Three-Year Growth Hormone Treatment in Short Children with X-Linked Hypophosphatemic Rickets: Effects on Linear Growth and Body Disproportion

Živičnjak, Miroslav; Schnabel, Dirk; Staude, Hagen; Even, Gertrud; Marx, Michaela; Beetz, Rolf; Holder, Martin; Billing, Heiko; Dc, Fischer; Rabl, Wolfgang; Schumacher, Marius; Hiort, Olaf; Haffner, Dieter; Nephrologie, Gesellschaft für Pädiatrische

doi:10.1210/jc.2011-0399

Cited by 62 publications

(37 citation statements)

References 48 publications

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“…The only randomized study by Zivicnjak et al . (39) showed significant improvement of linear growth (+1.1 height SDS) in eight patients treated with rGH out of 16 short (mean height SDS −3.3) prepubertal children with XLHR. Addition of rGH induces a rise in mineral needs, which should be accompanied with a 20–30% increment in vitamin D analogs dosage.…”

Section: Therapy In Childrenmentioning

confidence: 91%

Therapeutic management of hypophosphatemic rickets from infancy to adulthood

Linglart¹,

Duplan²,

Briot³

et al. 2014

Endocrine Connections

280

389

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In children, hypophosphatemic rickets (HR) is revealed by delayed walking, waddling gait, leg bowing, enlarged cartilages, bone pain, craniostenosis, spontaneous dental abscesses, and growth failure. If undiagnosed during childhood, patients with hypophosphatemia present with bone and/or joint pain, fractures, mineralization defects such as osteomalacia, entesopathy, severe dental anomalies, hearing loss, and fatigue. Healing rickets is the initial endpoint of treatment in children. Therapy aims at counteracting consequences of FGF23 excess, i.e. oral phosphorus supplementation with multiple daily intakes to compensate for renal phosphate wasting and active vitamin D analogs (alfacalcidol or calcitriol) to counter the 1,25-diOH-vitamin D deficiency. Corrective surgeries for residual leg bowing at the end of growth are occasionally performed. In absence of consensus regarding indications of the treatment in adults, it is generally accepted that medical treatment should be reinitiated (or maintained) in symptomatic patients to reduce pain, which may be due to bone microfractures and/or osteomalacia. In addition to the conventional treatment, optimal care of symptomatic patients requires pharmacological and non-pharmacological management of pain and joint stiffness, through appropriated rehabilitation. Much attention should be given to the dental and periodontal manifestations of HR. Besides vitamin D analogs and phosphate supplements that improve tooth mineralization, rigorous oral hygiene, active endodontic treatment of root abscesses and preventive protection of teeth surfaces are recommended. Current outcomes of this therapy are still not optimal, and therapies targeting the pathophysiology of the disease, i.e. FGF23 excess, are desirable. In this review, medical, dental, surgical, and contributions of various expertises to the treatment of HR are described, with an effort to highlight the importance of coordinated care.

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Section: Therapy In Childrenmentioning

confidence: 91%

Therapeutic management of hypophosphatemic rickets from infancy to adulthood

Linglart¹,

Duplan²,

Briot³

et al. 2014

Endocrine Connections

280

389

View full text Add to dashboard Cite

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“…[21] A recent study has demonstrated the efficacy of GH in children with XLH where there was significant improvement in height SDS without worsening of skeletal disproportion. [22] Administration of single dose of calcitonin in XLH patients causes a significant and sustained drop in the circulating levels of FGF23 and an increase in the serum levels of phosphorus. [23] Short-term treatment with cinacalcet suppresses PTH, leading to increase in TMP/GFR and serum phosphate.…”

Section: X-linked Hypophosphatemic Ricketsmentioning

confidence: 99%

Hypophosphatemic rickets

Jagtap

Sarathi

Lila

et al. 2012

Indian J Endocr Metab

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Hypophosphatemic rickets is a disorder of bone mineralization caused due to defects (inherited/acquired) in the renal handling of phosphorus. This group includes varied conditions, X-linked hypophosphatemic rickets being the most common inheritable form of rickets. The other common forms are autosomal dominant hypophosphatemic rickets and tumor-induced osteomalacia. Although these conditions exhibit different etiologies, increased phosphatonins form a common link among them. Fibroblast growth factor 23 (FGF23) is the most widely studied phosphatonin. Genetic studies tend to show that the phosphorus homeostasis depends on a complex osteo-renal axis, whose mechanisms have been poorly understood so far. Newer disorders are being added as the mechanisms in this axis get discovered. This review focuses on the clinical, biochemical, genetic features and management of hypophosphatemic disorders leading to defective mineralization.

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“…Growth hormone has been used to treat short stature in children with XLH. However, despite apparent improved linear growth over 3 years in a randomized open‐label study of XLH patients, there was no significant difference in final adult height between those treated with growth hormone and controls . Interestingly, the randomized study excluded patients with severe leg deformities, meaning that we have no controlled trial data on the potential for benefit or harm in that group.…”

Section: Medical Therapy Of Fgf23‐mediated Skeletal Disordersmentioning

confidence: 97%

FGF23, Hypophosphatemia, and Emerging Treatments

2019

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FGF23 is an important hormonal regulator of phosphate homeostasis. Together with its co‐receptor Klotho, it modulates phosphate reabsorption and both 1α‐hydroxylation and 24‐hydroxylation in the renal proximal tubules. The most common FGF23‐mediated hypophosphatemia is X‐linked hypophosphatemia (XLH), caused by mutations in the PHEX gene. FGF23‐mediated forms of hypophosphatemia are characterized by phosphaturia and low or low‐normal calcitriol concentrations, and unlike nutritional rickets, these cannot be cured with nutritional vitamin D supplementation. Autosomal dominant and autosomal recessive forms of FGF23‐mediated hypophosphatemias show a similar pathophysiology, despite a variety of different underlying genetic causes. An excess of FGF23 activity has also been associated with a number of other conditions causing hypophosphatemia, including tumor‐induced osteomalacia, fibrous dysplasia of the bone, and cutaneous skeletal hypophosphatemia syndrome. Historically phosphate supplementation and therapy using analogs of highly active vitamin D (eg, calcitriol, alfacalcidol, paricalcitol, eldecalcitol) have been used to manage conditions involving hypophosphatemia; however, recently a neutralizing antibody for FGF23 (burosumab) has emerged as a promising treatment agent for FGF23‐mediated disorders. This review discusses the progression of clinical trials for burosumab for the treatment of XLH and its recent availability for clinical use. Burosumab may have potential for treating other conditions associated with FGF23 overactivity, but these are not yet supported by trial data. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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Three-Year Growth Hormone Treatment in Short Children with X-Linked Hypophosphatemic Rickets: Effects on Linear Growth and Body Disproportion

Abstract: The 3-yr GH treatment improved linear growth without progression of body disproportion in short children with XLH.

Cited by 62 publications

References 48 publications

Therapeutic management of hypophosphatemic rickets from infancy to adulthood

Therapeutic management of hypophosphatemic rickets from infancy to adulthood

Hypophosphatemic rickets

FGF23, Hypophosphatemia, and Emerging Treatments

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