Long-term low-dose glucocorticoid therapy in hyperandrogenized women: utility and effects on bone mineral content and hypothalamic-pituitary-adrenocortical function.

The effect of chronic low-dose glucocorticoid administration on bone mineral content and corticotrope reserve was investigated in 12 hyperandrogenized women treated with 1-6 mg oral evening doses of 16 beta-methylprednisone for 12-58 months. The hypothalamic-pituitary-adrenal axis was evaluated in 9 patients by a standard metyrapone test after 45-75 days off steroid therapy. All the patients had a normal rise in serum 11-deoxycortisol after metyrapone. Bone densitometry was assessed at the end of therapy using dual photon absorptiometry. No significant differences between patients and age-matched hyperandrogenic controls were found either in spine (1.048 +/- 0.096 vs. 1.023 +/- 0.175 g/cm2) or femoral neck (0.863 +/- 0.115 vs. 0.899 +/- 0.216 g/cm2), respectively. In conclusion, absence of quantitative bone mass reduction and normal corticotrope reserve were observed even after 58 months of daily steroid administration.     

Mass properties of the human mandible

Computer simulation of human masticatory dynamics requires specification of the jaw's mass properties. These are difficult to estimate, especially in living subjects. Here, we used calibrated computed tomography (CT) to determine the properties of eight osseous jaw specimens with adult dentitions. When the CT numbers were converted to mineral densities, the mean estimated jaw mass was 13% greater than the mean wet weight. Putative bone marrow accounted for an extra 7% of mass. The mean bone densities for the sample were very consistent (1.72+/-0.02g/cm(3)). The mass and geometric centers were close (mean linear difference 0.43+/-0.18mm), and were always located anteroposteriorly between the second and third molars. The largest moment of inertia (MI) occurred around the jaw's superoinferior axis, and the smallest around its transverse axis. Bone marrow added an extra 7% to the MIs. There were linear relationships between the mandibular length (expressed three dimensionally), the actual and estimated masses, and the moments of inertia. Our study suggests non-invasive imaging (such as magnetic resonance) and even direct linear measurement, may be adequate to estimate jaw mass properties in living humans.     

Cross sectional and longitudinal study of bone mineral content of the distal forearm in adult premenopausal women

The range of fat corrected distal forearm mineral content (FMC) (at a site which comprises approximately 75% cortical and 25% trabecular bone) and the effect of aging on FMC were determined in normal premenopausal women. In 106 women (mean age 39; range 18-56) the mean FMC was 1.184 (SD 148) g/cm; fat correction increased this to 1.239 (SD 148) g/cm. There were significant correlations between fat corrected FMC and height, weight and BMI (r greater than 0.16; P less than 0.05). In 43 of these women (mean age 35; range 18-51) repeat measurements of FMC were performed. The last measurement was separated from the first by a mean time interval of 27 +/- 3 months. There was no significant change in uncorrected FMC (baseline 1.185 +/- 0.21 g/cm compared with their final measurement 1.182 +/- .020 g/cm; P = 0.51). Fat-corrected FMC (baseline 1.229 +/- .021 g/cm compared with 1.223 +/- .020 g/cm later) tended to decrease although this change was not significant (P = 0.06). Age ranked cusum analysis demonstrated a non-significant fat-corrected rate of change in FMC of -.3% yr in those over 35 years of age (P less than 0.10). This data suggests that if there is any distal forearm bone loss before the menopause it is negligible.     

Exercise,smoking, and calcium intake during adolescence and early adulthood as determinants of peak bone mass. Cardiovascular Risk in Young Finns Study Group.

