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.     

Loss of Bone Mineral Density in Women Athletes During Aging

Total and regional bone mineral density (BMD) by dual-energy-X-ray absorptiometry (DXA) and bone turnover were tested in 50 highly trained women athletes and 21 sedentary control women (18–69 years; BMI < 25 kg/m²). VO_2max (ml · kg⁻¹· min⁻¹) and lean tissue mass (DXA) were significantly higher in the athletes versus controls (both P < 0.0001). Total body BMD did not decline significantly with age in the athletes whereas lumbar spine (L₂–L₄) BMD approached statistical significance (r =−0.26; P= 0.07). Significant losses of the femoral neck (r =− 0.42), Ward's triangle (r =−0.53), and greater trochanter BMD (r =−0.33; all P < 0.05) occurred with age in the athletes. In the athletes, total body BMD, L₂–L₄ BMD, and BMD of all sites of the femur were associated with lean tissue mass (r = 0.32 to r = 0.57, all P < 0.05) and VO_2max (r = 0.29 to r = 0.48, all P < 0.05). Femoral neck and greater trochanter BMD were higher in the athletes than in controls (both P < 0.05) and lumbar spine and Ward's triangle BMD approached statistical significance (both P= 0.07). Bone turnover was assessed by serum bone-specific alkaline phosphatase (B-ALP), urinary deoxypyridinoline cross-links (Dpd), and urinary aminoterminal cross-linked telopeptides (NTX). There were no relationships between B-ALP or Dpd with age whereas NTX increased with age (r = 0.46, P < 0.05) in the entire group. Levels of B-ALP and NTX were negatively associated with total body, L₂–L₄, femoral neck, Ward's triangle, and greater trochanter BMD (P < 0.05). B-ALP and Dpd were not significantly different between athletes and controls whereas NTX was lower in the athletes than in controls (P < 0.001). The high levels of physical activity observed in women athletes increase aerobic capacity and improve muscle mass but are not sufficient to prevent the loss of bone with aging. Received: 28 November 1997 / Accepted: 8 April 1998     

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     

Bone mineral density in Norwegian premenopausal women

The aims of this study were: 1) to determine bone mineral density (BMD) in different age groups, 2) to determine the prevalence of low BMD, and 3) to determine the possible association between BMD and a number of risk factors in Norwegian premenopausal women. BMD of the lumbar spine (L₂–L₄), total body, and the hip (total femur, femur neck, and trochanter) were measured using dual-energy X-ray absorptiometry (Prodigy, Lunar) in 145 randomly selected women aged 13–39 years. Information on other factors thought to influence BMD was obtained through questionnaire and a clinical interview. The group aged 25–29 years had the highest mean BMD in the total body, lumbar spine, and total femur while the group aged 13–19 years had the highest mean BMD in the femur neck and the trochanter. The mean BMD values of Norwegian premenopausal women were 3.4–5.1% higher than US/European reference data (P<0.05). Five percent of the study sample aged 20–39 years were defined with low BMD (Z-score <–2) using the standard values from this study. Weight-bearing physical activity, body weight, body height, and age were positively associated with BMD, whilst menstrual dysfunction and previous pregnancy were associated with lower BMD in some of the measurement sites. The results show that the factors associated with BMD are extensive, and the strategies to prevent low BMD have to be multifactorial. A follow-up study should be conducted on the study sample to investigate actual mean BMD values and BMD changes through time.     

Genetic and environmental influences on bone mineral density in pre- and post-menopausal women

Genetic factors influencing acquisition of peak bone mass account for a substantial proportion of the variation in bone mineral density (BMD), although the extent to which genes also contribute to variation in bone loss is debatable. Few prospective studies of related individuals have been carried out to address this issue. To gain insights into the nature of the genetic factors contributing to variation in BMD, we studied 570 women from large Amish families. We evaluated and compared the genetic contributions to BMD in pre- and post-menopausal women, with the rationale that genetic variation in pre-menopausal women is due primarily to genetic determinants of peak bone mass, while genetic variation in post-menopausal women is due to the combined genetic effects of peak bone mass and bone loss. Bone mineral density was measured at one point in time at the hip and spine by dual energy X-ray absorptiometry (DXA). We used variance decomposition procedures to partition variation in BMD into genetic and environmental effects common to both groups and to pre- and post-menopausal women separately. Total variation in BMD was higher in post- compared to pre-menopausal women. Genes accounted for 58–88% of the total variation in BMD in pre-menopausal women compared to 37–54% of the total variation in post-menopausal women. In absolute terms, however, the genetic variance was approximately similar between the two groups because the environmental variance was 3 1/2- to 4-fold larger in the post-menopausal group. The genetic correlation in total hip BMD was 0.81 between pre- and post-menopausal women and differed significantly from one, consistent with the presence of at least some non-overlapping genetic effects in the two groups for BMD at this site. Overall, these analyses suggest that many, but not all, of the genetic factors influencing variation in BMD are common to both pre- and post-menopausal women.     

