Development of a low-dose anti-resorptive drug regimen reveals synergistic suppression of bone formation when coupled with disuse.

Safe and effective countermeasures to spaceflight-induced osteoporosis are required to mitigate the potential for mission-critical fractures and ensure long-term bone health in astronauts. Two anti-resorptive drugs, the bisphosphonate zoledronic acid (ZOL) and the anti-receptor activator of NF-kappaB ligand protein osteoprotegerin (OPG), were investigated to find the minimum, comparable doses that yield a maximal increase in bone quality, while minimizing deleterious effects on turnover and mineralization. Through a series of five trials in normally loaded female mice (n = 56/trial), analysis of trabecular volume fraction and connectivity using microcomputed tomography, along with biomechanical testing, quantitative histomorphometry, and compositional analysis, was used to select 45 microg/kg ZOL and 500 microg/kg OPG as doses that satisfy these criteria. These doses were then examined for their ability to mitigate bone loss following short-term unloading through hindlimb suspension (HLS). Seventy-two mice were prophylactically administered ZOL, OPG, or PBS and assigned to loaded control or 2-wk HLS groups (n = 12 for each of 6 groups). Both anti-resorptives were able to preserve trabecular microarchitecture and femoral elastic and maximum force in HLS mice (+30-40% ZOL/OPG vs. PBS). In HLS mice, anti-resorptive dosing reduced resorption perimeter at the femoral endocortical surface by 30% vs. PBS. In loaded control mice, anti-resorptives produced no change in bone formation rate; however, reductions in bone formation rate brought about by HLS were exacerbated by anti-resorptive treatment, suggesting synergistic inhibition of osteoblasts during disuse. Refined anti-resorptive dosing will tend to target countermeasures to the period of disuse, resulting in faster recovery and less adverse effects for astronauts.     

<Emphasis Type="Italic">Neolindleya</Emphasis> Kraenzl. (Orchidaceae), an enigmatic and largely overlooked autogamous genus from temperate East Asia

The Asiatic orchid species Neolindleya camtschatica (Cham.) Nevski has been omitted from the majority of relevant taxonomic surveys, including the recent Genera Orchidacearum. In most studies where the species has been included, it has been assigned to the species-rich genera Gymnadenia or Platanthera. A few morphologists recognised a new monotypic genus, Neolindleya Kraenzl., to accommodate the species. More recent molecular phylogenetic studies showed barely sufficient molecular disparity to justify generic separation of this species, but demonstrated clearly that the genus Neolindleya is only distantly related to Gymnadenia. However, the molecular phylogenies show relationships of equal strength of Neolindleya with Galearis (including Amerorchis) on the one hand and Platanthera s.l. on the other. In an attempt to better resolve the phylogenetic placement of Neolindleya, and to more clearly understand its biology and ecology, we have re-examined the morphology of this enigmatic species. Our results, based partly on SEM studies, reinforce the validity of Neolindleya as a genus, indicate a closer relationship with Galearis s.l. than with Platanthera s.l., and strongly suggest that the species became an autogam following ‘accidental’ loss of a functional bursicle. Ecologically, N. camtschatica is an opportunistic species that benefits from anthropogenic habitat disturbance.