The Decrease in Serum Bone-Specific Alkaline Phosphatase Predicts Bone Mineral Density Response to Hormone Replacement Therapy in Early Postmenopausal Women

Hormone replacement therapy (HRT) prevents bone loss in postmenopausal women. Up to 20% of women demonstrate no increase in bone mineral density (BMD) on HRT. We examined whether early changes in serum bone alkaline phosphatase (B-ALP) predict long-term BMD changes in postmenopausal women on HRT. Ninety women within 1 year of menopause were randomly assigned to continuous or sequential estrogen/progestin (beta estradiol/norethisterone acetate) if naturally postmenopausal, or beta estradiol if within 1 month of surgical menopause. Spine, femoral neck BMD (DXA), and B-ALP were determined over 2 years. The mean percent BMD changes were 3.8%, 2.9%, 1.6% in the spine and 2.4%, 4.0%, 1.1% in the femoral neck in sequential, continuous, and estrogen alone treatment groups, respectively, significantly different from zero except for femoral neck BMD change in the estrogen alone group. HRT was associated with spine and femoral neck BMD loss in 17.4% and 25.3% of women, respectively. In estrogen/progestin-treated women, baseline B-ALP correlated with spine BMD change (r = 0.42, P < 0.01). At 3 months, B-ALP dropped significantly in the estrogen/progestin-groups with a maximal decrease at 12 months, but no change from baseline in the estrogen alone group. Using quartile analysis, women with the greatest drop in B-ALP (≥50%) at 6 months demonstrated the greatest gain in spine BMD at 2 years. A 40% decrease at 6 months in B-ALP had a 56% sensitivity, 83% specificity, 95% positive predictive value for spine BMD gain at 2 years. The decrease in B-ALP can be used to monitor BMD response to HRT. Received: 6 January 1999 / Accepted: 13 August 1999     

Rates of Change in Spinal Bone Density Among Japanese Women

To determine the rates of change in bone mineral density (BMD) at the spine in healthy Japanese women, longitudinal measurements of spinal BMD using dual X-ray absorptiometry were collected from 984 women over 17 years of age (mean age 51.6) at eight medical research centers. They were followed up for 20.9 months on average without any treatment influencing bone and calcium metabolism. Measurements of BMD obtained by two different scanners were converted into standardized BMD (sBMD) values. The multiple linear regression model predicts that spinal sBMD increases up to about 23 years of age: the estimated average rates of increases were 0.13%/year for women aged 20 years. After the age of 23, the sBMD began decreasing: the rates of loss increased by 0.045%/year for each year increase in age among premenopausal women. In perimenopausal women, the rate of loss was 2.1%/year. In postnatural menopausal women, the rates of loss decreased exponentially with increasing years since menopause. The rates of loss increased by 0.04%/year for 1 kg decrease in body weight or by 0.1%/year for 1 kg/m² decrease in body mass index. No significant differences in changes in sBMD were found between scanners and between centers after multiple adjustment. We conclude that the rates of change in spinal sBMD are associated with age in premenopausal women, and with years since menopause and weight or BMI in postmenopausal women. Caution is needed, however, when using data from different densitometers to evaluate rates in bone loss in multicenter trials. Received: 13 March 1997 / Accepted: 27 January 1998     

Long-Term Vegetarian Diet and Bone Mineral Density in Postmenopausal Taiwanese Women

