Does Vitamin D Strengthen the Increase in Femoral Neck BMD in Osteoporotic Women Treated with Estrogen?

The long-term effects on bone of estrogen therapy (HRT) combined with vitamin D₃ supplementation were evaluated and compared with the effects of HRT without vitamin D₃ supplementation in a 4-year prospective, partly randomized study among 60 osteoporotic women (mean age 55.4 years; range 49.7–59.4 years). The women studied were a subgroup of the population-based Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) (n = 13100). The bone mineral densities (BMD) of the lumbar spine and femoral neck were determined by dual-energy X-ray absorptiometry (DXA) in 3236 perimenopausal women. Those 106 women with baseline BMD more than 2 SDs less than the mean value in this population, either at the lumbar spine (BMD < 0.826 g/cm²) and/or femoral neck (BMD < 0.684 g/cm²), were offered treatment for osteoporosis. After exclusions, 60 women were included in the analyses. Group allocation was: HRT (estradiol valerate (2 mg) plus cyproterone acetate, 1 mg, sequentially: Climen^R) (n = 21); HRT + Vit D: Climen + vitamin D₃ (cholecalciferol, 300 IU/day, no intake during June–August) (n = 23); controls: 16 women who refused all treatment served as a non-randomized control group. In the HRT group, the highly significant increase in lumbar BMD was 5.4%, 5.3%, 4.7% and 4.0% after 1, 2, 3 and 4 years of treatment, respectively, all compared with the baseline values and with the control group. The increase in femoral neck BMD was statistically insignificant (1.4%, 2.2%, 1.9% and 2.1%, respectively; p > 0.05). In the HRT + Vit D group, the lumbar BMD increased by 3.7%, 4.9%, 4.9% and 4.9% (p < 0.001), whereas the 5.8% increase in femoral neck BMD reached significance at 4 years (p < 0.01) when compared with the control group as well as with the baseline values. However, there were no statistically significant differences in lumbar or femoral BMD changes between the two HRT groups. In conclusion, estrogen can substantially increase lumbar bone mass in patients with postmenopausal osteoporosis. In addition, the combination of HRT and vitamin D₃ may increase femoral neck BMD in osteoporotic women more than estrogen alone.     

Effect of aging on vitamin D stores and bone density in women

Summary It has been suggested that the decrease in vitamin D stores with aging is a contributory cause of age-related osteoporosis. We studied this question by measuring bone mineral density (BMD) of the mid-radius, distal radius, and lumbar spine assessed by single and dual photon absorptiometry in 122 women, aged 33–94 years, selected from a random sample of Rochester, MN residents. We measured serum 25-hydroxyvitamin D (25OHD), the major storage from of vitamin D, as well as 25OHD₃ (representing both endogenous and exogenous sources of vitamin D), and 25OHD₂, (representing only exogenous sources). Both baseline serum total 25OHD (r=−0.29,P<0.001) and the metabolite 25OHD₃ (r=−0.41,P<0.001), were negatively associated with age at baseline. After adjusting for the effect of age by multiple regression analysis, there was no association between serum levels of 25OHD₂, 25OHD₃, or total 25OHD and BMD for any of the three skeletal scanning sites. Thus, in a northern American population we cannot demonstrate that reduced bioavailability of vitamin D plays a major role in age-related bone loss.     

Effects of a multi-component exercise program and calcium–vitamin-D3-fortified milk on bone mineral density in older men: a randomised controlled trial

