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     

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     

Lifestyle Determinants of Bone Mineral: A Comparison Between Prepubertal Asian- and Caucasian-Canadian Boys and Girls

The purpose of this study was to examine the difference in lifestyle and morphometric factors that affect bone mineral and the attainment of peak bone mass in 168 healthy Asian (n = 58) and Caucasian (n = 110) Canadian, prepubertal girls and boys (mean age 8.9 ± 0.7) living in close geographical proximity. DXA (Hologic 4500) scans of the proximal femur (with regions), lumbar spine, and total body (TB) were acquired. We report areal bone mineral densities (aBMD g/cm²) at all sites and estimated volumetric density (νBMD, g/cm³) at the femoral neck. Dietary calcium, physical activity, and maturity were estimated by questionnaire. Of these prepubertal children, all of the boys and 89% of the girls were Tanner stage 1. A 2 × 2 ANOVA demonstrated no difference between ethnicities for height, weight, body fat, or bone mineral free lean mass. Asian children consumed significantly less dietary calcium (35%) on average and were significantly less active (15%) than their Caucasian counterparts (P < 0.001). There were significant ethnicity main effects for femoral neck bone mineral content (BMC) and αBMD (both P < 0.001) and significant sex by ethnicity interactions (P < 0.01). The Asian boys had significantly lower femoral neck BMC (11%), aBMD (8%), and νBMD (4.4%). At the femoral neck, BMFL mass, sex, and physical activity explained 37% of the total variance in aBMD (P < 0.05). In summary, this study demonstrated differences in modifiable lifestyle factors and femoral neck bone mineral between Asian and Caucasian boys. Received: 21 July 1998 / Accepted: 30 September 1999     

Longitudinal Evaluation of Vitamin D Status in Healthy Subjects from Southern Italy: Seasonal and Gender Differences

Vitamin D status is currently considered among the relevant determinants of skeletal integrity. Since vitamin D levels present seasonal variations, we longitudinally studied young healthy men and women in order to investigate the related physiologic modifications of both calcium homeostasis and bone remodeling. Thirty-two men (mean age 39.4 ± 7.8 years) and 58 premenopausal women (aged 36.9 ± 6.4 years) from southern Italy were studied. In all subjects the following parameters were measured both in winter and in summer: serum calcium, phosphorus, creatinine, total alkaline phosphatase activity, 25-hydroxyvitamin D (25OHD), parathyroid hormone (PTH), osteocalcin (BGP), together with urinary calcium (Ca/Cr), total pyridinoline (Pyr/Cr) and deoxypyridinoline (d-Pyr/Cr), corrected for creatinine excretion. In both sexes 25OHD levels were significantly higher in summer, while PTH values were lower, than in winter. The prevalence of hypovitaminosis D, defined by concentrations of 25OHD lower than 30 nmol/l, was 17.8% in winter and 2.2% in summer in the whole sample, while it was 27.8% and 3.4%, respectively, among female subjects. Indeed male subjects did not display hypovitaminosis D, having throughout the year significantly higher calcium and 25OHD levels together with lower PTH values, than the women. Moreover, alkaline phosphatase total activity was more elevated in men both in winter and in summer. In women, during winter, bone remodeling markers levels were higher while urinary calcium levels were lower than in summer. In the whole sample serum 25OHD correlated positively with serum calcium and inversely with PTH. The seasonal percentage variations in PTH were inversely correlated with those of Ca/Cr. Our results show a relatively high prevalence of subclinical vitamin D deficiency among young healthy women from southern Italy. Significant gender-specific differences have been demonstrated in both calcium homeostasis and skeletal remodeling indexes; the seasonal fluctuations in the vitamin D–PTH axis are accompanied by cyclical variations of bone turnover rate, which were more pronounced in women. Received: 11 January 2001 / Accepted: 6 July 2001     