Relationships Between the Changes of Serum Levels of OPG and RANKL with Age, Menopause, Bone Biochemical Markers and Bone Mineral Density in Chinese Women Aged 20-75

The correlations between the serum levels of OPG, RANKL with age, menopause, bone markers, and bone mineral densities (BMDs) at the lumbar spine and proximal femur were studied in 504 pre- and postmenopausal Chinese women aged 20–75 years. We found that age was positively and negatively correlated with serum concentrations of OPG (r = 0.442, P < 0.001) and RANKL (r = –0.263, P < 0.001), respectively. Compared with premenopausal women, postmenopausal women showed higher serum OPG levels (107.6 ± 3.0 vs 72.0 ± 1.8 pg/ml, P < 0.001), lower serum RANKL concentrations (4.7 ± 0.4 vs. 5.8 ± 0.3 pg/ml, P < 0.001) and RANKL/OPG ratios (0.045 ± 0. 004 vs. 0.099 ± 0.008, P < 0.001). Neither serum levels of OPG nor RANKL or RANKL/OPG ratio correlated with BMDs after adjustment of age and menopause. They also showed no differences among normal, osteopenic and osteoporotic postmenopausal women. Serum levels of OPG were positively correlated with urinary excretion of NTx (r = 0.1453, P = 0.006). Serum levels of RANKL (r = –0.1928, P < 0.001) and RANKL/OPG ratio (r = –0.1303, P = 0.013) were inversely correlated with serum concentrations of OC. In multiple regression analysis, up to 20% variance (R² = 0.106–0.224) of the OPG-RANKL system in peripheral circulation can be explained by age, menopause and bone markers.These results suggest that although serum OPG and RANKL concentrations were unrelated with BMDs, the age– and menopause– dependent changes of serum OPG and RANKL might be a protective mechanism against the accelerated bone loss in postmenopausal women.     

Risk factors for low bone mineral density and the 6-year rate of bone loss among premenopausal and perimenopausal women

Risk factors that are associated with lower bone mineral density (BMD) may not necessarily be associated with increased bone loss among premenopausal and perimenopausal women. We determined risk factors for lower premenopausal and perimenopausal BMD while simultaneously determining risk factors for increased 6-year rate of bone loss among women aged 24–50 years within a population-based prospective cohort study. BMD of the lumbar spine and femoral neck, reported as t scores, were measured five times within the 6-year study among 614 women who were between the ages of 24 and 44 in 1992/1993. Rates of bone loss were calculated from the repeated BMD measurements. Risk factors for lower BMD over time at the lumbar spine included history of any fracture (P=0.005). The major risk factor for lower BMD over time at the femoral neck was family history of osteoporosis (P<0.002). The major protective factor for greater BMD over time at both skeletal sites was additional body weight (P<0.0001). Other protective factors for greater BMD over time at the femoral neck were modest alcohol consumption (P=0.0002) and high-school sports participation (P=0.002). Risk factors for greater bone loss at either skeletal site included postmenopausal status (P<0.0001 at the lumbar spine; P=0.01 at the femoral neck), and the reporting of a reproductive cancer (P<0.0001 at the lumbar spine; P=0.0008 at the femoral neck). Body weight was protective against bone loss at both skeletal sites (P<0.0001). Baseline age, calcium intake, smoking, and current physical activity were not associated with BMD or bone loss. The understanding of the relative importance of risk factors for both low BMD and bone loss may assist in the identification of women at greater risk for subsequent low postmenopausal BMD.     

