Peak Bone Mineral Density Research Articles

Changes in Bone Metabolism in Young Castrated Male Rats.

PurposeTo determine the window of time during which osteoporosis affects the management of spinal surgery and the mechanism of bone metabolism changes in males with osteoporosis by examining changes in bone metabolism in young castrated male rats.Materials and MethodsA total of 30 Sprague-Dawley rats were randomly allocated into two study groups. Group 1 (control) received a sham surgery and Group 2 received bilateral orchiectomy to change bone mineral density (BMD). Serum osteocalcin, alkaline phosphatase (ALP), and collagen type 1 cross-linked C-telopeptide (CTX) were analyzed at postoperative date (POD) 8, 10, and 12 weeks. BMDs were measured using micro computed tomography scans.ResultsFemoral and lumbar BMDs were decreased in the orchiectomy groups. BMDs in the sham and orchiectomy groups showed statistically differences at POD 8, 10, and 12 weeks for the femur (p=0.032, 0.008, 0.008) and lumbar spine (p=0.151, 0.008, 0.008, respectively). Serum osteocalcin, ALP, and CTX decreased gradually; however, N-terminal type 1 procollagen (P1NP) showed a slight increase yet no significant change.ConclusionIn young castrated male rats, a significant decrease in BMD was observed after orchiectomy due to the mixture of two detrimental factors. Young castrated male rats did not reach peak BMD. Increased bone turnover causes bone resorption to exceed bone formation. This study may contribute to the creation of a valuable model for studies of male osteoporosis and the spinal surgery field.

Osteoblast-Specific Overexpression of Human WNT16 Increases Both Cortical and Trabecular Bone Mass and Structure in Mice.

Previous genome-wide association studies have identified common variants in genes associated with bone mineral density (BMD) and risk of fracture. Recently, we identified single nucleotide polymorphisms (SNPs) in Wingless-type mouse mammary tumor virus integration site (WNT)16 that were associated with peak BMD in premenopausal women. To further identify the role of Wnt16 in bone mass regulation, we created transgenic (TG) mice overexpressing human WNT16 in osteoblasts. We compared bone phenotypes, serum biochemistry, gene expression, and dynamic bone histomorphometry between TG and wild-type (WT) mice. Compared with WT mice, WNT16-TG mice exhibited significantly higher whole-body areal BMD and bone mineral content (BMC) at 6 and 12 weeks of age in both male and female. Microcomputer tomography analysis of trabecular bone at distal femur revealed 3-fold (male) and 14-fold (female) higher bone volume/tissue volume (BV/TV), and significantly higher trabecular number and trabecular thickness but lower trabecular separation in TG mice compared with WT littermates in both sexes. The cortical bone at femur midshaft also displayed significantly greater bone area/total area and cortical thickness in the TG mice in both sexes. Serum biochemistry analysis showed that male TG mice had higher serum alkaline phosphatase, osteocalcin, osteoprotegerin (OPG), OPG to receptor activator of NF-kB ligand (tumor necrosis family ligand superfamily, number 11; RANKL) ratio as compared with WT mice. Also, lower carboxy-terminal collagen cross-link (CTX) to tartrate-resistant acid phosphatase 5, isoform b (TRAPc5b) ratio was observed in TG mice compared with WT littermates in both male and female. Histomorphometry data demonstrated that both male and female TG mice had significantly higher cortical and trabecular mineralizing surface/bone surface and bone formation rate compared with sex-matched WT mice. Gene expression analysis demonstrated higher expression of Alp, OC, Opg, and Opg to Rankl ratio in bone tissue in the TG mice compared with WT littermates. Our data indicate that WNT16 is critical for positive regulation of both cortical and trabecular bone mass and structure and that this molecule might be targeted for therapeutic interventions to treat osteoporosis.

Non-linear pattern of age-specific bone mineral density and related factors in women: data from the 5th Korea National Health and Nutrition Examination Survey.