OBJECTIVE--To evaluate the contribution to peak bone mass of exercise, smoking, and calcium intake in adolescents and young adults. DESIGN--Prospective cohort study with end point measurement (bone mineral density) after 11 years'' follow up for lifestyle. SETTING--Five university hospital clinics. SUBJECTS--264 (153 females, 111 males) subjects aged 9 to 18 years at the beginning of the follow up and 20 to 29 years at the time of measurement of bone mineral density. MAIN OUTCOME MEASURE--Bone mineral density of lumbar spine and femoral neck by dual energy x ray absorptiometry; measures of physical activity and smoking and estimates of calcium intake repeated three times during follow up. RESULTS--In the groups with the lowest and highest levels of exercise the femoral bone mineral densities (adjusted for age and weight) were 0.918 and 0.988 g/cm2 for women (P = 0.015, analysis of covariance) and 0.943 and 1.042 g/cm2 for men (P = 0.005), respectively; at the lumbar spine the respective values were 1.045 and 1.131 (P = 0.005) for men. In men the femoral bone mineral densities (adjusted for age, weight, and exercise) were 1.022 and 0.923 g/cm2 for the groups with the lowest and highest values of smoking index (P = 0.054, analysis of covariance). In women the adjusted femoral bone mineral density increased by 4.7% together with increasing calcium intake (P = 0.089, analysis of covariance). In multiple regression analysis on bone mineral density of the femoral neck, weight, exercise, age, and smoking were independent predictors for men; with weight, exercise, and age for women. These predictors together explained 38% of the variance in bone mineral density in women and 46% in men. At the lumbar spine, weight, smoking, and exercise were predictors for men; and only weight for women. CONCLUSIONS--Regular exercise and not smoking is important in achieving maximal peak bone mass in adolescents and young adults.     

Protein-containing nutrient supplementation following strength training enhances the effect on muscle mass, strength, and bone formation in postmenopausal women.

We evaluated the response of various muscle and bone adaptation parameters with 24 wk of strength training in healthy, early postmenopausal women when a nutrient supplement (protein, carbohydrate, calcium, and vitamin D) or a placebo supplement (a minimum of energy) was ingested immediately following each training session. At inclusion, each woman was randomly and double-blindedly assigned to a nutrient group or a placebo (control) group. Muscle hypertrophy was evaluated from biopsies, MRI, and dual-energy X-ray absorptiometry (DEXA) scans, and muscle strength was determined in a dynamometer. Bone mineral density (BMD) was measured using DEXA scans, and bone turnover was determined from serum osteocalcin and collagen type I cross-linked carboxyl terminal peptide. The nutrient group improved concentric and isokinetic (60 degrees /s) muscle strength from 6 to 24 wk by 9 +/- 3% (P < 0.01), whereas controls showed no change (1 +/- 2%, P > 0.05). Only the nutrient group improved lean body mass (P < 0.05) over the 24 wk. BMD responded similarly at the lumbar spine but changed differently in the two groups at the femoral neck (P < 0.05) [control: 0.943 +/- 0.028 to 0.930 +/- 0.024 g/mm(3) (-1.0 +/- 1.4%); nutrient group: 0.953 +/- 0.051 to 0.978 +/- 0.043 g/mm(3) (3.8 +/- 3.4%)] when adjusted for age, body mass index, and BMD at inclusion. Bone formation displayed an interaction (P < 0.05), mainly caused by increased osteocalcin at 24 wk in the nutrient group. In conclusion, we report that nutrient supplementation results in superior improvements in muscle mass, muscle strength, femoral neck BMD, and bone formation during 24 wk of strength training. The observed differences following such a short intervention emphasize the significance of postexercise nutrient supply on musculoskeletal maintenance.     

Effect of low-repetition jump training on bone mineral density in young women.

The hypothesis of the present study was that low-repetition and high-impact training of 10 maximum vertical jumps/day, 3 times/wk would be effective for improving bone mineral density (BMD) in ordinary young women. Thirty-six female college students, with mean age, height, and weight of 20.7+/-0.7 yr, 158.9+/-4.6 cm, and 50.4+/-5.5 kg, respectively, were randomly divided into two groups: jump training and a control group. After the 6 mo of maximum vertical jumping exercise intervention, BMD in the femoral neck region significantly increased in the jump group from the baseline (0.984+/-0.081 vs. 1.010+/-0.080 mg/cm2; P<0.01), although there was no significant change in the control group (0.985+/-0.0143 vs. 0.974+/-0.134 mg/cm2). And also lumbar spine (L2-4) BMD significantly increased in the jump training group from the baseline (0.991+/-0.115 vs. 1.015+/-0.113 mg/cm2; P<0.01), whereas no significant change was observed in the control group (1.007+/-0.113 vs. 1.013+/-0.110 mg/cm2). No significant interactions were observed at other measurement sites, Ward's triangle, greater trochanter, and total hip BMD. Calcium intakes and accelometry-determined physical daily activity showed no significant difference between the two groups. From the results of the present study, low-repetition and high-impact jumps enhanced BMD at the specific bone sites in young women who had almost reached the age of peak bone mass.     

