Computed Tomography Image Analysis of the Calcaneus in Male Osteoporosis

The present study aimed to characterize bone microarchitecture assessed by computed tomography (CT) at the calcaneus in male subjects suffering from osteoporosis. Seventy-nine subjects were assessed (45 with osteoporosis and 34 control subjects matched for age). Osteoporosis was defined according to the World Health Organization classification either at the lumbar spine or at the femoral neck. Thirty-three subjects (73%) had a past history of low-energy fracture mainly represented by vertebral fractures (24/33). Nine axial sections (1 mm in width and 2 mm apart) were selected for each subject. Bone microarchitecture analysis was performed using structural (binary and skeletonized images but also skeletonization from gray levels) and fractal analyses. Bone densitometry by dual-energy X-ray absorptiometry (DXA) at the calcaneus was also performed in 73 cases. Bone mineral density (BMD) was decreased in osteoporotic patients compared with controls both at the lumbar spine and hip and also at the calcaneus (p<0.01). Also 14 microarchitectural features among 25 measured were significantly different between the two groups (p<0.01). The odds ratio for fracture per 1 control group standard deviation decrease were also significant for 13 structural features but also for BMD at the calcaneus. The odds ratios after adjustment for BMD at the calcaneus were significant for the following features (p<0.05): number of valleys, 2.8 (1.2–6.9); trabecular partition, 3.3 (1.3–7.9); apparent trabecular spacing, 1.8 (1.0–3.1); trabecular bone pattern factor, 2.2 (1.1–4.3); Euler number, 3.0 (1.1–8.7); node-to-terminus strut count, 3.3 (1.4–7.8); terminus-to-terminus strut count, 2.9 (1.2–6.9); and fractal dimension, 3.7 (1.5–9.7). Few and weak correlations were found between BMD at the calcaneus measured with DXA and features obtained from CT, suggesting that these two methods give different information about bone status. In conclusion, male osteoporosis is a disease characterized by decreased bone mass but also by microarchitectural deterioration of bone tissue which is partly independent of BMD. Received: 24 April 2001 / Accepted: 6 July 2001     

Intravenous Pamidronate as Treatment for Osteoporosis after Heart Transplantation: A Prospective Study

Fractures due to osteoporosis are one of the major complications after heart transplantation, occurring mostly during the first 6 months after the graft, with an incidence ranging from 18% to 50% for vertebral fractures. Bone mineral density (BMD) decreases dramatically following the graft, at trabecular sites as well as cortical sites. This is explained by the relatively high doses of glucocorticoids used during the months following the graft, and by a long-term increase of bone turnover which is probably due to cyclosporine. There is some evidence for a beneficial effect on BMD of antiresorptive treatments after heart transplantation. The aim of this study was to assess prospectively the effect on BMD of a 3-year treatment of quarterly infusions of 60 mg of pamidronate, combined with 1 g calcium and 1000 U vitamin D per day, in osteoporotic heart transplant recipients, and that of a treatment with calcium and vitamin D in heart transplant recipients with no osteoporosis. BMD of the lumbar spine and the femoral neck was measured by dual-energy X-ray absorptiometry in all patients every 6 months for 2 years and after 3 years. Seventeen patients, (1 woman, 16 men) aged 46 ± 4 years (mean ± SEM) received only calcium and vitamin D. A significant decrease in BMD was observed after 6 months following the graft, at the lumbar spine (−6.6%) as well as at the femoral neck (−7.8%). After 2 years, BMD tended to recover at the lumbar spine, whereas the loss persisted after 3 years at the femoral neck. Eleven patients (1 woman and 10 men) aged 46 ± 4 years (mean ± SEM) started treatment with pamidronate on average 6 months after the graft, because they had osteoporosis of the lumbar spine and/or femoral neck (BMD T-score below −2.5 SD). Over the whole treatment period, a continuous increase in BMD at the lumbar spine was noticed, reaching 18.3% after 3 years (14.3% compared with the BMD at the time of the graft). BMD at the femoral neck was lowered in the first year by −3.4%, but recovered totally after 3 years of treatment. In conclusion, a 3-year study of treatment with pamidronate given every 3 months to patients with existing osteoporosis led to a significant increase in lumbar spine BMD and prevented loss at the femoral neck. However, since some of these patients were treated up to 14 months after the transplant, they may already have passed through the phase of most rapid bone loss. In patients who were not osteoporotic at baseline, treatment with calcium and vitamin D alone was not able to prevent the rapid bone loss that occurs immediately after transplantation. Received: 31 June 2000 / Accepted: 23 August 2000     

Do Men and Women Fracture Bones at Similar Bone Densities?

