Vitamin D and Bone Mineral Density in Ambulatory Women Living in Buenos Aires, Argentina

The aim of this study was to determine possible associations between bone mineral density (BMD), 25-hydroxyvitamin D (25(OH)D) and intact parathyroid hormone (PTH). In a retrospective study we examined the case notes of free-living postmenopausal women living in our city (34° S). We also report a low prevalence of vitamin D deficiency (25(OH)D <25 nmol/l, 5.6%) and of secondary hyperparathyroidism (intact PTH >65 pg/ml, 7.5%). Age was correlated with BMD at the lumbar spine (r=−0.25, p = 0.00038) and femoral neck (r=−0.252, p = 0.0003). Body mass index (BMI) was correlated with BMD at the femoral neck (r= 0.177, p = 0.021) but not at the lumbar spine. 25(OH)D was positively correlated with BMD at the femoral neck (r = 0.149, p=0.036) but not at the lumbar spine. PTH was positively correlated with age (r= 0.279, p = 0.012) and negatively correlated with 25(OH)D (r=−0.322, p = 0.0036). PTH was also negatively correlated with BMD at the lumbar spine (r=−0.258, p=0.02) and the femoral neck (r=−0.282, p = 0.011). Forward stepwise multiple regression showed that BMI, age and 25(OH)D made significant contributions to BMD at the femoral neck. PTH also showed a significant contribution to BMD at both sites. In conclusion, weak correlations found between PTH and 25(OH)D and BMD suggest these biochemical variables, among other factors, contribute to lumbar spine and femoral neck BMD. Received: 19 February 2000 / Accepted: 20 June 2000     

Bone Density in an Immigrant Population from Southeast Asia

The epidemiology of bone loss in populations of Asian heritage is still poorly known. This study compared the skeletal status of a convenience sample of 396 Southeast Asian immigrants (172 Vietnamese, 171 Cambodians and 53 Laotians) residing in Rochester, Minnesota in 1997 with 684 white subjects previously recruited from an age-stratified random sample of community residents. Areal bone mineral density (BMD, g/cm²) and volumetric bone mineral apparent density (BMAD, g/cm³) were determined for lumbar spine and proximal femur using the Hologic QDR 2000 instrument for the white population and the QDR 4500 for Southeast Asian subjects; the machines were cross-calibrated from data on 20 volunteers. Lumbar spine BMD was 7% higher in white than Southeast Asian women ( p < 0.001), and similar results were observed for the femoral neck; lumbar spine BMD was 12% higher in white than nonwhite men ( p < 0.001). Race-specific discrepancies were reduced by calculating BMAD: for premenopausal women, lumbar spine and femoral neck differences between whites and Southeast Asians were eliminated; for postmenopausal women the lumbar spine differences persisted ( p < 0.0001), while femoral neck BMAD was actually higher for Southeast Asians. There were no race-specific differences in femoral neck BMAD among men of any age ( p= 0.312), but lumbar spine BMAD was less for younger ( p= 0.042) but not older ( p= 0.693) Southeast Asian men. There were differences among the Southeast Asian subgroups, but no clear pattern emerged. Predictors of lumbar spine BMAD in Southeast Asian women were age ( p < 0.001), weight ( p= 0.015) and gravidity ( p= 0.037). Even after adjusting for bone size using BMAD, 32% and 9% of Southeast Asian women and men, respectively, would be considered to have osteoporosis at the femoral neck and 25% and 4%, respectively, at the lumbar spine. These findings indicate a need for culturally sensitive educational interventions for Southeast Asians and for physicians to pursue diagnosis and treatment to prevent osteoporosis-related disabilities in this population. Received: 12 October 2000 / Accepted: 15 February 2001     

Osteocalcin Gene Polymorphism is Related to Bone Density in Healthy Adolescent Females

