Comparison of Radiographic and pQCT Analyses of Healing Rat Tibial Fractures

Fracture healing and callus formation have traditionally been evaluated by using X-ray radiography. Here we compared X-ray radiography and peripheral quantitative computed tomography (pQCT) in evaluating the healing callus of standardized tibial fractures in 141 female rats after a 4- or 8-week follow-up. The results were compared with the tensile (4-week) and compressive (8-week) failure load of the callus. The projectional size of callus, as defined from lateral ex vivo radiographs, correlated significantly with the pQCT-defined cross-sectional area (CSA) of mid-callus. This relationship was dependent on the pQCT attenuation threshold, being higher for the CSA of compact bone (r = 0.85, P < 0.0001) than for the total bone CSA (r = 0.68, P < 0.0001). Radiographically defined callus projectional area also correlated strongly with bone mineral content (BMC) (r = 0.84–0.86, P < 0.0001). The mean optical density of the callus analyzed from the radiographs had only a weak correlation with the pQCT-defined bone mineral density (BMD) of callus. A weak negative relationship was found between CSA and BMD. The optical density analyzed from lateral radiographs did not correlate with the tensile or compressive failure load of callus. Callus size, BMC, and BMD were associated with the compressive failure load, whereas both radiographs and pQCT were poor in explaining the failure load in tension. Received: 28 June 1999 / Accepted: 28 October 1999     

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     

Effects of Promethazine on Bone Mass and on Bone Remodeling in Ovariectomized Rats: A Morphometric, Densitometric, and Histomorphometric Experimental Study

The effect of promethazine on bone is debated. We studied the effect of promethazine on bone and the mechanism of action involved by densitometric and histomorphometric measurements in female Wistar rats (100 days old, mean weight 25 ± 20 g). A control group of 15 rats was not manipulated. An experimental group of 15 rats were ovariectomized (OVX) at 100 days of life and fed a diet supplemented with 4.8 mg/kg promethazine hydrochloride (OVX + Prom). The group that underwent OVX and a group of 15 rats that underwent sham ovariectomy (Sham-OVX) were not treated with promethazine. After 30 days, all the rats were killed. Their femur and 5th lumbar vertebra were dissected and cleaned of soft tissue. Femoral length and vertebral height were measured with a caliper and bones were weighed on a precision balance. The bone mineral content (BMC) and bone mineral density (BMD) of the whole right femurs and 5th lumbar vertebras were measured by dual-energy X-ray absorptiometry (DXA). Trabecular bone volume (Cn-BV-TV%), trabecular number (Tb-N mm⁻¹), trabecular thickness (Tb-Th μm), and trabecular separation (Tb-Sp μm) were measured in the femurs by histomorphometric study of nondecalcified bone. Our results showed that promethazine significantly inhibited postovariectomy loss of bone mass (P < 0.0001) by significantly reducing bone resorption, as shown by the smaller trabecular spaces observed in the treated OVX rats (P < 0.0001). Received: 1 June 1998 / Accepted: 17 February 1999     

Unraveling the Role of Structure and Density in Determining Vertebral Bone Strength

