Correlation Between Vitamin D Receptor Genotypes and Bone Mineral Density in Japanese Patients with Osteoporosis

In order to better understand the pathogenesis of osteoporosis, we investigated the correlation between the vitamin D receptor (VDR) genotypes defined by BsmI restriction enzyme, as well as other related factors, and the bone mineral density (BMD) at the lumbar spine in 90 Japanese patients with osteoporosis. The same study was performed in 36 patients with osteoarthrosis of the hip joint and 92 healthy volunteers. The majority of the VDR genotypes were bb, and a few of the population showed either the BB or Bb genotype in all three groups. There was no statistical difference in the frequencies of these VDR genotypes in the three groups. The mean age-matched value of BMD (Z scores) at the lumbar spine in patients with osteoporosis was significantly lower than that in patients with osteoarthrosis or healthy volunteers. The mean Z scores of the healthy volunteers with bb genotype were significantly higher than those with BB genotype, whereas those of the osteoporosis patients with BB genotype were significantly higher than those with Bb genotype. There was no significant difference in the mean Z scores between bb and Bb genotypes in patients with osteoporosis and healthy volunteers. No significant difference was seen in the mean Z scores in patients with osteoarthrosis regardless of genotype. On the other hand, body weight significantly correlated with BMD in patients with osteoporosis by simple- and multiple-regression analysis. These results indicate that the BMD at the lumbar spine in Japanese patients with osteoporosis is affected by body weight, and might be affected partially by the VDR genotypes defined by BsmI. Received: 22 September 1995 / Accepted: 24 September 1996     

Correlation of Serum Osteocalcin Fractions with Bone Mineral Density in Women During the First 10 Years after Menopause

Serum immunoreactive osteocalcin (irOC) consists of two fractions that differ from each other by their affinity for hydroxyapatite. The high and low affinity fractions are referred to as irOC_bound and irOC_free, respectively. To evaluate whether these fractions are determinants for different characteristics of bone or bone metabolism, we have performed a cross-sectional study among 212 apparently healthy women between 20 and 90 years of age. Bone mineral density (BMD) was determined at the lumbar spine, and the right femur neck, trochanter, and Ward's triangle using dual-energy X-ray absorptiometry (DXA). Biochemical markers for bone formation and resorption were determined in serum and in urine. After classification according to menopausal age, an inverse correlation was found in the 1–10 years postmenopausal women between irOC_free and BMD, notably of the Ward's triangle and femur neck. It is concluded that in 1–10 years postmenopausal women, irOC_free is an independent marker for BMD, but that in other age groups the association is less clear or is absent. Received: 14 November 1997 / Accepted: 23 March 1998     

The Relation of Dietary Vitamin C Intake to Bone Mineral Density: Results from the PEPI Study

Ascorbic acid is a required cofactor in the hydroxylations of lysine and proline necessary for collagen formation; its role in bone cell differentiation and formation is less well characterized. This study examines the cross-sectional relation between dietary vitamin C intake and bone mineral density (BMD) in women from the Postmenopausal Estrogen/Progestin Interventions Trial. BMD (spine and hip) was measured using dual energy X-ray absorptiometry (DXA). The PEPI participants (n = 775) included in this analysis were Caucasian and ranged in age from 45 to 64 years. At the femoral neck and total hip after adjustment for age, BMI, estrogen use, smoking, leisure physical activity, calcium and total energy intake, each 100 mg increment in dietary vitamin C intake, was associated with a 0.017 g/cm² increment in BMD (P= 0.002 femoral neck; P= 0.005 total hip). After adjustment, the association of vitamin C with lumbar spine BMD was similar to that at the hip, but was not statistically significant (P= 0.08). To assess for effect modification by dietary calcium, the analyses were repeated, stratified by calcium intake (>500 mg/day and ≤500 mg/day). For the femoral neck, women with higher calcium intake had an increment of 0.0190 g/cm² in BMD per 100 mg vitamin C (P= 0.002). No relation between BMD and vitamin C was evident in the lower calcium stratum. Similar effect modification by calcium was observed at the total hip: the β coefficient in the higher calcium stratum was similar to that for the total sample (β= 0.0172, P= 0.01), but no statistically significant relation between total hip BMD and vitamin C was found in the lower calcium subgroup. Although the relation between vitamin C and lumbar spine BMD was of marginal statistical significance in the total sample, among women ingesting higher calcium, a statistically significant association was observed (β= 0.0199, P= 0.024). These data are consistent with a positive association of vitamin C with BMD in postmenopausal women with dietary calcium intakes of at least 500 mg. Received: 12 September 1997 / Accepted: 27 January 1998     

