Long‐Term Exercise and Bone Mineral Density Changes in Postmenopausal Women—Are There Periods of Reduced Effectiveness?

There is increasing evidence that physical exercise can prevent fractures in postmenopausal women. However, even with careful adaptation of the exercise program to subjects' changing bone, health, and fitness status, effectivity may still decrease over the time. This could be specifically the case where the limitations of higher age collide with the specification of the exercise program. Thus, the aim of this study was to monitor bone mineral density (BMD) changes over a 16‐year period of supervised exercise. Our hypothesis was that BMD differences at lumbar spine (LS) and femoral neck (FN) between exercisers (EG) and nontraining controls (CG) increased throughout the intervention with significant differences for each of the four 4‐year observation periods. Sixty‐seven (EG, n = 39 versus CG, n = 28) initially early‐postmenopausal osteopenic women of the Erlangen Fitness and Osteoporosis Prevention Study (EFOPS) with complete BMD data sets for baseline (1998) and 4‐, 8‐, 12‐, and 16‐year follow‐up were included in the analysis. The exercise protocol initially focused on a high‐intensity strategy that addressed bone but increasingly shifted to a more comprehensive intervention. LS‐BMD differences between the EG and CG continuously increased (year 4: 2.4% (95%‐ Confidence Interval 1.0% to 3.8%), year 8: 3.1% (1.6% to 4.7%), year 12: 3.9% (1.9% to 5.8), year 16: 4.5% (2.5% to 6.6%). Correspondingly, rising differences for FN‐BMD (0.9% (–0.2% to 2.1%) versus 1.9% (0.4% to 3.3%) versus 2.0% (0.5% to 3.8%) versus 3.0% (1.0% to 5.0%)) were observed. However, in contrast to our hypothesis, group differences within the four 4‐year periods were not consistently significant (LS, p = 0.001 to 0.097; FN, p = 0.026 to 0.673); further, BMD kinetics among the groups varied between LS and FN. Of particular importance, significant differences (p ≤ 0.030) for both regions were still found in the final period. We conclude that exercise—even when adapted for subjects' decreasing bone, health, and fitness status—is consistently effective in favorably affecting BMD in (initially) early‐postmenopausal osteopenic women without any leveling‐off effect after 16 years of exercise. © 2015 American Society for Bone and Mineral Research.     

Vertebral Fracture Risk Is Reduced in Women Who Lose Femoral Neck BMD With Teriparatide Treatment

Response to osteoporosis therapy is often assessed by serial BMD testing. Patients who lose BMD without secondary causes of bone loss may be considered to be “nonresponders” to treatment. We examined vertebral fracture (VF) risk, change in lumbar spine (LS) BMD, and change in amino‐terminal extension peptide of procollagen type I (PINP) in postmenopausal women whose femoral neck (FN) BMD decreased, increased, or was unchanged after receiving teriparatide (TPTD) or placebo (PL) in the Fracture Prevention Trial. FN and LS BMD were measured at baseline and 12 mo. VFs were assessed by lateral spine radiographs at baseline and study endpoint. A BMD change from baseline of >4% was considered to be clinically significant. Decreases of >4% FN BMD were less common in women receiving TPTD (10%) versus PL (16%, p < 0.05), yet women on TPTD who lost FN BMD still had significant reductions in VF risk compared with PL (RR = 0.11; 95% CI = 0.03–0.45). VF risk reduction with TPTD compared with PL was similar across categories of FN BMD change from baseline at 12 mo (loss >4%, loss 0–4%, gain 0–4%, or gain >4%; interaction p = 0.40). Irrespective of FN BMD loss or gain, TPTD‐treated women had statistically significant increases in LS BMD and PINP compared with PL. In both groups, losses or gains in FN BMD at 12 mo corresponded to losses or gains in BMC rather than changes in bone area. In conclusion, loss of FN BMD at 12 mo in postmenopausal women with osteoporosis treated with TPTD is nevertheless consistent with a good treatment response in terms of VF risk reduction.     

Association between DHEAS and Bone Loss in Postmenopausal Women: A 15-Year Longitudinal Population-Based Study

