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The influence of wet and dry apparent density, apparent and real percentage of mineral, organic and water contents on the tension and shear fracture toughness, i.e., the mode I and mode II strain energy release rate (G Ic and G IIc ), respectively, was investigated for the human femur and the tibia. The results suggest that the water content, apparent density, and age were the best...
The role of specific immunosuppressive agents in the development of avascular necrosis (AVN) following hematopoietic stem cell and solid organ transplantation remains unclear. To further explore this question, we conducted a case-control study of patients who underwent bone marrow transplantation (BMT) at the Fred Hutchinson Cancer Research Center. 96 of 1939 long-term survivors transplanted between...
There are at least nine tetracycline (TC) analogs (both antimicrobial and nonantimicrobial) with documented capacity to inhibit, both in vitro and in vivo, the connective tissue degrading activity of matrix metalloproteinases (MMPs). Of the three MMPs that can degrade native helical collagens, MMP-13 (initially identified as rat osteoblast and human breast cancer collagenase, and now known to also...
The molecular mechanisms whereby fluoride stimulates osteogenic cell proliferation are not clearly established. However, fluoride has been shown to enhance the protein tyrosine phosphorylation of various constituents of intracellular signaling cascades in osteoblastic cells following stimulation of growth factor receptors such as the insulin-like growth factor-I (IGF-I) receptor. Such in vitro findings...
Aging adversely affects the elastic and ultimate properties of human cortical bone as seen in uniaxial tests in quasi static loading, high strain rate impact or fatigue. Little is known about the full effects of aging on toughness and its relationship with strength. In the present article the elastic modulus (E), strength (σ f ), fracture toughness (K C and J-integral), and work of...
The etiology of osteoporosis is multifactorial, but there is evidence from both animal and human studies that the volume of marrow adipose tissue increases when bone volume is reduced in osteoporosis. The cell-related mechanism that may account for this inverse relationship between the volume of marrow adipose tissue and bone remains to be clarified, although it is known that both adipocytes and osteoblasts...
This study was performed to investigate the circadian variation of urinary CrossLaps (CTx), which was the type I collagen peptide released during bone matrix degradation, and peptide-bound and free forms of urinary pyridinium crosslinks. Urine was obtained during the 24 h of the study in seven separate collections as follows: from 23:00 h to the first void (FV) followed by FV at 11:00, 11:00–14:00,...
This study investigated the possible role in vitro of insulin-like growth factor I (IGF-I) as a mediator of the effects of growth hormone (GH) on osteoclastic resorption in an unfractioned rabbit bone cell model. After 4 days of rabbit bone cell culture, human GH (hGH) (50 ng/mL) and human IGF-I (hIGF-I) (50 ng/mL) significantly increased the formation of osteoclast-like cells with a lower level than...
Risedronate monosodium [1-hydroxy-2-(3-pyridinyl)ethylidene bisphosphonic acid monosodium salt] is a pyridinyl bisphosphonate drug under development as a treatment for Paget’s disease of bone and other metabolic bone disorders. An open-label, single-center study was conducted to determine the efficacy and safety of oral risedronate in patients with severe Paget’s disease [mean baseline serum alkaline...
The largest voluntary loads on bones come from muscles. To adapt bone strength and mass to them, special strain threshold ranges determine where modeling adds and strengthens bone, and where remodeling conserves or removes it, just as different thermostat settings control the heating and cooling systems in a house. If estrogen lowers the remodeling threshold, two things should occur. First, at puberty...
Impaired bone formation resulting from a decline of osteoblast activity has been implicated in the pathogenesis of diabetic osteopenia. We examined the effects of high glucose concentration alone, independent of insulin deficiency, on the growth of a human osteoblast-like cell line (MG-63). Sustained exposure to high glucose for 7 days inhibited cell growth in a concentration-dependent manner up to...
The etiology of Paget’s disease of bone is still unknown but several studies have reported a viral origin. At the electron microscopic level, characteristic nuclear and cytoplasmic inclusions have been found and mimic paramyxoviral nucleocapsids in osteoclasts (Oc). Sarcomatous degeneration is observed in 2% of pagetic patients. Nuclear organizer regions are parts of the nucleolus involved in the...
The architecture of trabecular bone is thought to be controlled by mechanosensitive bone cells, where hormones provide a background for their responses to mechanical signals. It has been suggested that, in osteoporosis, this response is hampered by changed hormonal levels, thereby increasing the mechanical set point of the cells, which would lead to bone loss. We have investigated if a temporary increase...
Bone mineral density (BMD) and bone turnover are both heritable. Although bone turnover affects bone mass, it is not clear whether these parameters are under common genetic or environmental control. The relative contribution of genetic and environmental factors to the determination of an index of bone turnover, bone specific alkaline phosphatase (BSAP), and the extent of common genetic regulation...
Although diffusion has been shown to be the major contributing mechanism for molecular transport in the extravascular spaces of organs and soft tissues, it is unlikely that diffusion alone can account for molecular transport in the porous, yet relatively impermeable matrix of bone. Rather, it has been proposed that fluid flow induced by the deformations that bone is subjected to during daily activities...
Oslo, Norway has the highest incidence of hip fractures ever reported. There are great differences in life expectancy between city regions in Oslo, and we investigated if there were any differences in incidence of hip fracture within the city. In 1989, all new fractures of the proximal femur in Oslo residents 50 years or older were registered with each patient s address. Patients in nursing homes...
Due to the increasing number of osteoporotic fractures of hip, spine, and wrist there is a growing need for methods to track down the subjects with inferior bone structure and to monitor the effects of therapeutic measures. This study aims at a noninvasive diagnostic tool, deriving architectural properties of trabecular bone from in vivo measurements on plane radiographic films. Pelvic radiographs...
Bone morphogenetic protein (BMP) is a potent inducer of ectopic bone formation, and TNP-470, a synthetic analog of fumagillin, is an antiangiogenic agent that strongly inhibits neovascular formation in vivo. We investigated the effects of TNP-470 on BMP-induced ectopic bone formation to clarify the role of angiogenesis in bone formation. Collagen pellets containing recombinant human BMP-2 (rhBMP-2)...
Patients with fragility fractures have low bone mineral density (BMD)-this statement is supported mainly by data on women. In this study, including only men, the objectives were to determine whether a decline in BMD alone or in combination with data on male sex hormones and skinfold thickness could be of value in predicting forthcoming fractures. We also wanted to find out whether high consumers of...
PEBP2αA/AML3/CBFA1 is one of the transcription regulators that belong to the PEBP2/AML family. The knockout mice, where the gene encoding PEBP2αA/AML3/CBFA1 was inactivated, showed no osteogenesis, indicating the critical role of this transcription factor in osteoblastic differentiation (Komori, Y. et al. Cell 89:755-764; 1997). The aim of this study is to examine the regulation of PEBP2αA/AML3/CBFA1...
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