Does the vitamin D receptor genotype predict bone mineral loss in haemodialysed patients?

Background. It has been suggested that the vitamin D receptor (VDR) gene BsmI-polymorphism is a genetic determinant of bone metabolism. Design. To test this hypothesis, the relationship between VDR genotypes, bone mineral density (baseline and after 18 months) and parameters of calcium metabolism and bone turnover were investigated prospectively in 88 haemodialysed patients not receiving active vitamin D metabolites. Methods. Whole body, lumbar spine and femoral neck bone mineral density (BMD) were assessed by dual energy X-ray absorptiometry (DEXA). In addition calcium, phosphorus, 25(OH)D3, 1,25(OH)2D3, osteocalcin serum concentrations, alkaline phosphatase activity and intact, 1,84 PTH levels were measured. Results. VDR genotype BB, Bb and bb were found in 27, 49 and 24% of patients. Initial BMD (g/cm²) of whole body, lumbar spine and femoral neck did not differ between genotypes (whole body: BB 1.055 ± 0.120, Bb 1.082 ± 0.102, bb 1.128 ± 0.120; lumbar spine: BB 1.075 ± 0.199, Bb 1.079 ± 0.185, bb 1.099 ± 0.170; femoral neck: BB 0.808 ± 0.160, Bb 0.862 ± 0.127, bb 0.842 ± 0.125; mean ± SD), but the decrease of whole body and femoral neck BMD during 18 months was significantly (P < 0.02) different between the genotype groups (whole body: BB -0.048 ± 0.028, Bb -0.031 ± 0.029, bb -0.024 ± 0.023; femoral neck BB -0.044 ± 0.069, Bb -0.032 ± 0.081, bb -0.012 ± 0.029 g/cm²). Conclusions. This preliminary study suggests faster mineral loss in BB genotype of VDR in haemodialysed patients.     

Preferential low bone mineral density of the femoral neck in patients with a recent fracture of the proximal femur

Bone mass is an important determinant of resistance to fractures. Whether bone mineral density (BMD) in subjects with a fracture of the proximal femur (hip fracture) is different from that of age-matched controls is still debated. We measured BMD of the femoral neck (FN) on the opposite side to the fracture, as well as femoral shaft (FS) and lumbar spine (LS) BMD by dual-photon absorptiometry in 68 patients (57 women and 11 men, mean age 78.8±1.0) 12.4±0.8 days after hip fracture following a moderate trauma. These values were compared with BMD of 93 non-fractured elderly control subjects (82 women and 11 men), measured during the same period. As compared with the controls, FN BMD was significantly lower in fractured women (0.592±0.013 v. 0.728±0.014 g/cm²,P<0.001) and in fractured men (0.697±0.029 v. 0.840±0.052,P<0.05). Expressed as standard deviations above or below the mean BMD of age and sex-matched normal subjects (Z-score), the difference in FN BMD between fractured women and controls was highly significant (–0.6±0.1 v. +0.1±0.1,P<0.001). As compared with mean BMD of young normal subjects, BMD was decreased by 36.9±1.4 and 22.4±1.5% (P<0.001) in fractured and control women, respectively. There was no significant difference between FN BMD of 33 women with cervical and 24 with trochanteric hip fractures (0.603±0.017 v. 0.577±0.020). FN BMD was lower than 0.705 g/cm² in 90% of fractured women. The prevalence of fracture increased with decreasing FN BMD, reaching 100% with values below 0.500 g/cm². FS and LS BMD were significantly lower in women with hip fracture than in controls (1.388±0.036 v. 1.580±0.030,P<0.001, for FS, and 0.886±0.027 v. 0.985±0.023,P<0.01, for LS), but these differences were not significant when expressed as a Z-score. In men with a recent hip fracture, FS BMD was significantly lower than in controls (1.729±0.096 v. 2.069±0.062,P<0.01), but the difference at the LS level did not reach statistical significance. These results indicate that both women and men with a recent hip fracture had decreased bone mineral density of the femoral neck, femoral shaft and lumbar spine. However, the difference appeared to be of higher magnitude for the femoral neck suggesting a preferential bone loss at this site.     

