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     

Measurement of Bone Mineral Density in Mother–Daughter Pairs for Evaluating the Family Influence on Bone Mass Acquisition: A GRIO Survey

The relative influence of genetic and environmental determinants on bone mass is still unclear. Using an original multicentric mode of recruitment, based on absorptiometry current practice, the hypothesis of a familial predisposition to low bone mineral content was assessed. The study was based on dual-energy X-ray absorptiometry (DXA) measurements of lumbar and femoral neck bone mineral density (BMD), using daughters of women with a low BMD (case mothers). These BMD values were compared with those of control daughters of women with a normal BMD. Case mothers (n= 72) aged 54.3 ± 4.8 years were recruited on the basis of a questionnaire and a vertebral Z-score < – 2 SD. Their healthy daughters of more than 20 years (n= 77) aged 28.2 ± 4.9 years had their vertebral and femoral BMD Z-score determined. The control groups were composed of mothers aged 54.1 ± 4.7 years, paired by age ± 2 years to the case mothers, and of their daughters of more than 20 years old, aged 27.7 ± 5.8 years. For daughters, a significant difference was found between the mean vertebral Z-scores (–0.82 ± 1.08 for cases and 0.01 ± 1.14 for controls, p < 0.0001). The difference was in the same direction but was not statistically significant for mean femoral Z-scores (–0.58 ± 1.15 for cases and –0.22 ± 1.33 for controls, p <0.073). These findings confirm the hypothesis of a familial predisposition to low BMD. Received: 18 June 1997 / Accepted: 16 January 1998     

Reference Data and Predictive Diagnostic Models for Calcaneus Bone Mineral Density Measured with Single-Energy X-ray Absorptiometry in 7428 Chinese

Calcaneus bone mineral density (BMD) of 7428 Chinese (4126 women, 3302 men; aged 22–94 years) was measured using single-energy X-ray absorptiometry (SXA). A reference range of calcaneus BMD values for healthy Chinese men and women was established and the usefulness of this method for screening and diagnosis in osteoporosis was evaluated. The peak BMD occurred at 20–24 years old and peak BMD in women was significantly lower than in men. BMD loss in the calcaneus started at the age of 35 years for women, and at 63 years in men. BMD loss rate was 1.2%/year for women and 0.56 %/year for men after 50 years. The young normal reference for calcaneus BMD was 442.1±69.6 mg/cm² for men and 388.3±61.7 mg/cm² for women calculated from the mean BMD value of subjects whose age ranged from 20 to 49 years. The accumulated BMD loss in the calcaneus is similar to that of Ward’s triangle. Multiple linear regression showed that both age and weight were important factors. The incidence of osteoporosis in older men and women (≥60 years) is 6.6% and 32.1% respectively. We conclude that calcaneus BMD measurement is useful and sensitive for the screening and diagnosis of osteoporosis. A predictive diagnostic model for osteoporosis based on the calcaneus was constructed using multiple linear regression and the WHO criteria for diagnosing osteoporosis can be applied to calcaneus BMD. Received: 16 August 2000 / Accepted: 20 March 2001     

Geographic Differences in Bone Mineral Density of Mexican Women

The aim of this study was to generate standard curves for normal spinal and femoral neck bone mineral density (BMD) in Mexican women using dual-energy X-ray absorptiometry (DXA), to analyze geographic differences and to compare these with “Hispanic” reference data to determine its applicability. This was a cross-sectional study of 4460 urban, clinically normal, Mexican women, aged 20–90 years, from 10 different cities in Mexico (5 in the north, 4 in the center and 1 in the southeast) with densitometry centers. Women with suspected medical conditions or who had used drugs affecting bone metabolism, were excluded. Lumbar spine BMD was significantly higher (1.089 ± 0.18 g/cm²) in women from the northern part of Mexico, with intermediate values in the center (1.065 ± 0.17 g/cm²) and lower values (1.013 ± 0.19 g/cm²) in the southeast (p<0.0001). Similarly, femoral neck BMD was significantly higher in women from the north (0.895 ± 0.14 g/cm²), intermediate in the center (0.864 ± 0.14 g/cm²) and lower (0.844 ± 0.14 g/cm²) in the southeast part of Mexico (p<0.0001). Northern Mexican women tend to be taller and heavier than women from the center and, even more, than those from the southeast of Mexico (p<0.0001). However, these differences in BMD remained significant after adjustment for weight (p<0.0001). A significant loss (p<0.0001) in BMD was observed from 40 to 69 years of age at the lumbar spine and up to the eighth decade at the femoral neck. Higher and lower lumbar spine values, as compared with the “Hispanic” population, were observed in Mexican mestizo women from the northern and southeastern regions, respectively. In conclusion, there are geographic differences in weight and height of Mexican women, and in BMD despite adjustment for weight. Received: 1 September 1999 / Accepted: 20 October 1999     