This study examined bone density among postmenopausal Buddhist nuns and female religious followers of Buddhism in southern Taiwan and related the measurements to subject characteristics including age, body mass, physical activity, nutrient intake, and vegetarian practice. A total of 258 postmenopausal Taiwanese vegetarian women participated in the study. Lumbar spine and femoral neck bone mineral density (BMD) were measured using dual-photon absorptimetry. BMD measurements were analyzed first as quantitative outcomes in multiple regression analyses and next as indicators of osteopenia status in logistic regression analyses. Among the independent variables examined, age inversely and body mass index positively correlated with both the spine and femoral neck BMD measurements. They were also significant predictors of the osteopenia status. Energy intake from protein was a significant correlate of lumbar spine BMD only. Other nutrients, including calcium and energy intake from nonprotein sources, did not correlate significantly with the two bone density parameters. Long-term practitioners of vegan vegetarian were found to be at a higher risk of exceeding lumbar spine fracture threshold (adjusted odds ratio = 2.48, 95% confidence interval = 1.03–5.96) and of being classified as having osteopenia of the femoral neck (3.94, 1.21–12.82). Identification of effective nutrition supplements may be necessary to improve BMD levels and to reduce the risk of osteoporosis among long-term female vegetarians. Received: 10 May 1996 / Accepted: 9 August 1996     

Not All Postmenopausal Women on Chronic Steroid and Estrogen Treatment are Osteoporotic: Predictors of Bone Mineral Density

Chronic steroid use results in osteoporosis, and postmenopausal women are believed to be at a high risk for steroid-induced bone loss. The purpose of this study was to determine predictors of bone mineral density (BMD) in postmenopausal women on both chronic steroid and hormone replacement therapy. Seventy-six postmenopausal women (≥3 years postmenopausal, ≥2 years of steroid treatment of ≥5 mg/day of prednisone, and ≥1 year of hormone replacement therapy) were recruited into this study. Measurements of BMD of the lumbar spine and femoral neck were obtained in all subjects. Risk factors for osteoporosis were obtained by questionnaire. Discriminant analysis was performed to determine predictors of BMD. Osteoporosis, defined by a T score of <−2.5, was present in the lumbar spine or femoral neck in 34 of the 76 subjects. Based on these criteria, women with osteoporosis were significantly older, were more years postmenopausal, and had a lower body mass index (BMI) than women who did not have osteoporosis. Predictors of osteoporosis for both the femoral neck and spine included a low BMI (P < 0.05), more years postmenopausal (P < 0.01), and more years on steroids (P < 0.01). Low BMI was the only significant predictor of osteoporosis in the lumbar spine (P < 0.05), whereas for the femoral neck both years on steroids (P < 0.05) and BMI (P < 0.05) were significant predictors of low BMD. In summary, not all postmenopausal women on chronic steroid and hormone replacement therapy are osteoporotic but a low BMI, more years on steroids, and more years postmenopausal were significant predictors of osteoporosis in these subjects. Received: 8 November 1997 / Accepted: 21 May 1997     

Resistive Training Maintains Bone Mineral Density in Postmenopausal Women

We examined the effects of a total body resistive training program (RT) on total and regional bone mineral density (BMD) in older women. Twenty-seven healthy postmenopausal women (mean age 62 ± 1 years) participated in a strength training program three times/week for 16 weeks. Strength was assessed before and after training by either one or three repetition maximum (1RM and 3RM) tests. Both upper and lower body strength significantly increased by 36–65% and 32–98%, respectively, after training. There was a small but significant decrease in body weight and body mass index after training (P < 0.05), with no change in the waist-to-hip ratio. BMD, assessed by dual-energy X-ray absorptiometry, did not change over the duration of the training period in the anterioposterior spine (L₂–L₄), femoral neck, Ward's triangle, and greater trochanter. BMD of the total body, lateral spine (B₂–B₄), and the regions of the radius (1/3 radius and ultradistal radius) also did not fall in subsets of these women. Muscular strength of both the leg and chest press were significantly associated with L₂–L₄, femoral neck, Ward's triangle, and greater trochanter BMD (range r = 0.57–0.84, all P < 0.005). Markers of bone turnover, namely, bone-specific alkaline phosphatase, osteocalcin, and urinary aminoterminal cross-linked telopeptide of type I collagen did not change significantly. In conclusion, a resistive training program maintains BMD and improves muscular strength in healthy, older women. This may be important in preventing the negative health outcomes associated with the age-related loss of bone density. Received 5 June 1996 / Accepted: 26 June 1997     

