Bone Abstracts

Background: Vitamin D plays an important role in calcium and phosphate homeostasis. Circulating 25 hydroxyvitamin D [25(OH)D] is metabolised into its biologically active form 1,25-dihydroxyvitamin D [1,25-d(OH)D] by the actions of 1α hydroxylase, and into inactive 2metabolite 24,25-dihydroxyvitamin D [24,25-d(OH)D] by 24-hydroxylase. Recent studies suggest the production of 1,25-d(OH)D) from 25(OH)D is 24,25-d(OH)D dependent. Genetic mutations of CYP24A1 gene resulting in...

Background: Osteocalcin has an important role in bone metabolism. Uncarboxylated osteocalcin predicts risk for hip fracture and lower bone mineral density (BMD). Warfarin inhibits carboxylation of osteocalcin, providing a mechanistic link between warfarin and impaired bone metabolism. Studies examining the relationship between warfarin use and BMD have been inconsistent. The goal of this study was to further characterize this relationship.Population: CaM...

Objectives: In XLH, FGF23-mediated hypophosphatemia leads to defective bone mineralization and rickets. Investigational product KRN23 binds FGF23 and inhibits its activity. The objective of this Phase 2 study was to evaluate the safety and efficacy of KRN23 in 52 children with XLH (ages 5–12 years, ≤Tanner 2).Methods: Patients were randomized to receive KRN23 biweekly (Q2W) or monthly (Q4W) by SC injection. KRN23 dose was titrated (maximum 2 m...

Objectives: In XLH, musculoskeletal outcomes of current treatment with oral phosphate (Pi)/active vitamin D are suboptimal for many patients. In a Phase 2, open-label study, we tested the hypothesis that KRN23 improves rickets and functional outcomes in XLH children.Methods: Fifty-two children with XLH (ages 5–12 years at baseline) received KRN23 subcutaneously biweekly (Q2W) or monthly (Q4W). At study entry, most participants had received oral Pi/a...

Vitamin D deficiency in pregnancy is common, and is linked to increased risk of adverse outcomes including preterm birth, preeclampsia, infection, gestational diabetes and asthma. Vitamin D possesses well-recognized immunomodulatory functions, and programming of the immune system during foetal development can influence asthma-related risk factors and health outcomes in later life. We hypothesized that influencing vitamin D status during pregnancy would impact the immune profil...

Objective: We evaluated the long-term efficacy of burosumab, a monoclonal antibody against FGF23, in a Phase 2 Study (NCT02163577) in children with XLH.Methods: Fifty-two children with XLH (5-12 years-old, Tanner ≤ 2) were randomized 1:1 to receive subcutaneous burosumab Q2W or Q4W for 64 weeks. Doses were titrated up to 2 mg/kg/dose targeting serum phosphorus levels within 1.1–1.6 mmol/l. All subjects entered the long-term extension at Week 6...

Selenium (Se) is an essential trace element active in the catalytic sites of many redox enzymes, including glutathione peroxidase and the iodothyronine deiodinases that metabolize thyroid hormones. In humans 25 genes encode selenoproteins, in which a specific tRNA incorporates the amino acid selenocysteine during protein translation. Although specific roles for many selenoproteins are unclear, studies suggest an important role for Se in skeletal development and bone maintenanc...

Hypothyroidism delays bone development and linear growth, whereas thyrotoxicosis accelerates skeletal development and is an important risk factor for osteoporosis in adulthood. Even sub-clinical thyrotoxicosis is associated with fracture, and treatment with thyroxine at doses that suppress TSH results in increased bone turnover and low BMD in postmenopausal women.To investigate the mechanism of T3 action in the skeleton, we characterized mice ...

Objectives: To identify and determine the extent to which effective/ineffective steps in the implementation of the Kaiser Permanente Southern California Healthy Bones Model of Care were perceived by physician champions and Healthy Bones Care Managers.Methods: The subjects in the study included 20 Physician Champions and 35 Healthy Bones Care Managers employed in the Kaiser Permanente Southern California Healthy Bones Model of Care.25 have been employed i...

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...