Do Both Areal BMD and Injurious Falls Explain the Higher Incidence of Fractures in Women than in Men?

The higher incidence of fractures in women than in men is generally attributed to the lower areal bone mineral density (areal BMD, g/cm²) of the former. The purpose of the present study was to investigate both areal BMD and injurious falls as risk factors for fractures. In a first cohort, areal BMD was measured in 5,131 men and women (age range 40–95 years). In a second cohort, consisting of 26,565 men and women (age range 40–69 years), a health survey was conducted including questions about lifestyle and medication. Main outcome measures included validated prospective injurious falls and fractures in both cohorts. The higher areal BMD and femoral neck BMD in men compared to women (P < 0.001) were explained by a higher diameter of the femoral neck. Importantly, the diameter of the femoral neck was not associated with fractures in either sex (hazard ratio [HR] 0.94–1.04, P > 0.05 for all), suggesting that a higher areal BMD and lower incidence of osteoporosis in men do not explain their lower incidence of fractures. In contrast, women were more prone to sustain injurious falls than men in both cohorts investigated (HR for women = 1.61 and 1.84, P < 0.001 for both), resulting in a higher incidence of fractures (HR for women = 2.24 and 2.36, P < 0.001 for both). The number of injurious falls and fractures occurring each month during the study period showed a very strong correlation in both women (r = 0.95, P < 0.00001) and men (r = 0.97, P < 0.00001). In summary, low areal BMD, and thus osteoporosis, may not explain the higher fracture incidence in women than in men. Instead, a higher incidence of injurious falls in women was strongly associated with the higher fracture risk.     

Forearm bone mineral density in patients with rheumatoid arthritis

 The aims of the present study were to determine whether patients with rheumatoid arthritis (RA) show significantly lower forearm bone mineral density (BMD) than sex- and age-matched healthy controls, and to identify significant factors that are associated with their BMD loss. One hundred eighty-four patients with RA and 185 sex- and age-matched healthy controls were enrolled in the study: 71 men 37–68 years of age (RA, 31; controls, 40), 129 premenopausal women 30–48 years of age (RA, 67; controls, 62), and 169 postmenopausal women 48–69 years of age (RA, 86; controls, 83). The correlation of forearm BMD, measured by dual energy X-ray absorptiometry with anatomic grade in the wrist, functional class, duration of disease, steroid use, modified health assessment questionnaire (HAQ) score for the upper and lower extremities, levels of serum C-reactive protein and rheumatoid factor, erythrocyte sedimentation rate, and years since menopause (YSM) were examined by multiple regression analysis. In men with RA, no clinical factors were significantly correlated with forearm BMD, and the BMD did not differ significantly from that in controls (0.329 ± 0.060 [mean ± SD] vs. 0.351 ± 0.069 g/cm²). In premenopausal women with RA, the HAQ score for the upper extremities was positively correlated with forearm BMD (P < 0.05), but the BMD did not differ significantly from that in controls (0.298 ± 0.085 vs. 0.324 ± 0.088 g/cm²); in postmenopausal women with RA, YSM and anatomic grade in the wrist were negatively correlated with forearm BMD (P < 0.01 and P < 0.05), and the BMD was significantly lower than in controls (0.192 ± 0.063 vs. 0.223 ± 0.076 g/cm², P < 0.01). These findings suggest that forearm BMD loss in patients with RA may be accelerated in women after menopause, and that YSM and disuse of the wrist may be significant determinants of their forearm BMD loss. Received: February 18, 2002/ Accepted: May 23, 2002     

Bone mineral density and prevalent vertebral fractures in men and women

To test the hypothesis that the association between bone mineral density (BMD) and estimated volumetric BMD and prevalent vertebral fractures differs in men and women, we studied 317 Caucasian men and 2,067 Caucasian women (average age 73 years). A total of 43 (14%) men and 386 (19%) women had a vertebral fracture identified on lateral spine radiographs using vertebral morphometry. Hip and spine areal BMD was about 1/3 standard deviation lower among men and women with a vertebral fracture. A 0.10 g/cm² decrease in areal BMD was associated with 30–40% increased odds of having a fracture in men and 60–70% increased likelihood in women. Low bone mineral apparent density (BMAD) was also associated with 40–50% increased odds of a vertebral fracture in both genders. The probability of a man having a fracture was observed at higher absolute areal BMD values than observed for women (P=values for interaction of BMD × gender: trochanter, P=0.05; femoral neck, P=0.10; total hip, P=0.09). In contrast, the probability of fracture was similar in men and women across the range of estimated volumetric BMD (BMAD). In conclusion, low BMD and low BMAD are associated with increased odds of vertebral fracture in both men and women. Measures of bone mass that partially correct for gender differences in bone size may yield universal estimates of fracture risk. Prospective studies are needed to confirm this observation.     

