Association of osteoporotic fractures of femoral neck and femoral neck geometric parameters in native Chinese women.

BACKGROUND: Although it is generally believed that the femoral neck fracture is related to the femoral neck geometric parameters (FNGPs), the association between the risk of osteoporotic fracture of the femoral neck and FNGPs in native Chinese women is still unclear. METHODS: A total of 374 female patients (mean age 70.2 ± 9.32 years) with osteoporotic fracture of the femoral neck, and 374 non-fracture control groups were completely matched with the case group according to the age ratio of 1:1. Using DXA bone densitometer to measured eight FNGPs: the outer diameter (OD), cross-sectional area (CSA), cortical thickness (CT), endocortical diameter (ED), buckling ratio (BR), section modulus (SM), cross-sectional moment of inertia (CSMI), and compressive strength index (CSI) at the narrowest point of the femoral neck. RESULTS: Compared with the control group, the average values of OD (2.9%), ED (4.5%), and BR (26.1%) in the patient group significantly increased (p = 0.015 to < 0.001), while CSA (‒15.3%), CT (‒18.2%), SM (‒10.3%), CSMI (‒6.4%), and CSI (‒10.8%) significantly decreased (all p < 0.001). The prevalence of osteoporosis in the lumbar spine, femoral neck, and total hip was, respectively, 82%, 81%, and 65% in fracture patients. Cox proportional hazard model analysis showed that in the age adjusted model, the fracture hazard ratio (HR) of CSA, CT, BR, SM, and CSI significantly increased (HRs = 1.60‒8.33; 95% CI = 1.08‒16.6; all p < 0.001). In the model adjusted for age and femoral neck BMD, HRs of CT (HRs = 3.90‒8.03; 95% CI = 2.45‒15.1; all p < 0.001) and BR (HRs = 1.62‒2.60; 95% CI = 1.20‒5.44; all p < 0.001) were still significantly increased. CONCLUSION: These results suggest that the majority of osteoporotic fractures of the femoral neck of native Chinese women occur in patients with osteoporosis. CT thinning or BR increase of FNGPs may be independent predictors of fragility fracture of femoral neck in native Chinese women unrelated to BMD.

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.

Association of follicle-stimulating hormone with bone turnover markers and bone mineral density in Chinese women across the menopausal transition.

BACKGROUND: Elevated follicle-stimulating hormone (FSH) is associated with an increased risk of postmenopausal osteoporosis. This study investigated the association of serum FSH with bone turnover markers (BTMs) and bone mineral density (BMD) in healthy women undergoing menopausal transition. METHODS: A total of 487 healthy women (age 35-65 years, 50 ± 8.5 years) were enrolled in this study. Serum FSH, BTMs, and BMD at lumbar spine and total hip were measured in these subjects. RESULTS: Follicle-stimulating hormone was positively correlated with various BTMs (r = 0.339-0.583, all p < 0.001) and negatively correlated with lumbar spine and total hip BMD (r = -0.629 and -0.514, all p < 0.001). After adjusting for age and body mass index, the partial correlation coefficients of FSH with BTMs and BMD remained significant. Estimating from the regression equation, for every 10 IU/L increase in serum FSH, BTMs increased by 0.38-3.6 units, and BMD decreased by 0.03-0.05 g/cm2 , respectively. Multiple linear regression analysis showed that FSH was a positive factor for serum bone-specific alkaline phosphatase, osteocalcin, and N-telopeptide of collagen type 1 (ß = 0.188-0.403, all p < 0.001), and a negative factor for lumbar spine BMD and serum C-telopeptide of collagen type 1 (ß = -0.629 and -0.183, all p < 0.001). CONCLUSIONS: This study suggests that serum FSH levels are an independent risk factor for BTMs and BMD in menopause-transitioning women, particularly for serum BAP and lumbar spine BMD.

Effect of Body Surface Area on Severe Osteoporotic Fractures: A Study of Osteoporosis in Changsha China.

