One-year outcomes of an osteoporosis liaison services program initiated within a healthcare system.

Due to the huge gap in the care of patients with osteoporosis and fragility fractures, we aimed to explore the effectiveness of the osteoporosis liaison service (OLS) in osteoporosis care. We found that OLS can improve osteoporosis care, including increasing medication compliance, increasing calcium/vitamin D/protein intake, and reducing fall rate. INTRODUCTION: A significant gap exists in the care of patients with osteoporosis and fragility fractures. This study aimed to evaluate 1-year outcomes of an osteoporosis liaison service (OLS) program that includes two independent components: medication management services (MMS) to improve medication adherence and fracture liaison services (FLS) for secondary prevention. METHODS: Patients with new hip fracture or untreated vertebral fractures enrolled in the FLS program (n = 600), and those with osteoporosis medication management issues but not necessarily fragility fractures enrolled in the MMS program (n = 499) were included. To evaluate outcomes, care coordinators assessed baseline items adapted from the 13 Best Practices Framework (BPF) standards of the International Osteoporosis Foundation, with telephone follow-up every 4 months for 1 year. RESULTS: Mean age of this cohort was 76.2 ± 10.3 years, 78.8% were female. After 1-year participation in the program, all patients had received bone mineral density tests, and medication adherence for the entire cohort at 12 months was 91.9 ± 19.6%, with significant improvement in fall rates (23.4% reduction), exercise rates (16.8% increase), calcium intake (26.5% increase), vitamin D intake (26.4% increase), and adequate protein intake (17.3% increase) (all p < 0.05). After 1-year OLS program, the overall rates of mortality, incident fracture, and falls were 6.6%, 4.0%, and 24.3%, respectively. CONCLUSIONS: The OLS program is associated with improved osteoporosis care, including increased medication adherence, calcium/vitamin D and protein intake, and reduced fall rate.

Racial difference in bioavailability of oral ibandronate between Caucasian and Taiwanese postmenopausal women.

Following 150 mg of oral ibandronate, Taiwanese females have greater serum and urine levels of this drug and bone resorption marker suppression than Caucasian women. These inter-ethnic differences seems to be partly explained by a 2.48-fold higher bioavailability of ibandronate in Taiwanese postmenopausal women. INTRODUCTION: Interethnic differences in the pharmacokinetics of oral ibandronate for osteoporosis are unknown. We compared the disposition of oral ibandronate between Caucasian and Taiwanese postmenopausal women. METHODS: Ibandronate 150 mg was administered to 35 Caucasian and 16 Taiwanese postmenopausal women in two separate phase 1 studies. Interethnic comparisons were performed to assess pharmacokinetic properties, including the area under the concentration-time curve (AUC), peak concentration (Cmax), elimination half-life, urinary drug recovery (Ae%), renal clearance (CLr), apparent total clearance (CL/F), and apparent volume of distribution (Vd/F). RESULTS: The mean AUC, Cmax, and Ae% were 2.41-, 1.69-, and 2.95-fold greater in the Taiwanese than in the Caucasian subjects, and the average CL/F and Vd/F were 2.48- and 2.46-fold smaller. There were no significant differences in mean CLr and half-life between both groups. As bisphosphonates are not biotransformed but are mainly excreted in the urine, the total body clearance is close to the CLr. These results suggested a larger bioavailability in the Taiwanese group which resulted in the differences in the CL/F and Vd/F. Multiple linear regression analysis demonstrated ethnicity influences of the pharmacokinetic properties after adjusting for the other variables. CONCLUSIONS: Bioavailability was largely responsible for the interethnic pharmacokinetic differences following oral administration of 150 mg ibandronate and seemed greater in the Taiwanese compared with the Caucasian subjects. Further dose-ranging studies are warranted to determine the optimal dosages of oral ibandronate in patients of Asian or Taiwanese ethnicity.

Urban-rural disparity of preventive healthcare utilisation among children under the universal health insurance coverage in Taiwan: a national birth cohort analysis.

