Menopause-related changes in bone mineral density in Japanese women: A longitudinal study on lumbar spine and proximal femur

We investigated 2-year longitudinal changes of bone mineral density (BMD) in lumbar spine and proximal femur in 64 Japanese women aged 38–67. Forty subjects were premenopausal (mean age 44.9) and 24 postmenopausal (mean age 54.6) at enrollment of the study. Six subjects experienced menopause during the 2-year study period and were defined as the perimenopausal group. Measurements of BMD were performed using dual-energy X-ray absorptiometry at L2–4, femoral neck, greater trochanter, and Ward's triangle. Paired t test revealed no significant decrease in BMD at any site in the premenopausal group. Significant annual decrease in BMD was observed in the perimenopausal group at L2–4, femoral neck, and greater trochanter. A similar tendency was observed in Ward's triangle, but did not reach statistical significance. In the postmenopausal group, significant decrease in BMD was found at the proximal femur, but not at L2–4. Significant inverse correlation between age and change rate of BMD was found at L2–4, but not at the proximal femur, in premenopausal women. In postmenopausal women, there was a significant association between body weight (BW) change and change rate in BMD at L2–4, femoral neck, or greater trochanter. This association was not found in the premenopausal group. These results suggest that effect of menopause on BMD may be different in individuals and sites of the skeleton. BW change may affect change in BMD in postmenopausal women. However, the limited variability in both BW and BMD changes among premenopausal women in this study may explain the poor association between change in BW and change in BMD in the premenopausal group. As individual differences in each group is considerably large, annual measurements of BMD may be necessary to find possible candidates for early intervention.     

Spine and femur BMD by DXA in patients with varying severity spinal osteoporosis

Summary Bone mineral density (BMD) at the lumbar spine, femoral neck, trochanteric region, and Ward's triangle was measured using dual-energy X-ray absorptiometry (DXA) in 118 women with osteoporotic vertebral collapse (average age 65 years), divided into four groups according to numbers and SD of vertebral deformation below norms: group 1:-3SD deformations only; group 2: one-4SD deformation; group 3: two-four-4SD deformations; and group 4: 5 or more-4SD deformations. There were no significant differences between the groups. Results were compared with those from 80 premenopausal (average age 32 years, range 20–40 years) and 109 postmenopausal normal women (average age 64, range 60–70 years). Mean BMD in osteoporotic group 1 was lower than premenopausal normal women by 32% at the lumbar spine, 31% femoral neck, 30% trochanteric region, and 44% at Ward's triangle, and postmenopausal controls by 17% lumbar spine, 16% femoral neck, 17% trochanter, and 14% Ward's triangle. There was a clear trend to reduction in mean BMD between osteoporotic groups 1 and 4 at all four measured sites with significant differences at the spine of 0.102 g/cm² (P<0.01) and Ward's triangle 0.059 g/cm² (P<0.01). When compared with premenopausal controls, there was a reduction in mean BMD between osteoporotic groups 1 and 4 of 10% at the lumbar spine, 7% femoral neck, 8% trochanteric region, and 13% Ward's triangle. Receiver operating characteristic analysis showed no significant differences in diagnostic sensitivities among the four measured sites for vertebral fractures. We conclude from this crosssectional data that the majority of bone loss in spinal osteoporosis occurs before the onset of fractures.     

Bone mineral density measured by dual-energy X-ray absorptiometry in healthy finnish women

Summary A cross-sectional study of 351 healthy Finnish women aged 20–76 years was done to establish reference values of bone mineral density (BMD) using dual-energy X-ray absorptiometry (DEXA). The effects of age and of several physical and lifestyle factors on BMD of the lumbar spine and proximal femur (femoral neck, trochanter, and Ward's triangle area) were investigated. Altogether 58 women were excluded from the final analysis due to significant spinal osteoarthritis or other diseases or drugs known to influence calcium or bone metabolism. The precision of the method was 0.9, 1.2, 2.7, and 2.4% in the lumbar, femoral neck, Ward's triangle and trochanter area, respectively. Lumbar BMD was increased by 30% (P<0.001) in 15 patients with osteoarthritis (21% of women 50 years or older), but it was apparently unaffected in 5 cases with aortic calcification. Except for the trochanter area, BMD diminished along with age, and this was significant after the menopause. The peak of mean BMD was observed at the age of 31–35 years in the spine and at the age of 20–25 years in the femoral neck and Ward's triangle. BMD was in a positive relationship to weight both in premenopausal and postmenopausal women and to the use of oral contraceptives in premenopausal women and to that of estrogen replacement therapy in postmenopausal women. Labors and pregnancies had a weak positive effect on BMD in premenopausal women. As compared with nonusers premenopausal women who had used alcohol showed a slightly decreased BMD of Ward's triangle. In postmenopausal women there was a positive correlation between alcohol intake and BMD.     