Recently a polymorphism was found in the human osteocalcin gene, and its association with bone mass was investigated in healthy postmenopausal Japanese women. The osteocalcin gene allelic variant HH was found to be overrepresented in women with osteopenia. The purpose of this study was to investigate whether the previously demonstrated polymorphism of the osteocalcin gene was related to bone mineral density (BMD; g/cm²) or osteopenia in a group of 97 healthy Caucasian adolescent females (aged 16.9 ± 1.2 years, mean ± SD). BMD of the left humerus, right femoral neck, lumbar spine and total body was measured using dual-energy X-ray absorptiometry. The relation between the allelic variants and bone density was analyzed as presence or absence of the H allele. Presence of the H allele was found to be related to a lower BMD of the humerus (0.97 vs 1.02, p = 0.03). There was also a strong tendency towards significance at the femoral neck (p = 0.06) and total body (p = 0.11). Using a multiple linear regression and including physical activity, weight, height and years since menarche, presence of the H allele was found to be an independent predictor of humerus BMD (β=−0.21, p<0.05) and femoral neck BMD (β=−0.23, p<0.01). Using logistic regression, presence of the H allele was also independently associated with a 4.5 times increased risk of osteopenia (p = 0.03) in the whole group. Osteopenia was defined as at least 1 SD lower bone density than the mean for the whole group of at least one of the BMD sites measured. We have demonstrated that the osteocalcin HindIII genotype is independently related to bone density in healthy adolescent females. The present study also suggests that presence of the H allele is predictive of osteopenia at an early age. Received: 31 January 2000 / Accepted: 25 April 2000     

Intensive Insulin Therapy and Bone Mineral Density in Type 1 Diabetes Mellitus: A Prospective Study

To determine the effect of metabolic control on bone mineral density (BMD) in type 1 diabetes mellitus (type 1 DM), we studied BMD (by dual-energy X-ray energy absorptiometry) and bone remodeling parameters in 62 patients with type 1 DM both before and 7 years after commencement of intensive insulin therapy. Overall outcomes after the 7-year treatment included the stabilization of BMD at all sites, as well as a significant decrease in tartrate-resistant acid phosphatase (TRAP) (4.302 ± 2.62 vs 2.65 ± 0.97 IU/l; p = 0.0001) and increase in intact parathyroid hormone (PTHi) (28.05 ± 15.7 vs 39.78 ± 22.41 ng/l; p = 0.005). Presence of diabetic retinopathy (RTP) versus its absence (non-RTP) was associated with lower BMD in femoral neck (FN) (0.831 ± 0.142 vs 0.756 ± 0.153 mg/cm²; p = 0.03) and Ward’s triangle (WT) (0.736 ± 0.165 vs 0.632 ± 0.172 mg/cm²; p = 0.03), and with a lower T-score in FN (–0.93 ± 1.34 vs –1.70 ± 1.46; p = 0.04) and WT (–0.72 ± 1.42 vs –1.540 ± 1.55; p = 0.04) and Z-score in FN (–0.591 ± 1.23 vs –1.132 ± 1.46; p = 0.01). The percentage of patients with osteopenia or osteoporosis in the RTP group was significantly higher than in the non-RTP group (72% vs 53%, p = 0.05; RR= 3.2) and the glycosylated hemoglobin (HbA1c) levels of the RTP group were also higher (8.53 ± 1.6% vs 7.1 ± 1.1%; p = 0.05). The improvement in metabolic control, increase in body mass index and decrease in resorption parameters could contribute to the stabilization of bone mass in type 1 DM but the presence of retinopathy is a critical factor in the progression of diabetic osteopenia. Received: 4 June 1999 / Accepted: 16 November 1999     

Household Tobacco Smoke Exposure is Negatively Associated with Premenopausal Bone Mass

Subjects exposed to environmental tobacco smoke have been found to be at increased risk for several health problems. Whether exposure to passive tobacco smoke is associated with reduced bone mineral density (BMD) is unknown. In order to examine this, we measured BMD in 154 healthy premenopausal women (age range 40–45 years). BMD of the total hip, femoral neck, lumbar spine and total body was measured by dual-energy X-ray absorptiometry (DXA). Data were collected on exposure to household tobacco smoke from age 10 years to the present as well as on other lifestyle factors related to bone mass. We found that 67.5% of the subjects had a history of household tobacco smoke exposure. Subjects exposed to household tobacco smoke had a mean adjusted BMD that was significantly lower at the total hip (p= 0.021) and femoral neck (p= 0.018) compared with subjects who were not exposed. In addition, duration of household tobacco smoke exposure was negatively associated with BMD at the total hip (p = 0.010), femoral neck (p= 0.004), lumbar spine (p = 0.037) and total body (p = 0.031). Subjects exposed to household tobacco smoke for 15 years or more had mean adjusted BMD that was 4% lower at the total body, and more than 8% lower at the total hip, femoral neck and lumbar spine, compared with subjects who were not exposed. In conclusion, household tobacco smoke exposure during adolescence and young adulthood was found to be negatively associated with BMD at the total hip and femoral neck, and duration of exposure was negatively associated with BMD at the total hip, femoral neck, lumbar spine and total body in premenopausal women. Received: 17 December 2001 / Accepted: 16 February 2002     

