The effect of moderate impact exercise on skeletal integrity in master athletes

We measured bone mineral density (BMD) in senior athletes competing in running and swimming events and compared results to those of sedentary controls. Total body BMD was greatest among runners suggesting that moderate impact activities continue to play a role in maintaining skeletal integrity with age. INTRODUCTION: The role of moderate impact exercise in maintaining skeletal integrity as we age remains unclear. METHODS: To determine the effect of moderate impact exercise on skeletal integrity in the elderly, we recruited master athletes, including 44 runners (moderate impact exercise) and 43 swimmers, competing in the 2005 National Senior Olympic Games and 87 non-athletes, all over the age of 65 years. Height, weight, calcium, vitamin D intake, bone mineral density (BMD) of the total body, spine, hip (total hip, femoral neck, trochanter, intertrochanter), forearm (1/3 distal radius), and heel ultrasound, and Z-scores were characterized by mean +/- SD and compared by analysis of variance. T-scores were used to determine sites of osteopenia and osteoporosis. RESULTS: Total body BMD of runners was significantly greater than that of controls (1.11 +/- 0.13 versus 1.10 +/- 0.13 g/cm(2), p < 0.05) and marginally greater than that of swimmers when adjusted for age and weight. Heel ultrasound bone mass of runners was significantly greater than that of swimmers or controls. Runners also had higher BMD in the total hip, intertrochanter and 1/3 distal radius when compared to swimmers. CONCLUSION: These findings suggest that moderate impact exercise contributes to skeletal integrity in older age.     

Intermittent administration of bovine PTH-(1-34) increases serum 1,25-dihydroxyvitamin D concentrations and spinal bone density in senile (23 month) rats.

We examined the effect of intermittent administration of bovine parathyroid hormone (1-34) (bPTH) on spinal bone mineral content (BMC) and bone mineral density (BMD), serum 1,25-dihydroxyvitamin D concentrations, and serum markers of osteoblast function in senile male and female rats (23 and 24 months of age, respectively). Sexually mature young (3 month) male rats were similarly treated for comparison. bPTH administration increased serum osteocalcin concentrations without changing serum inorganic phosphate or calcium concentrations in either group of old animals. In young animals, PTH administration increased the serum calcium and inorganic phosphate concentrations significantly (p less than 0.05), although values remained within the normal range. In the vehicle-treated male rats, serum 1,25-dihydroxyvitamin D concentrations were lower in the senile than in the young animals (18 +/- 5 versus 47 +/- 6 pg/ml, p less than 0.05). PTH administration resulted in significantly increased serum 1,25-dihydroxyvitamin D concentrations in the senile and young male animals (both, p less than 0.05) and the final mean serum 1,25-dihydroxyvitamin D concentrations were not statistically different (68 +/- 9 versus 85 +/- 6 pg/ml respectively; p = NS). Serum 1,25-dihydroxyvitamin D concentrations were significantly (p less than 0.05) higher in the PTH-treated senile female rats than the sex-matched, vehicle-treated controls. The pretreatment spinal BMC and BMD as assessed by dual-energy x-ray absorptiometry (DEXA) were significantly higher in the senile male animals than in the young animals. Spinal BMC and BMD decreased in the vehicle-treated senile male rats (p less than 0.05) over the 3 weeks of the study despite a gain in weight.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bone mineral density among female sports participants

Training for and participation in impact-loading sports are associated with alterations in bone strength which are specific to anatomical site and type of strain. The effect of exercise on bone mineral density (BMD) depends on the type of activity engaged in. Sports with high impact loading seem to have a positive effect in promoting bone mineralisation, whereas those with low impacts may have negative or no effects. The aims of the present study were to compare BMD and body composition measures among female participants in three distinctly different sports and investigate differences from sedentary control subjects. Participants were club and university level Rugby Union football players (n = 30, age: 21.4 +/- 1.9 years, height: 1.67 +/- 0.05 m, mass: 73.3 +/- 10.7 kg), netball players (n = 20, 20.7 +/- 1.3 years, 1.68 +/- 0.07 m, 64.3 +/- 7.2 kg), distance runners (n = 11, 21.5 +/- 2.6 years, 1.68 +/- 0.04 m, 57.1 +/- 6.1 kg), and sedentary controls (n = 25, 21.4 +/- 1.1 years; 1.64 +/- 0.07 m, 56.8 +/- 6.8 kg). With the exception of three distance runners, all participants were eumenorrhoeic. Bone mineral density scans were performed for whole-body, left proximal femur, and lumbar spine (L1-4) using dual-energy X-ray absorptiometry. Fat mass, percent body fat, and fat-free soft tissue mass were assessed from whole-body scans. Regional and segmental analysis was also carried out on whole-body BMD data using standard procedures. The runners had a lower fat mass and percent body fat compared to the other sports participants and the controls. All sports groups had higher BMD values than had the controls. Density of bone in the upper body was most pronounced in the rugby football players and least pronounced in the runners. Positive effects were evident at all sites for the rugby players. There were significant correlations between BMD and fat-free soft tissue mass, BMD and body mass, and BMD and training volume. It is concluded that sports participation has positive effects on BMD. The effects are site-specific and depend on the loading characteristics of the sport.     

