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     

Effect of Soy Protein on Bone Metabolism in Postmenopausal Japanese Women

We conducted a cross-sectional study of the effects of soybean protein intake on bone mineral density and biochemical markers in 85 postmenopausal Japanese women. Nutrients in the diet of postmenopausal Japanese women visiting the osteoporosis unit, including subjects with normal lumbar spine bone mineral density (L2–4 BMD), were investigated by questionnaire, and the calculated daily energy, protein, soy protein and calcium intake were obtained. L2–4 BMD was measured with dual-energy X-ray absorptiometry, and assays done of serum alkaline phosphatase (ALP) and serum intact osteocalcin (IOC) as bone formation markers and urinary pyridinoline (UPYR) and urinary deoxypyridinoline (UDPYR) as bone resorption markers. Soy protein intake was significantly associated with the Z-score for L2–4 BMD (r= 0.23, p = 0.038) and UDPYR (r =−0.23, p = 0.034). Stepwise multiple regression analyses showed that soy protein intake is significantly associated with the Z-score for L2–4 BMD (β= 0.225, p = 0.04) and UDPYR (β=−0.08, p = 0.03) among four nutritional factors. These results suggest that high soy protein intake is associated with a higher bone mineral density and a lower level of bone resorption, but further studies are needed to confirm the causal dynamic mechanisms. Received: 17 September 1999 / Accepted: 29 February 2000     

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     

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     

Relation of Statin Use and Bone Loss: A Prospective Population-Based Cohort Study in Early Postmenopausal Women

Recent experimental and epidemiologic studies have suggested that the lipid-lowering drugs, statins, may have bone-protective effects. We studied the effects of statin use on the change in bone mineral density (BMD) in a prospective 4.5-year cohort study based on subjects from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) Study, Finland. Six hundred and twenty women aged 53–64 years were divided into four groups: 55 women reported continuous and 63 women occasional statin use during the follow-up; 142 non-users of statins reported hypercholesterolemia whereas 360 non-users did not. Spinal and femoral BMDs were measured by dual-energy X-ray densitometry in 1995–1996 and 1999–2000 and the BMD changes of the four groups were compared. Characteristics of the study population were obtained with postal inquiries. The mean annual spinal and femoral BMD changes of the study groups were 0.29% and −0.50% for the continuous statin users, 0.19% and −0.57% for the occasional statin users, 0.52% and −0.29% for the hypercholesterolemic non-users of statins, and 0.39% and −0.33% for the non-users of statins without hypercholesterolemia, (p= 0.398 and p = 0.404) respectively. The corresponding BMD changes adjusted for age, years since menopause, body mass index, BMD at baseline, calcium intake, estrogen and cortisone therapy, duration of follow-up and statin use before the baseline were −0.20% and −0.47%, 0.19% and −0.54%, 0.54% and −0.32%, 0.47% and −0.33% (p= 0.134 and p= 0.628), respectively. Our results suggest that statins do not protect from early postmenopausal bone loss. Randomized trials are needed to confirm these results. Received: 11 October 2001 / Accepted: 3 January 2002     

Response to Alendronate in Osteoporosis after Previous Treatment with Etidronate

Bisphosphonates such as etidronate and alendronate are widely accepted as effective agents for the treatment of osteoporosis. However, some physicians find the choice of which one to use in different patients, and the comparative magnitude of response, unclear. Fifty postmenopausal women with osteoporosis [group 1: 27 women who had received 3 years of previous cyclical etidronate treatment, mean age 70.5 years, bone mineral density (BMD) mean T-score lumbar spine (LS) −3.58 and femoral neck (FN) −2.51; group 2: 23 women who had not previously received cyclical etidronate treatment, mean age 73.7 years, BMD mean T-score LS −3.65 and FN −2.96] were treated with 10 mg alendronate daily, to determine whether pretreatment with etidronate affected the response to alendronate, and whether patients who did not respond to etidronate, responded to alendronate. There was a significant increase in LS BMD after 2 years of treatment with alendronate compared with baseline (group 1: 7.84%, p<0.001; group 2: 6.69%, p<0.001), but there was no statistical difference between the groups. In the group 1 patients there was a significant difference between the initial response (at the LS BMD) to 2 years of cyclical etidronate (1.86%) and later response to 2 years of alendronate (7.84%) (p<0.0001). The 10 patients who did not respond at the LS to etidronate alone, showed a significantly better response (mean BMD change +6.3%) when subsequently treated with alendronate (a net difference of 9.3%, p = 0.002). In 15 patients who did not respond at the FN to etidronate alone, the mean response to alendronate was +0.96% (a difference of 7%, p = 0.004). This study shows that pretreatment with 3 years of cyclical etidronate is not detrimental to the subsequent LS BMD response to alendronate. There is evidence that alendronate produced a greater bone density response than etidronate, and patients who did not respond to etidronate with an increase in LS bone density, subsequently did so following alendronate. Received: 22 June 1999 / Accepted: 18 January 2000     

