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     

A comparison between peripheral BMD and central BMD measurements in the prediction of spine fractures in men

Introduction: Most of the research on osteoporosis has been conducted on women. Few studies have compared central and peripheral densitometry and their association with vertebral fractures in men. The present study was designed to compare peripheral bone mineral density (BMD) measurements with central BMD measurements, and to examine their association with radiographic spine fracture in men. Methods: We studied 402 community-dwelling men aged 45–92 years (mean: 70 years) from the Rancho Bernardo Study cohort who attended a clinic visit between 1988 and 1992 when BMD measurements of the midshaft radius, ultradistal wrist, lumbar spine, and total hip were obtained, and who returned for lateral X-rays of the thoracic and lumbar spine an average of 4 years later. Logistic regression, T-scores, and quintiles were used to analyze BMD and its association with vertebral fractures. Results: The prevalence of osteoporosis defined by the National Osteoporosis Foundation criteria (for women) was 14.2% at the spine and 13% at the hip. Because there are no validated definitions of osteoporosis based on the ability to predict fracture risk for peripheral densitometry, the frequency of overlap by bone site was calculated among men in the lowest quintile of each site. Of the 402 men, 82 men (20.3%) had at least two sites with BMD measurements in the lowest quintile. After an average of 4 years, 33 (8.2%) men had at least one radiographic vertebral fracture, and ten (2.5%) men had at least two vertebral fractures. Low BMD at the spine (with and without covariate adjustment) was associated with having one or more vertebral fractures, whether using NOF T-score-defined osteoporosis [Odds ratio (OR): 3.81; confidence interval (CI): 1.52, 9.57] or the lowest quintile versus all others (OR: 2.53; CI: 1.03, 6.19). After age and/or other covariate adjustments, neither BMD at the total hip nor at the peripheral sites was associated with spine fractures using either NOF women-based criteria or male quintiles from this cohort. Conclusion: Although different men had osteoporosis defined by quintiles at different sites, only low BMD at the spine was associated with vertebral fracture.     

Effects of Gender and Age on the Association of Apolipoprotein E ε4 with Bone Mineral Density,Bone Turnover and the Risk of Fractures in Older People*

The aim of this study was to examine whether the presence of apolipoprotein E ε4 (ApoE ε4) is associated with a lower bone mineral density (BMD), lower quantitative ultrasound (QUS) measurements, higher bone turnover and fracture risk, and whether these relations are modified by gender and age. A total of 1406 elderly men and women (≥65 years) of the Longitudinal Aging Study Amsterdam (LASA) participated in this study. In all participants, QUS measurements were assessed, as well as serum osteocalcin (OC) and urine deoxypyridinolin (DPD/Cr urine). Follow-up of fractures was done each three months. In a subsample (n = 604), total body bone mineral content (BMC) and BMD of the hip and lumbar spine were measured. In addition, prevalent vertebral deformities were identified on radiographs. In women, the presence of ApoE ε4 was associated with significantly lower femoral neck BMD (g/cm²; mean ± SEM; ε4+, 0.64 ± 0.01 vs. ε4−, 0.67 ± 0.01; p= 0.04), lower trochanter BMD (g/cm²; mean ± SEM; ε4+, 0.58 ± 0.01 vs. ε4–, 0.61 ± 0.01; p= 0.01) and lower total body BMC (g; mean ± SEM; ε4+, 1787 ± 40.0 vs. ε4–, 1863 ± 23.8; p= 0.04). Women with ApoE ε4 also had a higher risk of severe vertebral deformities (OR=2.78; 95%CI: 1.21–6.34). In men, the associations between ApoE status and both hip BMD and QUS depended on age. Only among the younger men (65–69 years) was the presence of ApoE ε4 associated with lower BMD values. Bone markers and fractures were not associated with ApoE ε4 in either women, or men. In conclusion, this large community-based study confirms the importance of ApoE ε4 as a possible genetic risk factor related to BMD and vertebral deformities and demonstrates that its effect is gender related, and depends on age in men only. Received: 6 July 2001 / Accepted: 2 April 2002     

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     

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     

ApoE gene polymorphisms, BMD, and fracture risk in elderly men and women: the Rotterdam study.