Effect of long-distance running on bone mass in women

The effect of long-distance running on bone mass was assessed in 10 premenopausal and 9 estrogen-deprived postmenopausal women and compared to that in closely matched sedentary control women. Vertebral trabecular bone density (VBD) was determined by computed tomography and radial cortical bone density (CBD) by single-photon absorptiometry. Physical fitness was assessed by determining maximal oxygen consumption (VO2max) on a treadmill run to exhaustion. VBD was 183 +/- 7 mg/cm3 and VO2max was 48 +/- 1 ml/kg per minute in young women runners and 163 +/- 8 mg/cm3 and 32 +/- 2 ml/kg per minute in sedentary young women. A positive correlation was noted between VBD and VO2max in these groups (r = 0.509, p less than 0.03). Despite a significantly higher VO2max in postmenopausal women runners compared with sedentary controls (37 +/- 2 versus 24 +/- 2 ml/kg per minute), VBD was identical (112 +/- 5 versus 111 +/- 5 mg/cm3) and no correlation was seen between VBD and VO2max (r = 0.187, p = 0.457). Radial cortical bone density was not different between the runners or sedentary groups in young women (0.738 +/- 0.01 versus 0.732 +/- 0.1 g/cm2) or postmenopausal women (0.617 +/- 0.3 versus 0.665 +/- 0.4 g/cm2). These results suggest that although physical fitness enhances vertebral bone density in premenopausal women, it does not appear to prevent age- and/or sex steroid deficiency-induced bone loss in postmenopausal women.     

Swimming Enhances Bone Mass Acquisition in Growing Female Rats

Growing bones are most responsive to mechanical loading. We investigated bone mass acquisition patterns following a swimming or running exercise intervention of equal duration, in growing rats. We compared changes in bone mineral properties in female Sprague Dawley rats that were divided into three groups: sedentary controls (n = 10), runners (n = 8) and swimmers (n = 11). Runners and swimmers underwent a six week intervention, exercising five days per week, 30min per day. Running rats ran on an inclined treadmill at 0.33 m.s⁻¹, while swimming rats swam in 25⁰C water. Dual energy X-ray absorptiometry scans measuring bone mineral content (BMC), bone mineral density (BMD) and bone area at the femur, lumbar spine and whole body were recorded for all rats before and after the six week intervention. Bone and serum calcium and plasma parathyroid hormone (PTH) concentrations were measured at the end of the 6 weeks. Swimming rats had greater BMC and bone area changes at the femur and lumbar spine (p < 0.05) than the running rats and a greater whole body BMC and bone area to that of control rats (p < 0.05). There were no differences in bone gain between running and sedentary control rats. There was no significant difference in serum or bone calcium or PTH concentrations between the groups of rats. A swimming intervention is able to produce greater beneficial effects on the rat skeleton than no exercise at all, suggesting that the strains associated with swimming may engender a unique mechanical load on the bone.

Key points

• A six week swimming intervention is able to produce greater osteogenic effects on the rat skeleton than no exercise.
• A daily treadmill running intervention does not attenuate a rats propensity to run voluntarily at night.

Key words: Weight-bearing exercise, swimming, treadmill, DXA, bone mass, rats.     