The strength of bone is determined not only by bone density but also by structure. Therefore, quantification of the structure in radiographs by texture parameters may result in a better prediction of fracture risk. Since in radiographs density and structure are strongly correlated, the predictive power of texture parameters should be corrected for the influence of BMD to determine the additional information conveyed by these parameters. In this study, we evaluated the predictive power of various texture parameters based on the Grey-Level Dependence Method and the Morphological Gradient Method. This study was performed on 67 vertebrae obtained from 20 male and 12 female human cadaver thoracolumbar spines. BMD and area of the vertebral body were determined from QCT images and texture parameters were derived from direct magnification (DIMA) radiographs. The fracture force, measured under conditions simulating the in vivo situation, was corrected with the area of the vertebra to yield the fracture stress (FS). Results of the study indicate that BMD correlates significantly with FS r= 0.82 (P < 0.001, n= 24) and r= 0.94 (P < 0.001, n= 43) for female and male vertebrae, respectively. Correlation coefficients of the investigated texture parameters were as high as 0.80 (P < 0.001) and 0.67 (P < 0.001) for the female and male vertebrae, respectively. Multiple regression analysis showed that in female vertebrae, the addition of one texture parameter to BMD results in a better prediction of strength. The multiple correlation coefficient was 0.87 (P < 0.001) in this case. In male vertebrae, BMD was the best predictor of fracture stress. These results suggest that texture parameters, as measured in magnification radiographs, can predict bone strength. Whereas in all cases BMD is the best single predictor of bone strength, for women texture parameters contain useful additional information. Received: 9 July 1996 / Accepted: 24 March 1997     

Continuous Loss of Bone During Chronic Immobilization: A Monozygotic Twin Study

Acute immobilization is associated with rapid loss of bone. Prevailing opinion, based on population cross-sectional data, assumes that bone mass stabilizes thereafter. In order to address whole-body and regional skeletal mass in long-term immobilization, monozygotic twins were studied, one of each twin pair having chronic spinal cord injury (SCI) of a duration ranging from 3 to 26 years. The research design consisted of the co-twin control method using 8 pairs of identical male twins (mean ± SD age, 40 ± 10 years; range 25–58 years), one of each set with SCI. The twins were compared by paired t-tests for total and regional bone mineral content (BMC) and bone mineral density (BMD) measured by dual-energy X-ray absorptiometry. Linear regression analyses were performed to determine the associations of age or duration of injury with the differences between twin pairs for total and regional skeletal bone values. In the SCI twins, total-body BMC was significantly reduced (22%± 9%, p<0.001), with the predominant sites of reduction for BMC and BMD being the legs (42%± 14% 35%± 10%, p<0.0001), and pelvis (50%± 10% and 29%± 9%, p<0.0001). Duration of SCI, not age, was found to be linearly related to the degree of leg bone loss in SCI twins (BMC: r ²= 0.60, p<0.05; BMD: r ²= 0.70, p<0.01). Our findings suggest that pelvic and leg bone mass continues to decline throughout the chronic phase of immobilization in the individual with SCI, and this bone loss appears to be independent of age. Received: 28 September 1998 / Accepted: 28 December 1998     

Effects of Potassium Bicarbonate Supplementation on Axial and Peripheral Bone Mass in Rats on Strenuous Treadmill Training Exercise

We administered a potassium bicarbonate supplement to rats on strenuous treadmill training in order to determine the effect on bone mass and the metabolic acidosis seen with this type of training. A sample of 45 93-day-old female Wistar rats with a mean initial weight of 267 ± 17 g were studied. The control group (15 rats) was not exercised or given potassium bicarbonate (Ex− PB−). The experimental group (30 rats) was randomly divided into two subgroups of 15 rats each, one that exercised and did not receive potassium bicarbonate (Ex+ PB−) and one that exercised and received potassium bicarbonate (Ex+ PB+), at a dose of 0.05 mg/kg/day administered by esophageal catheter on exercise days. Training consisted of treadmill running on 5 out of 7 days for a period of 11 weeks. Running time, treadmill speed, and the percent grade were gradually increased until week 7, then maintained until rats were sacrificed at the ened of 11 weeks. The bone mineral content (BMC) and bone mineral density (BMD) of the whole right femur and 5th lumbar vertebra were measured. Femoral and vertebral length were also measured. Femur length, weight, BMC, and BMD, and femur BMC/final weight ratio, and vertebral weight, BMD, and BMC, and vertebral BMC/final weight ratio were lower in the Ex+ PB− group than in either the controls or the Ex+ PB+ group (P < 0.01–P < 0.0001); the length of the 5th lumbar vertebra did not differ between groups. Received: 21 July 1998 / Accepted: 12 March 1999     

