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1.
P N Sambrook 《Journal of bone and mineral research》2000,15(9):1645-1649
Corticosteroids are widely used and effective agents for control of many inflammatory diseases, but osteoporosis is a common problem associated with their long-term use. Several large double-blind controlled clinical trials in patients with corticosteroid osteoporosis recently have been published, indicating it is possible to prevent or reverse this bone loss. Ultimately, the aim of treatment is to prevent fractures, especially vertebral fractures that are the most common type of fracture associated with corticosteroid therapy, yet it remains unclear exactly which patients should receive prophylaxis. Understanding the differences between these trials is key to interpreting the results, which have important practical implications for patient management. 相似文献
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Michael R McClung Richard D Wasnich Robert Recker Jane A Cauley Charles H Chesnut Kristine E Ensrud Alexander Burdeska Tracy Mills 《Journal of bone and mineral research》2004,19(1):11-18
Oral daily ibandronate was investigated for the prevention of bone loss in postmenopausal women without osteoporosis (n = 653). BMD at the lumbar spine and hip were significantly increased (3.1% and 1.8%, respectively; p < or = 0.0001 versus placebo) with 2.5 mg ibandronate after 24 months. Oral ibandronate is a promising option for the prevention of postmenopausal bone loss. INTRODUCTION: Further strategies to manage patients most at risk from developing postmenopausal osteoporosis are required. The objectives of this multicenter, double-blind, randomized, placebo-controlled study were to examine the efficacy, tolerability, and optimal dose of oral daily ibandronate in the prevention of bone loss in postmenopausal women. MATERIALS AND METHODS: In total, 653 women (mean bone mineral density [BMD] T-score > -2.5 at the lumbar spine), who had been postmenopausal for at least 1 year, were allocated to one of four strata based on time since menopause and baseline lumbar spine BMD. Women were randomized to receive calcium (500 mg daily) plus either placebo (n = 162) or ibandronate 0.5 mg (n = 162), 1 mg (n = 166), or 2.5 mg (n = 163) as once-daily oral treatment for 2 years. The primary endpoint was the mean percent change in lumbar spine BMD with ibandronate versus placebo. RESULTS AND CONCLUSIONS: After 2 years, oral daily ibandronate produced a dose-related and sustained maintenance or increase in BMD at the lumbar spine and hip (total hip, femoral neck, trochanter), together with a dose-related reduction in the rate of bone turnover. The greatest nominal increases in spinal and hip BMD were observed with the 2.5-mg dose, which produced statistically significant BMD gains compared with placebo at 6 months and all subsequent time-points at the spine and hip (3.1% and 1.8% increase in lumbar spine and total hip BMD, respectively, versus placebo; p < or = 0.0001 after 24 months). Oral daily ibandronate was well tolerated with an incidence of upper gastrointestinal adverse events similar to placebo. No safety concerns were identified. In summary, oral daily ibandronate 2.5 mg decreases bone turnover, preserves or increases BMD in the spine and proximal femur, and is well tolerated. Oral ibandronate provides a promising option for the prevention of bone loss in postmenopausal women. 相似文献
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Iron homeostasis in osteoporosis and its clinical implications 总被引:1,自引:0,他引:1
Osteoporosis has until now been considered to be a disease associated with abnormal calcium metabolism. However, an increasing number of clinical observations strongly suggest the association of iron overload with bone diseases, particularly in osteoporosis in menopausal women. The recent identification of hepcidin sheds new light into the crucial role of iron homeostasis in bone metabolism. Decreasing iron overload in cell studies as well as in animal experiments has been shown to improve bone cell metabolism and growth in vitro and in vivo. In view of the significant iron overload found in the aging population, especially in females, the therapeutic potential of lowering iron overload for the treatment of osteoporosis is suggested. 相似文献
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Osteoporosis is one of the most common bone-related disorders in the elderly. It is a complex disease, and largely determined genetically. Traditional gene expression studies have shown that osteoporosis has complex regulating mechanisms which are controlled by multiple inherent factors, such as hormones, cytokines, various receptors, etc. The complex nature of osteoporosis, and the large number of genes involved in its onset and development, suggest the use of the state of the art microarray technique as a powerful tool to unravel mechanisms underlying etiology of osteoporosis. 相似文献