Summary  We examined the independent and combined effects of a multi-component exercise program and calcium–vitamin-D₃-fortified milk on bone mineral density (BMD) in older men. Exercise resulted in a 1.8% net gain in femoral neck BMD, but additional calcium–vitamin D₃ did not enhance the response in this group of older well-nourished men. Introduction  This 12-month randomised controlled trial assessed whether calcium–vitamin-D₃-fortified milk could enhance the effects of a multi-component exercise program on BMD in older men. Methods  Men (n = 180) aged 50–79 years were randomised into: (1) exercise + fortified milk; (2) exercise; (3) fortified milk; or (4) controls. Exercise consisted of high intensity progressive resistance training with weight-bearing impact exercise. Men assigned to fortified milk consumed 400 mL/day of low fat milk providing an additional 1,000 mg/day calcium and 800 IU/day vitamin D₃. Femoral neck (FN), total hip, lumbar spine and trochanter BMD and body composition (DXA), muscle strength 25-hydroxyvitamin D and parathyroid hormone (PTH) were assessed. Results  There were no exercise-by-fortified milk interactions at any skeletal site. Exercise resulted in a 1.8% net gain in FN BMD relative to no-exercise (p < 0.001); lean mass (0.6 kg, p < 0.05) and muscle strength (20–52%, p < 0.001) also increased in response to exercise. For lumbar spine BMD, there was a net 1.4–1.5% increase in all treatment groups relative to controls (all p < 0.01). There were no main effects of fortified milk at any skeletal site. Conclusion  A multi-component community-based exercise program was effective for increasing FN BMD in older men, but additional calcium–vitamin D₃ did not enhance the osteogenic response.     

Changes in Parameters of Bone Metabolism in Postmenopausal Women Following a 12-Month Intervention Period Using Dairy Products Enriched with Calcium, Vitamin D, and Phylloquinone (Vitamin K1) or Menaquinone-7 (Vitamin K2): The Postmenopausal Health Study II

The objective of the present study was to examine the effect of dairy products enriched with calcium, vitamin D₃, and phylloquinone (vitamin K₁) or menaquinone-7 (vitamin K₂) on parameters of bone metabolism in postmenopausal women following a 12-month intervention. Postmenopausal women were divided into three intervention groups and a control group (CG). All three intervention groups attended biweekly sessions and received fortified dairy products providing daily 800 mg of calcium and 10 μg of vitamin D₃ (CaD). Furthermore, in two of the three intervention groups the dairy products were also enriched with vitamin K, providing daily 100 μg of either phylloquinone (CaDK1) or menaquinone-7 (CaDK2). The increase observed for serum 25(OH)D levels in all intervention groups and the increase observed for serum IGF-I levels in the CaDK2 group differed significantly compared to the changes observed in CG (P = 0.010 and P = 0.028, respectively). Furthermore, both the CaDK1 and CaDK2 groups had a significantly lower mean serum undercarboxylated osteocalcin to osteocalcin ratio and urine deoxypyridinoline levels at follow-up compared to the CaD and CG groups (P = 0.001 and P = 0.047, respectively). Significant increases in total-body BMD were observed in all intervention groups compared to CG (P < 0.05), while significant increases in lumbar spine BMD were observed only for CaDK1 and CaDK2 compared to CG (P < 0.05) after controlling for changes in serum 25(OH)D levels and dietary calcium intake. In conclusion, the present study revealed more favorable changes in bone metabolism and bone mass indices for the two vitamin K-supplemented groups, mainly reflected in the suppression of serum levels of bone remodeling indices and in the more positive changes in lumbar spine BMD for these two study groups.     

Possible site-specific effect of an intervention combining nutrition and lifestyle counselling with consumption of fortified dairy products on bone mass: the Postmenopausal Health Study II