High Intensity Resistance Training: Effects on Bone in Older Men and Women

There is evidence that high intensity resistance training promotes bone maintenance in older women, however, the effect of high intensity free weight training has not been investigated in older men or women. Furthermore, little is known about the chronic effect of weight training on serum insulin growth factor-I (IGF-I) in this population. We compared the effects of a moderate intensity seated resistance-training program with a high intensity standing free weight exercise program on bone mass and serum levels of IGF-I and IGFBP3 in healthy older men and women. Twenty-eight men (54.6 ± 3.2 years) and 26 nonestrogen-replaced women (52.8 ± 3.3 years) served as their own controls for 12 weeks, then were randomly assigned to a moderate or high intensity training group and trained three times/week for 24 weeks. Prior to and after the control period and at the end of training, bone mass and body composition were assessed by dual energy X-ray absorptiometry (DXA), muscle strength by isokinetic dynamometry, muscular power by Wingate Anaerobic Power Test, and IGF-I by radioimmunoassay (RIA). A repeated measures analysis of covariance (ANCOVA) revealed that high intensity training resulted in a gain in spine BMD in men (1.9%), P < 0.05, but not in women, whereas moderate intensity training produced no changes in either gender at this site. Increases were observed at the greater trochanter, P < 0.03, in men regardless of training intensity, but not in women at any hip site. However, when compared with zero, both men and women in the high intensity group demonstrated significant increases in trochanteric BMD (1.3% and 2.0%, respectively) and a decrease in femoral BMD (−1.8%). Neither circulating serum IGF-I nor IGFBP3 were altered by either training regimen, but both training programs resulted in improvements in total body strength (37.62%) and lean mass (males 4.1%, females 3.1%). We conclude that although resistance training of moderate to high intensity produced similar muscle changes in older adults, a higher magnitude is necessary to stimulate osteogenesis at the spine. However, at the spine, intensity was not sufficient to offset low levels of estrogen in early postmenopausal women. Furthermore, bone changes were not accompanied by changes in circulating serum levels of IGF-I or IGFBP3. Received: 21 July 1999 / Accepted: 11 January 2000     

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

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

The Effect of Weight Change on DXA Scans in a 2-Year Trial of Etidronate Therapy

Variation in soft tissue composition is a potential cause of error in dual X-ray absorptiometry (DXA) measurements of bone mineral density (BMD). We investigated the effect of patients' change of weight on DXA scans in 152 women enrolled in a 2-year trial of cyclical etidronate therapy. Scans of the spine, hip, and total body were performed at baseline, 1 and 2 years on a Hologic QDR-2000. The study was completed by 135 subjects (64 on etidronate, 71 on placebo). Results were expressed as the percentage change in BMD (spine, femoral neck, total body) or bone mineral content (BMC) (total body only) at 2 years. Total body scans were analyzed using the manufacturer's `standard' and `enhanced' algorithms. Analysis was performed using multivariate regression with percentage change in BMD or BMC as the dependent variable, and treatment group and percentage change in weight as the independent variables. Weight change varied between −14.4% and +16.7%. All DXA variables showed a statistically significant treatment effect. Standard total body BMD and BMC and enhanced total body BMC all showed a significant dependence on weight change (P < 0.01, P < 0.001 and P < 0.01, respectively). No effect of weight change was seen on spine, femoral neck, or enhanced total body BMD. In order to investigate the effects of weight on long-term precision, patients were allocated to two groups according to baseline body mass index (BMI <25 and >25 kg/m², respectively). For femoral neck BMD the root mean square (RMS) residual percentage change was statistically significantly larger in the high BMI group (P < 0.05) but all other bone density variables showed no significant difference. With patients allocated to two groups according to their absolute percentage change in weight (<5% and >5%, respectively) the RMS residual percentage changes in the bone density variables were statistically significantly larger in the large weight change group for femoral neck BMD (P < 0.05) and for standard and enhanced total body BMC (P < 0.01 and P < 0.05, respectively). With the exception of the standard total body algorithm, weight change in a longitudinal study of postmenopausal women was not found to cause systematic errors in the results of DXA studies but may adversely affect precision. Received: 22 November 1996 / Accepted: 30 April 1997     