To study the association between the ApoE gene polymorphism and osteoporosis, we performed an association study in 5,857 subjects from the Rotterdam Study. We did not observe an association between the ApoE polymorphism and osteoporosis in this study, which is thus far the largest study on ApoE and osteoporosis. INTRODUCTION: The E*4 allele of the E*2, E*3, E*4 protein isoform polymorphism in the gene encoding apolipoprotein E (ApoE) has previously been associated with an increased fracture risk. We investigated the association between the ApoE polymorphism and BMD, bone loss, and incident fractures as part of the Rotterdam Study a prospective population-based cohort study of diseases in the elderly. MATERIALS AND METHODS: The study population consisted of 5,857 subjects (2,560 men; 3,297 women) for whom data on ApoE genotypes, confounding variables, and follow-up of nonvertebral fractures were available. Data on femoral neck and lumbar spine BMD were available for 4,814 participants. Genotype analyses for bone loss (defined as annualized percent change in BMD at the hip and lumbar spine) and BMD were performed using ANOVA. Fractures were analyzed using a Cox proportional-hazards model and logistic regression. All relative risks were adjusted for age and body mass index. RESULTS AND CONCLUSIONS: The genotype distribution of the study population was in Hardy-Weinberg equilibrium (p = 0.98) and did not differ by gender. At baseline, mean BMD of the lumbar spine and femoral neck did not differ between the ApoE genotypes of men and women. Bone loss (mean follow-up, 2.0 years) did not differ by ApoE genotype for women and men. During a mean follow-up of 6.6 years, 708 nonvertebral fractures (198 hip fractures and 179 wrist fractures) and 149 incident vertebral fractures occurred. No consistent differences in the distribution of alleles could be observed between subjects with or without these fractures. Our data do not support the hypothesis that the ApoE*4 risk allele is associated with BMD, increased bone loss, or an increased risk of osteoporotic fractures.     

Forearm Bone Mineral Densitometry Cannot be Used to Monitor Response to Alendronate Therapy in Postmenopausal Women

Alendronate significantly increases bone mass and reduces hip and spine fractures in postmenopausal women. To determine whether forearm densitometry could be used to monitor the efficacy of alendronate, we examined changes in bone mineral density (BMD) at the forearm (one-third distal, mid-distal, ultradistal radius) versus changes at the hip (femoral neck, total hip) and spine (posteroanterior and lateral) in a double-masked, randomized, placebo-controlled clinical trial of 120 elderly women (mean age 70 ± 4 years) treated with alendronate for 2.5 years. We found that among women in the treatment group, BMD increased by 4.0–12.2% at the hip and spine sites (all p<0.001), whereas BMD increased only nominally at the one-third distal radius (1.3%, p<0.001) and mid-radius (0.8%, p<0.05), and remained stable at the ultradistal radius. At baseline, forearm BMD correlated with that of the hip (r= 0.55–0.64, p<0.001), femoral neck (r= 0.54–0.61, p<0.001) and posteroanterior spine (r= 0.56–0.63, p<0.001). Changes in radial BMD after 1 year of therapy were not correlated with changes in hip and spine BMD after 2.5 years of therapy. In contrast, short-term changes in total hip and spine BMD were generally positively associated with long-term changes in total hip, femoral neck and spine BMD (r= 0.30–0.71, p<0.05). Furthermore, long-term BMD changes at the forearm did not correlate with long-term hip and spine BMD changes, in contrast to the moderate correlations seen between spine and hip BMD at 2.5 years (r= 0.38–0.45, p<0.01). We conclude that neither short- nor long-term changes in forearm BMD predict long-term changes in overall BMD for elderly women on alendronate therapy, suggesting that measurements of clinically relevant central sites (hip and spine) are necessary to assess therapeutic efficacy. Received: 18 February 1999 / Accepted: 20 May 1999     

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

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

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     

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     

Birth Weight as a Predictor of Adult Bone Mass in Postmenopausal Women: The Rancho Bernardo Study