Role of host immune system in BB/Wor rat. Predisposition to diabetes resides in bone marrow

The role of the immune system in the development of autoimmune diabetes mellitus in the BB/Wor rat was studied with bone marrow transplantation methodology. In the first experiment, diabetes-prone (DP) and diabetes-resistant (DR) BB/Wor rats were irradiated and reconstituted with bone marrow to create both reciprocal (DP donor----DR host; DR donor----DP host) and syngeneic (DR----DR; DP----DP) histocompatible chimeras. Both susceptibility and resistance to subsequent spontaneous diabetes in these chimeras were found to be a function of the type of donor bone marrow transplanted and not the genetic background of the host. In a second experiment, rats from three strains that share the RT1u major histocompatibility complex haplotype of the BB/Wor and rats from three non-RT1u strains were lethally irradiated and reconstituted with DP BB/Wor bone marrow. To rapidly induce diabetes and/or insulitis, they were then injected with mitogen-activated spleen cells from acutely diabetic DP BB/Wor donors, with standard passive-transfer methods. Diabetes and pancreatic insulitis were observed in RT1u recipients, whereas non-RT1u rats developed insulitis but not diabetes. The data suggest that predisposition to spontaneous diabetes in BB rats resides in bone marrow cells.     

Bone mineral density in patients with cervical and trochanteric fractures of the proximal femur

The bone mineral density (BMD) of the proximal femur, spine and radius shaft was determined in 75 women with atraumatic fractures of the proximal femur (FXf) (average age: 70.1±9.6 years) and 51 controls of similar age. Fractures were classified as either cervical (n=36) or trochanteric (n=39) on the basis of radiographic and surgical finding. The BMD of spine and proximal femur was determined by dual-photon absorptiometry (Lunar DP3) and the BMD of the radius shaft by single photon absorptiometry. The BMD of patients with FXf was significantly decreased over all skeletal sites compared to controls of similar age. No significant correlation was found between age and the BMD of the femoral neck in patients with FXf. Patients with trochanteric FXf were older and thinner (average: age, 72.9±9.4 years; weight, 53.1±7.8 kg) compared with patients with cervical fractures (age, 67.2±8.9 years; weight, 59.3±8.3 kg). Likewise the BMD of trochanteric FXf was lower at all measured sites: femoral neck, 0.548±0.066 g/cm² vs 0.624±0.055 g/cm² (P<0.001); L2-L4, 0.799±0.115 g/cm² vs 0.925±0.106 g/cm² (P<0.001); radius shaft, 0.454±0.057 g/cm² vs 0.502±0.083 g/cm² (P<0.05). Of the patients with trochanteric fractures 66% had concomitant vertebral fractures, while this occurred in only 28% of the patients with cervical fractures (P (Fisher)=0.0007). In summary, females with trochanteric FXf are older, thinner, have less bone mass in all measured sites and suffer with a significantly greater frequency of vertebral fractures. These patients have a generalized osteoporosis of the skeleton. Patients with cervical FXf seem to have more specific loss of the proximal femur (regional osteoporosis). The physiopathological process leading to trochanteric and cervical fractures is probably different.     

Alendronate decreases the fracture risk in patients with prostate cancer on androgen‐deprivation therapy and with severe osteopenia or osteoporosis

OBJECTIVE

To evaluate changes in bone mass and fracture risk in patients with prostate cancer on androgen‐deprivation therapy (ADT) and with a basal T‐score of >?2.0, who were treated with an oral bisphosphonate, as such patients treated with ADT are at increased risk of bone loss and bone fracture.

PATIENTS AND METHODS

We selected 61 patients with prostate cancer treated with ADT; 31 were treated with oral alendronate 70 mg once‐weekly and a control group of 30 were not. At baseline and 12 months we measured bone mineral density (BMD) of the lumbar spine, femoral neck and total hip by dual‐energy X‐ray absorptiometry. All patients had severe osteopenia or osteoporosis at baseline. The risk of femoral neck fracture was calculated at baseline and 12 months (Z‐score 2.7).

RESULTS

Patients treated with alendronate had a significant increase in BMD at the lumbar spine and femoral neck after 1 year of follow‐up, with mean (sd ) values of 1.06 (0.26) vs 1.01 (0.21) g/cm² at baseline (P < 0.001), and 0.75 (0.07) vs 0.73 (0.07) g/cm² (P = 0.03), respectively, while the control group had a significant loss of BMD at the total hip of 0.79 (0.14) vs 0.81 (0.13) g/cm² (P = 0.03). BMD was significantly improved at the three locations in patients treated with alendronate compared with the control group, with differences at the lumbar spine, femoral neck and total hip of 0.05 (0.07) vs 0.01 (0.10) (P = 0.001), 0.01 (0.04) vs ?0.002 (0.03) (P = 0.04) and 0.01 (0.04) vs ?0.01 (0.02) g/cm², respectively (P = 0.001). Patients treated with alendronate had a significant decrease in the fracture risk at the femoral neck, by ?0.54 (1.29) (P = 0.04) after 1 year of follow‐up.

CONCLUSIONS

Treatment with once‐weekly 70 mg alendronate significantly improved the BMD at the lumbar spine and femoral neck in patients with prostate cancer with severe osteopenia or osteoporosis and on ADT, and significantly decreased the risk of femoral neck fracture.     

