal or metaphyseal MAT in the model, diaphyseal and metaphyseal MAT did not predict aBMD Z-scores, but diaphyseal MAT inversely predicted total vBMD of the radius and tibia. These results did not change after adding percent body fat to the model.
  
  
  CONCLUSIONS
  VAT/SAT is an inverse predictor of lumbar spine aBMD Z-scores, while L4 MAT is an independent inverse predictor of aBMD Z-scores at the spine and hip and vBMD measures at the distal tibia and radius in athletes and non-athletes. Diaphyseal MAT independently predicts vBMD measures of the distal tibia and radius.
authors: Pediatric Endocrine Unit, Massachusetts General Hospital for Children and Harvard Medical School, 175 Cambridge Street, Boston, MA 02114, USA; Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA. Electronic address: vsinghal1@partners.org.
authors: Vibha
authors: V
authors: Singhal
authors: Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA. Electronic address: gmaffazioli@partners.org.
authors: Giovana D N
authors: GD
authors: Maffazioli
authors: Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA. Electronic address: ncanosokoloff@partners.org.
authors: Natalia
authors: N
authors: Cano Sokoloff
authors: Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA; Division of Sports Medicine, Boston Children's Hospital, 319 Longwood Avenue, Boston, MA 02115, USA. Electronic address: keackerman@partners.org.
authors: Kathryn E
authors: KE
authors: Ackerman
authors: Department of Medicine, Massachusetts General Hospital and Harvard Medical School, USA. Electronic address: hlee5@partners.org.
authors: Hang
authors: H
authors: Lee
authors: Department of Adolescent Medicine, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA. Electronic address: ngupta3@mgh.harvard.edu.
authors: Nupur
authors: N
authors: Gupta
authors: Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA. Electronic address: clarke.hannahm@gmail.com.
authors: Hannah
authors: H
authors: Clarke
authors: Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA. Electronic address: mslattery@partners.org.
authors: Meghan
authors: M
authors: Slattery
authors: Department of Radiology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA. Electronic address: mbredella@partners.org.
authors: Miriam A
authors: MA
authors: Bredella
authors: Pediatric Endocrine Unit, Massachusetts General Hospital for Children and Harvard Medical School, 175 Cambridge Street, Boston, MA 02114, USA; Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA. Electronic address: mmisra@partners.org.
authors: Madhusmita
authors: M
authors: Misra
mesh_terms: D015502:Absorptiometry, Photon; D000273:Adipose Tissue; D000293:Adolescent; D000328:Adult; D000568:Amenorrhea / Q000000981:diagnostic imaging / Q000473:pathology*; D056352:Athletes; D015519:Bone Density; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D055815:Young Adult
keywords: Athletes; BMD; Marrow fat; Microarchitecture; Oligo-amenorrhea; Visceral fat