Intensive Insulin Therapy and Bone Mineral Density in Type 1 Diabetes Mellitus: A Prospective Study

To determine the effect of metabolic control on bone mineral density (BMD) in type 1 diabetes mellitus (type 1 DM), we studied BMD (by dual-energy X-ray energy absorptiometry) and bone remodeling parameters in 62 patients with type 1 DM both before and 7 years after commencement of intensive insulin therapy. Overall outcomes after the 7-year treatment included the stabilization of BMD at all sites, as well as a significant decrease in tartrate-resistant acid phosphatase (TRAP) (4.302 ± 2.62 vs 2.65 ± 0.97 IU/l; p = 0.0001) and increase in intact parathyroid hormone (PTHi) (28.05 ± 15.7 vs 39.78 ± 22.41 ng/l; p = 0.005). Presence of diabetic retinopathy (RTP) versus its absence (non-RTP) was associated with lower BMD in femoral neck (FN) (0.831 ± 0.142 vs 0.756 ± 0.153 mg/cm²; p = 0.03) and Ward’s triangle (WT) (0.736 ± 0.165 vs 0.632 ± 0.172 mg/cm²; p = 0.03), and with a lower T-score in FN (–0.93 ± 1.34 vs –1.70 ± 1.46; p = 0.04) and WT (–0.72 ± 1.42 vs –1.540 ± 1.55; p = 0.04) and Z-score in FN (–0.591 ± 1.23 vs –1.132 ± 1.46; p = 0.01). The percentage of patients with osteopenia or osteoporosis in the RTP group was significantly higher than in the non-RTP group (72% vs 53%, p = 0.05; RR= 3.2) and the glycosylated hemoglobin (HbA1c) levels of the RTP group were also higher (8.53 ± 1.6% vs 7.1 ± 1.1%; p = 0.05). The improvement in metabolic control, increase in body mass index and decrease in resorption parameters could contribute to the stabilization of bone mass in type 1 DM but the presence of retinopathy is a critical factor in the progression of diabetic osteopenia. Received: 4 June 1999 / Accepted: 16 November 1999     

In Vivo MRI Measurements of Bone Quality in the Calcaneus: A Comparison with DXA and Ultrasound

Magnetic resonance imaging (MRI) has shown promise in the assessment of bone architecture. The precision and feasibility of MRI measurements in osteoporosis in vivo have been assessed in this study. T2′ was calculated from measurements of T2 and T2* in the calcaneus of 32 postmenopausal women using a gradient-echo sequence PRIME (Partially Refocused Interleaved Multiple Echo). This sequence allows the measurement of T2 and T2* in one acquisition. In vivo measurements of bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) were made in the calcaneus, spine and femoral neck. The ultrasound parameters broadband ultrasound attenuation (BUA) and speed of sound (SOS) were also measured in the calcaneus. These three techniques have not previously been compared in the same study population. The precision of the MRI technique was poor relative to the DXA and ultrasound techniques, with a CV of 6.9%± 4.4% for T2′ and 5.5%± 3.6% for T2*. Approximately 4% of this is due to system error as determined by phantom measurements. The postmenopausal women were classified as having low BMD if they had a lumbar spine (L2–4) BMD of less than 0.96 g/cm² (more than 2 standard deviations below normal peak bone mass). Calcaneal T2′ was significantly correlated with calcaneal BMD (r = –0.79, p <0.0001), BUA (r = –0.59, p = 0.0004) and SOS (r = –0.58, p = 0.0006). T2′ was significantly different in postmenopausal women with normal BMD and those with low BMD (p <0.01). However, the difference was of only borderline significance (p <0.06) after adjustment for age and years since menopause. Received: 8 July 1997 / Accepted: 29 April 1998     

