Searchable abstracts of presentations at key conferences on calcified tissues

ba0005ht6 | (1) | ECTS2016

Effect of KRN23, a fully human anti-FGF23 monoclonal antibody, on rickets in children with X-linked hypophosphatemia (XLH): 40-week interim results from a randomized, open-label Phase 2 study

Imel Erik , Carpenter Thomas , Boot Annemieke , Hogler Wolfgang , Linglart Agnes , Padidela Raja , van't Hoff William , Whyte Michael , Agarwal Sunil , Chen Chao-Yin , Skrinar Alison , Martin Javier San , Portale Anthony

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...

ba0005oc3.6 | Clinical trials, FGF-23 and focal osteoporosis | ECTS2016

Focal osteoporosis associated with hip fracture involves both trabecular and cortical bone; a 3D cortical bone mapping study of cases and controls using clinical CT

Poole Ken , Skingle Linda , Gee Andrew , Turmezei Thomas , Johannesdottir Fjola , Blesic Karen , Rose Collette , Vindlacheruvu Madhavi , Donnell Simon , Vaculik Jan , Dungl Pavel , Horak Martin , Stepan Jan , Reeve Jonathan , Treece Graham

Focal cortical thinning and loss of trabecular structure in the proximal femur is associated with hip fracture. We analysed clinical computed tomography (CT) scans in cases and controls to explore their contributions to hip fracture in women.We used cortical bone mapping (CBM) and statistical parametric mapping (SPM) after combining women with hip fracture from FEMCO and Prague Hip Joint in Trauma studies (n=138, 52 Trochanteric and 86 Femoral N...

ba0007oc14 | (1) | ICCBH2019

Burosumab resulted in greater improvement in clinical outcomes than continuation with conventional therapy in younger (1-4 years-old) and older (5-12 years-old) children with X-linked hypophosphatemia

Ward Leanne , Imel Erik , Whyte Michael , Munns Craig , Portale Anthony , Hogler Wolfgang , Simmons Jill , Padidela Raja , Namba Noriyuki , Cheong Hae , Nilsson Ola , Mao Meng , Skrinar Alison , Chen Chao-Yin , Martin Javier San , Glorieux Francis

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...

ba0001pp78 | Bone development/growth and fracture repair | ECTS2013

Sex-related differences of femur properties in silver foxes (Vulpes vulpes)

Tatara Marcin , Krupski Witold , Jakubczak Andrzej , Bienko Marek , Kostro Krzysztof

Considering limited information available on skeletal system properties in foxes, the aim of this study was to determine morphological, geometrical and densitometric parameters of femur obtained from males and females. The study was performed on 1-year old male (n=5) and female (n=6) silver foxes. Right femur was isolated and its weight and length were measured. Using quantitative computed tomography (QCT) technique and Somatom Emotion Siemens apparatus, bone...

ba0003pp190 | Genetics | ECTS2014

Premature aging of bone is delayed by dietary restriction

van der Eerden Bram , Botter Sander , Reiling Erwin , Hoeijmakers Jan , Dolle Martijn , van Leeuwen Johannes

Loss of genomic maintenance contributes to aging, as exemplified by mutations in Ercc DNA repair proteins that lead to a plethora of progeroid syndromes of which some display accelerated bone loss. It is generally accepted that dietary restriction (DR) increases life span and improves organ function. We therefore assessed the impact of DR on life span and bone mass in WT and bona fide prematurely aging hypomorphic Ercc-deficient mice (Ercc1−/Δ).<...

ba0005oc2.4 | Bone mass and bone strength Wnt signalling | ECTS2016

Up-regulation of Wnt antagonists contributes to the attenuated response of bone formation to repeat doses of sclerostin antibody in a mouse model

Holdsworth Gill , Greenslade Kevin , Stencel Zofia , Jose Joby , Kirby Hishani , Moore Adrian , Robinson Martyn , Ke David

Loss of the gene encoding the secreted Wnt antagonist sclerostin results in increased bone mass in humans and mice. Administration of antibodies to sclerostin (Scl-Ab) has been shown to increase bone mineral density (BMD) by increasing bone formation and decreasing bone resorption, in both animal studies and human clinical trials. In these studies, the magnitude and rate of increase in bone formation markers, and the rate of increase of BMD, diminishes upon repeat dosing with ...

ba0005p463 | Other diseases of bone and mineral metabolism | ECTS2016

Change in bone mineral density with high-dose prednisone in patients with rheumatoid arthritis

Rasch Linda , van Tuyl Lilian , Kremer Martijn , Bultink Irene , Boers Maarten , Lems Willem

Background: Recently, we showed that treatment with COBRA-light therapy including prednisone with initially 30 mg/day was as effective as the original COBRA scheme, with initially 60 mg/day (Ter Wee, ARD 2015), in the treatment of rheumatoid arthritis (RA). Since high-dose glucocorticoids are associated with bone loss, we investigated the differences in bone mineral density (BMD) after 1 year of treatment in both arms.Objective: To determine whether ther...

ba0003pp297 | Osteoporosis: treatment | ECTS2014

Contribution of circulating sclerostin and estradiol for inadequate response to bisphosphonate therapy in women with postmenopausal osteoporosis

Munoz-Torres M , Diez-Perez A , Olmos J M , Nogues X , Sosa M , Diaz-Curiel M , Perez-Castrillon J L , Perez-Cano R , Torrijos A , Jodar E , Rio L Del , Caeiro-Rey J R , Rubio V Avila , Garcia-Martin A , Reyes-Garcia R , Garcia-Fontana B , Gonzalez-Macias J , Morales-Santana S

Bisphosphonate treatment reduces fracture risk in women with postmenopausal osteoporosis. However, some patients have an inadequate response to treatment. Estradiol and sclerostin play an important role in bone metabolism. Sclerostin is an endogenous inhibitor of osteoblastic activity and estrogen deficiency increases osteoclast activity and bone resorption.We examined the influence of both measures on fracture incidence in postmenopausal osteoporosis in...

ba0002p115 | (1) | ICCBH2013

Bone mineral density in late adolescence of transsexuals treated with GnRH-analogues in their teens

Klink Daniel , Caris Martine , van Trotsenburg Mick , Rotteveel Joost

Young transsexuals at a minimum age of 12 years are treated with GnRH-analogues (GnRHa) to suspend pubertal development until the addition of hormones of the desired sex is started at a minimum age of 16 years. The effect of this treatment on adult bone mineral density (BMD) is still unknown. We aimed to assess BMD at the age of 22, as this is near its peak in healthy individuals.In this prospective observational study 19 female to male (FtM) and 16 male...

ba0003pp179 | Chondrocytes and cartilage | ECTS2014

Osteoclasts inhibit the Wnt canonical pathway in chondrocytes

Cherifi Chahrazad , Bouaziz Wafa , Cohen-Solal Martine , Hay Eric

Purpose: Osteoclastogenesis is enhanced in osteoarthritis (OA). We have demonstrated that cartilage breakdown is reduced when osteoclastogenesis is inhibited in murine models. Wnt activity, known to regulate the bone and chondrocyte cell function, might contribute to the mechanisms that promote cartilage catabolism. Our purpose was to evaluate whether osteoclast-secreted molecules affect the chondrocyte metabolism and assess the contribution of Wnt pathway.<p class="abstex...