北京地区汉族妇女雌激素受体基因XbaI多态性与骨密度和体重指数的关系

为探讨北京地区汉族妇女雌激素受体（ER）基因XbaI多态性与骨密度的关系,采用双能X线吸收仪检测腰椎、股骨及前臂骨密度;采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）法,对179例北京地区汉族妇女ER基因XbaI多态性进行分析。北京地区汉族妇女ER基因XX、Xx和xx基因型频率分布为0.302、0.464和0.234,绝经前与绝经后妇女XbaI型基因频率分布有明显差异,绝经后妇女腰椎骨密度（0.836±0.18）g/cm²明显低于绝经前妇女（1.038±0.14);绝经后妇女骨质疏松症的发病率为54%。ER基因XbaI基因型频率分布有明显的种族差异并受绝经影响,ER基因XbaI基因型与骨密度无明显相关性。与体重和BMI有明显相关性。     

Bone mineral loss in young women with amenorrhoea.

OBJECTIVE--To examine the impact of amenorrhoea on bone mineral density in women of reproductive age. DESIGN--Cross sectional study of 200 amenorrhoeic women compared with normally menstruating controls. SETTING--Teaching hospital outpatient clinic specialising in reproductive medicine. SUBJECTS--200 Women aged 16-40 with a past or current history of amenorrhoea from various causes and of a median duration of three years, and a control group of 57 age matched normal volunteers with no history of menstrual disorder. MAIN OUTCOME MEASURE--Bone mineral density in the lumbar spine (L1-L4) as measured by dual energy x ray absorptiometry. RESULTS--The amenorrhoeic group showed a mean reduction in bone mineral density of 15% (95% confidence interval 12% to 18%) as compared with controls (mean bone mineral density 0.89 (SD 0.12) g/cm2 v 1.05 (0.09) g/cm2 in controls). Bone loss was related to the duration of amenorrhoea and the severity of oestrogen deficiency rather than to the underlying diagnosis. Patients with a history of fracture had significantly lower bone density than those without a history of fracture. Ten patients had suffered an apparently atraumatic fracture. CONCLUSIONS--Amenorrhoea in young women should be investigated and treated to prevent bone mineral loss. Menopausal women with a past history of amenorrhoea should be considered to be at high risk of osteoporosis.     

Pregnancy-associated changes in bone density and bone turnover in the physiological state: prospective data on sixteen women.

Areal bone mineral density (BMD, g/cm 2) was measured for the total body, lumbar spine and hip with dual-energy x-ray absorptiometry (DXA) before pregnancy and after delivery in sixteen women aged 21 - 35 years. Additional measurements included quantitative ultrasound indices (broadband ultrasound attenuation, BUA, at the calcaneus at baseline and at 16, 26, and 36 weeks of pregnancy, and postpartum) as well as biochemical markers of bone formation and resorption (measured before pregnancy and during pregnancy at 16, 22, 26, 30, 34, and 36 weeks of pregnancy and postpartum). The results of measurements were as follows: 1. Postpartum BMD showed a significant reduction in the total body (- 13.4 %), in the spine (- 9.2 %) and in the hip (-7.8 % at the femoral neck and - 9.2 % at the Ward's triangle) compared to pre-pregnancy values. 2. Biochemical markers of bone resorption increased by 26 weeks. 3. Bone ultrasound measurements that provide information on bone density before delivery did not change throughout pregnancy. A significant reduction of BUA (- 14.5 % compared to baseline) was observed postpartum only. These data would suggest that pregnancy-induced bone loss develops rapidly after the 36 week of pregnancy, possibly via enhanced bone resorption.     