Bone Mineral Density in Flatwater Sprint Kayakers

To elucidate the possible skeletal benefits of the muscular contractions and the nonweight-bearing loading pattern associated with kayaking, we investigated the bone mineral density (BMD, g/cm²) of 10 elite kayakers, six males and four females, with a median age of 19 years. Each subject was compared with the mean value of two matched controls. BMD of the total body, head, ribs, humerus, legs, proximal femur (neck, wards, trochanter), spine, lumbar spine, and bone mineral content (BMC, g), of the arms was obtained using a dual energy X-ray absorptiometer (DXA). Body composition was also assessed. The kayakers had a significantly (P < 0.05–0.01) greater BMD in most upper body sites: left and right humerus (10.4% and 11.7%), respectively, ribs (6.4%), spine (10.9%), and a greater BMC of the left and right arm (15.7% and 10.6%, respectively). No significant differences in the BMD of the total body, head, or any of the lower body sites were found, except for the pelvis, which was significantly greater in kayakers (5.1%). The controls had a significantly lesser lean body mass (10.4%) and greater percentage of body fat (19.5%) than the kayakers. Bivariate correlation analysis in the controls demonstrated significant and strong relationships between BMD in upper body sites and lean body mass, weight, and fat; the effects of training seem to outweigh most such relationships in kayakers. In conclusion, it seems that the loading pattern and muscular contractions associated with kayaking may result in site-specific adaptations of the skeleton. Received: 21 April 1998 / Accepted: 1 October 1998     

Association of CTR and COLIA1 Alleles with BMD Values in Peri- and Postmenopausal Women

The variability of bone mass and bone strength is in part genetically determined. The pathophysiology of the disease is complex and its heritability is almost certainly polygenic. In a large group of women from north eastern Italy, homogeneous for calcium intake and other risk factors for osteoporosis, we investigated three different genetic polymorphic markers that have been associated with bone mineral density (BMD). The study includes 663 postmenopausal (aged 48–85 years) and 52 perimenopausal (aged 47–53 years) women. Lumbar spine and hip BMD were measured by dual energy X-ray absorptiometry (DXA). After DNA extraction, the restriction enzymes utilized were MscI for the SP1 site of the collagen type I regulatory region (COLIA1), AluI for the calcitonin receptor (CTR) gene, and BsmI for the Vitamin D receptor (VDR) gene. COLIA1 genotype was significantly associated with age-adjusted hip BMD, with the highest values in the SS group and the lowest in the ss group (p < 0.05). The COLIA1 effect was not visible until the sixth decade of life, but it increased thereafter with aging, becoming statistically significant also at the lumbar spine in subjects aged >70 years. CTR genotype was also significantly related to bone mass in the CC group, with the lowest age and weight-adjusted BMD values at the spine (p < 0.05). The CTR genotype effect was greater in the younger subset of women. This suggests that the CTR genotype might influence the process of acquiring peak bone mass rather than the process of bone loss along aging. No trend association was found between BMD values and VDR genotype. These findings suggest an association between the COLIA1 gene polymorphism more with the age-related rate of bone loss than with peak bone mass, which apparently is somewhat affected by CTR gene polymorphism. Received: 12 November 1999 / Accepted: 5 June 2000 / Online publication: 22 September 2000     

Specific Changes of Urinary Excretion of Cross-Linked N-Telopeptides of Type I Collagen in Pre- and Postmenopausal Women: Correlation with Other Markers of Bone Turnover