Regular Physical Exercise and Bone Mineral Density: A Four-Year Controlled Randomized Trial in Middle-aged Men. The DNASCO Study

The aim of the study was to investigate the effects of regular aerobic exercise training on bone mineral density (BMD) in middle-aged men. A population based sample of 140 men (53–62 years) was randomly assigned into the exercise and reference groups. BMD and apparent volumetric BMD (BMD_vol) of the proximal femur and lumbar spine (dual-energy X-ray absorptiometry, DXA) and anthropomorphic measurements were performed at the randomization and 2 and up to 4 years later. The participation rate was 97% and 94% at the second and third BMD measurements, respectively. As another indication of excellent adherence and compliance, the cardiorespiratory fitness (aerobic threshold) increased by 13% in the exercise group. The 2% decrease in the reference group is regarded as an age-related change in cardiorespiratory fitness. Regardless of the group, there was no association between the increase in aerobic threshold and change in BMD. In the entire group, age-related bone loss was seen in the femoral neck BMD and BMD_vol (p<0.01). BMD and BMD_vol values increased with age in L2–L4 (p<0.004). An increased rate of bone loss at the femoral neck was observed in men with a low energy-adjusted calcium intake (p = 0.003). Men who increased their alcohol intake during the intervention showed a decrease in the rate of bone loss at the femoral neck (p = 0.040). A decrease in body height associated with decreased total femoral BMD (r= 0.19, p = 0.04) and the change in body height was a predictor of bone loss in the femoral neck (β= 0.201). Long-term regular aerobic physical activity in middle-aged men had no effect on the age-related loss of femoral BMD. On the other hand, possible structural alterations, which are also essential for the mechanical strength of bone, can not be detected by the DXA measurements used in this study. The increase seen in lumbar BMD reflects age-related changes in the spine, thus making it an unreliable site for BMD follow-up in men. Received: August 2000 / Accepted: November 2000     

Time since Vertebral Fracture: An Important Variable Concerning Quality of Life in Patients with Postmenopausal Osteoporosis

The aim of the study was to identify factors affecting patients with postmenopausal osteoporosis who had experienced one or more vertebral fractures. The overall hypothesis was that time after fracture would influence patients’ perception of pain and well-being. The sample (50 patients) was split into two groups (group A, time after fracture ≤24 months; group B, time after fracture >24 months). A fracture was defined as a vertebral height reduction of more than 20% or at least 4 mm. The assessment was carried out using the Spine Deformity Index and was confirmed by an experienced radiologist. To assess quality of life (QoL) the following measures were used: ‘well-being scale’ including social extroversion as a subscale, pain scale, and limitations in everyday life. The Sense of Coherence questionnaire developed by Antonovsky measures the ability of a person to see life meaningful, manageable and explicable. This questionnaire may reflect patients’ coping abilities and was introduced to establish whether these influence the perception of pain and well-being after vertebral fracture. Variance and covariance analysis was carried out using SPSS (version 6.1). Differences between groups A and B were found for perception of average pain (p = 0.017), social extroversion (p = 0.003) and well-being (p = 0.024). No differences were found for limitations in everyday life (p = 0.607), Sense of Coherence (p = 0.638), the Spine Deformity Index (p = 0.171) and loss of height (p = 0.619). All analyses were corrected for age. Concurrent medication was not found to influence the results. Findings suggest that time after fracture is an important variable when considering QoL and well-being after vertebral fracture and should, therefore, be considered in future studies. Received: 25 June 1998 / Accepted: 10 November 1998     

Determinants of Bone Mineral Density in Middle Aged Men: A Population-Based Study

Osteoporosis is a growing health problem not only in women but also in men. To assess determinants of bone mineral density (BMD) at the spine and proximal femur, a randomly selected sample of 140 Finnish men aged 54–63 years was measured using fan beam dual-energy X-ray absorptiometry. Isometric muscle strength was measured using a computerized measurement system and cardiorespiratory fitness was assessed with maximal oxygen uptake (VO₂max) using breath-by-breath respiratory gas analyses during an incremental bicycle ergometer exercise. Intakes of calcium and energy were estimated using 4-day food records. Smoking habits and alcohol consumption were assessed from an interview and a 4 week diary, respectively. Isometric muscle strength of triceps and biceps brachii, extensors and flexors of thigh and rectus abdominis correlated significantly with BMD (r= 0.18–0.35, p= 0.02–0.000). Calcium intake correlated positively with femoral (r= 0.19–0.28, p= 0.03–0.003), but not with lumbar BMD. In addition, calcium intake adjusted for dietary energy content (mg/MJ) correlated with femoral BMD (r= 0.25–0.36, p= 0.03–0.000). Smoking had no effect on BMD, whereas alcohol intake correlated positively with BMD at L2–L4 (r = 0.19, p= 0.031). In the multiple linear regression analysis adjusted calcium intake predicted BMD in every site measured, while strength of abdominal muscles predicted BMD at Ward’s triangle and femoral neck. Body weight was a predictor of trochanteric BMD. Body height was the best predictor of lumbar and femoral neck area. We conclude that low dietary calcium intake, weak muscle strength and low body weight are risk factors for low BMD in men. Received: 30 August 1999 / Accepted: 29 December 1999     

