Mandibular Radiomorphometric Indices in the Diagnosis of Reduced Skeletal Bone Mineral Density

Diagnosis of osteoporosis allows the delivery of preventive and therapeutic intervention and is usually achieved using bone densitometric techniques. One referral criterion for densitometry is osteopenia on radiographs. The aim of this study was to measure the validity of mandibular cortical indices measured on panoramic radiographs in the diagnosis of reduced skeletal bone density. Seventy-four women underwent bone densitometry of the femoral neck, lumbar spine and the forearm. Fifty-five patients (74%) were classified as having a reduced bone density (T-score ≤–1). Twenty-seven patients had a T-score of <–2.5 observed at one or more of the three measurement sites. A panoramic radiograph was taken of each patient and two observers made measurements of cortical thickness at the mental foramen (mental index, MI), antegonion (antegonial index, AI) and gonion (gonial index, GI) regions. Logistic regression and receiver operating characteristic (ROC) curve analyses were used to measure the validity of cortical indices in the diagnosis of reduced bone mineral density. Only MI contributed significantly to a diagnosis of low skeletal bone mineral density (T-score ≤–1). The 95% limits of agreement between observers in measurement of MI were 1.32 to +1.32 mm. When data for both observers were combined, the area under the ROC curve was 0.733 (SE = 0.072; 95% confidence interval = 0.618 to 0.83), indicating moderate accuracy. A diagnostic threshold for MI of 3 mm (or less) is suggested as the most appropriate threshold for referral for bone densitometry. However, the study provided only limited support for the use of panoramic radiomorphometric indices in diagnosing low skeletal bone mineral density. They might, questionably, be used as part of a method of osteoporosis risk assessment. Received: 4 May 2001 / Accepted: 13 November 2001     

Prevalence of Reduced Bone Mineral Density in Patients with Anti-neutrophil Cytoplasmic Antibody Associated Vasculitis and the Role of Immunosuppressive Therapy: A Cross-Sectional Study

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a relapsing-remitting disease, which is treated with corticosteroids (CS) in combination with cyclophosphamide. One of the major side-effects of this treatment is osteoporosis, which may result in the increased occurrence of fractures. In the present study we measured the prevalence of reduced bone mineral density (BMD) in a cross-sectional cohort of patients and correlated BMD findings with cumulative doses of CS and/or cyclophosphamide. BMD was measured by dual-energy X-ray absorptiometry (DXA) of the lumbar spine, radius and proximal femur between January 1998 and December 1999. Cumulative doses of CS and cyclophosphamide were calculated by chart review. Ninety-nine consecutive patients (48 men, 51 women) aged 55 ± 16 years (mean ± SD) were studied 50 months (median; range 0–400 months) after a diagnosis of ANCA-associated vasculitis had been made. Sixty-nine patients were treated with 10.7 g (median cumulative dose; range 0.4–67.2g) of CS, and 88 patients were treated with 34.1 g (median cumulative dose; range 0.8–324.3g) of cyclophosphamide. Fifty-seven percent of the patients had osteopenia (T-score: –1 to –2.5 SD), and 21% had osteoporosis (T-score: <−2.5 SD) at least at one site. Thirty-four of 37 (92%) postmenopausal women, 9 of 14 (64%) premenopausal women, and 34 of 48 (71%) men had either osteopenia or osteoporosis. The mean age- and sex-adjusted BMD (Z-score) of the proximal femur in men was found to be significantly lower than zero. Cumulative dose of CS therapy showed an inverse relation with Z-scores at the lumbar spine (p= 0.035) and proximal femur (p = 0.011). Cumulative dose of cyclophosphamide was not correlated with Z-scores. Osteopenia and osteoporosis are thus frequently observed in patients with ANCA-associated vasculities. However, only in men is the mean Z-score significantly lower than zero. Cumulative dose of CS therapy is significantly associated with bone loss at the spine and femur. Received: 26 March 2001 / Accepted: 1 August 2001     

