Muthusamy, Kalpana

Abstract Background Osteoporosis and osteopenia are associated with increased fracture incidence in postmenopausal women. We aimed to determine the comparative effectiveness of various available pharmacological therapies. Methods We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ISI Web of Science, and Scopus for randomized controlled trials that enrolled postmenopausal women with primary osteoporosis and evaluated the risk of hip, vertebral, or nonvertebral fractures. A network meta-analysis was conducted using the multivariate random effects method. Results We included 107 trials (193,987 postmenopausal women; mean age, 66 years; 55% white; median follow-up, 28 months). A significant reduction in hip fractures was observed with romosozumab, alendronate, zoledronate, risedronate, denosumab, estrogen with progesterone, and calcium in combination with vitamin D. A significant reduction in nonvertebral fractures was observed with abaloparatide, romosozumab, denosumab, teriparatide, alendronate, risedronate, zoledronate, lasofoxifene, tibolone, estrogen with progesterone, and vitamin D. A significant reduction in vertebral fractures was observed with abaloparatide, teriparatide, parathyroid hormone 1-84, romosozumab, strontium ranelate, denosumab, zoledronate, risedronate, alendronate, ibandronate, raloxifene, bazedoxifene, lasofoxifene, estrogen with progesterone, tibolone, and calcitonin. Teriparatide, abaloparatide, denosumab, and romosozumab were associated with the highest relative risk reductions, whereas ibandronate and selective estrogen receptor modulators had lower efficacy. The evidence for the treatment of fractures with vitamin D and calcium remains limited despite numerous large trials. Conclusions This network meta-analysis provides comparative effective estimates for the various available treatments to reduce the risk of fragility fractures in postmenopausal women.

Plasma free fatty acid (FFA) kinetics in humans are often measured with only one tracer. In study 1, healthy volunteers received infusions of [U-13C]linoleate, [U-13C]oleate, and [U-13C]palmitate during continuous feeding with liquid meals low (n = 12) and high (n = 5) in palmitate and containing three labeled fatty acids to measure FFA appearance and fractional spillover of lipoprotein lipase–generated fatty acids. Study 2 used an intravenous lipid emulsion to increase FFA concentrations during infusion of linoleate and palmitate tracers. In study 1, there were no differences in spillover of the three fatty acids for the low-palmitate meal, but linoleate spillover was greater than oleate or palmitate for the high-palmitate meal. In studies 1 and 2, clearance was significantly greater for linoleate than for the other FFAs. There was a negative correlation between clearance and concentration for each fatty acid in the two studies. In study 1, concentration and spillover correlated positively for oleate and palmitate but negatively for linoleate. In conclusion, linoleate spillover is greater than that of other fatty acids under some circumstances. Linoleate clearance is greater than that of palmitate or oleate, indicating a need for caution when using a single FFA to infer the behavior of all fatty acids.