Volumetric and Areal Bone Mineral Density Measures Are Associated with Cardiovascular Disease in Older Men and Women: The Health, Aging, and Body Composition Study

The associations of volumetric (vBMD) and areal (aBMD) bone mineral density measures with prevalent cardiovascular disease (CVD) and subclinical peripheral arterial disease (PAD) were investigated in a cohort of older men and women enrolled in the Health, Aging, and Body Composition Study. Participants were 3,075 well-functioning white and black men and women (42% black, 51% women), aged 68–80 years. Total hip, femoral neck, and trochanter aBMD were measured using dual-energy X-ray absorptiometry. Quantitative computed tomography was used to evaluate spine trabecular, integral, and cortical vBMD measures in a subgroup (n = 1,489). Logistic regression was performed to examine associations of BMD measures with CVD and PAD. The prevalence of CVD (defined by coronary heart disease, PAD, cerebrovascular disease, or congestive heart failure) was 29.8%. Among participants without CVD, 10% had subclinical PAD (defined as ankle-arm index <0.9). Spine vBMD measures were inversely associated with CVD in men (odds ratio of integral [OR_integral] = 1.34, 95% confidence interval [CI] 1.10–1.63; OR_trabecular = 1.25, 95% CI 1.02–1.53; OR_cortical = 1.36, 95% CI 1.11–1.65). In women, for each standard deviation decrease in integral vBMD, cortical vBMD, or trochanter aBMD, the odds of CVD were significantly increased by 28%, 27%, and 22%, respectively. Total hip aBMD was associated with subclinical PAD in men (OR = 1.39, 95% CI 1.03–1.84) but not in women. All associations were independent of age and shared risk factors between BMD and CVD and were not influenced by inflammatory cytokines (interleukin-6 and tumor necrosis factors-α). In conclusion, our results provide further evidence for an inverse association between BMD and CVD in men and women. Future research should investigate common pathophysiological links for osteoporosis and CVD.     

Bone Mineral Density,Carotid Artery Intimal Medial Thickness,and the Vitamin D Receptor <Emphasis Type="Italic">Bsm</Emphasis>I Polymorphism in Mexican American Women

Low bone mineral density (BMD) is a predictor of cardiovascular mortality, suggesting that osteoporosis and cardiovascular disease may share common risk factors. We assessed the relationship between BMD and intimal medial thickening (IMT) of the common carotid artery, a marker of sub-clinical atherosclerosis, in 471 women examined as part of the San Antonio Family Osteoporosis Study, a population-based study of osteoporosis risk conducted in Mexican American families. Because of the documented role of vitamin D metabolism in bone metabolism and its possible role in cardiovascular function, we further evaluated whether allelic variation at the vitamin D receptor locus (VDR) influenced joint variation in BMD and IMT. The association of BMD with IMT depended on age, with low BMD being correlated with high IMT in older women, but with low IMT in younger women [age by IMT interaction effects significant at the spine (P = 0.042), radius ultradistal (P = 0.010), and hip (P = 0.006)]. In all women, the VDR BsmI BB genotype was associated with significantly higher forearm BMD (P = 0.005 for both radius ultradistal and midpoint), higher IMT (P = 0.05), and higher spine BMD in older women (P = 0.06), but not with hip BMD. The association of the VDR genotype with IMT was independent of its association with BMD. Although a functional consequence of the BsmI polymorphism on vitamin D metabolism has not been established, these findings support a possible biological relationship among VDR, bone metabolism, and atherosclerosis. We conclude that VDR polymorphisms may be one of multiple factors influencing the joint risk of atherosclerosis and osteoporosis.     

