Intramuscular Neridronate in Postmenopausal Women with Low Bone Mineral Density

Compliance to osteoporosis treatment with oral bisphosphonates is very poor. Intermittent intravenous bisphosphonate is a useful alternative, but this route is not readily available. Neridronate, a nitrogen-containing bisphosphonate that can be given intramuscularly (IM), was tested in a phase 2 clinical trial in 188 postmenopausal osteoporotic women randomized to IM treatment with 25 mg neridronate every 2 weeks, neridronate 12.5 or 25 mg every 4 weeks, or placebo. All patients received calcium and vitamin D supplements. The patients were treated over 12 months with 2-year posttreatment follow-up. After 12-month treatment, all three doses were associated with significant bone mineral density (BMD) increases at both the total hip and spine. A significant dose–response relationship over the three doses was observed for the BMD changes at the total hip but not at the spine. Bone alkaline phosphatase decreased significantly by 40–55% in neridronate-treated patients, with an insignificant dose–response relationship. Serum type I collagen C-telopeptide decreased by 58–79%, with a significant dose–response relationship (P < 0.05). Two years after treatment discontinuation, BMD declined by 1–2% in each dose group, with values still significantly higher than baseline at both the spine and the total hip. Bone turnover markers progressively increased after treatment discontinuation, and on the second year of follow-up the values were significantly higher than pretreatment baseline. The results of this study indicate that IM neridronate might be of value for patients intolerant to oral bisphosphonates and unwilling or unable to undergo intravenous infusion of bisphosphonates.     

Klotho Gene Polymorphisms are Associated with Osteocalcin Levels but not Bone Density of Aged Postmenopausal Women

Osteoporosis is known to have a strong genetic basis. It has been proposed that polymorphisms within the KL (klotho) gene have a significant effect on aging, in particular, the osteoblast defect of aging. The association between polymorphisms within this gene and biochemical markers of bone formation and resorption, bone structure, and fracture rates was studied in 1,190 postmenopausal women with a mean age of 75 years. Genotyping of these polymorphic sites was carried out using Matrix-Assisted Laser Desorption Ionization—Time of Flight (MALDI-ToF) mass spectrometry. The G allele of SNP c.1775G>A was associated with a lower osteocalcin level than the A allele (P = 0.004) in a codominant model. SNPs C-387T and IVS1+8262c>t both showed nonsignificant associations with osteocalcin (P values of 0.063 and 0.068, respectively), but a haplotype analysis of 2 of 5 haplotypes of the three SNPs with a frequency greater than 4% revealed a significant association with osteocalcin (P = 0.036). None of the individual polymorphisms or haplotypes analyzed showed any associations with a marker of bone resorption the deoxypyridinoline creatinine ratio, bone structure, or fracture data. Therefore, the G polymorphism within the c.1775G>A SNP site and a haplotype including this are associated with a reduced osteoblast product osteocalcin. These data suggest that variation in the KL gene product affects osteoblast activity independent of osteoclast activity but that this defect does not result in an effect on bone structure in this population, perhaps because of “rescue” by other genetic or environmental factors in this population.     

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.     

Determinants of Bone Mineral Density and Spinal Fracture Risk in Postmenopausal Japanese Women

The present study analyzed the factors that determine bone mineral density (BMD) and predict spinal fracture risk in postmenopausal Japanese women. Two hundred and five postmenopausal Japanese women aged 48–84 years (mean age 64 years) were enrolled in the cross-sectional study. BMD of the lumbar spine, femoral neck and total body as well as body composition were measured by dual-energy X-ray absorptiometry (DXA). Mid-radial BMD was measured by single-photon absorptiometry. We also determined serum levels of insulin-like growth factor (IGF)-I, IGF binding protein-2, -3 and osteocalcin as well as urinary levels of pyridinoline (Pyr), deoxy-Pyr (D-Pyr) and growth hormone. Multiple regression analysis revealed that lean body mass (LBM) was positively correlated with BMD at all sites. In contrast, femoral neck BMD was highly related to fat mass as well as LBM, although fat mass was not an independent correlate of total body and mid-radial BMD. LBM and urinary D-Pyr were crucial determinants at all sites except the mid-radius in stepwise regression analysis. Fat mass and serum IGF-I were determinants of femoral neck and mid-radial BMD, respectively. In terms of reproductive history, parity affected lumbar BMD. Factors affecting BMD differed according to the site. On the other hand, lumbar BMD as well as serum levels of IGF-I and albumin were selected as predictors of spinal fracture risk in multiple logistic regression analysis. Lumbar BMD, serum IGF-I and LBM were selected in women with lumbar BMD above 0.727 g/cm². In conclusion, the present study indicates that LBM is a more important determinant of BMD than fat mass at any site except the femoral neck. Age, serum IGF-I and urinary D-Pyr were also determinants of BMD, dependent on the regions measured. Lumbar BMD and LBM as well as serum levels of IGF-I and albumin were useful markers which predicted the risk of osteoporotic spinal fractures in postmenopausal Japanese women. Received: 6 June 2000 / Accepted: 11 January 2001     

