Quantitative ultrasound and bone mineral density are equally strongly associated with risk factors for osteoporosis.

Because resources do not allow all women to be screened for osteoporosis, clinical risk factors are often used to identify those individuals at increased risk of fracture who are then assessed by bone densitometry. The aim of this study was to compare calcaneal quantitative ultrasound (QUS) and axial bone mineral density (BMD) T and Z scores in a large group of women, some with no clinical risk factors and others with one or more risk factors for osteoporosis. The study population consisted of 1115 pre- and postmenopausal women. A subgroup of 530 women was used to construct reference data for calculating T and Z scores. A total of 786 women was found to have one or more of the following risk factors: (i) atraumatic fracture since the age of 25 years, (ii) report of X-ray osteopenia, (iii) predisposing medical condition or use of therapy known to affect bone metabolism, (iv) premature menopause before the age of 45 years or a history of amenorrhea of longer than 6 months duration, (v) family history of osteoporosis, (vi) body mass index (BMI) <20 kg/m2, and (vii) current smoking habit. Calcaneal broadband ultrasound attenuation (BUA) and speed of sound (SOS) measurements were performed on a Hologic Sahara and a DTUone and BMD was measured at the spine and hip using dual-energy X-ray absorptiometry (DXA). The Z score decrements associated with the seven risk factors calculated using multivariate regression analysis were similar for QUS and BMD measurements. Z score decrements (mean of BMD and QUS measurements combined) associated with a history of atraumatic fracture (-0.67), X-ray osteopenia (-0.36), a family history of osteoporosis (-0.23), and a low BMI (-0.53) were all statistically significant compared with women with no risk factors. Z score decrements associated with a medical condition or use of therapy known to affect bone metabolism, a premature menopause or prolonged amenorrhea, or those who were current smokers were not significantly different from zero. As the number of risk factors present in each individual increased, the mean Z score decrements became more negative, increasing from -0.28 for women with one risk factor to -1.19 for those with four or more risk factors. QUS and BMD measurements yielded similar mean Z scores for women with one, two, three, or more than four risk factors. Using the World Health Organization (WHO) criteria to diagnose osteoporosis for BMD measurements and revised diagnostic criteria for QUS, approximately one-third of postmenopausal women aged 50+ years with clinical risk factors were classified as osteoporotic compared with only 12% of women without clinical risk factors. Over two-thirds of postmenopausal women with risk factors were classified as osteopenic or osteoporotic and approximately 28% were classified as normal. The proportion of women classified into each diagnostic category was similar for BMD and QUS. In conclusion, clinical risk factors for osteoporosis affected calcaneal BUA and SOS Z score measurements to the same extent as axial BMD Z score measurements. Provided revised diagnostic criteria are adopted for QUS, similar proportions of postmenopausal women are identified as osteopenic or osteoporotic as with BMD.     

Does scoliosis causes low bone mass? A comparative study between siblings

The aim of this study is to assess the prevalence low bone mass among girls with adolescent idiopathic scoliosis (AIS) and their siblings. The subjects of this study were Saudi Arabian girls with AIS. Patients had their weight and height measured to calculate their body mass index (BMI). Clinical examination and investigations were done to rule out any other cause of scoliosis. All had bone mineral density (BMD) measurement of hip area and the spine using DEXA scan, Hologic Inc. Patients with a BMD of < −2.6 was taken as osteoporotic and those between < −1 and −2.5 was taken as osteopenic for analysis. As control subjects, siblings of the patients with normal spine had their BMI calculated and BMD measurement done. We were able to analyze the data of 32 girls with an average age of 18.42 ± 5.71 (14–26) years with mean BMI of 17.7 ± 0.69 (16.5–18.5) kg/M². Analysis of the scans of the hip revealed that 62.5% of the patients were osteoporotic with BMD of 0.837 (0.697–0.936) ± 0.04, T-score −3.8 ± 0.56 (−2.6 to −3.9) and Z-score. Nine (28.1%) were osteopenic with BMD of 0.768 ± 0.15 (0.638–0.878), mean T-score of −1.6 (−1.1 to 2.5) and Z-score −3.5 ± 0.63 (−2.9 to −3.9). Analysis of BMD of the spine showed similar results. In comparison to the scoliotics, girls with normal spine had higher BMI and BMD which was statistically significant at P < 0.001. T- and Z-score was also lower in scoliotic girls in comparison with girls with normal spine significant at P < 0.001 (CI 95%). Our study indicates that the scoliosis causes osteopenia and osteoporosis among girls while their siblings with normal spine remain with normal bone mass.     