The association of bone mineral density measures with incident cardiovascular disease in older adults

Summary The associations of volumetric and areal bone mineral density (BMD) measures with incident cardiovascular disease (CVD) were studied in a biracial cohort of 2,310 older adults. BMD measures were inversely related to CVD in women and white men, independent of age and shared risk factors for osteoporosis and CVD. Introduction We investigated the associations of volumetric (vBMD) and areal (aBMD) bone mineral density measures with incident cardiovascular disease (CVD) in older adults enrolled in the Health, Aging, and Body Composition study. Methods The incidence of CVD was ascertained in 2,310 well-functioning white and black participants (42% black; 55% women), aged 68–80 years. aBMD measures of the hip were assessed using DXA. Spine trabecular, integral, and cortical vBMD measures were obtained using QCT. Results During an average follow-up of 5.4 years, 23% of men and 14% of women had incident CVD. Spine vBMD measures were inversely associated with incident CVD in white men [HR(integral)=1.39, 95% CI 1.03–1.87; HR(cortical)=1.38, 95% CI 1.03–1.84], but not in black men. In women, aBMD measures of the total hip (HR = 1.36, 95% CI 1.03–1.78), femoral neck (HR = 1.44, 95% CI 1.10–1.90), and trochanter (HR = 1.34, 95% CI 1.04–1.72) exhibited significant associations with CVD in blacks, but not in whites. All associations were independent of age and shared risk factors between osteoporosis and CVD, and were not explained by inflammatory cytokines or oxidized LDL. Conclusion Our results provide support for an inverse association between BMD and incident CVD. Further research should elucidate possible pathophysiological mechanisms linking osteoporosis and CVD.     

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

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

Forearm bone mineral density in an unselected population of 2,779 men and women—The HUNT Study, Norway

The fracture incidence in Norway is among the highest in Europe, presumably due to osteoporosis. As part of a multipurpose health study in the county of Nord-Trøndelag, Norway (the HUNT study), a 5% randomly selected sample (n=4,646) of the population >19 years of age was invited to undergo single X-ray absorptiometry (SXA) of the forearm. A total of 1,274 men (50.5 years) and 1,505 women (49.9 years) participated (60%). The aim of the study was to describe the variation in bone mineral density (BMD) and the prevalence of forearm BMD 2.5 standard deviations (SD) below the mean value for young adults in an unselected population sample. In women the BMD remained stable until the age of 50 years, whereupon a strong decline in BMD was observed. In men, a BMD increase was observed until about the age of 40 years; the decline after the age of 65 was, however, similar to that in women. Based on age and gender-specific reference values, the age-adjusted prevalence of T-scores <–2.5 SD in women and men aged 50–69 years was 16.0% and 5.6%, respectively. In the age group of 70 years or older the prevalence was 65.8% and 30.6% for women and men, respectively. The accelerated BMD reduction in women aged 50–65 explains the higher prevalence of T-score <–2.5 SD in elderly women than in men. Further studies on bone loss and falls are required to explain the high fracture incidence in Norway.     

Influence of age and gender on associations of body mass index with bone mineral density, bone turnover markers and circulating calcium-regulating and bone-active sex hormones

Although it is well known that body mass index (BMI) and bone mineral density (BMD) are positively correlated, the mechanisms by which adiposity reduces the risk of osteoporotic fractures are not fully understood. The present study was initiated to gain deeper insight into the mechanisms underlying the osteoprotective effect of adiposity, and to assess particularly the relevance that BMI-associated changes in circulating hormone levels could have for the build-up of additional bone mineral density. Using data from a previous study on a large cohort of healthy adult Austrians, we analyzed correlations of BMI with (i) BMD at sites in the lumbar spine and hip region, (ii) bone resorption and formation markers, (iii) circulating levels of vitamin D, parathyroid hormone, testosterone and estrogen, and (iv) rates of daily vitamin D and calcium intake. After adjustment for age, positive correlations between BMI and BMD were highly significant (P < 0.0001) at all skeletal sites across the entire study cohort. Associations were stronger in post-menopausal women than in pre-menopausal women and in men. In absolute values, the gain in BMD at the lumbar spine from an incremental rise of BMI in post-menopausal women was 1.5-fold higher than in pre-menopausal women, and three times of that observed in men (P < 0.05). Inverse relations between BMI and β-crosslaps were consistently found in men (P < 0.01) and in women before and after menopause (P < 0.01 and P < 0.05, respectively), suggesting that inhibition of osteoclastic bone resorption is responsible at least in part for the positive effect of high BMI on BMD. Sub-group analysis revealed that increasing BMI was associated with a significant fall of testosterone in men (P < 0.05), and of 25-(OH)D in pre- and post-menopausal women (P < 0.001 and P < 0.05, respectively), but with a significant rise in PTH (P < 0.01) in women before menopause. Since all these hormonal changes would cause bone loss, this excludes their playing any role in the osteoprotective effect of adiposity.     