Association Study of Parathyroid Hormone Gene Polymorphism and Bone Mineral Density in Japanese Postmenopausal Women

Association of BST B1 restriction fragment length polymorphism (RFLP) of the parathyroid hormone (PTH) gene with bone mineral density (BMD) was examined in 383 healthy postmenopausal women in Japan who were unrelated. The RFLP was represented as B or b, the capital letter signifying the presence of and the small letter the absence of restriction site for BST B1. The frequency of each genotype—BB, Bb, and bb—was 82.5%, 16.7%, and 0.8%, respectively. When we statistically compared age, years after menopause, body height, and body weight between the BB genotype and the Bb genotype groups, there was no significant difference between the groups. However, the lumbar BMD and the score of BMD adjusted for age and body weight (Z score) were significantly lower in the group of genotype Bb than in the BB: 0.859 ± 0.019 g/cm² versus 0.925 ± 0.011 (mean ± SE, P= 0.01) and −0.412 ± 0.138 versus 0.067 ± 0.082 (mean ± SE, P= 0.01). In addition, the Z score of total body BMD in the Bb genotype group was lower than that in the BB group. Comparison of serum and urinary biochemical bone metabolic markers suggested that the subjects with Bb genotype might be in a relatively higher state of bone turnover than those with BB genotype. These results suggest that the polymorphism in the PTH gene would be a useful genetic marker for lower BMD and the susceptibility for osteoporosis. Received: 19 March 1998 / Accepted: 24 June 1998     

The Asn19Lys Substitution in the Osteoclast Inhibitory Lectin (OCIL) Gene is Associated with a Reduction of Bone Mineral Density in Postmenopausal Women

Osteoclast inhibitory lectin (OCIL) is a newly recognized inhibitor of mouse and human osteoclast differentiation whose cellular expression is similar to that of receptor activator of nuclear factor kappaB (RANKL). The main objective of the present work was to elucidate whether naturally occurring single-nucleotide polymorphisms (SNPs) in this gene could be associated with bone mass in postmenopausal women. To that end, we studied the association of bone mineral density (BMD) measured by dual-energy X-ray absorptiometry with two nonsynonymous SNPs in the OCIL gene resulting in Asn19Lys and Leu23Val substitutions in a population of 500 postmenopausal Spanish women. A weak association was detected for Asn19Lys SNP with femoral neck (FN) BMD and lumbar spine (LS) BMD in the whole population. When the population was stratified by age, however, the association was strong in older women (> or =53 years). Thus, in this group of participants, women with CG/GG genotype displayed reductions of 5.6% and 6.7% in FN BMD and LS BMD adjusted by age and body mass index (BMI), respectively, compared to women with CC genotype. The Asn19Lys SNP alleles explained about 7% of BMD variance in older women but only 1.7-3.9% in the whole population in regression models including age and BMI. In conclusion, women with a lysine (GG genotype) at position 19 of the OCIL protein displayed lower BMD at femoral neck and at lumbar spine sites than women having an asparagine residue. Since the OCIL protein inhibits osteoclast differentiation, this amino acid substitution could have consequences for OCIL functionality.     