悬吊模拟失重及解悬吊对大鼠骨密度及生物力学的影响

目的：观察尾部悬吊模拟失重及解悬吊后大鼠骨密度及生物力学的变化。方法：20只Wistar雄性大鼠随机分成空白组和模型组。模型组尾部悬吊14d,解悬吊后继续饲养14d,空白组则正常饲养28d。实验第14天活体检测各组大鼠颅骨、T2椎体、L4椎体、骨盆、右侧桡尺骨和右侧股骨的骨密度（bone mineral density,BMD）;实验第28天处死大鼠,检测右侧股骨及L4椎体BMD及生物力学强度。结果：与空白组相比,实验第14天,模型组大鼠股骨、骨盆、腰椎BMD明显低,差异有统计学意义（P〈0.001,P〈0.001,P〈0.01）;颅骨、胸椎、桡尺骨BMD无明显变化（P〉0.05）。实验第28天,模型组大鼠股骨、腰椎BMD和股骨最大载荷明显低,差异有统计学意义（P〈0.01,P〈0.001,P〈0.01）。结论：大鼠尾部悬吊14d即可引起骨代谢的紊乱：承重骨骨矿盐大量丢失;即使解悬吊14d后承重骨BMD及力学强度也明显降低,表明骨代谢紊乱短期内不能恢复正常。     

Improving Metabolic Control Reverses the Histomorphometric and Biomechanical Abnormalities of an Experimentally Induced Bone Defect in Spontaneously Diabetic Rats

Insulin-dependent type 1 diabetes mellitus (IDDM) has been shown to alter the properties of bone and to impair fracture-healing in both humans and animals. The objective of this study was to examine changes in the histomorphometric and mechanical parameters of bone and remodeling during bone-defect healing, depending on the diabetic metabolic state in spontaneously diabetic BB/O(ttawa)K(arlsburg) rats, a rat strain that represents a close homology to IDDM in humans.A standardized bone-defect model was chosen and based on blood-glucose values at the time of surgery (mg%), postoperative blood-glucose course (mg%), and postoperative insulin requirements (IU/kg). A total of 120 spontaneously diabetic BB/OK rats were divided into groups with a well-compensated (n = 60; 169 ± 102 mg%; 230 ± 126 mg%; and 2.2 ± 1.1 IU/kg) or poorly compensated (n = 60; 380 ± 159 mg%; 359 ± 89 mg%; and 5.4 ± 1.1 IU/kg) metabolic state. Sixty LEW.1A rats served as the normoglycemic controls (93 ± 19 mg%). Fifteen animals from each group were killed on postoperative days 7, 14, 24, and 42, and specimens were processed undecalcified for quantitative bone histomorphometry and for biomechanical testing.Our study showed in terms of bone histomorphometry, within the first 14 days, that severe mineralization disorders occurred exclusively in the rats with a poorly compensated diabetic metabolic state with a highly significant (P < 0.001) or significant (P < 0.01) decrease of all fluorochrome-based parameters of mineralization, apposition, formation and timing of mineralization, as well as significantly decreased values of biomechanical properties (P < 0.05) in comparison to the spontaneously diabetic rats with a well-compensated metabolic state and to the control rats.Bone-defect healing in spontaneously diabetic BB/OK rats is retarded exclusively in a poorly compensated diabetic metabolic state. This study suggests that strictly controlled insulin treatment resulting in a well-compensated diabetic metabolic state will ameliorate the impaired early and late parameters of IDDM bone-defect healing.     

Differential action of pamidronate on trabecular and cortical bone in women with involutional osteoporosis

Since osteoporotic fractures are mainly related to the diminution of the bone mineral density (BMD), the effect of pamidronate (3-amino-1-hydroxy-propylidene) 1,1-bisphosphonate on the BMD of the spine, proximal femur and radius shaft was evaluated in an initial cohort of 35 postmenopausal women with at least one vertebral fracture due to involutional osteoporosis.Pamidronate was given continuously during 18 months in a daily oral dose of 4.8 to 6.0 mg/kg supplemented with calcium (1 g/day).BMD — measured by dual photon absorptiometry — increased after one year 5.3±1.0% (P<0.001) in lumbar spine and 5.3±1.5% (P<0.001) over trochanter. However no significant changes were observed in the BMD of the femoral neck, Ward's triangle or in the cortical bone of the radius shaft measured by single photon absorptiometry.Pamidronate also decreased significantly urinary hydroxyproline-creatinine excretion after 6 months and thereafter maintained a plateau. After 18 months of treatment the diminution was 42.6±4.9% (P<0.001).The differing effects of pamidronate on the BMD of lumbar spine and proximal femur might be ascribed to dissimilarities between the proportions of trabecular and cortical bone in these. These results suggest that pamidronate may be prescribed to prevent fractures in cases of involutional osteoporosis with a significant decrease of BMD in lumbar spine and/or trochanter.     

