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The use of in vivo high-resolution computed tomography (CT) scanners provides the unique opportunity for evaluating temporal progression in healing of bone defects. However, these in vivo scanners impose ionizing radiation that could affect the healing and morphology of the bone. The primary objective of this study was to determine the effects of in vivo scanning at 2-week intervals on bone healing...
We previously showed that oral cholecalciferol and ergocalciferol have comparable effects in decreasing circulating parathyroid hormone (PTH), despite a greater increase in total serum 25-hydroxyvitamin D (25OHD) concentration with cholecalciferol supplementation. However, the effects of cholecalciferol and ergocalciferol on total serum 1,25-dihydroxyvitamin D (1,25(OH) 2 D), vitamin D-binding...
Translational evaluation of disease progression and treatment response is critical to the development of therapies for osteoporosis. In this study, longitudinal in-vivo monitoring of odanacatib (ODN) treatment efficacy was compared to alendronate (ALN) in ovariectomized (OVX) non-human primates (NHPs) using high-resolution peripheral computed tomography (HR-pQCT). Treatment effects were evaluated...
Atypical subtrochanteric femoral shaft fractures (AFFs) have recently emerged as a potential long-term complication of bisphosphonate therapy. In 2010, the American Society for Bone and Mineral Research (ASBMR) Task Force published a definition for AFF consisting of 5 major and 7 minor features. Little attention has so far been paid to the possibility that bisphosphonate-associated atypical fractures...
It is well known that loss of bone mass, quantified by areal bone mineral density (aBMD) using DXA, is associated with the increasing risk of bone fractures. However, bone mineral density alone cannot fully explain changes in fracture risks. On top of bone mass, bone architecture has been identified as another key contributor to fracture risk. In this study, we used a novel stochastic approach to...
Insulin-like growth factor 1 (IGF-1) is a determinant of bone mass and is inversely associated with vertebral fractures (VFs). Sclerostin regulates bone formation by inhibiting Wnt/β-catenin signaling. Currently, there is little information on circulating sclerostin levels among postmenopausal women with type-2 diabetes mellitus (T2DM) with VFs in relation to serum IGF-1 (s-IGF-1). We investigated...
Osteoclasts are specialized cells for bone-resorption originated from precursors of macrophage/monocyte lineage. The receptor activator of NFκB ligand (RANKL) initiates osteoclast differentiation, in which nuclear factor of activated T cell cytoplasmic 1 (NFATc1) plays a key role as a master transcription factor. In the present report, we show that microRNA-124 (miR-124) regulates osteoclastogenesis...
Bone acquisition in childhood impacts adult bone mass, and can be influenced by childhood socioeconomic conditions. Socioeconomic status is also associated with body weight which affects the load that bone is exposed to in a fall. We hypothesized that socioeconomic advantage in childhood is associated with greater bone strength relative to load in adulthood.Hip dual x-ray absorptiometry scans from...
Bone is permanently remodeled by a complex network of local, hormonal and neuronal factors that affect osteoclast and osteoblast biology. In this context, a role for gastro-intestinal hormones has been proposed based on evidence that bone resorption dramatically falls after a meal. Glucose-dependent insulinotropic polypeptide (GIP) is one of the candidate hormones as its receptor, glucose-dependent...
Human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) are useful tools for regenerative medicine due to their capacity for self-renewal and multi-lineage differentiation. The appropriate clinical application of MSCs for regenerative medicine requires an integrated understanding of multiple signaling pathways that regulate cell proliferation, stemness and differentiation. However,...
Bone grafts are well-established in the treatment of fracture non-unions but union is still not always achieved. Harvesting autograft is associated with donor site morbidity and the available amount of bone is limited. Allograft is more easily obtained and available in greater quantities but lacks the osteoinductive characteristics of autograft. We have previously shown a synergistic effect of bone...
Bone growth may occur in spaceflight as a response to skeletal unloading and head-ward fluid shifts. While unloading causes significant loss of bone mass and density in legs of animals exposed to microgravity, increased blood and interstitial fluid flows accompanying microgravity-induced fluid redistribution may elicit an opposite effect in the head. Seven 23-week-old, adult female wild-type C57BL/6...
Odanacatib (ODN) is a selective and reversible Cathepsin K (CatK) inhibitor currently being developed as a once weekly treatment for osteoporosis. Here, effects of ODN compared to alendronate (ALN) on bone turnover, DXA-based areal bone mineral density (aBMD), QCT-based volumetric BMD (vBMD) and geometric parameters were studied in ovariectomized (OVX) rhesus monkeys. Treatment was initiated 10days...
Hypophosphatasia (HPP) is an inherited disorder of mineral metabolism caused by mutations in ALPL, encoding tissue non-specific alkaline phosphatase (TNAP). Here, we report the molecular findings from monozygotic twins, clinically diagnosed with tooth-specific odontohypophosphatasia (odonto-HPP). Sequencing of ALPL identified two genetic alterations in the probands, including a heterozygous missense...
Progressive osseous heteroplasia (POH) is a rare autosomal dominant disorder of mesenchymal differentiation characterized by progressive heterotopic ossification (HO) of dermis, deep connective tissues and skeletal muscle. Usually, initial bone formation occurs during infancy as primary osteoma cutis (OC) then progressively extending into deep connective tissues and skeletal muscle over childhood...
Osteoporosis (OP) is associated with cardiovascular disease. Moreover, osteoporosis has been shown to be an independent predictor of cardiovascular mortality. Recent studies revealed that altered blood rheology plays a critical role in atherosclerosis. A study confirmed that whole blood viscosity (WBV) is a predictor of cardiovascular events. However, little research has been conducted to investigate...
Previous studies have shown that patients with Parkinson's disease (PD) are at increased risk of fractures. However, no specific prediction model for fracture estimation among PD patients is currently available. Therefore, the aim of this study was to develop a simple score for estimating the 5-year osteoporotic and hip fracture risks among patients with PD.The UK Clinical Practice Research Datalink...
In the FREEDOM study, denosumab treatment (60mg every 6months) decreased bone resorption, increased bone mineral density (BMD), and reduced new vertebral, nonvertebral, and hip fractures over 36months in postmenopausal women with osteoporosis. In a subset of these women, hip quantitative computed tomography (QCT) was performed at baseline and months 12, 24, and 36. These scans were analyzed using...
Extended periods of inactivity cause severe bone loss and concomitant deterioration of the musculoskeletal system. Considerable research has been aimed at better understanding the mechanisms and consequences of bone loss due to unloading and the associated effects on strength and fracture risk. One factor that has not been studied extensively but is of great interest, particularly for human spaceflight,...
Whole bone strength is determined by bone mass, microarchitecture and intrinsic properties of the bone matrix. However, few studies have directly investigated the contribution of bone tissue material properties to whole bone strength in humans. This study assessed the role of bone matrix composition on whole lumbar vertebra mechanics. We obtained 17 fresh frozen human lumbar spines (8 W, 9 M, aged...
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