Altered Calcium Homeostasis in Adults with Cystic Fibrosis

Bone mineral density (BMD) in cystic fibrosis (CF) patients falls progressively below normal with advancing age, in part due to steroid administration, low levels of sex hormones, chronic inflammatory disease, physical inactivity, and chronic malabsorption of calcium and/or vitamin D. The purpose of this study was to compare the fractional absorption of ⁴⁵Ca and urinary excretion of calcium in CF subjects and normal controls following a high-calcium breakfast containing ⁴⁵Ca. Seven young men and 5 young women with CF with pancreatic insufficiency were studied on two separate occasions, with and without administration of pancreatic enzymes. Eleven healthy young adults with normal BMD measurements served as controls. Mean T-scores at the lumbar spine and femur were significantly lower in the CF subjects (p<0.002). Following baseline, fasting collections, timed serum and urine samples were obtained for 5 h after the meal. Fractional absorption (FA) of ⁴⁵Ca was estimated by the method of Marshall and Nordin. At baseline, CF subjects had lower mean serum 25-hydroxyvitamin D, calcium and albumin values (p<0.03 for each), slightly, but not significantly (p= 0.12), lower albumin-corrected calcium values, equivalent serum 1,25-dihydroxyvitamin D values and a trend toward a higher mean serum parathyroid hormone (PTH) value (p= 0.10). Without pancreatic enzymes, CF subjects showed significantly impaired calcium absorption (5 h FA: 11.8 ± 0.5 for controls vs 8.9 ± 0.2 for CF subjects, p= 0.02) and excretion (4 h excretion: 0.20 ± 0.08 mg Ca/mg creatinine for controls vs 0.16 ± 0.09 mg Ca/mg for CF subjects, p= 0.025). Addition of pancreatic enzymes did not fully compensate for this deficiency. In addition, CF patients had higher serum PTH values after a high-calcium meal (p= 0.03), suggesting mild secondary hyperparathyroidism. Altered calcium homeostasis is likely to be a factor in the development of bone disease in CF patients. Received: 9 July 1998 / Accepted: 27 December 1998     

Long-term Loading and Regional Bone Mass of the Arm in Female Volleyball Players

In the present study, we compared the bone mineral content (BMC) and bone mineral density (BMD) in the arms of 11 female volleyball players (mean age 22.0 ± 2.6 years) training for about 8 hours/week, and 11 nonactive females aged 24.6 ± 3.1 years (mean ± SD) not participating in regular or organized sport activity. Using dual X-ray absorptiometry (DXA), BMC was measured in the proximal and distal humerus, and BMD in the distal radius. Isokinetic concentric peak torque (highest value attained during 5 or 10 repetitions) of the rotator muscles of the shoulder and flexor and extensor muscles of the elbow were measured using an isokinetic dynamometer. The volleyball players had significantly higher BMC (P < 0.05) at the proximal humerus of the dominant arm compared with the nonactive group, but there were no differences between the groups in BMC of the distal humerus and BMD of the distal radius. In the volleyball players, BMC was significantly higher at the proximal humerus, at the distal humerus, and at the distal radius in the dominant compared with the nondominant arm. In the nonactive group, there were no significant differences in BMC and BMD between the dominant and nondominant arm at any site measured. Except for shoulder internal rotation strength and elbow flexion strength at 90°/second that was higher in the dominant arm in the volleyball players, there were no significant differences in muscle strength of the rotator muscles of the shoulder and flexor and extensor muscles of the elbow between the dominant and nondominant arm in the volleyball players and nonactive controls. In the volleyball players, but not in the nonactive controls, there were several significant relationships between shoulder and elbow strength and BMC at the distal humerus of the dominant and especially the nondominant arm. These results show that young female volleyball players have a higher bone mass in the proximal humerus, distal humerus, and distal radius in the dominant compared with the nondominant arm, and a higher bone mass in the proximal humerus compared with nonactive controls. Muscle strength of the rotator muscles of the shoulder is not related to the higher bone mass in the proximal humerus of the dominant arm. Theoretically, the observed differences in bone mass can be related to the type of loading the skeleton undergoes when playing volleyball. Received: 21 June 1996 / Accepted: 3 September 1997     

Professional Football (Soccer) Players Have a Markedly Greater Skeletal Mineral Content, Density and Size Than Age- and BMI-Matched Controls