Vitamin K Administration to Elderly Patients with Osteoporosis Induces No Hemostatic Activation, Even in Those with Suspected Vitamin K Deficiency

The administration of menaquinone-4 (MK-4), one of subclasses of vitamin K2, significantly reduces bone loss in postmenopausal osteoporotic women. However, concerns have been raised about whether vitamin K administration alters the hemostatic balance by inducing a thrombotic tendency. We investigated were whether the administration of vitamin K in the form of MK-4 induced a thrombotic tendency in 29 elderly patients with osteoporosis (5 men, 24 women; age range 78.7+/-5.1 years). Patients were administered 45 mg/day (three times a day, 30 min after each meal) of MK-4 for 12 weeks. Blood samples were obtained from the patients at 0, 4 and 12 weeks after the start of MK-4 administration. A number of hemostatic parameters remained stable under the markedly increased plasma levels of MK-4. However, in patients with suspected vitamin K deficiency, whose plasma levels of vitamin K or factor VII were low, vitamin-K-dependent clotting factors such as factor VII and prothrombin were gradually increased after administration of MK-4. No changes in the sensitive molecular markers such as TAT and F1+2, which reflect the amount of thrombin generated in the blood stream, were observed, even in those patients with suspected vitamin K deficiency. These results indicate that MK-4 can be administered safely, with regard to maintaining the hemostatic balance, to osteoporotic patients receiving no anticoagulant therapy.     

Bone Mineral Density of Patients with Thalassemia Major: Four-Year Follow-Up

The purpose of this study was to evaluate the bone mineral density (BMD) of 50 patients aged 9–28 years, with thalassemia major and to assess the alterations of bone density in a 4-year follow-up study. They were measured with a DPX densitometer at the lumbar spine and femur area and divided into three groups: preadolescents, adolescents, and adults. All patients received calcium and vitamin D supplements, and 8 of the 50 received hormone replacement therapy (HRT). All patients had a significantly lower BMD compared with healthy subjects. Mean values of lumbar BMD of the three groups were 1.3, 2, and 3 standard deviations (SDs) lower than those of healthy subjects of the same age. All adolescent patients with normal gonadal function and those who received HRT showed an increase in BMD during the period of the study. Adult patients also showed an increase in bone density as long as the treatment lasted. However, adolescent and adult patients who had hypogonadotropic hypogonadism but could not get therapy showed a decrease in bone density. BMD of patients with thalassemia major shows a good index of bone status which should be evaluated, especially for the determination and follow-up of therapy. Received: 31 March 1997 / Accepted: 1 November 1998     

Vitamin D Receptor Genotype is Not Associated with Bone Mineral Density in Three Ethnic/Regional Groups

We report a cross-sectional study of 48 men, 56 premenopausal women, and 80 postmenopausal women who were of three ethnic/regional backgrounds: southern European (Greek, Italian), eastern European (Jewish, Polish, Hungarian), and western European (French, British). We determined bone mineral density (BMD) at four skeletal sites and assessed the vitamin D receptor (VDR) genotype by the Bsml restriction site polymorphism. Age and body mass index had significant effects on BMD by multiple regression analysis. In addition, ethnic/regional group had a significant effect on spinal BMD in premenopausal females (P= 0.014) and in males (P= 0.039). However, VDR genotype had no significant effect on BMD in any of the three study groups. Received: 4 December 1995 / Accepted: 27 March 1996     

