Clodronate Prevents Bone Loss in Aged Ovariectomized Rats

The purpose of this study was to investigate the ability of clodronate to prevent ovariectomy (OVX)-induced osteopenia in aged rats. Fourteen-month-old female Sprague-Dawley rats (n = 166) were randomized into six groups. One group was sacrificed at the start of the study, four groups were ovariectomized, and one group was sham-operated (Sham). The OVX rats were given subcutaneously either vehicle (veh) or clodronate at doses of 3, 7, or 25 mg/kg once a week for 3 months, and the Sham rats were given the vehicle. At all dose levels clodronate inhibited trabecular bone loss in the distal femur and in the fourth lumbar vertebral body (L4), and decreased bone resorption as evidenced by urinary deoxypyridinoline excretion. The lowest dose of clodronate preserved serum osteocalcin and endosteal bone formation of secondary spongiosa in L4 at the level of the Sham/veh group. The OVX-induced increase in periosteal bone formation of femoral diaphysis was unaffected by two smaller doses of clodronate, but was decreased to the level of Sham rats after the highest dose. After 3 mg/kg clodronate, the percentage of femoral cortical bone area and the mean relative cortical thickness were higher compared with the OVX/veh group. There was a good positive correlation between the maximum load in three-point bending of the tibia and tibial ash weight. Normal lamellar pattern of newly formed cancellous and cortical bone was found after clodronate treatment. No signs of adverse accumulation of osteoid or any deleterious effect on mechanical strength of long bones and lumbar vertebrae were found. Received: 28 August 1996 / Accepted: 5 March 1997     

Low Bone Density with Normal Bone Turnover in Ovariectomized and Streptozotocin-Induced Diabetic Rats

Diabetes and estrogen deficit are known causes of osteopenia, diabetes being associated with a low bone turnover and estrogen deficit with a high bone turnover. In the present work, we studied the effect of combined ovariectomy and diabetes on bone mineral content (BMC) and bone mineral density (BMD) and several bone markers in the rat. Four groups of rats were studied: control (C), ovariectomized (O), diabetic (D), and ovariectomized and diabetic (DO). Twelve weeks after starting the experiments, BMC and BMD of the first six lumbar vertebrae were measured; a bone formation marker (BGP) and a bone resorption marker (free collagen cross-links, PYD) were also analyzed. Diabetic rats showed diminished gain in bone mass, BMC (D: 0.417 ± 0.028 g, DO: 0.422 ± 0.020 g) and BMDs (D: 0.171 ± 0.006 g/cm², DO: 0.174 ± 0.006 g/cm²) both being significantly (P < 0.001) lower than those of control (C: BMC 0.727 ± 0.024 g and BMD 0.258 ± 0.004 g/cm²) and ovariectomized (O: BMC 0.640 ± 0.044 g and BMD 0.240 ± 0.009 g/cm²) groups. Moreover, the BMC and BMD of the C group were significantly (P < 0.05) higher than that of the O group. BGP and PYD levels were significantly (P < 0.01) higher in the O group (BGP: 138.2 ± 16.8 ng/ml, PYD: 270.2 ± 17.8 nM/mM) than those found in the control rats (BGP: 44.7 ± 4.8 ng/ml, PYD: 165.6 ± 12.5 nM/mM); the D group showed significantly (P < 0.01) lower values (BGP: 27.4 ± 14.6 ng/ml, PYD: 55.0 ± 7.4 nM/mM) than those of the control group. The DO group showed similar levels (BGP: 43.4 ± 5.1 ng/ml, PYD: 146.7 ± 14.6 nM/mM) to those found in the C group. Although bone marker levels in the O and D groups were in accordance with those expected in these situations, in the DO group the corresponding levels are apparently ``normal.' Also, the decrease of gain in bone mass observed after combining estrogen deficit and diabetes (DO group) did not seem to be more marked than that caused by diabetes alone. Received: 7 January 1997 / Accepted: 7 August 1997     