The total skeletal bone mineral content (BMC), bone mineral density (BMD), bone size, and body composition were measured by dual-energy x-ray absorptiometry (DXA) in all professional male football players of a 1st division team (n = 24) and age- and BMI-matched (n = 22) controls (less than 3 hours of recreational sport activities per week). Average (±1 SD) age of the athletes was 22.6 ± 2.5 years. Intensive training is conducted during 48 weeks a year for 20–22 hours/week. The length of the registered playing career before the study was 8.2 ± 2.7 years. Total skeleton BMC was 18.0% (P < 0.001) greater in the football players. The difference resulted from the sum of 5.2% (P < 0.02) increment of bone size and 12.3% (P < 0.001) increment of BMD. The analysis of skeletal subareas revealed that the difference of the BMC and BMD was greater at the level of the pelvis and legs compared with the arms or trunk. The BMC and BMD of the head was equal for both groups. Also, the bone size of the legs and pelvis was significantly greater for the players compared with controls; there was no difference at the level of the arms or head. Within the group of football players the increment of total skeleton BMD was similar in the young players, with less than 7 years of practice (age 20.6 ± 0.9 years) compared with relative older players (age 24.6 ± 1.9) with more than 7 years of practice. Lean body mass was significantly greater in the players (63.3 ± 4.0 kg) compared with the controls (56.7 ± 3.6, P < 0.001) whereas fat mass was markedly lower (9.4 ± 2.9 kg versus 14.9 ± 6.3 kg), P < 0.002). The BMD of the controls was significantly correlated to total weight, height, and lean mass whereas the BMD of the players was only correlated to muscle mass. The calcium intake from dairy products was similar in both groups. The range of calcium intake was wide among the players (184–2519 mg/day) but it was not significantly correlated to BMD (r = 0.03). In conclusion, male professional football players develop a significant increment of BMC as a result of increased bone size and density. This is already present at the end of the second decade and maintained at least to the end of the third decade in active players. As in other high impact loading sports, the effect on area is specific involving mainly the pelvis and legs. The increment was totally unrelated to the calcium intake from dairy products. The fate of the increased BMC after intensive training is discontinued should be assessed. However, if the findings of the present cross-sectional study are supported by detailed longitudinal investigations, the presently reported observations might be important for the prevention of future osteoporotic fractures. Received: 8 August 1997 / Accepted: 26 January 1998     

Effects of Potassium Bicarbonate Supplementation on Axial and Peripheral Bone Mass in Rats on Strenuous Treadmill Training Exercise

We administered a potassium bicarbonate supplement to rats on strenuous treadmill training in order to determine the effect on bone mass and the metabolic acidosis seen with this type of training. A sample of 45 93-day-old female Wistar rats with a mean initial weight of 267 ± 17 g were studied. The control group (15 rats) was not exercised or given potassium bicarbonate (Ex− PB−). The experimental group (30 rats) was randomly divided into two subgroups of 15 rats each, one that exercised and did not receive potassium bicarbonate (Ex+ PB−) and one that exercised and received potassium bicarbonate (Ex+ PB+), at a dose of 0.05 mg/kg/day administered by esophageal catheter on exercise days. Training consisted of treadmill running on 5 out of 7 days for a period of 11 weeks. Running time, treadmill speed, and the percent grade were gradually increased until week 7, then maintained until rats were sacrificed at the ened of 11 weeks. The bone mineral content (BMC) and bone mineral density (BMD) of the whole right femur and 5th lumbar vertebra were measured. Femoral and vertebral length were also measured. Femur length, weight, BMC, and BMD, and femur BMC/final weight ratio, and vertebral weight, BMD, and BMC, and vertebral BMC/final weight ratio were lower in the Ex+ PB− group than in either the controls or the Ex+ PB+ group (P < 0.01–P < 0.0001); the length of the 5th lumbar vertebra did not differ between groups. Received: 21 July 1998 / Accepted: 12 March 1999     

Bone Mineral Density of Opposing Hips Using Dual Energy X-Ray Absorptiometry in Single-Beam and Fan-Beam Design

