title: Slipped capital femoral epiphysis and its association with endocrine, metabolic and chronic diseases: a systematic review of the literature.
abstract: OBJECTIVE
  Puberty, obesity, endocrine and chronic systemic diseases are known to be associated with slipped capital femoral epiphysis (SCFE). The mechanical insufficiency of the physis in SCFE is thought to be the result of an abnormal weakening of the physis. However, the mechanism at the cellular level has not been unravelled up to now.
  
  
  METHODS
  To understand the pathophysiology of endocrine and metabolic factors acting on the physis, we performed a systematic review focussing on published studies reporting on hormonal, morphological and cellular abnormalities of the physis in children with SCFE. In addition, we looked for studies of the effects of endocrinopathies on the human physis which can lead to cause SCFE and focussed in detail on hormonal signalling, hormone receptor expression and extracellular matrix (ECM) composition of the physis. We searched in the PubMed, EMBASE.com and The Cochrane Library (via Wiley) databases from inception to 11th September 2012. The search generated a total of 689 references: 382 in PubMed, 232 in EMBASE.com and 75 in The Cochrane Library. After removing duplicate papers, 525 papers remained. Of these, 119 were selected based on titles and abstracts. After excluding 63 papers not related to the human physis, 56 papers were included in this review.
  
  
  RESULTS
  Activation of the gonadal axis and the subsequent augmentation of the activity of the growth hormone-insulin-like growth factor 1 (GH-IGF-1) axis are important for the pubertal growth spurt, as well as for cessation of the physis at the end of puberty. The effects of leptin, thyroid hormone and corticosteroids on linear growth and on the physis are also discussed. Children with chronic diseases suffer from inflammation, acidosis and malnutrition. These consequences of chronic diseases affect the GH-IGF-1 axis, thereby, increasing the risk of the development of SCFE. The risk of SCFE and avascular necrosis in children with chronic renal insufficiency, growth hormone treatment and renal osteodystrophy remains equivocal.
  
  
  CONCLUSIONS
  SCFE is most likely the result of a multi-factorial event during adolescence when height and weight increase dramatically and the delicate balance between the various hormonal equilibria can be disturbed. Up to now, there are no screening or diagnostic tests available to predict patients at risk.
authors.affiliation: Department of Orthopaedic Surgery, Research Institute MOVE, VU University Medical Center, De Boelelaan 1117, P.O. Box 7057, 1081 HV Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Witbreuk
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: F J
authors.initials: FJ
authors.lastname: van Kemenade
authors.affiliation: Department of Orthopaedic Surgery, Research Institute MOVE, VU University Medical Center, De Boelelaan 1117, P.O. Box 7057, 1081 HV Amsterdam, The Netherlands.
authors.forename: J A
authors.initials: JA
authors.lastname: van der Sluijs
authors.affiliation: Medical Library, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: E P
authors.initials: EP
authors.lastname: Jansma
authors.affiliation: Department of Pediatric Endocrinology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Rotteveel
authors.affiliation: Department of Orthopaedic Surgery, Research Institute MOVE, VU University Medical Center, De Boelelaan 1117, P.O. Box 7057, 1081 HV Amsterdam, The Netherlands.
authors.forename: B J
authors.initials: BJ
authors.lastname: van Royen
keywords: Endocrine, metabolic and chronic diseases; Slipped capital femoral epiphysis; Systematic review