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We investigated the differences in three-dimensional microstructure of bone in cases of osteopenia caused by two different procedures: ovariectomy (ovx) and sciatic neurectomy (nx). Thirty-nine 8-week-old female Lewis rats were divided into two groups: (1) ovx and sham operation; and (2) nx and sham operation. At 12 weeks of age these rats were killed to sample the right tibiae. The samples were scanned...
Intracellular signals generated by mechanical strain profoundly affect the metabolic function of osteoblast-like periodontal ligament (PDL) cells, which reside between the tooth and alveolar bone. In response to applied mechanical forces, PDL cells synthesize bone-resorptive cytokines to induce bone resorption at sites exposed to compressive forces and deposit bone at sites exposed to tensile forces...
Elevated extracellular calcium (Ca e ) stimulates both chemotaxis and mitogenesis of MC3T3-E1 osteoblasts via a calcium-sensing receptor (CasR). Ca e -mediated chemotaxis of these bone-forming cells is dependent on phospholipase C (PLC) and blocked by the Gi-protein inhibitor pertussis toxin. In this study, we examine the signaling mechanisms by which the CasR stimulates PLC activity...
The beneficial effects of hormone replacement therapy (HRT), selective estrogen receptor modulators (SERMs), or bisphosphonates in the prevention and treatment of osteoporosis in postmenopausal women have been well established. However, little is known about the effects of discontinuation of treatment on bone mineral density. We investigated the effect of 1 year of discontinuation of the SERM raloxifene...
Beside its well-known role in bone development, vascularization plays a major role in bone cell migration for bone remodeling and metastatic tumor invasion. However, the various techniques used to identify vessels in bone have never been tested for trabecular bone vessel quantification, whereas bone remodeling quantitative parameters are commonly assessed. In this context, we developed and compared...
Recent studies have shown that stimulation of osteoclastogenesis in cocultures of osteoblasts and spleen cells in response to prostaglandin E 2 (PGE 2 ) is markedly decreased when the osteoblasts are derived from cells lacking either the EP 2 or the EP 4 receptor. Induction of osteoclast formation requires upregulation of receptor activator of nuclear factor-κB ligand...
The objective of this study was to estimate the annual direct medical costs of osteoporosis and osteoporotic fractures incurred by French men =<50 years of age. Costs were assessed from a societal perspective for 1999 and expressed in Euros. An expert panel was consulted to identify fractures attributable to osteoporosis according to International Classification of Diseases (ICD)-10 codes. Available...
The positive effects of physical activity on human bone mass have been well documented in many cross-sectional studies comparing athletes with sedentary controls as well as in longitudinal follow-up. By applying peripheral quantitative computed tomography (pQCT), which has the advantage of measuring volumetric bone mineral density (BMD) and the ability to distinguish among trabecular and cortical...
An atomic force microscopy (AFM)-based nanoindenter was used to evaluate the mechanical properties of skeletal bones in wild-type and gene-mutated zebrafish (Danio rerio), stopsel dtl28d . Both skeletons were isolated from adult zebrafish and tested under a load of 5 mN. It was found that stp/stp bone has a similar nanohardness but significantly greater elastic modulus...
Recent studies have shown that a low bone mineral density (BMD) is associated with a higher risk of mortality. Most studies have investigated this relationship in women only and presented their risk estimates per standard deviation change in BMD. However, when using this approach, a BMD threshold might be missed when relative risks are presented in the traditional manner. Therefore, in this study...
In this study we examine the influence of number of years since menopause on spontaneous bone loss and response to hormone replacement therapy (HRT) in 274 women (56.1 +/- 4.2 years) completing two placebo-controlled HRT studies of 2 or 3 year duration. Both cross sectionally and longitudinally, bone loss in untreated women was greatest closest to menopause and declined thereafter (r = 0.34, p <...
Bone loss due to unloading of the skeleton may be caused by an acceleration of osteoclastic bone resorption as well as a decline of osteoblastic bone formation. Recently, two molecular species that play important roles in osteoclastogenesis were discovered: (i) the receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) ligand/osteoclast differentiation factor induces osteoclastogenesis;...
During the differentiation cascade of growth plate chondrocytes, cells undergo as much as a 10-15-fold increase in volume. This volume increase, which occurs to different extents in growth plates growing at different rates, has been demonstrated to be the single most significant variable in understanding the quantitative aspects of the cellular kinetics of long bone growth. Our hypothesis is that...
Although active vitamin D is used in certain countries for the treatment of osteoporosis, the risk of causing hypercalcemia/hypercalciuria means that there is only a narrow therapeutic window, and this has precluded worldwide approval. The results of our previous animal studies have suggested that the therapeutic effect of active vitamin D on bone loss after estrogen deficiency can be dissociated...
Collagen sponge disks (6 mm diameter, 1 mm thickness) were impregnated with recombinant human bone morphogenetic protein-2 (rhBMP-2) (5 μg/disk) and implanted onto the back muscles of mice. Ten or 20 mg/kg per day of Rolipram, a selective inhibitory agent to phosphodiesterase type 4 (PDE-4), or vehicle, was injected subcutaneously into the host mice for 3 weeks. After treatment, rhBMP-2-induced ectopic...
High endogenous sexual hormone levels and use of medium potency estrogens are associated with a reduced risk of hip fracture in postmenopausal women. However, it is not clear if low potency estrogens confer the same benefits as the more widely used forms of menopausal hormone replacement. We examined the association between postmenopausal use of low potency estrogens, mainly estriol, and hip fracture...
Otosclerosis is caused by abnormal bone homeostasis of the otic capsule, resulting in hearing impairment in 0.3%-0.4% of the white population. The etiology of the disease remains unclear and environmental as well as genetic factors have been implicated. We localized the first autosomal-dominant locus to chromosome 15 in 1998 (OTSC1) in an Indian family and, recently, we reported the localization of...
Osteoclasts resorb bone by attaching to the surface and then secreting protons into an extracellular compartment formed between osteoclast and bone surface. This secretion is necessary for bone mineral solubilization and the digestion of organic bone matrix by acid proteases. This study summarizes the characterization and role of each type of ion transport and defines the main biochemical mechanisms...
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