OBJECTIVE: In the context of universal health insurance coverage, this study aimed to determine whether urban-rural inequality still exists in preventive health care (PHC) amongst children in Taiwan. STUDY DESIGN: Prospective cohort study. METHODS: A total of 184,117 mothers and their children born in 2009 were identified as the study cohort. The number of children born in urban, satellite and rural areas was 40,176, 57,565 and 86,805, respectively. All children were followed for 7 years, before which a total of seven times PHC were provided by Taiwan's National Health Insurance (NHI) programme. Ordinal logistic regression models were used to associate urbanisation level with the frequency of PHC utilisation. Stratified analyses were further performed in accordance with the children's birth weight and the mothers' birthplace. RESULTS: Children from satellite areas had higher utilisation for the first four scheduled PHC visits. Children living in urban areas received more PHC for the fifth and sixth scheduled visits. Compared with those from rural areas, children in satellite areas exhibited a small but significant increase in odds in PHC utilisation, with a covariate-adjusted odds ratio (aOR) of 1.04 and 95% confidence interval (CI) of 1.02-1.06. By contrast, no significant difference was observed between rural and urban areas (aOR = 1.01). Further stratified analyses suggest more evident urban-rural difference in PHC utilisation amongst children with low birth weight and foreign-born mothers. CONCLUSIONS: Given a universal health insurance coverage and embedded mechanisms in increasing the availability of healthcare resources in Taiwan, a slight urban-rural difference is observed in PHC utilisation amongst children. Hence, sociodemographic inequality in utilisation of PHC still exists. This issue should be addressed through policy intervention.

Serum fibroblast growth factor 23 and mineral metabolism in patients with euthyroid Graves' diseases: a case-control study.

This study investigated the alterations of mineral metabolism in patients with Graves' disease (GD) who achieved euthyroidism. They had higher fibroblast growth factor 23 (FGF23) and phosphorus as compared with healthy subjects. Serum FGF23 was negatively correlated with serum phosphorus. These indicated abnormal mineral metabolism even after 1.6 years of euthyroid status. INTRODUCTION: FGF23 is involved in the mineral homeostasis, especially the regulation of serum phosphorus. Graves' disease (GD) is associated with accelerated bone turnover, hyperphosphatemia, and elevated serum FGF23. Evidence suggested that serum FGF23 decreased after a 3-month treatment of GD. However, it remains unclear whether serum FGF23, serum phosphorus, and other markers of mineral metabolism will be normalized after euthyroid status achieved. METHODS: A total of 62 patients with euthyroid GD and 62 healthy control subjects were enrolled, and the median duration of euthyroid status was 1.6 years. Endocrine profiles including thyroid function test, autoantibodies, serum FGF23, and bone turnover markers were obtained and compared between the two groups. RESULTS: Euthyroid GD patients had significantly higher serum FGF23 and phosphorus, and lower 25-hydroxyvitamin D (25(OH)D) and intact parathyroid hormone (iPTH) levels as compared with the control group. Serum FGF23 was significantly and negatively correlated with phosphorus level after adjusted for age, gender, calcium, iPTH, and 25(OH)D in the euthyroid GD group. CONCLUSION: Serum phosphorus and FGF23 levels remain higher in GD patients even after euthyroid status has been achieved for a median of 1.6 years. Serum FGF23 was negatively correlated with serum phosphorus in euthyroid GD patients. Underlying mechanisms warrant further investigations. TRIAL REGISTRATION: Registration number: NCT01660308 and NCT02620085.

Risk of refracture associated with compliance and persistence with bisphosphonate therapy in Taiwan.

SUMMARY: Bisphosphonates have been used for the treatment of postmenopausal osteoporosis since the early 1990s and studies show that compliant patients experience a lower fracture rate. This cohort study showed that the compliance of Taiwanese patients was poor and the refracture risk was related to compliance with bisphosphonate therapy. INTRODUCTION: Bisphosphonates are potent inhibitors of osteoclast activity, and reduce bone turnover by inhibiting bone resorption. According to Taiwanese reimbursement guidelines, patients with osteoporosis-related fractures are eligible for bisphosphonate treatment. This study aimed to elucidate the relationship of refracture risk with compliance/persistence with bisphosphonate therapy in Taiwan. METHODS: This was a retrospective, administrative, database analysis measuring the adherence status and impact of poor adherence to bisphosphonate therapy in Taiwan. Study data derived from the National Health Insurance Research Database (NHIRD) were used to assemble a cohort of all osteoporosis patients who initiated bisphosphonate treatment between January 1, 2004, and December 31, 2005. Patients were followed until death, end of registration in NHIRD, or end of study period (December 31, 2006), whichever occurred first. Compliance was calculated as medication possession ratio (MPR; sum of days of supply of osteoporosis medications divided by follow-up duration). RESULTS: The refracture rates for osteoporosis patients were 5.15 %, 7.36 %, and 8.49 % in the first, second, and third year, respectively, and were significantly lower for patients with >80 % compliance than with <80 % compliance (p < 0.05). Nearly 50 % patients were noncompliant (MPR < 80 %) at 3 months, and only around 30 % patients were adherent at 1 year. Refracture risk increased with MPR < 80 %, age, and co-morbidities like diabetes mellitus or dementia. Patients with concomitant statin medication had significantly lower refracture risk. CONCLUSIONS: The compliance of Taiwanese patients with osteoporosis medication is poor, and refracture risk is related to compliance with bisphosphonate therapy.