Abnormal Response to Physical Activity in Femurs after Heterozygous Inactivation of One Allele of the Col2a1 Gene for Type II Collagen in Mice

The objective of this study was to evaluate the influence of heterozygous inactivation of one allele of the type II collagen gene (Col2a1) on biomechanical properties and mineral density of bone under physical loading conditions. C57BL/6−TGN mice with heterozygous knockout (HZK) inactivation of Col2a1 gene and their nontransgenic littermate controls were housed in individual cages with running wheels for 9 and 15 months. The running activity of each mouse was monitored continuously throughout the experiment. Bone mineral density (BMD) of mice femora was measured using dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computerized tomography (pQCT). Biomechanical properties were determined using three-point bending tests. Vertebral bone samples were prepared for quantitative polarized light microscopy and digital densitometry of proteoglycans. The concentration of total collagen and collagen cross-links were analyzed using high-performance liquid chromatograpy (HPLC). The average daily running distance was shorter for the HZK mice between the age of 4 and 15 months as compared with normal runners (P < 0.05). The ultimate breaking force was 14.8% and 23.6% (9 vs. 15 months) lower in HZK-runners than in wild-type runners. BMD of the femur was 6.1% lower in HZK-runners at the age of 9 months (P < 0.05). Physical activity increased cortical BMD in wild-type runners but not in the HZK runners at the age of 9 months. The collagen network of the HZK mice was less organized. There were only minor changes in BMD and mechanical and structural properties between sedentary HZK mice and their wild-type controls. Increased physical activity induced significantly lower bone density, mechanical properties, and organization of collagen fibers in male HZK mice. However, there were no major differences in biomechanical parameters between sedentary HZK and wild-type male mice. This suggests an important guiding role of collagen type II in bone remodelling and maturation.     

Primary hyperparathyroidism: whole-body bone mineral density in surgically treated Danish patients: a three-year follow-up study

Whole-body bone mineral density (BMD) and body composition were measured before surgery in 25 patients (20 women and 5 men, aged 53 +/- 13 years, range 26-73 years) with mild to moderate primary hyperparathyroidism (PHPT) and compared with 25 controls exactly matched with respect to age, gender, and menopausal status. Fifteen pairs of matched patients and controls were reexamined 3 years later (5 men and 10 women, aged 53 +/- 12 years in both groups). In the untreated PHPT patients, whole-body BMD was 95.4% +/- 10.5% (SD) of control BMD (p < 0.05). Body weight and height, body mass index, whole-body fat mass, and lean body mass did not differ significantly between the groups. Relative to values in matched controls, whole-body bone mineral content (BMC) and BMD increased by 4.4% and 3.0%, respectively, in PHPT patients (p < 0.005) during the 3-year follow-up. Neither whole-body BMC nor BMD differed between patients and controls after the 3-year follow-up. A positive correlation was observed between initial serum calcium levels and the 3-year increase in whole-body BMD (r(s) = 0.645, p < 0.01). Baseline serum osteocalcin, serum pyridinoline crosslinked telopeptide of Type I collagen and several histomorphometric indices of trabecular bone turnover (eroded and labeled surfaces, bone formation rate, and activation frequency) also correlated positively with the subsequent increase in whole-body BMD. Six patients disclosed transient postoperative secondary hyperparathyroidism, probably due to hungry bones. Four of these patients completed 3 years of follow-up and had higher increases in whole-body BMD than the remaining normo-parathyroid patients (7.9% +/- 4.5%, range 4.3-14.3% versus 1.9% +/- 2.1%, p < 0.01). It is concluded that Danish patients with mild to moderate PHPT only reveal small reductions in whole-body mineral density. Furthermore, within 3 years after parathyroid surgery, most of the lost bone mineral is regained even in patients with initial high bone turnover. Finally, PHPT in these patients is not associated with substantial changes in body compositions.     

Modeling elite male athletes' peripheral bone mass,assessed using regional dual x-ray absorptiometry