Soy Product Intake and Serum Isoflavonoid and Estradiol Concentrations in Relation to Bone Mineral Density in Postmenopausal Japanese Women

To evaluate soy intake and serum concentrations of estradiol and isoflavonoids and their relationship to bone mineral density (BMD) and serum bone-specific alkaline phosphatase (bone ALP) activity, we conducted a cross-sectional study of 87 postmenopausal Japanese women. Soy product and isoflavone intake from soy products and intake of nutrients were assessed with a semiquantitative food-frequency questionnaire. BMD (mg/cm²) was measured by single-energy X-ray absorptiometry at the site of the calcaneus. Serum estradiol (E₂) and the sex hormone-binding globulin (SHBG) were measured by radioimmunoassay. Serum genistein and daidzein concentrations were measured by a high-performance liquid chromatography MS/MS method. A statistically significant correlation was observed between the ratio of E₂ to SHBG and BMD (Spearman r = 0.38, p = 0.0003) after controlling for age, body mass index, smoking status, age at menarche, and intake of vegetable fat, vitamin C and salt. Soy product and isoflavone intake and serum isoflavones were not significantly correlated with BMD after controlling for the covariates. Serum ALP was not significantly correlated with soy product and isoflavone intake, the E₂/SHBG ratio or serum isoflavones. The present study supports the association of BMD with serum estradiol; however, it does not support the association of BMD with soy or isoflavone intake or serum isoflavone levels. Received: 13 August 2001 / Accepted: 30 October 2001     

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.     

Teriparatide versus alendronate for treating glucocorticoid-induced osteoporosis: an analysis by gender and menopausal status

Summary  

The effects of teriparatide versus alendronate were compared by gender and menopausal status in patients with glucocorticoid-induced osteoporosis. At 18 months, increases in lumbar spine BMD were significantly greater in the teriparatide versus alendronate group in postmenopausal women (7.8% versus 3.7%, p < 0.001), premenopausal women (7.0% versus 0.7%, p < 0.001), and men (7.3% versus 3.7%, p = 0.03).     

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

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

Correlation between bone mineral density and intervertebral disk degeneration in pre- and postmenopausal women

 The purpose of this study was to investigate the relationship between intervertebral disk degeneration and bone mass. Magnetic resonance imaging was performed to evaluate lumbar disk degeneration according to Thompson's classification (grades 1 and 2, normal disk; grades 3, 4, and 5, degenerated disk), and bone mineral density (BMD) in the lumbar vertebrae, radius, and calcaneus was measured by dual-energy X-ray absorptiometry for 90 women (22–74 years old). The relationship between the grade of intervertebral disk degeneration and the BMD (Z score) was analyzed in pre- and postmenopausal women. In premenopausal women, BMD was significantly higher at all measured sites in the degenerated disk group judged at the L5–S1 level than in the normal disk group (P < 0.05). In postmenopausal women, BMD was significantly higher at the anteroposterior L2–L4, lateral L3, and calcaneus in the degenerated disk group judged at the L2–L3 level than in the normal disk group (P < 0.05). BMD at the anteroposterior L2–L4 and calcaneus was significantly higher in the degenerated disk group judged at the L3–L4 level than in the normal disk group (P < 0.05). In conclusion, the BMD of not only the lumbar vertebrae but also the calcaneus and radius was mutually related to lumbar intervertebral disk degeneration from an early stage of degeneration. Received: May 16, 2002 / Accepted: July 31, 2002 Offprint requests to: Y. Nanjo     

The effects of menopause on longitudinal bone loss from the spine

Summary Two hundred and thirty women aged 45–66 years were divided into three groups according to their menopausal status and were followed to assess the changes in vertebral bone mineral density (BMD). These included 71 premenopausal, 42 perimenopausal, and 117 postmenopausal women. Menopausal status was assessed through menstrual history and plasma concentrations of 17 estradiol and luteinizing hormone. BMD was measured by dual photon absorptiometry between 2 and 5 times over an average period of 27 months, and annual rates of changes were calculated by linear regression. BMD decreased significantly (P<0.0001) in the three groups during the follow-up. Mean (±SD) annual rate of change was-0.79±1.5% for premenopausal,-2.35±1.5% for perimenopausal, and-1.24±1.5% for postmenopausal women. There was no difference in the rates of bone loss between the perimenopausal group and the postmenopausal group within 3 years after menopause (1–2 years:-2.34±2.1%; 2–3 years:-1.9±1.5%). Thereafter, rates decreased exponentially with time since menopause to fall out at the same level as the premenopausal level. These longitudinal data indicate that vertebral bone loss begins before menopause and accelerates sharply during menopause to decline exponentially with time after 3 years.     