The effect of soy isoflavone on bone mineral density in postmenopausal Taiwanese women with bone loss: a 2-year randomized double-blind placebo-controlled study.

UNLABELLED: The treatment of 300-mg/day isoflavones (aglycone equivalents) (172.5 mg genistein + 127.5 mg daidzein) for 2 years failed to prevent lumbar spine and total proximal femur bone mineral density (BMD) from declining as compared with the placebo group in a randomized, double-blind, two-arm designed study enrolling 431 postmenopausal women 45-65 years old. INTRODUCTION: This study evaluated the effects of soy isoflavones on bone metabolism in postmenopausal women. METHODS: Four hundred and thirty-one women, aged 45-65 years, orally consumed 300-mg/day isoflavones (aglycone equivalents) or a placebo for 2 years in a parallel group, randomized, double-blind, two-arm study. Each participant also ingested 600 mg of calcium and 125 IU of vitamin D(3) per day. The BMD of the lumbar spine and total proximal femur were measured using dual-energy X-ray absorptiometry at baseline and every half-year thereafter. Serum bone-specific alkaline phosphatase, urinary N-telopeptide of type 1 collagen/creatinine, and other safety assessments were examined regularly. RESULTS: Two hundred out of 217 subjects in the isoflavone group and 199 out of 214 cases in placebo group completed the treatment. Serum concentrations of isoflavone metabolites, genistein and daidzein, of the intervention group were remarkably elevated following intake of isoflavones (p < 0.001). However, differences in the mean percentage changes of BMD throughout the treatment period were not statistically significant (lumbar spine, p = 0.42; total femur, p = 0.39) between the isoflavone and placebo groups, according to the generalized estimating equation (GEE) method. A significant time trend of bone loss was observed at both sites as assessed by the GEE method following repeated measurement of BMD (p < 0.001). Differences in bone marker levels were not significant between the two treatment groups. CONCLUSION: Treatment with 300-mg/day isoflavones (aglycone equivalents) failed to prevent a decline in BMD in the lumbar spine or total femur compared with the placebo group.

Efficacy and safety of bazedoxifene in postmenopausal Asian women.

UNLABELLED: This 6-month study examined the efficacy and safety of bazedoxifene 20 mg in postmenopausal Asian women. Bazedoxifene showed statistically significant improvements over placebo in bone mineral density at all skeletal sites evaluated. Bazedoxifene significantly reduced bone turnover and had favorable effects on lipid parameters. Bazedoxifene was safe and well tolerated. INTRODUCTION: This 6-month, randomized, double-blind, placebo-controlled phase 3 study conducted in China, Korea, and Taiwan evaluated the efficacy and safety of bazedoxifene in postmenopausal Asian women. METHODS: Generally, healthy postmenopausal Asian women (N=487; mean age, 57.2 years; mean lumbar spine bone mineral density [BMD], -1.1) were randomized to daily therapy with bazedoxifene 20 mg or placebo; all subjects received daily supplemental calcium carbonate 600 mg. The changes from baseline in BMD at the lumbar spine (primary end point) and at other skeletal sites, bone turnover markers, and lipid parameters were evaluated at 6 months. Safety assessments included adverse event (AE) reporting and physical/gynecologic examination. RESULTS: At 6 months, women who received bazedoxifene 20 mg had significantly greater BMD compared with those receiving placebo at the lumbar spine (0.41% vs -0.32%, P<0.01), femoral neck (-0.08% vs -0.69%, P=0.014), trochanter (0.50% vs -0.23%, P=0.010), and total hip (-0.03% vs -0.77%, P<0.001), respectively. Bazedoxifene 20 mg was also associated with significant differences from placebo in median percent reductions from baseline in serum C-telopeptide (-21.8%, P<0.001) and osteocalcin (-12.9%, P<0.001) levels and total (-5.0%, P<0.001) and low-density lipoprotein cholesterol (-9.5%, P<0.001) levels. The incidence of AEs was not different between subjects treated with bazedoxifene and those who received placebo. CONCLUSION: Bazedoxifene was generally safe and effective in preventing bone loss in this short-term study of postmenopausal Asian women.