The aim of the present study was to examine whether a holistic approach combining nutrition and lifestyle counselling with the consumption of milk and yoghurt enriched with calcium, vitamin D₃ and phylloquinone (vitamin K₁) or menaquinone (vitamin K₂) would have any additional benefit on bone mineral density (BMD) indices measured at various skeletal sites using two different techniques, dual energy X-ray absorptiometry and quantitative ultrasonography (QUS). A sample of 115 postmenopausal women were randomized to three intervention groups, receiving daily via fortified milk and yoghurt and for 12 months, 800 mg calcium and 10 μg vitamin D₃ (CaD group, n = 26); 800 mg calcium, 10 μg vitamin D₃ and 100 μg vitamin K₁ (CaDK1 group, n = 26); 800 mg calcium, 10 μg vitamin D₃ and 100 μg vitamin K₂ (CaDK2 group, n = 24); and a control group (CO group, n = 39) following their usual diet. All three intervention groups attended biweekly nutrition and lifestyle counselling sessions. Total BMD significantly increased in all three intervention groups and these changes were significantly higher compared to the CO (P < 0.001). Furthermore, the significant increases observed for L2–L4 BMD in the CaDK1 and CaDK2 groups were found to be significantly higher compared to the decrease observed in the CO (P = 0.001). No significant differences were observed for QUS parameters. The combined approach used in the current study led to favourable changes for all three intervention groups in total body BMD, while an additional benefit was observed for L2–L4 BMD in CaDK1 and CaDK2 groups. No significant differences were observed among groups in any of the QUS parameters.     

Effect of antioxidants combined to resistance training on BMD in elderly women: a pilot study

Summary  We determined the effect of antioxidants and resistance training on bone mineral density of postmenopausal women. After 6 months, we observed a significant decrease in the lumbar spine BMD of the placebo group while other groups remained stable. Antioxidants may offer protection against bone loss such as resistance training. Introduction  The purpose of this pilot study was to determine the effects of antioxidant supplements combined to resistance training on bone mineral density (BMD) in healthy elderly women. Methods  Thirty-four postmenopausal women (66.1 ± 3.3 years) were randomized in four groups (placebo, n = 7; antioxidants, n = 8; exercise and placebo, n = 11; and exercise and antioxidants, n = 8). The 6-month intervention consisted in antioxidant supplements (600 mg vitamin E and 1,000 mg vitamin C daily) or resistance exercise (3×/week). Femoral neck and lumbar spine BMD (DXA) and dietary intakes (3-day food record) were measured before and after the intervention. A repeated measure ANOVA and non-parametric Mann–Whitney U tests were used. Results  We observed a significant decrease in the placebo group for lumbar spine BMD (pre, 1.01 ± 0.17 g/cm²; post, 1.00 ± 0.16 g/cm²; P < 0.05 respectively) while it remained stable in all other groups. No changes were observed for femoral neck BMD. Conclusions  Antioxidant vitamins may offer some protection against bone loss in the same extent as resistance exercise although combining both does not seem to produce additional effects. Our results suggest to further investigate the impact of antioxidant supplements on the prevention of osteoporosis.     

Effects of combination treatment with alendronate and vitamin K2 on bone mineral density and strength in ovariectomized mice

Bisphosphonates increase bone mineral density (BMD) by suppressing remodeling space and elongating the duration of mineralization. Menatetrenone (vitamin K₂) reduces the incidence of fractures by improving bone quality through enhanced γ-carboxylation of bone glutamic acid residues of osteocalcin in osteoporotic patients. This study investigated the effects of combination treatment with alendronate (ALN) and vitamin K₂ on BMD and bone strength in ovariectomized (OVX) mice. Thirty-three female mice, 16 weeks of age, were assigned to four groups: (1) OVX-control group; (2) oral vitamin K₂ group; (3) subcutaneous ALN group; and (4) ALN + vitamin K₂ group. The treatment was started 4 weeks after OVX and continued for 4 weeks. BMD, geometric parameters measured by peripheral quantitative computed tomography, and mechanical strength at the femoral metaphysis and mid-diaphysis were evaluated after an 8-week treatment period. ALN alone significantly increased total BMD (20%, P < 0.05) and trabecular BMD (25%, P < 0.05), but not the mechanical parameters of the femur, compared with the OVX-control group. Combination treatment with ALN and vitamin K₂ increased not only total BMD (15%, P < 0.05) and trabecular BMD (32%, P < 0.05) but also maximum load (33%, P < 0.05) and breaking energy (25%, P < 0.05) of compression test at the distal metaphysis, and maximum load (20%, P < 0.05) and breaking force (33%, P < 0.05) of three-point bending test at the mid-diaphysis compared with the OVX-control group. These results suggest that ALN, alone or in combination with vitamin K₂, showed significant improvement in BMD, but that the combination treatment was more effective than ALN alone for improving bone strength in OVX mice.     