Effects of Alprazolam Supplementation on Vertebral and Femoral Bone Mass in Rats on Strenuous Treadmill Training Exercise

The ability of alprazolam to diminish cortisol response and favor ovarian function could make it useful in the prevention of osteopenia in athletes in selected cases. A sample of 45 female Wistar rats, all 93 days old and with a mean initial weight of 267 ± 17 g, were studied. Rats were exposed to a high-performance level of exercise and were divided into two groups—one group received an alprazolam supplement and one did not—and compared with controls to determine the effect of alprazolam on bone mass as measured by dual-energy X-ray absorptiometry (DKA). Exercise consisted of treadmill running on 5 out of 7 days during a period of 11 weeks. A steep grade treadmill inclination was used to stimulate high-intensity muscle activity. Final inclination was 17.5° and treadmill speed was 45 cm/second. Upon completion of the experiment, all the rats were killed and the femur and 5th lumbar vertebra were dissected and cleaned. Length, weight, bone mineral content (BMC), and density (BMD) of the whole right femur and 5th lumbar vertebra were measured. In the exercise only group (no alprazolam), the length, weight, BMC, BMD, and femur BMC/final rat weight ratio of the femur, and the vertebral weight, vertebral BMD and BMC, and vertebral BMC/final rat weight ratio were lower than in the control and the exercise-alprazolam groups (P < 0.0167 – < 0.0001). Alprazolam preserves bone mass in rats exposed to intense exercise. Received: 1 June 1998 / Accepted: 15 December 1998     

Influence of Body Mass Index on the Age-related Slope of Total and Regional Bone Mineral Content

The influence of body mass index (BMI) on T scores for total body bone mineral content (TBBMC) and regional bone mineral content (RBMC) was studied in 186 healthy women: 100 postmenopausal, 35 perimenopausal, and 51 premenopausal. The three groups were divided by BMI >25 kg/m² and BMI <25 kg/m² and the postmenopausal women were further subdivided by years since menopause (YSM): <10, 10–20, and >20. Tartrate-resistant acid phosphatase (TRAP) concentration was higher in perimenopausal and postmenopausal women with BMI <25 kg/m² (P < 0.001). T scores for TBBMC and for axial or peripheral RBMC differed (P < 0.05 in all) between women with BMI >25 kg/m² and BMI <25 kg/m². The rate of perimenopausal and postmenopausal age-related slope of BMC, as reflected in all measurements, differed with BMI. In the overall group of women, the T score for TBBMC correlated significantly with BMI (r = 0.46, P < 0.0001); this correlation increased when adjusted for age (r = 0.62, P < 0.0001). BMI correlated with TRAP only in postmenopausal women (r = 0.57, P < 0.0001). Yearly TBBMC decline was twice as high in postmenopausal women with BMI <25 kg/m² (P= 0.0004) than in those with BMI >25 kg/m²; the decline of trunk RBMC was more significant (P < 0.0001). These findings confirm the influence of BMI and gonadal status on bone mass. Received 20 February 1996 / Accepted 31 December 1996     

Total Body Bone Measurements in Spinal Osteoporosis by Dual-Energy X-Ray Absorptiometry

Changes in total body bone mineral content (BMC_TB) and density (BMD_TB), and the T-score of BMC_TB and (BMD_TB) were evaluated in relation to the number of vertebral fractures in women with postmenopausal osteoporosis for the purpose of defining deviations in these parameters that could be predictive of the occurrence of vertebral fracture. The study group consisted of 62 women diagnosed with postmenopausal osteoporosis. All of them had two or more spinal fractures. Regression analysis of the number of fractures against each parameter studied indicated that the following were predictive of the risk of fracture: a reduction of −0.5 in the T-score of both BMC_TB and BMD_TB (P < 0.0001) and a loss of about 135 g of BMC_TB or 0.058 g/cm² of BMD_TB (P < 0.0001). The fact that such changes were found during the follow-up of women with osteoporosis highlights the importance of bone mass measurements during follow-up. Received: 9 July 1996 / Accepted: 3 January 1997     