Comparison of spine and femur reference data in native Chinese women from different regions of China

The aim of this study is to explore the differences of BMD reference curves at various skeletal sites among Chinese women from different regions of China and to investigate the feasibility of establishing a unified national BMD reference database for Chinese women. We measured BMD at the posteroanterior (PA) lumbar spine, femoral neck, trochanter and Wards triangle by dual-energy X-ray absorptiometry bone densitometer in 3,422 Changsha women of South Central China, aged 20–84 years. The documented BMDs of reference populations of women in all other areas included Shanghai ( n =2,111) and Nanjing ( n =3,174) in the East, Shenyang ( n =1,213) in the Northeast, Kunming ( n =523) in the Southwest, Chongqing ( n =811) in the Midwest and Xian ( n =1,320) in the Northwest. We adopted the cubic regression as the fitting model for reference curves of BMD that varied with age, conducted conversions of BMD measured by various bone densitometers from different manufacturers and compared the differences between standardized BMD (sBMD) reference curves and combined ones for women from different areas. Our results revealed that by comparing variances in women from different areas, the average variances of non-standard BMD were 0.8–30.8% at the PA spine, 0.7–24.5% at the femoral neck, 0.6–29.9% at the trochanter and 1.1–54.7% at Wards triangle, while average variances of sBMD either significantly decreased or disappeared (0.8–3.9% at the PA spine, 0.7–8.6% at the femoral neck, 0.6–8.3% at the trochanter and 1.1–29.9% at Wards triangle). The sBMD reference curves were highly positive-dependent with combined ones ( r =0.913–0.999, P =0.000). At the PA spine and trochanter, the effect of combined sBMD curves presented well in women from different areas, except for those from Shanghai at the PA spine and Shenyang at the trochanter, indicating that sBMD curves were significantly different from pooled ones; at the femoral neck and Wards triangle, the effect of combined sBMD reference curves was poor, indicating that sBMD curves demonstrated significant differences from pooled ones in women from a majority of these areas. We conclude that, in high density population areas, sBMD reference curves showed no significant geographic differences in women from various regions. In women from different areas, sBMD reference curves present good pooled results at the PA spine and trochanter. The less ideal combining effect of the sBMD curves at both femoral neck and Wards triangle might be caused by the intrinsic differences from the different measuring instruments.     

Risk for developing osteoporosis in untreated premature menopause

Summary The bone mineral density (BMD) of the lumbar spine and proximal femur was determined by dual photon absorptiometry in 32 women with untreated premature menopause (cessation of menses before 45 years of age). The BMD of the spine and proximal femur in four obese patients was not different from the BMD of the age-matched controls. On the contrary, the BMD of the nonobese females with premature menopause was significantly lower with respect to the average values found in healthy young women, in age-matched and menopause-matched controls. The BMD deficit was greater over the lumbar spine than in the proximal femur. Forty three percent of nonobese patients were already under the vertebral fracture threshold and 25% of nonobese patients were below the hip fracture threshold. The BMD deficit in the lumbar spine was correlated to the loss observed in the femoral neck (r=0.59, P<0.001), in the trochanter (r=0.65, P<0.001) and in the Ward's triangle (r=0.73, P<0.001). A negative correlation was observed between years of menopause and the BMD of the lumbar spine (r=-0.39, P<0.05). The results indicate the high individual risk for osteoporotic fractures in nonobese females with untreated premature menopause. The BMD loss was greater over the skeletal areas that are predominantly composed of trabecular bone compared with cortical bone.     

Bone Mineral Density of the Spine and Femur in Early Postmenopausal Turkish Women with Endemic Skeletal Fluorosis

The aim of this prospective, comparative study was to investigate the bone mineral density (BMD) changes in a group of early postmenopausal Turkish women with endemic skeletal fluorosis and to study effects of endemic fluorosis on BMD. Bone mineral density of L₂–L₄ vertebra, femur neck, femur trochanter, and Wards triangle were measured in 45 female patients with endemic skeletal fluorosis and 41 age-matched controls by dual X-ray absorbtiometry (DXA). The BMD of L₂–L₄ vertebra and Wards triangle were higher in the endemic fluorosis group than in the control group (P < 0.001). Patients with endemic fluorosis had higher femur neck and femur trochanter BMDs than did controls (P < 0.01 and P < 0.05, respectively). There was a positive correlation between serum fluoride content and BMD at the spine (r = 0.345, P = 0.001), femoral neck (r = 0.274, P = 0.011), Wards triangle (r = 0.295, P = 0.006), and trochanter (r = 0.217, P = 0.045). In conclusion, higher bone mineral density levels were seen in early postmenopausal women with endemic skeletal fluorosis. BMD measurement is a tool in the diagnosis and management of this preventable crippling disease.     