PIXImus Bone Densitometer and Associated Technical Measurement Issues of Skeletal Growth in the Young Rat

The PIXImus dual-energy X-ray absorptiometer (DXA) is designed to measure body composition, bone mineral content (BMC), area (BA), and density (BMD) in mice and rats. The aims of this study were to longitudinally measure BMC, BA, and BMD in growing rats and to identify potential technical problems associated with the PIXImus. Total femur and lumbar DXA measurements, body weight, and length of initially 3-week-old rats (n = 10) were taken at weeks 5, 9, and 14. BMC and BMD of femoral metaphyseal and diaphyseal regions rich in trabecular and cortical bone, respectively, were obtained. Results showed significant increases in body weight, total femur BMC and BMD, lumbar area, length, BMC, and BMD at each time point. There was a significant positive correlation between body weight and total femur BMD (r = 0.97, P < 0.001) as well as lumbar BMD (r = 0.99, P < 0.001). BMD values for the femoral metaphyseal region and the lumbar spine were also positively correlated (r = 0.96, P < 0.01). Several technical issues (e.g., positioning of animals), difficulties (e.g., in analysis of images), and limitations (e.g., inability to detect underdeveloped calcified bone in growing animals and bone edge detection) of the software pertinent to the PIXImus were evident. In conclusion, despite limitations in the software, the PIXImus is a valuable tool for studying skeletal development of growing rats.     

Bone Mineral Density After Simultaneous Kidney-Pancreas Transplantation: Four Years Follow-up of 57 Recipients

Bone disease and an high risk of fractures are major problems in transplantation. Among diabetic patients undergoing simultaneous kidney-pancreas (SKP) transplantation, there are few studies assessing long-term effects on bone mass. The aim of this study was to evaluate bone mineral density (BMD) over 4 years follow-up after SKP transplantation. Fifty-seven patients had 22.8 ± 5.3 years of prior diabetes, 65% were female, and the overall mean age was 24.3 ± 5.93 years. At the time of transplantation, the lumbar spine and femoral neck T-scores were −1.75 ± 1.05 and −1.95 ± 0.73, respectively; 28% of subjects had evidence of osteoporosis. One year after transplantation, 77.6% of patients displayed improved lumbar T-scores to −1.33 ± 0.94 (P = .044) with stable femoral neck T-scores. Bone densitometry enhanced gradually through the 4 years follow-up: lumbar T-score to −1.04 ± 0.67 (P = .004) and femoral neck T-score to −1.69 ± 0.49 (P = .12). At year 4, no osteoporosis cases were detected but 86.7% of patients did not receive steroids in the immunosuppressive regimen. The graft function remained stable (serum creatinine, 1.2 mg/dL; fasting glucose, 87.7 mg/dL). During the follow-up, BMD improved more significantly at cortical sites. Our study reports a reduced prevalence of fractures (8.7%) compared with the literature, which could be related to a steroid-sparing protocol and/or aggressively treatment of osteoporosis.     

Femoral and spinal bone mineral density in Japanese osteoporotics with hip fracture

In the present study, bone mineral density (BMD) of femoral neck and lumbar spine was compared between 38 Japanese female patients with hip fracture (age 63–89 years, mean±SD 76±7 years) and 162 age-matched female controls (age 62–90 years, mean±SD 75±7 years). BMD was measured in the femoral neck and lumbar spine (L2–4) using dual-photon absorptiometry (Norland model 2600). BMD values of femoral neck as well as lumbar spine were significantly lower in patients with hip fracture than in controls (0.504±0.097 v 0.597±0.101,p<0.01, for femoral neck; 0.661±0.146 v 0.720±0.128,p<0.05, for lumbar spine). Patients with hip fracture and controls were stratified according to their BMD levels at two measuring sites, and the ratio of the number of patients and controls at each BMD level was calculated as an indicator of fracture rate. This ratio showed an exponential increase as the femoral neck BMD declined, but only a gradual increase as the lumbar spine BMD declined. Specificity-sensitivity analysis revealed that BMD values of 0.59 and 0.54 g/cm² at the femoral neck provided a specificity of 52% and 68% with a sensitivity of 90% and 75%, respectively. These findings suggest that Japanese patients with hip fracture are more osteoporotic than age-matched controls and that the selective measurement of femoral neck would be useful for predicting the risk of hip fracture.     