Prediction of Bone Loss Rate in Healthy Postmenopausal Women

Prevention of fractures is the only way to drastically reduce osteoporosis-related health expenditures. In order to optimize the cost/benefit ratio of a strategy of prevention, it is essential to identify, as early as possible, women who will develop fractures later in their life. Therefore, and since postmenopausal bone loss is an asymptomatic process, screening procedures should detect, at the time of the menopause, women whose postmenopausal bone loss is higher than the mean, and will, a couple of years later, exhibit a low mineral content and a subsequent high risk for fractures. For 3 years we have followed a cohort of 92 healthy women who had undergone menopause less than 36 months previously. By a multivariate discriminant analysis based on the differences in lumbar bone density, assessed by dual photon absorptiometry, and in a few routine biochemical parameters (serum phosphorus, estrone, androstenedione, and urine calcium) observed during the first 6 months of the study, we have been able to correctly predict the rate of spinal bone loss, observed at the end of the 3 years, in 76% of the subjects. All of the women who presented a bone loss higher than 10% over the 3 years were correctly isolated by our discriminant functions after 6 months of follow-up. We conclude that a measurement of lumbar bone mineral density coupled with a few routine biochemical determinations, repeated twice at a 6-month interval in healthy postmenopausal women, can isolate 100% of postmenopausal ``fast bone losers' with an overall specificity of 76%. Received: 22 December 1995 / Accepted: 23 September 1996     

The Mechanical Properties of Fluoride-Treated Bone in the Ovariectomized Rat

The effect of fluoride therapy on the osteopenic bone of the ovariectomized rat was studied by comparing the densitometric and biomechanical data. Forty retired breeder female Sprague-Dawley rats aged 10 months were randomly divided into five groups. One group (Group A) was killed at the beginning of the study and was used as a baseline. Three groups were ovariectomized and one was sham-operated (Group B) and observed for the same period as a sham-aged group. A group of ovariectomized rats was used as a sham therapy control (Group C) and received only deionized drinking water; the other two groups (F1 and F2) received L-glutamine monofluorophosphate and calcium at a rate of 1:30 F/Ca at different doses by gavage (0.57 mg F/17 mg Ca per kg/day-Group F1; 0.21 mg F/6.30 mg Ca per kg/day-Group F2). Densitometric and biomechanical (compression and three-point bending test) assays, X-ray diffraction, and Fourier transformed infrared spectroscopy were performed on femoral specimens. Biomechanical data showed that the femoral heads of Group F2 required a significantly greater energy-to-failure than Group C (P < 0.05) as well as treated femoral diaphysis when compared with the others (P < 0.01). Significant increases in the elastic modules were observed in fluoride-treated groups (P < 0.001) when compared with other groups. Diffractometric and spectroscopic data showed the presence of fluorine-apatite in both treated groups with a high component of carbonates. Also, fluoride therapy causes an increase of bone stiffness due to the presence of fluoroapatite. It seems to produce two opposed properties in the osteopenic rat bone: a higher resistance to compression loading and a greater frailty to flexion loading. Received: 18 November 1997 / Accepted: 28 January 1999     

Stimulation of Bone Formation In Vivo by Insulin-Like Growth Factor-II in Rats

Insulin-like growth factor-II (IGF-II) plays an important role in skeletal remodeling, however, little is known about its effect on bone formation in vivo. In our study of the stimulation of bone formation in vivo by IGF II we injected recombinant human IGF-II into the parietal bones of neonatal rats once a day for 12 days. The bone mineral density measured by dual energy X-ray absorptiometry and the thickness of IGF-II-injected parietal bones increased in a dose-dependent manner. The layers of osteoblasts were observed along the IGF-II-injected side. Received: 12 June 1997 / Accepted: 8 January 1998     