Catechin stimulates osteogenesis by enhancing PP2A activity in human mesenchymal stem cells.

SUMMARY: Using human mesenchymal stem cells, we identified catechin from a panel of herbal ingredients and Chinese traditional compounds with the strongest osteogenic effects. Catechin increased alkaline phosphatase activity, calcium deposition, and mRNA expression of Runx2 and osteocalcin. We further clarified the signaling pathway that catechin mediated to stimulate osteogenesis. INTRODUCTION: Human mesenchymal stem cells (hMSCs), useful as a species specific cell culture system for studying cell lineage differentiation, were examined as a tool to identify novel herbal ingredients and Chinese traditional compounds for enhancing osteogenesis. METHODS: Immortalized and primary hMSCs were induced in osteogenic induction medium in the presence of a variety of herbal ingredients and Chinese traditional compounds and osteogenic differentiation was evaluated by histochemical assays and quantitative RT-PCR. RESULTS: Using immortalized hMSCs, we first identified catechin, 18ß-glycyrrhetinic acid, baishao, and danggui with osteogenic properties, which enhanced calcium deposition at the dose without significant cytotoxic effects. Primary hMSCs were then applied for confirming the osteogenic effects of catechin, which increased alkaline phosphatase activity, calcium deposition, and mRNA expression of Runx2 and osteocalcin. We further found the extracellular signal-regulated kinase (ERK) pathway was downregulated upon stimulation with catechin. Catechin increased the level and activity of protein phosphatases 2A (PP2A) that dephosphorylates ERK kinase (MEK) and ERK. Further, PP2A inhibitor, okadaic acid, abolished the effect of catechin-mediated inactivation of ERK and stimulation of osteogenesis. The blocking effect of okadaic acid on osteogenesis was further reversed by PD98059, a specific inhibitor of MEK. Co-immunoprecipitation revealed the association of PP2A to both MEK and ERK. CONCLUSIONS: These studies propose catechin enhanced osteogenesis by increasing the PP2A level that inhibits the MEK and ERK signaling in hMSCs. These results prove the concept of using hMSCs as a convenient tool for rapid and consistent screening of the osteogenic herbal ingredients and traditional Chinese compounds.

The effects of strontium ranelate in Asian women with postmenopausal osteoporosis.

The aim of this study was to assess the efficacy and safety of strontium ranelate in the treatment of postmenopausal women with osteoporosis in Taiwan. In this 12-month multicenter, randomized, double-blind, placebo-controlled study, 125 women with osteoporosis were randomly given either strontium ranelate 2 g daily or placebo. Lumbar spine, femoral neck, and total-hip bone mineral density (BMD) and biochemical markers of bone turnover were measured; adverse events and tolerability were recorded and assessed. Subjects treated with strontium ranelate showed significant increases in BMD of 5.9% at the lumbar spine, 2.6% at the femoral neck, and 2.7% at the total hip, while the placebo group exhibited no significant change at 12 months. Serum level of a formation marker (bone-specific alkaline phosphatase) was also significantly increased at 6 and 12 months. Thus, although the sample size and the treatment duration of this study could not show its effect of reducing osteoprotic fractures, strontium ranelate showed bone protection effects by increasing BMD and concentrations of a bone formation marker. Safety assessment revealed adverse events were mild and not significantly different from placebo.

Impaired vitamin D metabolism with aging in women. Possible role in pathogenesis of senile osteoporosis.