Changes in Bone Mineral Density with Age in Men and Women: A Longitudinal Study

We performed a prospective study to evaluate the normal changes in bone mineral density (BMD) in the forearm, hip, spine and total body, and to study the agreement between changes in BMD estimated from cross-sectional data and the actual longitudinal changes. Six hundred and twenty subjects (398 women, 222 men; age 20–89 years) without diseases or medication known to affect bone metabolism undertook baseline evaluations, and 525 (336 women, 189 men) completed the study. BMD was measured twice 2 years apart by dual-energy X-ray absorptiometry. From cross-sectional evaluations the only premenopausal bone loss (<0.003 g/cm²/year) was found in the hip. In women after menopause and in men an age-related bone loss (0.002–0.006 g/cm²/year) was found at all sites. The data from the longitudinal evaluation showed a small bone loss in women before menopause at the hip and lumbar spine (<0.4%/year (<0.004 g/cm²/year)); this bone loss nearly tripled in the early postmenopausal years (<10 years since menopause), and thereafter decreased to the premenopausal rate for the hip, and to zero for the lumbar spine. The most pronounced bone loss after menopause occurred in the forearm (1.2 %/year (0.006 g/cm²/year)), and it remained constant throughout life. In men there was a small longitudinal bone loss in the hip throughout life, and a small bone loss in the distal forearm after the age of 50 years. In all groups, except for the early postmenopausal women, we found a small increase in total body BMD with age. When comparing the changes in BMD estimated from cross-sectional data with the longitudinal changes, only the hip and forearm generally displayed agreement, whereas the changes in the total body and spine generally were incongruous. In conclusion, the hip and forearm appear to be the sites with the best agreement between the cross-sectional estimated and the longitudinal age-related changes in BMD. Received: 22 August 2000 / Accepted: 22 June 2001     

Risk Factors for the Development of Vertebral and Total Skeleton Osteoporosis in Patients with Primary Biliary Cirrhosis

The objectives of this work was to (1) study the bone mineral density (BMD) of the lumbar spine, total skeleton, and body composition in patients with primary biliary cirrhosis (PBC) and (2) evaluate the risk factors (premature menopause, stages of the disease, hyperbilirubinemia) and bone and liver biochemical parameters for the development of osteoporosis. We studied 23 women with a compatible diagnosis of PBC. The BMD and body composition were evaluated by X-ray absorptiometry (Lunar DPX-L). The average age of the population was 56.7 ± 10.2 years. The BMD of the lumbar spine and of the total skeleton was 1.3 SDs below the normal population matched for sex and age. In the total skeleton, the legs were the most severely affected area (Z score −1.5). The body composition showed no significant difference compared with the normal population. The BMD of 56% of the patients was less than −2.5 SDs from the average normal young values. Patients with a history of vertebral fractures had diminished mineral density of the lumbar spine, as did those who had had no fractures. Of the risk factors studied, patients with premature menopause had a lower bone mass compared with patients with normal menopausal age (Z score of the total skeleton was −2.1 ± 1.8 versus −1.1 ± 1.0) but the difference did not reach statistical significance. The bone mass was not affected in patients with regular menstrual cycles. There were no statistically significant differences in high levels of bilirubin, advanced stages of the disease, or the biochemical variables studied. It is concluded that patients with primary biliary cirrhosis present diminished cortical and trabecular bone mass, whereas body composition was unaffected. Premature hormone deficit, possibly triggered by the chronic hepatic pathology, is a contributing factor to the osteoporosis in this population. Received: 21 October 1997 / Accepted: 5 March 1998     

Classification of osteoporosis in the elderly is dependent on site-specific analysis

