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     

Total Body and Regional Bone Mineral Density in Men: Effect of Age

Bone density is related to the risk of fracture, with a decrease in bone density resulting in an increased risk of fracture. The aims of this study were to characterize the relationship between bone mineral density (BMD) and age at different skeletal sites in men, and to determine whether the BMD pattern with age reflects the pattern of fracture in men. We studied 178 healthy Caucasian men, ages 20–79 years (approximately 30 per decade) from a general practitioner register. Spinal radiographs were obtained from men over 50 years of age and graded by a radiologist for spinal osteoarthritis by the method of Kellgren. BMD was measured by dual-energy X-ray absorptiometry at the anteroposterior (AP) lumbar spine, femoral neck, Ward’s triangle, trochanter, ultradistal forearm and total body (providing estimates for the pelvis, head, arms, legs, trunk, ribs and spine). Severe osteoarthritis (grades 3 and 4) was associated with increased spine BMD, and therefore individuals with severe osteoarthritis were excluded from analysis of the spine. There was a decrease in height of vertebrae L2–4 in men between 20 and 79 years of age (4%), resulting in a decrease in projected area. The change in BMD in standard deviation units (T-score) between 20 and 79 years was calculated: there were significant decreases at the femoral neck (–1.6), Ward’s triangle (–2.4), total body (–0.6), and its subregions the pelvis (–1.4), trunk (–0.8), ribs (–0.7) and legs (–0.7). There was no change in BMD with age at the AP lumbar spine, ultradistal forearm, or the total body subregion of the head. Similar results were found after adjusting for height and weight. Thus, there was only a small decrease in total body BMD across life, but a substantial decrease in BMD of the pelvis and proximal femur, sites rich in trabecular bone. These are the same sites associated with substantial increases in fracture incidence in men with aging. Received: 31 March 1998 / Accepted: 25 November 1998     

Case-Control Study of the Pathogenesis and Sequelae of Symptomatic Vertebral Fractures in Men

To investigate the pathogenesis and sequelae of symptomatic vertebral fractures (VF) in men, we have performed a case–control study, comparing 91 men with VF (median age 64 years, range 27–79 years) with 91 age-matched control subjects. Medical history, clinical examination and investigations were performed in all patients and control subjects, to identify potential causes of secondary osteoporosis, together with bone mineral density (BMD) measurements. BMD was lower at the lumbar spine and all sites in the hip in patients with VF than in control subjects (p<0.001). Potential underlying causes of secondary osteoporosis were found in 41% of men with VF, compared with 9% of control subjects (OR 7.1; 95% CI 3.1–16.4). Oral corticosteroid and anticonvulsant treatment were both associated with a significantly increased risk of VF (OR 6.1; 95% CI 1.3–28.4). Although hypogonadism was not associated with an increased risk of fracture, the level of sex hormone binding globulin was higher (p<0.001) and the free androgen index lower (p<0.001) in men with VF than control subjects. Other factors associated with a significantly increased risk of VF were family history of bone disease (OR 6.1; 95% CI 1.3–28.4), current smoking (OR 2.8; 95% CI 1.2–6.7) and alcohol consumption of more than 250 g/week (OR 3.8; 95% CI 1.7–8.7). Men with VF were more likely to complain of back pain (p<0.001) and greater loss of height (p<0.001) than control subjects, and had poorer (p<0.001) scores for the energy, pain, emotion, sleep and physical mobility domains of the Nottingham Health Profile. We conclude that symptomatic VF in men are associated with reduced BMD, underlying causes of secondary osteoporosis such as corticosteroid and anticonvulsant treatment, family history of bone disease, current smoking and high alcohol consumption, and that they impair the perceived health of the individual. Received: 23 February 1998 / Accepted: 13 May 1998     

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     

Bone Mineral Density, Hip Axis Length and Risk of Hip Fracture in Men: Results from the Cornwall Hip Fracture Study