Bone Mineral Density Is a Predictor of Survival

The purpose of this study was to examine the relationship between bone mineral density (BMD) and survival in both sexes and to compare BMD with other established risk factors such as blood pressure and cholesterol. A population-based prospective study of 1924 individuals (850 men, 1074 women) was performed in G?teborg from 1980 to 1983. Measurements of BMD were obtained in 1468 (76%) of the participants (653 men, 815 women). This selection of individuals generated 10,965 person years, and death was registered for 289 men and 197 women in the 7-year period (2661 days) after bone mineral measurement. Later information on date of death was obtained from the official population register. This information covers 7 years from the time of survey of the last examined participant (in Dec. 1983). At the beginning of the study, BMD was measured in the calcaneus by dual photon absorptiometry (DPA), and blood pressure, serum cholesterol, serum triglycerides, and body mass index (BMI) were also recorded. The study was coordinated with the National Register of Causes of Death and the National Cancer Register. A modified version of the Cox proportional hazards model was used to calculate and determine the age-adjusted relations between nontrauma mortality and BMD. When the various quartiles of BMD were compared prospectively from 70, 75, and 79 years of age with survival figures during the 2661-day follow-up period, the first and the second quartiles with the lowest BMD at entry showed the lowest survival rate in both men (P= 0.01) and women (P= 0.01). A decrease of 1 SD of BMD in a univariate analysis was associated with a 1.39-fold increase in mortality in both men (95% confidence interval 1.25–1.56, P < 0.001) and women (95% confidence interval 1.22–1.58, P < 0.001), and a multivariate analysis demonstrated a relative risk of 1.23 (95% confidence interval 1.10–1.41, P < 0.001) in men and 1.19 (95% confidence interval 1.02 to 1.39, P= 0.019) in women. All relations were adjusted for sex, age, and follow-up. This study indicates that BMD is a predictor of survival, especially for subjects over 70. Bone mineral density was found to be a better predictor of death than blood pressure and cholesterol. This study indicates that, after adjustments have been made for diseases, low bone mass is an independent predictor of mortality and might be a marker of general health or functional aging. Its measurement might therefore be a valuable tool in general health investigations. Received: 26 December 1996 / Accepted: 27 January 1998     

Body Size Accounts for Most Differences in Bone Density Between Asian and Caucasian Women

We compared bone mineral density (BMD) of the whole body (and subregions: arm, leg, and pelvis), hip, spine, lateral spine, wrist, and forearm among Caucasian and Asian women at four geographic centers (Honolulu, HI; Nottingham, UK; Portland, OR; Copenhagen, Denmark). Data were derived from the baseline examination of 1367 Caucasian and 162 Asian women enrolled in the 1609-subject Early Postmenopausal Interventional Cohort (EPIC) study. After adjusting for age, study site, years postmenopause, and years of estrogen use, BMD was approximately 4–6% lower (P < 0.05) among Asian women at most skeletal sites, but there was no significant difference for wrist or forearm BMD. Adding height, lean body mass, fat mass, and/or quadriceps muscle strength to the regression models reduced the racial differences at most skeletal sites; after these additional adjustments, Asian women had significantly lower BMD only for the lateral spine (−4.4%; P < 0.005), arm (−2.20%; P < 0.05) and leg (−1.65%; P < 0.05), whereas the wrist was significantly greater (4.64%; P < 0.005) for Asian women. Further research is needed to determine why racial differences in BMD persist at certain skeletal sites, but not others, after adjusting for body size. Received: 22 January 1996 / Accepted: 3 May 1996     