Bone mineral density and osteoporosis among a predominantly Caucasian elderly population in the city of São Paulo, Brazil

This cross-sectional study covered 301 individuals over 70 years of age—207 women (W) and 94 men (M)—living in the city of São Paulo, Brazil. Our aims were to evaluate the prevalence of low bone mineral density (BMD) in this population and the possible factors that influence BMD. The subjects were submitted to a bone densitometry scan (DXA) to evaluate the BMD at lumbar spine (LS), femoral neck (FN), trochanter (T), total femur (TF) and total body composition. At the time, the participants filled in a questionnaire about lifestyle habits, diet and medical history, as well as having blood samples taken to check hormone and biochemical levels. Anthropometric parameters were measured. Osteopenia and osteoporosis were defined in accordance with the criteria suggested by the World Health Organization. In the different sites studied, the prevalence of osteopenia and osteoporosis varied, in men ranging 33.3–57.4% and 6.4–16.1%, respectively, and in women ranging 36.6–56.5% and 22.2–33.2%, respectively. Weight was the variable that most strongly correlated with BMD at the proximal femur in both sexes (men, r =0.44–0.52; women, r =0.48–0.52) and with BMD at LS in women ( r =0.44). Height was the parameter that best correlated with BMD at LS in men ( r =0.34). In men follicle-stimulating hormone, growth hormone and glycemia correlated with BMD at T and TF, while plasma albumin only correlated with BMD at T. In women glycemia correlated with BMD at LS, and follicle-stimulating hormone correlated with BMD at FN, T and TF. In conclusion, we found a high prevalence of osteopenia and osteoporosis in this population, with weight being the best predictor of BMD. The prevalence of osteoporosis and osteopenia at FN was as high in men as that observed in women.     

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.     

Can the WHO definition of osteoporosis be applied to multi-site axial transmission quantitative ultrasound?

Osteoporosis is a highly prevalent but preventable disease and, as such, it is important that there are appropriate diagnostic criteria to identify those at risk of low trauma fracture. In 1994 the World Health Organization (WHO) introduced definitions of osteoporosis and osteopenia using T-scores, which identified 30% of all Caucasian post-menopausal women as having osteoporosis. However, the use of the WHO T-score thresholds of –2.5 for osteoporosis and –1.0 for osteopenia may be inappropriate at skeletal sites other than the spine, hip and forearm or when other modalities, such as quantitative ultrasound (QUS) are used. The aim of this study was to evaluate the age-dependence of T-scores for speed of sound (SOS) measurements at the radius, tibia, phalanx and metatarsal by use of the Sunlight Omnisense, to evaluate the prevalence of osteoporosis and osteopenia at these sites by use of the WHO criteria, and calculate appropriate equivalent T-score thresholds. The study population consisted of 278 healthy pre-menopausal women, 194 healthy post-menopausal women and 115 women with atraumatic vertebral fractures. All women had SOS measurements at the radius, tibia, phalanx and metatarsal and bone mineral density (BMD) measurements at the lumbar spine and hip. A group of healthy pre-menopausal women aged 20–40 years from the pre-menopausal group were used to estimate the population mean and SD for each of the SOS and BMD measurement sites. Healthy post-menopausal women were classified into normal, osteopenic or osteoporotic, based upon the standard WHO definition of osteoporosis and expressed as a percentage. We investigated the age-related decline in T-scores from 20–79 by stratifying the healthy subjects into 10-year age groups and calculating the mean T-score for each of these groups. Finally, we estimated appropriate T-score thresholds, using five different approaches. The prevalence of osteoporosis in the post-menopausal women aged 50 years and over ranged from 1.4 to 12.7% for SOS and 1.3 to 5.2% for BMD. The age-related decline in T-scores ranged from –0.92 to –1.80 for SOS measurements in the 60 to 69-year age group and –0.60 to –1.19 for BMD measurements in the same age group. The WHO definition was not suitable for use with SOS measurements, and revised T-score thresholds for the diagnosis of osteoporosis of –2.6, –3.0, –3.0 and –2.2 and for osteopenia of –1.4, –1.6, –2.3, and –1.4, for the radius, tibia, phalanx and metatarsal, respectively, were recommended.     