Bone Mineral Density in French Canadian Women

This cross-sectional study investigated bone mineral density (BMD) at the lumbar spine (L2–4) and femoral neck in French Canadian women residing in the Quebec city area. Data collection was initiated in 1988 and completed in 1994. A total of 747 French Canadian Caucasian women (16–79 years of age) with no metabolic bone disease were evaluated. BMD measurements were obtained using dual-photon absorptiometry (DPA) or dual-energy X-ray absorptiometry (DXA). Anthropometric measures such as weight, height and body mass index (BMI) were recorded. Medical files provided information on demographic characteristics, hormonal profile and lifestyle habits. Results show a curvilinear trend of BMD with aging. Furthermore, the peak BMD at the lumbar spine (L2–4) was reached at 29 years followed by a stable phase until 35 years, after which BMD started to decrease. The pattern of bone evolution at the femoral neck was different, peak BMD being achieved earlier, at 21 years, while after age 26 years a significant decrease was already observed. Women older than 60 years showed the lowest BMD. Regression analysis showed that age, weight and height are determinants of BMD at the lumbar spine and explained 33.9% of inter-individual variation. At the femoral neck, 29.1% of variation was explained by age and height only. In conclusion, our data suggest that French Canadian women have a different pattern of bone loss at the femoral neck compared with the lumbar spine, according to their mean BMD values. Received: 21 July 1997 / Accepted: 15 October 1997     

Cytokine Production and Bone Mineral Density at the Lumbar Spine and Femoral Neck in Premenopausal Women

Cytokines such as interleukin-1 (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) can influence both bone resorption and bone formation. The objective of this cross-sectional study was to examine the relationship between cytokine production by peripheral blood mononuclear cells (PBMC) and bone mineral density (BMD); the annual rate of change in BMD was examined. Subjects participating in a randomized clinical trial entitled the Women's Healthy Lifestyle Project in Allegheny County, Pennsylvania were used. They included 50 healthy premenopausal women, aged 45–52 years, who had regular menses within the past 3 months and were not on replacement estrogens. Dual-energy X-ray absorptiometry measurements at the AP lumbar spine and femoral neck were made at baseline and at the first annual exam using a Hologic QDR 2000 densitometer. Cytokine production of IL-1β, IL-6, and TNF-α by PBMC was measured at the annual exam. The median values for stimulated cytokine production by PBMC were 3.92 ng/ml, 31.3 ng/ml, and 1.05 ng/ml, for IL-1β, IL-6, and TNF-α, respectively. There were modest correlations between cytokine production and cross-sectional BMD, ranging from r =−0.30 to r =−0.13. Trends of greater spinal bone loss were observed in women with ``high' (≥75th percentile) cytokine production of stimulated IL-1β and IL-6 (IL-1β: ``high' =−1.56% ± 0.70 versus ``low' (<75th percentile) =−0.56% ± 0.35, P= 0.21). In contrast, greater annual gains in femoral neck BMD were observed in those with high cytokine production of IL-1β and IL-6 (IL-1β: high = 3.39% ± 1.16 versus low =−0.85 ± 0.58, P= 0.002). There was no association between stimulated TNF production and annual change in BMD. In this population of healthy premenopausal women, the relationship between cytokine production by PBMC and the rate of change in BMD was significantly different for the lumbar spine and femoral neck, possibly reflecting differences in the proportion of trabecular and cortical bone at these sites. Received: 5 February 1997 / Accepted: 11 May 1998     

Association of Methylenetetrahydrofolate Reductase (MTHFR) Polymorphism with Bone Mineral Density in Postmenopausal Japanese Women

The pathogenesis of osteoporosis is controlled by genetic and environmental factors. Considering the high prevalence of osteoporosis in homocystinuria, abnormal homocysteine metabolism would contribute to the pathogenesis of osteoporosis. It is known that the polymorphism of methylenetetrahydrofolate reductase (MTHFR), the enzyme catalyzing the reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, correlates with hyperhomocysteinemia. In this study, we examined the association of this polymorphism with bone mineral density (BMD). BMD was measured by dual-energy X-ray absorptiometry (DXA) in 307 postmenopausal women. MTHFR A/V polymorphism was analyzed using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). We compared BMD, clinical characteristics, and bone metabolic markers among MTHFR groups (AA, AV, VV). The groups did not differ in terms of baseline data. The values of lumbar spine BMD and total body BMD were as follows: lumbar spine: AA, 0.91 ± 0.18, AV, 0.88 ± 0.16, VV, 0.84 ± 0.14 g/cm²; total body: AA, 0.97 ± 0.11, AV, 0.96 ± 0.11, VV, 0.93 ± 0.09 g/cm². In the VV genotype, lumbar spine BMD values were significantly lower than those of the women with the AA genotype (P= 0.016) and total body BMD was significantly lower than those of the women with AA genotype (P= 0.03) and AV genotype (P= 0.04). This is the first report that suggests that the VV genotype of MTHFR is one of the genetic risk factors for low BMD. Received: 29 March 1999 / Accepted: 20 September 1999     