Lifestyle Determinants of Bone Mineral: A Comparison Between Prepubertal Asian- and Caucasian-Canadian Boys and Girls

The purpose of this study was to examine the difference in lifestyle and morphometric factors that affect bone mineral and the attainment of peak bone mass in 168 healthy Asian (n = 58) and Caucasian (n = 110) Canadian, prepubertal girls and boys (mean age 8.9 ± 0.7) living in close geographical proximity. DXA (Hologic 4500) scans of the proximal femur (with regions), lumbar spine, and total body (TB) were acquired. We report areal bone mineral densities (aBMD g/cm²) at all sites and estimated volumetric density (νBMD, g/cm³) at the femoral neck. Dietary calcium, physical activity, and maturity were estimated by questionnaire. Of these prepubertal children, all of the boys and 89% of the girls were Tanner stage 1. A 2 × 2 ANOVA demonstrated no difference between ethnicities for height, weight, body fat, or bone mineral free lean mass. Asian children consumed significantly less dietary calcium (35%) on average and were significantly less active (15%) than their Caucasian counterparts (P < 0.001). There were significant ethnicity main effects for femoral neck bone mineral content (BMC) and αBMD (both P < 0.001) and significant sex by ethnicity interactions (P < 0.01). The Asian boys had significantly lower femoral neck BMC (11%), aBMD (8%), and νBMD (4.4%). At the femoral neck, BMFL mass, sex, and physical activity explained 37% of the total variance in aBMD (P < 0.05). In summary, this study demonstrated differences in modifiable lifestyle factors and femoral neck bone mineral between Asian and Caucasian boys. Received: 21 July 1998 / Accepted: 30 September 1999     

Bone Mineral Density and Body Composition in Underweight and Normal Elderly Subjects

The importance of malnutrition as a risk factor in osteoporosis is emphasized by the evidence that patients with fractures of the proximal femur are often undernourished. In this study, nutritional status, bone mineral mass and its association with body composition were investigated in underweight and normal weight elderly subjects. Moreover the hypothesis that malnutrition in elderly is associated with a higher risk of osteoporosis was tested. The participants were 111 elderly subjects divided into two groups according to body mass index (BMI): 51 patients were underweight (BMI < 22 kg/m²) while in 60 subjects BMI ranged from 22 to 30 kg/m². In all patients anthropometric parameters and blood indices of malnutrition and of bone turnover were measured. Fat-free soft mass (FFSM), fat mass (FM), bone mineral content (BMC) and bone mineral density (BMD) ‘total body’ and at the hip were obtained by dual-energy X-ray densitometry. Dietary intake was evaluated with the diet history method, while resting energy expenditure (REE) was measured by indirect calorimetry. Underweight subjects had other signs of malnutrition, such as low visceral proteins, sarcopenia, and an inadequate energy intake. Moreover they showed a significant reduction of BMC and BMD compared with normal subjects. In men with BMI <22 kg/m², T-score was below −2.5 (−3 at femoral neck and −2.7 at total hip) while men in the control group had normal bone mineral parameters. T-score at different sites was lower in underweight women than in underweight men, always showing values under −3.5, with clear osteoporosis and a high fracture risk. In healthy women the T-score values indicated the presence of mild osteoporosis. In underweight subjects, low levels of albumin (< 35 g/l) were associated with higher femoral bone loss. Using a partial correlation model, BMC, adjusted for age, bone area, knee height and albumin showed a significant association with FM in women (r= 0.48; p < 0.01) and with FFSM in men (r= 0.48; p < 0.05). Albumin, when adjusted for other variables, was significantly correlated (r= 0.52; p < 0.05) with femoral neck BMC only in women. In conclusion, the underweight state in the elderly is associated with malnutrition and osteoporosis; other factors occurring in malnutrition, besides body composition changes, such as protein deficiency, could be involved in the association between underweight and osteoporosis. Moreover bone mineral status seems to be related to fat-free soft mass tissue in men while in women it is much more closely associated with total body fat. Received: 3 January 2000 / Accepted: 3 July 2000     