Vertebral osteoporosis accounts for over 500,000 spinal fractures annually, the majority of which occur in older women. Despite these statistics, data regarding the rate of spinal bone loss in this population are conflicting. Moreover, the site of skeletal evaluation may significantly alter classification of osteoporosis in this age group. To examine trabecular-rich spinal bone loss with a measurement less affected by age-related artifacts that the AP spine, we measured lateral lumbar spine bone density (BMD) using dual-energy X-ray absorptiometry in 120 healthy, ambulatory, community-dwelling women 65 years of age and older (mean 70±5 years, range 65–88). We also examined cortical-rich sites in the forearm and total body along with AP spine and femoral BMD to assess the impact of site specificity using the World Health Organization (WHO) classification of osteoporosis. Significant losses in BMD were observed at the lateral spine (−1.1%/year,P<0.01), forearm (−0.77%/year,P≤0.01), total hip (−0.75%/year,P≤0.01), femoral neck (−0.70%/year,P≤0.05), and trochanter (−0.78%/year,P≤0.01), but not the AP spine. Using the WHO criteria, lateral spine BMD determinations classified 66% of women with osteoporosis in contrast to 29% using the AP projection. Osteoporosis was diagnosed in 55% of women using measurements of the femoral neck, 43% using the total radius, and 19% using the total body. We conclude that elderly women lose bone at trabecular-and cortical-rich sites (lateral spine and total radius, respectively) in addition to sustaining significant age-related bone loss at mixed cortical/trabecular sites such as the hip. Classification of osteoporosis in this age group more than doubles using lateral versus AP spinal projections, supporting the necessity of developing more uniform agreement on site-specific analyses.     

A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual X-ray absorptiometry in women with a history of fracture at sites other than the spine and hip

The aim of this study was to determine whether calcaneal quantitative ultrasound can discriminate between women with and those without fragility fracture at (1) the wrist or (2) at sites other than the spine, hip, or forearm, as well as axial DXA measurements of BMD can. The study population consisted of 342 postmenopausal Caucasian women who were placed into one of three groups: (1) healthy women with no clinical risk factors for osteoporosis (n = 240); (2) women with a history of atraumatic fracture at the wrist (n = 50); (3) women with a history of atraumatic fracture at a skeletal site other than the spine, hip, or wrist (n = 52). Subjects had DXA measurements of the lumbar spine (LS), femoral neck (FN), and total hip (THIP), and calcaneal broadband ultrasound attenuation (BUA) and speed of sound (SOS) measurements on the Hologic Sahara (s) and Osteometer DTUone (d). Z-scores were calculated using the mean and SD obtained from the healthy postmenopausal group. All the BMD and QUS variables were significantly reduced in women reporting a fracture of the wrist or at a site other than the spine, hip, or forearm. When the group of women with a history of wrist fracture were compared with the postmenopausal controls, age-adjusted logistic regression yielded odds ratios associated with a 1 SD decrease, that were significant for both BMD and QUS, averaging 2.2. The AUC values ranged from 0.65 for FN BMD to 0.75 for BUAd. BMD and QUS measurements were also significantly reduced in women reporting a skeletal fracture at a site other than the spine, hip, or wrist, and odds ratios for BMD and QUS were significant, averaging 1.7. BMD and QUS showed similar fracture discriminatory abilities that were not significantly different from one another. In conclusion, calcaneal QUS can discriminate between women with and those without fracture at the wrist or at sites other than the spine, hip, or forearm as well as axial DXA measurements of BMD can.     

The effect of age and bone mineral density on the absolute, excess, and relative risk of fracture in postmenopausal women aged 50–99: results from the National Osteoporosis Risk Assessment (NORA)

Introduction This study evaluates the effect of age and bone mineral density (BMD) on the absolute, excess, and relative risk for osteoporotic fractures at the hip, wrist, forearm, spine, and rib within 3 years of peripheral BMD testing in postmenopausal women over a wide range of postmenopausal ages. Methods Data were obtained from 170,083 women, aged 50–99 years, enrolled in the National Osteoporosis Risk Assessment (NORA) following recruitment from their primary care physicians’ offices across the United States. Risk factors for fracture and peripheral BMD T-scores at the heel, forearm, or finger were obtained at baseline. Self-reported new fractures at the hip, spine, rib, wrist, and forearm were obtained from questionnaires at 1- and 3-year follow-ups. Absolute, excess (attributable to low BMD), and unadjusted and adjusted relative risks of fracture were calculated. Results At follow-up, 5312 women reported 5676 fractures (868 hip, 2420 wrist/forearm, 1531 rib, and 857 spine). Absolute risk of fracture increased with age for all fracture sites. This age-effect was most evident for hip fracture – both the incidence and the excess risk of hip fracture for women with low BMD increased at least twofold for each decade increase in age. The relative risk for any fracture per 1 SD decrease in BMD was similar across age groups (p>0.07). Women with low BMD (T-score <−1.0) had a similar relative risk for fracture regardless of age. Conclusions At any given BMD, not only the absolute fracture risk but also the excess fracture risk increased with advancing age. Relative risk of fracture for low bone mass was consistent across all age groups from 50 to 99 years. Funding/Support: NORA was funded and managed by Merck & Co., Inc. These data were presented in part as a poster at the annual meeting of the American Society of Bone and Mineral Research; October 1, 2004.     

