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Sclerostin antibody has demonstrated a bone-forming effect in pre-clinical models of osteogenesis imperfecta, where mutations in collagen or collagen-associated proteins often result in high bone fragility in pediatric patients. Cessation studies in osteoporotic patients have demonstrated that sclerostin antibody, like intermittent PTH treatment, requires sequential anti-resorptive therapy to preserve the anabolic effects in adult populations. However, the persistence of anabolic gains from either drug has not been explored clinically in OI, or in any animal model. To determine whether cessation of sclerostin antibody therapy in a growing OI skeleton requires sequential anti-resorptive treatment to preserve anabolic gains in bone mass, we treated 3 week old Brtl/+ and wild type mice for 5 weeks with SclAb, and then withdrew treatment for an additional 6 weeks. Trabecular bone loss was evident following cessation, but was preserved in a dose-dependent manner with single administration of pamidronate at the time of cessation. In vivo longitudinal near-infrared optical imaging of cathepsin K activation in the proximal tibia suggests an anti-resorptive effect of both SclAb and pamidronate which is reversed after three weeks of cessation. Cortical bone was considerably less susceptible to cessation effects, and showed no structural or functional deficits in the absence of pamidronate during this cessation period. In conclusion, while SclAb induces a considerable anabolic gain in the rapidly growing Brtl/+ murine model of OI, a single sequential dose of antiresorptive drug is required to maintain bone mass at trabecular sites for 6 weeks following cessation.

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PurposeThis study examines the analytic validity of a software tool designed to provide individuals with risk assessments for colorectal cancer (CRC) based on personal health and family history information. The software is compatible with the U.S. Surgeon General’s My Family Health Portrait.MethodsAn algorithm for risk assessment was created using accepted colorectal risk assessment guidelines, and programmed into a software tool (MFHP). Risk assessments derived from 150 pedigrees using the MFHP tool were compared to “gold standard” risk assessments developed by three expert cancer genetic counselors (GCs).ResultsGenetic counselor risk assessments showed substantial, but not perfect, agreement. MFHP risk assessments for CRC cancer yielded a sensitivity for CRC risk of 81% (95% CI 54–96%) and specificity of 90% (95% CI 83–94%), respectively, when compared to GC pedigree review. The positive predictive values for risk for MFHP was 48% (95% CI 29–68%), while the negative predictive values was 98% (95% CI 93–99%). Agreement between MFHP and GC pedigree review was moderate (Kappa = 0.54)ConclusionsThe analytic validity of the MFHP CRC risk assessment software is similar to other types of screening tools used in primary care. Future investigations should explore the clinical validity and utility of the software in diverse population groups.