Bone Size and Bone Mass in 10-Year-Old Danish Children: Effect of Current Diet

Lifestyle factors, such as diet, are believed to be involved in modifying bone health, although the results remain controversial, particularly in children and adolescents. The objective of the study was to identify associations between dietary factors and whole body bone measurements in 10-year-old children. The study was a cross-sectional analysis of a random sample of 105 healthy Danish children, aged 10 years (9.97 ± 0.09). Whole body bone mineral content (BMC) and bone area (BA) were determined by dual-energy X-ray absorptiometry. The influence of diet (7 day food records) on BMC and BA were examined in bi- and multivariate analyses. The mean intakes of calcium, protein, phosphorus and sodium were 1226 mg, 78 g, 1523 mg and 3.3 g, respectively. In bivariate analyses, BMC and BA were strongly positively correlated with height (p<0.001) and weight (p<0.001), and with intakes of energy (p<0.005) and several nutrients. BMC was adjusted for size by including BA, height and weight in the multiple linear regression, and BA was adjusted for size by including height and weight in the multiple linear regression. In multivariate analyses, size-adjusted BMC was positively associated with calcium intake (p = 0.02). Size-adjusted BA was positively associated with dietary protein (p = 0.003), and negatively associated with intakes of sodium (p = 0.048) and phosphorus (p = 0.01). In conclusion, calcium intake was positively associated with bone mineralization. There was a positive association between protein and BA, while for phosphorus and sodium the association was negative. The findings suggest that in addition to calcium, the intake of other nutrients influences bone development in prepubertal children. Received: 31 December 1999 / Accepted: 23 June 2000     

Influence of Spondylopathy on Bone Densitometry Using Dual Energy X-Ray Absorptiometry

Spinal cord injury (SCI), as well as other neuromuscular disorders, not only results in osteopenia but also induces various patterns of osseous, articular, and soft tissue alterations. In the spinal column, a variety of abnormalities occur. To evaluate the magnitude of discrepancy of bone densitometry results caused by spondylopathy in SCI patients, we analyzed anteroposterior (AP) radiographs of the lumbar spine [obtained within 1 month of dual energy X-ray absorptiometry (DXA)] in 116 SCI patients for various manifestations of spondylopathy, and matched the result to each vertebral level (L1, 2, 3, 4). The dataset was stratified by individual vertebra (totally 463 vertebrae) as valid (no demonstrable other abnormal density on plain radiograph except osteopenia), abnormal without, and abnormal with hardware. The influence of spondylopathy on bone densitometry results was determined by the analysis of variance (ANOVA) and post hoc analysis. Our results showed that 227 (49%) vertebrae were abnormal. Significant elevation (15%, 15%, 18%, 20%; P < 0.001–P < 0.05) of bone mineral density (BMD; g/cm²) was observed at all levels (L1, 2, 3, 4, respectively), particularly at those abnormal vertebrae without hardware compared with valid (no other abnormal density on radiograph except osteopenia (Table 1). The L4 level was most severely affected. We concluded that in SCI patients, owing to various secondary progressive skeletal abnormalities, particularly neuropathic spondylopathy, can have strongly and significantly elevated vertebral bone densitometry results, which can obscure underlying osteoporosis, leading to misinterpretation and underestimation of fracture risk. DXA, although characterized by improving spatial resolution, cannot replace radiography in establishing the magnitude of this skeletal pathology. Therefore, determination of bone density in this region with corresponding plain radiographs is highly recommended. Received: 30 July 1996 / Accepted: 3 December 1996     