When the World Health Organization (WHO) guidelines for the definition of osteoporosis in postmenopausal women were identified similar proposals were not developed for men as there was insufficient evidence about the relationship between bone density and fracture in men. We have therefore examined the relationship between bone density and vertebral fracture in men and women attending for assessment of possible osteoporosis. Two hundred and sixty-four women (age 64 [SD 10] years) and 37 men (age 55 [10] years) were studied. Bone density was measured in the lumbar spine and femoral neck by dual-energy X-ray absorptiometry and expressed both as bone mineral density (BMD; g/cm²) and as T-scores. In both sexes there was a sigmoid relationship between the cumulative frequency of vertebral fracture and bone density at both sites. There was a linear relationship between the log odds of fracture and bone mass for both sexes and both sites (r= 0.97–0.99; p<0.0001). The slope of these lines was significantly steeper for men than women. The BMD at which there was 50% risk of fracture was higher in men than women (0.908 vs 0.844 g/cm²). The difference between the slopes was similar when the bone mass was expressed as a T-score. However, the T-score associated with 50% prevalence of fracture was similar in the two sexes (F: −2.77 vs M: −2.60). We conclude that although there is a different relationship between bone density and fracture in the two sexes the current WHO definition of osteoporosis in postmenopausal women can be appropriately applied to men. Received: 24 February 1999 / Accepted: 12 July 1999     

Hand Ultrasound for Osteoporosis Screening in Postmenopausal Women

There is a need for low-cost screening methods to detect low bone mass (osteopenia or osteoporosis) in postmenopausal women. The utility of quantitative ultrasonography (QUS) of the hand was assessed for osteoporosis screening using the WHO criteria. Bone mineral density (BMD) was measured in 206 postmenopausal Mexican-American women at the total hip and lumbar spine by dual-energy X-ray absorptiometry (DXA). The amplitude-dependent speed of sound (AD-SoS) was measured in the phalanges by QUS. Subjects identified by DXA as having osteopenia or osteoporosis had significantly lower AD-SoS values in comparison with normals. Estrogen users had significantly higher spine and hip BMD and AD-SoS values compared with non-estrogen users. The areas under the receiver operating characteristic (ROC) curves (AUC) for AD-SoS to screen for osteoporosis (T-score ≤−2.5) at the spine or hip were 0.73 for all subjects, 0.74 for estrogen users and 0.68 for non-estrogen users. The AUC for non-estrogen users to screen for osteopenia (T-score −1 to −2.5) was 0.77. Performance comparisons of AD-SoS with SCORE (a risk factor questionnaire) and body weight showed AUC values of 0.73, 0.69 and 0.65, respectively. QUS was the superior screening test when considering both the AUC and the shape of the ROC curves. For non-estrogen users, the group at higher risk for osteoporosis, QUS correctly identified 31% as normal, and 62% as having low bone mass and needing DXA referral; and the remaining 7% were false negatives. These data suggest phalangeal QUS can be effectively used for screening osteoporosis in postmenopausal women. Received: 2 April 1998 / Accepted: 27 July 1999     

Bone Densitometry: A New, Highly Responsive Region of Interest in the Distal Forearm to Monitor the Effect of Osteoporosis Treatment

The bisphosphonates have been introduced as alternatives to hormone replacement therapy (HRT) for the treatment and prevention of postmenopausal osteoporosis. The expected increasing application in at clinical practice demands cost-effective and easily handled methods to monitor the effect on bone. The weak response at the distal forearm during antiresorptive treatment has restricted the use of bone densitometry at this region. We describe a new model for bone densitometry at the distal forearm, by which the response obtained is comparable to the response in other regions where bone densitometry is much more expensive and technically complicated. By computerized iteration of single X-ray absorptiometry forearm scans we defined a region with 65% trabecular bone. The region was analyzed in randomized, double-masked, placebo- controlled trials: a 2-year trial with alendronate (n= 69), a 1-year trial with ibandronate (n= 141) and a 2-year trial with HRT (n= 121). Bone mineral density (BMD) at the distal forearm revealed a highly statistically significant dose-related response and increased 3–5% per year with 2.5 mg ibandronate, 10 mg alendronate or HRT, whereas the decrease in the placebo groups was 1–3% (p<0.001). The response at the distal forearm was similar to the response at the lumbar spine and hip. In conclusion, trabecular bone at the distal forearm is as responsive to antiresorptive treatment as trabecular bone in other skeletal regions. Bone densitometry at the new region of interest in the distal forearm has comparable performance characteristics to more expensive and technically demanding methods. The method is more accessible clinically and has potential as an alternative for monitoring bone mass changes during antiresorptive treatment. Received: 9 February 1998 / Accepted: 30 July 1998     