Low Bone Density with Normal Bone Turnover in Ovariectomized and Streptozotocin-Induced Diabetic Rats

Diabetes and estrogen deficit are known causes of osteopenia, diabetes being associated with a low bone turnover and estrogen deficit with a high bone turnover. In the present work, we studied the effect of combined ovariectomy and diabetes on bone mineral content (BMC) and bone mineral density (BMD) and several bone markers in the rat. Four groups of rats were studied: control (C), ovariectomized (O), diabetic (D), and ovariectomized and diabetic (DO). Twelve weeks after starting the experiments, BMC and BMD of the first six lumbar vertebrae were measured; a bone formation marker (BGP) and a bone resorption marker (free collagen cross-links, PYD) were also analyzed. Diabetic rats showed diminished gain in bone mass, BMC (D: 0.417 ± 0.028 g, DO: 0.422 ± 0.020 g) and BMDs (D: 0.171 ± 0.006 g/cm², DO: 0.174 ± 0.006 g/cm²) both being significantly (P < 0.001) lower than those of control (C: BMC 0.727 ± 0.024 g and BMD 0.258 ± 0.004 g/cm²) and ovariectomized (O: BMC 0.640 ± 0.044 g and BMD 0.240 ± 0.009 g/cm²) groups. Moreover, the BMC and BMD of the C group were significantly (P < 0.05) higher than that of the O group. BGP and PYD levels were significantly (P < 0.01) higher in the O group (BGP: 138.2 ± 16.8 ng/ml, PYD: 270.2 ± 17.8 nM/mM) than those found in the control rats (BGP: 44.7 ± 4.8 ng/ml, PYD: 165.6 ± 12.5 nM/mM); the D group showed significantly (P < 0.01) lower values (BGP: 27.4 ± 14.6 ng/ml, PYD: 55.0 ± 7.4 nM/mM) than those of the control group. The DO group showed similar levels (BGP: 43.4 ± 5.1 ng/ml, PYD: 146.7 ± 14.6 nM/mM) to those found in the C group. Although bone marker levels in the O and D groups were in accordance with those expected in these situations, in the DO group the corresponding levels are apparently ``normal.' Also, the decrease of gain in bone mass observed after combining estrogen deficit and diabetes (DO group) did not seem to be more marked than that caused by diabetes alone. Received: 7 January 1997 / Accepted: 7 August 1997     

Skin autofluorescence Is associated With low bone mineral density in type 2 diabetic patients

Although the risk of bone fracture is increased in type 2 diabetes (T2DM), bone mineral density (BMD) is increased rather than decreased. Accumulation of advanced glycation end products (AGEs) adversely influences the fracture resistance of bone in T2DM. We hypothesized that SAF is also associated with BMD levels in type 2 diabetic patients and aimed to evaluate the association of SAF with BMD and the presence of osteoporosis. This cross-sectional case-control study included 237 patients with T2DM (F/M: 133/104, 56.2±11.9 yrs) and 100 age- and sex-matched controls (F/M: 70/30, 54.8±8.8 yrs). Skin autofluorescence, a validated non-invasive measure of tissue AGEs, is used to detect the accumulation of AGEs in skin collagen using AGE Reader (DiagnOptics B.V., Groningen, The Netherlands). In addition, BMD was measured with DEXA (Lunar DPX-L). Patients with T2DM had higher SAF values compared to control group (2.21±0.53 AU vs. 1.79±0.33 AU, p < 0.001). Male subjects had higher SAF compared to women (2.34±0.53 AU vs. 2.11±0.50 AU, p < 0.001). Subjects with below -2.5 femoral neck or lumbar T scores had higher SAF measurements compared to subjects with normal T scores (2.46±0.53 AU vs. 2.18±0.52 AU, p = 0.006). Femoral neck BMD was lower in subjects with T2DM (0.946±0.345 g/cm² vs. 1.005±0.298 g/cm², p = 0.002). There was a negative correlation between SAF and femoral neck BMD (r=?0.24, p < 0.001), femoral neck T scores (r=-0.24, p < 0.001), L1-4 BMD (r=?0.10, p = 0.005), L1-4 T score (r=?0.16, p=0.001) and a positive correlation between SAF and age (r=0.44, p < 0.001), body mass index (r:0.16, p = 0.002) and HbA1c (r=0.37, p < 0.001). Accumulation of skin AGEs was increased, and BMD levels were decreased in diabetic patients. A negative association between SAF and BMD was detected, indicating a relationship between higher AGE accumulation and low BMD and osteoporosis in diabetic patients. Long-term prospective studies are needed to identify the practical use of SAF measurement in diabetic bone disease.     