Treatment of Glucocorticoid-Induced Osteoporosis with Alfacalcidol/Calcium Versus Vitamin D/Calcium

Vitamin D/calcium substitution is generally regarded as an effective first step treatment for glucocorticoid-induced osteoporosis (GIOP). The aim of our study was to evaluate the efficacy of the active vitamin D metabolite alfacalcidol (1α) compared with the native vitamin D₃ in patients with established GIOP with or without vertebral fractures. Patients on long-term corticoid therapy were given either 1 μg alfacalcidol plus 500 mg calcium per day (group A, n = 43) or 1000 IU vitamin D₃ plus 500 mg calcium (group B, n = 42). The two groups were alike in age range, sex ratio, percentages of underlying diseases, average initial bone density values (lumbar spine: mean T-score −3.28 and −3.25, respectively), and rates of vertebral and nonvertebral fractures. During the 3-year study we found a small but significant increase of lumbar spine density in group 1α (+2.0%, P < 0.0001) and no significant changes at the femoral neck. In the D₃ group, there were no significant changes at both sites. At the end of the study, 12 new vertebral fractures had occurred in 10 patients of the group 1α and 21 in 17 patients of the D₃ group. In accordance with the observed fracture rates, the alfacalcidol group showed a significant decrease in back pain (P < 0.0001) whereas no change was seen in the vitamin D group. We conclude that with the doses used in this trial, alfacalcidol is superior to vitamin D in the treatment of established GIOP.     

No effect of vitamin K1 intake on bone mineral density and fracture risk in perimenopausal women

Introduction Vitamin K functions as a co-factor in the post-translational carboxylation of several bone proteins, including osteocalcin.Aim The aim of this study was to investigate the relationship between vitamin K₁ intake and bone mineral density (BMD) and fracture risk in a perimenopausal Danish population.Design The study was performed within the Danish Osteoporosis Prevention Study (DOPS), including a population-based cohort of 2,016 perimenopausal women. During the study approximately 50% of the women received hormone replacement therapy (HRT). Associations between vitamin K₁ intake and BMD were assessed at baseline and after 5-years of follow-up (cross-sectional design). Moreover, associations between vitamin K₁ intake and 5-year and 10-year changes in BMD were studied (follow-up design). Finally, fracture risk was assessed in relation to vitamin K₁ intake (nested case–control design).Results In our cohort, dietary vitamin K₁ intake (60 μg/day) was close to the daily intake recommended by the Food and Agriculture Organization (FAO). Cross-sectional and longitudinal analyses showed no associations between intake of vitamin K₁ and BMD of the femoral neck or lumbar spine. Neither did BMD differ between those 5% that had the highest vitamin K₁ intake and those 5% that had the lowest. During the 10-years of follow-up, 360 subjects sustained a fracture (cases). In a comparison between the cases and 1,440 controls, logistic regression analyses revealed no difference in vitamin K₁ intake between cases and controls.Conclusion In a group of perimenopausal and early postmenopausal women, vitamin K₁ intake was not associated with effects on BMD or fracture risk.     

Standard multivitamin supplementation does not improve vitamin D insufficiency after burns