Effect of dietary protein level and source on bone mineralization in rats

Bone mineralization was studied in rats. Animals were divided into three feeding groups: LCP - diet with 13.5% crude protein in DM (5% of gluten, 10% of casein), HCP - diet with 21.2% CP in DM (8% of gluten, 10% of casein), and LSM - diet based on grain meals and meat-bone meal (21% CP in DM). After 28 days feeding, animals were euthanased by cervical dislocation and femur bones were collected, weighed and kept frozen until analyses. Diets with 21% protein (HCP, LSM) significantly increased weight of femur bones. Despite of the substantially higher ash level (7.1%) in the LSM diet than in the LCP diet (3.4%), rats of both groups had the similar bone concentration of Ca (15.7 +/- 1.1 vs. 17.4 +/- 1.1 g/kg) and Zn (178.7 +/- 7.9 vs. 173.0 +/- 8.5 mg/kg). However bone density in LSM rats was significantly higher than in LCP ones. Although rats fed HCP diet had intermediate bone density, the bone concentration of Ca (11.4 +/- 0.5 g/kg) and Zn (145.1 +/- 2.9 mg/kg) was significantly lower, than in animals fed LCP and LSM diets. This was related to the very wide protein/calcium (37:1 g/g) and protein/zinc (5.3:1 g/mg) ratios in HCP diet. Those ratios were narrowest in the LSM diet: 16.2:1 (CP/Ca) and 2.6:1 (CP/Zn). It can be conluded that protein/mineral ratio in a diet is a very important factor in bone development, besides dietary protein and ash contents itselves.     

Regional skeletal muscle measurement: evaluation of new dual-energy X-ray absorptiometry model.

Although there is growing interest in studying muscle distribution, regional skeletal muscle (SM) mass measurement methods remain limited. The aim of the present study was to develop a new dual-energy X-ray absorptiometry (DEXA) model for estimating regional adipose tissue-free skeletal muscle mass (AT-free SM). Relationships were derived from Reference Man data between tissue-system- level components (i.e., AT-free SM, AT, skeleton, and skin) and molecular-level components including fat-free soft tissue, fat, and bone mineral. The proposed DEXA-SM model was evaluated by multiscan computerized axial tomography (CT). Twenty-seven male subjects [age, 36 +/- 12 (SD) yr; body mass, 73.2 +/- 12.4 kg; 20 were healthy, and 7 had acquired immunodeficiency syndrome] completed DEXA and CT studies. Identical landmarks for DEXA and CT measurements were selected in three regions, including calves, thighs, and forearms. There was a strong correlation for AT-free SM estimates between the new DEXA and CT methods (e.g., sum of three regions, r = 0.86, P < 0.001). Regional AT-free SM measured in the 27 subjects by DEXA and CT, respectively, were 3.44 +/- 0.60 and 3. 47 +/- 0.55 kg (difference 0.9%, P > 0.05) for calves, 10.49 +/- 1. 77 and 10.05 +/- 1.79 kg (difference 4.4%, P < 0.05) for thighs, 1. 36 +/- 0.49 and 1.20 +/- 0.41 kg (difference 13.3%, P < 0.01) for forearms, and 15.29 +/- 2.33 and 14.72 +/- 2.33 kg (difference 3.9%, P < 0.05) for the sum all three regions. Although the suggested DEXA-SM model needs minor refinements, this is a promising in vivo approach for measurement of regional SM, because DEXA is widely available, relatively inexpensive, and radiation exposure is low.     

Relation between body size and bone mineral density with special reference to sex hormones and calcium regulating hormones in elderly females.