Bone diminution of osteoporotic females at different skeletal sites

Summary The bone mineral density (BMD) of the radius and spine was determined by photo absorptiometry in a large number of controls (radius: n=111; spine: n=85; age range: 50–79 years) and osteoporotic women (radius: n=98; spine n=140; age range: 50–79 years) with at least one “atraumatic” vertebral compression fracture. Compared to age-matched controls, the BMD of the osteoporotic women showed the following diminutions: sixth decade: radius:−9.1%; spine:−25%; femur: −33%; seventh decade: radius:−16%; spine: −19%; femur:−23%; eighth decade: radius: −21%; spine:−20%; femur:−24%. The BMD was significantly diminished at all sites in all decades but in contrast to the radius, the difference from controls was bigger in the spine and femur in the sixth decade than in the seventh and eighth decade. In the osteoporotic women there was a significant correlation between radius BMD and age (4=−0.56;P<0.01) but not between spine or femoral BMD and age. The femoral neck BMD was also determined in a subset group of female controls (n=68), patients with crush fractures of the spine without a fracture of the hip (n=46), and in patients with fractures of the proximal femur (n=21). There was no difference among these groups in mean age (64±7, range: 50–79 years). Patients with hip fracture and spine fracture showed bone diminution in all three regions that was significantly below controls (P<0.001). The Ward's triangle region was specially diminished (−35%) and as a consequence the neck BMD was low (−26%). Trochanteric density was lower (−25%) in spine fracture cases than in hip fracture (−16%). The difference between the two groups of osteoporotic women was significant (P<0.05). In the hip fractures cases, spine BMD was reduced only moderately compared to controls (−14%,P<0.01) and slightly elevated compared to spinal osteoporosis where the diminution was greater (−24%,P<0.001). Again, the difference between the two osteoporotic groups was significant (P<0.05). It appeared that spinal osteoporosis involved loss of bone from both the spine and hip, whereas femoral osteoporosis showed a preferential loss of bone from the femur neck region, and a lesser loss from the trochanter or the spine.     

Physical training preserves bone mineral density in postmenopausal women with forearm fractures and low bone mineral density

Summary One hundred and twelve postmenopausal women with low bone mineral density (BMD) and forearm fractures were randomized to physical training or control group. After one year the total hip BMD was significantly higher in the women in the physical training group. The results indicate a positive effect of physical training on BMD in postmenopausal women with low BMD. Introduction The fivefold increase in hip fracture incidence since 1950 in Sweden may partially be due to an increasingly sedentary lifestyle. Our hypothesis was that physical training can prevent bone loss in postmenopausal women. Methods One hundred and twelve postmenopausal women 45 to 65 years with forearm fractures and T-scores from −1.0 to −3.0 were randomized to either a physical training or control group. Training included three fast 30-minute walks and two sessions of one-hour training per week. Bone mineral density (BMD) was measured in the hip and the lumbar spine at baseline and after one year. Results A per protocol analysis was performed, including 48 subjects in the training group and 44 subjects in the control group. The total hip BMD increased in the training group +0.005 g/cm2 (±0.018), +0.58%, while it decreased −0.003 g/cm2 (±0.019), −0.36%, (p = 0.041) in the control group. No significant effects of physical training were seen in the lumbar spine. A sensitivity intention to treat analysis, including all randomized subjects, showed no significant effect of physical training on BMD at any site. Conclusions The results indicate a small but positive effect of physical exercise on hip BMD in postmenopausal women with low BMD.     