The Effect of Vitamin K and D Supplementation on Ovariectomy-Induced Bone Loss

This study was designed to assess the effect of vitamin K and D supplementation on ovariectomy-induced bone loss. Female Sprague-Dawley rats aged 8–9 months were ovariectomized (OVX) or sham operated and divided into five experimental groups: (1) ovariectomy (OVX), (2) OVX plus vitamin K supplementation, (3) OVX plus vitamin D supplementation, (4) OVX plus vitamin K and vitamin D supplementation, and (5) sham operation. The trabecular bone area was estimated by bone histomorphometry by microradiography and histological examination. Bone loss in OVX plus vitamin K and vitamin D group was significantly reduced at both 7 and 14 weeks compared with the OVX group. No significant bone loss in OVX plus vitamin K or OVX plus vitamin D groups was found. A similar effect of vitamin K and D supplementation on ovariectomy-induced bone loss was recognized in histological examination. Our findings indicate that vitamins K and D may have a synergistic effect on reducing bone loss. This is valuable information for the treatment of bone loss in postmenopausal women with osteoporosis. Received: 1 September 1998 / Accepted: 10 January 1999     

Effect of Long-Term Growth-Hormone Substitution Therapy on Bone Mineral Density and Parameters of Bone Metabolism in Adult Patients with Growth Hormone Deficiency

Reduced bone mineral density (BMD) and the prevalence for osteoporotic vertebral fractures are symptoms of growth hormone deficiency (GHD) syndrome, and GH replacement therapy is now available for GH-deficient adults. We investigated the long-term effects of GH replacement therapy on bone mineral density (BMD) and bone metabolism in 19 adult patients with GHD over a period of 18 months. In response to GH treatment, the initially decreased IGF-I concentrations rose significantly during 18 months of therapy to levels within the normal range (matched for sex and age) (mean change 158.1 ± 50.8 ng/ml, P < 0.001). Parameters of bone formation such as osteocalcin (OC) and procollagen I-C-Peptide (PICP) showed a significant increase in the first 6 months of therapy, followed by a slight decrease in the next months. Markers of bone resorption (Crosslaps^R and deoxypyridinoline (D-Pyr) also increased significantly with a peak value after 6 months and all parameters except PICP remained above baseline values after 18 months. BMD of the femoral neck (FN) showed an increase after 18 months of therapy (mean change 0.01 ± 0.03 g/cm² after 18 months, n.s.). However, the increase in BMD was significant only in the lumbar spine (LS) (mean change 0.03 ± 0.04 g/cm², P < 0.05 after 18 months). We conclude that GH replacement therapy in adult patients with GHD over a period of 18 months causes a pronounced increase in bone turnover mainly during the first 12 months of therapy and increases BMD of the lumbar spine and the femoral neck after 18 months. Received: 13 March 1997 / Accepted: 7 August 1997     

Bone Mineral Density in Patients Taking H2-Receptor Antagonist

Osteoporosis after gastrectomy is a common clinical disorder. In gastrectomized patients, decreased gastric acidity may be associated with impaired calcium absorption. This study was undertaken to determine whether patients with chronic use of H₂-receptor antagonists (HRA) had demonstrable decreases in bone mineral density (BMD). Thirty-three patients taking cimetidine, ranitidine, or famotidine for more than 2 years were analyzed. We measured BMD of L2–L4 using dual energy X-ray absorptiometry (DXA). Osteoporosis (BMD less than 0.70 g/cm²) was found only in three patients (9%). As compared with healthy controls, age- and sex-matched BMD ranged from 74.4% to 132.9%, with a mean of 97.0%, and was not influenced by the period of HRA use (<5 years versus >5 years or more). Although the age- and sex-matched BMD was different among the kinds of HRA (98.6% for cimetidine, 101.3% for ranitidine, and 85.5% for famotidine), the relationship between the BMD and type of drug was not significant by multivariate analysis. These results indicate that chronic use of HRA has little influence on the degree of BMD, and suggest that decreased gastric acidity is not always associated with osteoporosis after gastrectomy. Received: 18 February 1977 / Accepted: 7 August 1997     

