Promoting Growth in Chronic Inflammatory Disease: Lessons from Studies of the Growth Plate

Ahmed, S Faisal; Sävendahl, Lars

doi:10.1159/000229763

Cited by 25 publications

(25 citation statements)

References 51 publications

(41 reference statements)

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“…below the mean of the population. Children suffering from chronic inflammation are exposed to several factors contributing to growth failure such as malnutrition, glucocorticoid (GC) therapy, and pro-inflammatory cytokines (Ahmed & Savendahl 2009. Altogether, these factors act both systemically and locally at the growth plate level to suppress bone growth (Fig.…”

Section: Impact Of Inflammation On Bone Growthmentioning

confidence: 99%

RECENT RESEARCH ON THE GROWTH PLATE: Impact of inflammatory cytokines on longitudinal bone growth

Sederquist¹,

Fernandez-Vojvodich²,

Zaman³

et al. 2014

Journal of Molecular Endocrinology

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Children with inflammatory diseases usually display abnormal growth patterns as well as delayed puberty. This is a result of several factors related to the disease itself, such as malnutrition, hypercortisolism, and elevated levels of pro-inflammatory cytokines. These factors in combination with glucocorticoid treatment contribute to growth retardation during chronic inflammation by systemically affecting the major regulator of growth, the GH/IGF1 axis. However, recent studies have also shown evidence of a direct effect of these factors at the growth plate level. In conditions of chronic inflammation, pro-inflammatory cytokines are upregulated and released into the circulation. The most abundant of these, tumor necrosis factor a, interleukin 1b (IL1b), and IL6, are all known to directly act on growth plate cartilage to induce apoptosis and thereby suppress bone growth. Both clinical and experimental studies have shown that growth retardation can partly be rescued when these cytokines are blocked. Therefore, therapy modulating the local actions of these cytokines may be effective for preventing growth failure in patients with chronic inflammatory disorders. In this review, we report the current knowledge of inflammatory cytokines and their role in regulating bone growth.

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Section: Impact Of Inflammation On Bone Growthmentioning

confidence: 99%

RECENT RESEARCH ON THE GROWTH PLATE: Impact of inflammatory cytokines on longitudinal bone growth

Sederquist¹,

Fernandez-Vojvodich²,

Zaman³

et al. 2014

Journal of Molecular Endocrinology

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“…These effects are induced indirectly by alterations of the GH-IGH-1 axis and directly by local effects through GC receptors that are expressed in the physis [14,18,[38][39][40]. Furthermore, GC inhibit the sulphation of cartilage matrix, mineralisation of new bone, osteoblast activity and stimulate bone resorption [22,38,40].…”

Section: Glucocorticoids and Scfementioning

confidence: 99%

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

Witbreuk

Kemenade

Sluijs

et al. 2013

Journal of Children's Orthopaedics

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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.

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“…Moreover, the increased energy expenditure observed in chronic inflammatory disorders could impair linear growth, and inflammatory cytokines can adversely affect a number of components of growth plate chondrogenesis (De Benedetti 2009;Ahmed and S€ avendahl 2009) and can also disrupt the GH/IGF-1 axis (Savage 2013).…”

Section: Discussionmentioning

confidence: 99%

Growth Hormone Deficiency and Lysinuric Protein Intolerance: Case Report and Review of the Literature

et al. 2014

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Background: Lysinuric protein intolerance (LPI; MIM# 222700) is a rare metabolic disorder caused by a defective cationic amino acids (CAA) membrane transport leading to decreased circulating plasma CAA levels and resulting in dysfunction of the urea cycle. Short stature is commonly observed in children with LPI and has been associated with protein malnutrition. A correlation between LPI and growth hormone deficiency (GHD) has also been postulated because of the known interaction between the AA arginine, ornithine, and lysine and growth hormone (GH) secretion. Our report describes a case of GHD in an LPI patient, who has not presented a significant increase in growth velocity with recombinant-human GH (rhGH) therapy, suggesting some possible pathogenic mechanisms of growth failure.Case Presentation: The proband was a 6-year-old boy, diagnosed as suffering from LPI, erythrophagocytosis (HP) in bone marrow, and short stature. Two GH provocative tests revealed GHD. The patient started rhGH therapy and a controlled-protein diet initially with supplementation of oral arginine and then of citrulline. At 3-year follow-up, no significant increase in growth velocity and in insulin-like growth factor-1 (IGF-1) levels was observed. Inadequate nutrition and low plasmatic levels of arginine, ornithine, lysine, and HP may have contributed to his poor growth. Conclusion:Our case suggests that growth failure in patients with GHD and LPI treated with rhGH could have a complex and multifactorial pathogenesis. Persistently low plasmatic levels of lysine, arginine, and ornithine, associated with dietary protein and caloric restriction and systemic inflammation, could determine a defect in coupling GH to IGF-1 production explaining why GH replacement therapy is not able to significantly improve growth impairment. We hypothesize that a better understanding of growth failure pathophysiology in these patients could lead to the development of more rational strategies to treat short stature in patients with LPI.

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Promoting Growth in Chronic Inflammatory Disease: Lessons from Studies of the Growth Plate

Cited by 25 publications

References 51 publications

RECENT RESEARCH ON THE GROWTH PLATE: Impact of inflammatory cytokines on longitudinal bone growth

RECENT RESEARCH ON THE GROWTH PLATE: Impact of inflammatory cytokines on longitudinal bone growth

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

Growth Hormone Deficiency and Lysinuric Protein Intolerance: Case Report and Review of the Literature

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