Slipped capital femoral epiphysis and its association with endocrine, metabolic and chronic diseases: A systematic review of the literature

Abstract

Purpose 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 11thSeptember 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 multifactorial 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.

Leptin Elevation as a Risk Factor for Slipped Capital Femoral Epiphysis Independent of Obesity Status

“…The 2 patients with idiopathic SCFE who were younger than the expected range were particularly notable, as they presented at the surprisingly young ages of 5 and 9 years, both with BMI of >95th percentile by age. Given the recommendation of evaluation for endocrine and metabolic aberrations for patients with SCFE who were younger than 10 years (for girls) or 12 years (for boys) 12 , thorough serology work-up was performed and both patients were shown to have no atypical sources for SCFE. Despite their expected serum leptin levels based on their age and sex being <5 ng/mL, both patients had leptin levels of >20 ng/mL.…”

“…This multifactorial theory is not new [11][12][13] , yet in the absence of the above-mentioned atypical causes, clinical exploration for other factors that may have weakened the physis are rarely pursued. Histologic evaluation of physes in patients with SCFE show substantial distortion and widening in the columnar architecture of the zone of hypertrophy and zone of proliferation, with decreased cellularity, clustered degenerated chondrocytes, and irregular orientation and degradation of collagen fibers [13][14][15][16][17][18][19] .…”

Trends in slipped capital femoral epiphysis: Is the rate declining?

“… 2 – 4 Obesity has been strongly associated with increased incidence, as well as endocrine disorders and systemic disorders. 5 – 10 A recent study implicates leptin elevation as a mediator of risk for SCFE. 11 …”

Obesity-related metabolic and endocrine disorders diagnosed during postoperative follow-up of slipped capital femoral epiphysis

“…Constitutional femoral retroversion, high BMI, increased vertical slope of the proximal femoral physeal line, and endocrine pathologies have been reported as potential predisposing factors for the pathogenesis of the disorder (Weiner 1996 , Witbreuk et al. 2013 ).…”