Resistive Training Maintains Bone Mineral Density in Postmenopausal Women

We examined the effects of a total body resistive training program (RT) on total and regional bone mineral density (BMD) in older women. Twenty-seven healthy postmenopausal women (mean age 62 ± 1 years) participated in a strength training program three times/week for 16 weeks. Strength was assessed before and after training by either one or three repetition maximum (1RM and 3RM) tests. Both upper and lower body strength significantly increased by 36–65% and 32–98%, respectively, after training. There was a small but significant decrease in body weight and body mass index after training (P < 0.05), with no change in the waist-to-hip ratio. BMD, assessed by dual-energy X-ray absorptiometry, did not change over the duration of the training period in the anterioposterior spine (L₂–L₄), femoral neck, Ward's triangle, and greater trochanter. BMD of the total body, lateral spine (B₂–B₄), and the regions of the radius (1/3 radius and ultradistal radius) also did not fall in subsets of these women. Muscular strength of both the leg and chest press were significantly associated with L₂–L₄, femoral neck, Ward's triangle, and greater trochanter BMD (range r = 0.57–0.84, all P < 0.005). Markers of bone turnover, namely, bone-specific alkaline phosphatase, osteocalcin, and urinary aminoterminal cross-linked telopeptide of type I collagen did not change significantly. In conclusion, a resistive training program maintains BMD and improves muscular strength in healthy, older women. This may be important in preventing the negative health outcomes associated with the age-related loss of bone density. Received 5 June 1996 / Accepted: 26 June 1997     

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     

Geranylgeranylacetone Inhibits Formation and Function of Human Osteoclasts and Prevents Bone Loss in Tail-Suspended Rats and Ovariectomized Rats

Vitamin K is used for protecting against osteoporosis. Recently, it has been reported that the inhibitory effect of vitamin K₂ (menatetrenone) on bone resorption may be related to its side chain. Geranylgeranylacetone (GGA), known as teprenone, an antiulcer drug, has almost the same chemical structure as that of the side chain of menatetrenone. We hypothesized that GGA also has an inhibitory effect on osteoclastogenesis both in vitro and in vivo. GGA in pharmacological concentrations directly inhibited osteoclastogenesis from human monocytes induced by soluble receptor activator of nuclear factor-κB ligand. In addition, GGA induced degradation of actin rings in mature osteoclasts, which was reversed by adding geranylgeranylpyrophosphatase. Moreover, GGA increased the bone mineral density of total femur, proximal metaphysis, and diaphysis of femur in ovariectomized rats. GGA also prevented bone loss induced by hindlimb unloading in tail-suspended rats. These results indicate that GGA prevents bone loss by maintaining a positive balance of bone turnover through suppression of both the formation and the activity of osteoclasts. Thus, GGA could be used to prevent and improve osteoporosis.     

The Effect of Tamoxifen on Bone Metabolism and Skeletal Growth is Different in Ovariectomized and Intact Rats

The effects of tamoxifen (TAM) treatment on bone metabolism and skeletal growth were studied in sexually mature intact or ovariectomized (OVX) rats. Experiment 1 was designed to observe the effects of TAM on bone metabolism and skeletal growth in intact rats and included two groups: (1) intact plus vehicle and (2) intact plus TAM. Experiment 2 was designed to investigate the effects of TAM on OVX rats and included the other two groups: (3) OVX plus vehicle and (4) OVX plus TAM. Serum calcium osteocalcin and urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr) were measured serially before and after TAM treatment for 6 weeks in order to monitor bone turnover. Bone mineral density (BMD) and bone mineral content (BMC) of excised right femora and lumbar vertebrae were determined by dual energy X-ray absorptiometry (DXA). To examine the effect of TAM on skeletal growth, the conventional parameters of femora and the histology of right tibiae were also measured. TAM did not induce significant change in the biochemical markers in intact rats during the 6-week experiment. Bone mass and skeletal growth were not changed by TAM treatment in intact rats. However, TAM treatment reduced the increase in serum osteocalcin and urinary pyridinium cross-links from 1 week to 6 weeks postovariectomy in the OVX rats. TAM inhibited the skeletal growth in OVX rats, because TAM treatment shortened femoral length and decreased the cell number in the growth plate in OVX rats in this study. Our findings indicate that TAM exerts an effect of estrogen agonist on bone metabolism and skeletal growth in OVX rats, however, it does not affect them in intact rats. Received: 1 September 1995 / Accepted: 20 February 1996     

Biochemical Markers of Bone Turnover and Bone Loss at the Lumbar Spine and Femoral Neck: The Taiji Study