Urinary excretion of cross-linked N-telopeptide of type I collagen (NTx) has been reported to be a specific marker of bone resorption [18]. We assessed a new immunoassay for NTx as an indicator of changes in bone resorption caused by spontaneous menopause and compared cross-sectionally the levels of urinary NTx, hydroxylysylpyridinoline (HP), lysylpyridinoline (LP), hydroxyproline (OH-Pr), other serum biochemical indices, and lumbar spine and proximal femur bone mineral density (BMD). Eighty-one Japanese women aged 22–77 participated in this study; 36 were premenopausal and 45 were postmenopausal. Urinary HP, LP, and NTx stayed at low levels in the premenopausal period and rose 21%, 30%, and 67% in the postmenopausal period, respectively. The rise in LP and NTx was statistically significant (P < 0.01), suggesting that NTx is mostly released from bone matrix when bone resorption is accelerated. When premenopausal women were divided into two age groups and postmenopausal women were divided into two groups according to years since menopause (YSM) there were significant differences in LP and NTx between women <4 YSM and women aged <40 and those women aged 41+ (P < 0.01 and P < 0.05, respectively). A significant 110% increase in urinary NTx and a 48% increase in urinary LP were observed in postmenopausal women compared with age-matched premenopausal women aged 45–55. All biochemical markers other than serum PTH correlated significantly with each other (r = 0.243–0.858, P < 0.05–0.0001). Urinary NTx inversely correlated with lumbar spine BMD. When postmenopausal women were divided into three groups, the correlation between bone resorption and formation markers in women 0-1 YSM was greater than in women 2–10 YSM and in women 11 + YSM, indicating that resorption and formation are coupled at the early postmenopausal period. We conclude that urinary NTx is responsive to changes in bone metabolism caused by estrogen deficiency and may be a more sensitive and specific marker than HP, LP, or OH-Pr in the early postmenopausal years. Received: 15 February 1995 / Accepted: 18 October 1996     

Bone Mineral Density in the Chronic Patellofemoral Pain Syndrome

Bone mineral density (BMD) and clinical status of 40 patients with a chronic, unilateral patellofemoral pain syndrome (PFPS) were determinated. The mean duration of the disease at the time of the follow-up was 7.6 ± 1.8 (SD) years. The BMD was measured at the spine (L2–L4), and the femoral neck, trochanter area of the femur, distal femur, patella, proximal tibia, and calcaneus of both lower extremities using a dual-energy X-ray absorptiometric (DXA) scanner. The mean BMD of the affected limb (compared with the unaffected side) was significantly lower in the distal femur (−3.3%; P= 0.002), patella (−2.5%; P= 0.016), and proximal tibia (−1.9%; P= 0.008). The femoral neck, trochanter area of the femur, and calcaneus showed no significant side-to-side differences, and the spinal BMDs of men and women with the PFPS were comparable with the manufacturer's age-adjusted reference values for Western European men and women. The relative BMDs of the affected knee showed strongest correlation with the muscle strength of the same knee: the better the muscle strength compared with the healthy knee, the higher the relative BMD (r = 0.56–0.58 with P < 0.001 in each anatomic site of the knee). In the stepwise regression analysis, low body weight or low body mass index, high level of physical activity, the patient's good subjective overall assessment of his/her affected knee, and short duration of the symptoms were also independent predictors of the high relative BMD in the affected knee so that along with the muscle strength these variables could account for 51% of the variation seen in the relative BMD of the femur, 61% in the patella, and 54% in the proximal tibia. In conclusion, chronic patellofemoral pain syndrome results in a significantly decreased BMD in the knee region of the affected limb. The spine, proximal femur, and calcaneus are not affected. Recovery of normal muscle strength and knee function seems to be of great importance for good BMD. Received: 30 May 1997 / Accepted: 8 January 1998     