Bone mineral density and its correlation with clinical and laboratory factors in chronic peritoneal dialysis patients

The aim of this study was to assess the clinical and laboratory correlations of bone mineral density (BMD) measurements among a large population of patients on chronic peritoneal dialysis (PD). This cross-sectional, multicenter study was carried out in 292 PD patients with a mean age of 56 ± 16 years and mean duration of PD 3.1 ± 2.1 years. Altogether, 129 female and 163 male patients from 24 centers in Canada, Greece, and Turkey were included in the study. BMD findings, obtained by dual-energy X-ray absorptiometry (DEXA) and some other major clinical and laboratory indices of bone mineral deposition as well as uremic osteodystrophy were investigated. In the 292 patients included in the study, the mean lumbar spine T-score was −1.04 ± 1.68, the lumbar spine Z-score was −0.31 ± 1.68, the femoral neck T-score was −1.38 ± 1.39, and the femoral neck Z score was −0.66 ± 1.23. According to the WHO criteria based on lumbar spine T-scores, 19.2% of 292 patients were osteoporotic, 36.3% had osteopenia, and 44.4% had lumbar spine T-scores within the normal range. In the femoral neck area, the prevalence of osteoporosis was slightly higher (26%). The prevalence of osteoporosis was 23.3% in female patients and 16.6% in male patients with no statistically significant difference between the sexes. Agreements of lumbar spine and femoral neck T-scores for the diagnosis of osteoporosis were 66.7% and 27.3% and 83.3% for osteopenia and normal BMD values, respectively. Among the clinical and laboratory parameters we investigated in this study, the body mass index (BMI) (P < 0.001), daily urine output, and urea clearance time × dialysis time/volume (Kt/V) (P < 0.05) were statistically significantly positive and Ca × PO₄ had a negative correlation (P < 0.05) with the lumbar spine T scores. Femoral neck T scores were also positively correlated with BMI, daily urine output, and KT/V; and they were negatively correlated with age. Intact parathyroid hormone levels did not correlate with any of the BMD parameters. Femoral neck Z scores were correlated with BMI (P < 0.001), and ionized calcium (P < 0.05) positively and negatively with age, total alkaline phosphatase (P < 0.05), and Ca × P (P < 0.01). The overall prevalence of fractures since the initiation of PD was 10%. Our results indicated that, considering their DEXA-based BMD values, 55% of chronic PD patients have subnormal bone mass—19% within the osteoporotic range and 36% within the osteopenic range. Our findings also indicate that low body weight is the most important risk factor for osteoporosis in chronic PD patients. An insufficient dialysis dose (expressed as KT/V) and older age may also be important risk factors for osteoporosis of PD patients.     

Validation and comparative evaluation of four osteoporosis risk indexes in Moroccan menopausal women

Introduction Measuring bone mineral density (BMD) is a widely accepted strategy for identifying subjects with an increased risk of fracture. However, because of limited availability of BMD technology in some communities and cost considerations, it has been proposed that BMD measurements be targeted to subjects with risk factors for osteoporosis. Recently, many risk assessment indices have been developed to identify women who are more likely to have low BMD and thus undergo BMD testing. The objective of this study was to compare the performance of four risk indices for osteoporosis in white women in Morocco. Methods We analysed in an epidemiological cross-sectional study the records for 986 postmenopausal white Moroccan women seen at an out-patient rheumatology centre. Four osteoporosis risk index scores were compared to bone density T-scores. The ability of each risk index to identify women with low BMD (T-score<−2.0) or osteoporosis (T<−2.5) was evaluated. Results Using an Osteoporosis Self-Assessment Tool (OST) score<2 to recommend DXA referral, we found that sensitivity ranged from 61% at the lumbar spine to 85% at the total hip to detect BMD T-scores of −2.5, and specificity ranged from 62% at the lumbar spine to 67% at the total hip. The negative predictive value was high at all skeletal sites (79–98%), demonstrating the usefulness of the OST to identify patients who have normal BMD and should not receive DXA testing. All risk indices performed similarly and showed better results in identifying women with osteoporosis or low BMD based on hip measurement. Conclusions This is the first study that validated several risk osteoporosis indexes in Moroccan women. The performance of these risk indices among women in Morocco was similar to that reported earlier for other samples in Asian countries, the US, and Belgium. The OST and other risk indices are effective and efficient tools to help target high-risk women for DXA measurement.     

Reproductive, Menstrual and Menopausal Factors: Which Are Associated with Bone Mineral Density in Early Postmenopausal Women?

