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     

Association of a G2014A Transition in Exon 8 of the Estrogen Receptor-α Gene with Postmenopausal Osteoporosis

We report the association of a newly identified synonymous G2014A single nucleotide polymorphism (SNP) which does not alter the amino acid sequence in exon 8 of the estrogen receptor-α (ERα) gene with osteoporosis in Thai postmenopausal women. Subjects consisted of 228 postmenopausal women aged more than 55 years divided into two groups – with vertebral or femoral osteoporosis (n= 106) or without osteoporosis (n= 122) – according to bone mineral density (BMD) criteria. The exon 8 G2014A SNP, which is 6 nucleotides upstream from the end of the stop codon, was identified by PCR-RFLP. Data are expressed as the mean and 95% CI. The allele frequency of the G2014A polymorphism was 26.4% in osteoporotic subjects and was significantly higher than that in non-osteoporotic women (15.2%) (p<0.05). By stepwise logistic regression analysis, it was found that the G2014A polymorphism was related to the presence of osteoporosis (odds ratio 2.7 per A allele, 95% CI 1.49–4.76) independently of body weight (odds ratio 0.93 per kg, 95% CI 0.89–0.96) and years since menopause (odds ratio 1.12 per year, 95% CI 1.08–1.19). In a multiple linear regression model, L2–L4 BMD of osteoporotic subjects was associated with body weight (p<0.05), endogenous estradiol levels (p<0.05) and the G2014A genotype (p<0.001), while it was related only to body weight (p<0.05) and estradiol levels in non-osteoporotic women (p<0.05). We conclude that a G2014A SNP in exon 8 of ERα is associated with the presence and severity of postmenopausal osteoporosis. Linkage disequilibrium between this polymorphism and the 3′-untranslated region of the ERα gene which may participate in the regulation of ERα gene expression remains to be determined. Received: 17 October 2000 / Accepted: 11 June 2001     

Metacarpal Morphometry Using a Semi-automated Technique in the Assessment of Osteoporosis and Vertebral Fracture Risk

Metacarpal morphometry represents a potentially cheap and widely available non-invasive assessment of skeletal status. In two cross-sectional studies, we compared the performance characteristics of a semi-automated technique (the Teijin Bonalyzer) with an in-house manual measurement, and with measures of skeletal strength at other sites. The metacarpal cortical index (mCI) was measured on hand radiographs of 178 osteoporotic women using both the Teijin Bonalyzer and a digitizing tablet. Measurements on the latter were consistently lower than with the Bonalyzer except for mCI (0.443 ± 0.080 vs 0.364 ± 0.060, p<0.001), although correlation coefficients between these two methods were highly significant (r= 0.62–0.83, p<0.001). The reproducibility errors of metacarpal bone mineral density (mBMD) were constant (1.1–1.2%) whilst those for mCI showed a marked operator-dependency (2.0–7.9%). In 379 elderly community-dwelling women, Bonalyzer mCI and mBMD showed a significant decline with age (r=−0.30 and −0.27 respectively, p<0.05). Both mCI and mBMD correlated significantly with forearm BMD (r= 0.50 and 0.57 respectively, p<0.001) and hip BMD (r= 0.48 and 0.53 respectively, p<0.001). After adjustment for age and weight, hip BMD demonstrated the best discrimination for prevalent vertebral fractures as judged by the gradient of risk for a 1 SD decrease in measurement (odds ratio (OR) 2.17, 95% CI 1.56–3.01). Similar but smaller gradients of risk were shown by Bonalyzer mCI (OR 1.32, 95% CI 1.00–1.75), mBMD (OR 1.35, 95% CI 1.02–1.78) and forearm BMD (OR 1.39, 95% CI 1.08–1.80). MCI, and in particular mBMD, may be useful assessments of bone mass and fracture risk. In our study, it is comparable to peripheral assessment of skeletal status by forearm densitometry. Received: 22 February 2000 / Accepted: 6 June 2000     

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     

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

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

Hormonal and Anthropometric Predictors of Bone Mass in Healthy Elderly Men: Major Effect of Sex Hormone Binding Globulin, Parathyroid Hormone and Body Weight