Our aim was to examine the association between serum dehydroepiandrosterone sulfate (DHEAS) at baseline and BMD change at the femoral neck (FN) and lumbar spine (LS) in postmenopausal women during a 15-year follow-up. All participants were from the Chingford Study. BMD at the FN and LS were measured eight times during the 15-year follow-up by dual-energy X-ray absorptiometry. DHEAS at baseline was measured using radioimmunoassay. Data on height, weight, and hormone-replacement therapy (HRT) status were obtained at each visit. Multilevel linear regression modeling was used to examine the association between longitudinal BMD change at the FN and LS and DHEAS at baseline. Postmenopausal women (n = 1,003) aged 45–68 years (mean 54.7) at baseline were included in the study. After adjustment for baseline age, estradiol, HRT, and BMI, BMD at the FN decreased on average 0.49% (95% CI 0.31–0.71%) per year; and the decline was slowed down by 0.028% per squared year. Increase of DHEAS (each micromole per liter) was associated with 0.49% less bone loss at the FN (95% CI 0.21–0.71%, P = 0.001). However, this strong association became slightly weaker over time. Similar but weaker results were obtained for LS BMD. Our data suggest that high serum DHEAS at baseline is associated with less bone loss at both FN and LS and this association diminishes over time. The nature of the association is unclear, but such an association implies that, in managing BMD loss, women might benefit from maintaining a high level of DHEAS.     

High-intensity resistance training and postmenopausal bone loss: a meta-analysis

Introduction Conflicting evidence exists regarding the optimum exercise for postmenopausal bone loss. A systematic review and meta-analysis was undertaken to evaluate the effects of randomised controlled trials (RCTs) of progressive, high-intensity resistance training on bone mineral density (BMD) amongst postmenopausal women.Methods Structured electronic searching of multiple databases and hand-searching of key journals and reference lists was undertaken to locate relevant studies up to December 2004. Study quality and possible publication bias were assessed using recognised methods. Primary outcomes were absolute changes in BMD at the lumbar spine (LS), femoral neck (FN) and total hip (TH). A priori defined subgroup analyses included concurrent hormonal or antiresorptive therapy or calcium supplementation during the intervention. The weighted mean difference method (WMD) was used for combining study group estimates. Random or fixed effect models were applied according to study heterogeneity observed from the I ² statistic.Results At the LS, 14 RCT study groups were homogenous (I ²=25.2%) in demonstrating a significant increase (P=0.006) in BMD of 0.006 g/cm² (fixed effect; 95% CI 0.002–0.011) following high-intensity resistance training. In contrast, marked heterogeneity (I ²=88.2%) was apparent within 11 RCT study groups evaluating FN. For this comparison, a random effects model showed a positive change in FN BMD of 0.010 g/cm² (95% CI −0.002 to 0.021; P = 0.11). Subgroup analyses showed more anatomical variability of BMD responses to resistance training according to participants’ hormone therapy use. Treatment effects for study groups increasing all participants’ calcium intake showed significant positive BMD changes at TH (P=0.007). Methodological quality of all included studies was low, and a reporting bias towards studies with positive BMD outcomes was evident.Conclusions These findings are relevant to the nonpharmacological treatment of postmenopausal bone loss.     

Preferential low bone mineral density of the femoral neck in patients with a recent fracture of the proximal femur

Bone mass is an important determinant of resistance to fractures. Whether bone mineral density (BMD) in subjects with a fracture of the proximal femur (hip fracture) is different from that of age-matched controls is still debated. We measured BMD of the femoral neck (FN) on the opposite side to the fracture, as well as femoral shaft (FS) and lumbar spine (LS) BMD by dual-photon absorptiometry in 68 patients (57 women and 11 men, mean age 78.8±1.0) 12.4±0.8 days after hip fracture following a moderate trauma. These values were compared with BMD of 93 non-fractured elderly control subjects (82 women and 11 men), measured during the same period. As compared with the controls, FN BMD was significantly lower in fractured women (0.592±0.013 v. 0.728±0.014 g/cm²,P<0.001) and in fractured men (0.697±0.029 v. 0.840±0.052,P<0.05). Expressed as standard deviations above or below the mean BMD of age and sex-matched normal subjects (Z-score), the difference in FN BMD between fractured women and controls was highly significant (–0.6±0.1 v. +0.1±0.1,P<0.001). As compared with mean BMD of young normal subjects, BMD was decreased by 36.9±1.4 and 22.4±1.5% (P<0.001) in fractured and control women, respectively. There was no significant difference between FN BMD of 33 women with cervical and 24 with trochanteric hip fractures (0.603±0.017 v. 0.577±0.020). FN BMD was lower than 0.705 g/cm² in 90% of fractured women. The prevalence of fracture increased with decreasing FN BMD, reaching 100% with values below 0.500 g/cm². FS and LS BMD were significantly lower in women with hip fracture than in controls (1.388±0.036 v. 1.580±0.030,P<0.001, for FS, and 0.886±0.027 v. 0.985±0.023,P<0.01, for LS), but these differences were not significant when expressed as a Z-score. In men with a recent hip fracture, FS BMD was significantly lower than in controls (1.729±0.096 v. 2.069±0.062,P<0.01), but the difference at the LS level did not reach statistical significance. These results indicate that both women and men with a recent hip fracture had decreased bone mineral density of the femoral neck, femoral shaft and lumbar spine. However, the difference appeared to be of higher magnitude for the femoral neck suggesting a preferential bone loss at this site.     