Effect of bone area on spine density in Chinese men and women in Taiwan

Areal bone mineral density (BMD), the quotient of bone mineral content (BMC) divided by the projectional bone area (BA), measured with dual-energy X-ray absorptiometers (DXA), is the most common parameter used today to evaluate spinal osteoporosis. To evaluate whether gender, age, weight, and height can determine spinal BA, and to compare BA and analyze its effects on spinal density in the two genders, we measured BA and BMC, and calculated areal BMD, and the bone mineral apparent density (BMAD = BMD/√BA) of the L-2 to L-4 vertebrate of 604 female and 223 male Chinese volunteers from 20 to 70 years of age using a Norland XR-26 DXA. Standardized for height and weight, BA showed a relatively large variation and a significant increase with increasing age in both genders. On the other hand, BMC stayed unchanged in men > 50 years of age and decreased with aging in postmenopausal women. Younger men (< 51 years) had a much larger mean BA (by 15.5%) and larger mean BMC (only 10%) than that of age-matched women. As a result, younger men had a slightly and significantly lower areal BMD (by 7.1%) and a much lower BMAD (by 16%) (p < 0.0001 for both) than premenopausal women of similar age. Men had higher areal BMD and BMAD values than age-matched women only after age 50 years. Although taller body height, heavier weight, and increasing age were associated with a larger BA, these factors could not explain most of the interindividual variations in BA in both genders. Thus anteroposterior BA of lumbar vertebrate measured with DXA seems to affect the areal BMD and BMAD readings in the two genders. The larger BA caused a low BMAD and probably underestimated the true volumetric spine density in men.     

Heritability of Spinal Trabecular Volumetric Bone Mineral Density Measured by QCT in the Diabetes Heart Study

The heritability of trabecular volumetric bone mineral density (BMD) determined by quantitative computed tomography (QCT) has not yet been reported. The purpose of this study was to investigate the heritability of BMD as determined by QCT and DXA in 124 women and 120 men (age 39–83 years, BMI 17–75, 84% type 2 diabetics) from 101 families (232 sibling pairs) in the Diabetes Heart Study. Volumetric BMD had a heritability (h²) estimate of 0.73 (SE = 0.15, P < 0.0001) at the lumbar spine and 0.71 (SE = 0.15, P < 0.0001) at the thoracic spine. Areal BMD heritability estimates were 0.56 for PA spine, 0.43 for total hip, 0.43 for femoral neck, 0.45 for distal radius, 0.42 for mid-radius, and 0.52 for whole body (all P < 0.01). After accounting for familial correlation using generalized estimating equations, volumetric BMD was inversely associated with age (r = –0.52, P < 0.0001) and duration of diabetes (r = –0.24, P < 0.01) and positively associated with body weight (r = 0.25, P < 0.01). In multivariate analysis, adjustment for age, sex, and race lowered the h² estimates for volumetric BMD at the lumbar (h² = 0.41, P < 0.01) and thoracic (h² = 0.48, P < 0.001) spine, increased the h² estimate for areal BMD at the mid radius (h² = 0.58, P < 0.0001), and had little effect on the h² estimate for areal BMD at other sites (h² = 0.41–0.55, all P < 0.01). Additional adjustment for BMI, duration of diabetes, and physical activity had little effect on the h² estimates for volumetric BMD or areal BMD except at the hip where they were lowered (h² = 0.31–0.33, all P < 0.05). These data suggest that, like areal BMD, volumetric BMD is highly heritable and may be used in designing linkage studies to locate genes governing bone metabolism.     

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     

Total and Visceral Adiposity Are Associated With Prevalent Vertebral Fracture in Women but Not Men at Age 62 Years: The Newcastle Thousand Families Study