We studied the relation between body size and bone mineral density in elderly females. The study included a total of 93 ambulatory females aged over 60 years. They were divided into 3 groups according to their body mass index (BMI; kg/m2): slender group with BMI less than 20 (n = 28), normal group with BMI of 20 to 24.9 (n = 43) and obese group with BMI greater than or equal to 25 (n = 22). Fracture incidence, bone mineral density, calcium regulating hormones and steroid hormones were studied in an intergroup comparative manner. The incidence of vertebral fracture was found to be negatively correlated with BMI (the incidences of vertebral fracture in slender, normal and obese were 78.6, 48.8 and 22.7%, respectively) and bone mineral density was also BMI-related (0.390 +/- 0.016, 0.456 +/- 0.015 and 0.493 +/- 0.018 g/cm2, respectively: p less than 0.01 in ANOVA; mean +/- SE). The number of years after menopause was shorter in patients with a higher BMI. There was no intergroup difference in serum levels of PTH, vitamin D and estrogens. On the other hand, serum levels of calcitonin, DHEA, DHEAS, delta-4 androstenedione and testosterone were found to be higher in subjects with a higher BMI. From the present results, it seems that bone mineral density is supported not only by weight-bearing stress upon bone, but also by serum levels of calcitonin and androgens in obese females.     

Low areal bone mineral density values in adolescents and young adult turner syndrome patients increase after long-term transdermal estradiol therapy

OBJECTIVE: To study the effects of long-term estradiol therapy on areal bone mineral density (aBMD) values in young adult Turner syndrome patients. METHODS: The effects of 2-year transdermal estradiol administration on lumbar, L2-L4, aBMD values were evaluated in 12 Turner syndrome patients, 15.41-21.85 years old, who had reached adult height and had low aBMD values. Puberty was induced in all at a chronological age above 12 years and menarche appeared between 13.82 and 15.40 years. The patients were on oral estrogen/gestagen therapy from then until the start of the study. Adhesive patches of 17-beta-estradiol designed to be worn for 72 h and deliver 100 microg of estradiol per day, which results in a steady mean serum estradiol level of 75 pg/ml, were used for 21 days. From day 11 to day 21, 10 mg of oral didrogesterone were also added. Nutritional and physical activity habits were evaluated at the beginning, after 1 year and at the end of the study. RESULTS: aBMD values significantly increased from 0.910 +/- 0.065 to 1.005 +/- 0.086 g/cm2 (10.06 +/- 3.37%) and the z-score from -2.38 +/- 0.63 to -1.54 +/- 0.71 (0.81 +/- 0.30 z-score). No significant differences were observed in body mass index, calcium intake and physical activity habits at the start, during and at the end of the study. CONCLUSION: In summary, our results underline the importance of estrogens for bone mass peaking and suggest that this therapeutic protocol may be useful in the therapy of Turner syndrome patients with low bone mass.     

Raloxifen prevents bone loss in castrated male mice

Raloxifen is a selective estrogen receptor modulator which prevents bone loss in ovariectomized female mice in a fashion similar to estrogens. Since testosterone-deficient male mice also lose bone mass, we were interested in testing the effects of raloxifen on bones in intact and castrated male mice. Bone density was significantly reduced in castrated animals (1.36+/-0.04 g/ml) as compared to intact animals (1.42+/-0.03 g/ml) (p<0.01). When castrated mice with extraordinarily low concentrations of testosterone and with reduced weight of seminal vesicles were treated with raloxifen, the changes in bone density and bone minerals resulting from castration (1.36+/-0.04 g/ml) were entirely prevented (1.40+/-0.01 g/ml). Cortical bone was lost in orchidectomized mice, and this decrease in cortical thickness of the femur was prevented by raloxifen administration. Raloxifen in a dose used in humans for treatment of osteoporosis decreased the weight of seminal vesicles, an organ which is highly sensitive to the androgenic effect, decreased the concentration of testosterone (12.5+/-2.8 micromol/l) (p<0.01) but not to the same level as in the case of castrated animals (0.6+/-0.3 micromol/l), and did not have any effect on bone density or mineral content in intact mice. The results of the present study may thus be interpreted as supporting the hypothesis that raloxifen is an effective agent against the deleterious effects of castration-induced osteopenia in male mice and also support the hypothesis that estrogens may have physiological skeletal effects in male mice.     

Weight-bearing exercise and markers of bone turnover in female athletes.