Understanding the determinants of adult bone mass may help to identify women for prevention of osteoporosis. We postulated that birth weight would predict low adult bone mass in old age. Subjects were 305 postmenopausal Caucasian women (mean age 70 years). Bone mineral content (BMC) and bone mineral density (BMD) were measured at the wrist, forearm, hip and lumbar spine. Birth weight was assessed by self-report. Birth weight was positively correlated with BMC at the forearm (r= 0.15), hip (r= 0.12) and lumbar spine (r= 0.18), and the age-adjusted mean BMC increased significantly from the lowest to the highest birth weight tertile. Adjusting for adult weight diminished this association at the forearm and hip, but not at the spine. Adjustment for multiple other covariates, including height, did not materially change these associations. Adult weight and height were significantly correlated with birth weight (r= 0.19 and r= 0.24, respectively). Birth weight was not independently correlated with BMD. Birth weight was thus positively correlated with adult weight and BMC 70 years later. These findings suggest that low birth weight may be a marker for future low bone mass and that different mechanisms exist for establishing the adult bone envelope (estimated by BMC) versus its density (estimated by BMD). Received: 18 August 1999 / Accepted: 21 January 2000     

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

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

Household Tobacco Smoke Exposure is Negatively Associated with Premenopausal Bone Mass

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

Serum Bone Alkaline Phosphatase and Calcaneus Bone Density Predict Fractures: A Prospective Study

The aim of this study was to assess the ability of serum bone-specific alkaline phosphatase (bone ALP), creatinine-corrected urinary collagen crosslinks (CTx) and calcaneus bone mineral density (BMD) to identify postmenopausal women who have an increased risk of osteoporotic fractures. Calcaneus BMD and biochemical markers of bone turnover (serum bone ALP and urinary CTx) were measured in 512 community-dwelling postmenopausal women (mean age at baseline 69 years) participating in the Hawaii Osteoporosis Study. New spine and nonspine fractures subsequent to the BMD and biochemical bone markers measurements were recorded over an average of 2.7 years. Lateral spinal radiographs were used to identify spine fractures. Nonspine fractures were identified by self-report at the time of each examination. During the 2.7-year follow-up, at least one osteoporotic fracture occurred in 55 (10.7%) of the 512 women. Mean baseline serum bone ALP and urinary CTx were significantly higher among women who experienced an osteoporotic fracture compared with those women who did not fracture. In separate age-adjusted logistic regression models, serum bone ALP, urinary CTx and calcaneus BMD were each significantly associated with new fractures (odds ratios of 1.53, 1.54 and 1.61 per SD, respectively). Multiple variable logistic regression analysis identified BMD and serum bone ALP as significant predictors of fracture (p = 0.002 and 0.017, respectively). The results from this investigation indicate that increased bone turnover is significantly associated with an increased risk of osteoporotic fracture in postmenopausal women. This association is similar in magnitude and independent of that observed for BMD. Received: 18 June 1999 / Accepted: 21 June 1999     

A Prospective Study of Bone Loss in Menopausal Australian-Born Women

Two hundred and twenty-four women (74 pre-, 90 peri-, 60 post-menopausal), aged 46–59 years, from a population-based cohort participated in a longitudinal study of bone mineral density (BMD). BMD was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and femoral neck and the time between bone scans was on average 25 (range 14–41) months. The aim of the study was to assess changes in BMD in relation to changes in normal menopausal status. During the study period women who were between 3 and 12 months past their last menstrual period (n= 22, late perimenopausal) at the time of the second bone scan had a mean (SE) annual change in BMD of 70.9% (0.4%) at the lumbar spine and 70.7% (0.6%) at the femoral neck (both p50.05 compared with women who remained premenopausal). In the women who became postmenopausal (n= 42) the mean annual changes in BMD were 72.5% (0.2%) at the lumbar spine and 71.7% (0.2%) at the femoral neck (both p50.0005), and in the women who remained postmenopausal (n= 60) they were 70.7% (0.2%) per year and 70.5% (0.3%) per year respectively (both p50.05), compared with women who remained premenopausal. In the 1–3 years after the final menstrual period (FMP) there was greater bone loss from the lumbar spine than the femoral neck (p50.05). In women who were menstruating at the time of the second bone scan and whose FMP could be dated prospectively (n= 35), higher baseline oestradiol levels were associated with less lumbar spine bone loss (p50.005). In the women who remained postmenopausal there was an association between baseline body mass index (BMI) and percentage change per year in femoral neck BMD (p50.05), such that women with higher BMI had less bone loss. In conclusion, during the time of transition from peri- to post-menopause, women had accelerated BMD loss at both the hip and spine. Received: 23 June 1997 / Accepted: 5 November 1997     