The Sp1 COLIA1 Gene Polymorphism, and Not Vitamin D Receptor or Estrogen Receptor Gene Polymorphisms, Determines Bone Mineral Density in Postmenopausal Greek Women

Several genetic polymorphisms are implicated as determinants of bone mineral density (BMD) in postmenopausal women. These include the Sp1 polymorphism of the collagen type Iα 1 (COLIA1) gene, the FokI and BsmI polymorphisms of the vitamin D receptor (VDR) gene, and the PvuII and XbaI polymorphisms of the estrogen receptor (ER) gene. The relative importance and the independence of these genetic effects have not been studied simultaneously in the same population. We evaluated the effects of these polymorphisms on lumbar spine BMD among 154 postmenopausal Greek women. BMD tended to differ across Sp1 genotypes (mean 0.842 g/cm² in SS, 0.851 g/cm² in Ss, 0.763 in ss, age-adjusted p = 0.056), mostly because ss homozygotes had lower BMD (p = 0.018 compared with SS and Ss). No other polymorphisms were associated with BMD in this population (p= 0.53 for FokI, p= 0.94 for BsmI, p = 0.80 for PvuII, p = 0.91 for XbaI). In multivariate modeling, the effect of ss homozygosity was clinically and statistically significant (–0.105 g/cm², p= 0.013) after adjusting for age, weight, height, hormone replacement use, and the other four polymorphisms. None of the other four polymorphisms was retained as an independent predictor of BMD in a backward elimination model and no significant synergistic effects were observed when gene interactions were tested. When all five polymorphisms are considered simultaneously, the Sp1 COLIA1 polymorphism seems to have the most unequivocal effect on BMD, at least in postmenopausal women. Received: 3 July 2000 / Accepted: 14 November 2000     

Quantitative Ultrasound and Symptomatic Vertebral Fracture Risk in Chinese Women

Quantitative ultrasound (QUS) is emerging as a simple, inexpensive and noninvasive method for assessing bone quality and assessing fracture risk. We assessed the usefulness of a contact calcaneal ultrasonometer by studying normal premenopausal women (group I, n= 53), normal postmenopausal women (group II, n= 198), and osteoporotic women without (group III, n= 141) and with vertebral fractures (group IV, n= 53). The osteoporotic subjects had a T-score of the spine or hip neck bone mineral density (BMD) <−2.5 based on the local Chinese peak young mean values. When compared with postmenopausal controls, mean broadband ultrasound attenuation (BUA), speed of sound (SOS), and quantitative ultrasound index (QUI) were 26%, 2.1% and 25% lower in women with vertebral fractures (p all <0.005). The correlation coefficients between QUS parameters and BMD of the spine and hip ranged between 0.4 and 0.5. The ability of the QUS to discriminate between patients groups was determined based on the mean value of normal premenopausal women in group I. The mean T-score for women with fractures was −2.87 ± 1.02 for BUA, −2.54 ± 0.79 for SOS, −3.17 ± 0.70 for QUI, −2.65 ± 0.86 for L2–4 BMD and −2.53 ± 0.66 for hip neck BMD. After adjustment for age and body mass index, the odds ratio of vertebral fracture was 1.71 (95% CI 1.2–2.6) for each 1 SD reduction in BUA, 2.72 (1.3–5.3) for SOS, 2.58 (1.4–4.6) for QUI, 2.33 (1.6–3.3) for L2–4 BMD, 2.09 (1.37–3.20) for femoral neck BMD and 1.88 (1.34–2.92) for total hip BMD. The association between the QUS parameters and vertebral fracture risk persisted even adjustment for BMD. The area under the receiver operating characteristic curve for BUA for vertebral fracture was 0.92, for SOS, QUI, L2–4 BMD and femoral neck BMD was 0.95, and for total hip was 0.91. Received: 7 January 1999 / Accepted: 18 May 1999     