Vitamin D and Bone Mineral Density in Ambulatory Women Living in Buenos Aires, Argentina

The aim of this study was to determine possible associations between bone mineral density (BMD), 25-hydroxyvitamin D (25(OH)D) and intact parathyroid hormone (PTH). In a retrospective study we examined the case notes of free-living postmenopausal women living in our city (34° S). We also report a low prevalence of vitamin D deficiency (25(OH)D <25 nmol/l, 5.6%) and of secondary hyperparathyroidism (intact PTH >65 pg/ml, 7.5%). Age was correlated with BMD at the lumbar spine (r=−0.25, p = 0.00038) and femoral neck (r=−0.252, p = 0.0003). Body mass index (BMI) was correlated with BMD at the femoral neck (r= 0.177, p = 0.021) but not at the lumbar spine. 25(OH)D was positively correlated with BMD at the femoral neck (r = 0.149, p=0.036) but not at the lumbar spine. PTH was positively correlated with age (r= 0.279, p = 0.012) and negatively correlated with 25(OH)D (r=−0.322, p = 0.0036). PTH was also negatively correlated with BMD at the lumbar spine (r=−0.258, p=0.02) and the femoral neck (r=−0.282, p = 0.011). Forward stepwise multiple regression showed that BMI, age and 25(OH)D made significant contributions to BMD at the femoral neck. PTH also showed a significant contribution to BMD at both sites. In conclusion, weak correlations found between PTH and 25(OH)D and BMD suggest these biochemical variables, among other factors, contribute to lumbar spine and femoral neck BMD. Received: 19 February 2000 / Accepted: 20 June 2000     

Bone Size and Bone Mass in 10-Year-Old Danish Children: Effect of Current Diet

Lifestyle factors, such as diet, are believed to be involved in modifying bone health, although the results remain controversial, particularly in children and adolescents. The objective of the study was to identify associations between dietary factors and whole body bone measurements in 10-year-old children. The study was a cross-sectional analysis of a random sample of 105 healthy Danish children, aged 10 years (9.97 ± 0.09). Whole body bone mineral content (BMC) and bone area (BA) were determined by dual-energy X-ray absorptiometry. The influence of diet (7 day food records) on BMC and BA were examined in bi- and multivariate analyses. The mean intakes of calcium, protein, phosphorus and sodium were 1226 mg, 78 g, 1523 mg and 3.3 g, respectively. In bivariate analyses, BMC and BA were strongly positively correlated with height (p<0.001) and weight (p<0.001), and with intakes of energy (p<0.005) and several nutrients. BMC was adjusted for size by including BA, height and weight in the multiple linear regression, and BA was adjusted for size by including height and weight in the multiple linear regression. In multivariate analyses, size-adjusted BMC was positively associated with calcium intake (p = 0.02). Size-adjusted BA was positively associated with dietary protein (p = 0.003), and negatively associated with intakes of sodium (p = 0.048) and phosphorus (p = 0.01). In conclusion, calcium intake was positively associated with bone mineralization. There was a positive association between protein and BA, while for phosphorus and sodium the association was negative. The findings suggest that in addition to calcium, the intake of other nutrients influences bone development in prepubertal children. Received: 31 December 1999 / Accepted: 23 June 2000     

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     

Regular Physical Exercise and Bone Mineral Density: A Four-Year Controlled Randomized Trial in Middle-aged Men. The DNASCO Study

