Effect of low dose denosumab on bone mineral density in postmenopausal women with osteoporosis after a transition from 60 mg dose: a prospective observational study.

INTRODUCTION: Denosumab is an effective antiresorptive molecule and reduces the risk of fracture in postmenopausal osteoporosis. Cessation of denosumab therapy however is associated with rapid declines in bone mineral density (BMD), rises in bone remodeling, and an increased risk of fracture. We evaluated the effect of low dose denosumab (30 mg every 6 months) on the prevention of bone loss following a switch from standard dose (60 mg of denosumab every 6 months) in a prospective observational study. METHODS: We recruited 114 women 50-90 years of age with postmenopausal osteoporosis at a moderate fracture risk without prior fragility fractures, who had been on denosumab 60 mg every 6 month. These women switched to low dose denosumab 30 mg every 6 months. Mean percentage change in lumbar spine (LS), femoral neck (FN), total hip (TH) and 1/3 distal radius (1/3RAD) BMD at 12 and 24 months were evaluated. Predictors for change in BMD were explored. Subgroup analysis for patients on denosumab 60 mg every 6 months for <3 years and for ≥3 years before switching to low dose denosumab 30 mg was evaluated. RESULTS: At 12 months following a switch from 60 mg to 30 mg of denosumab every 6 months we observed an increase in LS BMD mean percentage change (+2.03%, 95% CI 1.18-2.88, p < 0.001). BMD was stable at the hip and radial sites. Age was found to be a predictor of the mean percentage change in LS BMD for the overall sample. At 24 months, there was a further increase in LS BMD mean percentage change (+3.44%, 95% CI 1.74-5.12, p < 0.001), with stable BMD at other skeletal sites. The 12 month mean BMD percentage change at the LS (p = 0.015), FN (p < 0.001), TH (p < 0.001), and 1/3 RAD (p < 0.001) were found to be predictors of the 24 month mean BMD percentage change. No clinical fractures were reported during 24 months of follow up. CONCLUSION: We observed stable BMD following a switch from denosumab 60 mg every 6 months to 30 mg every 6 months in this prospective observational study conducted in postmenopausal women at a moderate fracture risk.

Sibling cannibalism in a web-building spider: effects of density and shared environment.

Sibling cannibalism occurs across diverse taxa and can affect population size and structure, as well as the fitness of parents and the cannibal, via density effects and variation in individual propensity to cannibalize. We examined these effects on sibling cannibalism in juveniles of a web-building spider (Latrodectus hasselti, Australian redbacks). Adult redbacks are solitary, but juveniles live in clusters of variable density for a week after hatching. We confined newly hatched siblings from a singly-mated female to a low or high density treatment in a split-clutch design, then left spiderlings unfed for a week. Our results showed no effect of density on overall cannibalism levels, but a strong correlation between cannibalism counts from the same maternal lines across densities. Unlike web-bound sit-and-wait predators, wandering spiders that are active hunters have been shown to experience density-dependent cannibalism. In contrast, we suggest sibling cannibalism in web-building spiders may be density independent because early cohabitation on the web selects for elevated tolerance of conspecifics. We conclude that, rather than being linked to density, cannibalism of siblings in these species may be controlled more strongly by variation in individual propensity to cannibalize.