Areal and volumetric bone density in Hong Kong Chinese: a comparison with Caucasians living in the United States

It is a common perception that Asians have lower bone density than Caucasians. However, such relationships could be confounded by bone size. In this study, the skeletal status of a convenience sample of 482 men and 887 women living in Hong Kong is compared with published data for Caucasians living in Rochester, Minnesota. Areal bone mineral density (BMD, g/cm²) and volumetric bone mineral apparent density (BMAD, g/cm³) were determined for the lumbar spine and proximal femur, using the Hologic QDR 2000 instrument. Cross-calibration was performed by measuring a common phantom, and the Hong Kong data were adjusted by a multiplication factor. Lumbar spine and femoral neck BMD and BMAD of Chinese men and women were all significantly lower (P<0.001 by t-test) than those of Caucasians, but the differences in BMAD were on average only about half the size of the differences in BMD. For instance, in postmenopausal Chinese women, BMD at the femoral neck and lumbar spine were 15.2% and 18.8% lower respectively, but BMAD at the femoral neck and lumbar spine were only 7.8% and 12.4% lower respectively. Similar trends were observed in men. After adjusting for age, body height and weight, the difference in BMAD between Caucasians and Chinese was further reduced and only statistically significant among postmenopausal women and among men younger than age 50 years for the lumbar spine. For instance, the adjusted BMAD in postmenopausal Chinese women at the femoral neck and lumbar spine were 3.9% (P=0.03 by ANCOVA) and 7.3% (P<0.001 by ANCOVA) lower respectively, while the adjusted BMAD at the lumbar spine for Chinese men younger than 50 years was 11.7% lower (P<0.01 by ANCOVA). Predictors of BMAD in Hong Kong Chinese women include body weight, age at menarche, cigarette smoking, and oral contraceptive use (P<0.001), while body weight was the only independent predictor of BMAD in Hong Kong Chinese men (P<0.001). We conclude that bone density is lower in Hong Kong Chinese men and women than in Caucasians, although such differences were attenuated by adjustments for bone size, body weight and height.     

Ultrasound and X-ray-Based Bone Densitometry in Patients with Anorexia Nervosa

In 20 patients (mean age 23 ± 5 years) with anorexia nervosa (AN), bone mass was evaluated by broadband ultrasound attenuation (BUA) of the calcaneus, peripheral quantitative computed tomography (pQCT) of the distal radius, and dual X-ray absorptiometry (DXA) of the lumbar spine and the hip. Compared with 20 age- and sex- matched healthy controls, patients with AN showed marked osteopenia at all measuring sites. Values of BUA (33.0 ± 9dB/MHz vs. 51.0 ± 5.7 dB/MHz; P < 0.0001) and of BMD of all regions of the hip (e.g., femoral neck: 0.71 ± 0.13 g/cm² versus 0.89 ± 0.07 g/cm²; P < 0.001), lumbar spine (0.82 ± 0.15 g/cm² versus 1.24 ± 0.06 g/cm²; P < 0.003) and total BMD of the peripheral radius (303.2 ± 75 g/cm³ versus 369.4 ± 53.2 g/cm³, P < 0.001) were significantly reduced. Calculating a Z-score we found the most prominent differences between AN and controls by BUA of the calcaneus (−3.2 ± 1.6), followed by DXA at the lumbar spine (−2.9 ± 2.2) and the hip (femoral neck −2.1 ± 1.7) and by pQCT at the distal radius (total BMD −1.2 ± 2.0). There were highly significant correlations between BUA of the calcaneus and BMD of the femoral neck (r = 0.78, P < 0.0001) and lumbar spine (r = 0.75, P < 0.0001) as well as between BMD values of the femoral neck and lumbar spine (r = 0.95; P < 0.0001). In addition, there were significant correlations (P < 0.001) between body mass index (BMI) and the three different measuring sites and between the duration of the disease and BUA (r = 0.5, P < 0.05). Our data suggest that BUA of the calcaneus is a valuable tool in the management of osteoporosis. Being a fast, radiation-free investigation method of good acceptance, it may be well suited for an assessment of the skeletal status in patients with AN. Received: 14 October 1998 / Accepted: 10 December 1999     

Bone gained from physical activity and lost through detraining: a longitudinal study in young males