The aim of the study was to investigate the effects of regular aerobic exercise training on bone mineral density (BMD) in middle-aged men. A population based sample of 140 men (53–62 years) was randomly assigned into the exercise and reference groups. BMD and apparent volumetric BMD (BMD_vol) of the proximal femur and lumbar spine (dual-energy X-ray absorptiometry, DXA) and anthropomorphic measurements were performed at the randomization and 2 and up to 4 years later. The participation rate was 97% and 94% at the second and third BMD measurements, respectively. As another indication of excellent adherence and compliance, the cardiorespiratory fitness (aerobic threshold) increased by 13% in the exercise group. The 2% decrease in the reference group is regarded as an age-related change in cardiorespiratory fitness. Regardless of the group, there was no association between the increase in aerobic threshold and change in BMD. In the entire group, age-related bone loss was seen in the femoral neck BMD and BMD_vol (p<0.01). BMD and BMD_vol values increased with age in L2–L4 (p<0.004). An increased rate of bone loss at the femoral neck was observed in men with a low energy-adjusted calcium intake (p = 0.003). Men who increased their alcohol intake during the intervention showed a decrease in the rate of bone loss at the femoral neck (p = 0.040). A decrease in body height associated with decreased total femoral BMD (r= 0.19, p = 0.04) and the change in body height was a predictor of bone loss in the femoral neck (β= 0.201). Long-term regular aerobic physical activity in middle-aged men had no effect on the age-related loss of femoral BMD. On the other hand, possible structural alterations, which are also essential for the mechanical strength of bone, can not be detected by the DXA measurements used in this study. The increase seen in lumbar BMD reflects age-related changes in the spine, thus making it an unreliable site for BMD follow-up in men. Received: August 2000 / Accepted: November 2000     

Changes in Levels of Biochemical Markers and Ultrasound Indices of Os Calcis Across the Menopausal Transition

The aim of this longitudinal study was to investigate the changes in the levels of biochemical markers and ultrasound indices of os calcis across the menopausal transition. One hundred and ten healthy women (age 35–59 years at the 1992 baseline) participated in this 4-year population-based longitudinal study. Serum intact osteocalcin (IOC), urinary pyridinoline (Pyr), urinary deoxypyridinoline (Dpyr) and ultrasound indices were measured at baseline and after 4 years. The percentage changes in biochemical markers (%DIOC, %DPyr and %DDpyr) and the percentage decreases in the ultrasound indices (%DSOS, %DBUA and %DStiffness) were calculated. The values of %DIOC and %DDpyr in the perimenopausal subgroup (−4 to−3 years since menopause) and the values of %DSOS and %DStiffness in the perimenopausal subgroup (−2 to 0 years since menopause) were significantly higher than those in other groups. Pyr was significantly correlated with %DSOS (r=−0.467, p<0.01) and %DStiffness (r = −0.330, p<0.05) and Dpyr was significantly correlated with %DSOS (r=−0.390, p<0.05), %DBUA (r=−0.353, p<0.05) and %DStiffness (r = −0.454, p<0.05), while %DIOC was significantly correlated with %DSOS (r=−0.278, p<0.05), %DBUA (r=−0.369, p<0.01) and %DStiffness (r = −0.383, p<0.01) in the peri- and postmenopausal groups. These results indicate that the increase in bone turnover occurs 4 years before menopause. However, the correlations between biochemical markers and ultrasound indices were too low to allow prediction of bone change in the individual patient. Received: 12 October 1999 / Accepted: 30 June 1999     

Quantitative Ultrasound of the Heel and Some Parameters of Bone Turnover in Patients with Acromegaly