Long-Term Vegetarian Diet and Bone Mineral Density in Postmenopausal Taiwanese Women

This study examined bone density among postmenopausal Buddhist nuns and female religious followers of Buddhism in southern Taiwan and related the measurements to subject characteristics including age, body mass, physical activity, nutrient intake, and vegetarian practice. A total of 258 postmenopausal Taiwanese vegetarian women participated in the study. Lumbar spine and femoral neck bone mineral density (BMD) were measured using dual-photon absorptimetry. BMD measurements were analyzed first as quantitative outcomes in multiple regression analyses and next as indicators of osteopenia status in logistic regression analyses. Among the independent variables examined, age inversely and body mass index positively correlated with both the spine and femoral neck BMD measurements. They were also significant predictors of the osteopenia status. Energy intake from protein was a significant correlate of lumbar spine BMD only. Other nutrients, including calcium and energy intake from nonprotein sources, did not correlate significantly with the two bone density parameters. Long-term practitioners of vegan vegetarian were found to be at a higher risk of exceeding lumbar spine fracture threshold (adjusted odds ratio = 2.48, 95% confidence interval = 1.03–5.96) and of being classified as having osteopenia of the femoral neck (3.94, 1.21–12.82). Identification of effective nutrition supplements may be necessary to improve BMD levels and to reduce the risk of osteoporosis among long-term female vegetarians. Received: 10 May 1996 / Accepted: 9 August 1996     

Occupational Activity and Bone Mineral Density in Postmenopausal Women in England

Few studies have assessed the relationship between occupational activity and bone mineral density (BMD), although two case–control studies have reported a protective effect of occupational activity on hip fracture. In the present study 580 postmenopausal women aged 45–61 years completed a risk factor questionnaire including a detailed occupational history. For each job, hours spent sitting, standing, walking, lifting and carrying were recorded; these measures, evaluated at ages 20, 30, 40 years, in the current job and over the working lifetime, were used in the analysis. BMD was measured with dual-energy X-ray absorptiometry, and measurements at five sites were used in a multiple regression analysis adjusting for potential confounding variables. There was a significant negative association between sitting at age 20 years and BMD at the radius (p= 0.037), with negative relationships of borderline significance at the anteroposterior spine (p = 0.091) and whole body (p= 0.078). There were significant positive associations between standing at age 30 years and BMD at all five sites (p<0.05), but no significant linear associations for standing at ages 20 and 40 years. No significant associations were found for lifetime or current occupational measures of sitting, standing, walking and lifting or carrying. The lack of consistency of these significant findings suggests that they may have occurred by chance, and that occupational activity has little if any effect on BMD in postmenopausal women. Received: 12 March 1999 / Accepted: 17 September 1999     

Bone Mineral Densitometry Substantially Influences Health-Related Behaviors of Postmenopausal Women

Although bone mineral density measurements are helpful in predicting future risk for osteoporotic fractures, there is limited information available on how the results of bone densitometry influence a woman's use of therapeutic alternatives. To assess the role of bone mineral densitometry in influencing postmenopausal women to change health behaviors associated with osteoporosis, we prospectively followed, for an average of 2.9 years, 701 postmenopausal women over 50 years of age referred to an osteoporosis prevention program in a large metropolitan area. Assessments included bone mineral densitometry by dual-energy X-ray absorptiometry (with classification of skeletal health), medical history, use of hormone replacement therapy, calcium intake, caffeine intake, exercise, smoking habits, and fall precaution measures. Women classified at baseline with moderate low bone mass were twice as likely (33%), and women with severe low bone mass more than three times as likely (47%) to start hormone replacement therapy compared with women with a normal result (13%, P < 0.001). This was true regardless of whether they had taken hormone replacement therapy in the past. Below-normal BMD was a strong predictor of a woman's initiation of hormone replacement therapy (OR 4.2; 95% CI 2.7–6.4; P < 0.05) even after adjustment for age, education, history of osteoporosis or fracture, and medical condition related to osteoporosis. Women with moderate or severe low bone mass were also much more likely to start calcium supplements (81–90% versus 67%), increase dietary calcium (71–82% versus 60%), decrease use of caffeine (44–60% versus 34%), start exercising (61–76% versus 52%), and quit smoking (22–24% versus 11%) relative to their behaviors prior to testing (P < 0.01). In conclusion, postmenopausal women report that the results of bone densitometry substantially influence the decision to begin hormone replacement therapy and calcium supplements, increase dietary calcium, decrease caffeine, increase exercise, decrease smoking, and take precautions to prevent falls. More studies are needed to measure the long-term effects of this influence. Received: 19 March 1999 / Accepted: 13 August 1999     