CD38 is associated with premenopausal and postmenopausal bone mineral density and postmenopausal bone loss

One goal of osteoporosis research is to identify the genes and environmental factors that contribute to low bone mineral density (BMD) and fracture. Linkage analyses have identified quantitative trait loci (QTLs), however, the genes contributing to low BMD are largely unknown. We examined the potential association of an intronic polymorphism in CD38 with BMD and postmenopausal bone loss. CD38 resides in 4p15, where a QTL for BMD has been described. CD38−/− mice display an osteoporotic phenotype at 3 months, with normalization of BMD by 5 months. The CD38 polymorphism was identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 457 postmenopausal and 173 premenopausal Caucasian women whose spine and hip BMD was measured by dual energy X-ray absorptiometry (DXA). Influence of the CD38 polymorphism on bone loss was analyzed in 273 postmenopausal women over a follow-up of 2.94 ± 1.50 years. The CD38-PvuII polymorphism was significantly associated with premenopausal and postmenopausal (P = 0.001) lumbar spine BMD. Women homozygous for the G allele had >14% lower spinal BMD than women with GC/CC genotypes. An allele dose effect was observed at the spine in premenopausal (P = 0.002) and postmenopausal (P < 0.001) cohorts. The CD38-PvuII polymorphism was significantly associated with femoral neck BMD in pre- and postmenopausal women (P = 0.002 and P = 0.011, respectively). However, significance was lost following adjustment of hip BMD for covariates in the postmenopausal cohort (P = 0.081). The CD38-PvuII polymorphism was weakly associated with bone loss at the spine (P = 0.024), in postmenopausal women not taking hormone replacement therapy. We suggest that the CD38-PvuII polymorphism may influence the attainment and maintenance of peak BMD and postmenopausal bone loss.     

The association of endogenous hormone concentrations and bone mineral density measures in pre- and perimenopausal women of four ethnic groups: SWAN

 We evaluated bone mineral density (BMD), hormone concentrations and menstrual cycle status to test the hypothesis that greater variations in reproductive hormones and menstrual bleeding patterns in mid-aged women might engender an environment permissive for less bone. We studied 2336 women, aged 42–52 years, from the Study of Women's Health Across the Nation (SWAN) who self-identified as African-American (28.2%), Caucasian (49.9%), Japanese (10.5%) or Chinese (11.4%). Outcome measures were lumbar spine, femoral neck and total hip BMD by dual-energy X-ray densitometry (DXA). Explanatory variables were estradiol, testosterone, sex hormone binding globulin (SHBG) and follicle stimulating hormone (FSH) from serum collected in the early follicular phase of the menstrual cycle or menstrual status [premenopausal (menses in the 3 months prior to study entry without change in regularity) or early perimenopause (menstrual bleeding in the 3 months prior to study entry but some change in the regularity of cycles)]. Total testosterone and estradiol concentrations were indexed to SHBG for the Free Androgen Index (FAI) and the Free Estradiol Index (FEI). Serum logFSH concentrations were inversely correlated with BMD (r = −10 for lumbar spine [95% confidence interval (CI): −0.13, −0.06] and r = −0.08 for femoral neck (95% CI: −0.11, −0.05). Lumbar spine BMD values were approximately 0.5% lower for each successive FSH quartile. There were no significant associations of BMD with serum estradiol, total testosterone, FEI or FAI, respectively, after adjusting for covariates. BMD tended to be lower (p values = 0.009 to 0.06, depending upon the skeletal site) in women classified as perimenopausal versus premenopausal, after adjusting for covariates. Serum FSH but not serum estradiol, testosterone or SHBG were significantly associated with BMD in a multiethnic population of women classified as pre- versus perimenopausal, supporting the hypothesis that alterations in hormone environment are associated with BMD differences prior to the final menstrual period. Received: 10 September 2001 / Accepted: 8 July 2002 RID="*" ID="*" see Appendix for details     