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     

Determinants of Bone Mineral Density in Older Men

Although osteoporosis in men is increasingly recognized as an important health issue and bone mass appears to be a major determinant of fracture, there remain few data concerning the determinants of bone mass in men. To determine the correlates of bone density in men, we studied a large group of older subjects recruited from three rural communities in the northwestern United States. Three hundred and fifty-five men over the age of 60 years (mean 71.5 ± 7.4 years) without known disorders of mineral metabolism were recruited by community advertising. Bone mineral density was measured at the lumbar spine, proximal femur and radius by dual-energy X-ray absorptiometry, and factors potentially related to skeletal status were assessed by direct measurements or questionnaire. In univariate analyses weight (positively) and age (negatively) were associated with bone density. After adjustment for these two factors, alcohol intake, osteoarthritis and thiazide use were associated with higher bone density, while previous fractures, gastrectomy, peptic ulcer disease, rheumatoid arthritis, glucocorticoid use, hypertension, previous hyperthyroidism, height loss since age 20 years, chronic lung disease and smoking were related to lower density. In multivariate models, only weight and a history of cancer were related to higher bone mass, and age, previous fracture, rheumatoid arthritis, gastrectomy and hypertension were associated with lower density. These data contribute to the emerging field of osteoporosis in men, and may help in the clinical identification of men at higher risk of osteopenia. Received: 27 September 1999 / Accepted: 20 March 2000     

Vertebral Deformities and Low Bone Mineral Density in Adults with Cystic Fibrosis: A Cross-sectional Study

Patients with cystic fibrosis (CF) have low bone mineral density (BMD). The clinical relevance of this is not clearly established. The aim of this study was to determine the prevalence of low BMD and vertebral deformities in CF adults with varied disease severity. One hundred and seven patients (58 men) aged 18–60 years underwent dual-energy X-ray absorptiometry scanning of the lumbar spine and hip, radiology of the spine and biochemical studies. Thirty-eight percent had a Z-score of <−1, with 13% having Z-scores <−2. Seventeen percent had evidence of vertebral deformity on radiography, mostly in the thoracic spine. Thirty-five percent reported past fractures, of which 9% were rib fractures. Percent predicted forced expiratory volume in 1 second (FEV1) and the amount of daily physical activity were positively related to BMD. The number of intravenous antibiotic courses in the previous 5 years was negatively related to BMD. Patients with a history of rib fracture and CF-related diabetes had significantly lower femoral neck BMD (p<0.02). The median serum 25-hydroxyvitamin D was 28 nmol/l, with 36% of patients having levels below 25 nmol/l despite vitamin D supplementation. Forty-four percent had raised levels of urinary pyridinium crosslinks (NTx). In conclusion, fragility fractures and hypovitaminosis D occur commonly in adult patients with CF. Low BMD occurs in patients with more severe disease and significantly relates to FEV₁, infective exacerbations and daily energy expended in physical activity. Received: 27 June 2000 / Accepted: 1 December 2000     

Bone Mineral Density and Body Composition in Ulcerative Colitis: A Six-Year Follow-up

Reduced bone mineral density (BMD) has been reported in ulcerative colitis (UC), but there are no data concerning body composition (fat and lean mass) in such patients. We used whole body dual-energy X-ray absorptiometry (Hologic QDR 1000W) at baseline and after 6 years of follow-up to study bone density, and fat and lean mass in 43 outpatients with mild UC (21 men, mean age 36 years, range 21–57 years, and 22 women, mean age 35 years, range 23–45 years at baseline; disease extent: 2 proctitis, 18 proctosigmoiditis, 8 left colitis, 5 substantial colitis, 10 pancolitis; mean disease duration 8 years, range 2–18 years; no hospitalization; few relapses during the follow-up) and 111 healthy volunteers matched by sex, age and body mass index. There were 5 drop-outs. We observed no significant difference in BMD, or fat and lean mass between the male patients and controls at baseline or after 6 years. The total lean mass (Z-score =−3.2, p=0.001) and trunk lean mass (Z-score =−2.01, p=0.03) of the female patients were lower than those of the controls at baseline, whereas their limb lean mass was higher at both the beginning and the end of the study (Z-score = 2.14, p=0.03; Z-score = 2.8, p=0.004, respectively). At baseline there was a significant negative correlation between lifetime steroid intake (enteral and parenteral) and lumbar spine BMD, obtained as whole body subregion (r=−0.53, p=0.0006). After 6 years there was a significant negative correlation in women between whole body and lumbar spine BMD and both steroid intake (r=−0.53, p=0.01; and r=−0.62, p=0.003) and the number of relapses (r=−0.49, p=0.02; and r=−0.44, p=0.05). Mild UC thus does not represent a risk factor for osteopenia per se. The differences in lean mass between the female patients and controls do not seem to be clinically relevant. Received: July 2000 / Accepted: October 2000     