Bone Mineral Density of the Spine and Femur in Healthy Moroccan Women

Bone mineral density (BMD) measurements using dual-energy X-ray absorptiometry (DXA) are widely used to diagnose osteoporosis and assess its severity. Previous studies show the necessity to establish reference data for bone mass measurements for each particular population. Such data are lacking for the Moroccan population. The aim of this study was to determine spine and femur BMD reference values for the Moroccan female population and to compare them with values from western and other Arab countries. A cross-sectional study of 569 Moroccan women, (randomly selected in the area of Rabat, the capital of Morocco, aged between 20 and 79 yr) was carried out to establish reference values of BMD. Measurements were taken at the lumbar spine and proximal femurs using DXA (Lunar Prodigy Vision, GE). The data were compared with published normative data taken by United States (U.S.), European, Kuwaiti, Lebanese, and Saudi women over 6 decades of age. The percentage of osteoporosis in postmenopausal women using our reference curve was compared to that observed when the other curves (US, European and Arab) implemented in the Lunar machine was used. Our results showed that the Moroccan women showed the expected decline in BMD at both sites with age after peaking at 20–29 years of age. Moroccan females have lower BMD at the spine than U.S., Europeans, and Kuwaitis (approximately 10–12% for patients older than 50 yr). The BMD values of the total femur in Moroccan females were close to western (European and American), and Kuwaitis, but higher than Lebanese and Saudis. Using our reference database, 37.9% of postmenopausal women had spine osteoporosis vs. 39.6% and 23.4% using US/European and Arabic Lunar reference values respectively. At the femurs, 6.7% had osteoporosis vs. 2.5% using the Arabic Lunar reference values. In conclusion, our study emphasizes the importance of using population-specific reference values for BMD measurements to avoid over or underdiagnosis of osteoporosis.     

Bone Mineral Density is a Prognostic Factor for Postmenopausal Caucasian Women with Breast Cancer

Numerous studies have convincingly shown that women with low bone mineral density have lower risk of breast cancer. As many risk factors for breast cancer are also prognostic factors, we hypothesized that women with breast cancer and low bone mineral density will have lower breast cancer recurrence rates than women with normal bone densities. A prospectively collected data base of breast cancer patients was used to identify postmenopausal Caucasian women. Their records were reviewed and 309 patients with complete follow‐up and bone density tests within 1 year of their surgery were identified. The outcome of patients with low bone density (t > ?1.0) was compared to the outcome for patients with normal bone density (t < ?1.1). Among the 193 patients with invasive breast cancers and low bone density, distant disease‐free survival at 5 years was 96% compared to 84% for 114 patients with invasive breast cancers and normal bone density (p = 0.0239). Local disease‐free survival was 94% for low bone density patients compared to 86% for patients with normal bone densities (p = 0.0794). Bone mineral density is a significant prognostic factor for postmenopausal Caucasian women with breast cancer. Low bone mineral density is associated with a lower local and distant rate of recurrence.     