There is still considerable debate as to whether bone mineral content (BMC) increases in proportion to the projected bone area, A(p), or an estimate of the skeletal bone volume, (A(p))(3/2), being assessed. The results from this study suggest that the bone mass acquisition of elite athletes' arms and legs increases in proportion to the projected bone area, A(p), having simultaneously controlled/removed the effect of the confounding variables of body mass and body fat. Although this supports the use of the traditional bone mineral density ratio (BMD=BMC/A(p)), it also highlights the dangers of overlooking the effect of known confounding variables. Ignoring the effect of such confounding variables, athletic groups whose activities involve upper body strength (rugby, rock climbing, kayaking, weight lifting) had the highest arm BMD, while runners were observed to have the lowest arm BMD (lower than that of the controls). Similarly, leg BMD was highest in rugby players, whose activities included both running and strength training. However, the rugby players were also observed to have the greatest body mass. When the important determinants of body mass, body fat, as well as projected bone area, A(p), were incorporated as covariates into a proportional allometric ANCOVA model for BMC, different conclusions were obtained. The introduction of these covariates had the effect of reducing the sporting differences on adjusted arm BMC, although the "sport" by "side" interaction still identified racket players as the only group with a greater dominant arm BMC (P < 0.05). In contrast, sporting differences in adjusted leg BMC remained highly significant, but with a rearranged hierarchy. The runners replaced the rugby players as having the greatest adjusted leg BMC. The results confirm the benefits of activity on peripheral bone mass as being site-specific but reinforce the dangers of making generalizations about the relative benefits of different exercises ignoring the effects of known confounding variables, such as body size, body composition, and age.     

Bone mass in obese diabetic Zucker rats: influence of treadmill running

Some controversy exists in the literature concerning bone mineral densitry (BMD) in obese, diabetic, leptin-resistant Zucker rats. To investigate this question further, we measured body composition and femoral bone mineral density (BMD) (by dual energy X-ray absorptiometry) in 10 male and 10 female 6 month-old Zucker rats and their homozygous lean controls. Fat mass (percent from body weight) was about 3 times higher in fatty rats than in lean controls. Total, diaphyseal, and distal metaphyseal BMD, total femoral Ca content, and femoral failure load were lower in Zucker rats than in controls. Moderate treadmill running (35% - 40% VO2 max, 20-50 minutes day, 6 days/ week, for 89 days) increased BMD in these animals, possibly by inhibiting bone resorption, as evidenced by no change in plasma osteocalcin concentration but decreased urinary deoxypyridinoline excretion in fatty runners.     

Effects of Diet-Induced Obesity and Voluntary Wheel Running on Bone Properties in Young Male C57BL/6J Mice

Both physical activity and body mass affect bone properties. In this study we examined how diet-induced obesity combined with voluntary physical activity affects bone properties. Forty 7-week-old male C57BL/6J mice were assigned to four groups evenly: control diet (C), control diet + running (CR), high-fat diet (HF, 60% energy from fat), and high-fat diet + running (HFR). After 21-week intervention, all mice were killed and the left femur was dissected for pQCT and mechanical measurements. Body mass increased 80% in HF and 62% in HFR, with increased epididymal fat pad weight and impaired insulin sensitivity. Except for total and trabecular volumetric bone mineral density (BMD), bone traits correlated positively with body mass, fat pad, leptin, and osteoprotegerin. Obesity induced by a high-fat diet resulted in increased femoral bone cross-sectional area, mineral content (BMC), polar moment of inertia, and mechanical parameters. Of the mice accessing the running wheel, those fed the control diet had thinner cortex and less total metaphyseal BMC and BMD, with enlarged metaphyseal marrow cavity, whereas mice fed the high-fat diet had significantly higher trabecular BMD and smaller marrow cavity. However, the runners had a weaker femoral neck as indicated by decreased maximum flexure load. These results suggest that voluntary running exercise affects bone properties in a site-specific manner and that there is a complex interaction between physical activity and obesity. Thus, both diet and exercise should be considered when optimizing the effects on body composition and bone, even though the underlying mechanisms remain partly unknown.     

Leisure-time physical activity and rate of bone loss among peri- and postmenopausal women: a longitudinal study.

We examined the association between continuous leisure-time physical activity and the change in bone mineral density (BMD) and bone mineral content (BMC) in a population-based random sample of 1873 peri- and postmenopausal women. Leisure-time physical activities were registered with self-administered questionnaires in 1989 and 1994, and with an assisted questionnaire in 1995-1997. BMD and BMC were measured from lumbar vertebrae L2-4 and left femoral neck using dual-energy X-ray absorptiometry (DXA) in 1989-1991 and 1994-1997. During the average 5.6 year follow-up, annual loss of lumbar BMC was 124 mg (311 vs. 435 mg, p = 0.036) and annual loss of lumbar BMD was 1.22 mg/cm(2) (4.15 vs. 5.37 mg/cm(2), p = 0.21) smaller among women with regular (at least 1 h each week) weight-bearing leisure-time exercise compared with sedentary women. The advantage was even larger in women with walking or jogging as their only regular weight-bearing leisure-time exercise; that is, their annual loss of lumbar BMC was 180 mg (272 vs. 452 mg, p = 0.022), and annual loss of lumbar BMD was 2.78 mg/cm(2) (2.96 vs. 5.74 mg/cm(2), p = 0.029) smaller than in sedentary women. Continuous leisure-time physical activity did not have any association with loss of BMC or BMD in the femoral neck Physical activity during 12 months before the last bone densitometry was not associated with loss of BMC or BMD at any site. Our results suggest that regular weight-bearing exercise diminishes lumbar bone loss, but might be ineffective in the prevention of femoral osteoporosis among peri- and early postmenopausal women.     