Bone mineral density (BMD) and hip axis length (HAL) are important determinants of fracture risk in women. There are, however, few data concerning their predictive risk in men. The aim of this study was to determine the relationship between BMD, HAL and the risk of hip fracture in men. A case–control design was used. Cases were men aged 50 years and over with a minimal-trauma hip fracture admitted to the Royal Cornwall Hospital, Truro, during 1995–1997. Controls were recruited from a large general practice within the catchment area of the hospital. Subjects were invited for assessment of BMD at the lumbar spine and proximal femur, using dual-energy X-ray absorptiometry. HAL was assessed using machine software. Data concerning BMD were available in 62 fracture cases and 100 controls. After adjusting for age, height and weight, a reduction in BMD was associated with a significant increase in the risk of hip fracture [odds ratio (OR) 1.8–4.0 per standard deviation (SD) reduction, depending on site]. HAL was similar in both fracture and control groups (12.0 cm vs 12.0 cm). After adjusting for height, there was no association between HAL and the risk of hip fracture (OR per 1 SD increase in HAL = 0.9; 95% confidence interval 0.6, 1.3). Compared with those with a cervical fracture (n= 31), those with an intertrochanteric fracture (n= 31) had lower BMD at all skeletal sites, though this was significant for the trochanteric site only. It is concluded that BMD though not hip axis length is a risk factor for low-trauma hip fracture in Caucasian men. Received: 28 September 1999 / Accepted: 21 April 2000     

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     

Effects of Alendronate on Bone Density in Men with Primary and Secondary Osteoporosis

Alendronate has been reported to increase bone mineral density (BMD) and reduce fracture risk in women with osteoporosis. As there are no proven safe and effective treatments available for men with osteoporosis, we compared the effects of alendronate (10 mg/day) on BMD, measured using dual-energy X-ray absorptiometry, in a 12-month prospective, controlled, open label study involving (i) men with primary (n= 23) or secondary osteoporosis (n= 18), (ii) postmenopausal women with primary (n= 18) or secondary (n= 21) osteoporosis, and (iii) 29 male and 14 female untreated controls matched by age, height and weight. The patients had one or more vertebral fractures and ranged in age from 34.6 to 85.1 years. BMD was detectably increased relative to baseline by 6 months, and increased by comparable amounts in males and females with primary or secondary osteoporosis. At 12 months, lumbar spine BMD was 5.4%± 1.1% to 7.0%± 2.2% higher in the treated groups compared with baseline and controls (p<0.05 to 0.0001). Trochanteric BMD increased by 2.6%± 1.5% and 3.7%± 1.7% in treated men with primary and secondary osteoporosis, respectively (p = 0.06 to 0.08), and by 3.9%± 1.3% in treated women with primary osteoporosis (p<0.01) after 12 months. No significant changes were detected at the femoral neck or Ward’s triangle. BMD remained unchanged in controls. We infer that alendronate has comparable incremental effects on BMD in men and women with primary and secondary osteoporosis within 12 months of treatment. The changes are in the order of 0.5 SD – effects associated with a clinically worthwhile reduction in fracture risk. The data provide room for optimism regarding the role of alendronate in the treatment of osteoporosis in men. Randomized, double-masked and placebo-controlled trials are needed to confirm these preliminary findings and demonstrate antifracture efficacy using vertebral and nonvertebral fracture rates as the primary endpoint. Received: 23 February 1999 / Accepted: 2 June 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     

