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"BONE"
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Bone by bone : comparing animal skeletons
\"This picture book will keep you guessing as you read about how human skeletons are like--and unlike--those of other animals\"--Dust jacket flap.
Book
BMP signalling in skeletal development, disease and repair
Key Points
Phylogenetic analysis indicates that the bone morphogenetic protein (BMP) pathway is ancient and highly conserved across the animal kingdom
Gene duplication and divergence has created a diverse matrix of BMP ligand–receptor pairs that achieve sophisticated control of signalling through variable activity profiles and functional redundancy
Members of the BMP superfamily affect almost all aspects of bone, cartilage and joint biology
Altered BMP signalling is a major underlying cause of human skeletal disorders
Modulation of BMP signalling is emerging as a promising therapeutic strategy for improving bone mass and bone quality, ameliorating diseases of skeletal overgrowth and repairing damage to bones and joints
Bone morphogenetic proteins (BMPs) have been implicated in almost all aspects of bone, cartilage and joint biology. Here, Valerie Salazar and colleagues discuss BMP superfamily signalling in the context of skeletal development and joint morphogenesis, and summarize the status of the BMP pathway as a therapeutic target for treating skeletal trauma and disease.
Since the identification in 1988 of bone morphogenetic protein 2 (BMP2) as a potent inducer of bone and cartilage formation, BMP superfamily signalling has become one of the most heavily investigated topics in vertebrate skeletal biology. Whereas a large part of this research has focused on the roles of BMP2, BMP4 and BMP7 in the formation and repair of endochondral bone, a large number of BMP superfamily molecules have now been implicated in almost all aspects of bone, cartilage and joint biology. As modulating BMP signalling is currently a major therapeutic target, our rapidly expanding knowledge of how BMP superfamily signalling affects most tissue types of the skeletal system creates enormous potential to translate basic research findings into successful clinical therapies that improve bone mass or quality, ameliorate diseases of skeletal overgrowth, and repair damage to bone and joints. This Review examines the genetic evidence implicating BMP superfamily signalling in vertebrate bone and joint development, discusses a selection of human skeletal disorders associated with altered BMP signalling and summarizes the status of modulating the BMP pathway as a therapeutic target for skeletal trauma and disease.
Journal Article
A box of bones
Twelve-year-old Kallie despises nonsense. She believes there's a rational explanation for everything, despite the good-natured prodding of her Grandpa Jess, who takes her to frivolous wastes of time like their town's local Festival of Fools. There, Kallie meets a faceless man (must be some kind of mask) who gives her a strange wooden puzzle box (must be some kind of gimmick). Intrigued despite herself, Kallie sets to work on unlocking its secrets and--lets something out.
Book
Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis
Among postmenopausal women with osteoporosis and a high risk of fracture, treatment with the monoclonal antibody romosozumab for 12 months followed by alendronate resulted in a significantly lower risk of fracture than alendronate for 12 months followed by alendronate.
Journal Article
Bone. Tall tales
Smiley tells a group of young scouts some tall tales about the founder of Boneville, Big Johnson Bone.
Book
Receptor-Activator of Nuclear KappaB Ligand Expression as a New Therapeutic Target in Primary Bone Tumors
The receptor-activator of nuclear kappaB ligand (RANKL) signaling pathway plays an important role in the regulation of bone growth and mediates the formation and activation of osteoclasts. Osteoclasts are involved in significant bone resorption and destruction. Denosumab is a fully human monoclonal antibody against RANKL that specifically inhibits osteoclast differentiation and bone resorption. It has been approved for use for multiple myeloma and bone metastases, as well as for giant cell tumor of bone. However, there is no previous report quantitatively, comparing RANKL expression in histologically varied bone tumors. Therefore, we analyzed the mRNA level of various bone tumors and investigated the possibility of these tumors as a new therapeutic target for denosumab. We examined RANKL mRNA expression in 135 clinical specimens of primary and metastatic bone tumors using real-time PCR. The relative quantification of mRNA expression levels was performed via normalization with RPMI8226, a human multiple myeloma cell line that is recognized to express RANKL. Of 135 cases, 64 were also evaluated for RANKL expression by using immunohistochemistry. Among all of the tumors investigated, RANKL expression and the RANKL/osteoprotegerin ratio were highest in giant cell tumor of bone. High RANKL mRNA expression was observed in cases of aneurysmal bone cyst, fibrous dysplasia, osteosarcoma, chondrosarcoma, and enchondroma, as compared to cases of multiple myeloma and bone lesions from metastatic carcinoma. RANKL-positive stromal cells were detected in six cases: five cases of GCTB and one case of fibrous dysplasia. The current study findings indicate that some primary bone tumors present new therapeutic targets for denosumab, particularly those tumors expressing RANKL and those involving bone resorption by osteoclasts.
Journal Article
Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial
Preclinical evidence demonstrates that senescent cells accumulate with aging and that senolytics delay multiple age-related morbidities, including bone loss. Thus, we conducted a phase 2 randomized controlled trial of intermittent administration of the senolytic combination dasatinib plus quercetin (D + Q) in postmenopausal women (
n
= 60 participants). The primary endpoint, percentage changes at 20 weeks in the bone resorption marker C-terminal telopeptide of type 1 collagen (CTx), did not differ between groups (median (interquartile range), D + Q −4.1% (−13.2, 2.6), control −7.7% (−20.1, 14.3);
P
= 0.611). The secondary endpoint, percentage changes in the bone formation marker procollagen type 1 N-terminal propeptide (P1NP), increased significantly (relative to control) in the D + Q group at both 2 weeks (+16%,
P
= 0.020) and 4 weeks (+16%,
P
= 0.024), but was not different from control at 20 weeks (−9%,
P
= 0.149). No serious adverse events were observed. In exploratory analyses, the skeletal response to D + Q was driven principally by women with a high senescent cell burden (highest tertile for T cell
p16
(also known as
CDKN2A
) mRNA levels) in which D + Q concomitantly increased P1NP (+34%,
P
= 0.035) and reduced CTx (−11%,
P
= 0.049) at 2 weeks, and increased radius bone mineral density (+2.7%,
P
= 0.004) at 20 weeks. Thus, intermittent D + Q treatment did not reduce bone resorption in the overall group of postmenopausal women. However, our exploratory analyses indicate that further studies are needed testing the hypothesis that the underlying senescent cell burden may dictate the clinical response to senolytics. ClinicalTrials.gov identifier:
NCT04313634
.
In a phase 2 randomized control trial, intermittent senolytic therapy administered to postmenopausal women did not result in a reduction in the bone resorption marker, serum CTx, compared to control at 20 weeks.
Journal Article
Bone, antler, ivory & horn : the technology of skeletal materials since the Roman period
\"Artefacts made from skeletal materials since the Roman period were, before this book, neglected as a serious area of study. This ... account, which reviews over fifty categories of artefact, ... starts with a consideration of the formation, morphology, and mechanical properties of the materials and illuminates characteristics concerning working with them. Following chapters discuss the organisation of the industry and trade in such items, including the changing status of the industry over time\"--Amazon.com.
Book
Fracture Prevention with Zoledronate in Older Women with Osteopenia
In this randomized trial, women 65 years of age or older who had osteopenia received four infusions of zoledronate or normal saline at 18-month intervals. Zoledronate was associated with a significantly lower risk of fragility fractures than placebo.
Journal Article