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 Metabolism and Gonad Function in Male Patients Undergoing Liver Transplantation: A Two-Year Longitudinal Study

Osteodystrophy is a major complication of end-stage liver disease, especially in postmenopausal women. Our aim in this study was to evaluate bone metabolism and gonad function in men undergoing orthotopic liver transplantation (OLTx). Twenty-three consecutive men (mean age 48 ± 13 years) evaluated for OLTx were studied, assessing the following parameters at baseline and 3, 6, 12 and 24 months after OLTx: lumbar spine (L2–L4) bone mineral density (BMD), parathyroid hormone (PTH), osteocalcin (BGP), 25-hydroxyvitamin D (25OHD), free testosterone (FT) and gonadotropins (FSH, LH). At baseline, 12 patients (52%) had a T-score <–2.5 SD and the mean BMD was 0.806 ± 0.11 g/cm² (range 0.470–1.045 g/cm²). The BMD was lower 3 months after OLTx and significantly higher 12 and 24 months after OLTx. A significant increase in serum BGP was observed at 6, 12 (p<0.05) and 24 months (p<0.005) after OLTx. The mean serum PTH level was 26.6 ± 3.1 pg/ml at baseline and increased significantly at 12 and 24 months (to 49.4 ± 9.9 and 61.2 ± 10.1 pg/ml, respectively; p<0.05). 25OHD serum levels were low at baseline and returned to the normal range after 12 and 24 months (baseline, 8.73 ± 1.54 ng/ml; 12 months, 16.4 ± 2.6 ng/ml; 24 months, 17.67 ± 3.1 ng/ml; p<0.05). FT was significantly lower at baseline than in a group of 10 healthy controls (5.09 ± 10.99, vs 10.3 ± 1.1 pg/ml; p<0.0001). After OLTx a significant increase in FT was recorded at 6, 12 (p<0.05) and 24 months (p<0.005). FT was not correlated with BMD, however. After OLTx an increase in FSH and LH was observed (but failed to reach statistical significance) at 3 and 6 months, followed by a slight reduction at 12 and 24 months. Thus a high proportion of men with end-stage liver disease do have osteoporosis. After OLTx, an early recovery of gonad function is observed, followed by an increase in bone mass, which occurs from the sixth month onward. Received: 3 October 2000 / Accepted: 21 March 2001     