Children suffering severe burns develop progressive vitamin D deficiency because of inability of burned skin to produce normal quantities of vitamin D₃ and lack of vitamin D supplementation on discharge. Our study was designed to determine whether a daily supplement of a standard multivitamin tablet containing vitamin D₂ 400 IU (10 μg) for 6 months would raise serum levels of 25-hydroxyvitamin D [25(OH)D] to normal. We recruited eight burned children, ages 5–18, whose families were deemed reliable by the research staff. These children were given a daily multivitamin tablet in the hospital for 3 months in the presence of a member of the research staff and then given the remainder at home. At 6 months, the subjects returned for measurements of serum levels of 25(OH)D,1,25-dihydroxyvitamin D [1,25(OH)₂D], intact parathyroid hormone (iPTH), Ca, P, albumin, and total protein as well as bone mass by dual energy X-ray absorptiometry. Serum 25(OH)D levels were compared to a group of seven age-matched burned children studied at an earlier date without the vitamin supplement but with the same method of determination of 25(OH)D at 6 months post-burn. In addition, the chewable vitamins were analyzed for vitamin D₂ content by high performance liquid chromatography. Serum concentration of 25(OH)D was 21 ± 11(SD) ng/ml (sufficient range 30–100) with only one of the eight children having a value in the sufficient range. In comparison, the unsupplemented burn patients had mean serum 25(OH)D level of 16 ± 7, P = 0.33 versus supplemented. Serum levels of 1,25(OH)₂D, iPTH, Ca, P, albumin, and total protein were all normal in the supplemented group. Vitamin D₂ content of the chewable tablets after being saponified and extracted was 460 ± 20 IU. Bone mineral content of the total body and lumbar spine, as well as lumbar spine bone density, failed to increase as expected in the supplemented group. No correlations were found between serum 25(OH)D levels and age, length of stay, percent body surface area burn or third-degree burn. Supplementation of burned children with a standard multivitamin tablet stated to contain 400 IU of vitamin D₂ failed to correct the vitamin D insufficiency.     

Relationship between bone mineral density and insulin resistance in polycystic ovary syndrome

The aim of the present study was to evaluate whether there is a relationship between bone mineral density (BMD) and insulin resistance and hyperinsulinemia in women with polycystic ovary syndrome (PCOS). The study consisted of 28 amenorrheic women with PCOS and 11 amenorrheic women without PCOS. Fifteen healthy women with normal ovulatory function, matched for age and body mass index (BMI), served as controls. BMD was measured at the lumbar spine and left femoral neck with dual-energy X-ray absorptiometry. Blood samples were obtained to measure serum levels of insulin, follicle-stimulating hormone, luteinizing hormone, sex hormone-binding globulin (SHBG), total and free testosterone, androstenedione and estradiol by radioimmunassay. Insulin resistance was estimated by the insulin tolerance test (ITT), and K_ITT was taken as the insulin sensitivity index. In the PCOS group, K_ITT was significantly lower and insulin levels were higher than in either of the control groups (P < 0.001). BMD in the PCOS group was lower than in the healthy group and higher than in the amenorrheic control group (P < 0.05). In the PCOS group, there were positive correlations of BMD of the lumbar spine with insulin (r = 0.42; P < 0.05) and negative correlations of BMD with K_ITT (r = −0.58; P < 0.001) and SHBG (r = −0.38; P < 0.05). The inverse association of BMD and K_ITT was independent of BMI, insulin, SHBG, androstenedione, and free testosterone. In conclusion, insulin resistance and hyperinsulinemia in women with PCOS may be a relative protective factor against bone mineral loss. Received: November 13, 2000 / Accepted: December 28, 2000     

Randomized Trial of Alendronate Plus Vitamin D<Subscript>3</Subscript> Versus Standard Care in Osteoporotic Postmenopausal Women with Vitamin D Insufficiency