Clinical vertebral fractures and femoral neck fractures are severe osteoporotic fractures that increase morbidity and mortality. Anthropometric variables are associated with an increased risk of osteoporotic fractures, but it is not clear whether body surface area (BSA) has an effect on clinically severe osteoporotic fractures. The study included total of 3,694 cases of clinical vertebral fractures and femoral neck fractures (2,670 females and 1,024 males) and 3,694 controls without fractures who were matched with the cases by sex and age. There was a significant positive correlation between BSA and bone mineral density (BMD) in female and male fracture patients (females: r = 0.430-0.471, P < 0.001; males: r = 0.338-0.414, P < 0.001). There was a significant systematic increase in BMD in both genders at various skeletal sites, grouped by BSA quartile. The osteoporosis rates of the lumbar spine (97.9%), femoral neck (92.4%) and total hip (87.1%) in the female Q1 group were significantly higher than those in the Q4 group (P < 0.001), which were 80.0%, 57.9% and 36.9%, respectively, in the Q4 group; the osteoporosis rates of the lumbar spine, femoral neck, and total hip were 53.9%, 59.4%, and 36.3% in the male Q1 group, and 15.2%, 21.9%, and 7.03% in the Q4 group, which were significantly lower than those in the Q1 group (P < 0.001). In age-adjusted Cox regression models, the risk of fracture in the remaining three groups (Q2, Q3, and Q4) for weight, BMI, and BSA for both genders, compared with the highest quartile (Q1 by descending quartile stratification) were significantly higher. In models adjusted for age and BMD, only men in the BSA Q3 (HR = 1.55, 95% CI = 1.09-2.19) and BSA Q4 groups (HR = 1.41, 95% CI = 1.05-1.87) had significantly higher fracture risks. In models adjusted for age, height, weight, BMI, and BSA, low BMD was the greatest fracture risks for both sexes. Our results showed that BSA was closely related to BMD, prevalence of osteoporosis, and fracture risk, and that a decline in BSA may be a new potential risk factor for osteoporotic fractures in Chinese men.

Prescreening for osteoporosis with forearm bone densitometry in health examination population.

BACKGROUND: Early detection and timely prophylaxis can retard the progression of osteoporosis. The purpose of this study was to determine the validity of peripheral Dual Energy X-ray Absorptiometry (DXA) test for osteoporosis screening. We examined peripheral bone mineral density (BMD) using AKDX-09 W-I DXA densitometer. Firstly, we acquired BMD data from manufacturer-supplied density-gradient phantoms and 30 volunteers to investigate its accuracy and precision, then we measured BMD for 150 volunteers using both AKDX (left forearm) and Hologic Discovery Wi (left forearm, left hip and L1 - L4 vertebrae) simultaneously. Correlation relationship of BMD results acquired from two instruments was assessed by simple linear regression analysis, the Receiver Operating Characteristic (ROC) curves and Areas Under the Curves (AUCs) were evaluated for the diagnostic value of left forearm BMD measured by AKDX in detecting osteoporosis. RESULTS: In vitro precision errors of AKDX BMD were 0.40, 0.20, 0.19%, respectively, on low-, medium-, and high-density phantom; in vivo precision was 1.65%. Positive correlation was observed between BMD measured by AKDX and Hologic at the forearm (r = 0.670), L1-L4 (r = 0.430, femoral neck (r = 0.449), and total hip (r = 0.559). With Hologic measured T-score as the gold standard, the sensitivity of AKDX T-score < - 1 for identifying suboptimal bone health was 63.0 and 76.1%, respectively, at the distal one-third radius and at any site, and the specificity was 73.9 and 90.0%, respectively; the AUCs were 0.708 and 0.879. The sensitivity of AKDX T-score ≤ - 2.5 for identifying osteoporosis at the distal one-third radius and at any site was 76.9 and70.4%, respectively, and the specificity was 80.4 and 78.0%, respectively; the AUCs were 0.823 and 0.778. CONCLUSIONS: Peripheral DXA appears to be a reliable tool for prescreening for osteoporosis.

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.

Relationship between bone mineral density and fragility fracture risk: a case-control study in Changsha, China.