Bone Mineral Density in Sixty Adult Patients with Marfan Syndrome

Sixty adult patients (40 women, 20 men) with Marfan syndrome (MFS) according to the Berlin criteria had a full clinical examination and bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry of the hip and nondominant forearm. BMD was expressed as a Z-score and compared with the reference population of the Hologic database. In MFS men, BMD (g/cm²) was compared with the BMD of 45 normal tall Caucasian adults. Osteocalcin was measured by radioimmunoassay. In patients with MFS, BMD was compared between patients with and without previous fractures and according to the phenotypic severity of MFS. The mean age of the patients was 32.9 ± 9.3 years (women 32.5 ± 9.7, men 33.4 ± 8.6), mean height was 180.3 ± 10.3 cm (women 176.3 ± 9.2, men 188.1 ± 7.5) and mean body mass index 20.9 ± 3.6 kg/m² (women 20.8 ± 3.4, men 20.95 ± 3.97). Hyperlaxity score (Beighton criteria) was 6.9 ± 1.1. Six patients (10%) had a previous fracture. Thirty per cent of patients had had at least one previous operation for scoliosis, aortic dilatation or eye problems. BMD values in the 60 patients were as follows: Z-score of the hip, −1.26 ± 0.93, p<10⁻⁹ (neck, −0.93 ± 1.09, p<10⁻⁹; trochanter, −1.31 ± 0.85, p<10⁻⁹; intertrochanter, −1.39 ± 0.99, p<10⁻⁹; Ward’s triangle, −0.93 ± 1.88, p<10⁻⁹); Z-score of the radius: −1.6 ± 1.06, p<10⁻⁹ (1/3 proximal, −1.29 ± 1.03; mid-radius, −1.94 ± 1.04; ultradistal, −0.68 ± 1.1, p<10⁻⁹). The decrease in BMD was similar in men and women at both the hip and the radius. BMD in MFS patients was significantly decreased at cortical compared with trabecular sites (radius 1/3 proximal vs ultradistal, p<0.0001; total femur vs Ward’s triangle, p<0.0005). No difference in BMD was found between MFS patients with or without previous fractures and those with severe or less severe phenotypic expression of MFS. An influence of height and weight in MFS on BMD is suspected. Osteocalcin was not increased in our group of MFS patients. Thus both men and women with MFS have a significant deficit of BMD at the hip and radius. The decrease in BMD is present equally in both sexes and is more pronounced at predominantly cortical sites. In our group of patients we found no increase in fractures and no relation between decreased BMD and phenotypic expression of the syndrome. Received: 30 October 1998 / Accepted: 26 May 1999     

Osteocalcin Gene Polymorphism is Related to Bone Density in Healthy Adolescent Females

Recently a polymorphism was found in the human osteocalcin gene, and its association with bone mass was investigated in healthy postmenopausal Japanese women. The osteocalcin gene allelic variant HH was found to be overrepresented in women with osteopenia. The purpose of this study was to investigate whether the previously demonstrated polymorphism of the osteocalcin gene was related to bone mineral density (BMD; g/cm²) or osteopenia in a group of 97 healthy Caucasian adolescent females (aged 16.9 ± 1.2 years, mean ± SD). BMD of the left humerus, right femoral neck, lumbar spine and total body was measured using dual-energy X-ray absorptiometry. The relation between the allelic variants and bone density was analyzed as presence or absence of the H allele. Presence of the H allele was found to be related to a lower BMD of the humerus (0.97 vs 1.02, p = 0.03). There was also a strong tendency towards significance at the femoral neck (p = 0.06) and total body (p = 0.11). Using a multiple linear regression and including physical activity, weight, height and years since menarche, presence of the H allele was found to be an independent predictor of humerus BMD (β=−0.21, p<0.05) and femoral neck BMD (β=−0.23, p<0.01). Using logistic regression, presence of the H allele was also independently associated with a 4.5 times increased risk of osteopenia (p = 0.03) in the whole group. Osteopenia was defined as at least 1 SD lower bone density than the mean for the whole group of at least one of the BMD sites measured. We have demonstrated that the osteocalcin HindIII genotype is independently related to bone density in healthy adolescent females. The present study also suggests that presence of the H allele is predictive of osteopenia at an early age. Received: 31 January 2000 / Accepted: 25 April 2000     

Influence of Heredity and Environment on Bone Density in Adolescent Boys: A Parent–Offspring Study

The purpose of the present parent–offspring study was to investigate the influence of heredity and environment on bone density in young men. Another aim was to discover whether the same genetic factors influence bone mass, lean mass and muscle strength. Fifty families including a father, mother and one son were investigated. The mothers (aged 44.5 ± 4.4 years) and fathers (aged 47.1 ± 4.4 years) generally had a sedentary lifestyle with little physical activity. As a contrast, all but three of the sons (aged 17.0 ± 0.4 years) were active in ice hockey training. Bone mineral density (BMD, g/cm²) of the total body, head, lumbar spine and femoral neck was measured using dual-energy X-ray absorptiometry. Muscle strength of the hamstrings and quadriceps muscles was also measured in the boys. BMD values of different sites in the fathers, mothers and sons were adjusted for weight, height, age, and any significant influence of environment. Heritability estimates were obtained as regression coefficients with the boys’ adjusted BMD as dependent variable and the adjusted midparent bone density (father BMD + mother BMD/2) as independent variable. Accordingly, heritability explained 34–54% of the variation in the sons’ BMD. Midparent BMD of several sites also predicted the boys’ lean mass and quadriceps strength, and midparent–offspring differences in lean mass predicted midparent–offspring differences in BMD of the total body, head and spine (β= 0.30–0.51, p<0.05). The sons were found to have almost 30% higher femoral neck BMD than their fathers, and physical activity (hours/week) predicted BMD at several sites among the sons β= 0.26–0.34, p <0.05). In conclusion, heritability is a main determinant of the variance in BMD in young men. Based on the results we suggest that the same genetic factors may influence bone mass, lean mass and muscle strength by affecting body size. The present study also emphasizes the importance of physical activity for the development and maintenance of BMD in men. Received: 26 October 1998 / Accepted: 24 February 1999     