Bone mineral density in prepubertal obese and control children: relation to body weight,lean mass,and fat mass

The aim of the study was to determine the influence of obesity on bone status in prepubertal children. This study included 20 obese prepubertal children (10.7 +/- 1.2 years old) and 23 maturation-matched controls (10.9 +/- 1.1 years old). Bone mineral area, bone mineral content (BMC), bone mineral density (BMD), and calculation of bone mineral apparent density (BMAD) at the whole body and lumbar spine (L1-L4) and body composition (lean mass and fat mass) were assessed by DXA. Broadband ultrasound attenuation (BUA) and speed of sound (SOS) at the calcaneus were measured with a BUA imaging device. Expressed as crude values, DXA measurements of BMD at all bone sites and BUA (69.30 versus 59.63 dB/MHz, P < 0.01) were higher in obese children. After adjustment for body weight and lean mass, obese children displayed lower values of whole-body BMD (0.88 versus 0.96 g/cm2, P < 0.05) and BMC (1190.98 versus 1510.24 g, P < 0.01) in comparison to controls. When results were adjusted for fat mass, there was no statistical difference between obese and control children for DXA and ultrasound results. Moreover, whole-body BMAD was lower (0.086 versus 0.099 g/cm3, P < 0.0001), whereas lumbar spine BMAD was greater (0.117 versus 0.100 g/cm3, P < 0.001) in obese children. Thus, it was observed that, in obese children, cortical and trabecular bone displayed different adaptation patterns to their higher body weight. Cortical bone seems to enhance both size and BMC and trabecular bone to enhance BMC. Finally, considering total body weight and lean mass of obese children, these skeletal responses were not sufficient to compensate for the excess load on the whole body.     

Effects of cerivastatin and parathyroid hormone on the lumbar vertebra of aging male Sprague-Dawley rats

Both men and women lose bone at a late age (aging bone loss). The aim of this study was to determine whether cerivastatin and parathyroid hormone (PTH) can prevent aging bone loss in men. Bone loss in aged male Sprague-Dawley (SD) rats was used as a model for age-related bone loss in men. Nine-month-old male SD rats were divided into six groups: (1) baseline controls (killed at the beginning of the study); (2) age-matched controls; (3) parathyroid hormone (PTH; 80 microg/kg body weight per day for 5 days/week) treated; (4) low-dose cerivastatin (0.2 mg/kg body weight per day) treated; and (5) medium-dose cerivastatin (0.4 mg/kg body weight per day) treated; and (6) high-dose cerivastatin (0.8 mg/kg body weight per day) treated. Groups 2-6 were treated for 23 weeks between the ages of 9 and 15 months and killed at the end of 23 weeks. The fourth lumbar vertebra was analyzed using peripheral quantitative computed tomography (pQCT). It is shown that age-matched controls had decreased cancellous bone mineral content (Cn. BMC) by 19% (p < 0.05) and cancellous bone mineral density Cn. BMD) by 22% (p < 0.01) when compared with baseline controls. All three doses of cerivastatin resulted in lower Cn. BMC and Cn. BMD when compared with age-matched controls, but this decrease was not statistically significant. In the PTH-treated group, Cn. BMC increased by 5% (p < 0.0001) and Cn. BMD increased by 37% (p < 0.0001) when compared with age-matched controls. In age-matched controls, cortical bone mineral content (Ct. BMC) and cortical bone mineral density (Ct. BMD) decreased slightly, but not significantly, when compared with baseline controls. Ct. BMD did not change significantly at any of the three doses in the cerivastatin-treated groups. In the PTH-treated group, Ct. BMC increased by 23% (p < 0.0001) when compared with age-matched controls. We confirmed that male SD rats lose bone with aging in the lumbar vertebra, and it is concluded that cerivastatin, at all doses administered, did not prevent this age-related bone loss. In contrast, PTH prevented age-related bone loss in the vertebra of male SD rats.     