Osteoporosis in men is a significant health problem, and factors associated with bone mass are being investigated. Although osteoporosis is a typical feature of hypogonadism, the influence of testosterone levels and other hormonal factors on bone mass of eugonadal males is unknown. Our aim was to identify several anthropometric and hormonal predictors that could be responsible for the variability in bone mineral density (BMD) in healthy men. One hundred elderly men (age 68 ± 7 years) were investigated in this cross-sectional study. BMD was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and femoral sites (femoral neck, Ward’s triangle, trochanter, intertrochanter and total femur). Anthropometric measures were obtained including: weight, height, body mass index (BMI), waist–hip ratio and testicular volume. Hormonal data measures were total, free and bioavailable testosterone, dihidrotestosterone, estradiol, sex hormone binding globulin (SHBG), insulin-like growth factor I (IGF-I), intact parathyroid hormone (iPTH) and 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃). One subject was excluded because primary hypogonadism was found. SHBG levels were increased in 53.5% of men, and 8% showed a mild increase in iPTH levels. Twenty-eight subjects had densitometric criteria of osteoporosis (T-score ≤−2.5). All BMD sites were positively correlated with body weight (r= 0.29–0.48, p<0.001) and BMI (r= 0.24–0.47, p<0.001). A negative correlation between SHBG levels and intertrochanter (IT) and total femur (TL) BMD was found (r=−0.24 and r=−0.22, p<0.05). After adjusting for age and BMI, SHBG and IGF-I levels were negatively correlated (r=−0.33, p<0.001). In multiple linear regression analysis independent predictors of bone mass were body weight, SHBG and iPTH levels. The best predictive model accounted for 24–40% of the observed variability of BMD. However, most of the BMD variability was explained by body weight. In conclusion, in our study body weight, SHBG and iPTH levels were predictors of BMD in healthy elderly men. Received: 9 June 2000 / Accepted: 27 September 2000     

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     

Inappropriate Reference Range for Peak Bone Mineral Density in Dual-energy X-ray Absorptiometry: Implications for the Interpretation of T-scores

An inappropriate reference range for peak bone mineral density (BMD) may result in identification of an incorrect proportion of subjects with osteopenia and osteoporosis at dual-energy X-ray absorptiometry (DXA). In this study, we assessed the prevalence of low BMD in Turkish young adults with respect to local population reference range T-scores and the US reference range T-scores. The BMD values of lumbar spine (L1–L4) and proximal femur (femoral neck, intertrochanter, trochanter, Ward”s triangle and total) were measured by DXA in 323 healthy young adults (171 women, 152 men) aged 19–25 years. The World Health Organization criteria for the diagnosis of osteopenia (−2.5 <T-score <−1) and osteoporosis (T-score ≤−2.5) were applied. In women, the means of the US reference range T-scores were significantly lower than zero at the spine and proximal femoral sites (p<0.0001). In men, the means of the US reference range T-scores were significantly lower than zero at the spine, femoral neck, intertrochanter, total femur (p<0.0001) and trochanter (p<0.05), but not at Ward”s triangle (p=0.92). When the diagnoses were based on local population reference range T-scores instead of the US reference range T-scores, the prevalence of low BMD (T-score <−1) in women fell from 50.3% to 14.0% at the lumbar spine and from 60.8% to 14.6% at the femoral neck, and in men from 42.8% to 15.8% at the lumbar spine and from 30.9% to 17.1% at the femoral neck. Our data suggest that individual populations should use their own reference range T-scores to avoid misdiagnoses of osteopenia and osteoporosis by DXA. Received: 4 November 1999 / Accepted: 29 March 2000     

High Bone Mineral Density in Male Elite Professional Volleyball Players

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

The Association of Bone Mineral Density with Vitamin D Receptor Gene Polymorphisms

A recent meta-analysis of 16 publications suggested that bone mineral density (BMD) is not associated with vitamin D receptor (VDR) gene polymorphism (VDRGP) at the 0.05 significance level when a study with genotyping mistakes is excluded. We wished to determine whether ‘positive’ findings supporting the BMD–VDRGP association may be explained by chance, and what factors affect the outcomes of these studies. Seventy-five articles and abstracts on the association of VDRGP with BMD and related skeletal phenotypes published before January 1997 were identified. Twenty-three of 67 (34.3%) studies on spinal BMD and 22 of 51 (43.1%) on femoral neck BMD had found a BMD–VDRGP association at p<0.05, significantly (p= 7 × 10^–14 for spinal BMD, p= 9 × 10^–16 for hip BMD) higher than the expected 5% false positive rate under the null hypothesis of ‘no association’. ‘Positive’ results were more frequently observed in studies on females before the menopause than those on females after the menopause (p<0.02) or on male and female subjects combined (p<0.05) when skeletal phenotypes at any bone sites were considered. The ‘positive rate’ among studies was also influenced by the age range of subjects studied and by the inclusion of subjects with osteoporosis. It is concluded that: (1) BMD is associated with VDRGP with high levels of confidence and (2) non-genetic factors and genetic heterogeneity interfere with the detection of the effects of VDRGP on bone phenotypes. Received: 20 January 1998 / Accepted: 7 April 1998     