Changes in Bone Mineral Density with Age in Men and Women: A Longitudinal Study

We performed a prospective study to evaluate the normal changes in bone mineral density (BMD) in the forearm, hip, spine and total body, and to study the agreement between changes in BMD estimated from cross-sectional data and the actual longitudinal changes. Six hundred and twenty subjects (398 women, 222 men; age 20–89 years) without diseases or medication known to affect bone metabolism undertook baseline evaluations, and 525 (336 women, 189 men) completed the study. BMD was measured twice 2 years apart by dual-energy X-ray absorptiometry. From cross-sectional evaluations the only premenopausal bone loss (<0.003 g/cm²/year) was found in the hip. In women after menopause and in men an age-related bone loss (0.002–0.006 g/cm²/year) was found at all sites. The data from the longitudinal evaluation showed a small bone loss in women before menopause at the hip and lumbar spine (<0.4%/year (<0.004 g/cm²/year)); this bone loss nearly tripled in the early postmenopausal years (<10 years since menopause), and thereafter decreased to the premenopausal rate for the hip, and to zero for the lumbar spine. The most pronounced bone loss after menopause occurred in the forearm (1.2 %/year (0.006 g/cm²/year)), and it remained constant throughout life. In men there was a small longitudinal bone loss in the hip throughout life, and a small bone loss in the distal forearm after the age of 50 years. In all groups, except for the early postmenopausal women, we found a small increase in total body BMD with age. When comparing the changes in BMD estimated from cross-sectional data with the longitudinal changes, only the hip and forearm generally displayed agreement, whereas the changes in the total body and spine generally were incongruous. In conclusion, the hip and forearm appear to be the sites with the best agreement between the cross-sectional estimated and the longitudinal age-related changes in BMD. Received: 22 August 2000 / Accepted: 22 June 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     

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     

Quantitative Ultrasound in Adults with Cystic Fibrosis: Correlation with Bone Mineral Density and Risk of Vertebral Fractures

In several conditions, including cystic fibrosis (CF) and corticosteroid-induced osteoporosis, bone mineral density (BMD) measurements provide a modest prediction of fracture risk. We investigated in adult CF patients whether quantitative ultrasound (QUS) parameters were able to discriminate between patients with and without prevalent vertebral fractures. One hundred seventy-two adults with CF, 91 men and 81 women, often on chronic oral or inhaled corticosteroid therapy, were studied. BMD at the lumbar spine, proximal femur, and total body were measured by dual-energy X-ray absorptiometry (DXA). QUS parameters were assessed by Achilles Express at the calcaneus and by the DBM Sonic 1200 at the phalanges. All bone measurements by DXA and QUS were significantly correlated with each other, with the exception of phalangeal amplitude-dependent speed of sound versus spine BMD. The mean T-score values in CF patients with and without prevalent vertebral fractures were similar for all DXA measurements and for stiffness index. A significant difference between the two groups was observed only for phalangeal ultrasound bone profile index (UBPI) values (relative risk = 1.25, 95% confidence interval 1.05–1.49 for each decrease in T score), and this difference was maintained after adjusting the values for age, body weight, forced expiratory volume in 1 second, gender, and corticosteroid use. In conclusion, only a phalangeal QUS parameter (UBPI), in contrast with calcaneus QUS or DXA measurements, was able to discriminate CF patients with from those without vertebral fractures, possibly as a result of qualitative alterations of bone tissue independent of BMD.     

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     

How Hip and Whole-Body Bone Mineral Density Predict Hip Fracture in Elderly Women: The EPIDOS Prospective Study

We conducted a population-based cohort study in 7598 white healthy women, aged 75 years and over, recruited from the voting lists. We measured at baseline bone mineral density (BMD g/cm²) of the proximal femur (neck, trochanter and Ward's triangle) and the whole body, as well as fat and lean body mass, by dual-energy X-ray absorptiometry (DXA). One hundred and fifty-four women underwent a hip fracture during an average 2 years follow-up. Each standard deviation decrease in BMD increased the risk of hip fracture adjusted for age, weight and centre by 1.9 (95% CL 1.5, 2.3) for the femoral neck, 2.6 times (2.0, 3.3) for the trochanter, 1.8 times (1.4, 2.2) for Ward's triangle, 1.6 times (1.2, 2.0) for the whole body, and 1.3 times (1.0, 1.5) for the fat mass. The areas under the receiver operating characteristic (ROC) curves were not significantly different between trochanter and femoral neck BMD, whereas ROC curves of femoral neck and trochanter BMD were significantly better than those for Ward's triangle and whole-body BMD. emsp;Women who sustained an intertrochanteric fracture were older (84 ± 4.5 years) than women who had a cervical fracture (81 ± 4.5 years) and trochanter BMD seemed to be a stronger predictor of intertrochanteric ([RR = 4.5 (3.1, 6.5)] than cervical fractures ([RR = 1.8 (1.5, 2.3]). emsp;In very elderly women aged 80 years and more, hip BMD was still a significant predictor of hip fracture but the relative risk was significantly lower than in women younger than 80 years. emsp;In the 48% of women who had a femoral neck BMD T-score less than –2.5, the relative risk of hip fracture was increased by 3, and the unadjusted incidence of hip fracture was 16.4 per 1000 woman-years compared with 1.1 in the population with a femoral neck BMD T-score 5–1. Received: 19 May 1997 / Accepted: 16 October 1997     

