Bone Abstracts

Sclerostin, a Wnt signaling antagonist encoded by the SOST gene, negatively regulates osteoblasts and inhibits bone formation. Mechanical loading, which induces bone formation, leads to a decrease in sclerostin levels. Recently, neutralizing antibodies against sclerostin were tested successfully for the treatment of osteoporosis in rodents. However, sclerostin is not the only signal involved in mechanotransduction. Therefore we investigated whether treatment with sclerostin an...

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Children with osteogenesis imperfecta (OI) still suffer from frequent fractures, despite bisphosphonate treatment. Thus new therapeutic approaches are needed. Sclerostin is a protein that is thought to inhibit bone formation. Treatment with sclerostin antibodies (SclAB) increases bone mass in animal models and in clinical trials and may be a rational therapy for OI as well.Transgenic (TgOI) Col1a1Jrt/+ mice were gene...

DMAb increases BMD and reduces bone resorption and risk of vertebral, nonvertebral and hip fractures in women with PMO. Transiliac crest bone biopsies in 47 subjects treated with DMAb for 1–3 years showed reduced bone turnover vs 45 Pbo-treated subjects, which reversed on treatment cessation. Since bone turnover reduction is sustained and fracture incidence low over 6 years’ DMAb treatment, we evaluated DMAb’s effects on tissue-level remodelling in the FREEDOM E...

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Low bone mineral density (BMD) is an important and modifiable risk factor for fracture in postmenopausal women with osteoporosis. Denosumab (DMAb) shows a stronger relationship between BMD increases and antifracture efficacy than oral bisphosphonate (BP) therapies. Subjects who remain at higher risk of fracture despite current BP therapy need treatment. In two studies, DMAb significantly increased BMD and decreased bone turnover markers vs a BP (ibandronate (IBN) or risedronat...

In XLH, high circulating FGF23 causes hypophosphatemia, rickets, and short stature. In our Phase 2 study, 52 XLH children (ages 5-12 years, ≥Tanner 2) were randomized to receive KRN23 subcutaneously biweekly (Q2W) or monthly (Q4W). Serum phosphate (Pi) was measured biweekly. KRN23 dose was titrated (maximum 2 mg/kg) targeting age-appropriate serum Pi concentrations.The first 36 subjects had a mean 6.6 years of standard-of-care treatment before wash...

Bisphosphonates are used in the treatment of a variety of diseases with skeletal complications. With the development of more potent compounds, there is the potential for further improvement. One concept is to use compounds with a reduced affinity for bone, reducing their long-term retention and possible adverse events, as well as potentially enhancing their non-skeletal benefits. We hypothesise that a highly potent bisphosphonate with low bone affinity, known as OX14, will be ...

Objective: Although there is adequate sunlight throughout the year, low serum 25OHD concentrations are being increasingly reported among Indian children (Gupta, 2014). Thus, quantifying individual sunlight exposure may be an important step in understanding hypovitaminosis D in sun-rich geographies. The objectives of our study were to quantify the sunlight exposure of school-children using a questionnaire and to use polysulphone film badges to validate the questionnaire adminis...

Objective: We compared the efficacy and safety of burosumab, a monoclonal antibody against FGF23, to conventional therapy [oral phosphate and active vitamin D (Pi/D)] in children with X-linked hypophosphatemia (XLH).Methods: In this Phase 3 trial (NCT02915705), 61 children with XLH (1-12 years-old) were randomized 1:1 after a 7-day Pi/D washout to receive burosumab starting at 0.8 mg/kg SC Q2W or reinitiate Pi/D optimally titrated by investigators. Eligi...