Age-specific bone mineral density (BMD) of Korean women showed a nonlinear pattern. According to our study, this pattern could be mainly attributed to the nonlinear effects of body composition. Interventions targeting these factors in premenopausal women could be critical for achieving peak BMD. The patterns of age-specific bone mineral density (BMD) of femur and spine in women showed a non-unidirectional decrease, with ups and downs around the point of achieving peak BMD, that are not evident in men. We investigated the factors associated with these age-specific BMD in women using linear and nonlinear models. A total of 4681 women recruited during the 5th Korean National Health and Nutrition Examination Survey 2010-2011 (KNHANES V) were included. A range of related factors were considered including body compositional, reproductive, and socio-behavioral factors. Age-specific BMD was demonstrated using a generalized additive model (GAM) with smoothing spline transformation. Age, lean body mass, fat mass, and age at menarche were significant predictors of BMD in premenopausal women. The GAM plot of BMD according to age revealed two peaks for total femur, femoral neck, and lumbar spine. After adjustment for body compositional factors, the peaks flattened. In the full model, the pattern for lumbar spine showed a single peak around the mid-40s. The GAM showed a generally better performance than the linear model for BMD at all three sites. Reduced models that included only lean body mass and fat mass best explained the variance of BMD in GAMs. The BMD of Korean women in reproductive period could be largely attributed to the nonlinear effects of age and body compositional factors. Intervention targeting these factors could be critical for maintaining peak BMD.

Liver Enzymes and Bone Mineral Density in the General Population.

Liver enzyme serum levels within and just above the normal range are strong predictors of incident morbidity and mortality in the general population. However, despite the close links between hepatic pathology and impaired bone health, the association of liver enzymes with osteoporosis has hardly been investigated. The aim of the present study was to clarify whether serum liver enzyme levels in the general population are associated with bone mineral density. This was an observational, cross-sectional study. Participants and Main Outcome: Data on 13 849 adult participants of the Third National Health and Nutrition Examination Survey were used to quantify the independent associations of γ-glutamyltransferase, alanine transaminase, and aspartate transaminase with femoral neck bone mineral density assessed by dual-energy x-ray absorptiometry. In multiple regression models adjusting for numerous confounding variables, γ-glutamyltransferase showed a weak inverse association with bone mineral density (P = .0063). There also was limited evidence of a nonmonotonous relationship with alanine transaminase, with peak bone mineral density in the second quartile of enzyme activity (P = .0039). No association was found for aspartate transaminase. Although mechanistically plausible associations were found in the present study, the rather weak nature of these patterns renders it unlikely that liver enzyme levels could be of substantial use for osteoporosis risk stratification in the general population.

Use of proton pump inhibitors is associated with fractures in young adults: a population-based study.

Proton pump inhibitors (PPIs) are associated with risk for fracture in osteoporotic adults. In this population-based study, we found a significant association between PPIs and fracture in young adults, with evidence of a dose-response effect. Young adults who use PPIs should be cautioned regarding risk for fracture. Proton pump inhibitors (PPIs) are associated with fracture in adults with osteoporosis. Because PPI therapy may interfere with bone accrual and attainment of peak bone mineral density, we studied the association between use of PPIs and fracture in children and young adults. We conducted a population-based, case-control study nested within records from general medical practices from 1994 to 2013. Participants were 4-29 years old with ≥ 1 year of follow-up who lacked chronic conditions associated with use of long-term acid suppression. Cases of fracture were defined as the first incident fracture at any site. Using incidence density sampling, cases were matched with up to five controls by age, sex, medical practice, and start of follow-up. PPI exposure was defined as 180 or more cumulative doses of PPIs. Conditional logistic regression was used to estimate the odds ratio and confidence interval for use of PPIs and fracture. We identified 124,799 cases and 605,643 controls. The adjusted odds ratio for the risk of fracture associated with PPI exposure was 1.13 (95% CI 0.92 to 1.39) among children aged < 18 years old and 1.39 (95% CI 1.26 to 1.53) among young adults aged 18-29 years old. In young adults but not children, we observed a dose-response effect with increased total exposure to PPIs (p for trend <0.001). PPI use was associated with fracture in young adults, but overall evidence did not support a PPI-fracture relationship in children. Young adults who use PPIs should be cautioned regarding potentially increased risk for fracture, even if they lack traditional fracture risk factors.