A Randomized Trial Comparing Hormone Replacement Therapy (HRT) and HRT Plus Calcitriol in the Treatment of Postmenopausal Osteoporosis with Vertebral Fractures: Benefit of the Combination on Total Body and Hip Density

We report a prospective, randomized, multicenter, open-label 2-year trial of 81 postmenopausal women aged 53-79 years with at least one minimal-trauma vertebral fracture (VF) and low (T-score below - 2) lumbar bone mineral density (BMD). Group HRT received piperazine estrone sulfate (PES) 0.625 – 1.25 mg/d ± medroxyprogesterone acetate (MPA) 2.5 – 5 mg/d; group HRT/D received HRT plus calcitriol 0.25 µg bd. All with a baseline dietary calcium (Ca) of <1 g/d received Ca carbonate 0.6 g nocte. Final data were on 66 – 70 patients. On HRT/D, significant (P < 0.001) BMD increases from baseline by DXA were at total body – head, trochanter, Wards, total hip, intertrochanter and femoral shaft (% group mean 4.2, 6.1, 9.3, 3.7, 3.3 and 3.3%, respectively). On HRT, at these 6 sites, significant s were restricted to the trochanter and Wards. Significant advantages of HRT/D over HRT were in BMD of total body (- head), total hip and trochanter (all P = 0.01). The differences in mean at these sites were 1.3, 2.6 and 3.9%. At the following, both groups improved significantly -lumbar spine (AP and lateral), forearm shaft and ultradistal tibia/fibula. The weightbearing, site — specific benefits of the combination associated with significant suppression of parathyroid hormone—suggest a beneficial effect on cortical bone. Suppression of bone turnover was significantly greater on HRT/D (serum osteocalcin P = 0.024 and urinary hydroxyproline/creatinine ratio P = 0.035). There was no significant difference in the number of patients who developed fresh VFs during the trial (HRT 8/36, 22%; HRT/D 4/34, 12% - intention to treat); likewise in the number who developed incident nonvertebral fractures. This is the first study comparing the 2 treatments in a fracture population. The results indicate a significant benefit of calcitriol combined with HRT on total body BMD and on BMD at the hip, the major site of osteoporotic fracture. Present address of K.J.: Department of Primary Health Care, Imperial College, London, UK     

Relationship Between Lipids and Bone Mass in 2 Cohorts of Healthy Women and Men

A number of recent findings seem to indicate that fat and bone metabolism are strictly connected. We investigated the relationship between lipid profile and bone mineral density (BMD) in 236 either pre- or postmenopausal women, aged 35–81 years, attending our osteoporosis center (clinic group). In order to verify the consistency of the results, 265 men and 481 women aged 68–75, participating in a population-based epidemiological investigation (community cohort), were also studied. Lumbar spine, femoral neck, total hip and total body BMD, total body fat, % fat mass and lean mass were measured using dual energy X-ray absorptiometry (DXA). In the clinic group, lumbar spine and hip BMD Z score values were both strongly related to all measured serum lipids: the relationship was negative for HDL cholesterol (P < 0.05) and Apo A lipoprotein (P < 0.000) and positive for LDL cholesterol (P < 0.05), Apo B lipoprotein (P < 0.001) and triglycerides (P < 0.05). When BMD values were adjusted for body weight and BMI, most relationships remained statistically significant. In the community cohort, total body and hip BMD values were strongly related in both men and women to age, body weight, height, BMI, fat mass, lean mass, % fat mass. Total body and hip BMD were significantly related to serum lipids in both women and men. The relationship was negative for HDL cholesterol and positive for total cholesterol, triglycerides and LDL cholesterol. Most of these relationships (triglycerides, HDL cholesterol, LDL/HDL cholesterol ratio in women, and all measured lipids in men) remained statistically significant (P values ranging from 0.000 to 0.03) when the BMD values were adjusted also for anthropometric measures (body weight, height, fat mass). This study demonstrates for the first time that the lipid profile is strictly related to bone mass in both men and women. The interpretation of this association remains hypothetical but it might open new perspectives for understanding the mechanisms controlling bone metabolism.     