Bone Loss at the Lumbar Spine and the Proximal Femur in a Rural Japanese Community, 1990–2000: The Miyama Study

Bone mineral density (BMD) was measured over a ten year period in a cohort study in Miyama village, Wakayama Prefecture, Japan, to provide information on rate of bone loss in the mature and elderly population. Four hundred subjects were selected by sex and age decade from the full list of residents born in 1910–1949, and aged 40–79 years at the end of 1989, with 50 men and 50 women in each age decade. Baseline BMD of the lumbar spine and the proximal femur was measured using dual energy X-ray absorptiometry (DXA) in 1990 and again in 1993, 1997 and 2000. Annual rate of change in BMD (% per year) in the lumbar spine in men in their forties, fifties, sixties and seventies was 0.17, 0.55, 0.01 and −0.16, respectively, and in women, −0.87, −0.83, −0.48 and −0.48, respectively. Thus in men, BMD at the lumbar spine increased in all age strata but the oldest, when it decreased, whereas in women, it decreased in all age strata. On the other hand, BMD at the proximal femur decreased in both sexes in all age strata. Our results show that bone loss rates differ depending on the site involved, demonstrating that different strategies are needed for the prevention of bone loss in the spine and hip.  Furthermore, we found evidence of differences in BMD for given age strata between birth cohorts. Data in 1990 and in 2000 showed significant improvements for men in their sixties and for women in their fifties, suggesting that future problems of osteoporosis might be less severe than has previously been predicted in Japan. Received: 11 January 2002 / Accepted: 22 April 2002     

Identification of Women with Reduced Bone Density at the Lumbar Spine and Femoral Neck using BMD at the Os Calcis

We assessed the clinical usefulness of bone density measurements at the os calcis as a screening tool to identify patients with low bone density at the lumbar spine and femoral neck. Bone mineral density (BMD) was recorded in 443 women (mean age 60 years) referred to a bone densitometry service. Measurements were made at the lumbar spine and femoral neck using a Lunar DPXL and at the right os calcis using a Peripheral Instantaneous X-ray Imaging (PIXI) dual-energy X-ray absorptiometry system. Average T-scores derived using the manufacturer”s data were: 1.59 for the lumbar spine, −1.41 for the femoral neck and −0.87 for the os calcis. The prevalence of osteoporosis using WHO criteria (T-scores of −2.5 or less) was 36% for the lumbar spine or femoral neck but only 9.7% for the os calcis. BMD of the os calcis correlated with that at the lumbar spine (r= 0.69, p<0.001) and femoral neck (r= 0.67, p<0.001). The area under the receiver operator characteristics curve was 0.836 (standard error 0.020) for the os calcis related to osteoporosis at the lumbar spine or femoral neck. Optimal accuracy was obtained at a T-score of ≤−1.3 (BMD 0.39 g/cm²) when the sensitivity was 69.6% (95% confidence interval 65.3, 73.9%) and specificity 82.6% (95% confidence interval 79.1, 86.1%). However, the probability of diagnosing low bone density from a given BMD at the os calcis varied by age and site scanned. Accordingly, for informing management strategies, the choice of a single cutoff BMD at the os calcis may not be appropriate and several thresholds may be adopted based on age, the site of interest (lumbar spine or femoral neck) and consideration of associated clinical features. Thus, the use of heel bone density scanners could reduce the number of axial bone density measurements required. The advantages of portability, low cost and shorter scan times should reduce the cost of detection and provide a greater opportunity for identification of women at risk of fracture. Received: 18 June 1999 / Accepted: 30 March 2000     

Age-Related Bone Mineral Density, Accumulated Bone Loss Rate and Prevalence of Osteoporosis at Multiple Skeletal Sites in Chinese Women