The aim of this study was to investigate the effect of training and detraining on bone mineral density of both weight-bearing and non-weight-bearing bone in a cohort of young males who participated in ice hockey training. Forty-three healthy adolescent ice hockey players (16.7±0.6 years) training for a mean of 9.7±2.4 h/week and 25 control subjects (16.8±0.3 years) training for 2.1±2.7 h/week, were included in this longitudinal study. Bone mineral density (BMD, g/cm²) of the arms, the dominant and non-dominant humerus, dominant and non-dominant femur, and the right femoral neck, total hip, and bone area of the femur, humerus and hip were measured at baseline and again after 30 and 70 months using dual-energy X-ray absorptiometry. From baseline to the first follow-up, athletes gained significantly more BMD in the femoral neck (0.07 versus 0.03 g/cm²) and arms (0.09 versus 0.06 g/cm²) compared with the controls (P=0.04 for both). Between the first and the second follow-up, 21 ice hockey players stopped their active sports career. These men lost significantly more BMD at the femoral neck (–0.02 versus –0.10 g/cm², P<0.001), total hip (–0.05 versus –0.09, P=0.04), dominant (0.02 versus –0.03 g/cm², P=0.009) and non-dominant humerus (0.03 versus –0.01 g/cm², P=0.03) than the still active ice hockey players (n=22). At the second follow-up examination, at 22 years of age, the former ice hockey players still had significantly higher BMD at the non-dominant humerus than the controls (P<0.01). During the total study period, the still active athletes (n=22) gained significantly more BMD compared with the controls at the femoral neck (0.09 g/cm²; P=0.008), total hip (0.05 g/cm², P=0.04) and arms (0.07 g/cm²; P=0.01). No differences were seen in bone areas when comparing the different groups. In conclusion, training associated with ice hockey is related to continuous accumulation of BMD after puberty in males. Reduced activity is followed by BMD loss within 3 years of cessation of sports career at predominantly weight-bearing sites. The effects are confined to bone density and not bone size.     

Bone Mineral Density Is not Sensitive Enough to Assess the Risk of Vertebral Fractures in Type 2 Diabetic Women

Although the association between diabetes and osteoporosis has been studied, it remains unclear if the pathogenesis of vertebral fractures in patients with type 2 diabetes would be similar to those without diabetes. One hundred and fifty female diabetic patients without apparent proteinuria as well as 716 women without diabetes (control group) were examined by lateral thoracic and lumbar spine radiographs as well as dual-energy X-ray absorptiometry. Vertebral fractures were found in 26 (17.3%) and 158 (22.1%) subjects in the diabetic and control groups, respectively. Diabetic patients had higher absolute and age-matched (Z score) values of lumbar bone mineral density (L-BMD) than controls despite their significantly higher mean age. By receiver operating characteristic (ROC) analysis, the absolute L-BMD values for detecting vertebral fractures were higher and sensitivity and specificity were lower in diabetic patients than controls (0.816 g/cm² vs. 0.716 g/cm² and 66.0% vs. 74.8%, respectively). Logistic regression analysis adjusted for age, body weight, and height also showed that L-BMD was not significantly associated with the presence of vertebral fractures in diabetic patients (odds ratio [OR] = 0.61, 95% confidence interval [CI] 0.34–1.09 per standard deviation increase, P = 0.0954), in contrast to the significant association in controls (OR = 0.23, 95% CI 0.16–0.33, P < 0.0001). These results show that L-BMD is not sensitive enough to assess the risk of vertebral fractures in female diabetic patients and suggest that bone fragility not defined by BMD might be related to the risk of vertebral fractures in them.     

High-intensity exercise in female athletes: effects on bone mass and body composition

Abstract We investigated bone mass and body composition in young healthy athletic women in order to determine the influence of high-impact physical activity on bone, fat and lean mass. In a case-control study, we studied 68 healthy women, aged 18–45 years, divided in two groups (age and body mass index matched): 39 sedentary women and 29 professional karate athletes. Family and medical histories and information on habits and dietary patterns were collected through a self-administered questionnaire. Bone mineral density (BMD, g/cm²) of whole body, lumbar spine and proximal femur was measured by means of dual energy X-ray absorptiometry (Hologic QDR 4500A scanner; Hologic,Waltham, USA; version 8.26). Total and subregional fat and lean whole body masses were also measured (grams). Significantly higher femoral and total body bone masses were found in active women compared to sedentary women (total femur: 1.00±0.09 vs. 0.95±0.10 g/cm², p<0.05; femoral neck: 0.94±0.11 vs. 0.87±0.11, p<0.05; trochanter: 0.77±0.10 vs. 0.70±0.08, p=0.002; intertrochanter: 1.17±0.09 vs. 1.11±0.12, p<0.05; total body: 1.19±0.06 vs. 1.14±0.08, p<0.05). Active women also had lower fat mass (total: 16510±4430 vs. 20736±7883 g, p=0.007; limbs: 9952±2779 vs. 11888±4147, p=0.027; trunk: 5807±1970 vs. 8325±4113 p=0.001) and higher limb lean mass (15574±2124 vs. 14532±2034 g, p=0.05). A significantly lower calcium intake was registered in active women. Oral contraceptive use appeared to significantly increase femoral bone density. Physical activity increased bone mass in young active women, and this effect seemed to be superior to that of dietary calcium intake.     

