Bone Abstracts

Relatively little is known about immediate consequences of continuing vs interrupting long-term bisphosphonate treatment. This report describes changes in bone turnover and BMD in a 1-year, dose-finding trial of the calcium-sensing receptor antagonist MK-5442 in postmenopausal, BP-treated women, randomized to continued alendronate 70 mg weekly, switch to placebo, or switch to MK-5442. Recruited women (n=526) had taken alendronate for ≥12 months and an oral BP fo...

Background: Genetic disorders of mineral metabolism causing nephrolithiasis and bone abnormalities are uncommon and have a varied clinical spectrum. Hypophosphataemic rickets with hypercalciuria (HHRH) is a rare autosomal-recessive condition, typically presenting with severe rickets and hypophosphataemia. Milder forms can present with hypercalciuria and nephrolithiasis without bone disease. The underlying pathophysiology is due to mutations in the SLC34A3 gene, which encodes t...

Recombinant human parathyroid hormone (rhPTH) (1–84) is currently being developed as PTH replacement therapy for patients with hypoparathyroidism. Because rhPTH(1–84) is administered subcutaneously, we compared the pharmacokinetic profile of PTH(1–84) and the calcemic response following S.C. rhPTH(1–84) injection in thigh and abdomen.In this phase 1, open-label, three-way crossover study, healthy postmenopausal women received three ra...

Fracture outpatient (FO) clinics aim to identify individuals at high fracture risk. Identification of individuals at high fracture risk has been improved since the introduction of vertebral fracture assessment (VFA). Unfortunately, participation rates in FO clinics are often low.The aim of this study is to i) assess the contributory value of VFA in addition to BMD measurements in identifying individuals with high fracture risk; ii) assess characteristics...

Skeletal development during childhood and adolescence is an important determinant of adult bone health. Patterns of growth differ between populations, but it is unclear how these differences relate to changes in bone size and volumetric density. We aimed to examine ethnic differences in skeletal phenotype in the context of pubertal growth and development in 279 adolescent males from Johannesburg, South Africa.We performed annual peripheral quantitative c...

Rheumatoid arthritis (RA) is characterised by periarticular bone destruction leading to permanent disability. Some other forms of arthritis, such as arthritis in systemic lupus erythematosus (SLE), rarely produce bone lesions. Corresponding to that, inactivation of Fas produces a murine SLE-like phenotype, but alleviates bone loss during antigen-induced arthritis (AIA). Aim of this study was to identify cell populations differentially regulated in non-resorptive vs. resorptive...

Background: Osteogenesis imperfecta (OI), the commonest inherited bone fragility disorder, affects 1/15,000 live births resulting in frequent fractures and reduced mobility, with significant impact on quality of life. Early diagnosis is important, as therapeutic advances can lead to improved clinical outcomes.Methodology and results: Trio whole exome sequencing in patients with OI identified, in two patients, compound heterozygous mutations in NBAS</...

Objectives: Neurofibromatosis 1 (NF1) is one of the most common autosomal dominant diseases. Skeletal involvement such as short stature, kyphoscoliosis, tibial bowing and pseudarthrosis are common osseous manifestations of NF1. Moreover, there is a growing evidence that reduced bone mineral density (BMD), is a common feature of NF1 subjects. The aim of the study was to evaluate the usefulness of Bone Mineral Density and Quantitative Ultrasound (QUS) at phalanxes in the assessm...

Objectives: Simultaneous pancreas kidney transplantation (SPKT) is a standard treatment option for adults with long-lasting (usually adolescence onset) type 1 diabetes (T1D) and concurrent renal failure. Despite the need for life-long immunosuppressive therapy the patients achieve better glycemic control, normalized renal function and an improved quality of life. Whether metabolic improvement is also reflected in the skeleton is not yet clear.Methods: Pa...

Childhood hypothyroidism results in delayed skeletal maturation and impaired growth. Thyroid hormones act via temporo-spatially regulated thyroid hormone receptors α (TRα) and (TRβ).In the skeleton, TRα is the predominant receptor and we hypothesise that the skeletal effects of hypothyroidism are mediated by TRα.To investigate this we assessed the response of wild-type (WT), TRα knockout (TRα...