Bone densitometry focuses on bone mineral area density (BMD in g/cm²) of the proximal femur and spine in anterior-posterior (AP) projections. Artifacts, such as osteoarthritis and osteophytic calcifications (OC) influence spine BMD, especially in AP scans. If only two sites are measured, as is usual in clinical practice, there may be advantages to measuring both femora rather than one femur and the spine. This would not be useful, however, if there was strong symmetry between the two sides. Furthermore, fan beam (FB) techniques have become available for measuring BMD with less data acquisition time. We compared densitometry of opposing femora in 421 patients (369 women, mean age 59.0 ± 4.8; 52 men, mean age 56.9 ± 7.4) using dual-energy X-ray absorptiometry (DXA): both single-beam (SB) and FB modes were evaluated. The precision errors in vivo (short- and midterm) of total BMD were 0.7% for both SB and FB. The total BMD and BMC of the left hip (0.817 ± 0.124 g/cm², 31.3 ± 6.4 g) were significantly (P < 0.001) higher (2–3%) than the corresponding values of the right hip (0.801 ± 0.125 g/cm², 30.3 ± 6.3 g) in both SB and FB (left BMD 0.802 ± 0.117 g/cm², BMC 30.0 ± 6.2 g versus right BMD 0.795 ± 0.117 g/cm², BMC 29.3 ± 6.3 g) modes. However, BMD of the femoral neck and Ward's triangle were not significantly (P > 0.05) different between the two sides. The FB results were generally 2% lower than SB results. There were highly significant (P < 0.001) correlations (r > 0.9) between both hips using both SB and FB. For diagnostic procedures and longitudinal studies, one should consider that there are bilateral differences of femur BMD, as well as differences between FB and SB scan modes.     

Dual Energy X-Ray Absorptiometry in Small Rats with Low Bone Mineral Density

The feasibility of dual energy X-ray absorptiometry (DXA) using the Norland XR-26 Mark II bone densitometer for measurements of bone mineral content (BMC) and bone mineral density (BMD) in small rats was evaluated. Thirty-two young, isogenic, Lewis rats (weights from 119 g to 227 g) were used; normal rats (n = 7) and rats with low BMD obtained from three different vitamin D-depleted models (n = 25). DXA measurements were performed using the special software for small animals. Duplicate scans of excised femurs performed at 2 mm/second (pixel size of 0.5 mm × 0.5 mm) were very precise measurements with a coefficient of variation (CV) below 1.6% in animals with normal BMD; in rats with low BMD, the CV was significantly higher (P= 0.02–0.04), 7.8% and 4.4% for BMC and BMD, respectively. Regression analysis demonstrated that these measurements were related to the ash weight (R² > 98.6%). The CV for measurements of the lumbar spine at 10 mm/second (pixel size 0.5 mm × 0.5 mm) was 2.6% and 2.2% for BMC and BMD, respectively in rats with normal BMD, and again higher (P= 0.03–0.14) in rats with low BMD, 7.3% and 4.7%, respectively, for BMC and BMD. Even though low CVs were obtained for total body duplicate scans (scan speed of 20 mm/second and a pixel size of 1.5 mm × 1.5 mm), the measurements were problematic for accuracy because of an overestimation of both BMC and the area of bone. Using these scan parameters the measurements of total body bone mineral could not be recommended in small rats with low BMD. Received: 21 May 1999 / Accepted: 3 August 2000 / Online publication: 22 December 2000     

