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BackgroundLow bone mineral density (LBMD), including osteoporosis and low bone mass, has becoming a serious public health concern. We aimed to estimate the disease burden of LBMD and its related fractures in 204 countries and territories over the past 30 years.MethodsWe collected detailed information and performed a secondary analysis for LBMD and its related fractures from the Global Burden of Disease Study 2019. Numbers and age-standardized rates related to LBMD of disability-adjusted life-years (DALYs) and deaths in 204 countries and territories were compared by age, gender, socio-demographic index (SDI), and location.ResultsGlobal deaths and DALYs number attributable to LBMD increased from 207 367 and 8 588 936 in 1990 to 437 884 and 16 647 466 in 2019, with a raise of 111.16% and 93.82%, respectively. DALYs and deaths number of LBMD-related fractures increased 121.07% and 148.65% from 4 436 789 and 121248 in 1990 to 9 808 464 and 301 482 in 2019. In 2019, the five countries with the highest disease burden of DALYs number in LBMD-related fractures were India (2 510 288), China (1 839 375), United States of America (819 445), Japan (323 094), and Germany (297 944), accounting for 25.59%, 18.75%, 8.35%, 3.29%, and 3.04%. There was a quadratic correlation between socio-demographic index (SDI) and burden of LBMD-related fractures: DALYs rate was 179.985-420.435SDI+417.936SDI2(R2 = 0.188, p<0.001); Deaths rate was 7.879-13.416SDI+8.839 SDI2(R2 = 0.101, p<0.001).ConclusionsThe global burden of DALYs and deaths associated with LBMD and its related fractures has increased significantly since 1990. There were differences in disease burden between regions and countries. These estimations could be useful in priority setting, policy-making, and resource allocation in osteoporosis prevention and treatment.

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Improving glucose sensitivity remains an unmet medical need in treating type 2 diabetes (T2D). Dorzagliatin is a dual-acting, orally bioavailable glucokinase activator that enhances glucokinase activity in a glucose-dependent manner, improves glucose-stimulated insulin secretion and demonstrates effects on glycemic control in patients with T2D. We report the findings of a randomized, double-blind, placebo-controlled phase 3 clinical trial to evaluate the efficacy and safety of dorzagliatin in patients with T2D. Eligible drug-naïve patients with T2D (n = 463) were randomly assigned to the dorzagliatin or placebo group at a ratio of 2:1 for 24 weeks of double-blind treatment, followed by 28 weeks of open-label treatment with dorzagliatin for all patients. The primary efficacy endpoint was the change in glycated hemoglobin from baseline to week 24. Safety was assessed throughout the trial. At week 24, the least-squares mean change in glycated hemoglobin from baseline (95% confidence interval) was −1.07% (−1.19%, −0.95%) in the dorzagliatin group and −0.50% (−0.68%, −0.32%) in the placebo group (estimated treatment difference, −0.57%; 95% confidence interval: −0.79%, −0.36%; P < 0.001). The incidence of adverse events was similar between the two groups. There were no severe hypoglycemia events or drug-related serious adverse events in the dorzagliatin group. In summary, dorzagliatin improved glycemic control in drug-naïve patients with T2D and showed a good tolerability and safety profile.