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     

Circulating β2 Microglobulin in Relation to Bone Metabolism: Implications for Bone Loss with Aging

The aim of this cross-sectional study was to evaluate the relationships between circulating β₂ microglobulin (β₂ m) and bone mineral density (BMD), parameters of bone remodeling, vitamin D metabolites, parathyroid hormone (PTH), estradiol levels, and age in a group of 165 clinically healthy or osteoporotic, but otherwise normal untreated women. In this group of women, systemic β₂ m correlated with BMD (g/cm²) levels for total hip and Ward's triangle (r =−0.298, P < 0.0001; and r =−0.299, P < 0.0001, respectively), but only at the borderline level with BMD at the spine (r =−0.145, P= 0.0604). Serum β₂ microglobulin markedly correlated with age (r = 0.512, P= 0.0001). β₂ m levels correlated with indices of bone remodeling, as well as with serum creatinine and estradiol levels. However, after stratification of all analyses by age, body mass index, and serum 25OHD₃, 1,25(OH)₂D₃, PTH, or estradiol levels (using standard multiple regression and stepwise forward regression models), only 25OHD₃ was found to be an independent predictor of BMD at the hip, including Ward's triangle, as estradiol of BMD at the spine. On the other hand, β₂ m was not associated with BMD at any of the measured regions. Also, no association was found between serum PTH and BMD values. Therefore, systemic β₂ m seems to be an indicator of bone remodeling in the course of natural skeletal aging rather than a variable independently predicting bone loss. Received: 21 July 1998 / Accepted: 10 June 1999     

Bone Mineral Density of the Spine and Femur in Healthy Saudi Females: Relation to Vitamin D Status, Pregnancy, and Lactation

Bone mineral density (BMD) measurements of the anterio-posterior lumbar spine and the proximal femur using dual-energy x-ray absorptiometry, as well as relevant clinical and biochemical parameters, were determined in 321 healthy Saudi females in order to establish reference values and to study the effects of physical and lifestyle factors on BMD. Mean ± SD of age, body mass index (BMI), number of pregnancies, and total duration of lactation were 35.4 ± 11.3 years, 26.5 ± 5.2 kg/m², 3.1 ± 3.1, and 23.7 ± 42.4 months, respectively. Mean ± SD of serum calcium, 25-hydroxyvitamin D (25OHD), and PTH levels were 2.37 ± 0.09 mmol/liter, 24.5 ± 17.2 nmol/liter, and 52.0 ± 30.8 pg/ml, respectively. Peak BMD values were observed around age 35 years at the spine and earlier at the femur. Compared with USA females, Saudi females had lower weight-matched Z scores at the spine (−0.126 ± 1.078, P= 0.04), femoral neck (−0.234 ± 0.846, P < 0.0001), and Ward's triangle (−0.269 ± 1.015, P < 0.0001). Further, the prevalence of osteopenia and osteoporosis in subjects ≥31 years old were 18–41% and 0–7%, respectively, depending on the site examined. Severe hypovitaminosis D (25OHD level ≤20 nmol/liter) was present in 52% of the subjects. However, there was no correlation between 25OHD level and BMD at any site. Parathyroid hormone (PTH) levels correlated significantly with 25OHD levels (r =−0.28, P < 0.0001) and with weight-matched BMD Z scores at the spine (r =−0.17, P= 0.005), femoral neck (r =−0.16, P= 0.007), and Ward's triangle (r =−0.2, P= 0.0008), suggesting that the distribution of 25OHD levels in the cohort is below the threshold needed for maintaining normal BMD. On the other hand, number of pregnancies and total duration of lactation correlated with weight-matched BMD Z scores at the spine (r =−0.17, P= 0.003; r =−0.1, P= 0.08, respectively). We conclude that BMD in healthy Saudi females is significantly lower than in their USA counterparts. This may be due in part to increased number of pregnancies and longer duration of lactation together with prevalent vitamin D deficiency. Received: 21 July 1998 / Accepted: 1 November 1998     

Effect of menatetrenone on bone mineral density and incidence of vertebral fractures in postmenopausal women with osteoporosis: a comparison with the effect of etidronate