Detailed Analyses of Periarticular Osteoporosis in Rheumatoid Arthritis

Periarticular osteopenia is the earliest radiographic sign of rheumatoid arthritis (RA). Recent studies using dual-energy X-ray absorptiometry (DXA) have indicated that the loss of periarticular BMD can be quantified by whole-hand bone mineral density (BMD) measurements. The aim of this study was to analyze periarticular BMD in more detail by DXA and quantitative ultrasound (QUS). In a cross-sectional study 23 women aged 30–76 years with early RA, mean disease duration 26 ± 19 months, and 18 men aged 42–69 years, mean disease duration 24 ± 25 months, were examined. All patients received antirheumatic therapy. The reference population consisted of 103 age-matched controls (68 females, 35 males) and young healthy controls. BMD measurements were performed using a DXA Expert XL densitometer (Lunar). BMD of the whole-hand and two subregions was determined: two subchondral regions of interest (S.CH.) were set within the trabecular bone, distal to the proximal interphalangeal joints of digits II and III excluding the dense subchondral bone of the metacarpophalangeal (MCP) joint and two metacarpal regions of interest (MCP) were set including the entire MCP joint of these fingers. QUS measurements at the proximal phalanges of digits II–V were performed using a DBM Sonic (Igea); amplitude-dependent speed of sound (Ad-SoS) was determined. In comparison with whole-hand BMD measurements, bone loss was pronounced in patients with a disease duration of 18–72 months at the subchondral regions of interest in both genders compared with age-matched controls (women: mean BMD loss S.CH. −23%, p<0.001, whole-hand −16%, p<0.001; men: mean BMD loss S.CH. −19%, p<0.05, whole-hand −12%, p<0.05). The bone changes were also shown by QUS (women: Ad-SOS values of 1950 ± 90 m/s in RA vs 2137 ± 35 m/s in young healthy controls (p<0.005); men AD-SOS 1956 ± 87 m/s in RA vs 2146 ± 41 m/s in young healthy controls (p<0.05)). These results show that BMD and Ad-SOS values are significantly lowered in patients with early RA and indicate that periarticular osteoporosis in early RA might possibly be better detected using detailed hand scan analyses. Received: 2 February 1999 / Accepted: 25 October 1999     

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     

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     

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 Density in an Immigrant Population from Southeast Asia

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

DXA of the Hip and Heel Ultrasound but not Densitometry of the Fingers Can Discriminate Female Hip Fracture Patients from Controls: A Comparison Between Four Different Methods

Dual-energy X-ray absorptiometry (DXA) of the proximal femur and in more recent years quantitative ultrasound (QUS) of the heel are the most established methods for assessing hip fracture risk. Measurement of the fingers offers a new approach. We performed DXA of the proximal femur, QUS of the heel and fingers, and radiographic absorptiometry (RA) of the fingers in 87 non-institutionalized women, 65–85 years of age, with a first hip fracture and compared them with 195 randomly selected age-matched controls. Bone mineral density (BMD) of the femoral neck and heel Stiffness Index were significantly lower among cases than among controls (by 15% and 17%, respectively; p<0.0001), whereas no significant differences were found for finger measurements. When applying the WHO criterion of osteoporosis, 62–98% of the patients were classified as osteoporotic, compared with 19–85% of the controls, depending on method and site. The risks of hip fracture, estimated as odds ratios for every 1 SD reduction in femoral neck BMD, heel Stiffness Index, finger QUS and finger RA, were: 3.6 (95% CI 2.4–5.5), 3.4 (95% CI 2.2–5.0), 1.0 (95% CI 0.7–1.3) and 1.2 (95% CI 0.8–1.6), respectively. Compared with women with normal BMD of the femoral neck, those classified as osteopenic had an odds ratio of hip fracture of 14 (95% CI 2-110), whereas those classified as osteoporotic had an odds ratio of 63 (95% CI 8–501). We conclude that hip DXA and heel QUS have similar capacities to discriminate the risk of a first hip fracture, whereas QUS and RA of the phalanges seem inferior techniques for differentiating female hip fracture patients from controls. Received: 10 March 2000 / Accepted: 21 September 2000     

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     

Prediction of Osteoporotic Fractures by Bone Densitometry and COLIA1 Genotyping: A Prospective, Population-Based Study in Men and Women

