Teriparatide (rDNA origin) injection [recombinant human PTH (1-34)] stimulates bone formation, increases bone mineral density (BMD), and restores bone architecture and integrity. In contrast, bisphosphonates reduce bone resorption and increase BMD. We compared the effects of teriparatide and alendronate sodium on BMD, nonvertebral fracture incidence, and bone turnover in 146 postmenopausal women with osteoporosis. Women were randomized to either once-daily sc injections of teriparatide 40 micro g plus oral placebo (n = 73) or oral alendronate 10 mg plus placebo injection (n = 73). Median duration of treatment was 14 months. At 3 months, teriparatide increased lumbar spine BMD significantly more than did alendronate (P < 0.001). Lumbar spine-BMD increased by 12.2% in the teriparatide group and 5.6% in the alendronate group (P < 0.001 teriparatide vs. alendronate). Teriparatide increased femoral neck BMD and total body bone mineral significantly more than did alendronate, but BMD at the one third distal radius decreased, compared with alendronate (P < or = 0.05). Nonvertebral fracture incidence was significantly lower in the teriparatide group than in the alendronate group (P < 0.05). Both treatments were well tolerated despite transient mild asymptomatic hypercalcemia with teriparatide treatment. In conclusion, teriparatide, a bone formation agent, increased BMD at most sites and decreased nonvertebral fractures more than alendronate.

In the CORE breast cancer trial of 4011 women continuing from MORE, the incidence of nonvertebral fractures at 8 years was similar between placebo and raloxifene 60 mg/day. CORE had limitations for assessing fracture risk. In a subset of 386 women, 7 years of raloxifene treatment significantly increased lumbar spine and femoral neck BMD compared from the baseline of MORE. Introduction:The multicenter, double-blind Continuing Outcomes Relevant to Evista (CORE) trial assessed the effects of raloxifene on breast cancer for 4 additional years beyond the 4-year Multiple Outcomes of Raloxifene Evaluation (MORE) osteoporosis treatment trial. Materials and Methods:In CORE, placebo-treated women from MORE continued with placebo (n ‫ס‬ 1286), whereas those previously given raloxifene (60 or 120 mg/day) received raloxifene 60 mg/day (n ‫ס‬ 2725). As a secondary endpoint, new nonvertebral fractures were analyzed as time-to-first event in 4011 postmenopausal women at 8 years. A substudy assessed lumbar spine and femoral neck BMD at 7 years, with the primary analysis based on 386 women (127 placebo, 259 raloxifene) who did not take other bone-active agents from the fourth year of MORE and who were Ն80% compliant with study medication in CORE. Results: The risk of at least one new nonvertebral fracture was similar in the placebo (22.9%) and raloxifene (22.8%) groups (hazard ratio [HR], 1.00; Bonferroni-adjusted CI, 0.82, 1.21). The incidence of at least one new nonvertebral fracture at six major sites (clavicle, humerus, wrist, pelvis, hip, lower leg) was 17.5% in both groups. Posthoc Poisson analyses, which account for multiple events, showed no overall effect on nonvertebral fracture risk, and a decreased risk at six major nonvertebral sites in women with prevalent vertebral fractures (HR, 0.78; 95% CI, 0.63, 0.96). At 7 years after MORE randomization, the differences in mean lumbar spine and femoral neck BMD with raloxifene were 1.7% (p ‫ס‬ 0.30) and 2.4% (p ‫ס‬ 0.045), respectively, from placebo. Compared with MORE baseline, after 7 years, raloxifene treatment significantly increased lumbar spine (4.3% from baseline, 2.2% from placebo) and femoral neck BMD (1.9% from baseline, 3.0% from placebo). BMDs were significantly increased from MORE baseline at all time-points at both sites with raloxifene. Conclusion: Raloxifene therapy had no effect on nonvertebral fracture risk after 8 years, although CORE had limitations for fracture risk assessment. BMD increases were maintained after 7 years of raloxifene.

Inertial focusing in a pressure-driven flow refers to the positioning of particles transverse to the mean flow direction that occurs as a consequence of a finite particle Reynolds number. In channels with rectangular cross-sections, and for a range of channel aspect ratios and particle confinement, experimental results are presented to show that both the location and the number of focusing positions depend on the number of particles per unit length along the channel. This axial number density is a function of both the channel cross-section and the particle volume fraction. These results are rationalized using simulations of the particle-laden flow to show the manner in which hydrodynamic interactions set the preferred locations in these confined flows. A criterion is presented for the occurrence of a stepwise transition from one to two or more trains of particles. At small but finite particle Reynolds numbers, particles in a well-established pipe flow migrate across streamlines to specific positions in the channel or tube cross-section. 1-8 Such focusing of particles is a consequence of inertia and was first observed in channels with a circular cross-section, where the particles migrate to an annular region approximately three-fifths of the radius from the center. 1 In this geometry, the underlying mechanisms have been studied extensively, and particle focusing is understood to arise from the force balance between a wall effect that pushes the particles toward the center of the channel and a shear-gradientinduced migration that pushes particles toward the boundary. 9-12 More recently, inertial focusing has been observed in channels with square and rectangular crosssections, where the particle size often approaches the dimensions of the channel cross-section. [6][7][8]13,14 Because this phenomenon localizes the particles to specific positions, it has been used for separation, filtration, and improved encapsulation efficiencies, and has the potential for incorporation into microfluidic lab-on-a-chip technologies. [6][7][8]15 While the focusing positions and particle ordering in these confined, rectangular cross-sections have been described [6][7][8]14 and the lift force on particles in square cross-section channels has been investigated, 13 questions remain. In particular, consequences of the combination of confining geometries, inertia, and particle concentration have not been characterized.Given the intense interest in the application of microfluidic approaches for manipulating particles and cells, there is a need to develop prediction methods based on understanding the basis of this inertially modulated ordering. To address this need, in this letter, we study the effects of particle concentration and channel geometry on inertial focusing in microfluidic channels with rectangular cross-sections. We find that both the location and the number of focusing positions depend on the number of particles per unit length along the channel, which is a function of both the channel crosssection and particle volume fraction. F...

This work examines the role of particle-scale inertia in a monodisperse suspension of non-Brownian and neutrally buoyant spherical particles subjected to simple-shear flow. The dimensionless parameters governing the problem are the solid-volume fraction ϕ and the Reynolds number defined Re=ργ̇a2∕μ, where a is the sphere radius, γ̇ is the shear rate, and μ and ρ are the viscosity and density of the fluid, respectively. Using numerical simulations in a wall-bounded domain via the lattice-Boltzmann method, the bulk rheological properties of relative viscosity, normal stress differences, and particle pressure are reported for 0.01⩽Re&lt;5 and 0.05⩽ϕ⩽0.3. The anisotropy in microstructure at finite Re is studied through the pair distribution function g(r). Also presented are the probability density functions of particle velocity fluctuations in gradient and vorticity directions. Comparisons to low Reynolds number theory and simulations are provided wherever possible.