Faktor Risiko Osteopenia pada Remaja

Introduction: Osteopenia is a condition which means the bone mineral density (BMD/Bone Mineral Density) is lower than the normal peak BMD but not low enough to be classified as osteoporosis. Risk factors that can lead to osteopenia are smoking, drinking softdrinks, less activity, dieting, rarely affected sun and drinking alcohol. This study aimed to identify the risk factors of asteopenia on adolesences. Method: The study design used descriptive. The sample used was a high school student Magetan total of 100 respondents were collected by random sampling. Data were collected with questionniare and analyzed with procentage. Result: From the results of a study of 100 respondents was obtained from less activity factors 5 respondents (5%), rarely exposed to sunlight obtained 32 respondents (32%), dieting factor obtained 34 respondents (34%) smoke got 49 respondents (49%), drink alcohol obtained 18 respondents (18%),and drink softdrink obtained 40 respondents (40%) at risk for osteopenia. Discussion: From the results it can be concluded that smoking is the highest risk factor in the incidence of osteopenia among adolescent. Nicotine contained in cigarettes can reduce absobsi calcium in the bones and cause a decrease in bone density. For any subsequent researchers are expected to conduct research about the relationship of smoking with risk factors for adolescent osteopenia .

Dietary isoflavones and bone mineral density during midlife and the menopausal transition: cross-sectional and longitudinal results from the Study of Women's Health Across the Nation Phytoestrogen Study.

This study aims to examine cross-sectional and longitudinal relations between dietary intake of isoflavones and bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN) in black, white, Chinese, and Japanese women during the menopausal transition. We tested whether tertiles of isoflavone intake were associated with baseline BMD when all women were premenopausal or early perimenopausal. To analyze whether isoflavone intake was associated with longitudinal BMD, we fitted piecewise linear models to repeated measurements of baseline-normalized LS or FN BMD as functions of time before or after the final menstrual period (FMP) date. Multiply adjusted mean FN BMD values of premenopausal Japanese women were monotonically positively related to isoflavone consumption (P for trend = 0.0003). Otherwise, no statistically significant baseline associations were observed. During the period of 1 year before the FMP through 5 years after the FMP, all participants lost LS and FN BMD. Loss was unrelated to isoflavone intake, except for Japanese women during the period of 1 year before the FMP to 2 years after the FMP: higher tertiles of isoflavone intake were associated with greater annual LS BMD loss rates (P for trend = 0.01) and FN loss rates (P for trend = 0.04). In Japanese women, higher isoflavone intake is associated with higher peak FN BMD but also with greater rates of LS and FN BMD loss during the menopausal transition. Results for the other racial/ethnic groups did not support a relation between dietary intake of isoflavones and either peak BMD or BMD loss during the menopausal transition.

Peak Bone Mineral Density Levels in Normal Omanis, a Pilot Study

Aims: To determine normal peak bone mineral density (PBMD) values in a cohort of healthy Omanis. Study Design: Cross-sectional study. Place and Duration of the study: in the Departments of Nuclear Medicine and Medicine at Sultan Qaboos University Hospital in Oman between 2012 and 2013. Methodology: Omani employees aged between 25 to 34 years at Sultan Qaboos University Hospital (SQUH) were randomly chosen and invited to participate. Fifty normal males and 50 females were studied. Their fully informed consent was obtained to establish PBMD values using dual energy X-ray absorptiometry (DXA). Blood was also taken to determine their serum calcium, Original Research Article Hadhrami et al.; BJMMR, 8(6): 526-531, 2015; Article no.BJMMR.2015.475 527 phosphate, alkaline phosphatase and parathyroid hormone (PTH) levels as well as a complete blood count (CBC), serum sodium, potassium and creatinine levels. Statistical analysis was done based on Hologic Delphi Reference Values on a reference curve generation using z-scores and the fitting a polynomial curve of third order. This data was interpolated, sampled and tested to verify the initial results. Results: Our results show that normal Omani PBMD values of L1-L4 in women were 0.94 0.11 and in men 0.99  0.12 g/cm. These are significantly lower than those of a normal Caucasian population by 26.5% in women P-value (<.001) and by 23.8% in men P-value (<.001). Only three subjects had values on or slightly above the mean Caucasian level but sixteen had values on or below -2SD. The blood tests were within the normal range in all subjects. Conclusion: Omani mean PBMD values obtained in this study are substantially lower than Caucasian values. To avoid the use of inappropriate anti-resorptive therapy we should consider revising our reference range. We recommend using normal Asian reference values as they are almost identical to those obtained in this study until a normal reference range is established for this country.