The purpose of this study was to ascertain whether biochemical markers of bone turnover predict bone loss. The survey was carried out in Taiji, Wakayama Prefecture, Japan. From a list of inhabitants aged 40–79 years, 400 participants (50 men and 50 women in each of four age groups) were selected randomly. Bone mineral density (BMD) was measured, and blood and urine samples of all participants were examined to obtain values for eight biochemical markers: alkaline phosphatase (ALP), bone Gla protein (BGP), type I procollagen (carboxyterminal peptide of type I procollagen; PICP), cross-linked carboxyterminal telopeptide region of type I collagen (ICTP), and urinary excretion of calcium (Ca), phosphate (P), pyridinoline (Pyr), and deoxypyridinoline (D-Pyr). Each marker was evaluated as a predictor of the rate of bone change in lumbar spine and femoral neck BMD over a 3-year period. The value of Pyr was significantly related to the change of lumbar spine BMD in men (P= 0.009), and that of BGP was found to be significant in women (P= 0.045). By contrast, none of the bone markers significantly correlated with bone loss at the femoral neck. The coefficient of determination at the lumbar spine was 5% and 7% at the femoral neck only. We conclude that biochemical markers of bone turnover cannot predict bone loss rates in middle-aged or elderly Japanese men and women over a 3-year period with sufficient accuracy for use in clinical decision making. Received: 26 January 1998 / Accepted: 9 July 1998     

Treatment with Fluoride or Bisphosphonates Prevents Bone Loss Associated with Colitis in the Rat

Idiopathic inflammatory bowel disease (IBD) is associated with osteoporosis in over 30% of cases. We have previously shown that 2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced colitis in rats is associated with considerable bone loss. In the current study we tested the ability of sodium fluoride (NaF) or the bisphosphonate pamidronate to prevent the bone loss associated with TNBS-induced colitis in 22-week-old male Wistar rats. As previously found, there was a 43% decrease in cancellous bone volume in rats with TNBS-induced colitis after 4 weeks. This was associated with marked suppression of the bone formation rate to less than 25% of control animals. Treatment with NaF had no effect on the severity of colitis, but the bone volume and bone formation rate were increased to levels indistinguishable from those of control animals. In animals treated with pamidronate, cancellous bone volume was also restored to that of control animals despite persistence of the colitis. In these animals there was marked suppression of bone formation, associated with suppression of bone resorption. This data shows the bone loss associated with colitis may be prevented by treatment with NaF or bisphosphonates without requiring improvement in severity of the colitis. Received: 20 May 1999 / Accepted: 19 June 2000 / Online publication: 22 September 2000     

Calcium Absorption and Bone Loss in Ovariectomized Rats Fed Varying Levels of Dietary Calcium

The following studies were undertaken to examine whether estrogen deficiency impairs calcium absorption in aged rats, and to determine whether impaired calcium absorption and the level of dietary calcium are related to the degree of bone loss due to estrogen deficiency. Sixty rats were sham operated (Sham) or ovariectomized (Ovx) to make them estrogen deficient and divided into three dietary groups of 10 rats per group: Group 1 (Sham) and Group 2 (Ovx) were maintained on a diet containing 0.5% calcium; Group 3 (Sham) and Group 4 (Ovx) were maintained on a diet containing 0.1% calcium; Group 5 (Sham) and Group 6 (Ovx) were maintained on a diet containing 0.02% calcium. Calcium absorption was measured in all animals at the beginning of the study and 2 weeks, 1 month, 2 months, and 3 months following surgery, then the animals were sacrificed. In Ovx rats fed 0.5% Ca diet, calcium absorption decreased progressively and the decrease became statistically significant 8 and 12 weeks following ovariectomy (P < 0.05). A similar ovariectomy-related impairment of calcium absorption was not observed in animals fed diets with lower calcium content, making the Ovx rat a tenuous model of intestinal calcium malabsorption. Low dietary calcium decreased cancellous bone mineral content and density at the proximal tibial metaphysis and the decrease was augmented by ovariectomy. The degree of osteopenia due to ovariectomy was not related to the level of dietary calcium or the efficiency of calcium absorption. Received: 7 July 1998 / Accepted: 23 December 1998     

Decreased Bone Mass and Strength in Ovariectomized Cynomolgus Monkeys (Macaca fascicularis)