Association of VDR and Estrogen Receptor Genotypes with Bone Mass in Postmenopausal Caucasian Women: Different Conclusions with Different Analyses and the Implications

Much work has been done on the association between vitamin D receptor (VDR) genotypes and bone mineral density (BMD). Despite considerable effort, the results are inconsistent. While the VDR association remains unresolved, studies have expanded to other candidate genes (i.e., estrogen receptor (ER) genotypes), also yielding inconsistent results. A few studies have suggested that interaction effects between VDR and ER genotypes significantly affect BMD. We assessed associations of BMD with VDR BsmI genotypes, and ER XbaI and PvuII polymorphisms (denoted as ERX and ERP respectively) with spine, femoral neck, distal radius BMD, and with total body bone mineral content (tbBMC) in 108 US Mid-western postmenopausal Caucasian women. We statistically controlled for confounding factors such as height, weight, etc., in the analysis. No significant association was detected for ER genotypes with spine and radius BMD, or for VDR genotypes with femoral neck and radius BMD and tbBMC. No significant interaction between VDR and ER genotypes was detected in our sample. However, the VDR genotypes are significantly (p = 0.004) associated with *5.8% spine BMD variation. Both ERX and ERP genotypes are significantly (p = 0.02) associated with *3.5% femoral neck BMD variation. ERX genotypes are significantly (p = 0.03) associated with *2.4% tbBMC variation. However, if the data were analyzed by simple ANOVA as in some previous studies, without adjusting statistically for confounding factors, all the significant results we found here would have gone undetected. Our findings suggest that: (1) VDR and ER genotypes may have different effects on BMD at different sites and on tbBMC; and (2) if significant factors influencing bone are not appropriately controlled, true significant associations can easily be missed. These findings may offer a partial explanation for some of the earlier inconsistent results of association studies on BMD with VDR and ER genotypes. Received: 4 August 1998 / Accepted: 2 November 1998     

In Vivo MRI Measurements of Bone Quality in the Calcaneus: A Comparison with DXA and Ultrasound

Magnetic resonance imaging (MRI) has shown promise in the assessment of bone architecture. The precision and feasibility of MRI measurements in osteoporosis in vivo have been assessed in this study. T2′ was calculated from measurements of T2 and T2* in the calcaneus of 32 postmenopausal women using a gradient-echo sequence PRIME (Partially Refocused Interleaved Multiple Echo). This sequence allows the measurement of T2 and T2* in one acquisition. In vivo measurements of bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) were made in the calcaneus, spine and femoral neck. The ultrasound parameters broadband ultrasound attenuation (BUA) and speed of sound (SOS) were also measured in the calcaneus. These three techniques have not previously been compared in the same study population. The precision of the MRI technique was poor relative to the DXA and ultrasound techniques, with a CV of 6.9%± 4.4% for T2′ and 5.5%± 3.6% for T2*. Approximately 4% of this is due to system error as determined by phantom measurements. The postmenopausal women were classified as having low BMD if they had a lumbar spine (L2–4) BMD of less than 0.96 g/cm² (more than 2 standard deviations below normal peak bone mass). Calcaneal T2′ was significantly correlated with calcaneal BMD (r = –0.79, p <0.0001), BUA (r = –0.59, p = 0.0004) and SOS (r = –0.58, p = 0.0006). T2′ was significantly different in postmenopausal women with normal BMD and those with low BMD (p <0.01). However, the difference was of only borderline significance (p <0.06) after adjustment for age and years since menopause. Received: 8 July 1997 / Accepted: 29 April 1998     

