title: The presence of both an energy deficiency and estrogen deficiency exacerbate alterations of bone metabolism in exercising women.
abstract: BACKGROUND
  Bone loss in amenorrheic athletes has been attributed to energy deficiency-related suppression of bone formation, but not increased resorption despite hypoestrogenism.
  
  
  OBJECTIVE
  To assess the independent and combined effects of energy deficiency and estrogen deficiency on bone turnover markers in exercising women.
  
  
  METHODS
  PINP, osteocalcin, U-CTX-I, TT3, leptin, and ghrelin were measured repeatedly, and bone mineral density (BMD) was measured once in 44 exercising women. Resting energy expenditure (REE) was used to determine energy status (deficient or replete) and was corroborated with measures of metabolic hormones. Daily levels of urinary estrone and pregnanediol glucuronides (E1G, PdG), were assessed to determine menstrual and estrogen status. Volunteers were then retrospectively categorized into 4 groups: 1) Energy Replete+Estrogen Replete (EnR+E2R), (n=22), 2) Energy Replete+Estrogen Deficient (EnR+E2D), (n=7), 3) Energy Deficient+Estrogen Replete (EnD+E2R), (n=7), and 4) Energy Deficient+Estrogen Deficient (EnD+E2D), (n=8).
  
  
  RESULTS
  The groups were similar (p>0.05) with respect to age (24.05+/-1.75 yrs), weight (57.7+/-2.2 kg), and BMI (21.05+/-0.7 kg/m2). By design, REE/FFM (p=0.028) and REE:pREE (p<0.001) were lower in the EnD vs. EnR group, and the E2D group had a lower REE:pREE (p=0.005) compared to the E2R group. The EnD+E2D group had suppressed PINP (p=0.034), and elevated U-CTX-I (p=0.052) and ghrelin (p=0.028) levels compared to the other groups. These same women also had convincing evidence of energy conservation, including TT3 levels that were 29% lower (p=0.057) and ghrelin levels that were 44% higher (p=0.028) than that observed in the other groups. Energy deficiency was associated with suppressed osteocalcin, and TT3 (p<0.05), whereas estrogen deficiency was associated with decreased E1G (p<0.02), and lower L2-L4 BMD (p=0.033). Leptin was significant in predicting markers of bone formation, but not markers of bone resorption.
  
  
  CONCLUSIONS
  When the energy status of exercising women was adequate (replete), there were no apparent perturbations of bone formation or resorption, regardless of estrogen status. Estrogen deficiency in exercising women, in the presence of an energy deficiency, was associated with bone loss and involved suppressed bone formation and increased bone resorption. These findings underscore the importance of avoiding energy deficiency, which is associated with hypoestrogenism, to avoid bone health problems.
authors.affiliation: Women's Exercise and Bone Health Laboratory, Department of Exercise Sciences, University of Toronto, Toronto, Ontario, Canada; Noll Laboratory, Department of Kinesiology, Penn State University, University Park, PA, USA. Electronic address: maryjane.desouza@utoronto.ca.
authors.forename: Mary Jane
authors.initials: MJ
authors.lastname: De Souza
authors.affiliation: Women's Exercise and Bone Health Laboratory, Department of Exercise Sciences, University of Toronto, Toronto, Ontario, Canada. Electronic address: sarah.west@utoronto.ca.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: West
authors.affiliation: Osteoporosis Prevention Program, Women's College Hospital, Department of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address: sophie.jamal@utoronto.ca.
authors.forename: Sophie A
authors.initials: SA
authors.lastname: Jamal
authors.affiliation: Osteoporosis Prevention Program, Women's College Hospital, Department of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address: g.hawker@utoronto.ca.
authors.forename: Gillian A
authors.initials: GA
authors.lastname: Hawker
authors.affiliation: Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, CT, USA. Electronic address: caren.gundberg@yale.edu.
authors.forename: Caren M
authors.initials: CM
authors.lastname: Gundberg
authors.affiliation: Noll Laboratory, Department of Kinesiology, Penn State University, University Park, PA, USA. Electronic address: niw1@psu.edu.
authors.forename: Nancy I
authors.initials: NI
authors.lastname: Williams
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D015992:Body Mass Index; D015519:Bone Density; D001842:Bone and Bones / Q000378:metabolism*; D004435:Eating; D004734:Energy Metabolism; D004967:Estrogens / Q000097:blood / Q000172:deficiency* / Q000652:urine; D015444:Exercise; D005260:Female; D006801:Humans; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers; D004967:Estrogens