Bone Mineral Density and Bone Size in Men With Primary Osteoporosis and Vertebral Fractures

The bone mineral density (BMD) at the lumbar spine, proximal femur, and total skeleton was evaluated in 38 men with primary osteoporosis and vertebral fractures. BMD of the patients was significantly reduced over all skeletal areas compared with controls. The Z-score of the lumbar spine (−2.8 ± 0.9) was less than that of the other areas (P < 0.001) except the legs (−2.5 ± 1.1) (p.n.s.) showing that bone loss had a tendency to be greater over the axial skeleton. Vertebral dimensions compared with age-matched controls were as follows: projected L2–L4 area (cm 2): 45.7 ± 5.6 versus 53.7 ± 3.6 (P < 0.001); vertebral width (cm): 4.37 ± 0.44 versus 4.90 ± 0.36 (P < 0.001). Serum biochemical parameters and testosterone levels were similar between osteoporotic and control men. We conclude that men with vertebral osteoporotic fractures have reduced vertebral BMD and vertebral dimensions compared with age-matched controls. Thus, these findings indicate that the achievement of a reduced bone size at the end of the growth period or a failure of periosteal increase during adult life is likely to contribute to the pathogenesis of the vertebral fractures observed in older men. Received: 31 January 1997 / Accepted: 2 July 1997     

Relationship Between Spine Bone Mineral Density and Vertebral Body Heights

The aim of this study was to investigate the correlation between lumbar spine bone mineral density (LS-BMD) and the vertebral body heights with advancing age and years since menopause. One hundred and sixty-three women ages 39–74 years (77 normal premenopausal, ages 39–54, and 86 normal postmenopausal, ages 46–74 years) were studied. LS-BMD was measured by dual energy X-ray absorptiometry. Vertebral heights were evaluated, using morphometry, as the sum of anterior (AHs), middle (MHs), and posterior (PHs) vertebral body heights from T₄ to L₅. The AHs/PHs ratio at the same level was also calculated. AHs, MHs, PHs, and AHs/PHs ratio directly correlated with LS-BMD; the correlations are AHs r = 0.80, P < 0.0001, MHs r = 0.75, P < 0.0001, PHs r = 0.76, P < 0.0001, and AHs/PHs r = 0.66, P < 0.001. Both LS-BMD and AHs are inversely correlated with age, and the regressions fit with both linear and cubic curves. The statistical significance of the correlations persists while maintaining age constant. The linear regression curve of AHs with age indicates that the spine height decrement rate is 2.12 mm/year, corresponding to 7.4 cm in 35 years. AHs decreases immediately after menopause fitting with a cubic curve model, with a decrement rate of about 3 cm in the first 5 years after menopause. We conclude that the measurement of the sum of vertebral body heights could usefully integrate LS-BMD evaluation in the clinical and epidemiological investigation of osteoporosis. Received: 30 May 1997 / Accepted: 14 November 1997     

Bone Mineral Density During Reduction, Maintenance and Regain of Body Weight in Premenopausal, Obese Women