The purpose of the present study was to compare the effects of etidronate and menatetrenone on bone mineral density (BMD) and the incidence of vertebral fractures in postmenopausal women with osteoporosis. Seventy-two osteoporotic women, more than 5 years after menopause, 53–78 years of age, were randomly divided into three administration groups: E group; intermittent cyclical etidronate (200 mg/day, 14 days per 3 months; n = 25); M group; menatetrenone (45 mg/day, daily; n = 23); and C group (control); calcium lactate (2 g/day, daily; n = 24). Forearm BMD was measured by dual-energy X-ray absorptiometry at 0, 6, 12, 18, and 24 months after the treatment started. There were no significant differences in age, body mass index, years since menopause, and initial BMD among the three groups. One-way analysis of variance (ANOVA) with repeated measurements showed a significant decrease in BMD in the C group (P < 0.0001). Two-way ANOVA with repeated measurements showed a significant increase in BMD in the M group compared with that in the C group (P < 0.0001), and a significant increase in BMD in the E group compared with that in the C and M groups (P < 0.0001 and P < 0.01, respectively). The indices of new vertebral fractures/1000 patient-years in the E and M groups were significantly higher than that in the C group (χ² = 47.7; P < 0.0001 and χ² = 42.4; P < 0.0001, respectively), and did not differ significantly between the E and M groups. The present preliminary study provides evidence to suggest that, despite the lower increase in BMD produced by me-natetrenone, this agent, as well as etidronate, may have the potential to reduce osteoporotic vertebral fractures in postmenopausal women with osteoporosis. Received: January 9, 2001 / Accepted: June 8, 2001     

Influence of Body Mass Index on the Age-related Slope of Total and Regional Bone Mineral Content

The influence of body mass index (BMI) on T scores for total body bone mineral content (TBBMC) and regional bone mineral content (RBMC) was studied in 186 healthy women: 100 postmenopausal, 35 perimenopausal, and 51 premenopausal. The three groups were divided by BMI >25 kg/m² and BMI <25 kg/m² and the postmenopausal women were further subdivided by years since menopause (YSM): <10, 10–20, and >20. Tartrate-resistant acid phosphatase (TRAP) concentration was higher in perimenopausal and postmenopausal women with BMI <25 kg/m² (P < 0.001). T scores for TBBMC and for axial or peripheral RBMC differed (P < 0.05 in all) between women with BMI >25 kg/m² and BMI <25 kg/m². The rate of perimenopausal and postmenopausal age-related slope of BMC, as reflected in all measurements, differed with BMI. In the overall group of women, the T score for TBBMC correlated significantly with BMI (r = 0.46, P < 0.0001); this correlation increased when adjusted for age (r = 0.62, P < 0.0001). BMI correlated with TRAP only in postmenopausal women (r = 0.57, P < 0.0001). Yearly TBBMC decline was twice as high in postmenopausal women with BMI <25 kg/m² (P= 0.0004) than in those with BMI >25 kg/m²; the decline of trunk RBMC was more significant (P < 0.0001). These findings confirm the influence of BMI and gonadal status on bone mass. Received 20 February 1996 / Accepted 31 December 1996     

Differences in Bone Resorption after Menopause in Japanese Women with Normal or Low Bone Mineral Density: Quantitation of Urinary Cross-Linked N-Telopeptides

The objective of this study was to examine the value of NTx, a urinary cross-linked N-telopeptides of type I collagen, as a marker of bone resorption. We assessed changes in pre- and postmenopausal bone resorption by evaluating the correlation of NTx with L2–4 bone mineral density (BMD) in a total of 1100 Japanese women, aged 19–80 years [272 premenopausal (45.2 ± 6.2 years) and 828 postmenopausal (59.5 ± 6.2 years)]. Postmenopausal women were divided into three groups based on the range of BMD (normal, osteopenic, and osteoporotic). Within each group, subjects were further segregated according to years since menopause (YSM). NTx values were then evaluated for each group. Our results showed that BMD was significantly decreased (P < 0.05) and NTx was significantly increased (P < 0.01) after menopause in age-matched analysis. Consistent with a previous report, NTx was inversely correlated with BMD for the entire cohort of study subjects (r =−0.299), although NTx correlated better with premenopausal than postmenopausal BMD (r =−0.240 versus r =−0.086). This may have been due to the fact that elevated values of NTx were exhibited over the entire range of BMD present in the postmenopausal women, suggesting that NTx might respond faster to the estrogen withdrawal than BMD. In all postmenopausal women, regardless of the range of BMD, the increase in NTx reached a peak within 5 YSM. After 11 YSM, however, NTx remained elevated in the osteoporotic group but it decreased in the osteopenic group, and showed no significant change in the group of postmenopausal women with normal BMD. These findings suggest that bone resorption is dramatically increased within 5 years after menopause but remains increased only in osteoporotic women. Received: 29 April 1997 / Accepted: 12 August 1997     

