Bone Abstracts

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...

The Wnt pathway engages both canonical and non-canonical signalling to accomplish a salutary benefit of increased bone mass, as evidenced by the presence of individuals with high bone mass, who exhibit specific functional variants in members of the pathway. This talk will highlight the importance of the influence on Wnt signalling being received by the bone in response to loading and the signals emanating from bone that influence overall metabolism and health in the whole anim...

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...

A randomized, placebo-controlled phase 2 study evaluated the safety and efficacy of BA058, an analog of hPTHrP(1–34), in postmenopausal women with severe osteoporosis. 221 patients were randomized to received BA058 20, 40, and 80 μg, placebo or teriparatide (TP) 20 μg, by daily s.c. injection. 184 (83%) patients completed an initial 24 weeks of treatment. The mean percent change in lumbar spine BMD at 24 weeks was 1.6% with placebo, 6.7% with BA058 80 μg, a...

see PP351....

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...

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...