Economic evaluation of four treatment strategies for postmenopausal patients with osteoporosis and a recent fracture in mainland China: a cost-effectiveness analysis.

Postmenopausal patients with osteoporosis who have a recent fracture are at very high risk of fracture, and this study finds that stratified treatment based on fracture risk would be a cost-effective treatment option for this population. PURPOSE: To evaluate the cost-effectiveness of four anti-osteoporosis medications (denosumab, zoledronate, teriparatide, and alendronate) for postmenopausal osteoporotic women in mainland China, using a stratified treatment strategy recommended by the American Association of Clinical Endocrinologists and the American College of Endocrinology (AACE/ACE). METHODS: A microsimulation Markov model was used to compare the cost-effectiveness of the four treatments in postmenopausal osteoporotic patients of different ages (65, 70, 75, and 80 years), with a recent fracture from the Chinese healthcare perspective. The primary outcome was the incremental cost-effectiveness ratio (ICER), which represent the incremental cost per quality-adjusted life-year (QALY) obtained. One-way deterministic sensitivity analysis (DSA) and probabilistic sensitivity analysis (PSA) were performed to assess the robustness of model findings. RESULTS: Alendronate was dominated by denosumab-to-alendronate and zoledronate at all ages examined, indicating that the costs of the two drugs were lower, but QALYs was greater. However, teriparatide-to-alendronate yielded an ICER of $76,432.07/ QALY, compared with alendronate at age 65, which exceeded the pre-determined willingness-to-pay threshold of $37,653/ QALY. The results were similar at other ages. The DSA showed that the most sensitive parameters were drug efficacy for vertebral and wrist fractures, the relative risk of vertebral fractures, and the persistence of the drugs. The PSA showed that zoledronate had a 100% probability of being the most cost-effective treatment, with a willingness-to-pay threshold of $37,653/ QALY. CONCLUSION: Stratified treatment based on very high fracture risk is more cost-effective than conventional pills in mainland China. Among the stratified treatments, zoledronate is the optimal option.

Development of a Nomogram for Predicting Very Low Bone Mineral Density (T-Scores <-3) in the Chinese Population.

PURPOSE: Fragility fractures, the most serious complication of osteoporosis, affect life quality and increase medical expenses and economic burden. Strategies to identify populations with very low bone mineral density (T-scores <-3), indicating very high fracture risk according to the American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE), are necessary to achieve acceptable fracture risk levels. In this study, the characteristics of persons with T-scores <-3 were analyzed in the Chinese population to identify risk factors and develop a nomogram for very low bone mineral density (T-scores <-3) identification. MATERIALS AND METHODS: We conducted a cross-sectional study using the datasets of the Health Improvement Program of Bone (HOPE), with 602 men aged ≥50 years and 482 postmenopausal women. Bone mineral density (BMD) was measured using dual energy X-ray absorptiometry (DXA). Data on clinical risk factors, including age, sex, weight, height, previous fracture, parental hip fracture history, smoking, alcohol intake >3 units/day, glucocorticoid use, rheumatoid arthritis, and secondary osteoporosis were collected. A multivariate logistic regression to evaluate the relationship between the clinical risk factors and very low BMD (T-scores <-3) was conducted. Parameter estimates of the final model were then used to construct a nomogram. RESULTS: Sixty-three of 1084 participants (5.8%) had BMD T-score <-3. In multivariable regression analysis, age (odds ratio [OR] = 1.068, 95% confidence interval [CI]: 1.037-1.099) and weight (OR = 0.863, 95% CI: 0.830-0.897) were significant factors that were associated with very low BMD (T-scores <-3). These variables were the factors considered in developing the nomogram. The area under the receiver operating characteristic (ROC) curve for the model was 0.861. The cut-off value of the ROC curve was 0.080. CONCLUSION: The nomogram can effectively assist clinicians to identify persons with very low BMD (T-scores <-3) and very high fracture risk in the Chinese population.

Association between Serum Magnesium and Hemoglobin in Patients with Primary Hyperparathyroidism.

BACKGROUND: There is a positive association between serum magnesium and hemoglobin levels in the general population. However, no studies have evaluated the association between serum magnesium and hemoglobin levels in patients with primary hyperparathyroidism (PHPT). We aimed to investigate whether there is a relationship between serum magnesium and hemoglobin levels in the patient population with PHPT. METHODS: This retrospective study included 307 hospitalized PHPT patients who were continuously admitted to the Second Xiangya Hospital of Central South University, from January 2010 to August 2020. Laboratory and demographic data of patients were collected. Hypomagnesemia was defined as serum magnesium <0.75 mmol/L. Patients with a hemoglobin level below 130 g/L in males and below 120 g/L in females were accepted as the anemic group. RESULTS: Among the 307 patients with PHPT included in our study, 77 (25.1%) patients (33 (32.4%) males and 44 (21.5%) females) had hypomagnesemia. A total of 138 (45.0%) patients (49 males (48.0%) and 89 females (43.4%)) had anemia. Compared with the nonanemic group, the anemic group had lower average albumin, eGFR, and serum magnesium levels in both males and females. In contrast, average creatinine, PTH, and corrected calcium were significantly higher in the anemic group than in the nonanemic group in both males and females. Lower serum magnesium levels were associated with lower hemoglobin levels independent of serum calcium, albumin, eGFR, and PTH in PHPT patients. CONCLUSIONS: Hypomagnesemia is a common electrolyte disorder in PHPT patients. Hypomagnesemia is independently associated with lower hemoglobin levels in patients with PHPT.

