Bone
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Randomized Controlled Trial
Calculated free and bioavailable vitamin D metabolite concentrations in vitamin D-deficient hip fracture patients after supplementation with cholecalciferol and ergocalciferol.
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)2D), vitamin D-binding protein (DBP), free 25OHD and free 1,25(OH)2D concentrations have not been previously studied. We randomized 95 hip fracture patients (aged 83±8 years) with vitamin D deficiency (serum 25OHD <50 nmol/L) to oral supplementation with either cholecalciferol 1000 IU/day (n=47) or ergocalciferol 1000 IU/day (n=48) for three months. ⋯ In vitamin D-deficient hip fracture patients, oral supplementation with cholecalciferol and ergocalciferol had no effect on total serum 1,25(OH)2D, and comparable effects on DBP and free vitamin D metabolite concentrations. This is despite cholecalciferol having greater effects than ergocalciferol in increasing total 25OHD, and in increasing ionized calcium in treatment-adherent subjects. These findings may explain why cholecalciferol and ergocalciferol supplementation result in similar magnitudes of PTH reduction, but implicate potential differences in other vitamin D metabolites, such as 24,25(OH)2D, that could explain their different effects on ionized calcium.
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Previous studies suggest that age and disc degeneration are associated with variations in vertebral trabecular architecture. In particular, disc space narrowing, a severe form of disc degeneration, may predispose the anterior portion of a vertebra to fracture. We studied 150 lumbar vertebrae and 209 intervertebral discs from 48 cadaveric lumbar spines of middle-aged men to investigate regional trabecular differences in relation to age, disc degeneration and disc narrowing. ⋯ Similarly, greater disc narrowing was associated with higher trabecular thickness in the anterior region (p<0.05). Better architecture of peripheral trabeculae relative to central trabeculae was associated with both age and disc degeneration. In contrast to the previous view that disc narrowing stress-shields the anterior vertebra, disc narrowing tended to associate with better trabecular architecture in the anterior region, as opposed to the posterior region.
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Increasing evidence has revealed a positive correlation between postmenopausal osteoporosis and intervertebral disc degeneration, the underlying mechanism of which might be associated with changes in the vertebral bone and endplate. Alendronate (ALN) can increase bone mass and improve the microstructure of osteoporotic vertebrae, which might be helpful in preserving disc morphology and mechanical properties. This study aims to investigate the effects of ALN on lumbar intervertebral disc degeneration related to osteoporosis using an ovariectomized (OVX) rat model. ⋯ ALN can retard the progression of lumbar intervertebral disc degeneration in OVX rats. The underlying mechanisms might be related to preservation of the structural integrity and function of the adjacent structures, including the vertebrae and endplates, which further links with modulations in extracellular matrix metabolism to protect the disc from degeneration. These results suggest that ALN might be a promising drug agent for preventing lumbar intervertebral disc degeneration related to osteoporosis.
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Sphingosine-1-phosphate (S1P) is a well-known signaling sphingolipid and bioactive lipid mediator. Recently, it was reported that S1P inhibits osteoclast differentiation and bone resorption. On the other hand, S1P effects on osteoblasts and bone formation are little known. ⋯ Both inhibitors for PI3K and Akt suppressed the nuclear localization of β-catenin and T-cell factor transcriptional activity induced by Wnt-3a. S1P increased the amount of osteoprotegerin at both mRNA and protein levels, and increased the activity of alkaline phosphatase, leading to the mineralization. These findings suggest that S1P activates the PI3K/Akt signaling pathway leading to the promotion of nuclear translocation of β-catenin in osteoblast-like cells, resulting in the upregulation of osteoptotegerin and osteoblast differentiation markers including alkaline phosphatase, probably relating to the inhibition of osteoclast formation and the mineralization, respectively.
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Radiation of the hip is an established method to prevent heterotopic ossification (HO) following total hip arthroplasty (THA) but the precise mechanism is unclear. As inflammatory processes are suggested to be involved in the pathogenesis of HO, we hypothesized that the preoperative irradiation impacts local immune components. Therefore, we quantified immune cell populations and cytokines in hematomas resulting from the transection of the femur in two groups of patients receiving THA: patients irradiated preoperatively (THA-X-hematoma: THA-X-H group) in the hip region (7 Gy) in order to prevent HO and patients who were not irradiated (THA-H group) but were postoperatively treated with non-steroidal anti-inflammatory drugs (NSAIDs). ⋯ In contrast, the concentration of the angiogenic VEGF was significantly suppressed in the THA-X-H group. We conclude that preoperative irradiation results in significant changes in immune cell composition and cytokine secretion in THA-hematomas, establishing a specific - rather proinflammatory - milieu. This increase of inflammatory activity together with the observed suppression in VEGF secretion may contribute to the prevention of HO.