Effect of Chronic Vitamin D Infusion Upon In Vivo Glucose Disposal

We have previously demonstrated that parathyroid hormone (PTH) infusion decreases glucose disappearance rate (K_g) in vivo. Because in the rodent model used it was not possible to determine whether the PTH itself, the induced hypercalcemia, or both contributed to the glucose intolerance, we examined the effect of vitamin D infusion on insulin-mediated glucose disposal. In this model also hypercalcemia is induced but PTH levels are suppressed. Thirty male Sprague Dawley rats were continuously infused with vit D for 5 days using an Alzet miniosmotic pump, at a rate of 9.7 pmol/hour. Thirty controls were infused with the vehicle alone. On the 5th day, glucose 700 mg/kg and insulin 0.35 U/kg were given as a bolus through the left femoral vein and blood samples were obtained from the right femoral vein just prior to and at 2, 5, 10, and 20 minutes post-glucose/insulin infusion. At the end of 5 days, plasma calcium levels were higher in the vit D-infused rats than in the control rats (12.8 ± 0.1 versus 10.0 ± 0.1 mg/dL, P < 0.01) and rat PTH levels were suppressed (2.1 ± 0.1 versus 62 ± 12 pg/ml, P < 0.01). Glucose levels were higher in the vit D animals only at 5 minutes following glucose/insulin bolus (375 ± 7 versus 350 ± 6 mg/dL, P < 0.01) but at no other time. There were no differences between serum insulin levels at any time. Unlike previous findings in PTH-infused rats, K_g (measured from 2 to 20 minutes following glucose/insulin bolus) was not different between groups (4.5 ± 0.3 versus 4.7 ± 0.2, P= 0.92.) A positive correlation between serum calcium and serum glucose was found only at 5 minutes (r = 0.55, P < 0.01) and only in the vit D animals. The areas under the glucose curves approached statistically significant differences (vit D-infused 5258 ± 142 mg/dL/18 minutes versus control 4947 ± 127, P= 0.06.) Analysis of serum glucose data by two-factor analysis of variance (ANOVA) suggests that the two groups differ slightly in glucose values (P= 0.03) but have parallel K_g. In order to define whether different effects of PTH (1–34) and vit D on intracellular calcium [Ca²⁺]_i levels could partly explain the different effects of PTH and vit D infusion on glucose disposal, we investigated the effect of PTH and vit D infusions on basal and concanavalin A (con A)-stimulated changes in mononuclear [Ca⁺²]_i levels. Following 5 days of PTH, vit D, or control infusion, peripheral mononuclear cells were incubated with 50 μg/ml con A. Changes in [Ca⁺²]_i over 5 minutes were calculated by flow cytometric measurement of the calcium sensitive fluo-3 AM dye. Despite achieving significant and comparable degrees of hypercalcemia in the PTH and vit D infused animals, there were no differences in basal or con A-stimulated [Ca⁺²]_i levels from control. Consequently, we conclude that vit D-induced hypercalcemia associated with suppressed PTH levels has mild affects on glucose homeostasis but does not affect glucose disappearance rate in vivo (K_g) as does hypercalcemia induced by PTH infusion, and that neither chronic PTH infusion nor chronic vit D infusion are associated with long-standing changes in [Ca²⁺]_i levels. Received: 24 March 1998 / Accepted: 29 June 1998     

Common Polymorphism of the Vitamin D Receptor Gene is Associated with Variation of Peak Bone Mass in Young Finns

Previous studies suggested a relation between polymorphism of the vitamin D receptor (VDR) gene and bone mineral density (BMD) at perimenopausal age. To enlighten the possible association of the VDR gene polymorphism and BMD, we studied young (20–29 years) adults whose BMD provides a measure of their maximal bone mass. After sequencing the DNA regions flanking the polymorphic BsmI site, we set up a specific solid-phase minisequencing technique to assay this allelic variation. BMD values were adjusted for age, sex, weight, physical activity, smoking, and calcium intake. Young subjects homozygous for the b allele (BsmI site present) had a significantly higher BMD in lumbar spine and femoral neck than those homozygous for the B allele (BsmI site absent). This data shows that the BsmI polymorphism of the VDR gene is associated with peak bone mass. The implication of this result regarding the prevention of osteoporosis deserves further attention. Received: 3 July 1995 / Accepted: 13 February 1996     

Increased Serum 1,25-Dihydroxyvitamin D after Growth Hormone Administration is not Parathyroid Hormone-Mediated

