Searchable abstracts of presentations at key conferences on calcified tissues

ba0003pp363 | Other diseases of bone and mineral metabolism | ECTS2014

Sustained efficacy and tolerability in infants and young children with life-threatening hypophosphatasia treated with asfotase alfa

Whyte Michael , Simmons Jill , Lutz Richard , Vallee Marc , Melian Agustin , Odrljin Tatjana , Bishop Nick

Background: Hypophosphatasia (HPP) results from inactivating mutation(s) in the gene for tissue non-specific alkaline phosphatase (TNSALP). Substantial improvement has been reported in skeletal mineralization and physical function in patients (pts) with life-threatening perinatal and infantile HPP treated for 48 weaks with asfotase alfa, a bone-targeted recombinant human TNSALP.Objective: To evaluate long-term efficacy and tolerability of asfotase alfa i...

ba0004lb1 | (1) | ICCBH2015

Maternal vitamin D depletion disrupts neonatal skeletal development in mice

Buckley Harriet , Borg Stephanie , Nicholson Kirsty , Kinch Mark , Hughes David , Skerry Tim , Bishop Nick

Fractures in infancy raise the spectre of child abuse; it has been suggested that lack of vitamin D could result in bone abnormalities that could predispose to fractures. We utilised a mouse model system to investigate whether vitamin D deficiency in utero alters early bone growth and development.C57BL/6 female mice received vitamin D deficient or replete diet for 6 weeks, then mated and continued on their respective diets until weaning. Pups were culled...

ba0004p153 | (1) | ICCBH2015

In-vivo high-resolution peripheral quantitative computer tomography assessment of skeletal microstructure in children with osteogenesis imperfecta

Digby Maria , Dimitri Paul , Arundel Paul , Bishop Nick , Paggiosi Margaret , Offiah Amaka

Objectives: The clinical assessment of bone mass in children with osteogenesis imperfecta (OI) is normally assessed by DXA. Further information about bone microarchitecture is obtained from bone biopsy which is invasive and requires anaesthetic. High-resolution peripheral quantitative computer tomography (HRpQCT) is an in-vivo imaging modality capable of assessing skeletal microstructure and integrity to a resolution of 80 μm. To date, no HRpQCT studies have incl...

ba0005p97 | Calciotropic and phosphotropic hormones and mineral metabolism | ECTS2016

Vitamin D therapy: the effects of race, skin colour and genotype

Sujatha Jaya , Kothandapani Gopal , Evans Lucy , Fatma Gossiel , Walsh Jennifer , Eastell Richard , Bishop Nick

Background: It is well established that Asians have lower levels of vitamin D (25OHD) when compared to Caucasians. Vitamin D binding protein (DBP) levels are also lower in some races than in Caucasians.Objectives: i) To find out whether DBP is lower in Asians; ii) To find out whether free 25OHD is lower in Asians; iii) To find out whether PTH is increased in Asians and interpret this in relation to 25OHD levels and iv) To find out whether the increment i...

ba0006p126 | (1) | ICCBH2017

A case of severe reaction following the use of Bisphosphonates in a patient with Osteogenesis Imperfecta

Park Julie , Alsaffar Hussain , Apperley Louise , Bishop Nick , Dharmaraj Poonam , Ramakrishnan Renuka

Background: We present a case of unusual delayed multi-systemic reaction, following treatment with Pamidronate. The reaction, resembling rhabdomyolysis, requiring intensive care support, has not been reported previously to our knowledge.Presenting problem: An 11 month old boy with severe osteogenesis imperfecta (OI) presented with hyperpyrexia and respiratory distress 10 days after his fifth cycle of Pamidronate. He had significant derangement of his bio...

ba0007oc18 | (1) | ICCBH2019

Developing a human-mouse hybrid model of osteogenesis imperfecta for investigating new therapies for children

Arshad Fawaz , Lefley Diane , Madan Sanjeev , Fernandes James , Bishop Nick , Ottewell Penelope

Objectives: Osteogenesis imperfecta (OI) displays a heterozygous phenotype even amongst similar genotypes. It has therefore been difficult to establish a mouse model which represents clinical OI in children. By engrafting human OI bone into mice we have developed a hybrid model enabling us to investigate the efficacy of new treatments for this phenotypically diverse condition.Methods: Bone chips, that would otherwise be discarded, were collected from chi...

ba0007p5 | (1) | ICCBH2019

Response of bone to mechanical stimulation in the offspring of MAVIDOS study mothers in a single centre; the effect of antenatal vitamin D supplementation

Gopal Sujatha , Rigby Alan , Moon Rebecca , Cooper Cyrus , Harvey Nick , Harrison Rachel , Bishop Nick

Background: Preclinical model studies suggest early life vitamin D depletion reduces bone’s response to mechanical loading. The MAVIDOS trial (randomised placebo controlled trial of vitamin D supplementation in pregnancy) reported winter-born infants of mothers receiving vitamin D supplementation had higher bone mass; the earlier Southampton Princess Ann Cohort study linked pregnancy blood vitamin D levels to later bone mass and size. We showed previously that bone respon...

ba0007p26 | (1) | ICCBH2019

Parathyroid hormone is higher in infants with fracture as opposed to without fracture undergoing skeletal survey for suspected non-accidental injury, and is inversely associated with mean corpuscular haemoglobin content

Lewis Lindsay , Alison Lilias , Hardisty Hannah , Parry-Okeden Sophie , Bishop Nick

Background: Biochemical and haematological testing is recommended in the United Kingdom when non-accidental injury is suspected. We examined the associations of test results with radiologically-confirmed fracture(s), and between test results, in a retrospective observational cohort.Methods: Infants up to age two years presenting with suspected non-accidental injury, without clinically-apparent bone disease, and where a skeletal survey was undertaken duri...

ba0007p27 | (1) | ICCBH2019

Response to mechanical stimulation of bone in children with osteogenesis imperfecta and the effect of bisphosphonate therapy

Sithambaran Sivagamy , Gopal Sujatha , Harrison Rachel , Gossiel Fatma , Rigby Alan , Bishop Nick

Objectives: Children with osteogenesis imperfecta (OI) suffer fragility fractures due to altered bone mass, architecture and material quality. Management is multidisciplinary, often including bisphosphonates and physiotherapy. We wished to determine whether bisphosphonates altered the skeletal response to mechanical stimulation in OI. Short term exposure to whole body vibration (WBV) in apparently healthy children results in increases in bone formation and resorption markers, ...

ba0007p77 | (1) | ICCBH2019

Long-term efficacy profile of asfotase alfa in the treatment of patients with hypophosphatasia: a pooled analysis

Hogler Wolfgang , Rockman-Greenberg Cheryl , Petryk Anna , Zhou Shanggen , Whyte Michael P , Bishop Nick

Objectives: Asfotase alfa (AA), an enzyme replacement therapy, is the only approved medical treatment for pediatric-onset hypophosphatasia (HPP), which is caused by deficient tissue-nonspecific alkaline phosphatase activity. We detail the long-term efficacy of AA observed from the pediatric clinical trial program.Methods: Efficacy data collected to study completion were pooled from 3 open-label, multicenter investigations of children who manifested HPP s...