A. W. C. Kung

Effect of environmental factors and gender on the heritability of bone mineral density and bone size

Bone mineral density (BMD), a risk factor for osteoporosis, is believed to be under genetic control. The effect of environmental factors and gender on the heritability of BMD and bone size is ill‐defined. In this study, heritability estimates (h2) were determined in 3,320 southern Chinese subjects from 1,019 families using the variance components model. The h2 for age, weight and height‐adjusted BMD was 0.63–0.71 for females, and 0.74–0.79 for males; and for bone size, 0.44–0.64 for females and 0.32–0.86 for males. Adjustment for lifestyle factors including calcium and phytoestrogen intake, exercise, smoking and alcohol consumption altered the h2 differently in males and females. The proportion of variance in BMD and bone size explained by all covariates varied between skeletal sites, but was consistently greater in females than males. A significant gender difference was observed in the genetic variance of BMD and bone size at the hip but not the spine. In conclusion, a gender difference was observed in the degree of heritability of BMD and bone size at specific skeletal sites. Environmental influences contributed variably at different sites in the two sexes.

Estrogen receptor β gene polymorphisms are associated with higher bone mineral density in premenopausal, but not postmenopausal southern Chinese women

Bone mineral density (BMD), the main determining risk factor for osteoporotic fractures, has a strong genetic component. Estrogen and its receptors play a critical role in both skeletal maturity and bone loss. We investigated the association between dinucleotide (cytosine-adenine; CA) repeat polymorphisms located in the flanking region of the estrogen receptor beta gene and bone mineral density (BMD) in 325 healthy southern Chinese women. BMD at the lumbar spine and hip region were measured using dual-energy X-ray absorptiometry (DEXA). The number of the repeats observed in our population ranged from 16 to 28. After adjusting for age, height, weight, and years of estrogen exposure, we observed that premenopausal subjects (n = 120) bearing at least one allele of 20 CA repeats had significantly higher BMD at the L2-4 lumbar spine (1.049 +/- 0.016 vs. 0.984 +/- 0.015; p = 0.01), total hip (0.836 +/- 0.014 vs. 0.813 +/- 0.013; p < 0.02), femoral neck (0.773 +/- 0.014 vs. 0.728 +/- 0.013; p = 0.02), trochanter (0.665 +/- 0.013 vs. 0.614 +/- 0.012; p = 0.01), and Wards triangle (0.715 +/- 0.017 vs. 0.651 +/- 0.016; p = 0.02). There was no difference in the vertebral area of L-3 and femoral neck width in these premenopausal women with or without 20 CA repeats. However, in postmenopausal women (n = 205), Estrogen receptor beta (ER beta) gene polymorphisms were not related to BMD at any skeletal site. We conclude that ER beta gene polymorphisms are associated with higher BMD in premenopausal women, suggesting that the ER beta gene may have a modulatory role in bone metabolism in young adulthood.

Does timing of surgery matter in fragility hip fractures

The effect of delay of surgery on the geriatric hip fractures has been a subject of interest in the past two decades. While the elderly patients will not tolerate long periods of immobilization, it is still unclear how soon these surgeries need to be performed. A review of existing literature was performed to examine the effect of timing of surgery on the different outcome parameters of these patients. Although there is conflicting evidence that early surgery would improve mortality, there is widespread evidence in the literature that other outcomes including morbidity, the incidence of pressure sores, and the length of hospital stay could be improved by shortening the waiting time of hip fracture surgery. We concluded that it is beneficial to the elderly patients to receive surgical treatment as an urgent procedure as soon as the body meets the basic anesthetic requirements.

Vitamin D receptor gene polymorphisms and peak bone mass in southern Chinese women.

Controversial results were reported on the association of vitamin D receptor (VDR) polymorphisms and bone mineral density (BMD). We studied allelic frequencies of the BsmI, ApaI, and TaqI restriction fragment length polymorphisms (RFLPs) in 144 normal healthy southern Chinese premenopausal women aged between 30 and 40 years, and correlated their peak bone mass with the VDR genotypes. In comparison to Western populations, the B allele of the BsmI site is only found in 5% of the Chinese population. The BBAAtt genotype is virtually nonexistent in Chinese people. Except for the slightly higher BMD values at the midlateral L-3 vertebra (13.8%, p = 0.045) and at the Wards triangle (13.3%, p = 0.08) in the bb subjects, no difference could be detected at other sites between the Bb and bb subjects. The same findings were observed when comparing the Tt to tt subjects. Analysis of the VDR genotype revealed that subjects with BbAaTt and BbAATt haplotypes had the lowest peak bone mass. Their L2-4 lumbar spine, midlateral L-3 vertebra, and Wards triangle BMD was 1.04, 0.90, and 0.75 standard deviation (SD), respectively, lower than the bbAATT counterparts, but none of the comparisons were statistically significant. However, with the low frequency of the B allele, our study had limited power to detect a small difference in the BMD of the various genotypes. In conclusion, although VDR polymorphism is believed to affect calcium absorption, this study failed to confirm a strong relationship between the VDR genotype and peak bone mass in our population with low dietary calcium intake.