To assess the effects of growth hormone (GH) on serum 1,25-dihydroxyvitamin D [1,25(OH)₂D], we performed the following prospective crossover study in six healthy, young, adult, white men. During each of two admissions for 2? days to a general clinical research center, subjects were placed on a daily dietary calcium intake of 400 mg. Serum calcium, phosphorus, 1,25(OH)₂D, immunoreactive intact parathyroid hormone (PTH), insulin-like growth factor I (IGF-I), IGF binding protein 3 (IGFBP3), tubular reabsorption of phosphate (TRP), and maximum tubular reabsorption of phosphate (TMP/GFR) were measured. Recombinant human GH (rhGH, Humatrope) (25 μg/kg/day subcutaneously for 1 week) was administered prior to and during one of the admissions. Results are expressed as mean ± SEM. Whereas serum 1,25(OH)₂D (58.9 ± 7.7 versus 51.6 ± 7.4 pg/ml, P < 0.01), serum phosphorus (4.5 ± 0.1 versus 3.7 ± 0.1 mg/dl, P < 0.01), TRP (92.0 ± 0.5 versus 87.8 ± 0.7 mg/dl, P < 0.005), TMP/GFR (4.6 ± 0.1 versus 3.5 ± 0.2, P < 0.005), and urinary calcium (602 ± 49 versus 346 ± 25 mg/day, P < 0.001) increased significantly, serum PTH decreased significantly (19.9 ± 1.9 versus 26.8 ± 4.0 pg/ml, P < 0.05) and serum calcium did not change when subjects received rhGH. These findings indicate that in humans, GH affects serum 1,25(OH)₂D independently of circulating PTH and that this effect is mediated by IGF-I. We propose, therefore, that one potential mechanism by which GH stimulates increases in bone mass is via modest increases in serum 1,25(OH)₂D. Received: 2 May 1996 / Accepted: 18 October 1996     

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

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

The Advantage of Alfacalcidol Over Vitamin D in the Treatment of Osteoporosis

Although alfacalcidol is widely used in the treatment of osteoporosis, its mechanism of action in bone is not fully understood. Alfacalcidol stimulates intestinal calcium (Ca) absorption, increases urinary Ca excretion and serum Ca levels, and suppresses parathyroid hormone (PTH) secretion. It remains to be clarified, especially under vitamin D-replete conditions, whether alfacalcidol exerts skeletal effects solely via these Ca-related effects, whether the resultant suppression of PTH is a prerequisite for the skeletal actions of alfacalcidol, and, by inference, whether alfacalcidol has an advantage over vitamin D in the treatment of osteoporosis. To address these issues, we (1) compared the effects of alfacalcidol p.o. (0.025–0.1 μg/kg BW) vis-à-vis vitamin D₃ (50–400 μg/kg BW) on bone loss in 8-month-old, ovariectomized (OVX) rats as a function of their Ca-related effects, and (2) examined whether the skeletal effects of alfacalcidol occur independently of suppression of PTH, using parathyroidectomized (PTX) rats continuously infused with hPTH(1–34). The results indicate that (1) in OVX rats, alfacalcidol increases BMD and bone strength more effectively than vitamin D₃ at given urinary and serum Ca levels: larger doses of vitamin D₃ are required to produce a similar BMD-increasing effect, in the face of hypercalcemia and compromised bone quality; (2) at doses that maintain serum Ca below 10 mg/dl, alfacalcidol suppresses urinary deoxypyridinoline excretion more effectively than vitamin D₃; and (3) alfacalcidol is capable of increasing bone mass in PTX rats with continuous infusion of PTH, and therefore acts independently of PTH levels. It is suggested that alfacalcidol exerts bone-protective effects independently of its Ca-related effects, and is in this respect superior to vitamin D₃, and that the skeletal actions of alfacalcidol take place, at least in part, independently of suppression of PTH. Together, these results provide a rationale for the clinical utility of alfacalcidol and its advantage over vitamin D₃ in the treatment of osteoporosis.     