Vitamin D insufficiency is common in patients with osteoporosis. We conducted a randomized trial comparing alendronate 70 mg combined with vitamin D₃ 5,600 IU in a single tablet (ALN/D5600, n = 257) with standard care chosen by the patients’ personal physicians (n = 258) in patients with postmenopausal osteoporosis (BMD T score ≤2.5 or ≤1.5 and a prior fragility fracture) who had vitamin D insufficiency (serum 25[OH]D values 8–20 ng/ml) and who were at risk of falls. Virtually all patients randomized to standard care received bisphosphonate therapy, and in approximately 70% of cases this was combined with vitamin D supplements. However, only 24% took ≥800 IU/day of supplemental vitamin D. At 6 months the proportion of patients with vitamin D insufficiency was 8.6% in the ALN/D5600 group compared with 31.0% in the standard care group (P < 0.001). Those in the ALN/D5600 group also had a greater reduction in urinary NTX/creatinine ratio (−57% vs. −46%, P < 0.001) and bone-specific alkaline phosphatase (−47% vs. −40%, P < 0.001). In the ALN/5600 group, by 12 months the increase in BMD was greater at the lumbar spine (4.9% vs. 3.9%, P = 0.047) and the total hip (2.2% vs. 1.4%, P = 0.035), significantly fewer patients were vitamin D—insufficient (11.3% vs. 36.9%, P < 0.001), and bone turnover marker (BTM) results were similar to those at 6 months. There was no difference between groups in those who experienced falls or fractures, and adverse events were similar. Based on the finding that ALN/D5600 was more effective than standard care at correcting vitamin D insufficiency, increasing BMD, and reducing BTMs in this patient group, greater attention needs to be directed toward optimizing the treatment of osteoporosis and correcting vitamin D deficiency in postmenopausal women.     

A longitudinal study for femoral neck bone mineral density increases in premenopausal caddies using dual-energy X-ray absorptiometry

This longitudinal study examined whether bone mineral density (BMD) of the lumbar spine and proximal femur is maintained in premenopausal caddies (n = 6; mean age 37.8 years) in comparison with desk workers (n = 6; mean age 40.8 years) at the same golf club. BMD was followed for 12 months using dual-energy X-ray absorptiometry (DXA) and bone metabolic markers and athletic ability were also examined. Longitudinally, for caddies, the change per year in BMD of the lumbar spine was +0.009 g/cm², while that of the proximal femur was +0.022 g/cm², showing significant differences (P < 0.05 by signed-rank test). Their athletic ability, in terms of leg-press power, also significantly increased, whereas bone metabolic markers, such as serum alkaline phosphatase, 1,25-(OH)₂ vitamin D₃, parathyroid hormone and the deoxypyridiniline/creatinine ratio, did not show significant changes. For desk workers, the change per year in BMD of the lumbar spine was +0.011 g/cm², while that of the proximal femur was −0.006 g/cm². Their BMD, athletic ability and bone metabolic markers did not show significant changes. These findings support the results of our previous study, that premenopausal women can achieve continuous gain in femoral neck BMD by regular intense athletic activity, and suggest that this is also true by the continuous extensive walking of golf caddies. Received: May 17, 2000 / Accepted: August 22, 2000     

Effect of early risedronate treatment on bone mineral density and bone turnover markers after liver transplantation: a prospective single‐center study

The aim of this study was to investigate the effect of risedronate (RIS) on bone loss and bone turnover markers after liver transplantation (LT). Patients with osteopenia or osteoporosis within the first month after LT were randomized to receive RIS 35 mg/week plus calcium 1000 mg/day and vitamin D₃ 800 IU/day (n = 45) or calcium and vitamin D₃ at same dosages (n = 44). Primary endpoint was change in bone mineral density (BMD) 6 and 12 months after LT. Secondary endpoints included changes in serum β‐CrossLaps (β‐CTX) and procollagen type 1 amino‐terminal peptide (P1NP) and fracture rate. Spine X‐rays were obtained at baseline and after 12 months. There was no significant difference in BMD changes between both treatment groups at any sites; either at 6 or 12 months. Spine BMD increased in both groups at 12 months vs. baseline (P = 0.001). RIS patients had a significant increase in intertrochanteric BMD at 12 months (P < 0.05 vs. baseline). Serum β‐CTX decreased in both groups (P < 0.01), with significant differences between groups at 3 months. No significant difference in vertebral fracture incidence was found. After 12 months, BMD improved at lumbar spine and did not change at hip in both groups. Significant differences between both groups were not found. Other factors (calcium and vitamin D replacement, early prednisone withdrawal) seem to have also positive effects in BMD.     