Bone Density of the Spine and Femur in Adult White Females

We measured bone mineral density (BMD in g/cm²) of the spine (L2-L4) and femur (four regions) in 1472 and 1487 cases, respectively, of ambulatory white women ages 20–79 years in the USA. A DPX densitometer was used in a mobile setting. The BMD values for women up to 69 years corresponded closely with published values for the USA, the UK, and northern Europe; our values were somewhat lower than those from other studies only in women over 70 years. The USA data were combined with data from Europe to give reference curves on about 12,000 subjects. Decreases of BMD with age in women below 50 years were much smaller than in older women (0.2% versus 0.6–1.0% per year). Femoral bone decreased from the neck region, but not the trochanter with age; the decrease of total femur BMD with age was due to loss from the former region. Loss of bone mineral content (BMC in g) from the femur neck and total femur region did not accelerate until after age 50 years, much like the spine. The apparent decrease of BMD in these regions that begins about age 40 actually is due to an increase of bone area. About 20% of USA women aged 50–79 years had BMD levels for the lumbar spine, or for the femur neck, more than −2.5 SD below the average values in young adult women 20–39 years old. Body weight had several times more impact on BMD than height, and in fact, a change of 1 kg in postmenopausal women was commensurate with the effect of a 1-year change in age. Subjects in the lowest quartile of body weight had T-scores that were 1 SD below those in the highest quartile. Received: 10 September 1998 / Accepted: 15 December 1998     

A Comparison of Bone Mineral Density and Muscle Strength in Young Male Adults with Different Exercise Level

The aim of this study was to investigate any differences in bone mass at different sites between young adults subjected to a high physical activity and a group of young adults with a low level of physical activity. In addition, we compared the relationship among bone mass, muscle strength, and body constitution in these two groups. The reference group consisted of 20 men, age 24.6 ± 2.3 years, not training for more than 3 hours per week. The ice hockey players consisted of 20 players, age 23.4 ± 4.9 years, from an ice hockey team in the second highest national Swedish league, training for about 10 hours per week. The groups were matched according to age, height, and weight. Areal bone mineral density (BMD) was measured in total body, head, humerus, spine, pelvis, femur, femoral neck, Ward's triangle, trochanter, femur diaphysis, proximal tibia, and tibia diaphysis using dual energy X-ray absorptiometry. BMD was significantly higher in the total body (8.1%), humerus (11.4%), spine (12.7%), pelvis (12.4%), femoral neck (10.3%), femur (7.4%), proximal tibia (9.8%), and tibia diaphysis (7.5%) in the high activity group. Fat mass was significantly lower in the high activity group (18.7%). The high activity group also had a significantly higher lean body mass (5.4%) and a significantly higher isokinetic muscle strength of the quadriceps muscle compared with the reference group. In the reference group, there was a general strong independent relationship between muscle strength of the thigh and all BMD sites, except for the head, tibia diaphysis, and proximal tibia. Furthermore, in the same group, body mass index (BMI) independently predicted pelvis BMD. On the contrary, in the high activity group, muscle strength did not predict any BMD site at all. In the same group, body constitutional parameters (weight, height, and fat mass) independently predicted pelvis BMD, and BMI was shown to be an independent predictor of humerus BMD. The differences in BMD between the groups seem to be site-specific and may be associated with the type and magnitude of loading during off season training and preferentially during ice hockey. High physical activity seems to weaken the relationship between BMD and muscle strength. Hence, impact forces may be of greater importance in regulating bone mass than muscle strength in itself in highly trained athletes. Received: 15 October 1997 / Accepted: 1 November     

PvuII Polymorphisms of the Estrogen Receptor α and Bone Mineral Density in Healthy Southern Chinese Women

The association between PvuII polymorphisms of the estrogen receptor α (ERα) gene and total as well as regional bone mineral density (BMD) in healthy Chinese women (n = 182) was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), where P indicated the absence and p the presence of PvuII restriction sites. Subjects with PP genotype had significantly higher BMD at the thoracic spine and ribs (both P < 0.05) when compared with those with Pp and pp genotypes. Although PP genotype had slightly higher BMD values at the lumbar spine L2-L4 region and hip by 8% and 7%, respectively, the results failed to reach statistical significance. After adjusting for age, height, weight, and years since menopause, PP genotype had higher BMD at the left (P < 0.02) and right (P < 0.05) rib region but not at the thoracic spine (P= 0.056). Analyzing the premenopausal subjects alone (n = 64) revealed that subjects with PP genotype had higher adjusted BMD at the right rib region (P < 0.05). When only the postmenopausal women (n = 118) were analyzed, the adjusted BMD of the PP genotype at the thoracic spine was significantly higher (P < 0.05) than the other two groups. In conclusion, estrogen receptor gene has a role in determining bone mass but the clinical impact on its own is probably small. Received: 10 September 1999 / Accepted: 11 January 2000     