The Analysis of Hormone Replacement Therapy Influence on Il-6 Expression and Mandible T-Score of Postmenopausal Women

Objective: Aim of the study was to investigate the effect of Hormone Replacement Therapy (HRT) on IL-6 gene expression and salivary concentration, bone mineral density (BMD) and T-score (the number of standard deviations below the average for a young adult at peak BMD) of mandible in menopausal women. Materials and Methods: Study was carried out on a group of 60 women during menopause - 30 untreated (control group) and 30 treated with HRT (test group). 30 patients has undergone natural menopause and other half of women were after ovariectomy. Examination of IL-6 gene expression was conducted on peripheral blood lymphocytes (PBL) and buccal epithelial lining (BEL). Saliva samples were collected and densitometry was conducted on the mandible. To evaluate the results of densitometric examination T-score index was calculated. Results: T-score index of the control groups reached values below (-2). T-score results for test group were higher than those in control group. HRT results in a slight decrease of the IL-6 level in saliva of the test group,compared with control group, but the differences between groups were not statistically significant. Only in groups after natural menopause treated with HRT significant increase of IL-6 gene expression was stated when compared to control groups. Conclusions: HRT has a significant osteoprotective effect on the mandible. This local beneficial effect of HRT may be exerted, inter alia, by local decrease in salivary concentration of proinflammatory cytokine IL-6, but further research is required to clearly confirm this thesis. Results of IL-6 gene expression do not allow stating any clear thesis. It needs to be clarified if HRT has the same effect on cytokine gene expression as hormones produced by ovaries.

The relationship between men hip geometric structure and body composition in Shanghai area

Objective To investigate the correlation between hip geometric structure and body composition including bone mineral density （BMD） , lean mass, and fat mass. Methods A total of 1 168 healthy mail residents in Shanghai were divided into three age groups ： young （ 21-40 years ） , middle-aged （ 41-60 years） , and older （ 〉 60 years） , and were evaluated by assessing BMD of lumber spine and hip, total lean mass, total fat mass, and hip geometric parameters such as cross-sectional area, average cortical thickness, and bucking ratio at narrow neck, intertrochanteric, and shaft. Correlation analysis was performed by Pearson （normal distribution ） or Pearson （ abnormal distribution） test, and attribution analysis was performed by stepwise test of multiple regressions. Results （ 1 ） The peak BMD values of the spine and total hip were observed in the 21-30 years old group. The peak lean mass and fat mass were observed in the 31-40 years old group. The hip geometric parameters including cross-sectional area and average cortical thickness at narrow neck, intertrochanteric and shaft, reached peaks by 21-30 years, and valley bucking ratio at three regions mentioned above was observed by 21-30 years as well. （2） The correlation between hip BMD and hip geometric structure was most marked at all three regions. Lean mass showed significantly positivecorrelalion with cross-sectional are and negalive correlation with bueking ratio.The effect of fat mass on hip geometric purneters al the three regions was inconsistent （ 3 ） Fat mass and percentage of body fat （ Fat % ） showed negalive correlation wilh cross-sectional area and average corlical Ihiekness and positive correlation with bucking ratio in young group. However, the negative contribution produced by fat mass and Fat% to hip geometric structure became weaker gradually in middle-aged and older groups. （4） Limb lean mass yiehled the largest positive eontrihution to cross- sectioual area and avere cortical thickness at all three regions in young group, However, Ihe conlribution produced by trunk lean mass became lhe largest positive conlribution to cross-seelional area and average em＇tic~ll thickness in older group. Conclusions Ainmg all the body composition parameters, hip BMD has showed the most marked correlaltion with hip geometric structure. Lean mass is ranked the second in the correlalion. The impacts of fat mass and lean mass on hip geometry are changing with aging and their different tissue distributions. Key words: Hip geometric structure; Body compsition; Bone mineral density; Lean mass ; Fat mass

Bone alterations associated with HIV.