Bone Mineral Density and Vertebral Fractures in Men

In women, many studies indicate that the risk of vertebral fragility fractures increases as bone mineral density (BMD) declines. In contrast, few studies are available for BMD and vertebral fractures in men. It is uncertain that the strength of the relationship between BMD and fractures is similar in magnitude in middle-aged men and in postmenopausal women. In the present study, 200 men (mean age 54.7 years) with lumbar osteopenia (T-score <−1.5) were recruited to examine the relationships between spine BMD and hip BMD and the associations of BMD with vertebral fractures. Lumbar BMD was assessed from L2 to L4, in the anteroposterior view, using dual-energy X-ray densitometry. At the upper left femur, hip BMD was measured at five regions of interest: femoral neck, trochanter, intertrochanter, Ward’s triangle and total hip. Spinal radiographs were analyzed independently by two trained investigators and vertebral fracture was defined as a reduction of at least 20% in the anterior, middle or posterior vertebral height. Spinal radiographs evidenced at least one vertebral crush fracture in 119 patients (59.5%). The results of logistic regression showed that age, femoral and spine BMDs were significant predictors of the presence of a vertebral fracture. Odds ratios for a decrease of 1 standard deviation ranged from 1.8 (1.3–2.8) for spine BMD to 2.3 (1.5–3.6) for total hip BMD. For multiple fractures odds ratios ranged from 1.7 (1.1–2.5) for spine BMD to 2.6 (1.7–4.3) for total hip BMD. In all models, odds ratios were higher for hip BMD than for spine BMD, particularly in younger men, under 50 years. A T-score <−2.5 in the femur (total femoral site) was associated with a 2.7-fold increase in the risk of vertebral fracture while a T-score <−2.5 in the spine was associated with only a 2-fold increase in risk. This study confirms the strong association of age and BMD with vertebral fractures in middle-aged men, shows that the femoral area is the best site of BMD measurement and suggests that a low femoral BMD could be considered as an index of severity in young men with lumbar osteopenia. Received: 27 October 1998 / Accepted: 22 February 1999     

Bone Mineral Density and Metabolism in Familial Dysautonomia

Familial dysautonomia (FD) patients suffer from multiple fractures and have reduced bone pain, which defers the diagnosis. The pathogenesis of bone fragility in FD is unknown. This study aimed to characterize bone mineral metabolism and density in FD. Seventy-nine FD patients aged 8 months to 48 years (mean age 13.9 ± 10.4 years, median 12.3) were studied. Clinical data included weight, height, bone age, weekly physical activity and history of fractures. Bone mineral density (BMD) of the lumbar spine (n= 43), femoral neck (n= 26), total hip (n= 22) and whole body (n= 15) were determined by dual-energy X-ray absorptiometry. Serum 25-hydroxyvitamin D₃, osteocalcin, bone alkaline phosphatase (B-ALP), parathyroid hormone and urinary N-telopeptide cross-linked type 1 collagen (NTx) were determined in 68 patients and age- and sex-matched controls. Forty-two of 79 patients (53%) sustained 75 fractures. Twenty-four of 43 patients had a spine Z-score <–2.0, and 13 of 26 had a femoral neck Z-score <–2.0. Mean femoral neck BMD Z-score was lower in patients with fractures compared with those without (–2.5 ± 0.9 vs –1.5 ± 1.0, p= 0.01). Mean body mass index (BMI) was 16 kg/m² in prepubertal patients and 18.4 kg/m² in postpubertal patients. Bone age was significantly lower than chronological age (75.5 vs 99.3 months in prepubertal patients, p<0.001; 151 vs 174 in post-pubertal patients, p<0.05). NTx and osteocalcin levels were higher in FD patients compared with controls (400 ± 338 vs 303 ± 308, BCE/mM creatinine p<0.02; 90 ± 59.5 vs 61.8 ± 36.9 ng/ml, p<0.001, respectively). B-ALP was lower in FD patients compared with controls (44.66 ± 21.8 vs 55.36 ± 36.6 ng/ml, p<0.04). Mean spine Z-score was significantly lower in physically inactive compared with active patients (–3.00 ± 1.70 vs –1.77 ± 1.3, respectively, p= 0.05). We conclude that fractures in FD patients are associated with reduced BMD. FD patients have increased NTx and osteocalcin. Contributing factors include reduced BMI, failure to thrive and reduced physical activity. Preventive therapy and early diagnosis are essential. Received: 21 May 2001 / Accepted: 27 November 2001     