Colles' Fracture of the Wrist as an Indicator of Underlying Osteoporosis in Postmenopausal Women: A Prospective Study of Bone Mineral Density and Bone Turnover Rate

Colles' fracture has been shown to be associated with an increased risk of hip fracture. The incidence of low bone mineral density (BMD) and high bone turnover in such patients is uncertain. The aim of this study was to prospectively assess BMD and bone turnover in a cohort of consecutive postmenopausal Colles' fracture patients. BMD (spine, hip and contra-lateral radius) was measured by dual-energy X-ray absorptiometry (DXA) within 2 weeks of fracture. Bone turnover was assessed within 4 days by measurement of serum osteocalcin, total alkaline phosphatase (TALP), bone-specific alkaline phosphatase (BSAP) and urine hydroxyproline. We recruited 106 (71%) of 149 consecutive patients. Fifty-one per cent of subjects had a history of previous fracture, and 25% a past history of wrist, hip or vertebral body fracture. The incidence of osteoporosis was 21%, 42% and 22% at the spine, hip and radius respectively. Fifty per cent of subjects had osteoporosis of at least one of these sites. When compared with the values expected for their age the patients were found to have higher BMD than expected at the spine, and slightly lower BMD at the hip and distal radius. Patients aged 65 years or less had lower hip BMD than expected from the age-matched normal range (p < 0.01). Osteocalcin and TALP levels did not differ from the normal ranges, but BSAP and hydroxyproline levels were significantly elevated (p < 0.001), within 37% and 25% of patients having levels above the respective normal ranges. We conclude that osteoporosis is common in patients with Colles' fracture; however, in older patients BMD is not lower than would be expected in the normal population. In patients aged 65 years or less BMD is lower than expected at the hip. Bone turnover rate is high in many such patients. Intervention to prevent future fracture would be appropriate in women aged 65 years or less with Colles' fracture.     

Low Sit-to-Stand Performance is Associated with Low Femoral Neck Bone Mineral Density in Healthy Women

Bone mass may be adjusted to control the strains produced by muscular activity. We assessed the relationship between maximum rising strength (MRS), a new measurement of sit-to-stand performance, and femoral neck (FN) bone mineral density (BMD), taking into account possible confounding variables. The study population consisted of 249 healthy women aged 18–76. We measured MRS with a dynamometer fixed on the ground and connected by an adjustable nonelastic cord to a padded belt. FN BMD was measured by dual X-ray absorptiometry. Women in the first quartile of FN BMD (<0.702 g/cm²) had significantly lower values of MRS, body weight, height, lean mass, past 5-year physical activity expenditures, blood 17 beta estradiol (E2), 25-hydroxyvitamin D (25(OH)D), dehydroepiandrosterone sulfate (DHEAS), and insulin like growth factor 1, and higher values of age and parathyroid hormone than other women. In the logistic regression model, FN BMD values in the lowest quartile were associated with age (adjusted odds ratio [OR_a] per 10-year increase = 1.84, 95% confidence interval [95% CI] = 1.33–2.54, P < 0.001), body weight (OR_a per 10-kg decrease = 3.67, 95% CI = 2.08–6.47, P < 0.001), MRS (OR_a per 20-kg decrease = 1.17, 95% CI = 1.02–1.34, P = 0.03), serum DHEAS (OR_a < 0.5 mg/ml vs ≥0.5 mg/ml = 2.83, 95% CI = 1.3–6.12, P = 0. 01), and serum E2 (OR_a per 10-pmol/l decrease = 1.02, 95% CI = 1.01–1.03, P = 0.03). The present study suggests a significant association between low FN BMD and low sit-to-stand performance in healthy women, independent of possible confounding variables.     

Age-Related Decline in Trabecular and Cortical Density: A 5-Year Peripheral Quantitative Computed Tomography Follow-Up Study of Pre- and Postmenopausal Women

This 5-year prospective study assessed changes in trabecular and cortical volumetric bone density at the non-weight-bearing radius and weight-bearing tibia among clinically healthy pre- and postmenopausal women. Altogether 79 premenopausal (mean age ± SD at baseline 33 ± 2 years) and 108 postmenopausal (68 ± 2 years) women participated in the baseline and follow-up measurements. Trabecular density (TrD) of the distal radius and tibia and cortical density (CoD) of the radial and tibial shafts were assessed by peripheral quantitative computed tomography (pQCT). Repeated measures analysis of variance was used to analyze differences of means and mean changes between the age groups. As expected, TrD and CoD values were greater among premenopausal than postmenopausal women. Changes in radial TrD were similar in both age groups: mean (95% confidence interval) TrD of the distal radius declined by 3.0 mg/cm³ (−0.9 to 7.0) and 5.1 mg/cm³ (1.8–8.5) in the younger and older age groups, respectively. The respective declines in TrD of the distal tibia were 4.1 mg/cm³ (2.1–6.0) and 2.8 mg/cm³ (1.2–4.3). Decline in CoD was greater in the older than younger age group at both the radial and tibial shafts (P < 0.001). The mean absolute declines in radial CoD were 33.3 mg/cm³ (27.9–38.7) and 49.4 mg/cm³ (44.9–53.9) in younger and older women, and the declines in tibial CoD were 16.5 mg/cm³ (12.6–20.2) and 28.1 mg/cm³ (25.0–31.2), respectively. In conclusion, volumetric TrD in the weight-bearing tibia and non-weight-bearing radius showed similar age-related declines among pre- and postmenopausal women, while the decline in CoD was greater among postmenopausal women.     