Osteoporosis is a common disease with a strong genetic component, characterized by reduced bone mineral density and increased fracture risk. Although the genetic basis of osteoporosis is incompletely understood, previous studies have identified a polymorphism affecting an Sp1 binding site in the COLIA1 gene that predicts bone mineral density and osteoporotic fractures in several populations. Here we investigated the role of COLIA1 genotyping and bone densitometry in the prediction of osteoporotic fractures in a prospective, population-based study of men (n= 156) and women (n= 185) who were followed up for a mean (± SEM) of 4.88 ± 0.03 years. There was no significant difference in bone density, rate of bone loss, body weight, height, or years since menopause between the genotype groups but women with the “ss” genotype were significantly older than the other genotype groups (p= 0.03). Thirty-nine individuals sustained 54 fractures during follow-up and these predominantly occurred in women (45 fractures in 30 individuals). Fractures were significantly more common in females who carried the COLIA1“s” allele (p= 0.001), although there was no significant association between COLIA1 genotype and the occurrence of fractures in men. Logistic regression analysis showed that carriage of the COLIA1“s” allele was an independent predictor of fracture in women with an odds ratio (OR) [95% CI] of 2.59 [1.23–5.45], along with spine bone mineral density (OR = 1.57 [1.04–2.37] per Z-score unit) and body weight (OR = 1.05 [1.01–1.10] per kilogram). Moreover, bone densitometry and COLIA1 genotyping interacted significantly to enhance fracture prediction in women (p= 0.01), such that the incidence of fractures was 45 times higher in those with low BMD who carried the “s” allele (24.3 fractures/100 patient-years) compared with those with high BMD who were “SS” homozygotes (0.54 fracture/100 patient-years). We conclude that in our population, COLIA1 genotyping predicts fractures independently of bone mass and interacts with bone densitometry to help identify women who are at high and low risk of sustaining osteoporotic fractures. Received: 16 November 2000 / Accepted: 9 June 2000     

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     

Pregnancy and Lactation Confer Reversible Bone Loss in Humans

The influence of pregnancy on bone mineral density (BMD) was evaluated by dual-energy X-ray absorptiometry (DXA) in 73 women (mean age 29 years, range 20–44 years) postpartum. Fifty-five age-matched women served as controls. The influence of lactation was evaluated in 65 of the delivered women who were followed with repeated measurements, a mean of 4.5 ± 0.1 and 11.5 ± 0.1 months after the delivery. The influence of multiple pregnancies was evaluated in 39 premenopausal women (mean age 38 years, range 31–54 years) with a minimum of four pregnancies (range 4–7). Fifty-eight age-matched healthy premenopausal women with a maximum of two pregnancies (range 0–2) served as controls. Data are presented as mean ± SEM. BMD data are adjusted for differences in total fat mass and total lean mass. Lumbar spine BMD was 7.6 ± 0.1% and total body BMD 3.9 ± 0.1% lower in women postpartum compared with controls (both p<0.001). BMD did not decrease significantly in non-breastfeeding mothers. Mothers breastfeeding for 1–6 months decreased femoral neck BMD by 2.0 ± 1.0% during the first 5 months postpartum (p<0.001). No further BMD loss was seen between 5 and 12 months postpartum. Femoral neck BMD 12 months after delivery was 1.3 ± 0.8% lower than after delivery in mothers breastfeeding for 1–6 months (p= 0.05). Mothers breastfeeding for more than 6 months decreased Ward’s triangle BMD by 8.5 ± 1.0% and lumbar spine BMD by 4.1 ± 0.8% during the first 5 months postpartum (both p<0.05). No further BMD loss was seen between 5 and 12 months postpartum. Femoral neck BMD 12 months after delivery was 4.0 ± 1.1% lower and Ward’s triangle BMD 5.3 ± 1.9% lower than after delivery in mothers breastfeeding for more than 6 months (both p<0.05). BMD loss was higher during the first 5 months following delivery in the lactating women compared with the non-lactating women (p< 0.05 comparing lumbar spine BMD loss in lactating mothers versus non-lactating mothers). However, in women with a minimum of four pregnancies the BMD was no lower than in age-matched women with fewer pregnancies. Total duration of lactation was not correlated with the present BMD. In summary, pregnancy seem to confer a low BMD with additional BMD loss during 5 months of lactation. Even if complete restoration in BMD was not reached within 5 months of weaning, women with four pregnancies or more had a BMD no lower than women with two pregnancies or fewer. We conclude that neither an extended lactation period nor multiple pregnancies could be used as a risk factor when predicting women at risk for future osteoporosis. Received: 15 November 2000 / Accepted: 21 March 2001