The associations between a number of reproductive and menopausal factors and bone mineral density (BMD) were studied in a sample of early postmenopausal women. The study included 580 women aged 45–61 years who completed a risk factor questionnaire containing sections on obstetric and menstrual history. BMD measurements were taken at the anteroposterior (AP) spine, greater trochanter, femoral neck, total radius and whole body, along with whole body bone mineral content (BMC). In analyses adjusting for key confounders, number of pregnancies was more strongly associated with increased BMD than number of live births at all sites (p<0.05 at femoral neck and total radius), and menstrual years was more strongly associated with increased BMD than years since menopause (p<0.05 at all sites). Hysterectomized women had a significantly higher adjusted mean BMD than non-hysterectomized women at all sites (AP spine: 0.999 g/cm² vs 0.941 g/cm², p<0.001), although there were no significant differences in BMD between hysterectomized women who had a bilateral oophorectomy and those whose ovaries were preserved. Negative associations between the duration of hot flushes and BMD were statistically significant (p<0.05) at the three non-hip sites. In multiple regression analyses containing all reproductive terms, duration of hormone replacement therapy (HRT) use, menstrual years and hysterectomy status were significantly associated with BMD at all five sites, whilst oral contraceptive use before the age of 23 years was significantly associated with increased BMD at all sites except the total radius. Breastfeeding duration, the duration of oral contraceptive use and premenopausal amenorrhea were found to have no association with BMD. Results for whole body BMC were consistent with those for the five BMD sites, across all the variables considered here. These findings confirm the importance of HRT use and duration of menses as predictors of BMD, whilst the results for hysterectomy status and early oral contraceptive use require further consideration. Received: 26 July 2000 / Accepted: 5 April 2001     

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

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

Association of upper arm circumference at muscle flexion with lumbar spine bone mineral density

We investigated the association of upper arm circumference at muscle flexion with lumbar spine (L2–L4) bone mineral density (BMD) in 252 postmenopausal Japanese women (mean age, 62.0 ± 7.6 years; range, 43–78 years) with right-side dominance. Age, age at menopause, years since menopause (YSM), weight, and height were recorded. Dominant upper arm circumference (cm) was measured at muscle flexion. Lumbar spine BMD was measured by dual-energy X-ray absorptiometry (DXA). Correlations between BMD and variables were determined using Pearson's correlation coefficient. Significant predictors of the lumbar spine BMD were determined using stepwise multiple regression analysis. Upper arm circumference, weight, and height were positively correlated with BMD (r = 0.397, 0.343, and 0.323, respectively), whereas YSM and age were inversely correlated with BMD (r = −0.415 and −0.392, respectively). On stepwise multiple regression analysis, YSM, upper arm circumference, and weight were significant predictors of BMD (R ² = 0.322, P < 0.0001). Predicted value of the lumbar spine BMD was calculated by the following formula: Predicted BMD = 0.249 − 0.0078 (YSM) + 0.016 (upper arm circumference) + 0.0046 (weight). Dominant upper arm circumference at muscle flexion in combination with YSM and weight is a useful predictor of lumbar spine BMD. Received: July 21, 1998 / Accepted: April 1, 1999     

Estrogen receptor α CA dinucleotide repeat polymorphism is associated with rate of bone loss in perimenopausal women and bone mineral density and risk of osteoporotic fractures in postmenopausal women

Summary The association between a newly identified CA repeat polymorphism of the estrogen receptor alpha gene (ESR1) with osteoporosis was investigated. Postmenopausal women with <18 CA repeats had low BMD, increased rate of bone loss and increased fracture risk. Introduction Studies have shown that intronic dinucleotide repeat polymorphisms in some genes are associated with disease risk by modulating mRNA splicing efficiency. D6S440 is a newly identified intronic CA repeat polymorphism located downstream of the 5’-splicing site of exon 5 of ESR1. Methods The associations of D6S440 with bone mineral density (BMD), rate of bone loss and fracture risk were evaluated in 452 pre-, 110 peri- and 622 postmenopausal southern Chinese women using regression models. Results Post- but not premenopausal women with less CA repeats had lower spine and hip BMD. The number of CA repeats was linearly related to hip BMD in postmenopausal women (β = 0.008; p = 0.004). Postmenopausal women with CA repeats <18 had higher risks of having osteoporosis (BMD T-score<−2.5 at the spine: OR 2.46, 95% CI 1.30–4.65; at the hip: OR 3.79(1.64–8.74)) and low trauma fractures (OR 2.31(1.29–4.14)) than those with ≥18 repeats. Perimenopausal women with <18 CA repeats had significantly greater bone loss in 18 months at the hip than those with ≥18 repeats (−1.96% vs. −1.61%, p = 0.029). Conclusions ESR1 CA repeat polymorphism is associated with BMD variation, rate of bone loss and fracture risk, and this may be a useful genetic marker for fracture risk assessment. Funding Source: This project is supported by CRCG Grant, Bone Health Fund, Matching Grant and Osteoporosis and Endocrine Research Fund of the University of Hong Kong.     