Evaluation of Differences Between Fan-Beam and Pencil-Beam Densitometers

We compared the bone and body composition results in vivo on two bone densitometers using fan-beam geometry (EXPERT and PRODIGY) with those using pencil-beam geometry (DPX). Measurements were made on large groups of adults ranging in weight from about 50 to 120 kg. Both spine and femur neck BMD on the fan-beam densitometers averaged within 1% of the pencil-beam results, and there was no magnitude dependence of the results by Bland-Altman analysis. Total body BMC and BMD on the PRODIGY and DPX were congruent, but on the EXPERT, BMC was about 2% lower and BMD 2% higher than corresponding values on the DPX. Soft-tissue composition was closely congruent for the PRODIGY and DPX; the comparable EXPERT-DPX differences showed greater scatter but no significant magnitude dependence. The smaller fan-angle of the PRODIGY (4°) probably contributed to its better congruence to pencil-beam results compared with the EXPERT (12°). Received: 23 February 2000 / Accepted: 14 April 2000 / Online publication: 27 July 2000     

Calcidiol and PTH Levels in Women Attending an Osteoporosis Program

We performed a retrospective study of 237 patients attending a specialty osteoporosis practice. Secondary causes for reduced bone mineral density (BMD) were evaluated in 196 postmenopausal women and 41 premenopausal women; mean age was 56 ± 13.8 years (mean ± SD). BMD was measured by dual-energy X-ray absorptiometry (DXA) (QDR 1000W/2000 Hologic). Levels of intact parathyroid hormone (iPTH), calcidiol [25(OH)D], thyroid-stimulating hormone, and 24-hour urinary calcium were measured, and serum and urine protein (SPEP and UPEP) electrophoresis were performed. Overall, 16% of our patients had 25(OH)D levels <15 ng/ml, the lowest acceptable vitamin D level without a concomitant rise in iPTH levels. Among the osteoporotic patients (T score <−2.5 SD), 17% had 25(OH)D levels <15 ng/ml and 7% <10 ng/ml. Among the osteopenic patients (−2.5 < T < −1.0 SD), 11% had 25(OH)D levels <15 ng/ml. Seventeen percent of patients with Z score ≤−1.0 SD (low range normal value) had 25(OH)D levels <15 ng/ml. Low 25(OH)D levels were inversely related to high iPTH values (r = 0.30, P < 0.0001). Hypercalciuria was present in 15% of our patients, elevations of PTH levels (>65 pg/ml, upper normal limit of assay) were present in 11.5%, and hyperthyroidism in 4%. A 25(OH)D level of <25 ng/ml in women (n = 86) with no known secondary causes of low BMD was associated with an iPTH level above 49 pg/ml. The measurement of 25(OH)D levels is recommended in the evaluation of secondary causes for reduced BMD. Supplementation with vitamin D appears needed to keep 25(OH)D above 25 ng/ml, the level required to prevent increments in iPTH levels. Received: 9 February 1998 / Accepted: 1 October 1998     

High Bone Mineral Density in Male Elite Professional Volleyball Players

The aim of this study was to assess bone mass in male elite athletes participating in an impact loading sport (volleyball) and, in particular, to determine whether the asymmetric nature of this sport leads to differences in the skeletal tissue composition of the limbs. Fifteen male volleyball players (VP) (26 ± 4 years, 192 ± 6 cm, 87 ± 9 kg; mean ± SD) and 15 non-active control subjects (25 ± 2 years, 177 ± 8 cm, 72 ± 11 kg; mean ± SD) were studied. VP training sessions (3–6 days/week) included a variety of jumping and weightlifting exercises. The VP were taller and heavier than the control subjects (p<0.001). Whole-body bone mineral content (BMC) and lean mass were higher in VP after adjustment for body mass and height (p<0.001). Axial skeleton and limb BMC and bone mineral density (BMD) were higher in VP than in control subjects (p<0.05). Adjusted lumbar spine (L2–4) BMD was 14% higher in VP than in control subjects (p<0.05). Similarly, a much greater adjusted BMD was observed in the femoral neck of VP (24%, 20%, 27% and 20% for the femoral neck, intertrochanteric, greater trochanter and Ward’s triangle subregions respectively; p<0.05). The dominant arm was slightly heavier (≈3%) and had 4% more muscle mass than the contralateral arm in both the VP (p<0.05) and control subjects (p<0.05). Greater BMC values (9%), BMD (7%) values and the area occupied by osseous pixels (5%) were recorded in the dominant arm as compared with the nondominant arm in VP (p<0.05). No differences between arms were observed in control subjects. Right and left leg BMC and BMD values were similar in control subjects while 4% higher BMC values were recorded for the left leg in the VP group (p<0.05). A close relationship between left leg muscle mass and BMD was observed in the femoral neck subregions of all the subjects (r= 0.81, 0.81, 0.78 and 0.79 for the femoral neck, intertrochanteric, greater trochanter and Ward’s triangle subregions respectively; p<0.001; n= 30). These findings clearly demonstrate a considerably high BMC and BMD in professional volleyball players which seems to be related to the loading type of exercise they perform. Received: 26 October 1998 / Accepted: 26 May 1999     