BACKGROUND: Fragility fracture is associated with bone mineral density (BMD), and most databases used in related researches are instrument-matched. Little is known about the relationship between BMD and fragility fracture risk of native Chinese, especially using local databases as reference databases. OBJECTIVE: To investigate relationship between BMD and risk of fragility fracture in native China. METHODS: 3,324 cases, including 2,423 women (67.7 ± 8.9 years) and 901 men (68.4 ± 11.6 years) having radiological fragility fractures and 3,324 age- and gender-matched controls participated in the study. We measured BMD at posteroanterior spine and hip using dual-energy X-ray absorptiometry (DXA), calculated BMD measurement parameters based on our own BMD reference database. RESULTS: BMDs and mean T-scores were lower in case group (with clinical fragility) than in control group (without clinical fragility). In patients with fragility fractures, prevalence of lumbar osteoporosis, low bone mass, and normal BMD were 78.9 %, 19.3 %, and 1.8 %, respectively, in women, and 49.5, 44.8 %, and 5.7 %, respectively, in men. In hip, these prevalence rates were 67.2 %, 28.4 %, and 4.4 % in females, and 43.2 %, 45.9 %, and 10.9 % in males, respectively, showing differences between females and males. Multivariate Cox regression analysis showed that after adjusting age, height, weight, and body mass index, fracture hazard ratio (HR) increased by 2.7-2.8 times (95 % CI 2.5-3.1) and 3.6-4.1 times (95 %CI 3.0-5.1) for women and men respectively with decreasing BMD parameters. In both sexes, risk of fragility fracture increased approximately 1.6-1.7 times (95 % CI 1.5-1.8) for every 1 T-score reduction in BMD. CONCLUSIONS: Risk of clinical fragility fracture increases with decreasing BMD measurement parameters and anthropometric indicators in native China, and fracture HR varies from gender and site.

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).

Comparison of strategies for setting intervention thresholds for Chinese postmenopausal women using the FRAX model.

PURPOSE: The two main strategies for managing osteoporosis using the Fracture Risk Assessment (FRAX®) are the fixed-probability threshold of the National Osteoporosis Foundation (NOF) and the age-dependent-probability threshold of the National Osteoporosis Guideline Group (NOGG), but there are no FRAX® Chinese-specific thresholds. This study examined the NOF and NOGG strategies for intervention thresholds using the Chinese FRAX® model for their appropriateness for Chinese postmenopausal women, and explored Chinese-specific thresholds. METHODS: Postmenopausal women (N = 264) >50 years old from community-medical centers in China were randomly selected. They completed a self-report questionnaire and underwent bone mineral density measurements and spinal X-rays. The 10-year risks for a major osteoporosis fracture and hip fracture were calculated using the Chinese FRAX® model. Using an osteoporosis diagnosis as the gold standard, we compared the abilities of the NOF and NOGG thresholds to detect osteoporosis by analyzing their sensitivity, specificity, accuracy, and positive and negative likelihood ratios. RESULTS: The 10-year risks for hip fracture and a major osteoporotic fracture increased with age. The NOF's accuracy in detecting osteoporosis was 83.33% and the NOGG's was 74.24%. The NOF thresholds showed higher accuracy and specificity than the NOGG thresholds. CONCLUSION: NOF thresholds are more appropriate for Chinese menopausal women.

Gender differences in a reference database of age-related femoral neck geometric parameters for Chinese population and their association with femoral neck fractures.