Spinal cord injury causes more damage to bone mass, bone structure, biomechanical properties and bone metabolism than sciatic neurectomy in young rats

Introduction Although both spinal cord injury (SCI) and sciatic neurectomy (NX) can cause osteopaenia in young rats, the effects of these two injuries on cortical and cancellous bone may differ. The objective of this study was to compare the effects of SCI and NX on bone weight, bone material property, bone mass, bone geometry, trabecular microarchitecture, mechanical strength and bone turnover in young rats.Materials and methods Thirty six-week-old male Sprague-Dawley rats were randomised into three groups (10 per group): SCI, bilateral sciatic NX and untreated control (CON). All rats were killed on day 21. Bone mineral density (BMD) was studied using dual-energy X-ray absorptiometry (DXA). At death, the right proximal tibial metaphysis and the fourth lumbar vertebra were examined for bone structural geometric analysis by micro-computed tomography (CT) and then processed for histomorphometry to assess bone cell activity. Serum N-terminal telopeptide of type I collagen (NTX) and osteocalcin (OC) levels were analysed by enzyme-linked immunosorbent assay (ELISA). Biomechanical strength properties of the femur and humerus were measured by three-point bending, and the third lumbar vertebra and the proximal end of tibia were tested by compression.Results BMD in the sublesional areas of SCI rats was significantly lower than that of NX rats (proximal tibia, 0.176±0.018 g/cm² vs. 0.224±0.015 g/cm², P<0.001). Bone volume (BV/TV), trabecular number (Tb.N) and thickness (Tb.Th) in the tibial second spongiosa of SCI rats were significantly less than those in NX rats (BV/TV: 7.15±1.18% vs. 12.32±1.83%, P<0.001; Tb.N: 1.23±0.22 vs. 2.38±0.45, P<0.001; Tb.Th: 33.73±5.15 μm vs. 42.80±7.44 μm, P<0.01) and trabecular separation (Tb.Sp: 1,053.37±164.24 μm vs. 748.32±129.36 μm, P<0.01) was significantly greater than in NX rats. Furthermore, poorer trabecular connectivity was found in SCI rats than in NX rats (number of nodes, N.Nd/TV: 1.04±0.09 vs. 3.29±0.53; number of terminus, N.Tm/TV: 28.53±3.17 vs. 21.64±2.31, P<0.01). The bone formation rate of the tibial second spongiosa in SCI rats was significantly higher than in NX rats (2.06±0.13 vs. 1.53±0.09, P<0.001) and, also, the eroded surface in SCI rats was significantly higher than in NX rats (13.42±1.24 vs. 10.36±1.07, P<0.001). In addition, biomechanical tests showed that SCI rats had poorer biomechanical properties of the femur, proximal tibia and fourth lumbar vertebra than in NX rats. There were significantly higher levels of OC in SCI rats compared with NX rats (30.19±1.17 vs. 21.15±1.76, P<0.001). Also, serum NTX levels were significantly higher than in NX rats (51.60±2.61 vs. 33.85±1.93, P<0.001).Conclusion SCI caused more damage to bone mass, bone structure, biomechanical properties and bone metabolism than NX in young rats. This suggests that different mechanisms may underlie osteopaenia following SCI and NX.     

A 3-Year Longitudinal Study of the Effect of Physical Activity on the Accrual of Bone Mineral Density in Healthy Adolescent Males

It has previously been suggested that physical activity predominantly influences the accumulation of bone density before puberty. The purpose of the present study was to examine the effect of physical activity on the accumulation of bone mass in male athletes between 16 and 19 years of age. The cohort studied consisted of 12 badminton players (aged 16.1 ± 0.5), 20 ice hockey players (aged 16.1 ± 0.5), and 24 age-matched controls (aged 16.1 ± 0.6). The bone mineral density (BMD, g/cm²) of the total body, spine, dominant and nondominant humerus, head and femoral neck was measured twice with a 3-year interval by dual energy X-ray absorptiometry (DXA). In addition, at the femoral neck, volumetric bone mineral density (vBMD, mg/cm³) was estimated. At baseline, the athletes as a whole group had significantly higher BMD at the total body (P = 0.03), dominant (P = 0.006) and nondominant humerus (P = 0.009) and femoral neck (P = 0.007) compared to the controls. At the 3-year followup, the athletes had significantly higher BMD at all sites (total body; P = 0.003, spine; P = 0.02, dominant humerus; P = 0.001, nondominant humerus; P = <0.001, femoral neck; P = 0.001) except for the head (P = 0.91) compared with controls. The athletes also had higher vBMD at the femoral neck compared with the controls (P = 0.01). Furthermore, to be an athlete was found to be independently associated with a higher increase in nondominant humerus BMD ( = 0.24; P < 0.05) and femoral neck BMD ( = 0.30; P < 0.05) compared with the controls, during the study period. In summary, these results suggests that it is possible to achieve continuous gains in bone mass in sites exposed to osteogenic stimulation after puberty in males by engaging in weight-bearing physical activity.