Bone Abstracts

Osteogenesis imperfecta (OI) is a heritable bone dysplasia with collagen-related defects. Dominantly inherited OI is caused by structural defects in type I collagen or IFITM5, while recessive forms are caused by deficiency of proteins that interact with collagen for modification, folding or cross-linking. We have identified the first X-linked form of OI, caused by a defect in regulated intramembrane proteolysis (RIP). One type of RIP involves sequential cleavage of regulatory ...

PTH replacement therapy in hypoparathyroidism (hypoPT) has become more accepted after proving successful in several clinical studies. Intact PTH (PTH1–84) was in 2012 withdrawn, leaving teriparatide (PTH1–34) the only therapeutic option available.All patients with postoperative HypoPT who changed medication from PTH1–84 (100 μg) to PTH1–34 (20 μg), after at least 12 months of conve...

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...

Bone remodeling is the key process in bone structural reorganization, and its alterations lead to changes in bone mechanical strength. Since osteons reflect different bone remodeling patterns, we hypothesize that the femoral cortex of females with miscellaneous age, disease, and treatment conditions will display distinct osteonal morphology and osteocyte lacunar numbers along with different mechanical properties.The specimens used in this study were coll...

Objective: Mobility is an important endpoint in patient care with implications for activities of daily living, community participation, and quality of life. We adapted the performance-oriented mobility assessment (POMA-G),1 a widely used and validated clinical gait assessment tool for adults, to use in children with hypophosphatasia (HPP). HPP is the rare metabolic disease caused by loss-of-function mutation(s) in the gene encoding tissue non-specific alkaline phosp...

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...

Changes in the ability of self-renewal and differentiation of mesenchymal stem cells may be affected by osteoporosis. The aim of this investigation was to compare the transcriptional profile of mRNAs and miRNAs of osteoblastic cells from calvaria and bone marrow of female rats after ovariectomy. Following the approval by ethics committee, 18 wistar rats were divided into control (sham) and ovariectomized groups. After 150 days, both groups were sacrificed to collect the femurs...

Although bone morphogenetic protein 6 (BMP6) is known for its ability to induce growth of bone and cartilage, recent studies identified BMP6 as a key endogenous regulator of hepcidin expression and iron metabolism. Here, we examined BMP6 presence in the serum and investigated whether circulating levels of BMP6 may reflect body iron status. First, we showed by liquid chromatography–mass spectrometry (LC–MS) and western blotting that BMP6 is present in the circulation ...

High fat diet (HFD), obesity, and physical inactivity characterize the modern lifestyle. This can lead to coronary heart diseases and type 2 diabetes mellitus. Recent studies have shown that these conditions frequently are associated with poor bone quality. However, the molecular mechanisms are poorly understood. To analyze the effect of HFD and exercise (EX) on bone homeostasis, we fed 6-week-old C57BL/6 mice a high fat (60% fat) or standard chow diet for 10 weeks (10–20...

Clinical data suggest that the mTOR inhibitor everolimus may have bone protective effects in addition to its anti-tumor effects in women with ER+/HER2− metastatic breast cancer receiving hormone-ablative therapies. Based on these findings, we tested the hypothesis, whether everolimus exerts concurrent anti-tumor effects while protecting the skeleton in murine models. Thus, we assessed bone metabolism and anti-tumor effects in osteolytic cancer models upon exposure to eve...