Polymorphism of the Vitamin D Receptor Gene and Corticosteroid-Related Osteoporosis

Corticosteroid therapy (CST) is associated with reduced intestinal calcium absorption, bone loss and increased fracture risk. As polymorphisms of the vitamin D receptor (VDR) gene may be associated with bone mineral density (BMD) and intestinal calcium absorption, we asked whether patients with a given VDR genotype receiving CST may be at increased or decreased risk for corticosteroid-related bone loss and osteoporosis. We measured areal BMD (g/cm²) by dual-energy X-ray absorptiometry in 193 women (50 premenopausal, 143 postmenopausal) and 70 men with rheumatoid arthritis (n= 44), obstructive airway diseases (n= 128) and other corticosteroid-treated diseases (n= 91). All patients received a cumulative dose greater than 1.8 g per year or a minimum of 5 mg daily of prednisolone or equivalent for at least 1 year. VDR alleles were typed by polymerase chain reaction assay based on the polymorphic BsmI and TaqI restriction sites. BMD in patients was expressed as a Z-score (mean ± SEM) derived from age- and gender-matched controls. BMD was reduced in patients at the lumbar spine (bb, −0.52 ± 0.12; Bb, −0.47 ± 0.11; BB, −0.65 ± 0.18 SD; p<0.01), femoral neck (bb, −0.46 ± 0.10; Bb, −0.34 ± 0.10; BB, −0.54 ± 0.14 SD; p<0.01), Ward’s triangle (bb, −0.44 ± 0.10; Bb, −0.31 ± 0.10; BB, −0.45 ± 0.13 SD; p<0.01), and trochanter (bb, −0.50 ± 0.10; Bb, −0.30 ± 0.10; BB, −0.44 ± 0.14 SD; p<0.01). However, there was no significant difference in the deficit in BMD in any of the genotypes, either before or after adjusting for age, sex, body mass index, disease type, age at onset of disease, disease duration, cumulative steroid dosage, smoking status and dietary calcium intake. Similarly, there were no detectable differences between the BsmI genotypes and the rate of bone loss in 79 patients with repeated BMD measurements at an interval of 4–48 months. The data suggest that the VDR genotypes may not be a means of identifying patients at greater risk of corticosteroid-related bone loss. Received: 23 December 1997 / Accepted: 26 May 1998     

Recovery of Bone Mineral Density after Surgical Cure, but not by Ketoconazole Treatment, in Cushing’s Syndrome

The aim of our study was to retrospectively assess the effect of treatment on bone mineral density (BMD) in patients with Cushing’s syndrome. Nineteen patients (17 women, 2 men; mean age ± SD, 41 ± 10 years; preoperative duration of disease 20 ± 15 months) were studied. Six patients had a cortisol-producing adenoma and 13 had pituitary-dependent bilateral adrenal hyperplasia. BMD of the lumbar spine (L2–L4) was measured by dual-energy X-ray absorptiometry just before and 1–10 years after adrenalectomy or pituitary adenomectomy. Patients were divided in two groups. The first group of 9 patients (6 adrenal and 3 pituitary adenomas; group A) included those treated successfully by surgery (>5 years follow-up in the case of pituitary surgery). The second group of 10 patients (group B) included those treated with the steroidogenesis inhibitor ketoconazole, 300–600 mg/day, after unsuccessful pituitary surgery. In group A, restoration of normal cortisol was associated with a significant increase in BMD (from 829 ± 112 mg/cm² to 952 ± 107 mg/cm²; p = 0.002). In group B, no changes in BMD were observed (from 857 ± 160 to 847 ± 163 mg/cm²), in spite of markedly decreased or normalized cortisol levels during ketoconazole treatment. These findings indicate that definitive correction of hypercortisolism restores BMD to normal levels in patients with Cushing’s syndrome. In patients treated with ketoconazole after unsuccessful pituitary surgery, even when normalization of cortisol levels was achieved, BMD remained low. This would suggest an interfering effect of this drug on bone metabolism. Received: 26 February 2001 / Accepted: 11 June 2001     