Influence of number of pregnancies on bone mineral density in postmenopausal women of different age groups

 As data on the relationship between parity and bone mineral density often seem to be controversial, ultimately, a comprehensive research study was thought to be necessary. This study focused on examining the influence of the number of pregnancies on bone mineral density and investigating the relationship between pregnancy and bone mineral density at four sites in postmenopausal women of different age groups. A total of 509 postmenopausal women, varying from 45 to 86 years of age (mean age of 60.85 ± 7.53 years) were considered for the study. A standardized interview was employed to obtain information on demographics, lifestyle, and, reproductive and menstrual histories. Patients were separated into four groups according to the number of pregnancies, i.e., nulliparae (52 patients), one to two parity (66 patients), three to five parity (178 patients), and more than five parity (213 patients). The patients were further classified into two age groups, 40–59 years (233 patients) and 60–80 years (276 patients), respectively. The number of pregnancies was found to range from 0 to 17 (with an overall mean of 5.42 ± 3.68), with 4.29 ± 2.74 (range, 0–16) accounting for live births, while 1.02 ± 1.53 (range, 0–14) were abortions. There were no significant differences among the groups with respect to parameters such as, age, body mass index (BMI), age at menarche, age at menopause, and years since menopause (P > 0.05) in all of the 509 women and in the 40- to 59- and 60- to 80-year groups. When all the patients were considered, the bone mineral density (BMD) values of the spine and the trochanter for the more-than-five-parity group, were found to be significantly lower than those of the other groups (P < 0.05), while the BMD values of the spine and the femur (neck, trochanter) appeared to decrease with increasing parity. In the 40- to 59-year group, the BMD of the spine in both the nulliparae and one-to-two-parity groups was significantly higher than that of the more-than-five-parity group (P < 0.05). No significant differences were found among the groups with respect to the BMD values at any femur sites. The nulliparae patients in the 60- to 80-year group exhibited significantly higher trochanter and Ward's BMD values than those of the more-than-five-parity group (P < 0.05), whereas in the one-to-two-parity group, spine BMD values appeared to be significantly higher than those of the more-than-five-parity group (p < 0.05). Significant correlations were found between the number of pregnancies and BMD values for the spine (r = −0.23; P < 0.01), trochanter (r = −0.16; P < 0.01), and Ward's triangle (r = −0.14; P < 0.05), with no significant correlation for femur neck BMD (r = −0.08; P > 0.05) values. In conclusion, the present study suggests that the number of pregnancies has an effect on the BMD values and that this situation shows a variation in different age groups. In addition, our study indicates that there is a significant correlation between the number of pregnancies and the spine, trochanter, and Ward's triangle BMD, but there is no correlation for the femur neck BMD. Received: April 30, 2002 / Accepted: January 16, 2003 RID="*" ID="*" Offprint requests to: A. Gur     

Association of Grip Strength Change with Menopausal Bone Loss and Related Fractures: A Population-Based Follow-Up Study

The aim of the present study was to investigate the association between grip strength change and bone health according to menopausal status. A random sample of 971 pre- to postmenopausal women from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study cohort was measured with dual X-ray absorptiometry in the lumbar spine (LS) and femoral neck (FN) and grip strength with pneumatic squeeze dynamometer at baseline (1989–1991), 5 years (1994–1997), and 10 years (1999–2001). Fractures were recorded based on self-reports and validated from medical records. Women were divided into two groups according to change in grip strength quartile from baseline to 5-year follow-up: not improved (n = 735) and improved (n = 236). In the total population, the greatest bone loss was observed in perimenopausal (beginning of menopause during follow-up, n = 311) women [P < 0.001 vs. premenopausal women (n = 139)], and it declined in postmenopausal (n = 521) women [P < 0.001 by analysis of covariance (ANCOVA)]. The perimenopausal bone loss rate was significantly lower in women in the improved group in comparison to the not improved group (P < 0.01) in contrast to the pre- and postmenopausal groups (P > 0.05). Accordingly, there was a greater decline in perimenopausal LS and FN T-scores in the improved group vs. the not improved group over the first 5-year follow-up interval (P < 0.05 by ANCOVA) and remained unchanged over the 10-year follow-up. In perimenopausal women, there was a trend toward higher fracture-free survival rate in the improved group (82%) vs. the not improved group (88%) after 10 years. Adjustments did not change the results. In conclusion, maintenance of grip strength is associated with menopausal bone loss and future fractures.     

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