Determinants of vitamin D status in older women living in a subtropical climate

Studies performed in the Northern Hemisphere and in areas distant from the equator have demonstrated significant seasonal variation in 25-hydroxyvitamin D (25OHD) levels. Whether such variation occurs in a subtropical area such as Australasia is not clear. We performed a cross-sectional study of 1,606 healthy, postmenopausal women recruited over a 33-month period. The study had three goals: to determine the normal levels of 25OHD in healthy postmenopausal women living in Auckland, New Zealand; to determine whether seasonal variation of 25OHD occurs at this latitude; to assess the relationship between 25OHD, biochemical indices, anthropometric variables and bone mineral density (BMD). We found significant seasonal variation in 25OHD levels, with the change in monthly ultraviolet dose from summer to winter being followed 6–8 weeks later by a corresponding change in 25OHD levels. Vitamin D insufficiency (25OHD <50 nmol/l) was common. During summer, 28–58% of participants had suboptimal vitamin D status, while in winter, the frequency increased to 56–74%. 25OHD levels correlated with participants age (r=–0.15), weight (r=–0.11), body mass index (r=–0.13), fat mass (r=–0.14), percentage body fat (r=–0.16), physical activity (r=0.10) and the month of blood sampling (all P<0.0001). Collectively, age, fat mass, physical activity, and month of sampling explained 21% of the variance in 25OHD. No significant relationships were noted between 25OHD and BMD at any site. Other variables that showed significant monthly variation were glucose (P=0.002), serum phosphate, alkaline phosphatase, and albumin (all P<0.0001). There was no monthly variation in BMD at the lumbar spine or proximal femur. In conclusion, there is significant seasonal variation in 25OHD levels, even in a subtropical climate. Furthermore, despite generous amounts of sunlight, considerable numbers of women have suboptimal vitamin D status, even in summer. Our findings support the suggestion that vitamin D supplementation should become standard practice in this population of women, particularly during winter.Jenny A. Lucas and Mark J. Bolland contributed equally to this work.     

Sexual differences in bone markers and bone mineral density of normal Chinese

We measured bone mineral density (BMD) at lumbar (L2–L4) vertebrae and proximal femurs of 385 healthy Chinese women aged 40–70 years and 156 healthy Chinese men aged 20–85, and four markers—bone alkaline phosphatase isozyme (BAP), procollagen-I C terminal propeptide (PICP), osteocalcin (BGP) in serum, and a bone resorption marker, urinary cross-linked N-telopeptide of type I collagen (NTX), of these subjects. The results indicate that in postmenopausal women, levels of all the markers increased with age. In men, serum BAP, PICP, and urinary NTX decreased significantly, and serum BGP decreased with borderline significance (P=0.08). With increasing age, bone density decreased at both sites in post-menopausal women and at the proximal femur in men. The lumbar bone density showed no significant age-related changes in men. In premenopausal women, BMD at either site showed no significant change with increasing age. Despite the different trends between men and women of agerelated changes in BMD and bone markers, bone density of both proximal femur and spine in both sexes correlated inversely with levels of the bone markers in a manner independent of age or body weight. The meaning of opposite age effects on bone markers in men and women needs further investigation. In addition, higher bone marker levels, implying faster bone turnover rate, are associated with lower BMD in both sexes.     