Effects of different impact exercise modalities on bone mineral density in premenopausal women: a meta-analysis

Our objective was to assess the effects of differing modes of impact exercise on bone density at the hip and spine in premenopausal women through systematic review and meta-analysis. Electronic databases, key journals and reference lists were searched for controlled trials investigating the effects of impact exercise interventions on lumbar spine (LS), femoral neck (FN) and total hip (TH) bone mineral density (BMD) in premenopausal women. Exercise protocols were categorised according to impact loading characteristics. Weighted mean difference (WMD) meta-analyses were undertaken. Heterogeneity amongst trials was assessed. Fixed and random effects models were applied. Inspection of funnel plot symmetry was performed. Trial quality assessment was also undertaken. Combined protocols integrating odd- or high-impact exercise with high-magnitude loading (resistance exercises), were effective in increasing BMD at both LS and FN [WMD (fixed effect) 0.009 g cm⁻² 95% CI (0.002–0.015) and 0.007 g cm⁻² 95% CI (0.001–0.013); P = 0.011 and 0.017, respectively]. High-impact only protocols were effective on femoral neck BMD [WMD (fixed effect) 0.024 g cm⁻² 95% CI (0.002–0.027); P < 0.00001]. Funnel plots showed some asymmetry for positive BMD outcomes. Insufficient numbers of protocols assessing TH BMD were available for assessment. Exercise programmes that combine odd- or high-impact activity with high-magnitude resistance training appear effective in augmenting BMD in premenopausal women at the hip and spine. High-impact-alone protocols are effective only on hip BMD in this group. However, diverse methodological and reporting discrepancies are evident in published trials.     

Contribution of Lumbar Spine BMD to Fracture Risk in Individuals With T‐Score Discordance

Fracture risk estimates are usually based on femoral neck (FN) BMD. It is unclear how to address T‐score discordance, where lumbar spine (LS) T‐score is lower than FN T‐score. The objective of this work was to examine the impact of LS BMD on fracture risk, in individuals with lower LS T‐score than FN T‐score. Participants aged 60+ years from the Dubbo Osteoporosis Epidemiology Study with LS and FN BMD measured at first visit, and were followed from 1989 to 2014. Five‐hundred and seventy‐three (573) of 2270 women and 131 of 1373 men had lower LS than FN T‐score by ≥0.6 standard deviation (SD) (low‐LS group based on least significant change). In low‐LS women, each 1 SD lower LS T‐score than FN was associated with a 30% increase in fracture risk (hazard ratio [HR] 1.30; 95% CI, 1.11 to 1.45). For low‐LS men there was a 20% nonsignificant increase in fracture risk for each 1 SD lower LS than FN T‐score (HR 1.20; 95% CI, 0.10 to 1.67). Low‐LS women had greater absolute fracture risks than the rest of the women. This increased risk was more apparent for lower levels of FN T‐score and in older age groups. At an FN T‐score of –2, low‐LS women had a 3%, 10%, and 23% higher 5‐year absolute fracture risk than non‐low LS women in the 60 to 69 year, 70 to 79 year, and 80+ years age‐groups, respectively. Furthermore, an osteoporotic LS T‐score increased 5‐year absolute fracture risk for women with normal or osteopenic FN T‐score by 10% to 13%. Men in the low‐LS group had very few fractures; therefore, a meaningful analyses of fracture risk could not be conducted. This study shows the significant contribution of lower LS BMD to fracture risk over and above FN BMD in women. A LS BMD lower than FN BMD should be incorporated into fracture risk calculators at least for women in older age‐groups. © 2015 American Society for Bone and Mineral Research.     

Bone Mineral Density in Menopausal Women with Primary Hyperparathyroidism before and after Parathyroidectomy