We investigated the age-related bone mineral density (BMD), accumulated bone loss rate (ABLR) and the prevalence of osteoporosis at different skeletal sites in Chinese women. BMD was measured at the anteroposterior (AP) spine, supine lateral spine (areal BMD at the midarea [mLat] and the whole region [Lat], volumetric BMD at the middle region [MVD] and total region [TVD]), hip (femoral neck [FN], trochanter [Troc] and Ward’s triangle [Ward’s]) and forearm (radius + ulna ultradistal [RUUD], 1/3 region [RU1/3] and total region [RUT]) using a dual-energy X-ray absorptiometry (DXA) fan-beam bone densitometer (Hologic QDR 4500A) in 2702 females aged from 5 to 96 years old. Data were analyzed by eight different regression models. We found that the cubic regression model was the best for describing age-related changes in BMD. The coefficients of determination (R ²) of the fitting curve were 0.398 to 0.612 (p= 0.000). The data were then analyzed by 5-year age groups. This showed that the earliest peak BMD was at the age of 20–24 years at Troc and Ward’s, and the latest at the age of 40–44 years at RU1/3 and RUT of the distal forearm. Compared with BMD, the ABLRs were highest at Ward’s (−66.2%) and the lowest at RU1/3 of the distal forearm (−31.3%) in subjects over 80 years old. The prevalence of osteoporosis at at least one site in these women was 0.5 ± 0.4% in those 30–39, 4.6 ± 4.4% in those 40–49, 23.9 ± 13.3% in those 50–59, 56.3 ± 20.3% in those 60–69, 71.8 ± 16.7% in those 70–79 and 83.2 ± 12.1% those over 80 years of age, respectively. The prevalence of osteoporosis in these women was 8.6–11.1% at the age of 40–49 and 36.5–40.6% at the age of 50–59 at the lateral spine regions (mLat, Lat, MVD and TVD), and 0.5–3.7% at the age of 40–49 and and 3.9–21.7% at the age of 50–59 years at the other skeletal sites (AP, FN, Troc, Ward’s, RUUD, RU1/3 and RUT). Significant differences were found in the prevalence of osteoporosis between the lateral spine regions and other skeletal sites (p<0.001) at the age of 40–59 years. In summary, we demonstrated significant age-related differences in peak BMD, ABLR and osteoporosis prevalence among various skeletal sites. Our data suggest that the supine lateral spine is the most sensitive site for the diagnosis of osteoporosis, especially in the early menopausal period, although the prevalence of osteoporosis varied with age and with different sites measured. Received: 20 November 2001 / Accepted: 13 February 2002     

Association Between Colles’ Fracture and Low Bone Mass: Age-Based Differences in Postmenopausal Women

Colles’ fracture (CF) in postmenopausal women has been linked to low bone mass at the lumbar spine and hip. However, the diverse methodological approaches of previous studies make the results difficult to compare and thus the implications of CF in osteoporosis daily clinical practice are not clear. We explored the association between CF and low bone mineral density (BMD) in an incident case-control study in 58 postmenopausal Spanish women aged 45–80 years with recent CF and in 83 population-based controls of the same age range. The BMD of ultradistal distal forearm, lumbar spine and hip was measured by dual-energy X-ray absorptiometry (DXA) and WHO criteria were used to define osteoporosis and osteopenia. BMD was significantly lower in cases for all three areas (p<0.001). Osteoporosis was more prevalent in cases than controls in the wrist (60% vs. 35%, p<0.001), lumbar spine (47% vs. 20%, p<0.005) and hip (19% vs. 6%, p<0.005). After adjusting for age, menopausal status and body mass index, osteoporosis and osteopenia remained significantly associated with CF only in women aged 65 years or less (ultradistal forearm OR 5.7 (95% CI 1.2–27.2), lumbar spine OR 3.9 (95% CI 1.1–14.3)). We conclude that CF in postmenopausal women aged 65 or less may be used as a sentinel finding to identify patients with generalized osteoporosis. Additionally, 70% of all CF patients regardless of their age had low bone mass (T-score<−1SD) in any studied site. Received: 3 December 2001 / Accepted: 22 May 2002     