Limited Clinical Utility of a Self-Evaluating Risk Assessment Scale for Postmenopausal Osteoporosis: Lack of Predictive Value of Lifestyle-Related Factors

The aim of this study was to assess the efficiency of a self-administered questionnaire to identify subjects with postmenopausal osteoporosis in the setting of first line medical care. A sample of 300 postmenopausal women completed the questionnaire based on 18 items. Bone mineral density at the lumbar spine (BMD-L), total hip (BMD-H), and femoral neck (BMD-N) was used as objective criterion for evaluation. The mean risk score was 8.2 ± 3.21. BMD was correlated with total risk score: r =−0.32 for BMD-L, −0.36 for BMD-N, and −0.43 for BMD-H. Cutoff points for the risk score (equal likelihood points) according to a T-score threshold of −2.5 were 8.6 for BMD-L and BMD-N and 9.3 for BMD-H; specificity and sensitivity was 62% and 62%, respectively, for BMD-L, 65% and 62% for BMD-N, and 75% and 63% for BMD-H. Stepwise multiple regression analysis of the questionnaire items in relation to BMD showed higher correlation coefficients for models including individual items rather than the overall risk score. Items concerning low weight, older age, and wrist fracture after 50 years of age were always selected as significant determinants of BMD (R = 0.43–0.55). Hormonal replacement therapy was also an important determinant. Lifestyle-related items did not contribute significantly. In conclusion, the diagnostic performance of the 18-item self-administered questionnaire was poorer than a shortened questionnaire omitting lifestyle factors. The clinical utility of a questionnaire should ultimately be evaluated in the specific optic of a chosen global strategy for prevention of osteoporotic fractures. Received: 30 October 1998 / Accepted: 10 June 1999     

Effects of Tamoxifen and Toremifene on Urinary Excretion of Pyridinoline and Deoxypyridinoline and Bone Density in Postmenopausal Patients with Breast Cancer

Tamoxifen and toremifene are two mostly used antiestrogens in the treatment of breast cancer. To compare their effect on bone in postmenopausal breast cancer patients we measured the urinary output of two bone resorption markers, pyridinoline (Pyr) and deoxypyridinoline (Dpyr) as well as bone density (BMD) in 30 breast cancer patients using either tamoxifen (20 mg/day, n = 15) or toremifene (40 mg/day, n = 15) as adjuvant treatment of stage II breast cancer for 1 year. The urinary output of Pyr and Dpyr were assessed before and after 6 and 12 months of the antiestrogen regimen. Lumbar and femoral BMD were measured by dual energy X-ray absorptiometry (DXA) before and after 12 months of treatment. Both tamoxifen and toremifene were associated with significant decreases in Pyr (mean fall 19.6% and 12.6%, respectively) and Dpyr (mean fall 21.6% and 15.5%, respectively) at 6 months. After 12 months' treatment, Pyr decreased by 30.8% and Dpyr by 21.2% in women using tamoxifen and significantly less in women using toremifene (10.1% and 4.9%, respectively). BMD in the lumbar spine decreased by 1.8% in the toremifene group but increased by 0.4% in the tamoxifen group; in the proximal femur, BMD increased slightly during both tamoxifen and toremifene treatment in all sites measured. Individual changes in Pyr and Dpyr at 6 months showed no significant relation to the change in BMD at 12 months. We conclude that tamoxifen (20 mg/day) and toremifene (40 mg/day) reduce the bone resorption similarly, and this can be detected by falls in urinary output of Pyr and Dpyr at 6 months of treatment. Received: 1 October 1998 / Accepted: 23 April 1999     