Transforming Growth Factor-β1 Gene Polymorphisms and Bone Turnover, Bone Mineral Density and Fracture Risk in Southern Chinese Women

Genetic contributions play an important role in determining bone mineral density (BMD) and bone turnover. Transforming growth factor-β (TGF-β) is abundant in bone and has been implicated as an important regulator of both bone formation and resorption. Several polymorphisms of the TGF-β1 gene have recently been suggested to be associated with BMD and susceptibility to osteoporotic spine fractures. To determine the relationship between TGF-β1 polymorphisms and BMD in southern Chinese women, three SNPs at C−1348-T, T29-C, and T861-20-C of TGF-β1 gene were analyzed in 237 postmenopausal southern Chinese women by RFLP and direct sequencing. BMD at the lumbar spine and hip region, biochemical markers of bone turnover, as well as serum levels of TGF-β1 were measured. Only the T29-C polymorphism of TGF-β1 gene was associated with BMD and fracture risk. The prevalence of fragility fractures was significantly higher in individuals with TC genotype (P < 0.05). Serum alkaline phosphatase and osteocalcin levels as well as urinary N-telopeptide excretion were significantly higher in women with TC than with TT or CC genotypes, and the difference remained significant after adjusting for age and BMI (all P < 0.05). Women with TC genotype had lower BMD at the trochanteric (P < 0.03) and total hip region (P = 0.05). No difference was observed in the serum TGF-β1 levels among the three genotypes. In conclusion, an association between T29-C polymorphisms of TGF-β1 gene and BMD, bone turnover as well as fragility fractures were demonstrated in postmenopausal southern Chinese women.

Quantitative Ultrasound and Symptomatic Vertebral Fracture Risk in Chinese Women

Abstract: Quantitative ultrasound (QUS) is emerging as a simple, inexpensive and noninvasive method for assessing bone quality and assessing fracture risk. We assessed the usefulness of a contact calcaneal ultrasonometer by studying normal premenopausal women (group I, n= 53), normal postmenopausal women (group II, n= 198), and osteoporotic women without (group III, n= 141) and with vertebral fractures (group IV, n= 53). The osteoporotic subjects had a T-score of the spine or hip neck bone mineral density (BMD) <−2.5 based on the local Chinese peak young mean values. When compared with postmenopausal controls, mean broadband ultrasound attenuation (BUA), speed of sound (SOS), and quantitative ultrasound index (QUI) were 26%, 2.1% and 25% lower in women with vertebral fractures (p all <0.005). The correlation coefficients between QUS parameters and BMD of the spine and hip ranged between 0.4 and 0.5. The ability of the QUS to discriminate between patients groups was determined based on the mean value of normal premenopausal women in group I. The mean T-score for women with fractures was −2.87 ± 1.02 for BUA, −2.54 ± 0.79 for SOS, −3.17 ± 0.70 for QUI, −2.65 ± 0.86 for L2–4 BMD and −2.53 ± 0.66 for hip neck BMD. After adjustment for age and body mass index, the odds ratio of vertebral fracture was 1.71 (95% CI 1.2–2.6) for each 1 SD reduction in BUA, 2.72 (1.3–5.3) for SOS, 2.58 (1.4–4.6) for QUI, 2.33 (1.6–3.3) for L2–4 BMD, 2.09 (1.37–3.20) for femoral neck BMD and 1.88 (1.34–2.92) for total hip BMD. The association between the QUS parameters and vertebral fracture risk persisted even adjustment for BMD. The area under the receiver operating characteristic curve for BUA for vertebral fracture was 0.92, for SOS, QUI, L2–4 BMD and femoral neck BMD was 0.95, and for total hip was 0.91.

Evaluation of a New Calcaneal Quantitative Ultrasound System and Determination of Normative Ultrasound Values in Southern Chinese Women

Abstract: Quantitative ultrasound (QUS) assessment at the calcaneus has been found to be a safe and reliable method for evaluating skeletal status. The present study aimed at evaluating the precision of the Sahara bone ultrasound densitometer and to determine the normative QUS data in healthy southern Chinese women. Broadband ultrasound attenuation (BUA), speed of sound (SOS) and qualitative ultrasound index (QUI) were determined. The long-term in vitro precision of the Sahara machine over 6 months was 4.6% for BUA and 0.39% for SOS. The short-term in vivo precision was 3.2 ± 1.3% for BUA, 0.3 ± 0.2% for SOS and 1.8 ± 1.0% for QUI. The standardized precision for BUA, SOS and QUI was 4.4, 3.8 and 2.2 respectively. The normative data were determined in 1086 healthy subjects. Postmenopausal women had significantly lower BUA, SOS and QUI levels than the premenopausal women. Significant negative correlations were observed between QUS indices and age. Bone mineral density (BMD) assessments was performed on 349 of these subjects. BUA correlated significantly with lumbar spine BMD (r; = 0.326) and femoral neck BMD (r= 0.395). Similar correlations were observed between SOS, QUI and BMD, with r values ranging between 0.446 to 0.522. Despite the fact that Chinese women have significantly lower BMD values than Caucasian women, the mean BUA values for pre- and postmenopausal Chinese women (73 ± 18 and 59 ± 18 dB/MHz respectively) were almost the same as those reported for Caucasian womeo. These normative data will be useful in the assessment of southern Chinese women with fracture risk.