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Crucial bone histomorphometric indices, i.e., turnover-related indices, are based on tetracycline double labeling. However, these indices are particularly exposed to loss of information because of missing readings on double labels. If the failure to make the observation is related to its magnitude, then selection bias may invalidate the conclusions. Therefore, ignoring missing double labels may lead to a selection of high-turnover patients. The aim of this study was to analyze the dimension and the impact of excluding iliac crest bone biopsies with missing readings in women with spinal crush fracture osteoporosis (n = 158, median 68 years, range 49-80 years). Furthermore, two different lower limits of the mineral apposition rate (MAR) were examined to explore their usefulness as a biological minimum that can be used for cases with missing readings, i.e., recoding of missing values. The average MAR (calculated as the mean of all interlabel widths measured in each individual) shows a lower limit of 0.3 microm/day, suggesting an apparent minimum for the interlabel width (Ir.L.Wi) of 3-4 microm. Identifying the smallest interlabel width measured in each individual and calculating the minimal MAR shows that 77% of the minimal MAR values are below 0.3 microm/day and reach a minimum of 0.1 microm/day, corresponding to an interlabel width of about 1 microm. Therefore, the minimal MAR presents a biological minimum of 0.1 microm/day. This value is used for our recoding: if no labels are sampled (2% of our population), Ir.L.Wi is assigned the value 0; if none or an insufficient number of double labels are sampled (29% of our population), then Ir.L.Wi is assigned the value 1 microm. Excluding cases with missing readings on any dependent variable increases the mineralizing surface (MS/BS) by 60% (2p < 0.01); other indices show no significant change. The suggested recoding decreases the average MAR by 4% (2p < 0.01), prolongs the remodeling period by 19% (2p < 0.01), and tends to decrease the activation frequency (2p = 0.09). Furthermore, the number of excluded biopsies tends to be larger among the older (2p = 0.09) and more severely osteopenic individuals (2p = 0.09). We conclude that ignoring missing double labels leads to selection bias; therefore, specific measures such as recoding procedures are needed to allow proper representation of low turnover patients. There is also a risk of bias caused by the exclusion of the older, osteopenic patients in bone histomorphometric osteoporosis trials. 相似文献
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Transient osteoporosis (TO) is an uncommon entity whose principal characteristic is to be a self-limited syndrome. Diagnosis is made upon clinical presentation and x-ray evidence of diffuse osteopenia around the affected joint followed by spontaneous healing after several months. When recurrent episodes occur at different times and locations it is called regional migratory osteoporosis. Magnetic resonance imaging and technetium-99 bone scan may be helpful in diagnosis during the early phase. Good results may be achieved with nonsteroidal antiinflammatory medication, protected weight bearing and physical therapy. 相似文献
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Digital topological analysis of in vivo magnetic resonance microimages of trabecular bone reveals structural implications of osteoporosis. 总被引:13,自引:0,他引:13
F W Wehrli B R Gomberg P K Saha H K Song S N Hwang P J Snyder 《Journal of bone and mineral research》2001,16(8):1520-1531
Osteoporosis is a disease characterized by bone volume loss and architectural deterioration. The majority of work aimed at evaluating the structural implications of the disease has been performed based on stereologic analysis of histomorphometric sections. Only recently noninvasive imaging methods have emerged that provide sufficient resolution to resolve individual trabeculae. In this article, we apply digital topological analysis (DTA) to magnetic resonance microimages (mu-MRI) of the radius obtained at 137 x 137 x 350 microm3 voxel size in a cohort of 79 women of widely varying bone mineral density (BMD) and vertebral deformity status. DTA is a new method that allows unambiguous determination of the three-dimensional (3D) topology of each voxel in a trabecular bone network. The analysis involves generation of a bone volume fraction map, which is subjected to subvoxel processing to alleviate partial volume blurring, followed by thresholding and skeletonization. The skeletonized images contain only surfaces, profiles, curves, and their mutual junctions as the remnants of trabecular plates and rods after skeletonization. DTA parameters were compared with integral BMD in the lumbar spine and femur as well as MR-derived bone volume fraction (BV/TV). Vertebral deformities were determined based on sagittal MRIs of the spine with a semiautomatic method and the number of deformities counted after threshold setting. DTA structural indices were found the strongest discriminators of subjects with deformities from those without deformities. Subjects with deformities (n = 29) had lower topological surface (SURF) density (p < 0.0005) and surface-to-curve ratio (SCR; a measure of the ratio of platelike to rodlike trabeculae; p < 0.0005) than those without. Profile interior (PI) density, a measure of intact trabecular rods, was also lower in the deformity group (p < 0.0001). These data provide the first in vivo evidence for the structural implications inherent in postmenopausal osteoporosis accompanying bone loss, that is, the conversion of trabecular plates to rods and disruption of rods due to repeated osteoclastic resorption. 相似文献