Acromegaly caused by growth hormone (GH) hypersecretion is characterized by enhanced skeletal growth and soft tissue enlargement. Insulin-like growth factor-1 (IGF-1) is the main peripheral mediator of GH action and it has a crucial role in the maintenance of a normal bone mass. However, in some patients with acromegaly, secondary osteoporosis is observed, despite the strong anabolic effect of GH and IGF-1 in bones. It is thought to be due to hypogonadism. The bone changes are accompanied by increased turnover. The aim of this study was to assess bone properties by ultrasound and turnover in patients with acromegaly. The study was carried out in 26 patients (13 men, 13 women): 14 with active acromegaly and 12 cured by surgery who had non-active disease. Speed of sound (SOS), broadband ultrasound attenuation (BUA) and their combination Stiffness Index (SI) by quantitative ultrasound (QUS) of the heel, hormonal status, serum osteocalcin (OC) concentration and the urinary excretion of pyridinoline collagen crosslinks (PYR) were all studied. Controls were 20 age- and sex-matched healthy persons. We observed statistically significantly lower QUS values in patients with active disease than in those whose disease was cured. The differences were more pronounced in men. QUS values were lower in the entire group of patients compared with the controls; however, the differences were not statistically significant. Serum OC concentrations and urinary PYR excretion were higher in active disease. Statistically significant inverse correlations between serum GH levels and SOS (r=–0.58, p = 0.002); BUA (r=–0.66; p= 0.0001); T-score (r = −0,65, p= 0.0001) and Z-score (r=–0.66, p = 0.0001) were found only in male patients. No correlations between IGF-1, duration of the disease, OC, PYR and other data studied were observed. In conclusion, we have shown decreased QUS parameters suggesting impaired bone properties and quality in terms of density and elasticity in men, but not in women, with active acromegaly. This finding suggests osteoporosis with increased bone turnover. The above-mentioned changes might be caused by the action of GH on trabecular bone and its metabolism, since no hypogonadism in male patients was shown. Moreover, the influence of acromegaly on heel geometry and soft tissue swelling should also be considered. Received: 20 February 2001 / Accepted: 23 October 2001     

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

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

Fractal Analysis of Trabecular Bone Texture on Calcaneus Radiographs: Effects of Age, Time Since Menopause and Hormone Replacement Therapy

An analysis of trabecular bone texture based on fractal mathematics, when applied to trabecular bone images on plain radiographs, can be considered as a reflection of trabecular bone microarchitecture. It has been shown to be able to distinguish postmenopausal osteoporosis cases from controls. This cross-sectional study was carried out to investigate the influence of age, time since menopause and hormone replacement therapy (HRT) on the fractal dimension of trabecular bone texture at the calcaneus in a sample of 537 healthy women. Fractal analysis of texture was performed on calcaneus radiographs and the result expressed as the Hmean parameter (H = 2–fractal dimension). Total hip, femoral neck and lumbar spine bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. There was a statistically significant Hmean parameter decrease with age (p<0.0001) but the degree of correlation was low (r=–0.2) compared with the correlation between age and BMD (r=–0.36 to –0.61 according to the BMD site). We found a weak but statistically significant correlation between time since menopause and Hmean (r=–0.14, p= 0.03) in the 241 postmenopausal women included in the study. Hmean was significantly lower in a group of postmenopausal women without HRT (n= 110) compared with a group of age-matched postmenopausal women with HRT (n = 110): respectively 0.683 ± 0.043 and 0.695 ± 0.038 (p= 0.03). In conclusion, this study suggests that there is a menopause- and age-related decrease in the Hmean parameter and that HRT interferes with the results of the fractal analysis of trabecular bone texture on calcaneus radiographs. Received: 2 March 2001 / Accepted: 2 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     

Time since Vertebral Fracture: An Important Variable Concerning Quality of Life in Patients with Postmenopausal Osteoporosis

The aim of the study was to identify factors affecting patients with postmenopausal osteoporosis who had experienced one or more vertebral fractures. The overall hypothesis was that time after fracture would influence patients’ perception of pain and well-being. The sample (50 patients) was split into two groups (group A, time after fracture ≤24 months; group B, time after fracture >24 months). A fracture was defined as a vertebral height reduction of more than 20% or at least 4 mm. The assessment was carried out using the Spine Deformity Index and was confirmed by an experienced radiologist. To assess quality of life (QoL) the following measures were used: ‘well-being scale’ including social extroversion as a subscale, pain scale, and limitations in everyday life. The Sense of Coherence questionnaire developed by Antonovsky measures the ability of a person to see life meaningful, manageable and explicable. This questionnaire may reflect patients’ coping abilities and was introduced to establish whether these influence the perception of pain and well-being after vertebral fracture. Variance and covariance analysis was carried out using SPSS (version 6.1). Differences between groups A and B were found for perception of average pain (p = 0.017), social extroversion (p = 0.003) and well-being (p = 0.024). No differences were found for limitations in everyday life (p = 0.607), Sense of Coherence (p = 0.638), the Spine Deformity Index (p = 0.171) and loss of height (p = 0.619). All analyses were corrected for age. Concurrent medication was not found to influence the results. Findings suggest that time after fracture is an important variable when considering QoL and well-being after vertebral fracture and should, therefore, be considered in future studies. Received: 25 June 1998 / Accepted: 10 November 1998     