Bone Changes in Pre- and Postmenopausal Women with Thyroid Cancer on Levothyroxine Therapy: Evolution of Axial and Appendicular Bone Mass

The effects of suppressive doses of levothyroxine (LT₄) on bone mass are controversial. Our aim was to evaluate the effects on axial and appendicular bone mineral density (BMD) and bone metabolism of long-term LT₄ suppressive therapy in women by means of cross-sectional and longitudinal studies, and also to assess the potential influence of menopausal status and LT₄ dose. Seventy-six women (aged 47 + 13 years, 37 pre- and 39 postmenopausal) on suppressive therapy (67 + 34 months duration, mean LT₄ dose 168 + 41 mg/day) from our Thyroid Cancer Unit without previous hyperthyroidism or concomitant hypoparathyroidism were studied. Serum TSH, T₃ free T₄, calcium, phosphorus, alkaline phosphatase, BGP, iPTH and urinary calcium (uCA) were measured. BMD was measured by dual-energy X-ray absorptiometry (DXA) at lumbar spine, femoral neck, Ward's triangle, ultradistal and distal third radius and expressed as a Z-score. In a subset of 27 women aged 46 + 15 years (14 pre- and 13 postmenopausal) a second densitometry scan was performed 27 + 5 months later. Patients on suppressive therapy showed a small reduction in BMD at the distal third radius (Z-score: 70.77 + 0.98; 95% confidence interval: 71.11, 70.44) without differences between pre- and postmenopausal women. Significant relations with the regimen of suppressive therapy and bone turnover markers were detected except at the lumbar spine. In the longitudinal study a significant although mild reduction in femoral neck BMD was found that correlated with prior T₃ and iPTH. In conclusion, our data show a small detrimental effect of cautious LT₄ suppressive therapy on bone mass assessed by DXA; it remains to be established whether this increases the prevalence of fractures. Received: 30 June 1997 / Accepted: 7 November 1997     

Clinical Performance of a Highly Portable, Scanning Calcaneal Ultrasonometer

The aim of this study was to establish a normative database, assess precision, and evaluate the ability to identify women with low bone mass and to discriminate women with fracture from those without for a highly portable, scanning calcaneal ultrasonometer: the QUS-2. Fourteen hundred and one Caucasian women were recruited for the study. Among them were 794 healthy women 25–84 years of age evenly distributed per 10-year period to establish a normative database. Of these, 171 aged 25–34 years were defined as the young normal group for the purpose of T-score determination. Precision was assessed within 1 day (short-term) and over a 16-week period (long-term) in 79 women aged 25–84 years. Five hundred twenty-eight women ranging from 50 to 84 years of age with or without prevalent fractures of the spine, hip or forearm were measured to compare the QUS-2 with bone mineral density (BMD) of the hip and spine. Mean calcaneal broadband ultrasound attenuation (BUA) was constant in healthy women from 25 to 54 years of age and decreased with increasing age thereafter. Short-term precision, with and without repositioning of the heel, and long-term precision yielded comparable results (BUA SDs of 2.1–2.4 dB/MHz, coefficients of variations (CVs) of 2.5–2.9%). Calcaneal BUA was significantly correlated with BMD of the total hip (TH), femoral neck (FN) and lumbar spine (LS) in 698 women (r= 0.6–0.7, all p<0.0001). A similar relationship was observed for LS BMD compared with either TH or FN BMD (r= 0.7, p<0.0001). Prevalence of osteoporosis in our population (WHO criteria) was 20%, 17%, 21%, and 24% for BUA, BMD of the TH, FN and LS, respectively. Age-adjusted values for a 1 SD reduction in calcaneal BUA and TH and FN BMD predicted prevalent fractures of the spine, forearm, and hip with significant (p<0.05) odds ratios of 2.3, 2.0 and 2.1, respectively. Areas under the receiver operating characteristic curves for age-adjusted bone mass values predicting prevalent fracture were 0.62 for BUA, 0.59 for TH BMD, 0.60 for FN BMD, and 0.57 for LS BMD; all statistically equivalent. We conclude that the QUS-2 calcaneal ultrasonometer exhibits reproducible clinical performance that is similar to BMD of the spine and hip in identifying women with low bone mass and discriminating women with fracture from those without. Received: 19 July 2000 / Accepted: 6 December 2000     