HIV infection and initiation of antiretroviral therapy (ART) have been consistently associated with decreased bone mineral density (BMD), with growing evidence linking HIV to an increased risk of fracture. This is especially concerning with the expanding number of older persons living with HIV. Interestingly, recent data suggest that HIV-infected children and youth fail to achieve peak BMD, possibly increasing their lifetime risk of fracture. Elucidating the causes of the bone changes in HIV-positive persons is challenging because of the multifactorial nature of bone disease in HIV, including contribution of the virus, immunosuppression, ART toxicity, and traditional osteoporosis risk factors, such as age, lower weight, tobacco, and alcohol use. Thus, practitioners must recognize the risk of low BMD and fractures and appropriately screen patients for osteoporosis if risk factors exist. If fractures do occur or elevated fracture risk is detected through screening, treatment with bisphosphonate medications appears safe and effective in the HIV+population.

한국 남성의 연령에 따른 부위별 골밀도 변화 및 골 소실률

국민건강영양조사 제 5기 1 2차년도에 참여한 남성을 대상으로 연령에 따른 부위별 골밀도 변화, 골 소실률에 대해서 알아보고자 시도 하였다. 연령에 따른 골밀도 변화를 가장 잘 보여 주기 위해 Cubic regression을 사용하였고, 척추, 대퇴경부, 대퇴골 전자부, Ward 부위 골밀도 차이는 분산분석을 이용하여 분석하였다. 연구결과, 요추, 대퇴골 전체, 대퇴경부, 대퇴골 전자부, Ward 부위의 최대 골밀도는 20-24세였으며, 75-79세에서 골 소실률이 가장 높았다. 따라서, 남성에서는 75세 이상에서 골다공증의 집중적인 관리가 필요할 것이며, 남성에서의 골다공증 진단기준은 국제 임상 골밀도 학회(The International Society for Clinical Densitometry; ISCD)의 지침을 따르는 방안을 고려해 봐야 할 것이다. This study examined the age-related bone mineral density (BMD), accumulated bone loss rate (ABLR) at different skeletal sites in Korean men using the data from the Korea National Health and Nutrition Examination Survey (KNHANES)(the 1st (2010), 2nd (2010) and the year at the 5th survey). The cubic regression model was found to be the best for describing the age-related changes in BMD. The lumbar spine, total hip, femoral neck, trochanter, Ward's triangle in the bone mineral density difference were analyzed by ANOVA. The peak BMD was at 20-24 years at the lumbar spine, total hip, femoral neck, trochanter, Ward's triangle, and the 75-79 years of age group had the highest Accumulated Bone Loss Rate. Therefore, intensive management will be necessary for men over 75 years, and a diagnosis of osteoporosis in Korean men should be made according to The International Society for Clinical Densitometry; ISCD.

Menopause-related osteoporosis

Peak bone mass for spine and hip is reached in the mid-twenties and adolescents should be counselled on adequate nutrition to ensure sufficient calcium intake, regular weight-bearing exercise, maintaining normal body weight, avoiding smoking and limiting alcohol intake. These measures are important to prevent osteopenia and osteoporosis by obtaining a maximum peak bone mineral density (BMD) and to maintain it by avoiding excessive bone loss. One year before the onset of menopause, however, as a result of oestrogen deficiency, there is an increase in osteoclastic activity without a similar increase in osteoblastic activity, resulting in accelerated bone loss. The average decrease in BMD during the menopausal transition is estimated to be about 10% and a woman’s risk of sustaining an osteoporotic or fragility fracture doubles for each decade after the age of fifty. Half of women older than 50 years of age will be osteopenic compared to 10% who are osteoporotic and only 40% will have normal BMD. This article...