Vitamin D Receptor Start Codon Polymorphism (Fok I) and Bone Mineral Density in Chinese Men and Women

The relationship between Fok I polymorphism of the vitamin D receptor start codon, bone mineral density (BMD) and vertebral fractures was studied in 684 Chinese men and women. A significant trend was observed only in Chinese women aged 70–79 years. The mean BMD at the total body was 0.85 ± 0.01 g/cm², 0.82 ± 0.01 g/cm²and 0.84 ± 0.01 g/cm² for elderly women of the FF, Ff and ff genotypes respectively (p= 0.06 by ANOVA). Similar but statistically non-significant trends were observed at the hip and spine. However, no association between BMD and the Fok I genotype was observed in younger women (aged 50–59 years) and elderly men (aged 70–79 years). In all study groups, there was no effect of an interaction between Fok I polymorphism and calcium intake on BMD (p>0.05 for the interaction effects by two-way ANOVA). No significant association was observed between Fok I polymorphism and vertebral fracture in elderly men or women (p>0.05 by the chi-square test). We conclude that the Fok I polymorphism may have a weak effect on the BMD of elderly Chinese women. Received: 2 February 2001 / Accepted: 27 August 2001     

Semiquantitative Evaluation of Prevalent Vertebral Deformities in Men and their Relationship with Osteoporosis: The MINOS Study

Epidemiologic studies have shown a high prevalence of vertebral deformities in men without a steep increase with aging, suggesting that a substantial number of these deformities are not related to osteoporosis. To determine which vertebral deformities are likely to be osteoporotic fractures, we compared vertebral deformities and bone mineral density (BMD) in a cohort of 786 men aged 51-85 years (the MINOS study). Normal vertebral height ratios were defined in a group of 120 healthy men aged 21-50 years. We classified vertebral deformities by using the semiquantitative method described by Genant et al., which was slightly modified at the level of thoracic kyphosis (T6-T9). At that level, grade 1 wedge deformities were defined as a 25-30% decrease in anterior vertebral height and grade 2 by a 30-40% decrease. The same cutoff of 40% was used for grade 3 for all vertebrae from T4 to L4. BMD was measured with a Hologic 1500 device at the lumbar spine, hip and whole body and with an Osteometer DTX 100 device at the forearm. Z-scores were calculated in 10-year age groups. The prevalence of vertebral deformities increased significantly with age. After adjustment for age and body weight, BMD did not differ between those with and without vertebral deformities. In patients having grade 2 and 3 deformities, BMD was lower than in men having no deformities or only grade 1 deformities when adjusted for age and body weight. Using the age- and body-weight-adjusted test of linear trend for sextiles of BMD, prevalence of grade 2 and 3 vertebral deformities increased with a decrease in BMD at all the sites of measurement. Grade 1 deformities were not correlated with BMD at any site. Among 126 patients who had only grade 1 vertebral deformities, 32 deformities in 30 men were confirmed as vertebral fractures according to their morphology but their BMD did not differ from the nonfractured men. These findings were confirmed when vertebral deformities were measured by the conventional morphometric method in a subgroup of 131 men. Our data suggest that a cutoff of 30% for wedge deformities from T6 to T9 and of 25% for other deformities has a high specificity and a moderate sensitivity for identifying vertebral deformities related to low BMD in men. Grade 1 deformities are often either false positive or deformities related to nonosteoporotic disease of the spine.     