Image Analysis of the Distal Radius Trabecular Network Using Computed Tomography

Bone texture analysis might provide information about bone structure in a noninvasive manner. In a prospective case–control cross-sectional study we investigated the value of computed tomography (CT) image analysis of the distal radius in the assessment of osteoporosis. Twenty patients suffering from postmenopausal osteoporosis were studied and compared with 21 age-matched controls. Eight slices were selected in each patient: four consecutive coronal slices and four consecutive cross-sectional slices. Bone texture analysis was performed using statistical, fractal and structural methods leading to the measurement of 32 features. Structural variables derived from histomorphometric parameters were measured after segmentation from a binary or a skeletonized image. Bone mineral density was measured by dual-energy X-ray absorptiometry both at the lumbar spine and the femoral neck. Eight of the 9 statistical features were significantly different in osteoporotic women as compared with controls (coronal slices, p < 0.05). Seven structural variables were statistically different between the two groups on coronal slices (p < 0.05): valley surface area, bone volume/tissue volume, trabecular partition, Euler’s number, trabecular bone pattern factor, node-to-node strut count and terminus-to-terminus strut count. The most significant results on coronal slices (p < 0.01) concerned 4 structural features: trabecular partition, Euler’s number, trabecular bone pattern factor and terminus-to-terminus strut count. Three features were statistically different (p < 0.01) between the two groups on cross-sectional slices (skeletonization from gray levels). A few features yielded by texture analysis were correlated with both lumbar spine and femoral neck bone mineral density, but the level of these correlations was weak (r < 0.5). In conclusion, CT image analysis of the distal radius is a useful tool for characterizing bone texture alterations in osteoporotic women. These findings are in keeping with microarchitectural osteoporosis-related changes diagnosed on bone biopsies. Received: 8 April 1998 / Accepted: 14 September 1998     

Vertebral Bone Mineral Density, Content and Area in 8789 Normal Women Aged 33–73 Years Who Have Never Had Hormone Replacement Therapy

The vertebral bone mineral density (BMD), bone mineral content (BMC) and bone area of the lumbar spine were measured using a bone densitometer in 8789 women aged 33–73 years who had had no previous hormone replacement therapy (HRT). The overall relationship between BMD and age was analyzed on a year-by-year basis, and comprised three separate regions that could each be described by a straight line: 33–46 years (gradient = 0.00166 g cm⁻²/year), 47–63 years (gradient = 0.0121 g cm⁻²/year) and 64–73 years (gradient = 0.0045 g cm⁻²/year). Above the age of 50 years our results were higher than the BMD in most previous reports. In those 3198 women who knew the time of their last menstrual period (mean age 49.25 years, SD 4.83) bone loss was most rapid in the first 10 menopausal years. In the whole group, the relationship between BMC and age was found to be similar to that of BMD, with three distinct regions, including a rapid drop between the ages of 47 and 63 years (gradient 0.781 g/year). Bone area showed a much more gradual (though significant) decrease with age. Based on WHO definitions and using BMD as an indicator, the percentage of women with osteoporosis varied from zero in the younger age group to about 30% of women aged over 70 years; in contrast, where BMC was used, although the trend with age had a similar shape, the percentages at each year were about half those derived from the corresponding BMD values. Osteopenia derived in the same way occurred in about 50% of women over 70 years using either BMD or BMC. The results presented here provide a reliable local reference range for lumbar spine bone densitometry measurements. They also show that for this site BMD and BMC cannot be used interchangeably to define osteoporosis. Received: 13 March 1998 / Accepted: 23 September 1998     

A Comparison of the Effect of Risedronate and Etidronate on Lumbar Bone Mineral Density in Japanese Patients with Osteoporosis: A Randomized Controlled Trial

To demonstrate the clinical benefit of 2.5 mg daily risedronate in the treatment of involutional osteoporosis, the effect of risedronate on bone mineral density (BMD) of the lumbar spine was compared with that of etidronate, selected as a representative of the bisphosphonates currently marketed in Japan. In this multicenter, randomized, double-masked, active (etidronate) controlled comparative study, a total of 235 Japanese patients with involutional osteoporosis were randomized to receive either treatment with 2.5 mg/day of risedronate for 48 weeks or intermittent treatment with etidronate (4 cycles of 2 weeks of treatment with 200 mg/day followed by 10-week medication-free periods). All patients received 200 mg of calcium supplement daily in the form of the calcium lactate. Bone mineral density of the lumbar spine (L2–L4 BMD) was determined at 12, 24, 36 and 48 weeks by dual-energy X-ray absorptiometry. The primary endpoint was the percent change in L2–L4 BMD from baseline to the time of final evaluation. Changes in biochemical markers of bone turnover and safety profiles were also compared. A significant increase in L2–L4 BMD was observed at 12 weeks after initiation of therapy in both the risedronate (2.8%) and etidronate (1.8%) groups. The increase in L2–L4 BMD at the time of final evaluation in the risedronate group (4.9%) was significantly greater (p = 0.002) than that in the etidronate group (3.1%). The changes in bone resorption markers (urinary total deoxypyridinoline and N-terminal telopeptide of type I collagen) from baseline to 48 weeks were −37.6% and −41.3% for risedronate and −22.5% and −26.6% for etidronate, respectively. New vertebral fractures or deterioration of existing fractures were observed in 2.8% (3/106) of the patients in the etidronate group, while no such cases (0/101) were observed in the risedronate group. No significant difference in the incidence of adverse events was found between two treatments. Daily oral risedronate (2.5 mg) exhibited efficacy superior to that of intermittent cyclical etidronate (200 mg) in increasing L2–L4 BMD, and was well tolerated by Japanese patients with involutional osteoporosis. Received: 7 February 2002 / Accepted: 18 July 2002     

