Bone Abstracts

Objectives: XLH features renal phosphate (Pi) wasting, hypophosphatemia, rickets, and skeletal deformities from elevated circulating levels of fibroblast growth factor 23 (FGF23). KRN23, an investigational fully human monoclonal antibody, binds FGF23 and inhibits its action. Our Phase 2 study of KRN23 in XLH children (ages 5–12 years) is demonstrating improvements in serum Pi and rickets. Here we present our Phase 2 trial evaluating the efficacy and safety of KRN23 in you...

Dysosteosclerosis (DSS) is the rare osteopetrosis (OPT) distinguished by metaphyseal osteosclerosis with relative radiolucency of widened diaphyses and platyspondyly. In 2012, mutations in the SLC29A3 gene were discovered to cause DSS.Here, we report a new case of DSS presenting with severe anemia and having a unique homozygous mutation in SLC29A3.Our patient was the 3rd child of consanguineous Turkish parents. She present...

The activation of Wnt signaling pathway is blocked by soluble proteins such as WIF-1, sFRP, Dkk1, and sclerostin, which work by sequestering the ligand (Wnt) or the co-receptor/receptor moiety. Recent advances in developing anti blocking agents such as monoclonal antibodies to the sclerostin and Dkk1 protein have generated significant interest as potentially useful approaches to treat patients that could utilize a rapid gain in bone mineral density in the context of osteoporos...

Signaling pathways crucial in bone development, including Wnt, are also upregulated in breast cancer cells to promote tumor growth in the skeleton, a process known as osteomimicry. Thus, we hypothesized that bone metastatic tumor cells also aberrantly express osteogenic miRNAs to support osteomimetic properties. We have previously shown that miR-218 is highly expressed in osteoblasts and promotes osteogenic differentiation. Interestingly, expression analysis revealed a signifi...

Abaloparatide (BA058) is a synthetic analog of PTHrP1–34 which greatly increases bone mass and bone strength with preservation of normal bone quality in animal models of osteoporosis. Daily s.c. abaloparatide (ABLSC) at doses of up to 80 μg daily in postmenopausal women with osteoporosis for up to 48 weeks were associated with increases in spine and femoral neck BMD of up to 12.9 and 4.1% respectively and good safety and tolerability. The increa...

It has been previously reported that prolonged treatment with rhPTH(1–34) or rhPTH(1–84) in rats is associated with the development of bone neoplasms including osteosarcomas. However, to date there has been no evidence of an increased osteosarcoma risk of in patients treated with rhPTH(1–34) or rhPTH(1–84), or in diseases associated with chronic PTH elevation. Abaloparatide (ABL) is a novel analog of PTHrP(1–34) currently being developed as a treatment...

Background: Treatments that result in greater increases in bone mass of normal quality by increasing bone formation rather than decreasing resorption are needed. Abaloparatide is a synthetic analog of PTHrP1-34 that has shown strong efficacy to increase bone mass and bone strength in animals. We conducted two phase 2 placebo-controlled studies both of which included abaloparatide 80 μg sc daily (ABL) in postmenopausal women with osteoporosis. Study 1 also inclu...

see PP352....

Abaloparatide (ABL) is a novel analog of hPTHrP (1–34) in clinical development for treatment of osteoporosis. This study evaluated the long-term effects of ABL on BMD and bone strength in aged osteopenic, ovariectomized (OVX) monkeys. Four groups of ≥9-year-old female cynomolgus monkeys underwent OVX and one group underwent Sham surgery. After a 9-month bone depletion period, increases in bone markers and decreases in BMD by DXA and pQCT were observed for OVX groups...

Objective: To evaluate bone and muscle mass in children with inflammatory bowel disease (IBD) following infliximab (IFX) therapy.Methods: Prospective longitudinal study of 19 children (12 males), 17 crohn’s disease (CD), 1 ulcerative colitis (UC), 1 IBD unclassified (IBDU) of bone evaluation commencing treatment with IFX. Bone and muscle parameters were measured by pQCT at the non-dominant distal radius at 4 and 66% at baseline and 6 months. pQCT pa...