Clinical risk factor assessment had better discriminative ability than bone mineral density in identifying subjects with vertebral fracture

SummaryThis study evaluated the characteristics of patients with vertebral fractures and examined the discriminative ability of clinical risk factors. The findings provide further insights into possible development of a simple, cost-effective scheme for fracture risk assessment using clinical risk factors to identify high-risk patients for further evaluation.IntroductionVertebral fractures are the most common complication of osteoporosis. The aim of this study was to evaluate the characteristics of patients with vertebral fractures and to determine the discriminative ability of bone mineral density (BMD) and other clinical risk factors.MethodsPostmenopausal Southern Chinese women (2,178) enrolled in the Hong Kong Osteoporosis Study since 1995 were prospectively followed up for fracture outcome. Subjects (1,372) with lateral spine radiographs were included in this study. Baseline demographic, BMD, and clinical risk factor information were obtained from a structured questionnaire.ResultsSubjects (299; 22%) had prevalent vertebral fractures. The prevalence of vertebral fractures increased with increasing age, number of clinical risk factors, and decreasing BMD. The odds of having a prevalent vertebral fracture per SD reduction in BMD after adjustment for age in Hong Kong Southern Chinese postmenopausal women was 1.5 for the lumbar spine and femoral neck. Analysis of the receiver operating characteristic curve revealed that bone mineral apparent density did not enhance fracture risk prediction. Subjects with ≥4 clinical risk factors had 2.3-fold higher odds of having a prevalent vertebral fracture while subjects with ≥4 clinical risk factors plus a low BMD (i.e., femoral neck T-score <−2.5) had 2.6-fold. Addition of BMD to clinical risk factors did not enhance the discriminative ability to identify subjects with vertebral fracture.ConclusionsBased on these findings, we recommend that screening efforts should focus on older postmenopausal women with multiple risk factors to identify women who are likely to have a prevalent vertebral fracture.

Management of osteoporosis in patients hospitalized for hip fractures

Hip fracture is associated with high morbidity, mortality, and economic burden worldwide. It is also a major risk factor for a subsequent fracture. A literature search on the management of osteoporosis in patients with hip fracture was performed on the Medline database. Only one clinical drug trial was conducted in patients with a recent hip fracture. Further studies that specifically address post-fracture management of hip fracture are needed. The efficacy of anti-osteoporosis medication in older individuals and those at high risk of fall is reviewed in this paper. Adequate nutrition is vital for bone health and to prevent falls, especially in malnourished patients. Protein, calcium, and vitamin D supplementation is associated with increased hip BMD and a reduction in falls. Fall prevention, exercise, and balance training incorporated in a comprehensive rehabilitation program are essential to improve functional disability and survival. Exclusion of secondary causes of osteoporosis and treatment of coexistent medical conditions are also vital. Such a multidisciplinary team approach to the management of hip fracture patients is associated with a better clinical outcome. Although hip fracture is the most serious of all fractures, osteoporosis management should be prioritized to prevent deterioration of health and occurrence of further fracture.

Ethanolic extract of Actaea racemosa (black cohosh) potentiates bone nodule formation in MC3T3-E1 preosteoblast cells

Aceaea racemosa (formerly Cimicifuga racemosa, black cohosh, AR) extracts have been widely used as an alternative to hormonal replacement therapy for menopausal symptoms. Recent evidences suggest AR extracts are also effective in protecting against postmenopausal bone loss. To determine whether AR has any direct anabolic effect on osteoblasts, we investigated the ethanolic extract of AR on bone nodule formation in mouse MC3T3-E1 preosteoblast cells. AR did not stimulate osteoblast proliferation. Rather, at high doses of 1000 ng/mL for 48 h, AR suppressed (7.2+/-0.9% vs. control) osteoblast proliferation. At 500 ng/mL, a significant increase in bone nodule formation was seen with Von Kossa staining. Using quantitative PCR analysis, AR was shown to enhance the gene expression of runx2 and osteocalcin. Co-treatment with ICI 182,780, the selective estrogen receptor antagonist, abolished the stimulatory effect of AR on runx2 and osteocalcin gene induction, as well as on bone nodule formation in MC3T3-E1 cells. This is a first report of the direct effect of AR on enhancement of bone nodule formation in osteoblasts, and this action was mediated via an estrogen receptor-dependent mechanism. The results provide a scientific rationale at the molecular level for the claim that AR can offer effective prevention of postmenopausal bone loss.