Bone Abstracts

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...

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...

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...

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...

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...

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...

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...

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...

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, ...

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...