Proximal Femoral Dimension in Elderly Chinese Women with Hip Fractures in Taiwan

To investigate the relationship between proximal femoral geometry and the occurrence of hip fracture, we compared the geometry of contralateral normal hips of 120 elderly Chinese women with hip fractures, including 63 femoral neck fractures (group A) and 57 intertrochanteric fractures (group B) due to minor trauma, with that of 72 normal elderly Chinese women (group C). The mean ages for group A, B and C subjects were 77.3, 79.7 and 72.9 years, respectively. The femoral neck length (NL), neck width (NW), diameter of femoral head, femoral shaft width just below the lesser trochanter, and neck–shaft angle (θ) were measured on the anteroposterior plain pelvic radiographs. The mean ± SD of NL for group A was 50.4 ± 3.3 mm; for group B, 50.6 ± 3.1 mm; and for group C, 48.8 ± 3.6 mm. Statistical analysis by ANOCOVA and regression showed that only NL of women with hip fractures was significantly longer than controls after correction for age, body height and weight (p <0.01). However, the difference in NL between group A and group B was not significant. By linear regression, the probability of fracture increased only with older age (p <0.001), longer NL (p <0.005) and lighter body weight (p <0.05). By logistic regression, each standard deviation increase in NL increased the risk of hip fracture (age-adjusted odds ratio 1.84; 95% CI, 1.11–3.06). The results confirm the relationship between proximal femoral geometry and the occurrence of hip fracture in elderly Chinese women in Taiwan. Received: 7 August 1998 / Accepted: 6 January 1999     

Determinants of Bone Loss in Elderly Men and Women: A Prospective Population-Based Study

While several studies have described the rate and pattern of involutional bone loss in women, far less information is available for men. Furthermore, the roles of lifestyle and body build in determining bone loss rate in both sexes have been largely extrapolated from cross-sectional studies. We addressed this issue in a population-based longitudinal study which sought to ascertain rates of bone loss at the femoral neck and lumbar spine in a cohort of men and women aged 60–75 years at baseline, and to relate this loss to anthropometric and lifestyle variables. We additionally investigated the capacity of biochemical markers of bone turnover to predict bone loss rates in these subjects. Women lost bone at all sites; this ranged from 0.20%/year at the lumbar spine to 1.43%/year at the femoral trochanteric region. By contrast, men lost only 0.20%/year at the trochanteric region, and gained at the lumbar spine (0.33%/year) and at Ward’s triangle (0.27%/year) over the 4-year period. Anthropometric measurements were associated with bone loss in both sexes; lower baseline body mass index (BMI) and a greater rate of loss of adiposity over the follow-up period were both associated with greater bone loss at all proximal femoral sites. These attained statistical significance after Bonferroni correction at the total proximal femur among both men (r= 0.29), p<0.01) and women (r= 0.31, p<0.05). Lifestyle factors associated with lower rates of bone loss (after adjustment for BMI) included alcohol consumption at the femoral neck among women (p= 0.007) and physical activity at the lumbar spine among men (p = 0.05). Serum parathyroid hormone, 25-hydroxyvitamin D and biochemical markers of bone turnover did not predict bone loss after adjustment for adiposity. Received: 8 December 1998 / Accepted: 8 April 1999     

Effect of Soy Protein on Bone Metabolism in Postmenopausal Japanese Women

We conducted a cross-sectional study of the effects of soybean protein intake on bone mineral density and biochemical markers in 85 postmenopausal Japanese women. Nutrients in the diet of postmenopausal Japanese women visiting the osteoporosis unit, including subjects with normal lumbar spine bone mineral density (L2–4 BMD), were investigated by questionnaire, and the calculated daily energy, protein, soy protein and calcium intake were obtained. L2–4 BMD was measured with dual-energy X-ray absorptiometry, and assays done of serum alkaline phosphatase (ALP) and serum intact osteocalcin (IOC) as bone formation markers and urinary pyridinoline (UPYR) and urinary deoxypyridinoline (UDPYR) as bone resorption markers. Soy protein intake was significantly associated with the Z-score for L2–4 BMD (r= 0.23, p = 0.038) and UDPYR (r =−0.23, p = 0.034). Stepwise multiple regression analyses showed that soy protein intake is significantly associated with the Z-score for L2–4 BMD (β= 0.225, p = 0.04) and UDPYR (β=−0.08, p = 0.03) among four nutritional factors. These results suggest that high soy protein intake is associated with a higher bone mineral density and a lower level of bone resorption, but further studies are needed to confirm the causal dynamic mechanisms. Received: 17 September 1999 / Accepted: 29 February 2000     

Proximal Femur Geometry To Detect and Distinguish Femoral Neck Fractures from Trochanteric Fractures in Postmenopausal Women