Early postmenopausal diminution of forearm and spinal bone mineral density: A cross-sectional study

Diminution of bone mineral density (BMD) in the spine and forearm was studied cross-sectionally in 363 women who were 6 months to 10 years postmenopausal. BMD was determined by dual-energy X-ray absorptiometry (DXA) (Hologic QDR-2000) in the lumbar spine, in both the supine lateral (LAT) and anteroposterior (AP) projections, and in the distal third of the forearm. The postmenopausal diminution of BMD was best described by an exponential fit. The initial rate of postmenopausal diminution of BMD was highest in the most trabecular sites (LAT>AP> forearm), but 10-year diminution was similar at all sites (12%–13%, corresponding to about 1.0–1.5 SD), and extrapolation suggested reverse order of the rates of diminution thereafter (forearm>AP>LAT). When bone mineral content of the entire L3 vertebra (tBMC) was measured in vivo, AP tBMC could account for only 67% of the variation in LAT tBMC, compared withr ²=0.997 in vitro. This observation suggests an accuracy problem in vivo in one of the spine measurement methods. We conclude that the initial rate of BMD diminution after the menopause seems to be highest in the spine, especially when measured laterally, but that this rate levels off within the first decade. The lower precision error of a forearm measurement (0.8% v 1.6 for AP and 3.1 for LAT) therefore implies that this method may require a shorter observation period than spine measurements for the detection of bone loss 5–10 years after menopause. Long-term longitudinal spine and forearm measurements are, however, needed to confirm these conclusions.     

Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes—a meta-analysis

Introduction and hypothesis Diabetes affects bone metabolism. The hypothesis was that type 1 (T1D) and type 2 (T2D) affects BMD and fracture risk differently. Material and methods Pubmed, Embase, and Web of Science were searched using the terms “diabetes”, “fracture”, and “bone mineral”. Results Hip fracture risk was increased in T1D (RR = 6.94, 95% CI: 3.25–14.78, five studies) and T2D (1.38, 95% CI: 1.25–1.53, eight studies) compared to subjects without diabetes. The increase in relative hip fracture risk was significantly higher in T1D than in T2D. BMD Z-score was decreased in the spine (mean ± SEM −0.22 ± 0.01) and hip (−0.37 ± 0.16) in T1D and increased in the spine (0.41 ± 0.01) and hip (0.27 ± 0.01) in T2D. A meta-regression showed that body mass index (BMI) was a major determinant for BMD in both the spine and hip. Glycated haemoglobin (HbA1C) was not linked to BMD. The increase in fracture risk was higher and BMD lower in patients with complications to diabetes. Conclusions Hip fracture risk is increased in both T1D and T2D, whereas BMD is increased in T2D and decreased in T1D. A common factor such as complications may explain the increase in fracture risk, whereas BMI may ameliorate the increase in fracture risk in T2D.     

Nitrate use and changes in bone mineral density: the Canadian Multicentre Osteoporosis Study

Summary  Nitrates may have beneficial effects on bone. To determine if nitrates were associated with increased bone mineral density (BMD), we conducted a secondary analysis using data from subjects in a prospective study. Subjects reporting nitrate use had increased BMD compared with non-users, confirming that nitrates have positive BMD effects in women and men. Introduction  Prior studies suggest positive associations between nitrates and bone. Methods  We used linear regression models, stratified by gender and adjusted for age, weight, and baseline differences, to determine the association between daily nitrate use and BMD among subjects participating in the Canadian Multicentre Osteoporosis Study. All results are reported as annualised percent change in BMD at the hip and spine among nitrate users compared to non-users. Results  We included 1,419 men (71 reported daily nitrate use) and 2,587 women (97 reported daily nitrate use). Male non-users had decreased hip BMD (−1.3%; 95% confidence interval [95%CI] = −1.6 to −1.1) and increased spine BMD (2.8%; 95%CI = 2.5 to 3.1). Male nitrate users had increased hip BMD (1.4%; 95%CI = 0.1 to 2.8) and spine BMD (4.5%; 95%CI = 3.2 to 5.7). Among women, non-users had decreased hip BMD (−1.9; 95%CI = −2.1 to −1.7) and increased spine BMD (2.1%; 95%CI = 1.9 to 2.4) whilst users had an increase in hip BMD (2.0%; 95%CI = 1.2 to 2.8) and spine BMD (4.1%; 95%CI = 3.4 to 4.9). Conclusion  Nitrate use is associated with increased BMD at the hip and spine in men and women.     