SIBLING family genes and bone mineral density: Association and allele-specific expression in humans

Osteoporosis is a common complex disorder with reduced bone mineral density (BMD) and increased susceptibility to fracture. Peak BMD is one of the primary determinants of osteoporotic fracture risk, and is under substantial genetic control. Extracellular matrix, a major component of the bone, influences BMD by regulating mineral deposition and maintaining cellular activity. It contains several SIBLING family proteins, null mutations of which cause mineralization defects in humans. In this study, we tested 59 single-nucleotide polymorphisms (SNPs) located in the 5 SIBLING family genes (DSPP, DMP1, IBSP, MEPE and SPP1) for association with normal variation in peak BMD in healthy men and women. We measured femoral neck (FN) and lumbar spine (LS) areal BMD by dual energy x-ray absorptiometry (DXA) in 1692 premenopausal European-American women, 512 premenopausal African-American women and 715 European-American men. SNPs were tested for association with FN and LS-BMD in the 3 subsamples. In the European-American women, we observed association (p≤0.005) with LS-BMD for SNPs in DSPP, IBSP and MEPE, and for FN-BMD with SNPs in DMP1 and IBSP. Allele-specific regulation of gene expression (ASE) is an important mechanism in which an allele giving rise to modest influence in transcript abundance might result in a predisposition to disease. To identify whether there was ASE of SIBLING family genes at these SNPs, we examined 52 human bone samples obtained from the femoral neck during surgical hip replacement (27 female, 25 male; 44 European-American and 8 African-American). We observed unidirectional ASE for the IBSP gene, with lower expression of the G allele compared to the A allele for SNP rs17013181. Our data suggest that SNPs within the SIBLING genes may contribute to normal variation of peak BMD. Further studies are necessary to identify the functional variants and to determine the mechanisms underlying the differences in ASE and how these differences relate to the pathophysiology of osteoporosis.

Bone mineral density, growth, pubertal development and other parameters in Brazilian children and young adults with sickle cell anaemia

To evaluate the occurrence of low bone mineral density (BMD) and its relationship with clinical and laboratorial characteristics in children and young adults with sickle cell anaemia living in Northeast-Brazil, and to assess the role of radiography in diagnosing low BMD. Bone mineral density of lumbar spine was measured by dual energy X-ray absorptiometry (DXA) in 27 patients with Sickle cell anaemia (SCA) aged 7-28years. Clinical history, calcium and calorie intake, laboratory measurements, anthropometrics and pubertal development were assessed, and X-rays were obtained. Z-scores and T-scores for weight, height, Body Mass Index (BMI) and BMD were calculated using age and gender matched reference data. Mean lumbar spine BMD Z-scores and T-scores were -1.81 SD in boys and -0.80 SD in girls. BMD Z-scores were below -2 SD in 33.3% of girls and in 46.7% of boys. Low BMD (<-2 SD) occurred significantly more in patients with low height-for-age (P=0.02), low weight-for-age (P=0.001) and low BMI-for-age (P=0.006). No significant relationships were found between BMD and other clinical and laboratory parameters. Radiography had a sensitivity of 75% and a specificity of 36% to detect low BMD, and was considered not useful in this context. Patients with low height and/or low weight-for-age seem to be at high risk for developing low BMD.

