Xing-Zhi Cao

Determination of age-specific bone mineral density and comparison of diagnosis and prevalence of primary osteoporosis in Chinese women based on both Chinese and World Health Organization criteria

The aim of this study was to determine age-specific bone mineral density (BMD) at various skeletal regions in a native Chinese reference population, and to explore the differences in the diagnosis of primary osteoporosis and estimated prevalence of osteoporosis based on both Chinese criteria (BMD of subjects, 25% lower than the peak BMD) and WHO criteria (BMD of subjects, 2.5 SD [T-score ≤ −2.5] lower than the young adult mean [YAM]). There were 3406 subjects in our female reference population, ranging in age from 10 to 90 years. A dual-energy X-ray absorptiometry (DXA) fan-beam bone densitometer (Hologic QDR 4500A) was used to measure the BMD in subjects at the posteroanterior (PA) spine (L1–L4), supine lateral spine (L2–L4 including areal BMD [aBMD] and volumetric BMD [vBMD]), hip (including femoral neck and total hip), and radius + ulna ultradistal (R + UUD) of the forearm. Cross-sectional data analysis in stratified 5-year age intervals revealed that the peak BMD (PBMD) at various skeletal regions occurred within the age range of 30–44 years, with PBMD at the lateral spine and femoral neck occurring at 30–34 years, posteroanterior spine and total hip at 35–39 years, and ultradistal forearm at 35–44 years. The reference values of BMD (PBMD) calculated using Chinese criteria for the diagnosis of primary osteoporosis were significantly higher than the young adult mean (YAM) using WHO criteria for all skeletal regions except for the total hip, at a range of 0.9%–3.8% higher. The BMD cutoff values using Chinese criteria for the diagnosis of osteoporosis were 3.7%–10.9% higher than those using WHO criteria for various skeletal regions. The prevalence rate of primary osteoporosis according to Chinese criteria in subjects ranging from 50 to 90 years was 41.5% at the PA spine, 53.9% at the lateral spine, 34.2% at the femoral neck, 30.7% for total hip, and 51.4% at R + UUD; while according to WHO criteria, this rate was 32.1% at the PA spine, 34.9% at the lateral spine, 16.3% at the femoral neck, 18.9% for total hip, and 45.2% at R + UUD. The prevalence of primary osteoporosis according to both criteria varied with the age and skeletal region of the subjects. The prevalence of primary osteoporosis using Chinese criteria, compared with WHO criteria was 31% higher at the lumbar spine, 109% higher at the femoral neck, and 14% higher at the ultradistal forearm. In conclusion, PBMD occurs in the age range of 30–44 years in native Chinese females. The BMD reference values, BMD cutoff values, and prevalence of primary osteoporosis determined by Chinese criteria are all higher than those determined by the WHO criteria; thus, the application of Chinese criteria may overestimate the number of patients with primary osteoporosis.

Age-related changes in bone biochemical markers and their relationship with bone mineral density in normal Chinese women.

Measurements of bone biochemical markers are increasingly being used to evaluate the state of bone turnover in the management of bone metabolic diseases, especially osteoporosis. However, changes in the bone turnover rate vary with age. The aim of this study was to establish the laboratory reference range of serum bone-specific alkaline phosphatase (sBAP), serum type I collagen cross-linked C-terminal telopeptide (sCTx), and urine CTx (uCTx), based on values from 665 healthy Chinese women aged 20–80 years. We measured the levels of sBAP, sCTx, serum alkaline phosphatase (sALP), and uCTx and evaluated the age-related changes and their relationship with bone mineral density (BMD) in the anteroposterior (AP) lumbar spine, hip, and left forearm. We found significant correlations between biochemical markers and age, with coefficients of determination (R2) of 0.358 for sBAP, 0.126 for sCTx, 0.125 for uCTx, and 0.336 for sALP. The net changes in different biochemical markers were inversely correlated with the rates of BMD loss in the AP lumbar spine. After correction for age, body weight, and height, the levels of the markers had significant negative correlations with the BMD of the AP lumbar spine, femoral neck, and ultradistal forearm. All four biochemical markers had the highest negative correlation with BMD of the AP lumbar spine (partial correlation coefficients of −0.366, −0.296, −0.290, and −0.258 for sBAP, sCTx, uCTx, and sALP, respectively). The mean and SD values of these markers in premenopausal and postmenopausal women with normal BMD values were used as the normal reference ranges. The reference ranges of sBAP, sCTx, and uCTx for pre- vs postmenopausal women were 17.3 ± 6.23 vs 18.9 ± 7.52 U/l, 3.18 ± 1.49 vs 3.23 ± 1.57 nmol/l, and 15.5 ± 11.4 vs 16.2 ± 12.4 nM bone collagen equivalents/mM urinary creatinine, respectively. Levels of the bone formation marker (sBAP) and bone resorption markers (sCTx, uCTx) increased rapidly in women with osteopenia or osteoporosis, indicating that they may be sensitive markers to determine the bone turnover rate in healthy Chinese women.