Loss of Bone Mineral Density in Women Athletes During Aging

Total and regional bone mineral density (BMD) by dual-energy-X-ray absorptiometry (DXA) and bone turnover were tested in 50 highly trained women athletes and 21 sedentary control women (18–69 years; BMI < 25 kg/m²). VO_2max (ml · kg⁻¹· min⁻¹) and lean tissue mass (DXA) were significantly higher in the athletes versus controls (both P < 0.0001). Total body BMD did not decline significantly with age in the athletes whereas lumbar spine (L₂–L₄) BMD approached statistical significance (r =−0.26; P= 0.07). Significant losses of the femoral neck (r =− 0.42), Ward's triangle (r =−0.53), and greater trochanter BMD (r =−0.33; all P < 0.05) occurred with age in the athletes. In the athletes, total body BMD, L₂–L₄ BMD, and BMD of all sites of the femur were associated with lean tissue mass (r = 0.32 to r = 0.57, all P < 0.05) and VO_2max (r = 0.29 to r = 0.48, all P < 0.05). Femoral neck and greater trochanter BMD were higher in the athletes than in controls (both P < 0.05) and lumbar spine and Ward's triangle BMD approached statistical significance (both P= 0.07). Bone turnover was assessed by serum bone-specific alkaline phosphatase (B-ALP), urinary deoxypyridinoline cross-links (Dpd), and urinary aminoterminal cross-linked telopeptides (NTX). There were no relationships between B-ALP or Dpd with age whereas NTX increased with age (r = 0.46, P < 0.05) in the entire group. Levels of B-ALP and NTX were negatively associated with total body, L₂–L₄, femoral neck, Ward's triangle, and greater trochanter BMD (P < 0.05). B-ALP and Dpd were not significantly different between athletes and controls whereas NTX was lower in the athletes than in controls (P < 0.001). The high levels of physical activity observed in women athletes increase aerobic capacity and improve muscle mass but are not sufficient to prevent the loss of bone with aging. Received: 28 November 1997 / Accepted: 8 April 1998     

Bone Mineral Density and Bone Turnover in Patients with Knee Osteoarthritis Compared with Generalized Osteoarthritis

The aim of this study was to investigate bone mineral density (BMD) and bone turnover in patients with primary knee osteoarthritis (KOA) and to compare them with generalized OA (GOA) and nonGOA patients. A total of 88 postmenopausal primary KOA patients were studied. OA was graded by using knee radiographs. BMD of the lumber spine, femur, and radius, and biochemical markers of bone turnover, pyridinoline (Pyr), deoxypyridinoline (Dpyr), CTx, and osteocalcin were compared among each grade. BMD was also compared with 88 normal controls who were age and weight-matched. In 88 KOA patients, 56 were divided into 28 GOA and 28 non-GOA groups by grading hand radiographs. BMD and biochemical markers were compared between GOA and non-GOA. KOA patients had higher BMD at several skeletal sites compared with age- and weight-matched normals. A significant difference of BMD between each grade was observed between grades 0–1 and 3 (0.774 ± 0.143 versus 0.940 ± 0.185 g/cm², P < 0.001), grades 2 and 3 (0.781 ± 0.125 versus 0.940 ± 0.185 g/cm², P < 0.01) in the spine, and between grades 0–1 and 3 (0.505 ± 0.100 versus 0.564 ± 0.127 g/cm², P < 0.05) in the trochanter. A significant difference of biochemical bone markers was observed between grades 0–1 and 3 (P < 0.05) and between grades 2 and 3 (P < 0.05) in Pyr and grades 0–1 and 3 (P < 0.05) and between grades 1 and 4 (P < 0.05) in Dpyr, but not in osteocalcin and CTx. GOA patients had higher BMD of the spine (0.902 ± 0.175 versus 0.747 ± 0.138 g/cm², P < 0.01), trochanter (0.535 ± 0.107 versus 0.480 ± 0.107 g/cm², P < 0.05), and one-third of the radius (0.526 ± 0.068 versus 0.472 ± 0.089 g/cm², P < 0.05) and had significantly higher biochemical markers in Pyr and Dpyr than non-GOA patients. It is concluded that KOA patients had higher BMD at several skeletal sites. Biochemical bone markers were influenced by some degree of cartilage damage in OA patients. This tendency was stronger in GOA patients than in non-GOA patients. Received: 12 February 1999 / Accepted: 2 November 1999     

