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Birmingham, AL, United States

Lips P.,VU University Amsterdam | Jameson K.,University of Southampton | Bianchi M.L.,Instituto Auxologico Italiano IRCCS | Goemaere S.,Ghent University | And 8 more authors.
Osteoporosis International

Introduction: Wrist fracture causes pain and decreased physical, social and emotional function. The International Osteoporosis Foundation has developed a specific questionnaire to assess quality of life in patients with wrist fracture. This questionnaire, including 12 questions, was validated in a multicentre study and compared with an osteoporosis-specific questionnaire (Qualeffo-41) and a generic questionnaire (EQ-5D). Methods: The study included 105 patients with a recent wrist fracture and 74 sex- and age-matched control subjects. The questionnaire was administered as soon as possible after the fracture, at 6 weeks, 3 months, 6 months and 1 year after the fracture. Test-retest reproducibility, internal consistency and sensitivity to change were assessed. Results and discussion: The results showed adequate repeatability and internal consistency of the International Osteoporosis Foundation (IOF) wrist fracture questionnaire. The discriminatory capacity between patients and control subjects was very high, with significant odds ratios for each question and domain. The IOF-wrist fracture questionnaire domain scores showed significant improvement after 3 and 6 months and some improvement from 6 months up to 1 year. The sensitivity to change was much higher for the IOF-wrist fracture total score than for Qualeffo-41 and EQ-5D. Conclusion: In conclusion, the IOF-wrist fracture questionnaire appears to be a reliable and responsive quality of life questionnaire. © 2009 International Osteoporosis Foundation and National Osteoporosis Foundation. Source

Roux C.,University of Paris Descartes | Binkley N.,University of Wisconsin - Madison | Boonen S.,Center for Metabolic Bone Disease | Kiel D.P.,Harvard University | And 5 more authors.
Calcified Tissue International

Vitamin D supplementation is recommended for women with osteoporosis. In the FOCUS-D trial comparing the combination tablet alendronate plus vitamin D3 5,600 IU (ALN/D) with standard care (SC) prescribed by patients' personal physicians, ALN/D was more effective in improving serum 25(OH)D and bone turnover markers by 6 months and increasing spine and hip bone mineral density (BMD) after 1 year than SC. This post hoc analysis examined the relationship between BMD gain and 25(OH)D in women in SC receiving alendronate (SC/ALN, n = 134, 52 % of the SC group) and in the ALN/D group (n = 257). At baseline, participants were of mean age 73 years and 72 % were Caucasian, with a mean 25(OH)D of 14.9 ng/mL. In the SC/ALN group, most received vitamin D, although intake of vitamin D varied extensively (51 % received <400 μg/day). In this group, end-of-study 25(OH)D correlated positively with mean percent increases from baseline in lumbar spine and femoral neck BMD [Pearson correlation coefficients (95 % CI) = 0.23 (0.02-0.41) and 0.24 (0.03-0.41), respectively]. Baseline 25(OH)D correlated with increases in only lumbar spine BMD [Pearson correlation coefficient (95 % CI) = 0.22 (0.01-0.40)]. No correlations between mean BMD change and 25(OH)D were seen with ALN/D. In conclusion, in postmenopausal women with osteoporosis and low 25(OH)D receiving alendronate and a wide range of vitamin D doses, the increase in lumbar spine and femoral neck BMD was positively correlated with serum 25(OH)D achieved by the end of the study and, to some extent, with 25(OH)D concentrations at baseline. The degree of success of alendronate therapy for osteoporosis may depend on the vitamin D status of patients. © 2013 Springer Science+Business Media New York. Source

Trevisan C.,University of Milan Bicocca | Ortolani S.,Center for Metabolic Bone Disease | Romano P.,SPA Societa Prodotti Antibiotici | Isaia G.,University of Turin | And 6 more authors.
Calcified Tissue International

The efficacy of clodronate to reduce bone loss around uncemented stems after total hip arthroplasty (THA) was evaluated. Ninety-one patients operated with uncemented THA were randomized to receive either intramuscular clodronate at a dose of 100 mg weekly for 12 months or no treatment. Periprosthetic and contralateral bone mineral density (BMD) scans were performed and biochemical markers of bone turnover measured at baseline and at 3, 6, and 12 months. At month 12, with the exception of Gruen zones 4 and 5, patients treated with clodronate showed less bone loss at all zones, reaching statistical significance (P < 0.05) in Gruen zones 2 and 6 (difference of 6.6 and 5.9%, respectively). Analysis of data according to gender revealed sex-related differences in bone loss and efficacy of treatment. After 12 months, the difference in bone loss between treated and untreated women in five out of seven Gruen zones ranged from 6.2 to 13.3% (SS at zones 2 and 6), whereas comparison between treated and untreated men showed no BMD differences in all zones (P > 0.05). Median percent changes in serum levels of markers of bone metabolism by gender were consistent with BMD changes. A 1-year treatment with intramuscular clodronate determined a significant reduction of bone loss after THA. This was mainly attributed to its greater efficacy in the female population, which is at higher risk for bone loss. This observation suggests the need for the characterization of high-risk subjects as potential candidates for prevention strategies. © 2010 Springer Science+Business Media, LLC. Source

