Effect of denosumab on glucose metabolism in postmenopausal osteoporotic women with prediabetes: a study protocol for a 12-month multicenter, open-label, randomized controlled trial.

BACKGROUND: Participants with prediabetes are at a high risk of developing type 2 diabetes (T2D). Recent studies have suggested that blocking the receptor activator of nuclear factor-κB ligand (RANKL) may improve glucose metabolism and delay the development of T2D. However, the effect of denosumab, a fully human monoclonal antibody that inhibits RANKL, on glycemic parameters in the prediabetes population is uncertain. We aim to examine the effect of denosumab on glucose metabolism in postmenopausal women with osteoporosis and prediabetes. METHODS: This is a 12-month multicenter, open-label, randomized controlled trial involving postmenopausal women who have been diagnosed with both osteoporosis and prediabetes. Osteoporosis is defined by the World Health Organization (WHO) as a bone mineral density T score of ≤ - 2.5, as measured by dual-energy X-ray absorptiometry (DXA). Prediabetes is defined as (i) a fasting plasma glucose level of 100-125 mg/dL, (ii) a 2-hour plasma glucose level of 140-199 mg/dL, or (iii) a glycosylated hemoglobin A1c (HbA1c) level of 5.7-6.4%. A total of 346 eligible subjects will be randomly assigned in a 1:1 ratio to receive either subcutaneous denosumab 60 mg every 6 months or oral alendronate 70 mg every week for 12 months. The primary outcome is the change in HbA1c levels from baseline to 12 months. Secondary outcomes include changes in fasting and 2-hour blood glucose levels, serum insulin levels, C-peptide levels, and insulin sensitivity from baseline to 12 months, and the incidence of T2D at the end of the study. Follow-up visits will be scheduled at 3, 6, 9, and 12 months. DISCUSSION: This study aims to provide evidence on the efficacy of denosumab on glucose metabolism in postmenopausal women with osteoporosis and prediabetes. The results derived from this clinical trial may provide insight into the potential of denosumab in preventing T2D in high-risk populations. TRIAL REGISTRATION: This study had been registered in the Chinese Clinical Trials Registry. REGISTRATION NUMBER: ChiCTR2300070789 on April 23, 2023. https://www.chictr.org.cn .

Preoperative Anemia and Risk of In-hospital Postoperative Complications in Patients with Hip Fracture.

Purpose: To evaluate the impact of preoperative anemia on postoperative complications after hip fracture surgery. Patients and Methods: We conducted a retrospective study including hip fracture patients at a teaching hospital between 2005 and 2022. We defined preoperative anemia as the last hemoglobin measurement level before surgery < 130 g/L for men and < 120 g/L for women. The primary outcome was a composite of in-hospital major complications, including pneumonia, respiratory failure, gastrointestinal bleeding, urinary tract infection, incision infection, deep venous thrombosis, pulmonary embolism, angina pectoris, arrhythmia, myocardial infarction, heart failure, stroke, and death. Secondary outcomes were cardiovascular events, infection, pneumonia, and death. We used multivariate negative binomial or logistic regression to evaluate the impact of anemia and its severity, categorized as mild (90-130 g/L for men, 90-120 g/L for women) or moderate-to-severe (< 90 g/L for both) anemia on outcomes. Results: Of the 3540 included patients, 1960 had preoperative anemia. 188 anemic patients experienced 324 major complications, while 63 non-anemic patients had 94 major complications. The risk of major complications was 165.3 (95% CI, 149.5-182.4) and 59.5 (95% CI, 48.9-72.3) per 1000 persons in anemic and non-anemic patients, respectively. Anemic patients were more likely to have major complications than non-anemic patients (adjusted incidence rate ratio (aIRR), 1.87; 95% CI, 1.30-2.72), which was consistent in mild (aIRR, 1.77; 95% CI, 1.22-2.59) and moderate-to-severe (aIRR, 2.97; 95% CI, 1.65-5.38) anemia. Preoperative anemia also increased the risk of cardiovascular events (aIRR, 1.96; 95% CI, 1.29-3.01), infection (aIRR, 1.68; 95% CI, 1.01-2.86), pneumonia (adjusted odds ratio (aOR), 1.91; 95% CI, 1.06-3.57), and death (aOR, 3.17; 95% CI, 1.06-11.89). Conclusion: Our findings suggest that even mild preoperative anemia is associated with major postoperative complications in hip fracture patients. This finding highlights considering preoperative anemia as a risk factor in surgical decision-making for high-risk patients.