Bone Mineral Density Is a Predictor of Survival

The purpose of this study was to examine the relationship between bone mineral density (BMD) and survival in both sexes and to compare BMD with other established risk factors such as blood pressure and cholesterol. A population-based prospective study of 1924 individuals (850 men, 1074 women) was performed in G?teborg from 1980 to 1983. Measurements of BMD were obtained in 1468 (76%) of the participants (653 men, 815 women). This selection of individuals generated 10,965 person years, and death was registered for 289 men and 197 women in the 7-year period (2661 days) after bone mineral measurement. Later information on date of death was obtained from the official population register. This information covers 7 years from the time of survey of the last examined participant (in Dec. 1983). At the beginning of the study, BMD was measured in the calcaneus by dual photon absorptiometry (DPA), and blood pressure, serum cholesterol, serum triglycerides, and body mass index (BMI) were also recorded. The study was coordinated with the National Register of Causes of Death and the National Cancer Register. A modified version of the Cox proportional hazards model was used to calculate and determine the age-adjusted relations between nontrauma mortality and BMD. When the various quartiles of BMD were compared prospectively from 70, 75, and 79 years of age with survival figures during the 2661-day follow-up period, the first and the second quartiles with the lowest BMD at entry showed the lowest survival rate in both men (P= 0.01) and women (P= 0.01). A decrease of 1 SD of BMD in a univariate analysis was associated with a 1.39-fold increase in mortality in both men (95% confidence interval 1.25–1.56, P < 0.001) and women (95% confidence interval 1.22–1.58, P < 0.001), and a multivariate analysis demonstrated a relative risk of 1.23 (95% confidence interval 1.10–1.41, P < 0.001) in men and 1.19 (95% confidence interval 1.02 to 1.39, P= 0.019) in women. All relations were adjusted for sex, age, and follow-up. This study indicates that BMD is a predictor of survival, especially for subjects over 70. Bone mineral density was found to be a better predictor of death than blood pressure and cholesterol. This study indicates that, after adjustments have been made for diseases, low bone mass is an independent predictor of mortality and might be a marker of general health or functional aging. Its measurement might therefore be a valuable tool in general health investigations. Received: 26 December 1996 / Accepted: 27 January 1998     

Bone Mineral Density in the Chronic Patellofemoral Pain Syndrome

Bone mineral density (BMD) and clinical status of 40 patients with a chronic, unilateral patellofemoral pain syndrome (PFPS) were determinated. The mean duration of the disease at the time of the follow-up was 7.6 ± 1.8 (SD) years. The BMD was measured at the spine (L2–L4), and the femoral neck, trochanter area of the femur, distal femur, patella, proximal tibia, and calcaneus of both lower extremities using a dual-energy X-ray absorptiometric (DXA) scanner. The mean BMD of the affected limb (compared with the unaffected side) was significantly lower in the distal femur (−3.3%; P= 0.002), patella (−2.5%; P= 0.016), and proximal tibia (−1.9%; P= 0.008). The femoral neck, trochanter area of the femur, and calcaneus showed no significant side-to-side differences, and the spinal BMDs of men and women with the PFPS were comparable with the manufacturer's age-adjusted reference values for Western European men and women. The relative BMDs of the affected knee showed strongest correlation with the muscle strength of the same knee: the better the muscle strength compared with the healthy knee, the higher the relative BMD (r = 0.56–0.58 with P < 0.001 in each anatomic site of the knee). In the stepwise regression analysis, low body weight or low body mass index, high level of physical activity, the patient's good subjective overall assessment of his/her affected knee, and short duration of the symptoms were also independent predictors of the high relative BMD in the affected knee so that along with the muscle strength these variables could account for 51% of the variation seen in the relative BMD of the femur, 61% in the patella, and 54% in the proximal tibia. In conclusion, chronic patellofemoral pain syndrome results in a significantly decreased BMD in the knee region of the affected limb. The spine, proximal femur, and calcaneus are not affected. Recovery of normal muscle strength and knee function seems to be of great importance for good BMD. Received: 30 May 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 Content and Density in Professional Tennis Players