Noninvasive assessment of ulnar bending stiffness in women

The load-carrying capacity of cortical bone is closely related to its geometry and to its fundamental material properties, including mineral content (BMC). Together these determine the bending stiffness EI, where I is the cross-sectional moment of inertia and E is Young's modulus of elasticity. To assess the relationship of BMC and bone width (BW) to EI in healthy women, we used mechanical response tissue analysis (MRTA), a noninvasive method that involves analysis of tissue responses to ulnar vibration. A total of 48 healthy women were enrolled into an older (64 +/- 1y, n = 25) and a younger (25 +/- 0.6y, n = 23) group. BMC and BW of the dominant ulna were measured by single-photon absorptiometry (SPA). EI was determined by MRTA. BMC (0.75 +/- 0.02 versus 0.63 +/- 0.02 g/cm), BMC/BW (0.75 +/- 0.02 versus 0.63 +/- 0.02 g/cm2), and EI (27.7 +/- 1.3 versus 21.3 +/- 1.1 N.m2) were significantly greater (p less than 0.005) in the young subjects. BW did not change with age (1.00 +/- 0.01 versus 1.01 +/- 0.01 cm). In young women, simple correlations of BMC and BW with EI were both significant. By multiple regression analysis only BW independently predicted EI (EI = -0.35 + 39.1 x BMC, R2 = 0.52). In older women BMC and BW correlated with EI, but in multiple regression only BMC was significant (EI = -34.5 + 62.1 x BW; R2 = 0.45). When this analysis of older women included only those whose BMC values were within 2 SD of the young mean, BMC remained the only significant predictor of EI.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of resistance and endurance exercise on bone mineral status of young women: a randomized exercise intervention trial.

A substantial body of cross-sectional data and a smaller number of intervention trials generally justify optimism that regular physical activity benefits the skeleton. We conducted an 8 month controlled exercise trial in a group of healthy college women (mean age = 19.9 years) who were randomly assigned to a control group or to progressive training in jogging or weight lifting. We measured the following variables: bone mineral density (BMD) of the spine (L2-4) and right proximal femur using dual-energy x-ray absorptiometry, dynamic muscle strength using the 1-RM method, and endurance performance using the 1.5 mile walk/run field test. A total of 31 women completed the 8 month study. For women completing the study, compliance, defined as the percentage of workout sessions attended, was 97% for the runners (range 90-100%) and 92% (range 88-100%) for the weight trainers. Body weight increased by approximately 2 kg in all groups (p less than 0.05). Weight training was associated with significant increases (p less than 0.01) in muscle strength in all muscle groups. Improvement ranged from 10% for the deep back to 54% for the leg. No significant changes in strength scores were observed in the control or running groups. Aerobic performance improved only in the running group (16%, p less than 0.01). Lumbar BMD increased (p less than 0.05) in both runners (1.3 +/- 1.6%) and weight trainers (1.2 +/- 1.8%). These results did not differ from each other but were both significantly greater than results in control subjects, in whom bone mineral did not change.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of growth hormone replacement therapy on bone metabolism in adult-onset growth hormone deficiency: a 2-year open randomized controlled multicenter trial.

Adult hypopituitary patients with growth hormone deficiency (GHD) show a significant decrease in bone mass and an increased fracture rate. Replacement therapy with GH increases bone turnover. Most of the long-term data on bone mineral content (BMC) and bone mineral density (BMD) have been acquired in open, noncontrolled trials involving limited numbers of patients. To determine whether long-term GH therapy is beneficial for bone despite the increased bone turnover, 100 patients (59 men and 41 women), aged 25-65 years (mean, 49.7 years) with adult-onset GHD were randomized to treatment with GH (40 men and 28 women; mean dose, 0.18 IU/kg per week) or to a nontreated control group (19 men and 13 women) for 24 months. Despite a similar increase in parameters of bone turnover (osteocalcin [OC], procollagen type I carboxy-terminal propeptide [PICP], and pyridinolines ([PYD]) in male and female GH-treated patients compared with controls, the effects on BMC and BMD as evaluated by dual-energy X-ray absorptiometry were gender specific. A significant increase in spine BMC and BMD and total hip BMD and a decrease in BMD at the ultradistal radius over time was observed in male GH-treated patients compared with the evolution in controls (mean +/- SEM change at 24 months: +6.8 +/- 1.1% and p = 0.009, +5.1 +/- 0.8% and p = 0.005, +3.5 +/- 0.7% and p = 0.02, and -2.6 +/- 0.8% and p = 0.008, respectively). No significant treatment effects were observed in female patients. Despite the increase in the total remodeling space induced by GH treatment, prolonged GH therapy in adult-onset GHD has a positive effect on bone balance, maintaining bone mass in women, and even increasing it in men over a 2 year-period.     