Serum Albumin and Bone Mineral Density in Healthy Older Men and Women: The Rancho Bernardo Study

Serum albumin has been found to be positively correlated with bone mass in small studies of ambulatory men or women with diagnosed osteoporosis. In this study the relation between serum albumin and bone mineral density (BMD) was examined in 1593 white, community-dwelling men and women aged 50–95 years. BMD was determined using single-photon absorptiometry (SPA) at the ultradistal radius and the midshaft radius, and using dual-energy X-ray absorptiometry (DXA) at the hip and spine. Albumin was measured from a fasting blood sample using the Technicon SMA 12 autoanalyzer. Mean albumin levels in both men and women decreased significantly with increasing age. All but four values were within the normal range (3.5–5.0 g/dl). BMD decreased with increasing age at all sites. In both sexes there was weak positive correlation between serum albumin and BMD in the unadjusted model (Pearson's rvalues <0.3, p values <0.005). After age adjustment, however, the relationship was no longer significant (Pearson's r values <0.05, p values >0.18). Men and women were divided into three sex-specific categories – osteoporotic, osteopenic and normal – based on World Health Organization criteria in relation to young adult means (normal, BMD > –1 SD; osteopenia, BMD between –1 SD and –2.5 SD; osteoporosis, BMD <–2.5 SD). Mean albumin values did not differ significantly across the three BMD categories in men or women. BMD levels stratified for albumin levels and calcium supplement status (a marker for osteoporosis awareness) also did not differ. Albumin levels were also not associated with a history of low-trauma fractures. In summary, there was no age-independent association between serum albumin within the normal range and low BMD or fractures in community-dwelling healthy older adults. We conclude that previously reported associations most likely reflect inadequate adjustment for the age-related decrease in albumin levels and the selection of very frail osteoporotic subjects. Received: 7 October 1997 / Revised: 21 January 1998     

Calcium Absorption in Postmenopausal Osteoporosis: Benefit of HRT Plus Calcitriol, but not HRT Alone, in both Malabsorbers and Normal Absorbers

In a randomized trial involving 71 postmenopausal osteoporotic women with vertebral compression fractures, radiocalcium absorption studies using the ⁴⁵Ca single isotope method (α) were performed at baseline and after 8 months of treatment with either continuous combined hormone replacement therapy (HRT, as piperazine estrone sulfate 0.625–0.937mg daily ± medroxyprogesterone acetate 2.5 mg daily depending on uterine status) or HRT plus calcitriol 0.25 μg twice daily. A calcium supplement of 600 mg nocte was given to only those women who had a daily calcium intake of less than 1 g per day at baseline, as assessed by recalled dietary intake. There was a significant decrease [0.74 (± 0.35 SD) to 0.58 (± 0.22), Dα=−0.17 (± 0.26), p<0.0005] in α at 8 months compared with baseline in the HRT-treated group, but a significant increase [0.68 (± 0.31) to 0.84 (± 0.27), Dα=+0.16 (± 0.30), p<0.003] in the HRT-plus-calcitriol treated patients, resulting in α being significantly higher after 8 months in the latter group than in the HRT-only group. Although 72% of the patients had been supplemented with calcium between the first and second studies, separate analyses revealed that the change in calcium intake had not affected the result. Further breakdown of the groups into baseline ‘normal’ absorbers (α≥0.55) and ‘malabsorbers’ (α <0.55) revealed that α decreased with HRT treatment only in the normal absorbers, and remained stable in the malabsorbers. Conversely, following HRT plus calcitriol treatment, α increased only in the malabsorbers, the normal absorbers in this group remaining unchanged. In conclusion, our data show that HRT, of the type and dose used in this study, did not produce an increase in absorption efficiency; it was in fact associated with a fall. Increased absorption efficiency cannot be achieved unless calcitriol is used concurrently, and then only in patients with malabsorption. Calcitriol also had a significant effect in normal absorbers in that it prevented the decline in α seen with HRT alone, and thus should be considered in all patients with postmenopausal osteoporosis treated with HRT. Received: 6 October 1998 / Accepted: 3 May 1999     

Influence of Current and Past Hormone Replacement Therapy on Bone Mineral Density: A Study of Discordant Postmenopausal Twins

