The Doris Duke Clinical Scientist Development Award: implications for early-career physician scientists.

Purpose: The Doris Duke Charitable Foundation Clinical Scientist Development Award (CSDA) supports early-career physician scientists in their transition to independent research funding. The authors aimed to analyze the characteristics associated with success in CSDA competitions, determine whether attainment of a CSDA is associated with receiving subsequent research funding, and assess whether alumni remain in research.

Method: In 2011, the authors tested for associations between gender, age, race/ethnicity, academic degree, National Institutes of Health (NIH) funding rank of the applicant's institution, and success in CSDA competitions.

Similarities and differences in philanthropic and federal support for medical research in the United States: an analysis of funding by nonprofits in 2006-2008.

Purpose: The medical community currently has no detailed source of information on philanthropic research funding. The authors sought to identify trends in research funding by members of the Health Research Alliance (HRA), a consortium of nonprofit funders of biomedical research, and compare findings with research support from the federal government.

Method: Thirty-two HRA members uploaded information about grants with start dates in 2006, 2007, and 2008.

Assessing the stiffness of spinal fusion in animal models.

The clinical goal of spinal fusion is to reduce motion and the associated pain. Therefore, measuring motion under loading is critical. The purpose of this study was to validate four-point bending as a means to mechanically evaluate simulated fusions in dog and rabbit spines.

Dynamics of an intervertebral disc prosthesis in human cadaveric spines.

Low-back pain is a common, disabling medical condition, and one of the major causes is disc degeneration. Total disc replacements are intended to treat back pain by restoring disc height and re-establishing functional motion and stability at the index level. The objective of this study was to determine the effect on range of motion (ROM) and stiffness after implantation of the ProDisc-L device in comparison to the intact state.

Bone mass is preserved and cancellous architecture altered due to cyclic loading of the mouse tibia after orchidectomy.

Introduction: The study of adaptation to mechanical loading under osteopenic conditions is relevant to the development of osteoporotic fracture prevention strategies. We previously showed that loading increased cancellous bone volume fraction and trabecular thickness in normal male mice. In this study, we tested the hypothesis that cyclic mechanical loading of the mouse tibia inhibits orchidectomy (ORX)-associated cancellous bone loss.

The effects of RANKL inhibition on fracture healing and bone strength in a mouse model of osteogenesis imperfecta.

Currently, the standard treatment for osteogenesis imperfecta (OI) is bisphosphonate therapy. Recent studies, however, have shown delayed healing of osteotomies in a subset of OI patients treated with such agents. The current study sought to determine the effects of another therapy, RANKL inhibition, on bone healing and bone strength in the growing oim/oim mouse, a model of moderate to severe OI.

In vivo cyclic axial compression affects bone healing in the mouse tibia.

Abundant evidence exists that fracture healing can be influenced by mechanical loading. However, the specific loading parameters that are osteogenic remain unknown. We hypothesized that the bone healing response in mouse tibial osteotomies would be different with a short delay before loading compared to immediate load application, as well as with higher and lower load magnitudes applied.

Cancellous bone adaptation to in vivo loading in a rabbit model.

Biophysical stimuli are important to the development and maintenance of cancellous bone, but the regulatory mechanisms need to be understood. We investigated the effects of mechanical loading applied in vivo to native cancellous bone in the rabbit on bone formation and trabecular realignment. A novel device was developed to apply controlled compressive loads to cancellous bone in situ.

DMP1 depletion decreases bone mineralization in vivo: an FTIR imaging analysis.

Unlabelled: The role of DMP1 in mineralization was analyzed by comparing bone mineral and matrix properties in dmp1-null female mice to heterozygous and wildtype controls by FTIR imaging spectroscopy. The observed decreased mineral content in dmp1 null mice indicates a key role for dmp1 in bone mineralization. Indirect effects of DMP1 on other systems also determine the KO phenotype.

Bone density accumulation is not affected by brace treatment of idiopathic scoliosis in adolescent girls.

Bracing for adolescent scoliosis has been postulated to cause permanent loss of bone mass and to predispose to adult osteoporosis. To determine whether brace use affects the rate of bone accretion with growth, the authors conducted a prospective study of 52 girls with adolescent idiopathic scoliosis. Dual-energy x-ray absorptiometry (DEXA) showed a significant increase in spinal bone mineral density (BMD) over a 1-year period of brace wear.

Combined bone morphogenetic protein-2 and -7 gene transfer enhances osteoblastic differentiation and spine fusion in a rodent model.

Unlabelled: To enhance the osteogenic activity of BMP, combination BMP2 and BMP7 gene transfer was performed. This approach led to a significant increase in osteoblastic differentiation of mesenchymal precursors compared with single BMP gene transfer in vitro. When tested in 78 rats, combination gene transfer enhanced mechanically stable spine fusion and bone formation rate versus single BMP gene transfer.

High-dose alendronate uncouples osteoclast and osteoblast function: a study in a rat spine pseudarthrosis model.

The effect of alendronate on osteoclast and osteoblast function was studied in a novel spine pseudarthrosis model in rats. Sixty-three Sprague-Dawley rats were divided into three groups: control group (saline), therapeutic dose group (1 microg/kg/week), and one-log overdose group (10 microg/kg/week). Animals had L4-L5 posterior intertransverse process fusion with limited bone graft and were sacrificed at 2, 4, and 6 weeks.