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J H Kinney D L Haupt M Balooch A J Ladd J T Ryaby N E Lane 《Journal of bone and mineral research》2000,15(10):1981-1991
This article summarizes the results of a three-dimensional study of changes in the morphology of the L6 rat vertebra at 120 days after ovariectomy (OVX), with estrogen replacement therapy used as a positive control. Synchrotron radiation microtomography was used to quantify the structural parameters defining trabecular bone architecture, while finite-element methods were used to explore the relationships between these parameters and the compressive elastic behavior of the vertebrae. There was a 22% decrease in trabecular bone volume (TBV) and a 19% decline in mean trabecular thickness (Tb.Th) with OVX. This was accompanied by a 150% increase in trabecular connectivity, a result of the perforation of trabecular plates. Finite-element analysis of the trabecular bone removed from the cortical shell showed a 37% decline in the Young's modulus in compression after OVX with no appreciable change in the estrogen-treated group. The intact vertebrae (containing its trabecular bone) exhibited a 15% decrease in modulus with OVX, but this decline lacked statistical significance. OVX-induced changes in the trabecular architecture were different from those that have been observed in the proximal tibia. This difference was a consequence of the much more platelike structure of the trabecular bone in the vertebra. 相似文献
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S Roux 《Joint, bone, spine : revue du rhumatisme》2001,68(6):482-486
A genetic component clearly contributes to bone mass determination by influencing peak bone mass acquisition or, to a lesser degree, bone loss later in life. The analysis of genetic markers for osteoporosis is complex because multiple genes are involved and because osteoporosis is a multifactorial disease. The influence of a number of candidate gene alleles on bone mass has been studied in various populations. Results have been inconsistent and, at times, contradictory, as illustrated by studies on the vitamin D receptor gene. The most conclusive finding is the association linking the Sp1 polymorphism of type I collagen to bone mineral density and osteoporotic fractures. Polymorphisms of other genes either have very little influence or remain unexplored. In all likelihood, the best predictive value will be obtained by using a combination of several gene polymorphisms. 相似文献
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T. Thomas S. Horlait J. D. Ringe A. Abelson D. T. Gold P. Atlan J. L. Lange 《Osteoporosis international》2013,24(1):263-269
Summary
This study aims to estimate bisphosphonate effectiveness by comparing fracture incidence over time on therapy in glucocorticoid-induced osteoporosis (GIO). From this observational study, alendronate and risedronate decreased clinical vertebral and nonvertebral fractures over time. The effectiveness of each bisphosphonate is consistent with their efficacies demonstrated on surrogate markers in randomized controlled trials (RCTs).Introduction
This study aims to estimate bisphosphonate effectiveness by comparing fracture incidence over time on therapy with fracture incidence during a short period after starting a therapy.Methods
The study population was a subgroup of a larger cohort study comprising two cohorts of women aged ≥65 years, prescribed with alendronate or risedronate. Within the two study cohorts, 11,007 women were identified as having received glucocorticoids. Within each cohort, the baseline incidence of clinical fractures at nonvertebral and vertebral sites was defined by the initial 3-month period after starting therapy. Relative to these baseline data, we then compared the fracture incidence during the subsequent 12 months on therapy.Results
The baseline incidence of clinical nonvertebral and vertebral fractures was similar in the alendronate cohort (5.22 and 5.79/100 person-years, respectively) and in the risedronate cohort (5.51 and 5.68/100 person-years, respectively). Relative to the baseline incidence, fracture incidence was significantly lower in the subsequent 12 months in both cohorts of alendronate (33 % lower at nonvertebral sites and 59 % at vertebral sites) and risedronate (28 % lower at nonvertebral sites and 54 % at vertebral sites).Conclusion
From this observational study not designed to compare drugs, both alendronate and risedronate decreased clinical vertebral and nonvertebral fractures over time. The reductions observed in fracture incidence, within each cohort, suggest that the effectiveness of each bisphosphonate in clinical practice is consistent with their efficacies demonstrated on surrogate markers in randomized controlled trials. 相似文献17.