Agents for prevention or treatment of osteoporosis must now be tested in a large animal species that exhibits bone remodeling. Ovariectomized, nonhuman primates provide one such model, and they consistently develop osteopenia accompanied by high bone turnover rates. The goal of this study was to further characterize this model, and particularly to determine the effect of ovariectomy on bone strength in vertebrae and femoral necks. Longitudinal evaluations of spinal bone mass and serum markers of bone turnover were performed in 19 sham-ovariectomized (SHAM) and 18 ovariectomized (OVX), domestically reared cynomolgus monkeys, aged >9 years. OVX monkeys lost bone relative to both baseline values and SHAM controls. Serum markers of bone turnover were increased by OVX. After 72 weeks, both vertebral bone compressive strength and femoral neck breaking strength were significantly decreased in OVX animals compared with SHAM. Ovariectomized cynomolgus monkeys, like postmenopausal women, develop accelerated bone loss, increased bone turnover, and reduced bone strength, and provide a suitable large animal model for efficacy studies with agents for prevention or treatment of osteoporosis. Received: 24 June 1996 / Accepted: 3 September 1996     

Spinal Trabecular Bone Loss and Fracture in American and Japanese Women

This study examined trabecular bone mineral density (BMD) in Japanese women with and without spinal fracture, and compared the results to American women with and without fracture. The quantitative computed tomography (QCT) systems used at the University of California, San Francisco (UCSF) and at Nagasaki University were cross-calibrated. Normative BMD was assessed with the K₂HPO₄ liquid phantom in 538 Americans aged 20–85 years, and with the B-MAS200 phantom in 577 Japanese aged 20–83 years. These BMD were adjusted for use with the Image Analysis solid phantom using the result of cross-calibration. The trabecular BMD in 111 postmenopausal American women (55 with fracture), and in 185 postmenopausal Japanese women (67 with fracture) were compared for investigation of the difference in BMD values relative to fracture status. The absolute BMD values in Japanese were lower than those in Americans, and the differences were greater with advancing age. The magnitude of the BMD difference was 8.6, 20.5, 38.1 mg/cm³ in women aged 20–24 years, 40–44 years, 60–64 years, respectively. In premenopausal women, BMD began to decrease at the age of 20 in Japanese, whereas the peak bone mass was maintained until the age of 35 in the American women. In immediate postmenopausal women, BMD significantly decreased in both populations. In later postmenopausal women, BMD significantly decreased with age in the Japanese women but decreased less rapidly in the American women. The aging decrease of BMD was 1.4% and 2.2% per year in the later postmenopausal American and Japanese women, respectively. The fracture threshold is considered to be lower in Japanese women. However, the BMD difference between American and Japanese women with fracture was similar to that without fracture. The Z-scores of fracture subjects versus controls were 2.9 in American and 1.8 in Japanese women. In conclusion, Japanese women were found to have a lower BMD and lower fracture threshold than American women. The significant decrease of spinal trabecular BMD in late postmenopause is potentially responsible for the higher prevalence of spinal fracture in Japanese women. Received: 18 December 1995 / Accepted: 23 September 1996     

Systematic Review of Randomized Trials of the Effect of Exercise on Bone Mass in Pre- and Postmenopausal Women

Studies of the effect of exercise programs on bone mass appear inconsistent. Our objective was to systematically review and meta-analyze randomized trials of the effect of exercise on bone mass in pre- and postmenopausal women. A computerized MEDLINE search was conducted for the years 1966–1997. Thirty-five randomized trials were identified. Meta-analytic methods were used to statistically pool results of studies of the effect of impact (e.g., aerobics) and non-impact (e.g., weight training) exercise on the lumbar spine and femoral neck. The most studied bone site was the lumbar spine in postmenopausal women (15 studies), where both impact [1.6% bone loss prevented, 95% confidence intervals (CI): 1.0%–2.2%] and non-impact (1.0%, 95% CI: 0.4%–1.6%) exercise programs had a positive effect. Results for the lumbar spine in premenopausal women (eight studies) were similar: 1.5% (95% CI: 0.6%–2.4%) less bone loss (or net gain) after impact exercise and 1.2% (95% CI: 0.7%–1.7%) after non-impact exercise. Impact exercise programs appeared to have a positive effect at the femoral neck in postmenopausal women (five studies), 1.0% (95% CI: 0.4%–1.6%) bone loss prevented, and possibly in premenopausal women, 0.9% (95% CI: −0.2%–2.0%) bone loss prevented. There were too few trials to draw conclusions from meta-analyses of the effect of nonimpact exercise on the neck of femur. This systematic review of randomized trials shows that both impact and non-impact exercise have a positive effect at the lumbar spine in pre- and postmenopausal women. Impact exercise probably has a positive effect at the femoral neck. More studies are required to determine the optimal intensity and type of exercise. Received: 11 May 1999 / Accepted: 18 January 2000     