There is controversy about the ideal timing of hormone replacement therapy (HRT) and duration of treatment. In this study we have examined intrapair differences in bone mineral density (BMD) in twins who were discordant for HRT use. Twin pairs in which only one co-twin had been exposed to HRT for more than 12 months continuously were selected from 365 postmenopausal monozygotic (MZ) and dizygotic (DZ) pairs recruited as part of the St Thomas’ Adult UK Twin Registry of normal volunteers. BMD was measured by dual-energy X-ray absorptiometry at the lumbar spine and femoral neck. Intrapair differences in BMD between HRT users and non-users were compared. A total of 65 HRT-discordant pairs were identified, of which 36 were discordant for current HRT use (mean age: 55.3 years, median duration of HRT use: 36 months) and 29 were discordant for past HRT use (mean age: 60.4 years, median HRT duration: 30 months). Among current users BMD was consistently and significantly higher than in non-users at both sites (lumbar spine mean intrapair difference (IPD%): 12.3%, 95% confidence interval (CI): 7.1%, 17.5%; femoral neck IPD%: 8.6%, 95% CI: 3.4%, 13.7%). The intrapair differences were substantially smaller when past users and non-users were compared (lumbar spine IPD%: 2.4%, 95% CI: −3.7%, 8.6%; femoral neck IPD%: 0.4%, 95% CI: −5.3%, 6.0%). These differences remained little changed after adjusting for the potential confounding effects of the duration of HRT use, and intrapair differences in alcohol and tobacco consumption and physical exercise. The results confirm, in a closely matched design, the findings of other observational research that current use of HRT has a major effect on BMD at the lumbar spine and femoral neck. Past users of HRT do not, however, show the same benefits. The clinical implications of these findings are that HRT needs to be used continuously to influence BMD and that alternative treatments need to be considered in those who discontinue HRT. Received: 18 August 1997 / Accepted: 4 June 1998     

Bone Mineral Density in the Long Term after Liver Transplantation

Hepatic osteodystrophy is a complication of chronic liver disease and bone mass is known to decline further in the first year after liver transplantation. The present study focused on bone mineral density (BMD) between 1 and 15 years after liver transplantation under a prednisolone- and azathioprine-based immunosuppressive regimen. Three groups of adult patients were studied: group 1, 45 patients with a follow-up of 5–9 years after transplantation, had BMD measurements done at 1, 2 and 5 years after transplantation; group 2, 17 patients with a follow-up of 10–14 years, had BMD measurements done at 5 and 10 years; group 3, 4 patients with a follow-up of more than 15 years, had BMD measurements done at 10 and 15 years. BMD of lumbar spine (L1–L4) and proximal femur was measured using dual-energy X-ray absorptiometry, and at the same time radiographs of the spine and hips were made. Spinal BMD increased significantly, during the second post-transplant year; subsequently no significant changes were seen. Proximal femur BMD decreased slightly, but significantly during the second year, and remained stable afterwards. About one-third of patients had a BMD below the fracture threshold (= 0.798 g/cm² for the lumbar spine and 0.675 g/cm² for the hip) during the follow-up. In 5 of the 66 patients studied, new vertebral fractures occurred. No fractures or avascular necrosis of the hips were seen. Furthermore, after transplantation lower Z-scores of the hip were found in patients with pre-transplant cholestatic liver diseases, and lower Z-scores of the lumbar spine were found in men compared with women. Long-term follow-up of BMD up to 15 years after transplantation revealed an improvement mainly in the second postoperative year with no deterioration afterwards. Nevertheless a substantial number of patients (around one-third) kept a BMD below the fracture threshold, and new fractures may occasionally occur. The overall outcome appeared somewhat less favorable in men and patients transplanted for cholestatic liver diseases. Received: 15 July 1999 / Accepted: 11 January 2000     

The Profile of Bone Mineral Density in Chinese Women: Its Changes and Significance in a Longitudinal Study

Bone mineral density (BMD) has been shown to be different in different ethnic groups. When lifestyle and diet evolve, there is a possibility of a change in the normal reference BMD values within an ethnic group over a period of time. As the osteoporotic risk uses the T-score as the bench mark, it is pertinent to evaluate whether such changes do occur. Two measurements, 5 years apart, of the BMD of the spine and the hip were made in a cohort of Chinese women in Hong Kong. A kernel function smoothing method, a nonparametric statistical method, was employed to present the BMD data. The greatest rate of bone loss was found to occur between 50 and 59 years of age, but this rate of loss was reduced from age 60 onwards. The BMD values obtained in these two measurements were different from the previous studies in the same population and were found to be higher at the lumbar spine and neck of femur in women over 65 years of age. Even within the cohort, there seemed to be a reduction in the BMD values of the hip in a span of 5 years, although the differences were statistically insignificant. These studies suggest that BMD values could change in a population for a variety of possible reasons. Hence, the reference BMD values might need to be evaluated at regular intervals for the T-score to be meaningful. Received: 26 April 2000 / Accepted: 8 February 2001     