The Effects of Pregnancy and Lactation on Bone Mineral Density

We performed a prospective study of bone mineral density (BMD) in 38 women during their first full-term pregnancy until 12 months postpartum. BMD measurements at lumbar spine [L2–L4 (LS)] and forearm [distal 33% (RD) and ultradistal (RUD) region of the radius] were made within 3 months before conception, after delivery, and at 6 and 12 months postpartum. In mid-pregnancy the DXA examination was carried out only at the forearm. Patients were grouped according to duration of lactation as group I, II or III (0–1, 1–6, 6–12 months respectively). During pregnancy there was a significant difference between baseline and delivery (p< 0.001) in the LS, RUD and RD BMD values. In group I there was no statistically significant difference in LS BMD between visits following pregnancy. The RUD BMD loss was recovered by 6 months postpartum (PP6). Group II showed continuous bone loss from delivery until PP6 at LS and RUD. In group III the LS BMD loss continued throughout the lactation period. The RUD BMD dropped (4.9%) until PP6 then increased by 3.0% as measured at 12 months postpartum (PP12). There was no significant change in RD BMD in any of three groups during lactation. At LS bone loss between delivery and PP12 correlated well with the duration of lactation (r=−0.727; p<0.001). We suggest that calcium needed for fetal skeletal growth during pregnancy was gained from maternal trabecular and cortical sites and that calcium needed for infant growth during lactation was drawn mainly from the maternal trabecular skeleton in our patients. The effect of pregnancy and lactation on the maternal bone mass was spontaneously compensated after weaning. Received: 13 July 2000 / Accepted: 19 April 2001     

Longitudinal Study of Bone Loss in Pre- and Perimenopausal Women: Evidence for Bone Loss in Perimenopausal Women

Bone loss before and around the time of menopause is not well characterized by longitudinal studies. We measured bone mineral density at various skeletal sites – total body, femoral neck, trochanter, anteroposterior (AP) and lateral spine, and forearm – with dual-energy X-ray absorptiometry in a large prospective cohort of 272 untreated pre- and perimenopausal women aged 31–59 years, at 1 year intervals for 3 years. Sex steroids and the following markers of bone remodeling were measured: serum osteocalcin (OC), procollagen I carboxyterminal extension peptide, bone alkaline phosphatase (BAP) and urinary crosslinks (CTX and NTX). Seventy-six women were classified as perimenopausal and 196 as premenopausal. Over the 3 years, premenopausal women had no significant bone loss at any site and a small but significant increase in bone mineral density at the trochanter, total hip, AP spine and radius. Perimenopausal women significantly lost bone from cancellous and cortical sites, i.e., the femoral neck, trochanter and lumbar spine. In perimenopausal women with increased follicle stimulating hormone, the rate of bone loss at the femoral neck correlated negatively with OC and BAP. In perimenopausal women, serum estradiol levels decreased during the 3 years of follow-up and bone loss from the trochanter and the AP spine was correlated with serum estradiol after 3 years. In conclusion, among premenopausal women there is no bone loss. In contrast, there is a rapid and diffuse bone loss in perimenopausal women, related to decreased estrogen secretion. Bone markers may be useful to identify these women losing bone. Received: 13 October 1997 / Accepted: 19 October 1998     

Site-Specific Variation in the Classification of Osteoporosis, and the Diagnostic Reclassification Using the Lowest Individual Lumbar Vertebra T-score Compared with the L1–L4 Mean, in Early Postmenopausal Women