Vitamin K1 Supplementation Retards Bone Loss in Postmenopausal Women Between 50 and 60 Years of Age

Although several observational studies have demonstrated an association between vitamin K status and bone mineral density (BMD) in postmenopausal women, no placebo-controlled intervention trials of the effect of vitamin K₁ supplementation on bone loss have been reported thus far. In the trial presented here we have investigated the potential complementary effect of vitamin K₁ (1 mg/day) and a mineral + vitamin D supplement (8 µg/day) on postmenopausal bone loss. The design of our study was a randomized, double-blind, placebo-controlled intervention study; 181 healthy postmenopausal women between 50 and 60 years old were recruited, 155 of whom completed the study. During the 3-year treatment period, participants received a daily supplement containing either placebo, or calcium, magnesium, zinc, and vitamin D (MD group), or the same formulation with additional vitamin K₁ (MDK group). The main outcome was the change in BMD of the femoral neck and lumbar spine after 3 years, as measured by DXA. The group receiving the supplement containing additional vitamin K₁ showed reduced bone loss of the femoral neck: after 3 years the difference between the MDK and the placebo group was 1.7% (95% Cl: 0.35–3.44) and that between the MDK and MD group was 1.3% (95% Cl: 0.10–3.41). No significant differences were observed among the three groups with respect to change of BMD at the site of the lumbar spine. If co-administered with minerals and vitamin D, vitamin K₁ may substantially contribute to reducing postmenopausal bone loss at the site of the femoral neck.     

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

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

Associations of vitamin C, calcium and protein with bone mass in postmenopausal Mexican American women

We investigated the associations of vitamin C, calcium and protein intakes with bone mass at the femoral neck and lumbar spine in postmenopausal Mexican American women. Bone mass was measured by dual-energy X-ray absorptiometry (DXA) and expressed as areal (BMD, g/cm²) and volumetric (bone mineral apparent density or BMAD, g/cm³) bone mineral density. Diet was assessed using a modified version of the National Cancer Institute Food Questionnaire, which was administered by trained bilingual interviewers familiar with Mexican dietary practices. Data gathered from 125 subjects were analyzed using multiple linear regression analysis with age, body mass index (BMI), acculturation, years of estrogen use, physical activity, total energy intake, and the nutrient of interest as independent variables. Neither calcium nor calcium/protein ratio was associated with bone mineral density. There was evidence of a positive association between dietary vitamin C intake and femoral neck BMD (β=0.0002 g/cm² per mg/day, SE=0.0001,p=0.07) and BMAD (β=0.0001 g/cm³ per mg/day, SE=0.00006,p<0.05), but vitamin C was not associated with lumbar spine bone mass. Further investigation of the role of vitamin C in skeletal health is warranted.     

Calcium and Vitamin D Supplementation Increases Spinal BMD in Healthy, Postmenopausal Women

We undertook a double-masked, randomized, placebo-controlled trial to evaluate the effect of a calcium and vitamin D supplement and a calcium supplement plus multivitamins on bone loss at the hip, spine and forearm. The study was performed in 240 healthy women, 58–67 years of age. Duration of treatment was 2 years. Bone mineral density (BMD) was measured at the lumbar spine, hip and forearm. A dietary questionnaire was administered twice during the study and revealed a fairly good calcium and vitamin D intake (919 mg calcium/day; 3.8 mg vitamin D/day). An increase in lumbar spine BMD of 1.6% was observed in the treatment group after 2 years (p50.002). In the placebo group no significant changes were observed during the 2 years. Lumbar spine BMD was significantly higher in the treatment group at both 1 (p50.01) and 2 years (p50.05) compared with the placebo group. Though not significant, the same trend was seen at the hip. No significant changes from baseline values were observed at the distal forearm in either the treatment or the placebo group. In conclusion, we found a significant increase in urinary calcium excretion in the treatment group compared with the placebo group. Together with significant changes in serum calcium and serum parathyroid hormone, this indicates that a long-term calcium and vitamin supplement of 1 g elementary calcium (calcium carbonate) and 14 mg vitamin D₃ increases intestinal calcium absorption. A positive effect on BMD was demonstrated, even in a group of early postmenopausal age, with a fairly good initial calcium and vitamin D status. Received: 2 July 1997 / Accepted: 28 October 1997     