Measurement of bone in the os calcis: a clinical evaluation

Bone mineral content (BMC) was measured in the os calcis of 232 normal subjects aged 17-82 years. The mean reproducibility (coefficient of variation) of the measurement was 1.8%. Substantial bone loss occurred between the ages of 20 and 50 years, and in females the menopause was associated with additional bone loss. There was no significant difference in the rate of bone loss in females and males, but the mean BMC was greater at all ages in males than in females. We also compared os calcis BMC with spinal bone mineral density (BMD), measured by quantitative computed tomographic (CT) scanning, in 85 subjects: 33 were normal controls, 19 had osteoporosis defined by the presence of one or more pathological fractures, and in the remainder the CT examination was performed at the patient's request. Os calcis BMC correlated with spinal BMD in both females (r = 0.69, p less than 0.001) and males (r = 0.84, p less than 0.001). However, the os calcis BMC did not reliably predict spine values around the CT "fracture threshold" of 90-100 mg/cm3 and did not correlate with osteoporotic fracture as well as did spinal BMD. It is concluded that measurement of the os calcis BMC is of limited clinical usefulness for the early diagnosis of osteoporosis.     

Low lumbar spine bone mineral density in both male and female endurance runners

There have been many reports of low bone mineral density (BMD) in female endurance runners. Although there have been several reports of low BMD in male runners, it is unclear how comparable the problem is to that in females. We compared BMD between male and female endurance runners and with a reference population. One hundred and nine endurance runners (65 females, 44 males) aged 19-50 years participated and had been training regularly for at least 3 years (32-187.2 km week(-1)) in events from 3 km to the marathon. BMD was measured at the lumbar spine (L2-L4) and hip by DXA. A questionnaire assessed training and menstrual status. Lumbar spine T scores were similar in male and female runners (-0.8 (0.8) versus -0.8 (0.7); f = 0.015; P = 0.904) as were total hip T scores (0.6 (7.9) versus 0.5 (9.2); f = 0.192; P = 0.662). The proportion of male runners with low lumbar spine BMD (<-1.0) (n = 16 from 44) compared to that of females (n = 27 from 65) (P = 0.675). Males had lower spine T scores than eumenorrhoeic females (-0.8 (0.7) versus -0.4 (0.7); f = 5.169; P = 0.03). There were moderate negative correlations between weekly running distance and lumbar spine BMD in males and females (r(2) = 0.267; 0.189; P < 0.001), independent of menstrual status in females (r(2) = 0.192; P < 0.001). Lumbar spine but not hip T scores were greater in runners who participated in resistance training at least twice-a-week (male: -0.4 versus -1.1; female: -0.5 versus -1.1; P < 0.01). Using multiple regression, running distance (-) and BMI (+) together best predicted lumbar spine T scores (r(2) = 0.402; P < 0.01) in females. Although weak, BMI (+) best predicted hip T scores (r(2) = 0.167; P < 0.05). In males, running distance and training years (-) together best predicted lumbar spine T scores (r(2) = 0.400; P < 0.01). Training years (-) best predicted hip T scores (r(2) = 0.361; P < 0.01). To conclude, our findings suggest that male runners face the same bone threat at the spine, as female runners. Further research in male athletes is required. Incorporation of regular resistance training into an athlete's training programme may be a useful preventative strategy.     

The effects of gonadectomy on bone size, mass, and volumetric density in growing rats are gender-, site-, and growth hormone-specific.