Total and regional bone mineral content (BMC) as well as lean and fat mass were measured in nine male professional tennis players (TPs) and 17 nonactive subjects; dual-energy X-ray absorptiometry (DXA) was used for measuring. The mean (±SD) age, body mass, and height were 26 ± 6 and 24 ± 3 years, 77 ± 10 and 74 ± 9 kg, and 180 ± 6 and 178 ± 6 cm for the TP and the control group (CG), respectively. The whole body composition for BMC, lean mass, and fat of the TP was similar to that observed in the CG. The tissue composition of the arms and legs was determined from the regional analysis of the whole-body DXA scan. The arm region included the hand, forearm, and arm, and was separated from the trunk by an inclined line crossing the scapulo-humeral joint. In the TP, the arm tissue mass (BMC + fat + lean mass) was about 20% greater in the dominant compared with the contralateral arm because of a greater lean (3772 ± 500 versus 3148 ± 380 g, P < 0.001) and BMC (229.0 ± 43.5 versus 188.2 ± 31.9 g, P < 0.001). In contrast, no significant differences were observed either in BMC or BMD between arms in the CG. Total mass, lean mass, and BMC were greater in the dominant arm of the TP than in the CG (all P < 0.05). In the TP, BMD was similar in both legs whereas in the CG, BMD was greater in the right leg. Lumbar spine (L2–L4) BMD, adjusted for body mass and height, was 15% greater in the TP than in the CG (P < 0.05). Femoral neck BMDs (femoral neck, Ward's triangle, greater trochanter, and intertrochanteric regions) adjusted for body mass and height were 10–15% greater in the TP (all P < 0.05). Ward's triangle BMD was correlated with the maximal leg extension isometric strength (r = 0.77, P < 0.05) even when adjusted for body mass (r = 0.76, P < 0.05) and height (r = 0.77, P < 0.05). In summary, the participation in tennis is associated with increased BMD in the lumbar spine and femoral neck. These results may have implications for devising exercise strategies in young and middle-aged persons to prevent involutional osteoporosis later in life. Received: 29 April 1997 / Accepted: 14 November 1997     

Effects of Long-Term Administration of Methotrexate on Bone Mineral Density in Rheumatoid Arthritis

Because previous studies of high-dose methotrexate usage have demonstrated an effect on bone formation and resorption, this study was done to determine whether long-term, low-dose use of methotrexate for the treatment of rheumatoid arthritis causes bone loss. Bone mineral density (BMD) of the lumbar spine and hip was measured in 10 Caucasian postmenopausal women who had never received methotrexate and 10 Caucasian postmenopausal women who had received the drug for 3 or more years. There were no significant differences in BMD at the lumbar spine (L2–L4) between patients who had used long-term methotrexate compared with patients never treated with methotrexate (1.08 ± 0.08 g/cm² versus 0.98 ± 0.14 g/cm², respectively; P= 0.08). Similarly, there were no significant differences in BMD at the femoral neck between methotrexate users and nonusers (0.81 ± 0.08 g/cm² versus 0.76 ± 0.15 g/cm², respectively; P= 0.42). These results suggest that long-term low-dose methotrexate treatment for rheumatoid arthritis is not associated with accelerated bone loss. Received: 16 October 1997 / Accepted: 9 July 1998     

Bone Mineral Density and Androgen Levels in Elderly Males

To clarify the relationship of sex male hormones and bone in men, we studied in 140 healthy elderly men (aged 55–90 years) the relation between serum levels of androgens and related sex hormones, bone mineral density (BMD) at different sites, and other parameters related to bone metabolism. Our results show a slight decrease of serum-free testosterone with age, with an increase of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in a third of the elderly subjects studied. BMD decreased significantly with age in all regions studied, except in the lumbar spine. We found a positive correlation between body mass index (BMI) and BMD at the lumbar spine and femoral neck (P < 0.001). No relationship was found (uni- and multivariate regression analysis) between serum androgens or sex hormone-binding globulin (SHBG) and BMD. We found a positive correlation of vitamin D binding protein (DBP) and osteocalcin with lumbar spine BMD and with BMI, DBP, IGF-1, and PTH with femoral neck BMD. In conclusion, there is a slight decline in free testosterone and BMD in the healthy elderly males. However, sex male hormones are not correlated to the decrease in hip BMD. Other age-related factors must be associated with bone loss in elderly males. Received: 29 April 1997 / Accepted: 9 November 1997     

Not All Postmenopausal Women on Chronic Steroid and Estrogen Treatment are Osteoporotic: Predictors of Bone Mineral Density