The relationship between osteoporosis and primary hyperparathyroidism (pHPT) has not been definitely established because both diseases occur predominantly in postmenopausal women, and because PTH has a paradoxical effect on bone. We have investigated the prevalence of reduced bone mineral density (BMD) in women with pHPT, its relationship with metabolic parameters, and its course after parathyroidectomy. A prospective observational study was carried out on perimenopausal and postmenopausal women consecutively diagnosed and operated on for pHPT. Demographic data were recorded, as well as, PTH, Ca, calciuria/24h, P, vitamin D, adenoma weight. The BMD was measured at three sites: femoral neck (FN), proximal femur (PF), and lumbar spine (LS). Fifty-two patients were included with a mean age of 61 ± 12 years. The prevalence of reduced BMD ( 1SD, T-score) was 80%–100% depending on site. Parathyroid hormone was higher in patients with osteoporosis (319 ± 181 pg/ml) than in those with osteopenia (230 ± 83 pg/ml) or normal BMD (148 ± 81 pg/ml; p < 0,04). Twenty-eight patients were investigated 1 year after parathyroidectomy. The BMD improved significantly at all sites, particularly in patients with osteoporosis. Age correlated inversely with BMD increases at the femoral sites (r= –0,47; p = 0,02) but not at the LS. 25-OHD₃ plasma levels correlated inversely with BMD increases at PF (r= –0,76; p < 0,0001). In pHPT, there is a high prevalence of BMD abnormalities. No metabolic variables had a definite influence on BMD values but a tendency was observed for lower BMD in severe pHPT. One year after parathyroidectomy, there were significant BMD increases that were more marked at femoral sites, in younger patients, in patients with preoperative osteoporosis, and in those with lower plasma levels of 25-OHD₃.This article was presented at the International Association of Endocrine Surgeons meeting, Uppsala, Sweden, June 14–17, 2004.     

Effects of calcium supplements on femoral bone mineral density and vertebral fracture rate in vitamin-D-replete elderly patients

The efficacy of calcium (Ca) in reducing bone loss is debated. In a randomized placebo-controlled double-masked study, we investigated the effects of oral Ca supplements on femoral shaft (FS), femoral neck (FN) and lumbar spine (LS) bone mineral density (BMD), and on the incidence of vertebral fracture in vitamin-D-replete elderly. Ninety-three healthy subjects (72.1±0.6 years) were randomly allocated to three groups receiving 800 mg/day Ca in two different forms or a placebo for 18 months. Sixty-three patients (78.4±1.0 years) with a recent hip fracture were allocated to two groups receiving the two forms of Ca without placebo. FS BMD changes in Ca-supplemented non-fractured women were significantly different from those in the placebo group (+0.6±0.5% v –1.2±0.7%,p<0.05). There was no difference in effect between the two forms of Ca. The changes of +0.7±0.8% v –1.7±1.6% in FN BMD of Ca-supplemented women and the placebo group did not reach statistical significance. In fractured patients, FS, FN and LS BMD changes were –1.3±0.8, +0.3±1.6 and +3.1±1.2% (p<0.05 for the last). The rate of new vertebral fractures was 74.3 and 106.2 fractures per 1000 patient-years in Ca-supplemented non-fractured subjects and in the placebo group, respectively, and 144.0 in Ca-supplemented fractured patients. Thus, oral Ca supplements prevented a femoral BMD decrease and lowered vertebral fracture rate in the elderly.     

Prevalence and seasonal variation of hypovitaminosis D and its relationship to bone metabolism in community dwelling postmenopausal Hungarian women

Hypovitaminosis D can result in low bone mass. The prevalence of hypovitaminosis D has public health implications, especially where data are lacking. Since diet and sunlight are the two souces of vitamin D, the results obtained in one geographical region may not be universally applicable. The aim of this study is to characterize the prevalence and seasonal variation of hypovitaminosis D and its relationship to bone metabolism in community dwelling postmenopausal Hungarian women. We determined serum levels of 25-hydroxyvitamin D (25-OH-D), PTH, osteocalcin (OC), degradation products of C-terminal telopeptides of type-I collagen (CTx), dietary calcium intake and BMD at L2–L4 lumbar spine (LS) and femur neck (FN) in 319 randomly selected ambulatory postmenopausal women. The prevalence of hypovitaminosis D (serum 25-OH-D50 nmol/l) was 56.7%. On comparing patients with normal and low 25-OH-D, a significant difference was found in age (61.6±8.5 years versus 67.3±9.9 years; P<0.001), PTH (3.9±1.9 pmol/l versus 4.3±2.7 pmol/l; P<0.05), FN BMD (0.802±0.123 g/cm² versus 0.744±0.125 g/cm²; P<0.001) and dietary calcium intake (714.4±199.4 g/day versus 607.9±233 g/day; P<0.001). Osteoporotic patients had a significantly lower 25-OH-D (37.6±19.8 nmol/l versus 56.4±24 nmol/l; P<0.001) and dietary calcium intake (519.2±244.5 mg/day versus 718.2±164.3 mg/day; P<0.001). After controlling for all other variables, 25-OH-D was found to be significantly associated with age, the average hours of sunshine in the 3 months prior to 25-OH-D level determination and dietary calcium intake (r ²=0.190; P<0.001). For FN BMD, significant independent predictors were age, body mass index, 25-OH-D and dietary calcium intake (r ²=0.435; P<0.001). The prevalence of hypovitaminosis D during spring, summer, autumn and winter was 71%, 46.3%, 49.4% and 56.7%, respectively. There was significant seasonal variation in 25-OH-D, PTH, OC, calcium intake and FN BMD. There is a high prevalence of hypovitaminosis D in healthy postmenopausal Hungarian women, and FN BMD is associated with serum 25-OH-D and dietary calcium intake.     