Early and Late Postmenopausal Bone Loss is Associated with BsmI Vitamin D Receptor Gene Polymorphism in Japanese Women

To determine whether vitamin D receptor (VDR) gene polymorphisms are associated with bone mineral density (BMD) and bone loss in the Japanese population, VDR BsmI RFLPs were analyzed in 191 postmenopausal Japanese women by comparing B allele and b allele DNA sequences, and a point mutation was confirmed. We examined VDR BsmI restriction fragment length polymorphism (RFLP) with an amplification refractory mutation system (ARMS) using this point of mutation. The frequency of VDR BsmI alleles in the Japanese population was significantly different from that in whites. The bb genotype was identified in 79.6%, of the subjects, the Bb genotype in 19.3%, and the BB genotype was in only 1.1%. We find no significant differences in lumbar spine baseline BMD between the bb genotype and the Bb genotype. In both early and late postmenopausal periods, serial measurements of vertebral BMD revealed that subjects with the Bb genotype lost BMD faster than those with the bb genotype (P= 0.001). We conclude that there is a significant relationship between RFLPs of BsmI VDR and the annual rates of bone loss during early and late postmenopausal periods in the Japanese population. Received: 14 May 1997 / Accepted: 9 July 1998     

The relationship between phalangeal bone density and vertebral deformities

Radiographic absorptiometry (RA) of the phalanges is a convenient and reliable technique for measuring bone mineral density (BMD). It needs only a radiograph of the hand, which can be sent for evaluation to a central facility, whereas other techniques require specialized equipment. We assessed the relationship between RA measurements and the presence of vertebral deformities in a population-based cohort of postmenopausal women, and to compare the results with simultaneously obtained BMD of the hip by dual-energy X-ray absorptiometry (DXA). A total of 389 women aged 55–84 (mean age 67.2 years, SD 8.7) were randomly selected from a large general practice. RA, DXA of the hip, and vertebral deformities in the lateral spine X-rays by vertebral morphometry were assessed. Thirty-eight women (9.8%) had severe (grade II) vertebral deformities, and their BMD at the phalanges and femoral neck was significantly lower than that of women without severe vertebral deformities. Odds ratios for the presence of severe vertebral deformities of 1.5 (95% CI: 1.1–2.1) for RA and 1.3 (95% CI: 0.9–1.9) for DXA, together with similar receiver operating characteristics curves, were found using age-adjusted logistic regression. Phalangeal BMD is related to vertebral deformities at least as closely as BMD of the femoral neck BMD. RA may therefore help to evaluate fracture risk, especially if no DXA equipment is available. Received: 21 July 1998 / Accepted: 1 July 1999     

Osteoporosis and Coronary Atherosclerosis in Asymptomatic Postmenopausal Women

Estrogen deficiency is a risk factor for osteoporosis and coronary artery disease. Osteoporosis can be evaluated by measuring bone mineral density (BMD). Coronary atherosclerotic burden can be evaluated by measuring coronary calcium using electron beam computed tomography (EBT) of the heart. We compared coronary calcium scores in 45 asymptomatic postmenopausal women with normal and low BMD. BMD of the lumbar spine and proximal femur was measured by dual X-ray absorptiometry (DXA), and coronary calcium was measured quantitatively by EBT. Women were divided into control, osteopenia, and osteoporosis groups based on the T score of the lumbar spine. Women were similar in age, years since menopause, height, weight, and body mass index (BMI). BMD ± SD (g/cm²) of L1–L4 was 0.96 ± 0.11, 0.83 ± 0.03, and 0.73 ± 0.05, in control, osteopenia, and osteoporosis group, respectively. The total coronary calcium score ± SD (relative units) was 41.9 ± 83.1, 115.1 ± 181.9, and 221.7 ± 355.4 for control, osteopenia, and osteoporosis group, respectively; the score was significantly higher in the osteoporosis than in the control group. This study provides initial data suggesting that women with osteoporosis may have a higher risk of developing coronary atherosclerosis.