Pharmacological Treatment of Osteoporosis in Elderly People: A Systematic Review and Meta-Analysis.

BACKGROUND: The evidence supporting the use of antiresorptive and anabolic agents for fracture prevention in elderly patients is still inconclusive. Whether it is too late to alter the course of the disease in this age-group has remained uncertain. OBJECTIVES: The objective of this study was to determine the efficacy and safety of antiresorptive and anabolic agents in elderly patients. METHODS: PubMed, Web of Science, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) and post hoc analyses of RCTs reporting efficacy outcomes or adverse events of antiresorptive and anabolic agents in elderly patients. Statistical heterogeneity was assessed with the Cochran Q χ2 test and I2 statistic. All results were expressed as relative risk (RR) with 95% confidence intervals (CIs). RESULTS: The meta-analysis included 1 RCT and 11 post hoc analyses of data from 10 double-blind placebo-controlled RCTs. Antiresorptive therapy significantly reduced the pooled incidence of vertebral fractures (RR = 0.43; 95% CI = 0.35-0.53; and p < 0.001). It was also associated with lower risk of nonvertebral and hip fractures (RR = 0.84; 95% CI = 0.74-0.96; and p = 0.009 and RR = 0.75; 95% CI = 0.58-0.97; and p = 0.028, respectively). For any adverse events, no difference was observed between antiresorptive agents and placebo groups (RR = 1.01; 95% CI = 1.00-1.02; and p = 0.23). CONCLUSIONS: Both antiresorptive and anabolic agents represented potentially important osteoporosis treatments, showing significant effects on reducing vertebral, nonvertebral, or hip fracture risk, and were well-tolerated by elderly patients. Even in the elderly, maybe it is not too late to alter the course of the disease.

Clinical features, diagnosis and treatment of Paget's disease of bone in mainland China: A systematic review.

Paget's disease of bone (PDB) is a metabolic bone disease with distinct geographical and ethnic differences in its pathogenesis. In this study, we aimed to retrospectively analyze the clinical features and the status of diagnosis and treatment of PDB in mainland China to improve the clinician's understanding of this disease. For this purpose, we conducted a systematic review of 118 articles, including a total of 332 patients with PDB. The results showed that the onset age of PDB in mainland China was 46-60 years. The number of male patients in most age groups was slightly higher than that of female patients, but there was no statistical difference (p > 0.05). The gender ratio (male to female) of PDB in mainland China was significantly different from that in Japan (p < 0.05), but not from that in the USA (p > 0.05). The clinical manifestations of PDB patients in mainland China mainly included ostealgia, bone malformation, hearing loss, and fracture, and bisphosphonate was used as the main treatment drug. These findings were similar to those in Japan, UK, and USA. Total alkaline phosphatase (TALP) level was elevated in about 89.7% of patients, and no correlation between TALP level and ostealgia was observed (p > 0.05). In addition, no difference in TALP level between males and females in each group was observed (p > 0.05).

Targeting oncogenic KRAS in non-small cell lung cancer cells by phenformin inhibits growth and angiogenesis.

Tumors require a vascular supply to grow and can achieve this via the expression of pro-angiogenic growth factors. Many potential oncogenic mutations have been identified in tumor angiogenesis. Somatic mutations in the small GTPase KRAS are the most common activating lesions found in human cancer, and are generally associated with poor response to standard therapies. Biguanides, such as the diabetes therapeutics metformin and phenformin, have demonstrated anti-tumor activity both in vitro and in vivo. The extracellular regulated protein kinases (ERK) signaling is known to be a major cellular target of biguanides. Based on KRAS activates several down-stream effectors leading to the stimulation of the RAF/mitogen-activated protein kinase/extracellular signal-regulated kinase (RAF/MEK/ERK) and phosphatidylinositol-3-kinase (PI3K) pathways, we investigated the anti-tumor effects of biguanides on the proliferation of KRAS-mutated tumor cells in vitro and on KRAS-driven tumor growth in vivo. In cancer cells harboring oncogenic KRAS, phenformin switches off the ERK pathway and inhibit the expression of pro-angiogenic molecules. In tumor xenografts harboring the KRAS mutation, phenformin extensively modifies the tumor growth causing abrogation of angiogenesis. These results strongly suggest that significant therapeutic advantage may be achieved by phenformin anti-angiogenesis for the treatment of tumor.