Bone Mineral Density Increases in Trans Persons After 1 Year of Hormonal Treatment: A Multicenter Prospective Observational Study

Sex steroids are important determinants of bone acquisition and bone homeostasis. Cross‐sex hormonal treatment (CHT) in transgender persons can affect bone mineral density (BMD). The aim of this study was to investigate in a prospective observational multicenter study the first‐year effects of CHT on BMD in transgender persons. A total of 231 transwomen and 199 transmen were included who completed the first year of CHT. Transwomen were treated with cyproterone acetate and oral or transdermal estradiol; transmen received transdermal or intramuscular testosterone. A dual‐energy X‐ray absorptiometry (DXA) was performed to measure lumbar spine (LS), total hip (TH), and femoral neck (FN) BMD before and after 1 year of CHT. In transwomen, an increase in LS (+3.67%, 95% confidence interval [CI] 3.20 to 4.13%, p < 0.001), TH (+0.97%, 95% CI 0.62 to 1.31%, p < 0.001), and FN (+1.86%, 95% CI 1.41 to 2.31%, p < 0.001) BMD was found. In transmen, TH BMD increased after 1 year of CHT (+1.04%, 95% CI 0.64 to 1.44%, p < 0.001). No changes were observed in FN BMD (–0.46%, 95% CI –1.07 to 0.16%, p = 0.144). The increase in LS BMD was larger in transmen aged ≥50 years (+4.32%, 95% CI 2.28 to 6.36%, p = 0.001) compared with transmen aged <50 years (+0.68%, 95% CI 0.19 to 1.17%, p = 0.007). In conclusion, BMD increased in transgender persons after 1 year of CHT. In transmen of postmenopausal age, the LS BMD increased more than in younger transmen, which may lead to the hypothesis that the increase in BMD in transmen is the result of the aromatization of testosterone to estradiol. © 2017 American Society for Bone and Mineral Research.     

A C >T polymorphism located at position −1 of the Kozak sequence of CD40 gene is associated with low bone mass in Spanish postmenopausal women

SUMMARY: This study evaluated the association of a polymorphism in the CD40 gene with BMD and risk of osteopenia or osteoporosis in a population of 602 postmenopausal women. Results showed that women with the TT genotype had lower BMD at femoral neck and spine sites and increased risk of osteopenia or osteoporosis. INTRODUCTION: Recent findings have demonstrated that the CD40/CD40L system, which is of main importance for the immune system, can also be implied in the regulation of bone metabolism. The main objective of the present work has been to clarify whether single nucleotide polymorphisms (SNPs) affecting genes of CD40/CD40L system could be linked with abnormalities in the level of bone mineral density (BMD) in menopausal women. METHODS: We performed an association study of BMD values with a SNP located at position -1 of the Kozak consensus sequence of CD40 gene (rs1883832; C>T) in a population of 602 postmenopausal women. RESULTS: Women with the TT genotype (8.6% of women) displayed a reduction in femoral neck BMD (FN BMD) and lumbar spine BMD (LS BMD) of 6.2% and of 6.3%, respectively, as compared to women with CC + CT genotype. Logistic regression analysis adjusted for age, weight, and height showed that women with the TT genotype had increased risk for FN (odds ratio: 2.34; 95% CI: 1.12-4.89) and LS (odds ratio: 2.49; 95% CI: 1.19-5.24) osteopenia or osteoporosis. CONCLUSIONS: Women with the TT genotype in rs1883832 SNP affecting to Kozak consensus sequence of CD40 gene had lower BMD at FN and at LS sites and increased risk of osteopenia or osteoporosis.     

The Prevention of Osteoporosis Using Sequential Low-Dose Hormone Replacement Therapy with Estradiol-17β and Dydrogesterone