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     

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     

Estimation of the Prevalence of Low Bone Density in Canadian Women and Men Using a Population-Specific DXA Reference Standard: The Canadian Multicentre Osteoporosis Study (CaMos)

The Canadian Multicentre Osteoporosis Study (CaMos) is a prospective cohort study which will measure the incidence and prevalence of osteoporosis and fractures, and the effect of putative risk factors, in a random sample of 10 061 women and men aged ≥25 years recruited in approximately equal numbers in nine centers across Canada. In this paper we report the results of studies to establish peak bone mass (PBM) which would be appropriate reference data for use in Canada. These reference data are used to estimate the prevalence of osteoporosis and osteopenia in Canadian women and men aged ≥50 years. Participants were recruited via randomly selected household telephone listings. Bone mineral density (BMD) of the lumbar spine and femoral neck were measured by dual-energy X-ray absorptiometry using Hologic QDR 1000 or 2000 or Lunar DPX densitometers. BMD results for lumbar spine and femoral neck were converted to a Hologic base. BMD of the lumbar spine in 578 women and 467 men was constant to age 39 years giving a PBM of 1.042 ± 0.121 g/cm² for women and 1.058 ± 0.127 g/cm² for men. BMD at the femoral neck declined from age 29 years. The mean femoral neck BMD between 25 and 29 years was taken as PBM and was found to be 0.857 ± 0.125 g/cm² for women and 0.910 ± 0.125 g/cm² for men. Prevalence of osteoporosis, as defined by WHO criteria, in Canadian women aged ≥50 years was 12.1% at the lumbar spine and 7.9% at the femoral neck with a combined prevalence of 15.8%. In men it was 2.9% at the lumbar spine and 4.8% at the femoral neck with a combined prevalence of 6.6%. Received: 23 April 1999 / Accepted: 14 April 2000     

Uneven Deficits in Vertebral Bone Density in Postmenopausal Patients with Primary Hyperparathyroidism as Evaluated by Posterior–Anterior and Lateral Dual-Energy Absorptiometry

This investigation was undertaken to determine whether the preservation of bone mass in patients with mild primary hyperparathyroidism (PHPT) could be detected when measuring spine density in the lateral projection. We compared the bone mineral density (BMD) of L2–L4 utilizing the posterior–anterior (PA) and lateral projections in postmenopausal patients with PHPT and in a group of 27 postmenopausal normal women. Thirty-three consecutive postmenopausal patients with PHPT were studied; 25 were asymptomatic whereas the remaining 8 suffered complications related to the disease. Based upon the criteria established by the Consensus Conference on the Management of Asymptomatic PHPT, only 10 of the 25 asymptomatic patients could be considered affected by mild disease; the remaining patients were classified as having moderate disease. Patients with mild disease had mean lateral total BMD values (0.682 ± 0.113 g/cm²) significantly higher than normal women (0.588 ± 0.076, p<0.02) and patients with moderate disease (0.599 ± 0.077, p<0.05). There were significant differences among the three groups in both PA L2–L4 and L1–L4 levels: patients with mild disease had significantly higher mean BMD values than patients with moderate disease and normal women, when either three or four vertebrae were considered. Interestingly, at this latter site, patients with moderate disease had significantly (p<0.05) lower values than normal women. Our results indicate that patients with mild PHPT have a preservation of vertebral mass when compared with the other hyperparathyroid patients and normal women, when taking into account both the mainly trabecular portion and the whole vertebra. The finding that when the PA projection was assessed, BMD values of patients with moderate disease were significantly lower than those of normal women, might be attributed to the detrimental effect of raised parathyroid hormone levels on the cortical component of the vertebral body. Received: 20 October 2001 / Accepted: 26 February 2002     