Relationship of circulating MMP–2, MMP–1, and TIMP–1 levels with bone biochemical markers and bone mineral density in postmenopausal Chinese women

IntroductionOsteoblast-derived matrix metalloproteinase (MMP)–2, MMP–1 and tissue inhibitor of metalloproteinase (TIMP)–1 have been shown to play a role in bone metabolism by degrading the bone matrix.MethodsThe present study was performed to investigate the relationships between serum MMP–2, MMP–1, or TIMP–1 levels and bone mineral density (BMD), as well as bone biochemical markers, in 297 Chinese postmenopausal women aged 42–80 years.ResultsWe found a significant negative weak correlation between MMP–2 and BMD at various skeletal regions. After adjustment for age and BMI, the correlation with BMD at the femoral neck and total hip disappeared. Multiple linear stepwise regression analysis showed that MMP–2 was not a determinant factor for BMD. The significant positive correlations between MMP–2 and bone cross-linked N–telopeptides of type I collagen (NTX), alkaline phosphatase (BAP), and osteocalcin (OC) and were found, and remained significant after adjustment for age and BMI. Moreover, serum MMP–2 concentrations were significantly higher in postmenopausal women with osteoporosis than in age-matched normal controls. There were no significant correlations between MMP–1, TIMP–1 and BMD. There were no significant relationships between MMP–1 and BAP, OC, and NTX. The associations between TIMP–1 and BAP and OC were not specific and constant.ConclusionsIn conclusion, our results suggest that circulating MMP–2 and markers of bone turnover are correlated, and serum MMP–2 levels may rise with increase in bone turnover.

Differences in age-related bone mass of proximal femur between Chinese women and different ethnic women in the United States

Substantial racial differences in bone mass and bone loss rate have been reported, but the extent of the difference between native Chinese women and women of different races in the United States is not clear. We used a DXA bone densitometer to measure bone mineral density (BMD), bone mineral content (BMC), bone area (BA), and volumetric BMD (vBMD) in different regions of the proximal femur in 3614 Chinese women aged 20 years and older. Regression models were chosen to best fit the changes of these parameters with increasing age. The values in their fitted curves were determined by the Cartesian coordinate numeration system. Subsequently, we compared these fitted curves to full-matched data of non-Hispanic black, non-Hispanic white, and Mexican American women reported by the third National Health and Nutrition Examination Survey (NHANES III). We found that all fitted curves of bone mass of non-Hispanic black women were significantly higher than those of Chinese, non-Hispanic white, and Mexican American women (P = 0.000). The BMD and BMC fitted curves in various regions of the hip for non-Hispanic blacks were 22%–28% and 26%–43% higher than those for Chinese women, 8.3%–13% and 7.9%–9.5% higher than those for non-Hispanic whites, and 8.8%–10% and 13%–19% higher than those for Mexican Americans, respectively. However, when the expression of difference was transformed from BMD to vBMD at the femoral neck, the difference between Chinese and non-Hispanic black women was reduced from 22% to 18% and that between Chinese and non-Hispanic white women from 7.4% to 0.8%, but the difference increased from 3.2% to 9.6% between non-Hispanic white and Mexican American women and from 13% to 17% between non-Hispanic white and non-Hispanic black women. By the age of 80 years, the accumulated bone loss rate in various regions of the proximal femur for Chinese, Mexican Americans, non-Hispanic whites, and non-Hispanic blacks were −38.9% ± 1.8%, −34.4% ± 3.1%, −27.8% ± 5.9%, and −28.4% ± 4.8%, respectively. In conclusion, bone mass in the proximal femur of native Chinese women is significantly lower, and the bone loss rate greater, than those of non-Asian women in the United States. At the femoral neck, the vBMD of Chinese women is similar to that of non-Hispanic white women.