Bone Mineral Density at the Hip Predicts Mortality in Elderly Men

Low bone density as assessed by calcaneal ultrasound has been associated with mortality in elderly men and women. We examined the relationship between bone density measured at the hip and all cause and cardiovascular mortality in elderly men. Men aged 65–76 years from the general community were recruited from general practices in Cambridge between 1991 and 1995. At baseline survey, data collection included health questionnaires, measures of anthropometry and cardiovascular risk factors, as well as bone mineral density (BMD) measured using dual energy X-ray absorptiometry. All men have been followed up for vital status up to December 1999. BMD was significantly inversely related to mortality from all causes and cardiovascular disease, with decreasing rates with increasing bone density quartile, and an approximate halving of risk between the bottom and top quartile (p <0.002, test for trend all causes and p <0.025, test for trend for cardiovascular deaths). In multivariate analyses using the Cox proportional hazards model, an increase of 1 standard deviation (0.144 g/cm²) in total hip bone density was significantly associated with an age-adjusted 0.77 relative risk (95% CI 0.66–0.91) for all-cause mortality and 0.76 relative risk (95% CI 0.62–0.93) for cardiovascular disease mortality. The association remained significant after adjusting for age, body mass index, cigarette smoking status, serum cholesterol, systolic blood pressure, past history of heart attack, stroke or cancer and other lifestyle factors which included use of alcohol, physical activity and general health status. Low bone density at the hip is thus a strong and independent predictor of all-cause and cardiovascular mortality in older men. Received: 16 August 2000 / Accepted: 27 October 2000     

The Prevalence of Low Bone Mineral Density in Dutch Perimenopausal Women: The Eindhoven Perimenopausal Osteoporosis Study

The aim of this study was to estimate the prevalence of osteopenia and osteoporosis in perimenopausal women, and to assess determinants of low bone mineral density (BMD). All women born between 1941 and 1947 (aged between 46 and 54 years) living in the city of Eindhoven were invited to participate in the study; 5896 white Dutch women, representing 73% of the total number of Dutch women in this age group, were studied. Of these, 24% were using estrogen preparations and 19% had undergone hysterectomy, with or without oophorectomy. All women were interviewed and bone mineral density (BMD) of the lumbar spine was measured by dual-energy X-ray absorptiometry (DXA). Osteopenia and osteoporosis were defined according to the criteria proposed by a WHO working group. In the population studied the prevalence of osteopenia and osteoporosis was 27.3% and 4.1%, respectively. With progression from premenopause to menopause, the prevalence of osteoporosis increased from 0.4% to 12.7%, and that of osteopenia from 14.5% to 42.8%. An increased risk for low BMD (osteopenia and osteoporosis) was associated with age, menopausal status and smoking, while alcohol consumption, high body mass index (BMI) and use of estrogens had a protective effect. This study of a large population-based cohort of perimenopausal women revealed a high prevalence of low bone mass and, therefore, a higher risk for osteoporotic fractures. The data further suggest that, when issues on the long-term efficacy and safety of preventive treatments are resolved, it may be possible to identify women at higher risk who are most likely to benefit from screening strategies. Received: 2 June 1997 / Accepted: 21 January 1998     

Occupational Activity and Bone Mineral Density in Postmenopausal Women in England

Few studies have assessed the relationship between occupational activity and bone mineral density (BMD), although two case–control studies have reported a protective effect of occupational activity on hip fracture. In the present study 580 postmenopausal women aged 45–61 years completed a risk factor questionnaire including a detailed occupational history. For each job, hours spent sitting, standing, walking, lifting and carrying were recorded; these measures, evaluated at ages 20, 30, 40 years, in the current job and over the working lifetime, were used in the analysis. BMD was measured with dual-energy X-ray absorptiometry, and measurements at five sites were used in a multiple regression analysis adjusting for potential confounding variables. There was a significant negative association between sitting at age 20 years and BMD at the radius (p= 0.037), with negative relationships of borderline significance at the anteroposterior spine (p = 0.091) and whole body (p= 0.078). There were significant positive associations between standing at age 30 years and BMD at all five sites (p<0.05), but no significant linear associations for standing at ages 20 and 40 years. No significant associations were found for lifetime or current occupational measures of sitting, standing, walking and lifting or carrying. The lack of consistency of these significant findings suggests that they may have occurred by chance, and that occupational activity has little if any effect on BMD in postmenopausal women. Received: 12 March 1999 / Accepted: 17 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     