Organochlorines and Bone Mineral Density in Swedish Men from the General Population

Persistent organochlorines (POCs), such as polychlorinated biphenyls (PCBs) and DDT, are present at relatively high concentrations in food and show estrogenic, anti-estrogenic or anti-androgenic activity in biological test systems. Because bone mineral density (BMD) in men is influenced by sex hormones, we looked for associations between BMD and serum concentrations of POCs in 115 men (mean age 63 years, range 40–75 years) from the general Swedish population. Ten PCB congeners, five DDT isomers, hexachlorobenzene, three hexachlorocyclohexane isomers, trans-nonachlor and oxychlordane were analyzed by gas chromatography. Quantitative bone measurements were performed by dual-energy X-ray absorptiometry at three sites: whole body, the L2–L4 region of the lumbar spine, and the neck region of the proximal femur, as well as by quantitative ultrasound on the left os calcis (broadband ultrasound attenuation (BUA) and speed of sound (SOS)). After adjustment for confounding factors in linear regression analyses we found no strong association between serum concentrations of single POCs and the five BMD and ultrasound variables. When POCs were grouped according to hormonal activity (estrogenic, anti-estrogenic, anti-androgenic) and the study subjects were divided into organochlorine concentration quartiles, a weak association was indicated between increased serum concentrations of p,p′-DDE (anti-androgenic) and decreased BMD, BUA and SOS. This may suggest that p,p′-DDE could cause negative effects on bone density, but the findings might also be due to chance since multiple comparisons were made in the statistical analysis. Overall our results do not suggest that the studied POCs caused major effects on bone density in our study group. Received: 23 March 2000 / Accepted: 23 June 2000     

Vertebral Fractures Predict Subsequent Fractures

This population-based study documents an increase in most types of fractures following the occurrence of a clinically recognized vertebral fracture among 820 Rochester, Minnesota, residents. During 4349 person-years of follow-up, 896 new fractures were observed. Relative to incidence rates in the community, there was a 2.8-fold increase in the risk of any fracture, which was greater in men (standardized incidence ratio (SIR), 4.2; 95% CI, 3.2–5.3) than women (SIR, 2.7; 95% CI, 2.4–3.0). The estimated cumulative incidence of any fracture after 10 years was 70%. The greatest increase in risk was for subsequent fractures of the axial skeleton, in particular a 12.6-fold increase (95% CI, 11–14) in additional vertebral fractures. There was a lesser increase in most limb fractures, including a 2.3-fold increase (95% CI, 1.8–2.9) in hip fractures and a 1.6-fold increase (95% CI, 1.01–2.4) in distal forearm fractures. There was a slightly greater association with distal forearm fractures among those whose first vertebral fracture occurred before age 70 years but a similar relationship with hip fractures, including cervical and intertrochanteric hip fractures separately, regardless of age at the initial vertebral fracture. There was also an equivalent increase in subsequent fracture risk whether the initial vertebral fracture was attributed to severe or moderate trauma. These data show that vertebral fractures represent an important risk factor for fractures in general, not just those of the spine and hip. Received: 2 September 1998 / Accepted: 9 February 1999     

Sex Difference in the Validity of Vertebral Deformities as an Index of Prevalent Vertebral Osteoporotic Fractures: A Population Survey of Older Men and Women