Fibroblast Growth Factor 21 Is Associated With Bone Mineral Density,but not With Bone Turnover Markers and Fractures in Chinese Postmenopausal Women

Fibroblast growth factor 21 (FGF21) is a member of the endocrine FGF subfamily and an important metabolic regulator that has multiple beneficial effects on glucose homeostasis and lipid metabolism. However, it was unclear whether FGF21 would induce bone defects in humans. This study evaluated the associations of FGF21 levels, bone mineral density (BMD), osteoporotic fracture, and bone turnover marks (BTMs) in postmenopausal women. A total of 1342 postmenopausal Chinese Han women (511 cases of fragility fracture in the case group and 831 cases in nonfragility fracture group) were enrolled. Serum FGF21 concentration was measured by ELISA (Quantikine), serum calcium (Ca), phosphate (P), alkaline phosphatase, 25-hydroxyvitamin D, parathyroid hormone, β-crosslinked C-telopeptide of type l collagen, were measured using an automated Roche electro-chemiluminescence system. BMD was measured using dual-energy X-ray absorptiometry. The association with age, BMD, 25-hydroxyvitamin D, parathyroid hormone, β-crosslinked C-telopeptide of type l collagen, and FGF21 levels were also evaluated in postmenopausal women. In nonfracture group and fragility fracture group, postmenopausal women's FGF21 level was 226.57pg/mL (149.11–354.43 pg/mL) and 219.43pg/mL (147.21–323.74 pg/mL), respectively. There is no significant difference in serum FGF21 levels between the fragility fracture group and the nonfracture group (p = 0.160). There was a significant statistical difference in BMD between the fragility fracture group and the nonfracture group (p?=?0.000). In multiple linear regression analysis, FGF21 levels were significantly positive associated with lumbar BMD in postmenopausal women (L1-4, p?=?0.007), independent of other factors, especially in fragility fracture group (L1-4, p?=?0.001). In addition, a significant positive association was also observed between serum FGF21 levels and age in postmenopausal women (p < 0.05). We reveal a positive correlation between serum FGF21 concentrations with lumbar BMD in Chinese Han postmenopausal women. No significant correlations are present between serum FGF21 and bone turnover marks or serum FGF21 and fragility fracture in our study.     

Influence of Grip Strength on Metacarpal Bone Mineral Density in Postmenopausal Japanese Women: A Cross-Sectional Study

Most published studies on the role of muscle strength in the maintenance of bone mineral density (BMD) focused on the relationship between specific muscle groups and adjacent bones, mostly in young and premenopausal women. This study examined the influence of grip strength on BMD of the metacarpal index in postmenopausal Japanese women. Subjects included 1168 postmenopausal women aged 40–70 years. BMD measurement was done with computed X-ray densitometry (CXD) by analyzing X-ray films of the right second metacarpal index. Grip strength was measured in both the dominant and nondominant hands using a squeeze dynamometer. Grip strength (r = 0.2474; P= 0.0001) and age (r =−0.5443; P= 0.0001) significantly correlated positively and negatively, respectively, with BMD. Physical activity (r = 0.1318; P= 0.0001) also correlated positively with BMD. Breastfeeding (r =−0.1658; P= 0.0001), however, correlated negatively with BMD. Subjects with a history of regular physical activity had higher grip strengths and BMD, than those with no physical activity. Adjustment for age, physical activity, calcium intake, BMI, breastfeeding, testing site, and menopausal type indicated a significant (P for trend = 0.0013) positive association of grip strength with BMD. Subjects with stronger grip strengths had a decreased risk for low BMD. Received: 24 February 1998 / Accepted: 7 August 1998