Low body weight is an established risk factor for osteoporosis and fracture, but the skeletal risks of higher adiposity are unclear and appear sex‐specific and site‐dependent. The aim of this study was to investigate associations of total fat mass (TFM), visceral adipose tissue (VAT), and C‐reactive protein (CRP) with bone mineral density (BMD) and prevalent vertebral fracture (VF) in men and women aged 62 years. A total of 352 men and women aged 62.5 ± 0.5 years from the Newcastle Thousand Families Study cohort received dual‐energy X‐ray absorptiometry (DXA) evaluations of femoral neck and lumbar spine BMD, of the lateral spine for vertebral fracture assessment, and of the whole body for TFM and VAT (GE Lunar CoreScan, Madison, WI, USA). Plasma CRP, FRAX scores, falls in the last 12 months, and occupation at age 50 years were also included in the analysis. Vertebral fractures were less prevalent in women than in men (odds ratio [OR] = 0.33, p < 0.001) and BMD or FRAX scores did not differ between participants with and without VF. Women with VF were heavier and had higher TFM, VAT, and CRP than women without (p < 0.001). In women, greater (+1 SD) TFM and VAT increased the odds of any grade VF (TFM: OR = 1.06, p = 0.001; VAT: OR = 2.50, p = 0.002), and greater VAT mass increased the odds of prevalent mild VF (OR = 2.60, p = 0.002). In contrast, there were no associations in men. In both sexes, after controlling for body weight, neither VAT nor CRP were associated with BMD. In conclusion, irrespective of BMD, total and visceral adiposity were associated with prevalent VF in women but not in men. High fat mass, particularly if visceral, should be considered when assessing VF risk in women. Risk factors for VF in men require further investigation, particularly given their high prevalence. © 2017 American Society for Bone and Mineral Research.     

Association of Adenylate Cyclase 10 (<Emphasis Type="Italic">ADCY10</Emphasis>) Polymorphisms and Bone Mineral Density in Healthy Adults

Phenotypic variation in bone mineral density (BMD) among healthy adults is influenced by both genetic and environmental factors. Sequence variations in the adenylate cyclase 10 (ADCY10) gene, which is also called soluble adenylate cyclase, have previously been associated with low spinal BMD in hypercalciuric patients. Since ADCY10 is located in the region linked to spinal BMD in our previous linkage analysis, we tested whether polymorphisms in this gene are also associated with normal BMD variation in healthy adults. Sixteen single-nucleotide polymorphisms (SNPs) distributed throughout ADCY10 were genotyped in two healthy groups of American whites: 1692 premenopausal women and 715 men. Statistical analyses were performed in the two groups to test for association between these SNPs and the femoral neck and lumbar spine areal BMD. We observed significant evidence of association (p < 0.01), with one SNP each in men and women. Genotypes at these SNPs accounted for <1% of hip BMD variation in men but 1.5% of spinal BMD in women. However, adjacent SNPs did not corroborate the association in either men or women. In conclusion, we found a modest association between an ADCY10 polymorphism and the spinal areal BMD in premenopausal white women.     

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     

Forearm bone mineral density in postmenopausal women with osteoarthritis of the knee

The aims of the present study were to clarify whether postmenopausal women with osteoarthritis (OA) of the knee show higher bone mineral density (BMD) than healthy controls, and to investigate the relationship between BMD and the Kellgren and Lawrence radiological grade in postmenopausal women with OA of the knee. A total of 674 postmenopausal women, 46–90 years of age, were enrolled in the study: 305 patients with OA of the knee and 369 healthy controls. Forearm (distal radius) BMD, measured by dual-energy X-ray absorptionetry (DXA), using a DTX-200 (Osteometer), was significantly higher in the OA group than in the control group (P < 0.001), even when adjusted for age, height, body weight, body mass index, years since menopause, and grip strength (P < 0.01). Analysis of variance (ANOVA) with Fisher's protected least significant difference (PLSD) test showed that BMD in radiological grades 2, 3, and 4 was significantly higher than that in grade 1 (P < 0.05, P < 0.001, and P < 0.05, respectively), and BMD in grade 3 was significantly higher than that in grade 2 (P < 0.01), but BMD in grade 4 was significantly lower than that in grade 3 (P < 0.05). These findings suggest that forearm BMD appears to be significantly higher in postmenopausal women with OA of the knee than in healthy controls. Although BMD may be increased in low to moderate radiological grades of OA, severe grade OA may not always develop from moderate grade OA. Some cases of severe grade OA may be associated with low BMD. Received: May 1, 2001 / Accepted: September 26, 2001     

Association between bone mineral densities and serum lipid profiles of pre- and post-menopausal rural women in South Korea