Calcium absorption decreases with aging, particularly after age 70 yr. We investigated the possibility that this was due to abnormal vitamin D metabolism by studying 10 normal premenopausal women (group A), 8 normal postmenopausal women within 20 yr of menopause (group B), 10 normal elderly women (group C), and 8 elderly women with hip fracture (group D) whose ages (mean +/- SD) were 37 +/- 4, 61 +/- 6, 78 +/- 4, and 78 +/- 4 yr, respectively. For all subjects, serum 25-hydroxyvitamin D [25(OH)D] did not decrease with age, but serum 1,25-dihydroxyvitamin D [1,25(OH)2D], the physiologically active vitamin D metabolite, was lower (P = 0.01) in the elderly (groups C and D; 20 +/- 3 pg/ml) than in the nonelderly (groups A and B; 35 +/- 4 pg/ml). The increase of serum 1,25(OH)D after a 24-h infusion of bovine parathyroid hormone fragment 1-34, a tropic agent for the enzyme 25(OH)D 1 alpha-hydroxylase, correlated inversely with age (r = -0.58; P less than 0.001) and directly with glomerular filtration rate (r = 0.64; P less than 0.001). The response was more blunted (P = 0.01) in elderly patients with hip fracture (13 +/- 3 pg/ml) than in elderly controls (25 +/- 3 pg/ml). We conclude that an impaired ability of the aging kidney to synthesize 1,25(OH)2D could contribute to the pathogenesis of senile osteoporosis.

Genetic algorithm for the efficient selection of disyllabic word lists used in Mandarin speech discrimination tests.

Speech audiometric tests have been widely used for advanced hearing diagnoses and in rehabilitation. However, there are no standardised speech tests for more than 90% of the world's population, who do not speak English. A major problem in the design of a speech audiometric test is that the selection of test materials is subject to multiple criteria, and its complexity rises dramatically as the structure of test items changes from phonemic or monosyllabic forms to disyllabic or polysyllabic forms. A genetic algorithm is presented that can automatically select a set of disyllabic words from a large Mandarin corpus. The selection accords with the following principal criteria for the items constituting a speech discrimination test: similarity in structure, familiarity to the subjects, and a phonemically balanced composition. The performance of the genetic algorithm was evaluated by computation of the distance between a target vector, specifying the desired distribution of initial and final syllables and tone patterns for daily disyllabic word usage, and the vector derived by the search results of the algorithm. The use of the genetic algorithm was illustrated by its application to the selection of test lists from two Mandarin corpora. The results showed that, for a given corpus, at least 12 disyllabic word lists with a distance of less than 20 could be generated within 72 h. The genetic algorithm performed an efficient, robust and low-complexity search of the problem space and can be easily modified to adapt to the material selection of other languages.

Effect of acute increases in bone matrix degradation on circulating levels of bone-Gla protein.

Serum bone Gla-protein (BGP), also called osteocalcin, is a specific and sensitive measure of bone turnover in a variety of metabolic bone disorders. Although some BGP diffuses into the circulation after synthesis by osteoblasts, most is incorporated into bone matrix where it remains until bone is resorbed. Thus, serum BGP could reflect bone formation, bone resorption, or a combination of both. The relationship of serum BGP to the components of bone turnover was evaluated in 18 normal women (mean age 48 yr; range 30-70) who received a continuous 24-h intravenous infusion of the 1-34 synthetic fragment of bovine parathyroid hormone. Mean +/- SE for urinary hydroxyproline excretion, an index of bone resorption, increased (from 22.7 +/- 2.2 to 38.5 +/- 3.7 micrograms/100 ml glomerular filtrate [GF], p less than .001), whereas levels of serum alkaline phosphatase, an index of bone formation, were unchanged (from 20 +/- 1 to 20 +/- 1 U/liter, NS). Despite the increase in bone resorption, levels of serum BGP decreased (from 8.8 +/- 0.8 to 6.8 ng/dl, p less than .001). The data suggest that circulating levels of BGP are a measure of bone formation but, at least in subjects with normal renal function, not a measure of bone resorption. Presumably BGP in bone matrix is degraded during osteoclastic resorption into fragments that either are not recognized by an antiserum raised against the native molecule or are rapidly cleared from the circulation.

Comparison of bone mineral content among Japanese, Koreans, and Taiwanese assessed by dual-photon absorptiometry.

Throughout the world the diagnosis and management of osteoporosis currently involves the measurement of bone mineral content. There are, however, no studies comparing bone mineral content among Asian people. This cross-sectional study was designed to quantify spine and femur bone mineral density (BMD) in Japanese and compare BMD among Asian people (Japanese, Koreans, and Taiwanese) using the same model dual-photon system (Norland Model 2600). Following a peak BMD in the third and fourth decades, the Japanese BMD values of the lumbar spine and femoral neck showed a clear decrease (annual loss of 0.99 and 0.74%, respectively) with age in females. On the other hand, Japanese BMD values were stable in males until the fifth decade. There was some decrease in BMD with age after the fifth decade, which was much less obvious than that in females. An age-dependent loss of BMD was clearly observed in Japanese and Korean but not in Taiwanese females. Korean males seemed to have a clearer age-dependent loss of BMD compared to Japanese males. Our findings indicate that differences may exist in the BMD of Asian people and that in addition to the quantitative determination of individual BMD, dual-photon absorptiometry may be useful for the comparison of BMD among different ethnic and cultural groups.