Bone mineral density of the spine and femur in healthy Saudis

The reference values of bone mineral density (BMD) were determined in healthy Saudis of both sexes and compared with US / northern European and other reference data. BMD was determined by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and femur including subregions: trochanter, Wards triangle, and neck, in 1,980 randomly selected Saudis (age range 20–79 years; 915 males and 1,065 females) living in the Jeddah area. Age-related changes in BMD were similar to those described in US / northern European and Lebanese reference data. Decreases in BMD of males were evident (% per year): 0.3–0.8 (lumbar spine), 0.2–0.4 (femoral trochanter), 0.2–1.4 (Wards triangle), and 0.2–0.7 (femoral neck). Also, decreases in BMD of females were observed (% per year): 0.8–0.9 (lumbar spine), 0.7–0.9 (Wards triangle), and 0.3–0.7 (femoral neck). Using stepwise multiple regressions that included both body weight and height, the former had 2–4 times greater effect on BMD than the latter. Using the mean BMD of the <35-year-old group the T-score values were calculated for Saudis. The prevalence of osteoporosis in Saudis (50–79 years) at the lumbar spine using the manufacturers vs Saudi reference data was 38.3–47.7% vs 30.5–49.6 (P<0.000), respectively. Similarly, based on BMD of total femur, the prevalence of osteoporosis using the manufacturers vs Saudi reference data was 6.3–7.8% vs 1.2–4.7% (P<0.000), respectively. Saudis (50 years) in the lowest quartile of body weight exhibited higher prevalence of osteoporosis (25.6% in females and 15.5% in males) as compared to that of the highest quartiles (0.0% in females and 0.8% in males). The present study underscores the importance of using population-specific reference values for BMD measurements to avoid overdiagnosis and/or underdiagnosis of osteoporosis.     

Dual-energy X-ray absorptiometry at the lumbar spine in German men and women: A cross-sectional study

A cross-sectional, population-based study of 238 randomly selected females and 224 males with German ethnic background (aged 20–80 years) was carried out to establish lumbar spine bone mineral density (BMD) values, using dual X-ray absorptiometry (DXA), for a German population. Comparison was made to the reference range provided by the manufacturer of the DXA equipment. No sex difference in peak spine BMD was found in our study (1.091±0.114 g/cm² for males versus 1.070±0.113 g/cm² for females, n.s.). Different patterns of bone loss could be detected in both sexes. In premenopausal women there was no significant correlation between age and BMD (y = 1.044 + 0.00047x, r=0.03, P=0.73) whereas reduction of female BMD at the spine was demonstrated in postmenopausal women (y = 1.189–0.0041x, r=-0.28, P=0.01), underscoring the important role of the menopause for later manifestation of spinal osteoporosis in women. In contrast, in males we found no significant change of BMD with aging (y = 1.071–0.0007x, r=-0.08, P=0.25). Employing commonly used exclusion criteria, BMD values of the study subjects were found mostly within the normal range of BMD. The major finding of our study was good concordance between female data of our study population and the reference data provided by the manufacturer. Clinically significant discrepancies between our data and the Hologic reference range for males could be detected. Our data on males (30–39 years of age) were up to 7% lower than those provided by the manufacturer, probably due to differences in sampling procedures.     

Effects on bone mineral density of 12-month goserelin treatment in over 40-year-old women with uterine myomas

We evaluated the effects on bone mineral density (BMD) of a 12-month treatment with goserelin depot, a gonadotropin-releasing hormone agonist, in a group of women with symptomatic uterine myomas requiring hysterectomy. Sixteen women, mean age 45.6±5.0, reporting menorrhagia associated with uterine myomas, candidates for hysterectomy, were scheduled to be treated with goserelin depot for 12 months. BMD was measured at the vertebral (L2–L4) and proximal femur level (femoral neck and trochanter) at the start of therapy and 6, 12, and 18 months later using dual energy X-ray absorptiometry (Hologic QDR 1000/W). The patients were followed for a minimum of 6 months after the end of treatment. Thirteen of the 16 women enrolled completed the treatment and three suspended it after 5, 6, and 7 months, respectively, because of side effects (hot flashes, insomnia, depression). Of the 13 women who completed the treatment, three underwent hysterectomy because of myoma regrowth and the recurrence of symptoms 3–18 months later; four reached the menopause 5–16 months later, and six were all menstruating normally with a follow-up varying from 6 to 18 months. After 12 months of therapy we observed a bone loss at vertebral, femoral neck, and trochanter of 4.4% (P<0.05 versus baseline; P = not significant versus 6 months), 7.5% (P<0.01 versus baseline, P<0.01 versus 6 months), and 7.6% (P<0.001 versus baseline, P<0.05 versus 6 months), respectively. Six months later, BMD increased slightly and not significantly at different sites (0.9% at the spine, and 0.3% at femoral neck, and 1.1% at trochanter). A 12-month treatment with goserelin may avoid the need for hysterectomy in women over 40 with symptomatic myomas. However, this therapy is associated with a marked bone loss which is not significantly reversed at its suspension.