Weight loss may lead to bone loss but little is known about changes in bone mass during regain of reduced weight. We studied changes in bone mineral density (BMD) and bone mineral content (BMC) during voluntary weight reduction and partial regain. The study consisted of three phases: a 3 month weight reduction with very-low-energy diet (VLED), a 9 month randomized, controlled walking intervention period with two training groups (target energy expenditure 4.2 or 8.4 MJ/week) and a 24-month follow-up. The participants were premenopausal women with a mean body mass index of 34.0 (SD 3.6) kg/m². Seventy-four of 85 subjects completed the whole study. Total body, lumbar spine, proximal femur and dominant radius BMD and BMC were measured with dual-energy X-ray absorptiometry (DXA). The mean weight loss during VLED was 13.2 (3.4) kg, accompanied by unchanged total body BMC and decreased lumbar, trochanteric and radial BMD (p<0.05). During months 3–36, an average of 62% of the weight loss was regained, total body BMC decreased and trochanteric BMD increased (p<0.05). At the end of the study, total body BMC and lumbar and femoral neck BMD were lower than initially (p<0.05). Weight change throughout the study correlated significantly with the change in radial (r= 0.54), total body (r= 0.39) and trochanteric (r= 0.37) BMD. Exercise-group assignment had no effect on BMD at weight-bearing sites. In conclusion, the observed changes in BMD and BMC during weight reduction and its partial regain were clinically small and partly reversible. More studies are needed to clarify whether the observed weight changes in BMD and BMC are real or are artifacts arising from assumptions, inaccuracies and technical limitations of DXA. Received: 20 April 2000 / Accepted: 20 September 2000     

Determinants of Bone Mass and Bone Geometry in Adolescent and Young Adult Women

Bone mass and bone geometry are considered to have independent effects on bone strength. The purpose of this study was to obtain data on bone mass and geometry in young female populations and how they are influenced by body size and lifestyle factors. In a cross-sectional, observational study in six European countries, 1116 healthy Caucasian girls aged 11–15 and 526 women aged 20–23 participated. Their radius was scanned at the ultradistal site and at a site approximately 30% of the radius length from the distal end with dual energy X-ray absorptiometry (DXA). The following parameters were assessed from the scans: bone mineral content (BMC), bone mineral density (BMD), cortical wall thickness (CWT), middistal diameter (D), cortical index (CI = 2CWT/D), and the Breaking Bending Resistance Index (BBRI = (D⁴− [D-CWT]⁴)/D). Calcium intake was assessed by 3-day food records and physical activity by questionnaire. Body size parameters were measured by anthropometry. All parameters showed an increasing trend with pubertal stage and age, except for physical activity and calcium intake. BMC and BMD were relatively more dependent on body weight and age at menarche, whereas variation in D and the mechanical index BBRI was better explained by differences in height and grip strength. CI and CWT were relatively independent of variation in body size, whereas BMC and BBRI especially were explained for a substantial proportion (25–33% in the young adults) by body size parameters. Dietary intake of calcium and level of physical activity seem to contribute little to variation in bone parameters. Received: 1 October 1998 / Accepted: 26 July 1999     

Differing Lumbar Vertebral Mineralization Rates in Ambulatory Pediatric Patients with Osteogenesis Imperfecta

The purpose of this study was to evaluate serial changes in bone mineral density (BMD) of the lumbar spine in individual children and adolescents with untreated osteogenesis imperfecta (OI) using dual X-ray absorptiometry (DXA). Twenty-seven pediatric patients with OI who had no historical or radiographic evidence of lumbar fracture, required no assistive device for mobility, and were taking no medications known to affect skeletal mineralization during the study period comprised the investigational group. Absolute BMD and age- and gender-matched BMD (Z-scores) were assessed relative to standard parameters of growth (height, weight, age, height adjusted for age and gender and body surface area) and severity of disease (lifetime fracture rate). The spinal mineralization rate (SMR) between examinations for 15 patients with more than one measurement (n= 20 intervals) was expressed as the magnitude of the change in BMD Z-score per year. Both BMD and BMD Z-score were closely correlated with height, height Z-score, weight and body surface area and were inversely related to fracture rate (P < 0.001 for all comparisons). BMD was also highly correlated with patient age (P < 0.001). Stepwise regression analysis showed that together height Z-score and lifetime fracture rate improved the prediction of BMD Z-score (r= 0.71; P < 0.001). SMRs ranged from −0.5 to 3.5. The average change in SMR between sequential measurements was 168% for the five children who had more than two DXA examinations. Linear regression showed a significant negative correlation between SMR and height Z-score (r=−0.79, P < 0.001). We conclude that vertebral body size is a critical determinant of BMD and BMD Z-score in OI because DXA results are expressed per unit area, not per unit volume. Pediatric patients with OI mineralize their lumbar vertebrae at rates similar to healthy children but tend to lag behind in overall mineralization. The rate of mineralization at any age appears to be related to the patient's height (adjusted for age- and gender-matched controls) and inversely related to the patient's lifetime rate of fractures. Our data suggest that vertebral mineralization in children with OI is related primarily to rapid increases in vertebral volume and only secondarily to increases in vertebral mineral density. Received: 2 March 1997 / Accepted: 5 June 1997     