Bone responsiveness to parathyroid hormone in normal and osteoporotic postmenopausal women.

Increased bone loss in estrogen-deficient normal and osteoporotic postmenopausal women may be due mainly to increased sensitivity of bone-resorbing cells to circulating PTH, but this is supported only by indirect data. Therefore, we tested the responsiveness of bone to PTH directly by using a 3-day iv infusion of bovine PTH-(1-34) at 400 U/day in 9 normal premenopausal women, 10 normal postmenopausal women, and 12 osteoporotic postmenopausal women. Serum calcium and urinary hydroxyproline concentrations increased (P less than 0.001) over baseline values during infusion, but the mean increases in both variables did not differ among groups. The data do not support the hypothesis that estrogen deficiency increases the sensitivity of bone to PTH or that the sensitivity in osteoporotic women is greater than that in normal postmenopausal women. Within the constraints imposed by the method of testing, we conclude that the additional bone resorption induced by menopause and by osteoporosis may be due to mechanisms that are not due to enhanced responsiveness of bone to PTH.

Vitamin D stores of urban women in Taipei: effect on bone density and bone turnover, and seasonal variation.

This study was performed to survey the vitamin D nutritional status of urban Chinese women, and to define its role in determining bone metabolic rate and bone mineral density (BMD). We measured serum 25-hydroxyvitamin D (25-OHD), the major storage form of vitamin D, and BMD, at the spine, hip, and total body skeleton, of 262 healthy Chinese women aged from 40 to 72 years, residing in Taipei city. Bone turnover markers, including serum osteocalcin, bone alkaline phosphatase isozyme, and C-terminal propeptide of type I procollagen, and a urinary bone resorption marker, N-terminal crosslinked fragment of type I collagen, were also measured. We found generally adequate vitamin D nutritional stores. The mean concentration of serum 25-OHD was 30.7 (SD = 8.2) ng/mL for all 262 subjects and there were no significant age-related changes. Those who had serum sampled during the summer showed higher serum 25-OHD levels (N = 138; mean +/- SD: 32.7 +/- 7.6 ng/mL) than those who had serum sampled during winter (N = 124; mean +/- SD: 28.5 +/- 8.3 ng/mL; Student's t-test, p < 0.001), but these two groups showed similar BMD and bone marker values. Those with serum 25-OHD concentration in the lowest or highest tertile did not show different BMD or bone marker values than those in the other tertiles. Multiple regression demonstrated no correlation between 25-OHD and any bone marker or BMD at any site. Thus, in this free-living urban Chinese population, in a subtropical region, we could not demonstrate a role of vitamin D stores in determining bone turnover rate or BMD in women aged 40-70 years.

Risk of underestimation of the bone mineral density of proximal femur.

Decreased bone mineral density (BMD) in the elderly increases the risk of hip fracture. Measurement of proximal femoral BMD can help us predict the risk of hip fracture, especially in the elderly. Since the BMD of proximal femur is usually measured on the unilateral side, we studied the risk of underestimation with measurement of unilateral proximal femur BMD in 266 normal Chinese women. In order to evaluate the effect of age, these subjects were divided into group A (18-59 years, n = 189) and group B (60-88 years, n = 77). BMDs of both proximal femurs were assessed with Norland 2600 dual photon absorptiometry. Using a cutoff T score of -1, the negative predictive value (NPV) in the entire group was 86.9% for femoral neck BMD and 85.7% for trochanter, and 82.2% for Ward's triangle: in group A, the NPV was 88.9% for femoral neck, 88.8% for trochanter, and 97.2% for Ward's triangle, but in group B, the NPV was 60.0% for femoral neck, 71.0% for trochanter, and 24.1% for Ward's triangle. The accuracy in the entire group was 86.1% for femoral neck, 84.2% for trochanter, and 86.3% for Ward's triangle: in group A the accuracy was 84.6% for femoral neck, 84.9% for trochanter, and 92.8% for Ward's triangle, but in group B, the accuracy was 89.6% for femoral neck, 81.7% for trochanter, and 90.0% for Ward's triangle. In general, NPV and accuracy increased at the expense of positive predictive value when the cutoff T score was changed to -2.5. This study suggested that measurement of unilateral proximal femur BMD was sufficient for screening the contralateral hip BMD in group A at a cutoff T score of -1. However, a T score of -2.5 was recommended for group B, and one should be careful in its application to Ward's triangle.