Weight-bearing activity provides an osteogenic stimulus, while effects of swimming on bone are unclear. We evaluated bone mineral density (BMD) and markers of bone turnover in female athletes (n = 41, age 20.7 yr) comparing three impact groups, high impact (High, basketball and volleyball, n = 14), medium impact (Med, soccer and track, n = 13), and nonimpact (Non, swimming, n = 7), with sedentary age-matched controls (Con, n = 7). BMD was assessed by dual-energy X-ray absorptiometry at the lumbar spine, femoral neck (FN), Ward's triangle, and trochanter (TR); bone resorption estimated from urinary cross-linked N-telopeptides (NTx); and bone formation determined from serum osteocalcin. Adjusted BMD (g/cm; covariates: body mass index, weight, and calcium and calorie intake) was greater at the FN and TR in the High group (1.27 +/- 0.03 and 1.05 +/- 0.03) than in the Non (1.05 +/- 0.04 and 0.86 +/- 0.04) and Con (1.03 +/- 0.05 and 0.85 +/- 0.05) groups and greater at the TR in the Med group (1.01 +/- 0.03) than in the Non (0.86 +/- 0.04) and Con (0.85 +/- 0.05) groups. Total body BMD was higher in the High group (4.9 +/- 0.12) than in the Med (4.5 +/- 0.12), Non (4.2 +/- 0.14), and Con (4.1 +/- 0.17) groups and greater in the Med group than in the Non and Con groups. Bone formation was lower in the Non group (19.8 +/- 2.6) than in the High (30.6 +/- 3.0) and Med (32.9 +/- 1.9, P < or = 0.05) groups. No differences in a marker of bone resorption (NTx) were noted. This indicates that women who participate in impact sports such as volleyball and basketball had higher BMDs and bone formation values than female swimmers.     

Musculoskeletal adaptations to 16 weeks of eccentric progressive resistance training in young women

We investigated the musculoskeletal adaptations and efficacy of a whole-body eccentric progressive resistance-training (PRT) protocol in young women. Subjects (n = 37; mean age, 24.3) were randomly assigned to one of 3 groups: high-intensity eccentric PRT (HRT), low-intensity eccentric PRT (LRT), or control. Subjects performed 3 sets of 6 repetitions at 125% intensity or 3 sets of 10 repetitions at 75% intensity in the HRT and LRT groups, respectively, 2 times per week for 16 weeks. Strength was determined by the concentric 1-repetition maximum (1RM) standard. Bone mass and body composition were measured by dual-energy x-ray absorptiometry (DXA). Blood and urine samples were obtained for deoxypyridinoline, osteocalcin, creatine kinase, and creatinine. Data were analyzed by repeated-measures analysis of variance with post hoc comparisons. Strength increased 20-40% in both training groups. Lean body mass increased in the LRT (0.7 +/- 0.6 kg) and HRT (0.9 +/- 0.9 kg) groups. Bone mineral content increased (0.855 +/- 0.958 g) in the LRT group only. Deoxypyridinoline decreased and osteocalcin increased in the HRT and LRT groups, respectively. These findings suggest that submaximal eccentric training is optimal for musculoskeletal adaptations and that the intensity of eccentric training influences the early patterns of bone adaptation.     

A selective androgen receptor modulator that reduces prostate tumor size and prevents orchidectomy-induced bone loss in rats

The pharmacological activity of JNJ-26146900 is described. JNJ-26146900 is a nonsteroidal androgen receptor (AR) ligand with tissue-selective activity in rats. The compound was evaluated in in vitro and in vivo models of AR activity. It binds to the rat AR with a K(i) of 400nM and acts as a pure androgen antagonist in an in vitro cell-based assay. Its in vitro profile is similar to the androgen antagonist bicalutamide (Casodex). In intact rats, JNJ-26146900 reduces ventral prostate weight with an oral potency (ED(50)) of 20-30mg/kg, again comparable to that of bicalutamide. JNJ-26146900 prevented prostate tumor growth in the Dunning rat model, maximally inhibiting growth at a dose of 10mg/kg. It slowed tumor growth significantly in a CWR22-LD1 mouse xenograft model of human prostate cancer. It was tested in aged male rats for its ability to prevent bone loss and loss of lean body mass following orchidectomy. After 6 weeks of dosing, bone volume decreased by 33% in orchidectomized versus intact vehicle-treated rats with a probability (P) of less than 0.05, as measured by micro-computerized tomography analysis. At a dose of 30mg/kg, JNJ-26146900 significantly reduced castration-induced tibial bone loss as indicated by the following parameters: bone volume, trabecular connectivity, trabecular number and spacing between trabeculae. Bone mineral density decreased from 229+/-34mg/cm(3) of hydroxyapatite to 166+/-26mg/cm(3) following orchidectomy, and was maintained at 194+/-20mg/cm(3) with JNJ-26146900 treatment (P<0.05 relative to orchidectomy alone). Using magnetic resonance imaging, the compound was found to partially prevent orchidectomy-induced loss of lean body mass. Our data show that selective androgen receptor modulators (SARMs) have the potential for anabolic effects on bone and muscle while maintaining therapeutic efficacy in prostate cancer.     