Intracapsular Hip Fracture: Increased Cortical Remodeling in the Thinned and Porous Anterior Region of the Femoral Neck

It has been shown previously that the antero-inferior cortex is subjected to maximal tensile stress during a fall onto the greater trochanter. We have recently shown that in cases of femoral neck fracture, cortical thinning and porosity is greatest in the anterior and antero-inferior region of the femoral neck. To investigate whether this is due to increased remodeling, we have quantified surface-based parameters associated with Haversian remodeling in femoral neck biopsies from women with intracapsular hip fracture and post-mortem controls. Cryostat sections of chilled biopsies were reacted for either tartrate-resistant acid phosphatase (TRAP) or alkaline phosphatase (ALP) activity. Proportions of active canals were determined in each quadrant (inferior, anterior, superior, posterior) of the femoral neck. The biopsies were then embedded in methacrylate to permit histomorphometry using Goldner’s and Solochrome sections. In the cases there was no significant increase in the proportion of canals undergoing remodeling in the cortex as a whole (p = 0.846), but the regional distribution of remodeling was markedly different from that in the controls. In the anterior cortex, the proportion of canals undergoing remodeling was increased by 56% (p = 0.0087); in contrast there was a relative decrease of 35% in the superior region (p = 0.0047). In the anterior cortex of cases there were 76% and 42% increases in the proportions of eroded (p = 0.019) and osteoid-bearing (p = 0.041) canals, respectively. In the superior region, the decrease in the proportion of remodeling sites was due to a marked decrease in canals with an osteoid surface (51%; p = 0.0031). Covariance analysis with cortical porosity as the dependent variable showed that porosity was significantly dependent on the regional distribution of eroded (p = 0.033) but not on the distribution of forming (p = 0.153) canals (R ²adj = 0.51). Cellular levels of TRAP and ALP were significantly elevated in the anterior region of cases compared with the controls (TRAP 55%, p = 0.006; ALP 36%, p = 0.003). For the posterior and inferior regions there were no marked differences in cellular TRAP and ALP levels compared with control values. These data show that the increased cortical thinning and increased porosity we have previously observed in the anterior cortex in cases of hip fracture are associated with increased indices of Haversian remodeling. These findings are consistent with the hypothesis that, in cases of hip fracture, remodeling imbalance in the anterior cortex is a continuing process up to the time of fracture and is due to increased osteoclastic cellular activity associated with an osteoblastic response that is inadequate to prevent bone loss. Received: 16 November 1998 / Accepted: 17 February 1999     

The Tromsø Study: Artifacts in Forearm Bone Densitometry – Prevalence and Effects

Suboptimal performance of bone densitometer, operator and/or subject may cause artifacts of consequence both for individual patient management and research. The prevalence and effects of such artifacts are largely unknown in densitometry. A cross-sectional population-based study was carried out of artifacts in forearm bone densitometry with single X-ray Absorptiometry (SXA) of the nondominant hand (distal and ultradistal site). After the screening, all scans were reviewed for artifact detection and reanalysis. The effect on the bone mineral density (BMD) result was found by comparing artifactual scans with a reanalyzed version or with normal repeat scans. All women aged 50–74 years, all men aged 55–74 years and 5–10% samples of other age groups aged ≥25 years attending the fourth Troms? health study were invited to have bone densitometry. The response rate from the background population was 80% (n= 7948). Fourteen percent of subjects had a movement artifact at either the distal or ultradistal site. The individual BMD variation was twice as large in scans with a movement artifact (0.94%) compared with normal scans (0.58%) (p= 0.0027). The radial endplate was inaccurately detected in 74% of the scans. Reanalysis of these scans led to a mean 3.8% decrease in the BMD value and an increase in the prevalence of osteoporosis of 10%. Artifacts were thus common, and their effects were clinically relevant in forearm bone densitometry. Artifacts and their effects need to be characterized in other bone densitometry settings also. Received: 25 February 1999 / Accepted: 3 May 1999