Bone Abstracts

Atypical femur fractures (AFF) have been associated with antiresorptive therapy. In a retrospective case-control study, we identified AFF using ASBMR 2013 criteria. Femoral shaft fractures were identified using ICD9 codes. We screened 1479 radiographs. Radiographs were excluded for high-energy trauma, tumor, or periprosthetic fracture. Two radiologists blinded to treatment scored 482 radiographs for AFF features, and jointly adjudicated discrepancies. The required AFF feature,...

To evaluate the regeneration of alveolar bone after treatment with bone-resorption inhibitors in old acyclic rats that had been through a long period of low estrogen. Thirty-two female Wistar rats with 20 months old intact and ovariectomized (OVX at 4 months of age), were randomized into four groups (n=8/group): i) intact; ii) OVX/O (corn oil); iii) OVX/E2 (17β-estradiol, 400 μg) and iv) OVX/RLX (Raloxifene, 1 mg/kg per day). All treatments began ...

Objectives: Osteogenesis imperfecta (OI) is a bone disease mainly caused by collagen type I mutations and characterized by bone fragility. No definitive cure is available and the search for novel treatments is necessary. The small teleost D. rerio is particularly appealing for drug screening approaches. A zebrafish OI model (Chihuahua) carrying in heterozygosis the G574D substitution in the α1 chain of collagen type I is available. To use this model for ...

Introduction: The creatine kinase (CK) is a dimeric enzyme, involved in energetical metabolism. It is present in many tissues, but higher concentration in skeletal and cardiac muscle.Therefore, conditions that involve muscle tissue may increase this serum enzyme. Such enzyme elevation is usually observed in inflammatory myopathies and others autoimmune diseases.Sometimes some elevation in CK is not fully understood out off these co...

Background: Elevated plasma homocysteine levels are a risk factor for osteoporotic fractures. Supplementation with vitamin B12/folic acid lowers homocysteine levels. This study aimed to determine whether vitamin B12/folic acid supplementation reduces osteoporotic fracture incidence in hyperhomocysteinemic elderly.Methods: B-PROOF is a double-blind, randomized, placebo-controlled trial including 2 919 participants aged ≧65 years with elevated homocyste...

Introduction: Standard clinical treatments for postmenopausal osteoporosis utilize resorption-inhibiting drugs such as bisphosphonates, which selectively bind to bone mineral but also suppress bone formation over time. Prostaglandin E2 (PGE2) has bone-anabolic effects in vivo, but its clinical utility is hindered by side effects upon systemic administration. Since PGE2 acts on bone via the EP4 receptor, our approach utilizes a specific...

Screening gene function in vivo is a powerful approach to discover novel drug targets in the human genome (Nat Rev Drug Discov 2 38–51, 2003). We present data for 3776 distinct gene knockout (KO) mouse lines with viable adult homozygous mice generated using both gene-trapping and homologous recombination technologies. Bone mass was determined from PIXImus DEXA scans of male and female mice at 14 weeks of age and by microCT analyses of bones from ...

Background: Hyperphosphatemic Familial Tumoral Calcinosis (HFTC) and Hyperphosphatemic Hyperostosis Syndrome (HHS) are two phenotypes of a disease associated with autosomal recessive mutations in FGF23, GALNT3 and KL, leading to reduced levels and clinical effects of fibroblast growth factor 23 (FGF23). We describe a consanguineous family with two affected individuals with HFTC and HHS caused by a novel homozygous mutation in GALNT3. We also...

Introduction: Prostaglandin E2 has bone-anabolic effects through EP4 receptor but its clinical utility is hindered by gastrointestinal side effects. To avoid these side effects, EP4 agonists (EP4a) were covalently linked to the bisphosphonate alendronate (ALN) to create two ALN-EP4a conjugate drugs, C1 and C2. When administered systemically, C1 and C2 will be target delivered to bone through ALN, where local hydrolytic enzymes liberate EP4a from ALN to exert bone an...

Introduction: Giant cell tumour of the bone (GCTB) is a benign, locally aggressive tumour whose neoplastic stromal cells express receptor activator of nuclear factor kappa-B ligand (RANKL) and activate its receptor RANK on osteoclast-like giant cells. Denosumab (RANKL inhibitor) is an FDA/EMA approved treatment for GCTB in adults and ‘skeletally mature’ adolescents. Safety concerns include oversuppression of bone remodelling, with risk of osteonecrosis of the jaw [ON...