In this study we report first the concordance and variation in diagnostic osteoporosis classification using multiple skeletal site measurements compared with the lumbar spine only; and secondly, at the lumbar spine, the variation and diagnostic osteoporosis reclassification using the lowest individual vertebra T-score compared with the L1–L4 mean T-score. One hundred and fifty early postmenopausal women were evaluated as part of the recruitment for a multicenter osteoporosis prevention study. Bone mineral density (BMD) was restricted such that no more than 10% of the subjects had a lumbar spine BMD below 0.8 g/cm². Forty-seven per cent of the subjects were classified as having low bone mass (T-score ≤−1.0) at the lumbar spine, 63% at the mid-forearm, 39% at the distal forearm and 50% at the hip (p<0.05). The greatest proportion of subjects were categorized as osteoporotic at the lumbar spine, followed by the forearm and then the hip. Correlation between sites ranged from 0.57 to 0.60 (p<0.01). Eighty-one percent of the subjects had a significant difference between their highest and lowest individual lumbar vertebra T-score (defined as a difference outside the 90% confidence interval coefficient of variation T-score value). Using the lowest individual lumbar T-score, recategorized 33% of the subjects classified as osteopenic (based on the mean L1–L4 T-score) as osteoporotic, and 23% of those classified as normal as osteopenic (p<0.05). Of all four vertebrae, L2 had the highest T-score in 37.7% of the subjects (mean −0.3) and L4 the lowest in 61% (mean −1.5) (mean difference 1.2 units, 95% CI 0.7 to 1.7). The classification of osteoporosis varies according to skeletal site, with pronounced differences in the early menopausal population. T-scores are useful for characterizing subjects with the highest risk of osteoporosis but BMD and fracture risk must be recognized in a continuum. Individual T-scores of the lumbar vertebrae show wide variation in the absence of degenerative spinal disease or vertebral collapse and the use of the lowest, significantly different, individual lumbar vertebra T-score reclassified over half of the subjects in this study. This poses a great therapeutic dilemma in clinical practice, particularly if these fractures are at higher risk of future collapse. Received: 9 November 1999 / Accepted: 27 April 2000     

Pregnancy-Associated Osteoporosis: Does the Skeleton Recover?

Osteoporosis in pregnancy is a rare clinical problem of unknown cause. If the bone loss results from the pregnancy alone it should improve toward normal after delivery; in contrast, where bone density was low before pregnancy, due to some other secondary cause, significant postpartum improvement might not be expected. Thirteen women (age 23–37 years) with pregnancy-associated osteoporosis presenting with either pain in the back and vertebral collapse (8 subjects) or pain in the hip (5 subjects) had consecutive dual-energy X-ray absorptiometry measurements of bone mineral density (BMD) for up to 8 years after an affected pregnancy. The BMD results were expressed as a Z-score in relation to an age-matched mean. The mean initial (0–6 months postpartum) BMD was low in both groups and at both sites. In the back pain group the mean spine Z-score (L1–L4) was –3.34 (range –2.25 to –4.66) and mean total hip Z-score was –2.41 (range –1.44 to −3.82). In the hip pain group the mean spine Z-score was –2.00 (range –1.48 to –2.65) and mean hip Z-score was –2.19 (range –1.12 to –3.26). Subsequent mean hip and spine BMD increased significantly toward the lower end of the normal range. We conclude that a reversible part of the bone loss is related to the pregnancy itself. A low BMD before pregnancy cannot be excluded. Knowledge that the bone density increases after an affected pregnancy, combined with the known rarity of recurrent symptoms in subsequent pregnancies, is important in prognosis. Received: 29 June 1999 / Accepted: 16 November 1999     

Prevalence of Low Serum Estradiol Levels in Male Osteoporosis

Estrogen deficiency has recently been implicated in the pathogenesis of male osteoporosis. We therefore investigated estrogen and androgen status in 63 men admitted to our clinic with the diagnosis of osteoporosis over a period of 2 years. The diagnosis was based on the presence of either low-energy fractures of the spine or a BMD T-score < −2.5 in the spine or hip. Thirty-six patients had one or more low-energy fractures of the spine, 47 displayed a lumbar BMD T-score <−2.5 and 39 a hip BMD T-score <−2.5. Based on the history, clinical examination and extensive biochemical testing, 42 of the 63 were classified as having primary osteoporosis. Of these 42 patients, 14 (33%) exhibited serum estradiol levels below the normal range (p<0.001). Two of the patients (3%) displayed male hypogonadism with serum testosterone below the normal range. In 37 of the 63 patients a complete estrogen status was available. In this group 26 were classified as having primary osteoporosis. Of these, no single case of male hypogonadism was demonstrable, while 10 (38%) exhibited undetectable serum estradiol levels (<48 pM). Thus, estrogen deficiency is much more prevalent than androgen deficiency in primary male osteoporosis. Future screening tests for osteoporosis in men should therefore include assessment of serum estradiol. Received: 2 September 1999 / Accepted: 27 December 1999     