Early Postmenopausal Bone Loss is Prevented by Estrogen and Partially by 1α-OH-vitamin D3: Therapeutic Effects of Estrogen and/or 1α-OH-vitamin D3

A total of 79 Japanese women who were within 5 years of menopause were randomly assigned 1α-hydroxyvitamin D₃ [1α(OH)D₃] 1.0 μg/day, conjugated estrogens 0.625 mg/day, a combination of both, or control (no treatment). Lumbar spine and proximal femur bone mineral density (BMD) and biochemical indices were monitored over 2 years. In the 1α(OH)D₃-treated group, there was a nonsignificant decrease in lumbar spine BMD compared with controls, and no significant loss in the femoral neck compared with controls. In the estrogen-treated group, there was a nonsignificant increase in spine BMD (+2.17% in the first year and +1.71% in the second year), and no loss in femoral neck BMD. The combination of conjugated estrogens +1α(OH)D₃ was more effective in increasing BMD in the spine (+3.68% in the first year and +3.63% in the second year) and femur (+2.56% in the first year and +4.44% in the second year) BMD. There was a significant difference in lumbar spine BMD in both the first and second years between the combination-treated group and the 1α(OH)D₃-treated and control groups (P < 0.01). Serum osteocalcin (OC) significantly decreased in the combination-treated group (−23.8% in the first year) and the estrogen-treated group (−37.6% and −41.2% at 6 and 18 months, respectively), and serum alkaline phosphatase (Alp) decreased significantly in the first year in the combination-treated (−31.5%), estrogen-treated (−27.3%), and 1α(OH)D₃-treated (−7.9%) groups, whereas serum OC increased (+45.4% in the first year) in women without treatment. The results of this study indicate that early postmenopausal bone loss in the femoral neck is prevented by conjugated estrogens, 1α(OH)D₃, or both, whereas bone loss in the spine is not prevented by 1α(OH)D₃. Estrogen proves effective in preventing early postmenopausal bone loss by markedly inhibiting bone turnover. Moreover, a synergistic bone-sparing effect can be expected when estrogen is administered concomitantly with 1α(OH)D₃ rather than when used alone. Received: 28 April 1998 / Accepted: 23 December 1998     

Characteristics of bone mineral density and soft tissue composition of obese Japanese women: Application of dual-energy X-ray absorptiometry

We studied the characteristics of bone mineral density (BMD) and soft tissue composition in obese Japanese women using dual-energy X-ray absorptiometry. Eighty-nine women, aged 45–85 years, were divided into three groups according to their body mass index (BMI): a thin group (n = 38; BMI < 21), a standard weight group (n = 31; BMI, 21–25), and an obese group (n = 20; BMI ≥ 25). The mean BMD of the second to fourth lumbar vertebrae and BMD of the lumbar spine, thoracic spine, pelvis, legs, and ribs of the thin group were significantly lower than those of the standard weight group or the obese group (P < 0.05), whereas no significant difference in total body BMD was observed among the three groups. There was a significant difference in total and regional fat mass among the three groups (P < 0.05). Lean mass of legs and total lean mass showed a significant difference between the thin group and the obese group (P < 0.05). The results showed that obesity was associated with higher BMD of weight bearing-bones and ribs, high total and regional fat mass, and high lean mass of bilateral legs and total lean mass. We suggest that obesity may contribute to the prevention of bone loss of weight-bearing bones and ribs and muscular atrophy of the legs. Received: Sept. 30, 1998 / Accepted: Dec. 10, 1998