Dual Energy X-Ray Absorptiometry in Small Rats with Low Bone Mineral Density

The feasibility of dual energy X-ray absorptiometry (DXA) using the Norland XR-26 Mark II bone densitometer for measurements of bone mineral content (BMC) and bone mineral density (BMD) in small rats was evaluated. Thirty-two young, isogenic, Lewis rats (weights from 119 g to 227 g) were used; normal rats (n = 7) and rats with low BMD obtained from three different vitamin D-depleted models (n = 25). DXA measurements were performed using the special software for small animals. Duplicate scans of excised femurs performed at 2 mm/second (pixel size of 0.5 mm × 0.5 mm) were very precise measurements with a coefficient of variation (CV) below 1.6% in animals with normal BMD; in rats with low BMD, the CV was significantly higher (P= 0.02–0.04), 7.8% and 4.4% for BMC and BMD, respectively. Regression analysis demonstrated that these measurements were related to the ash weight (R² > 98.6%). The CV for measurements of the lumbar spine at 10 mm/second (pixel size 0.5 mm × 0.5 mm) was 2.6% and 2.2% for BMC and BMD, respectively in rats with normal BMD, and again higher (P= 0.03–0.14) in rats with low BMD, 7.3% and 4.7%, respectively, for BMC and BMD. Even though low CVs were obtained for total body duplicate scans (scan speed of 20 mm/second and a pixel size of 1.5 mm × 1.5 mm), the measurements were problematic for accuracy because of an overestimation of both BMC and the area of bone. Using these scan parameters the measurements of total body bone mineral could not be recommended in small rats with low BMD. Received: 21 May 1999 / Accepted: 3 August 2000 / Online publication: 22 December 2000     

Plasma Leptin Values in Relation to Bone Mass and Density and to Dynamic Biochemical Markers of Bone Resorption and Formation in Postmenopausal Women

After the menopause it has been noted that heavier women conserve bone better than those with lower body weight. The protective effect of obesity on bone mass has been ascribed to a high body fat content. The present study of 54 postmenopausal women was undertaken to determine whether circulating plasma levels of leptin, the newly described hormone produced in adipocytes, were correlated with age-adjusted total body bone mineral content (BMC) or bone mineral density (BMD), or with dynamic biochemical markers of bone resorption or of bone formation. Leptin values were strongly correlated with all measures of adiposity (P < 0.001). Age-adjusted values for BMC and BMD, respectively, were also positively correlated (P < 0.001) with body weight (r = 0.643, r = 0.502), total fat mass (r = 0.557, r = 0.510) and with plasma leptin concentrations (r = 0.480, r = 0.551), confirming a positive relationship between fat mass and bone mass. By contrast, no significant correlations were observed between plasma leptin and dynamic markers of bone resorption (urinary deoxypyridinoline/creatinine r =−0.105, hydroxyproline/creatinine r =−0.193) or formation (plasma osteocalcin r = 0.103). Because there was no evidence for an association between ciculating plasma levels of leptin and biochemical markers of either osteoclastic or osteoblastic activity we conclude it is unlikely that circulating leptin plays any significant direct role in controlling bone cell activity. Our results do not support the hypothesis that leptin mediates the bone-sparing effects of obesity. Received: 23 September 1997 / Accepted: 11 May 1998