Some proximal femur geometry (PFG) parameters, measured by dual-energy X-ray absorptiometry (DXA), have been reported to discriminate subjects with hip fracture. Relatively few studies have tested their ability to discriminate femoral neck fractures from those of the trochanter. To this end we performed a cross-sectional study in a population of 547 menopausal women over 69 years of age with femoral neck fractures (n= 88), trochanteric fractures (n= 93) or controls (n= 366). Hip axis length (HAL), neck–shaft angle (NSA), femoral neck diameter (FND) and femoral shaft diameter (FSD) were measured by DXA, as well as the bone mineral density (BMD) of the nonfractured hip at the femoral neck, trochanter and Ward’s triangle. In fractured subjects, BMD was lower at each measurement site. HAL was longer and NSA wider in those with femoral neck fractures. With logistic regression the age-adjusted odds ratio (OR) for a 1 standard deviation (SD) decrease in BMD was significantly associated at each measurement site with femoral neck fracture (femoral neck BMD: OR 1.9, 95% confidence interval (95% CI): 1.4–2.5; trochanter BMD: OR 1.6, 95% CI 1.2–2.0; Ward’s triangle BMD: OR 1.7, 95% CI 1.3–2.2) and trochanteric fracture (femoral neck BMD: OR 2.6, 95% CI 1.9–3.6; trochanter BMD: OR 3.0, 95% CI 2.2–4.1; Ward’s triangle BMD: OR 1.8, 95% CI 1.4–2.3). Age-adjusted OR for 1 SD increases in NSA (OR 2.2, 95% CI 1.7–2.8) and HAL (OR 1.3, 95% CI 1.1–1.6) was significantly associated with the fracture risk only for femoral neck fracture. In the best predictive model the strongest predictors were site-matched BMD for both fracture types and NSA for neck fracture. Trochanteric BMD had the greatest area (0.78, standard error (SE) 0.02) under the receiver operating characteristic curve in trochanteric fractures, whereas for NSA (0.72, SE 0.03) this area was greatest in femoral neck fractures. These results confirm the association of BMD with proximal femur fracture and support the evidence that PFG plays a significant role only in neck fracture prediction, since NSA is the best predictive parameter among those tested. Received: 24 April 2001 / Accepted: 1 August 2001     

Digital X-ray Radiogrammetry Predicts Hip,Wrist and Vertebral Fracture Risk in Elderly Women: A Prospective Analysis from the Study of Osteoporotic Fractures

Digital X-ray radiogrammetry (DXR) is a technique that uses automated image analysis of standard hand radiographs to estimate bone mineral density (DXR-BMD). Previous studies have shown that DXR-BMD measurements have high precision, are strongly correlated with forearm BMD and are lower in individuals with prevalent fractures. To determine whether DXR-BMD measurements predict wrist, hip and vertebral fracture risk we conducted a case–cohort study within a prospective study of 9704 community-dwelling elderly women (the Study of Osteoporotic Fractures). We compared DXR-BMD, and BMD of the radius (proximal and distal), calcaneus, femoral neck and posteroanterior lumbar spine in women who subsequently suffered a wrist (n= 192), hip (n= 195), or vertebral fracture (n= 193) with randomly selected controls from the same cohort (n= 392–398). DXR-BMD was estimated from hand radiographs acquired at the baseline visit. The radiographs were digitized and the Pronosco X-posure System was used to compute DXR-BMD from the second through fourth metacarpals. Wrist fractures were confirmed by radiographic reports and hip fractures were confirmed by radiographs. Vertebral fractures were defined using morphometric analysis of lateral spine radiographs acquired at baseline and an average of 3.7 years later. Age-adjusted odds ratio (OR, vertebral fracture) or relative hazard (RH, wrist and hip fracture) for a 1 SD decrease in BMD were computed. All BMD measurements were similar for prediction of wrist (RH = 1.5–2.1) and vertebral fracture (OR = 1.8–2.5). Femoral neck BMD best predicted hip fracture (RH = 3.0), while the relative hazards for all other BMD measurements were similar (RH = 1.5–1.9). These prospective data indicate that DXR-BMD performs as well as other peripheral BMD measurements for prediction of wrist, hip and vertebral fractures. Therefore, DXR-BMD may be useful for prediction of fracture risk in clinical settings where hip BMD is not available. Received: 27 April 2001 / Accepted: 10 October 2001     

Vitamin D Receptor Gene Polymorphisms, Bone Mass, Bone Loss and Prevalence of Vertebral Fracture: Differences in Postmenopausal Women and Men

