hrp0084s10.2 | Growth plate in chronic diseases | ESPE2015

Molecular Response of the Growth Plate to Inflammatory Cytokines

Savendahl Lars

Background: 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. In conditio...

hrp0084p1-15 | Bone | ESPE2015

Lithium Chloride Prevents Glucocorticoid-Induced Growth Failure in Cultured Foetal Rat Metatarsal Bones

Soucek Ondrej , Zaman Farasat , Savendahl Lars

Background: Glucocorticoids (GCs) are frequently used to treat numerous chronic diseases in children. Beside their desired anti-inflammatory and immunosuppressive effects, GCs are well known to cause osteoporosis and impaired linear bone growth. These serious side effects of GCs have at least partially been linked to impairment of Wnt/β-catenin signalling. There is no therapy available to rescue from the undesired skeletal effects of GCs.Objective a...

hrp0084p3-1014 | Growth | ESPE2015

Altered Gene-Expression in Human Growth Plate Cartilage Tissue Exposed to Dexamethasone

Cedervall Therese , Zaman Farasat , Savendahl Lars

Background: Synthetic glucocorticoids (GCs) are widely used drugs but their suppression of growth in pediatric patients is a well-known problem. Different mechanisms have been suggested but we still do not know the sensitivity of human growth plate cartilage to GC treatment. Here in this study, we have investigated the direct effects of GC treatment on the expression of crucial genes in the growth plate, such as collagen-2A1, osterix (Osx), and transforming growth factor &#946...

hrp0089fc2.5 | Bone, Growth Plate & Mineral Metabolism 1 | ESPE2018

Radial ESWT Stimulates Longitudinal Bone Growth in Cultured Rat Fetal Metatarsal Bones

Ramesh Sowmya , Zaman Farasat , Madhuri Vrisha , Savendahl Lars

Background: Extracorporeal shock wave therapy (ESWT) is widely used in the clinic for non-union of fractures. However, effect of ESWT on longitudinal bone growth has not been well studied. We explored the in vitro and in vivo effects of low/high dose radial shock wave treatment (SWT) on growth plate (GP) cartilage. A positive or negative effect on growth could be harnessed for therapeutic growth modulation while no change establishes safety.<p class="abst...

hrp0086p1-p105 | Bone &amp; Mineral Metabolism P1 | ESPE2016

Effects of Selective GPER-1 Agonist G1 on Bone Growth

Iravani Maryam , Karimian Elham , Chagin Andrei , Savendahl Lars

Background: Abnormal growth is a common problem in children. Some children do not respond to growth hormone therapy and alternative treatments selectively targeting the growth plate are needed. High doses of estrogens induce growth plate closure and stop further growth. However, high-dose estrogen treatment may also have severe side effects, including increased risk of cancer and reduced fertility. The expression of estrogen receptors (ER), including GPER-1, has been demonstra...

hrp0084fc4.6 | Growth | ESPE2015

Positive Association between Height and Cancer in the Swedish Population

Benyi Emelie , Linder Marie , Adami Johanna , Palme Marten , Savendahl Lars

Background: Previous studies have indicated that taller individuals have a higher risk of developing different types of cancer, including breast cancer and melanoma.Objective and hypotheses: Our goal was to study any association between height and the risk of cancer in general-, and breast cancer and melanoma specifically in a very large cohort composed of most Swedish women and men followed over a long period of time.Method: We ha...

hrp0084p1-17 | Bone | ESPE2015

Humanin Prevents Undesired Apoptosis of Chondrocytes without Interfering with the Anti-Inflammatory Effect of Dexamethasone in a Model of Arthritis

Sederquist Bettina , Aulin Cecilia , Zaman Farasat , Savendahl Lars

Background: Glucocorticoids (GCs) are widely used for treatment of inflammatory and autoimmune conditions. Prolonged use of GCs, however, has several negative side effects, including bone growth impairment in children. Previous studies have shown that GC-induced apoptosis in growth plate chondrocytes is mediated by inhibition of the PI3K–Akt signaling pathway and activation of the pro-apoptotic protein Bax. Humanin, a small mitochondrial derived peptide, has shown promisi...

hrp0084p2-232 | Bone | ESPE2015

Regulation of Bone Growth Via Ligand-Specific Activation of Oestrogen Receptor α

Iravani Maryam , Lagerquist Marie , Ohlsson Claes , Savendahl Lars

Background: Oestrogens are well known for their capacity to promote bone maturation and at high doses to induce growth plate closure and thereby stop further growth. High-dose oestrogen treatment has therefore been used to limit growth in extremely tall girls. However, recent data suggest that this treatment may have severe side effects, including increased risk of cancer and reduced fertility.Objective and hypotheses: We hypothesised that oestrogenic ef...

hrp0089p2-p252 | Growth &amp; Syndromes P2 | ESPE2018

Final Results of NordiNet® International Outcome Study: Key Outcomes in Paediatric Patients

Polak Michel , Blair Jo , Rohrer Tilman R. , Pietropoli Alberto , Tonnes Pedersen Birgitte , Savendahl Lars

Background: NordiNet® International Outcome Study ([IOS]; NCT00960128), a non-interventional study (2006–2016), assessed the effectiveness and safety of real-world treatment with Norditropin®. Outcomes were assessed in children with growth hormone deficiency (GHD), born small for gestational age (SGA), Turner syndrome (TS), chronic renal disease (CRD), idiopathic short stature (ISS), Noonan syndrome (NS) and Prader-Willi syndrome (PWS)....

hrp0086p2-p643 | Growth P2 | ESPE2016

An Analysis of the Safety of Childhood Growth Hormone (GH) Therapy: Data from the NordiNet® International Outcome Study (IOS)

Savendahl Lars , Rohrer Tilman R , Pournara Effie , Pedersen Birgitte Tonnes , Blankenstein Oliver

Background: NordiNet® IOS (NCT00960128), a non-interventional study, collects long-term effectiveness and safety data of GH (Norditropin®, Novo Nordisk) treatment in everyday clinical practice.Objective and hypotheses: Identify paediatric patients more likely to experience a second adverse event (AE).Method: Based on diagnosis at GH treatment start and associated risk for mortality, patients were cla...