Low-dose hormone replacement therapy (HRT) in postmenopausal women may produce fewer side-effects but its efficacy in the prevention of bone loss and osteoporosis is not established. To address this we compared the effect of 1 mg estradiol-17β with a 2 mg dose, in combination with cyclical dydrogesterone, in the prevention of postmenopausal bone loss. We conducted a multicenter double-masked prospective randomized, placebo-controlled study in 595 apparently healthy postmenopausal women randomized to either placebo, or continuous oral estradiol-17β 1 mg or 2 mg with sequential dydrogesterone for 2 years. The primary endpoint was the percentage change from baseline in bone mineral density (BMD) in the lumbar spine (LS) and femoral neck (FN) of actively treated groups compared with placebo. Women taking either 1 mg or 2 mg estradiol-17β showed a significant increase in BMD of the LS (mean ± SD, 5.2 ± 3.8% and 6.7 ± 4.0% respectively, both p <0.001) whilst BMD in the placebo group decreased (–1.9 ± 4.0%). Increases were also observed in FN BMD in both treated groups (2.7 ± 4.2% and 2.5 ± 5.2% respectively, both p <0.001) in contrast to the placebo group (–1.8 ± 4.8%). The oldest women showed the greatest treatment response. One milligram estradiol-17β in combination with dydrogesterone is effective in conserving LS and proximal femur bone mass, both of which are clinically important sites of osteoporotic fracture, and is as effective as 2 mg in preventing FN bone. The lower dose of estradiol-17β is a particularly suitable treatment for osteoporosis management in older women since it should minimize side-effects and improve the acceptability of HRT. Received: 19 June 2000 / Accepted: 26 October 2000     

High prevalence of spine–femur bone mineral density discordance and comparison of vertebral fracture risk assessment using femoral neck and lumbar spine bone density in Korean patients

The aim of this study was to evaluate the prevalence of spine–femur discordance, and to compare the effectiveness of femoral neck (FN) and lumbar spine (LS) bone mineral density (BMD) for estimation of the risk of vertebral fractures. Women who were evaluated with dual energy X-ray absorptiometry between January 2001 and December 2005 were enrolled in this study. Vertebral fracture risk was calculated using initial FN and LS BMD. The follow-up vertebral X-rays from all subjects were reviewed, and the calculated estimated risk using the Fracture Risk Assessment Tool (FRAX^®) was compared with the actual prevalence of vertebral fractures during the follow-up period. Among a total of 443 women with a mean age of 58.5 years, 130 women (29.3 %) demonstrated femur–spine discordance (i.e., a difference between FN and LS BMD of >1 SD). Most subjects having discordance showed lower LS BMD (73.1 %) compared to FN BMD. During the mean 7-year follow-up period, 12 (2.7 %) vertebral fractures occurred. In cases with high estimated fracture risk (>20 % for estimated fracture risk), using LS BMD significantly reflected the actual vertebral fracture in total subjects [odds ratio (OR) 19.29, 95 % confidence interval (CI) 4.21–88.46], in subjects with spine–femur discordance (OR 16.00, 95 % CI 1.91–134.16), and in subjects with spine–femur discordance having lower LS BMD (OR 20.67, 95 % CI 1.63–262.71). In comparison, the estimated risk using FN BMD did not reflect the actual occurrence of vertebral fractures. In conclusion, a significant number of Korean subjects exhibited spine–femur discordance, and LS BMD might be more appropriate for estimation of vertebral fracture risk.     

Influence of weight and weight change on bone loss in perimenopausal and early postmenopausal Scottish women

Weight is recognized as an important factor in determining an individuals risk of osteoporosis. However, little is known about whether weight or weight change influences bone loss around the time of the menopause, and the relationship with energy intake and physical activity level remains largely undefined. Healthy premenopausal women (1,064 selected from a random population of 5,119 women aged 45–54 years at baseline) each had bone mineral density (BMD), weight and height measurements, and completed a food frequency and physical activity questionnaire. Of the original participants, 907 women (85.2%) returned 6.3 ± 0.6 years later for repeat BMD measurements, and 896 women completed the questionnaires. Bone loss at the hip (FN) and spine (LS) occurred before the menopause. Weight change rather than weight was associated with FN BMD loss (r=0.102, p=0.002), but weight at follow-up was associated with LS BMD change (r=0.105, p=0.002). Although an increase in physical activity level (PAL) appeared to be beneficial for FN BMD in women who were heavy weight gainers, PAL was associated with increased LS BMD loss in women who lost weight. For current HRT users, neither weight nor weight change was associated with change in BMD. Postmenopausal women not taking HRT should be made aware that low body weight or losing weight during this particularly vulnerable period may worsen bone loss.     

