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Both tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) have been associated with an increased risk of fractures. The serotonin transporter (5-HTT) has been located in the bone and may play a role in bone physiology. We assessed the association between antidepressant drug use, categorized in a therapeutical-based way and on basis of their affinity for the 5-HTT, and...
Expression of the PTH gene is known to be under strict tissue-specific control and is also regulated by extracellular calcium and 1,25(OH) 2 D. However, the precise mode of transcriptional regulation remains to be elucidated, because of the unavailability of appropriate cell lines derived from the parathyroid gland. We tried to identify the transcription factor(s) regulating the human PTH...
It is well known that bone fracture healing is delayed in diabetes mellitus, but the mechanism remains to be elucidated. Since several studies have demonstrated that diabetes causes abnormalities in bone marrow-derived cells, we used the streptozotocin (STZ)-induced diabetic mouse model after bone marrow transfer from green fluorescent protein (GFP) transgenic mice, and examined fracture healing....
Low bone mineral density is highly prevalent in postmenopausal women. Osteopenia in postmenopausal women is a predictor of adverse cardiovascular events. A potential mechanism contributing to the increased cardiovascular risk in postmenopausal women with osteopenia is endothelial vasomotor dysfunction. Endothelin (ET)-1 is a potent vasoconstrictor peptide that is associated with endothelial vasomotor...
Three experiments were conducted to investigate the effect of intermittent administration of parathyroid hormone (PTH) (1–34) applied at different regimes on fracture healing and muscle in healthy and ovariectomized (Ovx at 3months of age) rats. Five-month old rats underwent bilateral transverse metaphyseal osteotomy of tibia and were divided into groups (12 rats each). In Exp 1, Ovx rats were either...
Postmenopausal osteoporosis and hyperparathyroidism are to two common forms of bone loss caused primarily by an expansion of the osteoclastic pool only partially compensated by a stimulation of bone formation. The intimate mechanisms by which estrogen deficiency and excessive production of PTH cause bone loss remain to be determined in part because in vitro studies do not provide the means to adequately...
Mandibuloacral dysplasia (MAD) is a rare recessively inherited premature aging disease characterized by skeletal and metabolic anomalies. It is part of the spectrum of diseases called laminopathies and results from mutations in genes regulating the synthesis of the nuclear laminar protein, lamin A. Homozygous or compound heterozygous mutations in the LMNA gene, which encodes both the precursor protein...
This multicenter study assessed the safety and efficacy of teriparatide 20µg/day in Japanese men and women with osteoporosis at high risk of fracture during a 12-month, randomized, double-blind, placebo-controlled treatment period followed by second and third treatment periods (to 18 and 24months, respectively,) in which all subjects received open-label teriparatide.Subjects (93% female; median age...
Masticatory functional changes have been shown to influence the quantity and quality of the alveolar bone during growth. This study was designed to investigate the effect of masticatory function rehabilitation on the morphology and the trabecular architecture of the mandibular alveolar bone after cessation of growth. Forty-four Sprague–Dawley male rats received soft diet in order to develop masticatory...
Neurofibromatosis 1 syndrome (NF1) presents with skeletal involvement suggesting that altered bone dynamics is associated with NF1. Histological analysis of three cases of NF1-related pseudarthrosis revealed numerous osteoclasts in contact with adjacent bone, and within the pseudarthrosis tissue itself. These findings prompted us to evaluate the differentiation and resorption capacity of NF1-osteoclast...
It is now well established that important regulatory interactions occur between the cells in the hematopoietic, immune and skeletal systems (osteoimmunology). B lymphocytes (B cells) are responsible for the generation and production of antibodies or immunoglobulins in the body. Together with T cells these lymphocytes comprise the adaptive immune system, which allows an individual to develop specific...
We have reported previously that long-term participation of weight-bearing exercise is associated with increased QCT-derived cortical bone size and strength in middle-aged and older men, but not whole bone cortical volumetric BMD. However, since bone remodeling and the distribution of loading-induced strains within cortical bone are non-uniform, the aim of this study was to examine the effects of...
Spinal cord injury (SCI), as a primarily neurological disorder that causes muscular atrophy, is well known to be associated with sub-lesional bone losses. These losses are more pronounced from epiphyseal than from diaphyseal regions. We hypothesized that this discrepancy may be explained by anatomical variation in endocortical circumference.Nine men who had attracted SCI 9 to 32 (mean 21.4) years...
The purpose of the present study was to investigate the influence of different types of weight bearing physical activity on bone mineral density (BMD, g/cm 2 ) and evaluate any residual benefits after the active sports career. Beginning at 17years of age, BMD was measured 5 times, during 12years, in 19 badminton players, 48 ice hockey players, and 25 controls. During the active career, badminton...
Genetic factors are important for the development of osteoporosis. During the search for novel markers of single-nucleotide polymorphisms (SNPs) associated with bone mineral density (BMD) by performing a large-scale SNP screen with 251 Japanese postmenopausal women utilizing 50K SNP array, we here focused on the rs1370005 in the WD repeats and SOF1 domain-containing (WDSOF1) gene because we could...
Bone mass is correlated with body weight during growth. However, it is unclear how bone mass is influenced by weight gain following skeletal maturity. The purpose of this study was to determine the effects of weight maintenance and two rates of weight gain on bone metabolism using skeletally mature female rats. Eight-month-old female rats were fed one of 3 diets for 13weeks: Lieber–DeCarli liquid...
Apolipoprotein E (ApoE) is implicated in the pathogenesis of osteoporosis.To investigate possible association of the non-classical APOE gene +113C/G (rs440446) intron 1 enhancer polymorphism with bone mineral density (BMD) in a homogeneous Chinese population in Singapore.A total of 655 volunteers, males and females, aged between 31 and 72years, from the public participated. BMD was measured using...
Extracellular inorganic phosphate (P i ) concentrations are the highest in the growth plate just before the onset of mineralization. The study reported here demonstrates that P i not only is required for hydroxyapatite mineral formation but also modulates terminal differentiation and apoptosis of growth plate chondrocytes. Extracellular P i stimulated terminal differentiation...
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