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Robert J Temple 《Journal of bone and mineral research》2003,18(6):1129-1132
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An oral calcium load test (CLT) (1 gm Ca/50 kg) was administered to 11 control subjects and 35 patients with overt hyperparathyroidism to assess its efficacy in diagnosis of hyperparathyroidism. All participants were placed on a low-calcium diet 3 days before the CLT. Intact parathormone and ionized calcium (Cai) levels were measured 0, 1, 2, and 3 hours after CLT. Initial Cai and parathormone (mean +/- SE) were 1.22 +/- 0.01 mmol/L and 2.94 +/- 0.03 pmol/L in the control group compared with 1.43 +/- 0.02 mmol/L and 10.6 +/- 2.2 pmol/L in the group with hyperparathyroidism. Both groups had a similar percent increase in Cai values (control, 5.9% +/- 0.8%; hyperparathyroidism, 6.3% +/- 0.6% (p greater than 0.1). A decline in parathormone levels of 47.6% +/- 2.8% in patients with hyperparathyroidism was significantly less than the 75.3% +/- 5.3% decline observed in control subjects (p less than 0.025). Three hours after CLT, parathormone was suppressed in control subjects, whereas a rebound occurred in patients with hyperparathyroidism. Postoperative CLT demonstrated a higher mean percent Cai increase and percent parathormone decline (Cai, 8.9% +/- 1.1%; parathormone, 67.9% +/- 1.8%) compared with preoperative values (Cai, 6.0% +/- 1.0%; PTH, 49.6% +/- 4.3%) (p less than 0.025), and 3 hours after calcium intake, parathormone remained suppressed, similar to control subjects. After surgery, three patients had elevated parathormone and low normal Cai levels and parathormone response to a CLT confirmed the diagnosis of secondary hyperparathyroidism. In conclusion, a CLT (1) can confirm the diagnosis of hyperparathyroidism and successful parathyroidectomy, (2) distinguished postoperative secondary from persistent primary hyperparathyroidism, (3) demonstrated nonautonomy of abnormal parathyroid glands with a parathormone response to a calcium load characterized by an earlier nadir, decreased suppressibility, and more rapid recovery, and (4) produced dynamic changes that did not distinguish patients with hyperparathyroidism from control subjects or hyperplasia from adenoma. 相似文献
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Chiang CH Huang CC Chan WL Huang PH Chen TJ Chung CM Lin SJ Chen JW Leu HB 《Journal of bone and mineral research》2012,27(9):1951-1958
The association between use of oral bisphosphonates and cancer development in elderly women is still uncertain, and previous studies have shown controversial results. We used a nationwide, population-based database to explore the relationship between the use of alendronate, an oral bisphosphonate agent used for the treatment of osteoporosis, and the risk of all malignancies in women with osteoporosis and age over 55 years. In the study group, we included 6906 women with osteoporosis (age, mean ± SD, 73.4 ± 8.4 years) taking oral alendronate, who were selected from a 1,000,000 sample cohort dataset collected between January 1998 and December 2009. Another 20,697 age- and comorbidity-matched women (73.5 ± 8.4 years) without bisphosphonates treatment were included in the control group. No subjects had any history of being diagnosed with cancer before inclusion. We used a log-rank test to analyze the differences in accumulated cancer-free survival rates between these two groups. A Cox proportional-hazard model, adjusted for confounding factors, was used to evaluate the association between alendronate use and the development of all cancer events in postmenopausal women with osteoporosis. During the mean follow-up period of 4.8 years, 821 patients from the study group and 2646 patients from the control group had new cancers. There was no significant difference in cancer incidence between alendronate users and controls (11.9% versus 12.8%, p = 0.054). The person-year incidence of newly-developed cancer in alendronate users and controls was 28.0 and 29.4 per 1000 person-years, respectively. Alendronate use was not associated with increased risk of cancer development in women with osteoporosis (adjusted hazard ratio, 1.05; 95% confidence interval [CI], 0.97–1.13; p = 0.237). However, due to the limited study size and underpowered results, further larger prospective studies or meta-analysis are suggested to further confirm our findings. © 2012 American Society for Bone and Mineral Research. 相似文献