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     

A Histomorphometric Long-Term Longitudinal Study of Trabecular Bone Loss in Glucocorticoid-Treated Patients: Prednisone Versus Deflazacort

Administration of a corticosteroid with minor osteopenic effects is considered an effective prevention of glucocorticoid osteoporosis. Deflazacort, an oxazolinic derivative of prednisolone, is reported to be less harmful to cancellous bone mass than other equally effective corticosteroids. However, comparative long-term studies, particularly on trabecular bone, are needed before a smaller detrimental effect on bone of deflazacort can be unequivocally confirmed. We conducted such a prospective long-term study using histomorphometric analysis of iliac bone. For the study, 18 pairs of nonimmobilized patients, matched for age, sex, menopausal state, corticosteroid dose, and type and severity of the disease, were randomly submitted to treatment with therapeutically equivalent doses of prednisone or deflazacort. Bone biopsies from iliac crest were taken before and at various times during treatment. In order to represent the time-related trabecular bone loss and find out possible differences between patients on prednisone or deflazacort, a previously described model of bone loss kinetics was applied. No significant differences in biochemical indices of bone turnover or in histomorphometric variables between prednisone- and deflazacort-treated patients were recorded before treatment. The mean duration of treatment at the final biopsy was similar for prednisone and deflazacort (15.8 and 15.2 months, respectively). Patients showed evident clinical improvement with both treatments. Osteoid and resorption surfaces showed no significant differences throughout the observation period in any of the 18 pairs. On the contrary, both steroids induced a significant decrease in trabecular bone, although the bone loss rate induced by prednisone was significantly higher than that induced by deflazacort (P < 0.05). The kinetics of bone loss and the different osteopenic effects of the two drugs are described by the negative exponential function fitted to data from patients never previously given glucocorticoids; the model yields highly significant difference (P≅ 0.01) between the two drugs and allows estimation of the difference even 3 years after the beginning of treatment (−3.0%/year versus −1.1%/year for prednisone and deflazacort, respectively). This prospective long-term study confirms that an exponential model accurately describes the trabecular bone loss induced by long-term corticosteroid treatment and demonstrates that deflazacort, at therapeutically effective doses, induces less trabecular bone loss than prednisone. Received: 30 January 1997 / Accepted: 7 August 1997     

Bone Disease After Liver Transplantation: A Long-Term Prospective Study of Bone Mass Changes, Hormonal Status and Histomorphometric Characteristics

After liver transplantation there is a high incidence of fractures, with important rates of bone loss during the first months. However, the long-term evolution of bone mass and metabolism parameters have been scarcely studied. In order to determine the incidence and risk factors involved in the development of skeletal fractures and to analyze the long-term evolution of bone mass, bone turnover and hormonal status after liver transplantation, a 3-year prospective study was performed in 45 patients following liver transplantation. Serum osteocalcin, parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OH D) and testosterone levels (men), and bone mass at the lumbar spine and femur were measured before and sequentially at different time points during 3 years. Spinal X-rays were obtained during the first year. Histomorphometric analysis of bone biopsies obtained in 24 patients within the first 12 hours after surgery and 6 months after transplantation was performed. Fifteen patients (33%) developed fractures after liver transplantation, and pre- transplant risk factors for fractures were age and low bone mass (odd”s ratio for osteoporosis, 95% confidence interval: 5.69, 1.32–24.53). Serum PTH, osteocalcin, 25-OH D, testosterone and creatinine levels increased after transplantation. Moreover, PTH correlated with creatinine and osteocalcin values. Bone mass decreased during the first 6 months and reached baseline values at the lumbar spine the second year, with posterior significant recovery at the femoral neck. Long term evolution of femoral neck BMD correlated with PTH levels. Six months after transplantation bone histomorphometric data showed an increase in bone formation parameters. After liver transplantation there is a high incidence of fractures, specially in elderly patients and those with osteoporosis. Bone mass decreased in the short-term period and improved, initially at the lumbar spine and later at the femur, according to histomorphometric evidences of an increase in bone formation. The increase in creatinine values induces a secondary hyperparathyroidism that influences the changes in femoral bone mass. Treatment of osteoporosis shortly after liver transplantation may be important in the prevention of bone fractures, particularly in patients with low bone mass. Received: June 2000 / Accepted: November 2000