Bone mineral density (BMD), the major determinant of fracture risk, is under strong genetic control. Although polymorphisms of the vitamin D receptor (VDR) gene have been suggested to account for some of the genetic variation in bone mass, the influence of VDR genotypes on osteoporosis remains controversial. Previous published studies have focused mainly on women, but the pattern of response in men has not been determined. Using the BsmI restriction enzyme, we studied the influence of the different VDR genotypes on bone mass, bone loss and the prevalence of vertebral fractures in a population-based sample of both sexes (n = 326). BMD was measured at the lumbar spine and femoral neck, with a 4-year interval, using dual-energy X-ray absorptiometry. Vertebral fractures were assessed by two lateral radiographs at the beginning and end of the study. The prevalence of the three possible VDR genotypes was similar to those in other Caucasian populations and no differences were found between men and women. Women with the favorable bb genotype showed significantly higher BMD values at the lumbar spine and femoral neck, and a positive rate of BMD change at the femoral neck compared with women with the BB and Bb genotypes. Moreover, women with the bb genotype showed a trend toward a lower prevalence and incidence of vertebral fractures (p= 0.07). We have not found any differences between VDR genotypes in men. In conclusion, VDR gene polymorphisms are related to bone mass and bone loss in women; also a trend in the prevalence of vertebral fractures was observed in postmenopausal women but not in men. Received: 8 June 1998 / Accepted: 7 December 1998     

A Randomized Trial of Sodium Fluoride (60 mg) ± Estrogen in Postmenopausal Osteoporotic Vertebral Fractures: Increased Vertebral Fractures and Peripheral Bone Loss with Sodium Fluoride; Concurrent Estrogen Prevents Peripheral Loss, But Not Vertebral Fractures

Postmenopausal Caucasian women aged less than 80 years (n= 99) with one or more atraumatic vertebral fracture and no hip fractures, were treated by cyclical administration of enteric coated sodium fluoride (NaF) or no NaF for 27 months, with precautions to prevent excessive stimulation of bone turnover. In the first study 65 women, unexposed to estrogen (–E study), age 70.8 ± 0.8 years (mean ± SEM) were all treated with calcium (Ca) 1.0–1.2 g daily and ergocalciferol (D) 0.25 mg per 25 kg once weekly and were randomly assigned to cyclical NaF (6 months on, 3 months off, initial dose 60 mg/day; group F CaD, n= 34) or no NaF (group CaD, n= 31). In the second study 34 patients, age 65.5 ± 1.2 years, on hormone replacement therapy (E) at baseline, had this standardized, and were all treated with Ca and D and similarly randomized (FE CaD, n= 17; E CaD, n= 17) (+E study). The patients were stratified according to E status and subsequently assigned randomly to ± NaF. Seventy-five patients completed the trial. Both groups treated with NaF showed an increase in lumbar spinal density (by DXA) above baseline by 27 months: FE CaD + 16.2% and F CaD +9.3% (both p= 0.0001). In neither group CaD nor E CaD did lumbar spinal density increase. Peripheral bone loss occurred at most sites in the F CaD group at 27 months: tibia/fibula shaft –7.3% (p= 0.005); femoral shaft –7.1% (p= 0.004); distal forearm –4.0% (p = 0.004); total hip –4.1% (p = 0.003); and femoral neck –3.5% (p= 0.006). No significant loss occurred in group FE CaD. Differences between the two NaF groups were greatest at the total hip at 27 months but were not significant [p<0.05; in view of the multiple bone mineral density (BMD) sites, an alpha of 0.01 was employed to denote significance in BMD changes throughout this paper]. Using Cox’s proportional hazards model, in the –E study there were significantly more patients with first fresh vertebral fractures in those treated with NaF than in those not so treated (RR = 24.2, p= 0.008, 95% CI 2.3–255). Patients developing first fresh fractures in the first 9 months were markedly different between groups: –23% of F CaD, 0 of CaD, 29% of FE CaD and 0 of E CaD. The incidence of incomplete (stress) fractures was similar in the two NaF-treated groups. Complete nonvertebral fractures did not occur in the two +E groups; there were no differences between groups F CaD and CaD. Baseline BMD (spine and femoral neck) was related to incident vertebral fractures in the control groups (no NaF), but not in the two NaF groups. Our results and a literature review indicate that fluoride salts, if used, should be at low dosage, with pretreatment and co-treatment with a bone resorption inhibitor. Received: 22 August 2000 / Accepted: 23 July 2001     