Calcitriol and Bone Mass Accumulation in Females During Puberty

Adolescence is characterized by rapid skeletal development and high demands for bone minerals. Though the stimulative effect of calcitriol on intestinal calcium and phosphorus absorption is well understood, its effect on bone development is not completely clear. It may be directly involved in the facilitation of calcium economy during this critical phase of skeletal development. Therefore, we evaluated the serum concentrations of calcitriol in relation to skeletal development in a cross-sectional study of 178 healthy Caucasian females during different pubertal stages, extending from childhood to young adulthood. In addition, a subsample of 57 younger girls was followed for a 1-year period to evaluate the association among serum calcitriol, nutrition parameters (dietary calcium, phosphorus, and vitamin D), bone mass accumulation, and biochemical markers of bone turnover. The serum calcitriol concentration in a cross-sectional sample was the highest during pubertal growth spurt (sexual maturity index 3–4, age 11–13 years) (ANOVA: F = 2.4945; P= 0.0329). This correlated to the peak skeletal calcium accretion (g/year) and bone mass accumulation in total body and forearm. In a longitudinal sample, there was a positive association between annual change in TBBMC (P= 0.0255); TBBMD (P= 0.0168); proximal radius (1/3 distance from styloid process) BMC (P= 0.0096); BMD (P= 0.0541), and baseline calcitriol level in forward stepwise regression analyses. The results of the forward stepwise regression analyses with serum calcitriol as a dependent variable and different serum, urinary, and dietary parameters measured at baseline (age 11 years, n = 114) and after 1 year (age 12 years, n = 57) showed that osteocalcin was positively associated with calcitriol in both years; more so in a second year (P= 0.0514, P < 0.0001, respectively). Dietary vitamin D and phosphorus showed negative association with serum calcitriol at age 11, and dietary Ca and P were selected at age 12. The results of this study show that calcitriol is a significant correlate of bone mass accumulation during pubertal growth, presumably in response to the high requirements for calcium during this critical phase of skeletal development. Received: 5 June 1996 / Accepted: 31 December 1996     

Can the fast bone loss in osteoporotic and osteopenic patients be stopped with active vitamin D metabolites?

The aim of this study was to evaluate whether fast trabecular bone loss in osteoporotic and osteopenic patients can effectively be treated with active vitamin D metabolites. Thirty-one osteoporotic and osteopenic patients were monitored between 4 and 22 months before and between 8 and 18 months during the treatment. Fast bone losers were designated as osteoporotic or osteopenic patients with a loss of trabecular bone density in the radius of 3% or more calculated for 1 year. For this differentiation, the high precise peripheral quantitative computed tomography system (DENSISCAN 1000) was used (reproducability 0.3% in mixed collectives). The pretreatment loss and the ``gain' under treatment with active vitamin D metabolites was calculated for 1 year. The treatment consisted of either 0.5 μg calcitriol daily or 1 μg of alfacalcidol daily. Before treatment, the trabecular bone loss in the radius/year was −6.6 ± 0.5% (mean ± SEM). After treatment with vitamin D metabolites, the trabecular bone gain in the radius/year was 0.01 ± 0.6% (mean ± SEM). The difference was highly significant (P < 0.001). In contrast to this, the loss of cortical bone density before treatment was −1.8 ± 0.3% (mean ± SEM) and the reduced loss after treatment −0.2 ± 0.4% (mean ± SEM), both values calculated for 1 year. This difference was less significant (P < 0.05). This study shows that the treatment with active vitamin D metabolites is very effective in slowing fast trabecular bone loss in osteoporotic and osteopenic patients.