Effects of icariin and genistein on peak bone mass in rats

To compare the effects of icariin (ICA) and genistein (GEN) on rats bone peak mass and thus screen for a drug that can more effectively prevent osteoporosis. Totally 36 one-month SD rats were randomly divided into three groups: ICA group [25 mg/(kg·d), intragastric administration], GEN group [10 mg/(kg·d), intragastric administration], and control group (fed with equal volume of distilled water). The body weight was monitored weekly and the bone mineral density of total body was measured monthly. All rats were sacrificed three months later. The femoral bone mineral density and the serum levels of osteocalcin and anti-tartaric acid phosphatase 5b, N-terminal propeptide of type 1 procollagen, and C-terminal propeptide of type 1collagen were measured. The bone microarchitectures were analyzed with micro-CT and the bone biomechanics properties were tested with universal material machine. The body weight and organ index showed no significant difference among these three groups(P>0.05). No obvious pathological change was found. The bone mineral density was also not significantly different in the first and second months; however, in the third months, the ICA group had significant higher bone mineral density for both total body and femur than those in the control and GEN group (P<0.05). The same trends were found for both femur bone mineral density and whole-body bone mineral density (P<0.05). The ICA group also had significantly higher serum levels of osteocalcin (P<0.05) and lower level of anti-tartaric acid phosphatase 5b(P<0.05). Besides, rats in the ICA group had significantly larger bone volume/tissue volume, trabecular thickness, and trabecular number than the control group, whereas the trabecular spacing and model coefficients were signicantly lower(all P<0.05), which, however, were not significantly different between ICA group and GEN group (P>0.05). Femoral maximum load, Youg's modulus, and yield load were significantly higher in these two groups than in the control group (P<0.05), which, again, were not significantly different between ICA group and GEN group (P>0.05). Orally administered ICA is more efficient than GEN in inhibiting resorption and promoting bone formation, and thus can dramatically improve the peak bone mineral density and bone quality.

Associations Between Ethnicity, Body Composition, and Bone Mineral Density in a Southeast Asian Population

Chinese men in Singapore have a higher incidence of hip fractures than Malay and Indian men. We investigated whether there were corresponding ethnic differences in peak bone mineral density (BMD) in young men and whether differences in body composition influenced peak BMD. This was a cross-sectional study of healthy volunteers in a tertiary medical center. A total of 100 Chinese, 82 Malay, and 80 Indian men aged 21 to 40 years, with body mass index between 18 and 30 kg/m(2) underwent dual-energy x-ray absorptiometry to assess BMD, lean mass (LM) and fat mass (FM), and magnetic resonance imaging to quantify abdominal subcutaneous and visceral adipose tissue. Multiple linear regression models, with adjustment for age and height (as a proxy for skeletal size), were used. Malay and Indian men had significantly higher BMD than Chinese men at the lumbar spine (Malay: B, 0.06 ± 0.02, P = .001; Indian: B, 0.03 ± 0.02, P = .049), femoral neck (Malay: B 0.04 ± 0.02, P = .034; Indian: B, 0.04 ± 0.02, P = .041), hip (Malay: B, 0.05 ± 0.02, P = .016; Indian: B, 0.06 ± 0.02, P = .001), and ultradistal radius (Malay: B, 0.03 ± 0.01, P < .001; Indian: B, 0.02 ± 0.01, P = .029), and this difference was retained after adjustment for LM and FM, except in Malay men at the femoral neck and in Indian men at the ultradistal radius. LM was an important independent determinant of BMD at all sites, whereas FM, subcutaneous adipose tissue, and visceral adipose tissue were not significantly associated with BMD at any site. Lower peak BMD in Chinese men may partly explain the higher fracture incidence in this ethnic group. Further studies are needed to elucidate the reasons for these ethnic differences in bone accumulation.

Mechanical Assessment of Local Bone Quality to Predict Failure of Locked Plating in a Proximal Humerus Fracture Model

The importance of osteoporosis in proximal humerus fractures is well recognized. However, the local distribution of bone quality in the humeral head may also have a significant effect because it remains unclear in what quality of bone screws of standard implants purchase. The goal of this study was to investigate whether the failure of proximal humerus locked plating can be predicted by the DensiProbe (ARI, Davos, Switzerland). A 2-part fracture with metaphyseal impaction was simulated in 12 fresh-frozen human cadaveric humeri. Using the DensiProbe, local bone quality was determined in the humeral head in the course of 6 proximal screws of a standard locking plate (Philos; Synthes GmbH, Solothurn, Switzerland). Cyclic mechanical testing with increasing axial loading until failure was performed. Bone mineral density (BMD) significantly correlated with cycles until failure. Head migration significantly increased between 1000 and 2000 loading cycles and significantly correlated with BMD after 3000 cycles. DensiProbe peak torque in all screw positions and their respective mean torque correlated significantly with the BMD values. In 3 positions, the peak torque significantly correlated with cycles to failure; here BMD significantly influenced mechanical stability. The validity of the DensiProbe was proven by the correlation between its peak torque measurements and BMD. The correlation between the peak torque and cycles to failure revealed the potential of the DensiProbe to predict the failure of locked plating in vitro. This method provides information about local bone quality, potentially making it suitable for intraoperative use by allowing the surgeon to take measures to improve stability.