Peak volumetric bone mineral density (BMD) is determined by the growth in bone size relative to the mineral accrued within its periosteal envelope. Thus, reduced peak volumetric BMD may be the result of reduced mineral accrual relative to growth in bone size. Because sex steroids and growth hormone (GH) influence bone size and mass we asked: What are the effects of gonadectomy (Gx) on bone size, bone mineral content (BMC), areal and volumetric BMD in growing male and female rats? Does GH deficiency (GH-) reduce the amount of bone in the (smaller) bone, i.e., reduce volumetric BMD? Does GH- alter the effect of Gx on bone size and mineral accrual? Gx or sham surgery was performed at 6 weeks in GH- and GH replete (GH+) Fisher 344 male and female rats. Changes in bone size, volume, BMC, areal and volumetric BMD, measured using dual X-ray absorptiometry (DPX-L), were expressed as percentage of controls at 8 months (mean +/- SEM). All results shown were significant (p < 0.05 level) unless otherwise stated. In GH+ and GH- males, respectively, Gx was associated with: lower femur volume (24%, 25%), BMC (43%, 45%), areal BMD (21%, 14%), and volumetric BMD (30%, 28%); lower spine (L1-L3) volume (26%, 28%), BMC (26%, 30%), and areal BMD (28%, 12%), but not volumetric BMD. Following Gx, GH+ females had increased femur volume (11%), no effect on BMC, decreased areal BMD (6%) and decreased volumetric BMD (17%); GH- females had no change in femur volume, but decreased femur BMC (24%), areal BMD (10%), and volumetric BMD (25%). In GH+ and GH- females, respectively, Gx was associated with a decrease in spine (L1-L3) BMC (12%, 15%), areal BMD (16%, 15%), and volumetric BMD (10%, 16%) with no change in volume. Deficits in non-Gx GH- relative to non-Gx GH+ (males, females, respectively) were: femur BMC (49%, 37%), areal BMD (23%, 8%), volume (19%, 19%) and volumetric BMD (37%, 22%); spine (L1-L3) BMC (46%, 42%), areal BMD (37%, 43%), volume (10%, 15%), and volumetric BMD (40%, 33%). Testosterone and GH are growth promoting in growing male rats, producing independent effects on bone size and mass; deficiency produced smaller appendicular bones with reduced volumetric BMD because deficits in mass were greater than deficits in size. At the spine, the reduction in size and accrual were proportional, resulting in a smaller bone with normal volumetric BMD. In growing female rats, estrogen was growth limiting at appendicular sites; deficiency resulted in a GH-dependent increase in appendicular size, relatively reduced accrual, and so, reduced volumetric BMD in a bigger bone. At the spine, accrual was reduced while growth in size was normal, thus volumetric BMD was reduced in the normal sized bone. Understanding the pathogenesis of low volumetric BMD requires the study of the differing relative growth in size and mass of the axial and appendicular skeleton in the male and female and the regulators of the growth of these traits.     

Pamidronate reduces PTH-mediated bone loss in a gene transfer model of hyperparathyroidism in rats.

We evaluated spinal and femoral bone mass and density utilizing dual-energy x-ray absorptiometry (DEXA) in rats in which severe hyperparathyroidism was produced by the expression of the gene for human PTH-(1-84) (hPTH). This gene was incorporated into a retroviral vector that was transfected into fibroblasts which were subsequently injected into their peritoneal cavities. Further, we examined the effect of the administration of pamidronate on bone mass and density in the presence of extremely high concentrations of hPTH. Three groups of rats were studied. Groups 1 and 2 receive the hPTH-secreting fibroblasts; group 2 subsequently received pamidronate (2.5 mg/kg IV) 18 and 27 days after receiving the fibroblasts. These animals developed levels of hPTH greater than 1.0 microgram/liter and became hypercalcemia within 20 days. These animals became lethargic and were significantly lower in weight than age-matched controls (group 3, p less than 0.05). After accounting for the animal weight there was a further significant decrease in bone mineral content and density (BMC and BMD) on day 29 attributable to hPTH-mediated bone loss. Treatment with pamidronate resulted in a higher BMC of the lumbar spine than in the untreated animals, with elevated concentrations of hPTH. The BMD was significantly higher at both the lumbar spine and femur in the pamidronate-treated animals (p less than 0.05). The CV of paired measurements of BMD was 2.7% at the spine and 1.5% of a femur, respectively. The BMC of the lumbar spine and femur was closely correlated with the ashed weight of the same bones (r = 0.92 and 0.85, respectively).