Center for Metabolic Bone Disease

Birmingham, AL, United States

Center for Metabolic Bone Disease

Birmingham, AL, United States
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Vandenbroucke A.,UZ Leuven | Luyten F.P.,Catholic University of Leuven | Luyten F.P.,Center for Metabolic Bone Disease | Flamaing J.,Catholic University of Leuven | And 2 more authors.
Clinical Interventions in Aging | Year: 2017

The incidence of osteoporotic fractures increases with age. Consequently, the global prevalence of osteoporotic fractures will increase with the aging of the population. In old age, osteoporosis is associated with a substantial burden in terms of morbidity and mortality. Nevertheless, osteoporosis in old age continues to be underdiagnosed and undertreated. This may, at least partly, be explained by the fact that evidence of the antifracture efficacy of osteoporosis treatments comes mainly from randomized controlled trials in postmenopausal women with a mean age of 70–75 years. However, in the last years, subgroup analyses of these landmark trials have been published investigating the efficacy and safety of osteoporosis treatment in the very elderly. Based on this evidence, this narrative review discusses the pharmacological management of osteoporosis in the oldest old (≥80 years). Because of the high prevalence of calcium and/or vitamin D deficiency in old age, these supplements are essential in the management of osteoporosis in the elderly people. Adding antiresorptive or anabolic treatments or combinations, thereof, reduces the risk of vertebral fractures even more, at least in the elderly with documented osteoporosis. The reduction of hip fracture risk by antiresorptive treatments is less convincing, which may be explained by insufficient statistical power in some subanalyses and/or a higher impact of nonskeletal risk factors in the occurrence of hip fractures. Compared with younger individuals, a larger absolute risk reduction is observed in the elderly because of the higher baseline fracture risk. Therefore, the elderly will benefit more of treatment. In addition, current osteoporosis therapies also appear to be safe in the elderly. Although more research is required to further clarify the effect of osteoporosis drugs in the elderly, especially with respect to hip fractures, there is currently sufficient evidence to initiate appropriate treatment in the elderly with osteoporosis and osteoporotic fractures. © 2017 Vandenbroucke et al.

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 | Year: 2014

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.

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 | Year: 2010

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.

News Article | February 15, 2017

NDA Partners Chairman Carl Peck, MD, announced today that Deborah Wenkert, MD a former Clinical Research Medical Director at Amgen and pediatrics, rheumatology, and bone disease expert has joined the company as an Expert Consultant. Following an immunology postdoc at Harvard University, Dr. Wenkert was an instructor at Washington University School of Medicine and then, for eleven years, an Adjunct Assistant/Associate Clinical Professor at St Louis University School of Medicine in the division of rheumatology. Concurrent with her position at St. Louis University, Dr. Wenkert conducted research in adult and pediatric metabolic bone and genetic disorders and provided care to affected children as the Associate Director of the Center for Metabolic Bone Disease and Molecular Research at Shriners Hospital for Children, St Louis. “Dr. Deborah Wenkert’s knowledge and expertise in adult and pediatric metabolic bone and genetic disorders, in addition to, her extensive experience in pediatric rheumatology and pediatric clinical trials will provide an excellent resource to our clients and to our growing Pediatric Practice,” said Dr. Peck. “We are very pleased to welcome her to NDA Partners.” Dr. Wenkert earned her MD from the University of Texas Medical Branch (Galveston, Texas), attended graduate school at Baylor College of Medicine Graduate School, and obtained a BA in Biochemistry from Rice University. She is board certified in pediatrics and pediatric rheumatology, a member of the American Society for Bone and Mineral Research, and a Fellow of the American Academy of Pediatrics and American College of Rheumatology. About NDA Partners NDA Partners is a strategy consulting firm specializing in expert product development and regulatory advice to the medical products industry and associated service industries such as law firms, investment funds and government research agencies. The highly experienced Principals and Premier Experts of NDA Partners include three former FDA Center Directors; the former Chairman of the Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK; an international team of more than 100 former pharmaceutical industry and regulatory agency senior executives; and an extensive roster of highly proficient experts in specialized areas including nonclinical development, toxicology, pharmacokinetics, CMC, medical device design control and quality systems, clinical development, regulatory submissions, and development program management. Services include product development and regulatory strategy, expert consulting, high-impact project teams, and virtual product development teams.

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 | Year: 2010

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.

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 | Year: 2014

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.

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