Femoral neck geometric parameters (FNGPs) are closely related to the strength of the femoral neck and the risk of fragility fractures. No reference database is available for FNGPs for Chinese population, and gender-related differences in FNGPs as well as their association with the risk of femoral neck fractures are unknown. This investigation aimed to set up reference databases for FNGPs, understand gender-related differences in FNGPs, and examine the association between FNGPs and the risk of osteoporotic fractures of the femoral neck. This study included 5268 females and 2156 males (aged 15-91years) from Chinese population. A total of 384 patients (282 females and 102 males) had sustained femoral neck fractures; 384 age- and sex-matched individuals without any fractures served as controls. Femoral neck DXA images were used to measure bone mineral density (BMD) and eight FNGPs. Our results showed that the age-related trends of FNGPs were fitted with the best goodness-of-fit by applying the cubic regression model. The trends shown by FNGPs were significantly different between male and female subjects, and the fitting curves were significantly higher in male subjects. After adjustments were made for age, height, weight, and body mass index, Cox regression analysis showed that changes in all FNGPs were related to increased hazard ratios (HRs) of femoral neck fractures. After further adjustment was made for BMD of the femoral neck, the HRs related to a cortical thickness (CT) decrease and buckling ratio (BR) increase in females went up by 3.35-folds (95% CI: 2.75-4.07) and 1.86-folds (95% CI: 1.33-2.60), respectively. In males, the HRs related to the decrease in CT and cross-sectional area (CSA) increased by 3.21-folds (95% CI: 2.32-4.45) and 1.88-folds (95% CI: 1.03-3.44), respectively. In conclusions, the reference databases of FNGPs established in this study will assist in the evaluation and prediction of femoral neck fracture risk in the clinic. The decrease in CT and increase in BR of the femoral neck were independent risk factors for osteoporotic fractures of the femoral neck in females from mainland China, while a decrease in CT and CSA were risk factors in male.

Epidemiology and management of osteoporosis in the People's Republic of China: current perspectives.

With the progressive aging of the population, osteoporosis has gradually grown into a global health problem for men and women aged 50 years and older because of its consequences in terms of disabilities and fragility fractures. This is especially true in the People's Republic of China, which has the largest population and an increasing proportion of elderly people, as osteoporosis has become a serious challenge to the Chinese government, society, and family. Apart from the fact that all osteoporotic fractures can increase the patient's morbidity, they can also result in fractures of the hip and vertebrae, which are associated with a significantly higher mortality. The cost of osteoporotic fractures, moreover, is a heavy burden on families, society, and even the country, which is likely to increase in the future due, in part, to the improvement in average life expectancy. Therefore, understanding the epidemiology of osteoporosis is essential and is significant for developing strategies to help reduce this problem. In this review, we will summarize the epidemiology of osteoporosis in the People's Republic of China, including the epidemiology of osteoporotic fractures, focusing on preventive methods and the management of osteoporosis, which consist of basic measures and pharmacological treatments.

Age-related bone turnover markers and osteoporotic risk in native Chinese women.

BACKGROUND: The rate of bone turnover is closely related to osteoporosis risk. We investigated the correlation between bone turnover markers and BMD at various skeletal sites in healthy native Chinese women, and to study the effect of changes in the levels of bone turnover markers on the risk of osteoporosis. METHODS: A cross-section study of 891 healthy Chinese women aged 20-80 years was conducted. The levels of serum osteocalcin (OC), bone-specific alkaline phosphatase (BAP), serum cross-linked N-terminal telopeptides of type I collagen (sNTX), cross-linked C-terminal telopeptides of type I collagen (sCTX), urinary NTX (uNTX), urinary CTX (uCTX) and total urinary deoxypyridinoline (uDPD) were determined. BMD at the posteroanterior spine and the hip was measured using DXA. RESULTS: Pearson's correlation coefficient found significant negative correlation between bone turnover marker and BMD T-score at different skeletal sites (r = -0.08 to -0.52, all P = 0.038-0.000). After adjustments for age and body mass index, the partial correlation coefficients between the OC, BAP, sNTX, sCTX and uCTX, and the T-scores at various skeletal sites were still significant. After adjustment of height and weight, the correlation coefficients between most BTMs and PA lumbar spine BMD were also significant. Multiple linear regression analysis showed that bone turnover markers were negative determinants of T-scores. BAP and OC accounted for 33.1% and 7.8% of the variations in the T-scores of the PA spine, respectively. Serum OC, BAP, uDPD, and sNTX accounted for 0.4-21.9% of the variations in the femoral neck and total hip T-scores. The bone turnover marker levels were grouped as per quartile intervals, and the T-scores, osteoporosis prevalence and risk were found to markedly and increase with increase in bone turnover marker levels. CONCLUSIONS: This study clarified the relationship between bone turnover markers and osteoporosis risk in native Chinese women. Bone turnover marker levels were found to be important determinants of BMD T-scores. Furthermore, osteoporotic risk significantly increased with increase in the levels of bone turnover markers.