Characterization of bone aluminum,a potential biomarker of cumulative exposure,within an occupational population from Zunyi,China

ObjectivesAluminum (Al) is a neurotoxicant; however, efforts to understand Al toxicity are limited by the lack of a quantitative biomarker of cumulative exposure. Bone Al measurements may address this need. Here, we describe and compare non-invasive bone Al measurements with fingernail Al and Al cumulative exposure indices (CEIs).MethodsWe completed a cross-sectional study of 43 factory workers in Zunyi, China. Bone Al measurements were taken with a compact in-vivo neutron activation analysis system (IVNAA). Fingernail samples were analyzed using inductively coupled plasma mass spectrometry. CEIs, based on self-reported work history and prior literature, were calculated for the prior 5, 10, 15, 20 years and lifetime work history. Linear regressions adjusted for age and education compared fingernail Al and Al CEIs with bone Al.ResultsMedian (interquartile range (IQR)) Al measurements were: 15 μg/g dry bone (IQR = 28) for bone Al; 34.9 μg/g (43.3) for fingernail; and 24 (20) for lifetime CEI. In adjusted regression models, an increase in 15-year CEI was significantly associated with increased bone Al (β = 0.91, 95% confidence interval (CI): 0.16, 1.66). Associations of bone Al with 10- and 20-year CEI were approaching statistical significance (β = 0.98, 95% CI: -0.14, 2.1; β = 0.59, 95% CI: -0.01, 1.18, respectively). Other models were not statistically significant.ConclusionsBone Al was significantly associated with 15-year Al CEI, but not other Al CEIs or fingernail Al. Bone Al may be a useful measure of cumulative, rather than short-term, Al exposure. Additional refinement of this method is ongoing.     

Spatial and temporal patterns of bone formation in ectopically pre-fabricated, autologous cell-based engineered bone flaps in rabbits

Biological substitutes for autologous bone flaps could be generated by combining flap pre-fabrication and bone tissue engineering concepts. Here, we investigated the pattern of neotissue formation within large pre-fabricated engineered bone flaps in rabbits. Bone marrow stromal cells from 12 New Zealand White rabbits were expanded and uniformly seeded in porous hydroxyapatite scaffolds (tapered cylinders, 10-20 mm diameter, 30 mm height) using a perfusion bioreactor. Autologous cell-scaffold constructs were wrapped in a panniculus carnosus flap, covered by a semipermeable membrane and ectopically implanted. Histological analysis, substantiated by magnetic resonance imaging (MRI) and micro-computerized tomography scans, indicated three distinct zones: an outer one, including bone tissue; a middle zone, formed by fibrous connective tissue; and a central zone, essentially necrotic. The depths of connective tissue and of bone ingrowth were consistent at different construct diameters and significantly increased from respectively 3.1 +/- 0.7 mm and 1.0 +/- 0.4 mm at 8 weeks to 3.7+/- 0.6 mm and 1.4 +/- 0.6 mm at 12 weeks. Bone formation was found at a maximum depth of 1.8 mm after 12 weeks. Our findings indicate the feasibility of ectopic pre-fabrication of large cell-based engineered bone flaps and prompt for the implementation of strategies to improve construct vascularization, in order to possibly accelerate bone formation towards the core of the grafts.