Estimation of Bone Mineral Density by Digital X-ray Radiogrammetry: Theoretical Background and Clinical Testing

A new automated radiogrammetric method to estimate bone mineral density (BMD) from a single radiograph of the hand and forearm is described. Five regions of interest in radius, ulna and the three middle metacarpal bones are identified and approximately 1800 geometrical measurements from these bones are used to obtain a BMD estimate of the distal forearm, referred to as BMD_DXR (from digital X-ray radiogrammetry, DXR). The measured dimensions for each bone are the cortical thickness and the outer width, in combination with an estimate of the cortical porosity. The short-term in vivo precision of BMD_DXR was observed to be 0.60% in a clinical study of 24 women and the in vitro variation over 12 different radiological clinics was found to be 1% of the young normal BMD_DXR level. In a cohort of 416 women BMD_DXR was found to be closely correlated with BMD at the distal forearm measured by dual-energy X-ray absoptiometry (r= 0.86, p<0.0001) and also with BMD at the spine, total hip and femoral neck (r= 0.62, 0.69 and 0.73, respectively, p<0.0001 for all). The annual decline was estimated from the cohort to be 1.05% in the age group 55–65 years. Relative to this age-related loss, the reported short-term precision allows for monitoring intervals of 1.0 years and 1.6 years in order to detect expected age-related changes with a confidence of 80% and 95%, respectively. It is concluded that the DXR method offers a BMD estimate with a good correlation with distal forearm BMD, a low variation between geographical sites and a precision that potentially allows for relatively short observation intervals. Received: 8 November 2000 / Accepted: 14 June 2001     

High Bone Mineral Density in Male Elite Professional Volleyball Players

The aim of this study was to assess bone mass in male elite athletes participating in an impact loading sport (volleyball) and, in particular, to determine whether the asymmetric nature of this sport leads to differences in the skeletal tissue composition of the limbs. Fifteen male volleyball players (VP) (26 ± 4 years, 192 ± 6 cm, 87 ± 9 kg; mean ± SD) and 15 non-active control subjects (25 ± 2 years, 177 ± 8 cm, 72 ± 11 kg; mean ± SD) were studied. VP training sessions (3–6 days/week) included a variety of jumping and weightlifting exercises. The VP were taller and heavier than the control subjects (p<0.001). Whole-body bone mineral content (BMC) and lean mass were higher in VP after adjustment for body mass and height (p<0.001). Axial skeleton and limb BMC and bone mineral density (BMD) were higher in VP than in control subjects (p<0.05). Adjusted lumbar spine (L2–4) BMD was 14% higher in VP than in control subjects (p<0.05). Similarly, a much greater adjusted BMD was observed in the femoral neck of VP (24%, 20%, 27% and 20% for the femoral neck, intertrochanteric, greater trochanter and Ward’s triangle subregions respectively; p<0.05). The dominant arm was slightly heavier (≈3%) and had 4% more muscle mass than the contralateral arm in both the VP (p<0.05) and control subjects (p<0.05). Greater BMC values (9%), BMD (7%) values and the area occupied by osseous pixels (5%) were recorded in the dominant arm as compared with the nondominant arm in VP (p<0.05). No differences between arms were observed in control subjects. Right and left leg BMC and BMD values were similar in control subjects while 4% higher BMC values were recorded for the left leg in the VP group (p<0.05). A close relationship between left leg muscle mass and BMD was observed in the femoral neck subregions of all the subjects (r= 0.81, 0.81, 0.78 and 0.79 for the femoral neck, intertrochanteric, greater trochanter and Ward’s triangle subregions respectively; p<0.001; n= 30). These findings clearly demonstrate a considerably high BMC and BMD in professional volleyball players which seems to be related to the loading type of exercise they perform. Received: 26 October 1998 / Accepted: 26 May 1999