The Less Potent Estrogenic Effect of Tamoxifen on Bone in Ovariectomized Rats With Established Osteopenia

The longitudinal effects of tamoxifen (TAM) treatment on bone metabolism, spinal bone mineral density (BMD), and bone mineral content (BMC) were compared with those of estrogen in ovariectomized (OVX) rats with established osteopenia. The 6-month-old rats were divided into Sham (n = 8) and OVX (n = 24) groups. First, the OVX rats were allowed to lose bone for 6 weeks. Six weeks after ovariectomy they were divided into three groups: (1) OVX rats treated with solvent vehicle (OVX+Vehicle), (2) OVX rats injected with TAM subcutaneously six times a week at a dosage of 1.0 mg/kg body weight (OVX+TAM), (3) OVX rats injected with 17-β estradiol subcutaneously six times a week at a dosage of 0.1 mg/kg body weight (OVX+ET). The longitudinal effects of TAM and estrogen on bone were studied by dual energy X-ray absorptiometry (DXA) and biochemical markers including urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr). Ovariectomy resulted in a significant increase in urinary Pyr, Dpyr, and a significant decrease in spine BMD and BMC. TAM treatment completely inhibited the further bone loss in OVX rats with established osteopenia, however, estrogen increased spine BMD and BMC significantly compared with OVX+Vehicle, OVX+TAM, and baseline of treatment. Both TAM and estrogen treatment decreased urinary Pyr and Dpyr significantly in OVX rats. Our findings indicate that TAM acts as an estrogen agonist with respect to effects on spine BMD, BMC, and bone resorption in OVX rats with established osteopenia, but fails to restore spine BMD and BMC to the extent observed with estrogen in this study.     

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     

Effect of Psoas Training on Postmenopausal Lumbar Bone Loss: A 3-Year Follow-Up Study

The present study completed a previous randomized trial that demonstrated the protective effect of 1-year psoas training on lumbar bone loss in postmenopausal women. Computerized tomography had been carried out at the beginning (CT1) and at the end (CT2) of this trial. In the present study, 67 women having completed the first trial were asked to practice psoas exercises (60 hip flexions in sitting position with a 5 kg weight on the knee) for 2 additional years with a third CT control at the end of this period (CT3). The aim of this complementary study was to assess the compliance rate and long-term effect on bone of daily psoas muscle training over a longer period. Twenty-one women performed this daily psoas training for 3 years from CT1 to CT3, and 14 acted as controls during the same period. Fourteen women were controls during the first year (from CT1 to CT2) but practiced psoas training during the following 2 years (from CT2 to CT3). Four women were psoas trained during the first year (from CT1 to CT2) and subsequently crossed over to the control group for the last 2 years. The compliance rate was 42%, with an attendance rate of 88%. The lumbar bone loss was lower in the 21 women trained over the 3 years (−3.26 ± 28.45 mg/cm³) than in the 14 untrained women (−16.79 ± 8.51 mg/cm³) (P= 0.02). The bone loss was not significantly reduced between the two periods of the study in the 12 women having been controls from CT1 to CT2 and having crossed over to the active training group from CT2 to CT3. Psoas training may be effective against lumbar bone loss. We conclude that specific training may play a contributing role in the preventive strategy to avoid osteoporosis. Received: 23 February 1996 / Accepted: 25 October 1996     

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     

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