The contribution of serum osteoprotegerin to bone mass and vertebral fractures in postmenopausal women

Regulation of osteoclastic activity is critical for understanding bone loss associated with the postmenopausal period. In vitro and animal studies have revealed the role of OPG as a decoy receptor that neutralizes the effect of RANKL on the differentiation and activation of osteoclasts. However, the role of the OPG-RANKL system in postmenopausal osteoporosis is controversial. Thus, the aim of this study was to investigate the relationship among circulating levels of OPG, RANKL, bone turnover markers (BTM), bone mineral density (BMD) and vertebral fractures in postmenopausal women. We determined anthropometric parameters, circulating OPG and RANKL, BTM, estradiol, BMD by dual X-ray absorptiometry at the lumbar spine (LS) and femoral neck (FN), and pre-existing vertebral fractures in 206 ambulatory postmenopausal women of a mean age of 62 years (SD 7). Circulating OPG was significantly related to age ( r =0.158; P =0.023), years since menopause ( r =0.167; P =0.016) and BMD (LS Z-score: r =0.240; P =0.001, FN Z-score: r =0.156; P =0.025). Over half of the women had undetectable RANKL ( n =113; 54.9%). There were no significant differences in clinical variables, BTM or BMD among women with detectable vs. undetectable RANKL. OPG was found to be independently associated with osteoporosis (OR: 2.9, 1.4–5.9) and prevalent vertebral fractures (OR: 2.5, 1.2–5.4). We conclude that serum OPG levels are independently associated with bone mass and prevalent vertebral fractures in postmenopausal women.     

Sodium monofluorophosphate increases vertebral bone mineral density in patients with corticosteroid-induced osteoporosis

Corticosteroid-induced osteoporosis, which particularly affects the axial skeleton and the proximal femur, is characterized by a state of low bone remodelling. Fluoride is a potent stimulator of trabecular bone formation which could potentially be useful in the treatment of corticosteroid-induced osteoporosis. We investigated the effects of sodium monofluorophosphate (26 mg/day of fluoride) combined with 1000 mg of calcium (MFP-calcium-treated group), or of calcium alone (control), given for 18 months, on bone mineral density (BMD) of lumbar spine (LS), femoral neck (FN) and midfemoral shaft (FS) in 48 patients with corticosteroid-induced osteoporosis. Mean ages were 49.4±3.1 and 51.6±3.0 years (mean± SEM), duration of corticosteroid therapy 7.5±1.8 and 9.3±1.7 years, and mean daily dose of prednisone 18.2±2.3 and 12.1±1.1 mg in the MFP-calcium-treated group and controls, respectively. Initial BMDs (expressed as theZ-score, i.e. the difference in standard deviations from age- and sex-matched normal subjects) were –1.5±0.2 and –1.2±0.2 for LS, –1.4± 0.2 and –1.3±0.2 for FN, and –0.8±0.3 and –0.6±0.3 for FS, in the MFP-calcium-treated group and controls, respectively. Analysis by linear regression of 6-monthly measurement values revealed BMD changes of +7.8 ±2.2 versus + 3.6±1.3% (p<0.02) for LS, –1.5±1.8 versus +0.9 ±1.8% for FN, and –1.1±1.1 versus –0.5±1.4% for FS after 18 months of follow-up in the MFP-calcium-treated group and controls, respectively. For comparison, 17 patients with idiopathic osteoporosis (mean age 63.9±2.0 years), with initial BMDs of –1.3±0.4, –1.6±0.3 and –0.8±0.4 (Z-score for LS, FN and FS, respectively), received MFP and calcium for 22.1±1.7 months. BMD changes in idiopathic osteoporosis were +9.3±2.7% (p<0.005), –1.3±2.0% and +0.6± 0.9% for LS, FN and FS, respectively. These results indicate that the combination sodium monofluorophosphate and calcium was more efficient than calcium alone in increasing lumbar spine BMD in patients with corticosteroid-induced osteoporosis; neither femoral neck nor femoral shaft BMD was affected. Moreover, these effects were similar in patients with corticosteroid-induced and idiopathic osteoporosis.     

Determinants of bone mineral density in Chinese-American women

Summary Few data are available regarding bone mineral density (BMD) and its determinants among Chinese Americans. We identified determinants of BMD among 359 Chinese-American women in order to identify risk factors for low BMD in this burgeoning population. BMD in Chinese-American women is influenced by a number of factors, including immigration. Introduction Osteoporosis and low BMD are common among Chinese women, including Chinese Americans, who are a growing population at risk for osteoporosis in the US. Few data are available regarding BMD and its determinants among Chinese-American women. Methods In this study, we examined predictors of BMD in 359 ambulatory Chinese-American women, ages 20–90, using stepwise multiple regression analysis. Variables in the model included age, weight, height, menarche age, years since menopause, immigration age, years in US, percentage of life in US, number of pregnancies, oral contraceptive use, family history of osteoporosis, family history of hip fracture, daily calcium intake, exercise, time outdoors, alcohol consumption and tobacco use. Results Among premenopausal women, weight was the strongest predictor of BMD, accounting for 10.5% of the variance at the lumbar spine (LS), 15.2% at the total hip (TH) and 16.6% at the femoral neck (FN). Time outdoors was also a positive predictor of BMD (1.4% at LS, 2.8% at TH and 1.6% at FN), while family history of osteoporosis (1.4% at TH) and age (3.7% at FN) were negative predictors. Among postmenopausal women, greater BMD at the LS and TH was associated with greater weight and earlier immigration age. Weight accounted for 16.4% of the variance at the LS and 19.8% at the TH; immigration age accounted for 3.1% of the variance at the LS and 4.1% at the TH. At the FN, years since menopause and weight were predictors of BMD, accounting for 14.4% and 8.7% of the variance, respectively. While older age at immigration had a negative effect on BMD, years in and proportion of life in the United States were not significant predictors of BMD. Conclusions Bone mineral density in Chinese-American women is influenced by a number of biological and lifestyle factors, including immigration. The results of this study provide new insights into risk factors for low bone density as they relate to environmental determinants in the growing population of Chinese-American women.     