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     

Radial Bending Breaking Resistance Derived by Densitometric Evaluation Predicts Femoral Neck Fracture

Bone mineral density (BMD) measurement by hip dual-energy X-ray absorptiometry (DXA) is considered the best predictor of osteoporotic fracture risk. BMD takes into account only in part the bone cross-sectional area that is an important determinant of both bone compression strength and of bending breaking resistance. From DXA measurements of proximal radius (Osteoplan, NIM, Verona, Italy) we obtained the projected outer diameter (D) and the mean diameter of the medulla (d), by an algorithm based on the assumption of a constant cortical volumetric density of 1050 g/cm³. The algorithm was validated by the good correlation found (r= 0.8) between calculated d and that actually measured by peripheral quantitative tomography (pQCT; XCT 960, Stratec, Unitrem, Italy) at the same radial site. The D and d values were used to calculate a bending breaking resistance index (BBRI) that is a component of the cross-sectional moment of inertia. The BBRI measured in 5460 women aged 35–89 years, was stable up to the age of 65–70 years and rapidly declined thereafter by 0.7% per year. This profile appears to be due to the fact that the increase in medullary area is compensated in terms of mechanical resistance by enlargement of cross-sectional area. In 68 women with either previous femoral neck (n= 41) or pertrochanteric fracture (n= 27) DXA measurements at proximal and ultradistal radius, lumbar spine and femoral neck were obtained together with the evaluation of proximal radius BBRI. The diagnostic accuracy of BBRI was somewhat comparable to that of spine and femoral neck BMD and significantly superior to that of ultradistal and proximal radius BMD, from which it was derived. Despite the obvious limitation of the cross-sectional nature of this study, our results indicate that a simple re-elaboration of the data obtained by peripheral radial densitometry may achieve diagnostic accuracy for hip fracture risk assessment only marginally lower than that of the direct measure of the BMD of the femoral neck. They also give additional support to the view that bone geometry, particularly for compact skeletal segments, is a determinant of its strength at least as important as bone density. Received: 25 July 2000 / Accepted: 9 April 2001     

Leptin predicts BMD and bone resorption in older women but not older men: the Rancho Bernardo study.

We studied the relation of leptin to bone, bone loss, and bone turnover in community-dwelling men and women. Leptin predicted higher BMD and lower bone turnover only in women. Leptin was not associated with 4-year bone loss in either sex. INTRODUCTION: Leptin, the protein product of the obesity (OB) gene produced in fat tissue, was originally thought to be involved only in the regulation of food intake and energy balance. Recent evidence suggests that leptin may play a role in the pathophysiology of several chronic diseases. Studies of the association between leptin and bone have been numerous yet inconclusive. Only one previous longitudinal study has been reported, which showed no association of leptin with BMD after adjusting for body size. MATERIALS AND METHODS: We report the association of serum leptin with BMD at the hip, spine, and midshaft radius in community-dwelling men (n = 498) and nonestrogen-using postmenopausal women (n = 411) 45-92 years of age. Serum leptin was measured in blood obtained between 1984 and 1987. Between 1988 and 1991, BMD was measured at the midshaft radius by single photon absorptiometry and at the femoral neck, total hip, and lumbar spine by DXA; at the same visit, height, weight, and body fat (by bioelectrical impedance analysis) were measured, and bone resorption was assessed in a subset of men (n = 286) and women (n = 241) using urine N-telopeptide (NTX). Four years later, axial BMD was remeasured in 536 participants. Sex-specific associations of leptin with BMD, NTX, and bone loss were tested using regression analysis. RESULTS: In unadjusted analyses, leptin was associated with BMD at the femoral neck, total hip, lumbar spine, and midshaft radius in both sexes (p < 0.01). In multiple regression analyses, adjusted for age, BMI, and other bone-related factors, only women showed a graded stepwise positive association between serum leptin and BMD at all sites and a negative stepwise association with NTX (all p for trend < 0.01). Baseline leptin levels did not predict 4-year bone loss in either sex. CONCLUSIONS: A favorable dose-dependent leptin-BMD association unexplained by obesity was observed only in women. The reason for the sex difference is unknown.