The objectives of this population-based study were to investigate the potential association between bone mineral density (BMD) and serum lipid profiles and to compare the effects of serum lipids on BMD at various skeletal sites in pre- and post-menopausal women. In July and August of 2004, BMD was measured at a variety of skeletal sites [lumbar spine (L_1–4), femoral neck, trochanter, Wards triangle, shaft and proximal total hip] using the GE/Bravo Lunar DPX dual-energy X-ray absorptiometer in a South Korean population-based sample of 375 pre-menopausal and 355 post-menopausal rural women aged 19–80 years. The levels of serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were inversely associated with BMD in both pre- and post-menopausal women. In the pre-menopausal women, correlations were shown only for lumbar 1–4 (TC: r =–0.12, P <0.05; LDL-C: r =–0.12, P <0.05), whereas in the post-menopausal women, no correlation was evident for the lumbar sites. In the post-menopausal subjects, the TC levels showed significant correlations with the BMD values at the trochanter ( r =–0.15, P <0.01), shaft ( r =–0.16, P <0.001) and proximal total hip ( r =–0.15, P <0.01) sites, while the LDL-C levels showed significant correlations with the BMD values at the neck ( r =–0.13, P <0.05), trochanter ( r =–0.21, P <0.001), shaft ( r =–0.20, P <0.001) and proximal total hip ( r =–0.20, P <0.001) sites. The levels of triglyceride (TG) were shown to have a significant positive correlation with BMD values at the trochanter site ( r =0.11, P =0.05) in the post-menopausal women; by contrast, subjects in a higher quartile of TG levels show lower lumbar BMD values in the pre-menopausal women. The levels of high-density lipoprotein cholesterol (HDL-C) were not associated with BMD values at any of the sites in the pre- and post-menopausal subjects. Our data indicate a relationship between BMD values and serum lipid levels and suggest differences between pre- and post-menopausal women in terms of the effects of serum lipids on BMD at various skeletal sites.     

The relationship between endogenous estrogen,sex hormone-binding globulin,and bone loss in female residents of a rural Japanese community: the Taiji Study

 The aim of this study was to clarify the relationship between endogenous estrogen, sex hormone-binding globulin (SHBG), and bone loss in pre-, peri-, and postmenopausal female residents of Taiji, a rural Japanese community. From a list of inhabitants aged 40 to 79 years, 200 participants—50 women in each of four age decades—were randomly selected, and baseline bone mineral density (BMD) at the lumbar spine and proximal femur were measured by dual-energy X-ray absorptiometry in 1993. Total estradiol (total E2) and SHBG were measured, and SHBG-unbound E2 (UBE2) was calculated using SHBG and the percent SHBG-unbound fraction ratio. BMD was measured again 3 years later, in 1996. Participants with ovariectomy or hysterectomy were excluded, and the remaining participants were categorized into four groups: premenopausal (n= 38), perimenopausal (n= 14), postmenopausal group 1 (5 years or less since menopause; n= 18), and postmenopausal group 2 (6 years or more since menopause; n= 74). The mean value of total E2 was highest in the premenopausal group (49.1 pg/ml), followed by the perimenopausal group (26.4 pg/ml), and the postmenopausal groups (0.83 pg/ml in postmenopausal group 1 and 0.96 pg/ml in postmenopausal group 2). The means for UBE2 showed the same pattern across the groups. After the multiple regression analysis of BMD at follow-up and endogenous estrogens, in premenopausal women, there were no significant associations between BMD at follow-up and serum total E2 and UBE2. In perimenopausal women, however, serum total E2 and UBE2 were significantly correlated with trochanteric BMD at follow-up (P < 0.05); and in postmenopausal group 2, they were significantly correlated with lumbar spine and Ward's triangle BMD at follow-up (P < 0.001 at lumbar spine, P < 0.05 at Ward's triangle). Concerning the association between BMD at follow-up and SHBG, in the premenopausal group, serum levels of SHBG were negatively correlated with BMD at the femoral neck (P < 0.05). In regard to partial regression coefficients for the change rates of BMD over 3 years and serum estrogens and SHBG concentrations, in perimenopausal women, UBE2 was correlated with the change rate of BMD at Ward's triangle (P < 0.05), and in postmenopausal group 1, serum levels of SHBG were significantly negatively related to change in BMD at the trochanter (P < 0.01). No other relationships with change in BMD were observed at any sites. These findings suggest that serum E2, UBE2, and SHBG levels differentially predict BMD levels in groups of differing menstrual status. It would, however, be difficult to predict bone loss in middle-aged and elderly Japanese women over a 3-year period using these indices alone. Received: November 29, 2001 / Accepted: February 28, 2002