Bone Abstracts

Background: Osteoporosis in children with osteogenesis imperfecta (OI) type 1 and acute lymphoblastic leukaemia (ALL) is characterised by high bone turnover. However the ability of spontaneous healing and reshaping of bone is retained in ALL even in the absence of bisphosphonate (BP) therapy, but impaired in OI.Aim: To compare the response to BP therapy in children with ALL and OI.Methods: Retrospective case note review of children...

Objectives: Osteogenesis imperfecta (OI) is a bone fragility disorder associated with reduced muscle size, dynamic muscle function and mobility. This paired randomised controlled pilot study assessed the effect of whole body vibration (WBV) training on bone density and geometry, muscle size and function, mobility, and balance in children with OI.Methods: Twenty-four children (5–16 years) with OI types 1,4 and limited mobility (defined as a Childhood...

Background: Most patients with hypoparathyroidism are controlled under conventional treatment with calcium and vitamin D analogues. However, this treatment may be difficult to manage, especially in patients with ADHH who have an increased risk of nephrocalcinosis and chronic renal insufficiency. ADHH is caused by activating mutations in the calcium-sensing receptor (CaSR) resulting in suppressed PTH secretion and decreased calcium reabsorption within the thick ascending limb o...

Osteogenesis imperfecta (OI) classification has recently been broadened to include genes that primarily affect osteoblast differentiation. TMEM38B encodes TRIC-B, a ubiquitously expressed monovalent cation-specific channel protein involved in calcium release from the endoplasmic reticulum. How alterations in TMEM38B cause OI remains poorly understood and bone matrix characteristics in affected patients have not previously been described.<p class="abstext"...

Objective: Hypophosphatasia (HPP) is a rare, inherited metabolic disease characterized by bone mineralization defects and osteomalacia, as well as systemic manifestations, including seizures, respiratory insufficiency, muscle weakness, nephrocalcinosis, and pain. The biochemical hallmark of HPP is low serum alkaline phosphatase, resulting from loss-of-function mutations in the gene encoding tissue non-specific alkaline phosphatase. HPP presents a broad spectrum of disease seve...

Objectives: In XLH, FGF23-mediated hypophosphatemia leads to defective bone mineralization and rickets. Investigational product KRN23 binds FGF23 and inhibits its activity. The objective of this Phase 2 study was to evaluate the safety and efficacy of KRN23 in 52 children with XLH (ages 5–12 years, ≤Tanner 2).Methods: Patients were randomized to receive KRN23 biweekly (Q2W) or monthly (Q4W) by SC injection. KRN23 dose was titrated (maximum 2 m...

Background: The development of hypophosphataemic rickets in infants fed with the elemental formula (EF) Neocate® has been recently reported. We present seven cases of exclusively Neocate-fed babies who developed hypophosphataemic rickets.Presenting problem: Three patients (P1,3,4) had incidental findings of rickets on chest X-rays, two (P2,6) developed leg deformities and rickets was confirmed on X-rays, and two (P5,6) presented with femu...

Objectives: In XLH, musculoskeletal outcomes of current treatment with oral phosphate (Pi)/active vitamin D are suboptimal for many patients. In a Phase 2, open-label study, we tested the hypothesis that KRN23 improves rickets and functional outcomes in XLH children.Methods: Fifty-two children with XLH (ages 5–12 years at baseline) received KRN23 subcutaneously biweekly (Q2W) or monthly (Q4W). At study entry, most participants had received oral Pi/a...

Objectives: Limited data exist on growth parameters in children with hypophosphatasia (HPP), a rare metabolic disease characterized by impaired bone mineralization. We aimed to describe growth characteristics in untreated children with HPP enrolled in the Global HPP Patient Registry.Methods: Children (<18 years old) with a diagnosis of HPP who were not receiving enzyme replacement therapy with asfotase alfa at the time of evaluation were identified f...

Objective: We evaluated the long-term efficacy of burosumab, a monoclonal antibody against FGF23, in a Phase 2 Study (NCT02163577) in children with XLH.Methods: Fifty-two children with XLH (5-12 years-old, Tanner ≤ 2) were randomized 1:1 to receive subcutaneous burosumab Q2W or Q4W for 64 weeks. Doses were titrated up to 2 mg/kg/dose targeting serum phosphorus levels within 1.1–1.6 mmol/l. All subjects entered the long-term extension at Week 6...