Douglas J.T.,Gene Therapy Center | Rivera A.A.,Obstetrics and Gynecology | Lott P.F.,University of Alabama at Birmingham | Wang D.,University of Alabama at Birmingham | And 5 more authors.
Journal of Spinal Disorders and Techniques

Study Design: Ex vivo gene transfer for spinal fusion. Objective: This study aimed to evaluate ex vivo transfer of the nuclear-localized Hoxc-8-interacting domain of Smad1 (termed Smad1C) to rabbit bone marrow stromal cells (BMSCs) by a tropism-modified human adenovirus serotype 5 (Ad5) vector as a novel therapeutic approach for spinal fusion. Summary of Background Data: Novel approaches are needed to improve the success of bone union after spinal fusion. One such approach is the ex vivo transfer of a gene encoding an osteoinductive factor to BMSCs which are subsequently reimplanted into the host. We have previously shown that heterologous expression of the Hoxc-8-interacting domain of Smad1 in the nuclei of osteoblast precursor cells is able to stimulate the expression of genes related to osteoblast differentiation and induce osteogenesis in vivo. Gene delivery vehicles based on human Ad5 are well suited for gene transfer for spinal fusion because they can mediate high-level, short-term gene expression. However, Ad5-based vectors with native tropism poorly transduce BMSCs, necessitating the use of vectors with modified tropism to achieve efficient gene transfer. Methods: The gene encoding Smad1C was transferred to rabbit BMSCs by an Ad5 vector with native tropism or a vector retargeted to αv integrins, which are abundantly expressed on rabbit BMSCs. Transduced BMSCs were maintained in osteoblastic differentiation medium for 30 days. Alkaline phosphatase activity was determined and cells stained for calcium deposition. As positive controls for osteogenesis, we used Ad5 vectors expressing bone morphogenetic protein 2. As negative controls, BMSCs were mock-transduced or transduced with an Ad5 vector expressing β- galactosidase. In an immunocompetent rabbit model of spinal fusion, transduced BMSCs were coated onto absorbable gelatin sponge and implanted between decorticated transverse processes L6 and L7 of 8-week-old female New Zealand white rabbits. Animals were killed 4 weeks after implantation of the sponges, the fusion masses harvested and the area of new bone quantified using image analysis software. Results: The Smad1C-expressing tropism-modified Ad5 vector mediated a significantly higher level of alkaline phosphatase activity and calcium deposition in transduced rabbit BMSCs than all other vectors. The rabbit BMSCs transduced ex vivo with the Smad1C-expressing tropism-modified Ad5 vector mediated a greater amount of new bone formation than BMSCs transduced with any other vector. Conclusions: Delivery of the Smad1C gene construct to BMSCs by an αv integrin-targeted Ad5 vector shows promise for spinal fusion and other applications requiring the formation of new bone in vivo. © 2010 by Lippincott Williams & Wilkins. Source

Zhao X.,University of Alabama at Birmingham | Rezonzew G.,University of Alabama at Birmingham | Wang D.,University of Alabama at Birmingham | Wang D.,Comprehensive Cancer Center | And 6 more authors.
Clinical and Experimental Metastasis

A significant percentage of breast cancer victims will suffer from metastases indicating that new approaches to preventing breast cancer metastasis are thus needed. Dietary stearate (ST) and chemotherapy have been shown to reduce breast cancer metastasis. We tested the complementary use of dietary ST with a taxol-based chemotherapy which work through separate mechanisms to reduce breast cancer metastasis. We therefore carried out a prevention study in which diets were initiated prior to human MDA-MB-435 cancer cells being injected into the host and a treatment study in which diets were combined with paclitaxel (PTX). Using an orthotopic athymic nude mouse model and three diets [corn oil (CO) control diet, low fat (LF) or ST] the prevention study demonstrated that the ST diet decreased the incidence of lung metastasis by 50 % compared to both the LF and CO diets. The ST diet also reduced the number and size of metastatic lung nodules compared to the LF diet. Results of the treatment study indicated that both the CO and ST diets decreased the number of mice with lung metastasis compared to the LF diet. Both CO and ST also decreased the number of lung metastases per mouse compared to the LF diet however only the ST diet cohort was significant. Histomorphometric analysis of the lung tumor tissue indicated that the ST diet plus PTX decreased angiogenesis compared to the LF diet plus PTX. In conclusion these results support combining diet with chemotherapy in both treatment and prevention settings. © 2014 Springer Science+Business Media. Source

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