Sclerostin antibody stimulates periodontal regeneration in large alveolar bone defects.

Destruction of the alveolar bone in the jaws can occur due to periodontitis, trauma or following tumor resection. Common reconstructive therapy can include the use of bone grafts with limited predictability and efficacy. Romosozumab, approved by the FDA in 2019, is a humanized sclerostin-neutralizing antibody (Scl-Ab) indicated in postmenopausal women with osteoporosis at high risk for fracture. Preclinical models show that Scl-Ab administration preserves bone volume during periodontal disease, repairs bone defects surrounding dental implants, and reverses alveolar bone loss following extraction socket remodeling. To date, there are no studies evaluating Scl-Ab to repair osseous defects around teeth or to identify the efficacy of locally-delivered Scl-Ab for targeted drug delivery. In this investigation, the use of systemically-delivered versus low dose locally-delivered Scl-Ab via poly(lactic-co-glycolic) acid (PLGA) microspheres (MSs) was compared at experimentally-created alveolar bone defects in rats. Systemic Scl-Ab administration improved bone regeneration and tended to increase cementogenesis measured by histology and microcomputed tomography, while Scl-Ab delivered by MSs did not result in enhancements in bone or cemental repair compared to MSs alone or control. In conclusion, systemic administration of Scl-Ab promotes bone and cemental regeneration while local, low dose delivery did not heal periodontal osseous defects in this study.

Spatial scale and structure of complex life cycle trematode parasite communities in streams.

By considering the role of site-level factors and dispersal, metacommunity concepts have advanced our understanding of the processes that structure ecological communities. In dendritic systems, like streams and rivers, these processes may be impacted by network connectivity and unidirectional current. Streams and rivers are central to the dispersal of many pathogens, including parasites with complex, multi-host life cycles. Patterns in parasite distribution and diversity are often driven by host dispersal. We conducted two studies at different spatial scales (within and across stream networks) to investigate the importance of local and regional processes that structure trematode (parasitic flatworms) communities in streams. First, we examined trematode communities in first-intermediate host snails (Elimia proxima) in a survey of Appalachian headwater streams within the Upper New River Basin to assess regional turnover in community structure. We analyzed trematode communities based on both morphotype (visual identification) and haplotype (molecular identification), as cryptic diversity in larval trematodes could mask important community-level variation. Second, we examined communities at multiple sites (headwaters and main stem) within a stream network to assess potential roles of network position and downstream drift. Across stream networks, we found a broad scale spatial pattern in morphotype- and haplotype-defined communities due to regional turnover in the dominant parasite type. This pattern was correlated with elevation, but not with any other environmental factors. Additionally, we found evidence of multiple species within morphotypes, and greater genetic diversity in parasites with hosts limited to in-stream dispersal. Within network parasite prevalence, for at least some parasite taxa, was related to several site-level factors (elevation, snail density and stream depth), and total prevalence decreased from headwaters to main stem. Variation in the distribution and diversity of parasites at the regional scale may reflect differences in the abilities of hosts to disperse across the landscape. Within a stream network, species-environment relationships may counter the effects of downstream dispersal on community structure.