Chronic steroid use results in osteoporosis, and postmenopausal women are believed to be at a high risk for steroid-induced bone loss. The purpose of this study was to determine predictors of bone mineral density (BMD) in postmenopausal women on both chronic steroid and hormone replacement therapy. Seventy-six postmenopausal women (≥3 years postmenopausal, ≥2 years of steroid treatment of ≥5 mg/day of prednisone, and ≥1 year of hormone replacement therapy) were recruited into this study. Measurements of BMD of the lumbar spine and femoral neck were obtained in all subjects. Risk factors for osteoporosis were obtained by questionnaire. Discriminant analysis was performed to determine predictors of BMD. Osteoporosis, defined by a T score of <−2.5, was present in the lumbar spine or femoral neck in 34 of the 76 subjects. Based on these criteria, women with osteoporosis were significantly older, were more years postmenopausal, and had a lower body mass index (BMI) than women who did not have osteoporosis. Predictors of osteoporosis for both the femoral neck and spine included a low BMI (P < 0.05), more years postmenopausal (P < 0.01), and more years on steroids (P < 0.01). Low BMI was the only significant predictor of osteoporosis in the lumbar spine (P < 0.05), whereas for the femoral neck both years on steroids (P < 0.05) and BMI (P < 0.05) were significant predictors of low BMD. In summary, not all postmenopausal women on chronic steroid and hormone replacement therapy are osteoporotic but a low BMI, more years on steroids, and more years postmenopausal were significant predictors of osteoporosis in these subjects. Received: 8 November 1997 / Accepted: 21 May 1997     

Cross-Sectional Study of Weight-Bearing Activity on Proximal Femur Bone Mineral Density

In this cross-sectional study we investigated the effect of compressive and tensile forces applied on the proximal femur during weight-bearing activities. Ninety-seven men (29.9 ± 1.7 years) were divided into two groups: 69 exercisers who had practiced regular high-impact weight-bearing activities for at least 5 years and 28 controls who had been sedentary for at least 5 years. The maximum isometric hip abduction strength was measured. The bone mineral density (BMD) of the femoral neck and the greater trochanter was assessed using dual-energy X-ray absorptiometry (DXA). Controls were considered as the reference population to calculate the Z score. Mean BMD values of the femoral neck were 0.97 g/cm² on both sides in the exercisers and 0.83 g/cm² on the right side and 0.84 g/cm² on the left side in the controls. Mean BMD values of the greater trochanter were 0.86 g/cm² on the right side and 0.87 g/cm² on the left side in the exercisers, 0.73 g/cm² on the right side and 0.72 g/cm² on the left side in the controls. The BMD was significantly higher in exercisers at both trochanteric and cervical sites (P= 0.0001). Both left and right hip abduction strength was significantly greater in the exercisers than in the controls (P < 0.05) and was positively correlated to cervical and trochanteric BMD (P < 0.01). In the exerciser group, the trochanteric Z score was higher than the cervical Z score at both right (P= 0.06) and left (P= 0.002) sides. Therefore, the proximal femoral BMD was significantly greater in exercised subjects as compared with sedentary controls. The difference was observed at the level of both the femoral neck (where it is known anatomically that only compressive gravitational forces are exerted) and the greater trochanter (where it is known that tensile forces are exerted). This result suggests the participation of both compressive and tensile forces in the mechanisms by which exercise influences bone trophicity. Received: 19 November 1997 / Accepted: 7 August 1998     

Bone Mineral Density and Bone Size in Men With Primary Osteoporosis and Vertebral Fractures

The bone mineral density (BMD) at the lumbar spine, proximal femur, and total skeleton was evaluated in 38 men with primary osteoporosis and vertebral fractures. BMD of the patients was significantly reduced over all skeletal areas compared with controls. The Z-score of the lumbar spine (−2.8 ± 0.9) was less than that of the other areas (P < 0.001) except the legs (−2.5 ± 1.1) (p.n.s.) showing that bone loss had a tendency to be greater over the axial skeleton. Vertebral dimensions compared with age-matched controls were as follows: projected L2–L4 area (cm 2): 45.7 ± 5.6 versus 53.7 ± 3.6 (P < 0.001); vertebral width (cm): 4.37 ± 0.44 versus 4.90 ± 0.36 (P < 0.001). Serum biochemical parameters and testosterone levels were similar between osteoporotic and control men. We conclude that men with vertebral osteoporotic fractures have reduced vertebral BMD and vertebral dimensions compared with age-matched controls. Thus, these findings indicate that the achievement of a reduced bone size at the end of the growth period or a failure of periosteal increase during adult life is likely to contribute to the pathogenesis of the vertebral fractures observed in older men. Received: 31 January 1997 / Accepted: 2 July 1997