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The purpose of this cross-sectional study was to evaluate the effects of human parathyroid hormone(1-84) (hPTH) followed by maintenance treatment with 17β-estradiol (E 2 ), risedronate (Ris), or a reduced dose of hPTH (LowPTH) on cortical bone in the ovariectomized (ovx) rat. Eight groups of ovx and one group of intact female rats (3.5 months) were left untreated for 11 weeks. For the following...
Aging is associated with gradual bone loss in men and premenopausal women, with an accelerated rate of loss after menopause in women. Although many studies have investigated bone loss due to surgically induced estrogen depletion, little is known regarding normal age-related changes in bone mass in animal models. We used dual-energy X-ray absorptiometry (DXA) to measure bone mineral density (BMD),...
Porous collagen 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. Pentoxifylline (PTX), which is a methylxanthine-derived inhibitor of phosphodiesterases (PDEs), or vehicle, was injected (5, 25, 50, 100, 200, and 300 mg/kg body weight/day) into the mice subcutaneously once a...
The hormonal actions of 1α,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] are mediated by its cognate receptor protein, the vitamin D receptor (VDR). Despite the growing importance of the VDR system as a modulator of cell growth and differentiation, convenient assays for quantitative measurement of VDR are not readily available, and [ 3 H]1,25(OH) 2 D 3 ligand...
This prospective study evaluated bone loss in the peri- and postmenopausal period in 156 women followed from age 48 to 64 years. All women were premenopausal at the start of the study. Areal bone mineral density (g/cm 2 ) was measured by single-photon absorptiometry (SPA) of the forearm at the 1 cm level (BMD 1 cm) and the 6 cm level (BMD 6 cm) every second year. Onset of menopause (MP) was...
Macrophage-colony stimulating factor (M-CSF) is an essential requirement for human osteoclast formation, but its effect on the proliferation and differentiation of circulating osteoclast precursor cells is unknown. Other growth factors and cytokines are also known to support/stimulate osteoclast formation from mouse marrow precursors, but it is not certain whether these factors similarly influence...
Interleukin-13 (IL-13) inhibits cell proliferation and stimulates interleukin-6 (IL-6) formation in isolated human osteoblasts (hOBs). Because the related cytokine, interleukin-4 (IL-4), is known to exert effects similar to IL-13 in other tissues, and because IL-4 has been implicated as a regulator of bone metabolism, we compared the effects of IL-13 and IL-4 on cell proliferation, IL-6 synthesis,...
Cathepsin K (cat K) is the major cysteine protease expressed in osteoclasts and is thought to play a key role in matrix degradation during bone resorption. However, little is known regarding the synthesis, activation, or turnover of the endogenous enzyme in osteoclasts. In this study, we show that mature cat K protein and enzyme activity are localized within osteoclasts. Pulse-chase experiments revealed...
The purpose of this cross-sectional study was to evaluate the effects of human parathyroid hormone (1-84) (hPTH) followed by maintenance administration of 17β-estradiol (E 2 ), risedronate (Ris), or a reduced dose of hPTH (LowPTH) on vertebral body bone mineral density (BMD) and bone strength in ovariectomized (ovx) rats. Eight groups of ovx (219 rats) and one group of intact female rats (48...
Osteolysis is a common complication of tumors that arise in, or metastasize to, bone. The recent discovery of key regulators of osteoclast formation and activity, including receptor activator of nuclear factor of κB ligand (RANKL), RANK, and osteoprotegerin (OPG), may facilitate new treatment regimes for certain tumors associated with excessive bone loss. We recently showed that the stromal cells...
The distribution and incorporation of strontium into bone has been examined in rats, monkeys, and humans after oral administration of strontium (either strontium chloride or strontium ranelate). After repeated administration for a sufficient period of time (at least 4 weeks in rats), strontium incorporation into bone reaches a plateau level. This plateau appears to be lower in females than in males...
A bone defect model was developed in the distal metaphysis of the femur for studies on bone healing in the mouse. The circular defect involving 20% of the bone circumference resulted in a 34% reduction in the bending moment compared to intact bone. The healing process was followed using histomorphometry, peripheral quantitative computed tomography (pQCT), biomechanical testing, and molecular biological...
Gene and protein expressions of brain-derived neurotrophic factor (BDNF) and TrkB, the high-affinity receptor of BDNF, were investigated in the femur and mandibular condyle of rats by in situ hybridization and immunohistochemistry. BDNF and TrkB mRNA showed overlapped expression in chondrocytes in proliferating and mature zones of the epiphyseal growth plate cartilage and mandibular condylar cartilage,...
The differentiating chick limb-bud mesenchymal cell micro-mass culture system has been used as a model for monitoring the effects of matrix modification on cell-mediated calcification. In this study, we show that treating these micro-mass cultures with homocysteine (Hcys) impairs cartilage calcification. Cultures were treated from day 2 to day 7 with two nonphysiological concentrations of Hcys equivalent...
Interleukin-17 (IL-17) is a proinflammatory cytokine produced exclusively by activated memory T cells and has recently been found to stimulate osteoclastic resorption. Like other proinflammatory cytokines, IL-17 may affect osteoclastic bone resorption indirectly via osteoblasts, possibly by mechanisms previously reported for chondrocytes that respond in very similarly to osteoblasts. As in chondrocytes,...
Oncogenic osteomalacia (OOM) is characterized by renal phosphate wasting and abnormal metabolism of vitamin D, somewhat similar to the phenotype of X-linked hypophosphatemic rickets (HYP). DNA from OOM tumor cells was analyzed for mutations in the PHEX gene, which is mutated in HYP. Screening for mutations by single-strand conformation polymorphism analysis and subsequent sequencing of all the exons...
In vitro and in vivo studies have demonstrated an osteoinductive effect of growth factors such as insulin-like growth factor-1 (IGF-1) and transforming growth factor-β1 (TGF-β1). However, for therapeutic use in fracture treatment, questions remain with regard to the local application of these proteins. A controlled, local release of growth factors from a biodegradable polylactide coating of osteosynthetic...
An archaeological investigation of a medieval cemetery gave us the opportunity to investigate 49 Danish skeletons dating from 1000 to 1250 A.D. and to compare them with 298 contemporary Danes (aged 19-79 years) and assess the millennial trend in bone mineral density (BMD) in populations considered genetically closely related. BMD and bone mineral apparent density (BMAD) of the femoral neck were measured...
Androgens accelerate bone maturation, but it is unclear to what extent this process may be mediated by estrogens derived from aromatization of androgens. In this study, we investigated whether an estrogen-blocking agent, Faslodex (ICI 182,780), can attenuate testosterone-accelerated skeletal maturation in immature mice. On days of life 2-8, mouse pups received either testosterone propionate (50 μg/100...
The aim of this study was to model the effect of short (3-year) treatments with hormone replacement therapy (HRT) at the time of menopause on the risk of osteoporotic fracture, and to assess the impact of strategies to target high-risk individuals. From the relationship between bone mineral density (BMD) and fracture risk, treatment that increased bone mineral density at the hip by 6% over untreated...
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