Age-related bone mineral density, osteoporosis rate and risk of vertebral fracture in mainland Chinese women with type 2 diabetes mellitus

Few data are available regarding bone mineral density (BMD) and the risk of vertebral fracture among mainland Chinese women with type 2 diabetes mellitus (T2DM). A decrease in the bone projective area (BPA) can be an indirect marker reflecting compressed vertebral fracture. We investigated age-related BMD, BPA, and the prevalence of osteoporosis in women with T2DM in mainland China. BMD and BPA of the posteroanterior lumbar spine (L1–L4) and hip were measured by dual-energy X-ray absorptiometry in 1253 women with T2DM and 1194 control subjects without diabetes aged 40–80 yr. BMD of the lumbar spine and hip decreased with age. BMD of the lumbar spine was higher in T2DM than controls (p<0.05–0.001), as was BPA at some vertebral bodies (p<0.05–0.001), whereas no significant intergroup differences in BPA were observed at the hip. The prevalence of osteoporosis in the women with T2DM increased with age: 0–2.58% at age 40–49 yr, 6.94–28.4% at age 50–59 yr, 32.7–76.7% at age 70–80 yr, with the range reflecting differences between skeletal sites. In subjects over 60 yr, the rates of osteoporosis at posteroanterior spine were significantly lower in T2DM patients than in controls (p<0.05–0.001). In conclusion, women with T2DM had higher BMD and lower risk of osteoporosis. Higher BPA of the vertebrae indicated that women with T2DM in mainland China would have a lower risk of vertebral fracture than non-diabetic women.

Establishment of BMD reference databases for the diagnosis and evaluation of osteoporosis in central southern Chinese men

Osteoporosis in men is an increasingly important public health problem. This study was designed to establish bone mineral density (BMD) reference databases for central southern Chinese men at multiple skeletal sites. We recruited 2433 native Chinese males for BMD assessment. Of these, 1537 were healthy volunteers (age range, 15–85 years), and 896 were suspected to have osteoporosis. BMD values were measured at the posteroanterior (PA) and lateral spine, hip, and distal forearm using a Delphi A absorptiometer. The quadratic regression model provided the best fit for age-related changes in BMD in the spine and hip. The cubic regression model was the best for describing age-related BMD changes in the distal forearm. Peak BMD in the lumbar spine, femoral neck, and total hip occurred at 15–19 years. Peak BMD at the distal forearm occurred at 40–44 years. The prevalence of primary osteoporosis in subjects ranging from 50–85 years was 4.3%–27.7% at various skeletal sites. Compared to the databases established here, the Hologic databases led to significantly higher osteoporosis detection rates. The BMD reference databases established for central southern Chinese men provide the most reliable diagnostic standards for osteoporosis detection in men of central south China.

Relationship of body surface area with bone density and its risk of osteoporosis at various skeletal regions in women of mainland China

The aim of this study was to investigate the relationship between body surface area (BS) and bone mineral density (BMD) and the associated osteoporosis risk at various skeletal regions in women from mainland China. BMD was measured at the posteroanterior (PA) spine (L1–L4), supine lateral spine (L2–L4) including volumetric BMD (vBMD), hip including femoral neck, trochanter and total hip, and forearm, including radius+ulna ultradistal (R+UUD), 1/3 site (R+U1/3) and total region (R+UT) using a dual-energy X-ray absorptiometry (DXA) fan-beam bone densitometer (Hologic QDR 4500A) in 3418 females aged from 18 to 75 years. Data analysis revealed a positive correlation between BS and BMD at the various skeletal regions (r=0.114–0.373, all P=0.000), but no correlation with vBMD (r=0.000, P=0.934). Using the stepwise regression model, BMDs at various skeletal regions were dependent variables while height, weight, body mass index (BMI), BS and projective bone area (BA) were independent variables; BS was determined to be the most important variable that affected the PA spine, hip and forearm BMDs. Subjects were divided into three groups according to size: large BS group (LBSG), intermediate BS group (IBSG) and small BS group (SBSG). The BMD at different skeletal regions of subjects between groups exhibited a significant gradient difference, with LBSG>IBSG>SBSG, but this was not seen for vBMD. On the fitting curves where BMD varied with age at the PA spine, femoral neck, total hip and R+UUD, BMDs of LBSG were 6.93–9.29% higher than those of IBSG and 12.1–16.9 % higher than those of SBSG, whereas those of SBSG were 6.12–9.59% lower than those of IBSG at various skeletal regions, respectively. The prevalence rates and risks of osteoporosis of LBSG were significantly lower than those of SBSG and IBSG, whereas those of IBSG were obviously lower than those of SBSG at various skeletal regions, respectively, presenting a gradient difference among the three study groups, LBSG<IBSG<SBSG. Our study shows that the relationship between BS and BMD exceeds that between BMD and height or weight in women in mainland China. When areal BMD is employed, those with a larger BS have higher areal BMD and lower risks of osteoporosis while, conversely, those with a smaller BS have lower areal BMD, and therefore higher risk for osteoporosis. However, when vBMD is used, these differences diminish or even disappear.