Morphometric methods have been developed for standardized assessment of vertebral deformities in clinical and epidemiologic studies of spinal osteoporosis. However, vertebral deformity may be caused by a variety of other conditions. To examine the validity of morphometrically assessed vertebral deformities as an index of osteoporotic vertebral fractures, we developed an algorithm for radiological differential classification (RDC) based on a combination of quantitative and qualitative assessment of lateral spinal radiographs. Radiographs were obtained in a population of 50- to 80-year-old German women (n= 283) and men (n = 297) surveyed in the context of the European Vertebral Osteoporosis Study (EVOS). Morphometric methods (Eastell 3 SD and 4 SD criteria, McCloskey) were validated against RDC and against bone mineral density (BMD) at the femur and the lumbar spine. According to RDC 36 persons (6.2%) had at least one osteoporotic vertebral fracture; among 516 (88.9%) nonosteoporotics 154 had severe spondylosis, 132 had other spinal disease and 219 had normal findings; 14 persons (2.4%) could not be unequivocally classified. The prevalence of morphometrically assessed vertebral deformities ranged from 7.3% to 19.2% in women and from 3.5% to 16.6% in men, depending on the stringency of the morphometric criteria. The agreement between RDC and morphometric methods was poor. In men, 62–86% of cases with vertebral deformities were classified as nonosteoporotic (severe spondylosis or other spinal disease) by RDC, compared with 31–68% in women. Among these, most had wedge deformities of the thoracic spine. On the other hand, up to 80% of osteoporotic vertebral fractures in men and up to 48% in women were missed by morphometry, in particular endplate fractures at the lumbar spine. In the group with osteoporotic vertebral fractures by RDC the proportion of persons with osteoporosis according to the WHO criteria (T-score <−2.5 SD) was 90.0% in women and 86.6% in men, compared with 67.9–85.0% in women and 20.8–50.0% in men with vertebral deformities by various methods. Although vertebral deformities by most definitions were significantly and inversely related to BMD as a continuous variable in both sexes [OR; 95% CI ranged between (1.70; 1.07–2.70) and (3.69; 1.33–10.25)], a much stronger association existed between BMD and osteoporotic fractures defined by RDC [OR; 95% CI between (4.85; 2.30–10.24) and (15.40; 4.65–51.02)]. In the nonosteoporotic group individuals with severe spondylosis had significantly higher BMD values at the femoral neck (p <0.01) and lumbar spine (p <0.0004) compared with the normal group. On the basis of internal (RDC) and external (BMD) validation, we conclude that assessment of vertebral osteoporotic fracture by quantitative methods alone will result in considerable misclassification, especially in men. Criteria for differential diagnosis as used within RDC can be helpful for a standardized subclassification of vertebral deformities in studies of spinal osteoporosis. Received: 5 February 1999 / Accepted: 24 June 1999     

Comparison of Bone and Total Alkaline Phosphatase and Bone Mineral Density in Postmenopausal Osteoporotic Women Treated with Alendronate

Alendronate therapy in osteoporotic women decreases bone turnover and increases bone mineral density (BMD). Optimal patient management should include verification that each patient is responding to therapy. Markers of bone turnover and BMD have both been proposed for this purpose. We have investigated changes resulting from alendronate therapy with an enzyme immunoassay for bone alkaline phosphatase (BAP) and compared it with total alkaline phosphatase (TAP) and BMD of the lumbar spine, hip, and total body. Subjects were drawn from a multicenter randomized, placebo-controlled trial of alendronate in postmenopausal women with osteoporosis. BAP and TAP levels were measured at baseline and following 3, 6 and 12 months of therapy with either placebo (n= 180) or alendronate 10 mg/day (n= 134). All subjects also received 500 mg/day supplemental calcium. BMD was measured at baseline and following 3, 6, 12, 18, 24 and 36 months of therapy. To compare BAP, TAP and BMD at each site for identifying women that experienced a skeletal effect of alendronate, we calculated least significant change (LSC) values from the long-term intraindividual variability in each placebo-treated woman. Median levels of BAP decreased by 34%, 44% and 43% at 3, 6 and 12 months, respectively, in alendronate-treated women (p<0.0001 compared with baseline and with placebo). These changes were significantly greater (p<0.0001) than changes observed for TAP. Following 6 months of alendronate therapy, 90% of the women had experienced a decrease in BAP exceeding the LSC compared with only 71% for TAP. The greatest number of women similarly identified with BMD at any site (i.e. a gain in BMD exceeding the LSC) was 81% for spinal BMD at 36 months. All other sites were less than 70% at 36 months. Short-term changes in BAP and TAP were modestly associated with subsequent changes in BMD at all sites (Spearman’s rho −0.22 to −0.52, p<0.05). Compared with TAP and BMD, BAP testing rapidly and sensitively identified skeletal effects of alendronate thus enabling appropriate drug monitoring of osteoporotic women. Though BAP and TAP changes were modestly predictive of BMD changes, the value of the bone marker tests is their ability to detect rapidly a skeletal effect of therapy. Received: 19 May 2000 / Accepted: 31 October 2000