Use of Phalangeal Bone Mineral Density and Multi-site Speed of Sound Conduction to Monitor Therapy with Alendronate in Postmenopausal Women

In women with postmenopausal osteoporosis (PMO), response to therapy with bisphosphonates is conventionally monitored using central-site (hip and spine) bone mineral density (BMD), but more convenient alternatives are desirable. During a randomized parallel-group study of the efficacy of once-weekly (80 mg vs 160 mg) oral alendronate in the treatment of PMO, 81 women (mean age 70.2 years ± 4.6 SD) had BMD measurements of total hip (TH) and lumbar spine (LS) (L1–L4, Hologic); and of the middle phalanx of the middle digit of the non-dominant hand (accuDXA) at baseline and after 6 and 12 months of therapy with alendronate. At the same timepoints, subjects also had measurements of speed of sound (SOS) through bone at four sites (distal 1/3 radius, proximal phalanx of the third finger, midshaft of the tibia and fifth metatarsal) using the Sunlight Omnisense Ultrasound Bone Sonometer. Data from both patient groups were pooled for this analysis. Mean TH BMD at baseline was 0.705 g/cm²± 0.093 (SD) and increased by 1.7%± 2.3% and 2.5%± 2.3% at 6 and 12 months respectively (p= 0.09 and p<0.0001). Mean LS BMD at baseline was 0.718 ± 0.076 g/cm² and increased by 3.9%± 3.6% and 6.1%± 3.5 % at 6 and 12 months respectively (both p<0.0001). There was no statistically significant change from baseline in mean BMD by accuDXA at either 6 or 12 months. The only statistically significant changes in SOS were at the radius (decrease in SOS at 12 months, p = 0.04) and tibia (increase at 6 months, p<0.01, but no change between baseline and 12 months). Baseline correlation coefficients between accuDXA and LS and TH DXA were 0.22 (p= 0.05) and 0.27 (p= 0.02) respectively. Correlation coefficients between SOS and LS DXA ranged from 0.05 to 0.22; and between SOS and TH DXA ranged from –0.08 to 0.10 (all p= NS). These data suggest that the response to alendronate therapy over this time period cannot be measured by accuDXA or Sunlight SOS at the sites studied. Received: 26 June 2001 / Accepted: 27 September 2001     

Age and Sex Differences in the Bone Mineral Density of the Distal Forearm Based on Health Check-up Data of 6343 Japanese

Bone mineral density (BMD) predicts osteoporotic fractures. The incidence of osteoporotic fractures in Japan is lower than among Caucasians, but fewer data on the BMD of Asians have been reported. This study attempted to clarify the age and sex differences in the forearm BMD of healthy adult Japanese and to assess racial differences between Japanese and Caucasians. The subjects were 6343 healthy adult Japanese (5281 females, 1062 males) who underwent a health check-up at a health care service center between February 1995 and August 1999. Subjects’ age ranged from 15 to 80 years. The BMD of the distal radius and ulna of the non dominant forearm was measured by dual-energy X-ray absorptiometry. Overall, the forearm BMD of men was greater than that of women in all age groups. Peak BMD was 0.484 g/cm² in the 40–44 year age group of women and 0.590 g/cm² in the 30–34 year age group of men. The forearm BMD of women under 50 years of age (the average age at menopause) increased slightly with age (2.0%/decade, p<0.0001), but it did not among their male counterparts. After 50 years of age, BMD of the women decreased linearly (–1.6%/year, p<0.0001) with age, the rate of decrease being 1.7-fold faster than in their male counterparts. Rates of gain and loss of forearm BMD differ between the sexes. In comparison with data previously reported, we did not find any evidence of racial differences in BMD as an explanation for the lower incidence of osteoporotic fractures in Japan. Received: 23 November 1999 / Accepted: 17 March 2000     

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