Menstrual cycle lengths and bone mineral density: a cross-sectional, population-based study in rural Chinese women ages 30–49 years

Introduction The menstrual cycle involves periodic fluctuations in estrogen and progesterone levels. Longer cycles have been associated with longer follicular phase, delayed estrogen peak and a lower mean oestradiol level of the entire cycle. Methods We hypothesized that prolonged menstrual cycle length is associated with decreased bone mineral density (BMD) in a population of pre- and perimenopausal women. This population-based cross-sectional study was conducted in rural Anhui province, China. It includes 4,771 women, aged 30 to 49 years, who did not smoke or drink alcohol, and did not use oral contraceptives or breastfeed during the previous year. Dual-energy X-ray absorptionometry (DEXA) BMD measurements were taken at four skeletal sites: whole body, total hip, femoral neck and lumbar spine. Menstrual cycle characteristics (polymenorrhea, short normal, long normal, oligomenorrhea, 90-day amenorrhea, irregular cycle) in the prior year were assessed by questionnaire. Results Prolonged menstrual cycle was consistently associated with decreased BMD at whole body, total hip, and femoral neck in both age 30–39, and age 40–49 stratum (p_trend<0.05). Prolonged menstrual cycle was also associated with decreased lumbar spine BMD for women aged 40–49 (p_trend<0.05). Among women with normal cycles aged 30–39, menstrual cycle length in the previous year was inversely associated with whole-body BMD (p<0.05). Women with 90-day amenorrhea had significantly lower mean total hip and femoral neck BMD relative to women with short normal cycles in the 30–39 age group; and had significantly lower whole body and total hip BMD relative to short normal cycles in the 40–49 age group. BMD in poylmenorrheic women did not differ from BMD in women with short normal cycles at any of the skeletal sites. Conclusions We conclude that prolonged menstrual cycle length is associated with decreased BMD in pre- and perimenopausal women in this population.     

Bone Mineral Density and Vertebral Fractures in Men

In women, many studies indicate that the risk of vertebral fragility fractures increases as bone mineral density (BMD) declines. In contrast, few studies are available for BMD and vertebral fractures in men. It is uncertain that the strength of the relationship between BMD and fractures is similar in magnitude in middle-aged men and in postmenopausal women. In the present study, 200 men (mean age 54.7 years) with lumbar osteopenia (T-score <−1.5) were recruited to examine the relationships between spine BMD and hip BMD and the associations of BMD with vertebral fractures. Lumbar BMD was assessed from L2 to L4, in the anteroposterior view, using dual-energy X-ray densitometry. At the upper left femur, hip BMD was measured at five regions of interest: femoral neck, trochanter, intertrochanter, Ward’s triangle and total hip. Spinal radiographs were analyzed independently by two trained investigators and vertebral fracture was defined as a reduction of at least 20% in the anterior, middle or posterior vertebral height. Spinal radiographs evidenced at least one vertebral crush fracture in 119 patients (59.5%). The results of logistic regression showed that age, femoral and spine BMDs were significant predictors of the presence of a vertebral fracture. Odds ratios for a decrease of 1 standard deviation ranged from 1.8 (1.3–2.8) for spine BMD to 2.3 (1.5–3.6) for total hip BMD. For multiple fractures odds ratios ranged from 1.7 (1.1–2.5) for spine BMD to 2.6 (1.7–4.3) for total hip BMD. In all models, odds ratios were higher for hip BMD than for spine BMD, particularly in younger men, under 50 years. A T-score <−2.5 in the femur (total femoral site) was associated with a 2.7-fold increase in the risk of vertebral fracture while a T-score <−2.5 in the spine was associated with only a 2-fold increase in risk. This study confirms the strong association of age and BMD with vertebral fractures in middle-aged men, shows that the femoral area is the best site of BMD measurement and suggests that a low femoral BMD could be considered as an index of severity in young men with lumbar osteopenia. Received: 27 October 1998 / Accepted: 22 February 1999