Fractal Analysis of Trabecular Bone Texture on Calcaneus Radiographs: Effects of Age, Time Since Menopause and Hormone Replacement Therapy

An analysis of trabecular bone texture based on fractal mathematics, when applied to trabecular bone images on plain radiographs, can be considered as a reflection of trabecular bone microarchitecture. It has been shown to be able to distinguish postmenopausal osteoporosis cases from controls. This cross-sectional study was carried out to investigate the influence of age, time since menopause and hormone replacement therapy (HRT) on the fractal dimension of trabecular bone texture at the calcaneus in a sample of 537 healthy women. Fractal analysis of texture was performed on calcaneus radiographs and the result expressed as the Hmean parameter (H = 2–fractal dimension). Total hip, femoral neck and lumbar spine bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. There was a statistically significant Hmean parameter decrease with age (p<0.0001) but the degree of correlation was low (r=–0.2) compared with the correlation between age and BMD (r=–0.36 to –0.61 according to the BMD site). We found a weak but statistically significant correlation between time since menopause and Hmean (r=–0.14, p= 0.03) in the 241 postmenopausal women included in the study. Hmean was significantly lower in a group of postmenopausal women without HRT (n= 110) compared with a group of age-matched postmenopausal women with HRT (n = 110): respectively 0.683 ± 0.043 and 0.695 ± 0.038 (p= 0.03). In conclusion, this study suggests that there is a menopause- and age-related decrease in the Hmean parameter and that HRT interferes with the results of the fractal analysis of trabecular bone texture on calcaneus radiographs. Received: 2 March 2001 / Accepted: 2 October 2001     

Effect of Intra-Abdominal Position of the Bladder Neck and Stability of its Supporting Structures on Pressure Transmission Ratio After Colposuspension

The aim of this prospective study was to evaluate the influence of the higher intra-abdominal position of the bladder neck and the stability of its supporting structures after colposuspension, on pressure transmission to the urethra at the level of the bladder neck. Twenty-eight patients were included in the study. The pressure transmission ratio (PTR) was calculated at the level of the bladder neck, whereas the position and mobility of the bladder neck during coughing were evaluated with perineal ultrasound examination. The measurements were performed before and 3 months after colposuspension. After colposuspension we found a significant elevation of the PTR (P = 0.001), a significantly higher intra-abdominal position (P = 0.001) and decreased mobility (P = 0.001) of the bladder neck during coughing. Also, a negative correlation between the elevation of PTR and decreased mobility of the bladder neck during coughing (r=−0.5049; P = 0.006) and a weak correlation between the elevation of PTR and a higher intra-abdominal position of the bladder neck during coughing were found (r= 0.3828; P = 0.044). Reinforced tension resistance of the bladder neck supporting structures seems to be more important than intra-abdominal position of the bladder neck in achieving effective pressure transmission after colposuspension.     

Targeted exercises against hip fragility

Summary  Compared to high-impact exercises, moderate-magnitude impacts from odd-loading directions have similar ability to thicken vulnerable cortical regions of the femoral neck. Since odd-impact exercises are mechanically less demanding to the body, this type of exercise can provide a reasonable basis for devising feasible, targeted bone training against hip fragility. Introduction  Regional cortical thinning at the femoral neck is associated with hip fragility. Here, we investigated whether exercises involving high-magnitude impacts, moderate-magnitude impacts from odd directions, high-magnitude muscle forces, low-magnitude impacts at high repetition rate, or non-impact muscle forces at high repetition rate were associated with thicker femoral neck cortex. Methods  Using three-dimensional magnetic resonance imaging, we scanned the proximal femur of 91 female athletes, representing the above-mentioned five exercise-loadings, and 20 referents. Cortical thickness at the inferior, anterior, superior, and posterior regions of the femoral neck was evaluated. Between-group differences were analyzed with ANCOVA. Results  For the inferior cortical thickness, only the high-impact group differed significantly (~60%, p = 0.012) from the reference group, while for the anterior cortex, both the high-impact and odd-impact groups differed (~20%, p = 0.042 and p = 0.044, respectively). Also, the posterior cortex was ~20% thicker (p = 0.014 and p = 0.006, respectively) in these two groups. Conclusions  Odd-impact exercise-loading was associated, similar to high-impact exercise-loading, with ~20% thicker cortex around the femoral neck. Since odd-impact exercises are mechanically less demanding to the body than high-impact exercises, it is argued that this type of bone training would offer a feasible basis for targeted exercise-based prevention of hip fragility.