Gene-by-diet interactions influence calcium absorption and bone density in mice.

Dietary calcium (Ca) intake is needed to attain peak bone mineral density (BMD). Habitual low Ca intake increases intestinal Ca absorption efficiency to protect bone mass, but the mechanism controlling, and the impact of genetics on, this adaptive response is not clear. We fed 11 genetically diverse inbred mouse lines a normal (0.5%) or low (0.25%) Ca diet from 4 to 12 weeks of age (n = 8 per diet per line) and studied the independent and interacting effects of diet and genetics on Ca and bone metabolism. Significant genetic variation was observed in all bone, renal, and intestinal phenotypes measured including Ca absorption. Also, adaptation of Ca absorption and bone parameters to low dietary Ca was significantly different among the lines. Ca absorption was positively correlated to femur BMD (r = 0.17, p = 0.02), and distal femur bone volume/tissue volume (BV/TV) (r = 0.34, p < 0.0001). Although Ca absorption was correlated to 1,25 dihydroxyvitamin D (1,25(OH)2 D) (r = 0.35, p < 0.0001), the adaptation of Ca absorption to low Ca intake did not correlate to diet-induced adaptation of 1,25(OH)2 D across the 11 lines. Several intestinal proteins have been proposed to mediate Ca absorption: claudins 2 and 12, voltage gated Ca channel v1.3 (Cav1.3), plasma membrane Ca ATPase 1b (PMCA1b), transient receptor potential vanilloid member 6 (TRPV6), and calbindin D9k (CaBPD9k). Only the mRNA levels for TRPV6, CaBPD9k, and PMCA1b were related to Ca absorption (r = 0.42, 0.43, and 0.21, respectively). However, a significant amount of the variation in Ca absorption is not explained by the current model and suggests that novel mechanisms remain to be determined. These observations lay the groundwork for discovery-focused initiatives to identify novel genetic factors controlling gene-by-diet interactions affecting Ca/bone metabolism.

Body Fat Mass is a Strong and Negative Predictor of Peak Stimulated Growth Hormone and Bone Mineral Density in Healthy Adolescents During Transition Period

The adipose tissue has detrimental effects on growth hormone secretion, even in the absence of obesity. The majority of previous studies have shown an inverse relationship between fat mass and the growth hormone response to several stimulation tests in adults and in children. The contribution of body fat mass on growth hormone response to provocative tests during the transition age is not known. We analyzed the GH-IGF1 axis by GHRH-arginine test in 30 healthy adolescents with normal stature during the transition period from 14 to 18 years. All subjects underwent body composition analysis by dual-energy X-ray absorptiometry (DXA). We found that total body fat mass was inversely correlated with peak GH to provocative test (r=-0.6, p=0.004). GH deficiency was shown in 2 of our healthy patients if diagnosis was based on GH peak below 19 μg/l. Both children who failed the GHRH-arginine were overweight (BMI for age above 85th percentile). However, their GH status was normal when assessed by insulin tolerance test. Multivariate analysis demonstrated strong correlation between peak stimulated GH and measures of body adiposity, including body mass index and fat mass index, with the latter showing the most important effect on GH secretion. Fat mass index alone explained 34.5% of the variability in peak GH. This study has shown for the first time that during the transition period, GH response to GHRH-arginine test is strongly influenced by body composition, and cutoff values appropriate for overweight and obese adolescents are needed.