Bone densitometry of proximal femur in Chinese subjects: gender differences in bone mass and bone areas.

Bone mineral content (BMC), bone areas (BA), and bone mineral density (BMD) of the proximal femur were measured in 202 healthy Chinese men and 507 healthy Chinese women, aged 21-70 years, to investigate gender differences in densitometry of the femur. Densitometric values measured at the femoral neck, trochanter, and Ward's triangle were generally greater in men than women of the same age, except at Ward's triangle. While BMD decreased with aging with similar slopes of -0.2 approximately -1% per year, the actual readings were 10%-15% lower than those of Caucasian subjects of the same age and gender for Chinese men and women. Furthermore, with increasing age, trochanteric BA increased in women but not in men, and femoral neck BA increased in men but not in women. These different trends of change in bone dimensions were independent of weight or height. They may reflect a structural difference at the proximal femur and imply differences in mechanical strength, and thus may have played some roles in the different incidence of hip fractures between the elderly men and women.

Bone mineral density and bone markers in relation to vitamin D receptor gene polymorphisms in Chinese men and women.

Whether vitamin D receptor gene (VDRG) polymorphism can be used as a predictor for bone turnover rate or bone mass remains controversial. Its role within various ethnic populations are also unsettled. We examined VDRG polymorphism using restrictive enzymes Bsm-I, Apa-I, and Taq-I in 155 men aged 22-88 and 113 premenopausal women aged 40-53. The bone mineral density (BMD) of the vertebrae (L2-4), proximal femur, and total body bone mineral content (tb-BMC) (women only), as well as urinary N-terminal crosslinked fragment of type I collagen (NTX), serum osteocalcin, bone isozyme of alkaline phosphatase, and caboxyterminal propeptide of type I procollagen levels were measured. Chinese men and women exhibited a low prevalence for B (absence of Bsm-I restriction site) phenotypes than white and Japanese. Within the tested samples there were 0.4% BB homozygotes, 6.7% Bb heterozygotes, and 93% bb homozygotes. The distributions of Apa-I polymorphism (9.0% AA, 42.5% Aa, and 48.5% aa) also differed from those reported for the white populations. Most of the Chinese men and women were TT homozygous (96.6%). A comparison of actual values and values adjusted for age and weight of tb-BMC and BMD at the lumbar spine, Trochanter, Ward's triangle, and femoral neck showed no significant difference among three subgroups in each of the three sets of polymorphism. Furthermore, the actual values and adjusted values (adjusted for age) of the four bone markers, respectively, showed no significant differences. We conclude that given the very low prevalence of the suspected high risk genotypes (B, A, and t), and the lack of difference among the polymorphic subgroups, VDRG polymorphism may not be an important determinant of the bone turnover rate and bone mass of Chinese men and women.

Effects of alendronate on osteopenic postmenopausal Chinese women.

To evaluate the effects of alendronate on postmenopausal Chinese women with osteopenia, we treated 46 subjects daily with either 10 mg alendronate (N = 24) or placebo plus 500 mg calcium supplement (N = 22), and measured their bone mineral density (BMD) at the lumbar spine and hip, and urinary bone resorption markers before, during, and after the 1 year treatment period. The bone markers included N-telopeptide of type I collagen (NTx) and deoxypyridinoline (Dpd); both were corrected by the concentration of creatinine in the same sample (NTx/Cr and Dpd/Cr). Both NTx/Cr and Dpd/Cr decreased significantly by 44% and 28%, respectively (p < 0.05 for both), in 1 month in the active treatment group but did not change in the placebo group. BMD at the spine, femoral neck, trochanter, and Ward's triangle increased significantly by 6 months and showed a further increase through month 12 at the spine in the alendronate-treated group. Relative to the placebo group, BMD changes at various sites in the alendronate-treated group were higher at 12 months by 6%-11%. Thus, our data suggest that 10 mg alendronate daily resulted in significant increases in spine and hip BMD, and decreases of urinary resorption markers in the osteopenic postmenopausal Chinese women studied. The amplitude of responses was higher than in previous reports in the USA and Europe.