Response to Alendronate in Osteoporosis after Previous Treatment with Etidronate

Bisphosphonates such as etidronate and alendronate are widely accepted as effective agents for the treatment of osteoporosis. However, some physicians find the choice of which one to use in different patients, and the comparative magnitude of response, unclear. Fifty postmenopausal women with osteoporosis [group 1: 27 women who had received 3 years of previous cyclical etidronate treatment, mean age 70.5 years, bone mineral density (BMD) mean T-score lumbar spine (LS) −3.58 and femoral neck (FN) −2.51; group 2: 23 women who had not previously received cyclical etidronate treatment, mean age 73.7 years, BMD mean T-score LS −3.65 and FN −2.96] were treated with 10 mg alendronate daily, to determine whether pretreatment with etidronate affected the response to alendronate, and whether patients who did not respond to etidronate, responded to alendronate. There was a significant increase in LS BMD after 2 years of treatment with alendronate compared with baseline (group 1: 7.84%, p<0.001; group 2: 6.69%, p<0.001), but there was no statistical difference between the groups. In the group 1 patients there was a significant difference between the initial response (at the LS BMD) to 2 years of cyclical etidronate (1.86%) and later response to 2 years of alendronate (7.84%) (p<0.0001). The 10 patients who did not respond at the LS to etidronate alone, showed a significantly better response (mean BMD change +6.3%) when subsequently treated with alendronate (a net difference of 9.3%, p = 0.002). In 15 patients who did not respond at the FN to etidronate alone, the mean response to alendronate was +0.96% (a difference of 7%, p = 0.004). This study shows that pretreatment with 3 years of cyclical etidronate is not detrimental to the subsequent LS BMD response to alendronate. There is evidence that alendronate produced a greater bone density response than etidronate, and patients who did not respond to etidronate with an increase in LS bone density, subsequently did so following alendronate. Received: 22 June 1999 / Accepted: 18 January 2000     

Home-based resistance training improves femoral bone mineral density in women on hormone therapy

This study tested whether moderate resistance training would improve femoral bone mineral density (BMD) in long-term users of hormone therapy with low BMD. The study was a 2-year randomized, controlled, trial (RCT) of moderate resistance training of either the lower extremity or the upper extremity. Eighty-five women participated in a 6-month observation period. The setting was center-based and home-based training. The participants were 189 women aged 59–78 years, with total femur T-scores from –0.8 to –2.8 and on hormone therapy (HT) for a minimum of 2 years (mean 11.8 years); 153 completed the trial. Lower extremity training used weight belts (mean 7.8 kg) in step-ups and chair rises; upper extremity training used elastic bands and dumbbells. Measurements were BMD and body composition [dual-energy X-ray absorptiometry (DXA)], bone turnover markers. Total femoral BMD showed a downward trend during the observation period: 0.35%±0.18% (P=0.14). The response to training was similar in the upper and lower groups in the primary outcomes. At 2 years, total femoral BMD increased 1.5% (95% CI 0.8%–2.2%) in the lower group and 1.8% (95% CI 1.1%–2.5%) in the upper group. Trochanter BMD increased 2.4% (95% CI 1.3%–3.5%) in the lower group and 2.5% (95% CI 1.4%–3.6%) in the upper group (for both analyses time effect P<0.001). At 1 year, a bone resorption marker (C-telopeptide) decreased 9% (P=0.04). Bone formation markers, bone-specific alkaline phosphatase, decreased 5% (P<0.001), and N-terminal type I procollagen peptide decreased 7% (P=0.01). Body composition (percent lean and percent body fat) was maintained in both groups. We concluded that long-term moderate resistance training reversed bone loss, decreased bone turnover, increased femur BMD, and maintained body composition. The similarity of response in upper and lower groups supports a systemic response rather than a site-specific response to moderate resistance training.