Receptor activator of nuclear factor-kappaB ligand (RANKL) is a cytokine essential for osteoclast differentiation, activation, and survival. Denosumab, a human monoclonal antibody against RANKL, constitutes a promising antiresorptive agent for osteoporosis. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), and other trial registries through January 2009. We selected randomized controlled trials (RCTs) of denosumab in women with low bone mass that described the changes on bone markers and bone mineral density (BMD) as well as the adverse events including fracture risk. We analyzed data from nine RCTs involving 10 329 participants. Although denosumab universally decreased bone markers and increased lumbar and hip BMD, the efficacy evaluation based on percentage (%) mean change from the baseline was not possible due to missing data. Denosumab was not associated with a significant reduction in fracture risk [OR (95% CI) 0.74 (0.33 to 1.64), p=0.45]. Increased risk of serious adverse events [OR (95% CI) 1.83 (1.10 to 3.04), p=0.02] and serious infections [OR (95% CI) 4.45 (1.15 to 17.14), p=0.03] were evident. In conclusion, although effective as an antiresorptive agent, denosumab has not yet proved its efficacy on fracture risk reduction while increased infection risk questions its safety.

Objective: Pregnancy represents a state of insulin resistance (IR). Vaspin (SERPINA12) is a novel insulin-sensitizing adipokine that might be implicated in endogenous glucose regulation. However, its role in pregnancy and its circulating levels have not been adequately studied. We aimed to evaluate serum vaspin levels in pregnancy and their correlation with known markers of IR. Design: A group of 106 women (age 27.9G0.4 years) at the 24-30th week of gestation (pregnancy group) and another 106 age-matched healthy non-pregnant controls (control group) were included in the study. Methods: Serum glucose, insulin, vaspin, adiponectin, and lipid parameters were measured. The quantitative insulin sensitivity check index (QUICKI) was used as an insulin sensitivity index. Results: Pregnant women had significantly higher body mass index (BMI), lipids, and serum insulin and lower serum glucose and vaspin levels than controls. Vaspin was positively correlated to adiponectin in both groups (P!0.001 and P!0.004 respectively) but was not correlated to BMI, serum insulin levels, or the QUICKI index in either group. Furthermore, vaspin was negatively correlated to lipid parameters (total cholesterol, triglycerides, and low-density lipoproteins) in the pregnant but not in the non-pregnant women. Conclusions: Vaspin cannot serve as a marker of IR in either pregnant or non-pregnant women, although it is significantly correlated with adiponectin. On the other hand, vaspin might be useful as a surrogate marker of lipid metabolism in pregnancy if confirmed by subsequent studies.

The diagnosis of SAT at a pregnancy setting may be intriguing. The measurement of circulating cytokines is not helpful in the differential diagnosis or monitoring of the disease.

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