Glucoregulation during exercise: hypoglycemia is prevented by redundant glucoregulatory systems, sympathochromaffin activation, and changes in islet hormone secretion.

During mild or moderate nonexhausting exercise, glucose utilization increases sharply but is normally matched by increased glucose production such that hypoglycemia does not occur. To test the hypothesis that redundant glucoregulatory systems including sympathochromaffin activation and changes in pancreatic islet hormone secretion underlie this precise matching, eight young adults exercised at 55-60% of maximal oxygen consumption for 60 min on separate occasions under four conditions: (a) control study (saline infusion); (b) islet clamp study (insulin and glucagon held constant by somatostatin infusion with glucagon and insulin replacement at fixed rates before, during and after exercise with insulin doses determined individually and shown to produce normal and stable plasma glucose concentrations prior to each study); (c) adrenergic blockage study (infusions of the alpha- and beta-adrenergic antagonists phentolamine and propranolol); (d) adrenergic blockade plus islet clamp study. Glucose production matched increased glucose utilization during exercise in the control study and plasma glucose did not fall (92 +/- 1 mg/dl at base line, 90 +/- 2 mg/dl at the end of exercise). Plasma glucose also did not fall during exercise when changes in insulin and glucagon were prevented in the islet clamp study. In the adrenergic blockade study, plasma glucose declined initially during exercise because of a greater initial increase in glucose utilization, then plateaued with an end-exercise value of 74 +/- 3 mg/dl (P less than 0.01 vs. control). In contrast, in the adrenergic blockade plus islet clamp study, exercise was associated with glucose production substantially lower than control and plasma glucose fell progressively to 58 +/- 7 mg/dl (P less than 0.001); end-exercise plasma glucose concentrations ranged from 34 to 72 mg/dl. Thus, we conclude that: (a) redundant glucoregulatory systems are involved in the precise matching of increased glucose utilization and glucose production that normally prevents hypoglycemia during moderate exercise in humans. (b) Sympathochromaffin activation, perhaps sympathetic neural norepinephrine release, plays a primary glucoregulatory role by limiting glucose utilization as well as stimulating glucose production. (c) Changes in pancreatic islet hormone secretion (decrements in insulin, increments in glucagon, or both) are not normally critical but become critical when catecholamine action is deficient. (d) Glucoregulation fails, and hypoglycemia can develop, both when catecholamine action is deficient and when changes in islet hormones do not occur during exercise in humans.

Calciotropic hormones and bone markers in the elderly.

There is a lack of substantial data on changes in calciotropic hormones and bone markers in elderly subjects living in North America. Parathyroid hormone (PTH), serum 25-hydroxyvitamin D (25(OH)D) and bone markers (serum osteocalcin and urine N-telopeptide), were measured in 735 Caucasian subjects (235 men and 500 women) aged 65-87 years. There was a significant increase in serum osteocalcin and urine N-telopeptide with age in men, and a significant increase in serum osteocalcin with age in women. Serum PTH and 25(OH)D showed no significant change with age in men or women. After adjusting for age, calcium intake, serum creatinine, season, and weight, mean serum PTH (p = 0.01), serum osteocalcin (p = 0.0001) and 24 h urine N-telopeptide (p = 0.0001) were higher in women than men, and mean serum 25(OH)D (p = 0.0001) and 24 h urine calcium (p = 0.0001) were higher in men than women. Serum PTH was correlated with serum osteocalcin in men and women, r = 0.24, r = 0.17, p < 0.001, but not with urine N-telopeptide. Serum PTH was inversely correlated with serum 25(OH)D (r = -0.25, r = -034,p < 0.001), and positively correlated with serum creatinine (r = 0.14, r = 0.17,p < 0.01) in men and women. The prevalence of serum 25(OH)D levels below 12 ng/ml was only 33% in females and 0.4% in men. Thus vitamin D deficiency was very uncommon in the U.S.A. compared with Europe. Although mean serum PTH was increased in the elderly, only 4-6% had PTH levels above the normal range. In summary, the increase in serum PTH in the elderly can be explained more by changes in vitamin D status than by declining renal function. These data also show significantly higher (p = 0.001) bone remodeling markers in women.

Effects of teriparatide [recombinant human parathyroid hormone (1-34)] on cortical bone in postmenopausal women with osteoporosis.

Treatment with teriparatide (rDNA origin) injection [teriparatide, recombinant human parathyroid hormone (1-34) [rhPTH(1-34)]] reduces the risk of vertebral and nonvertebral fragility fractures and increases cancellous bone mineral density in postmenopausal women with osteoporosis, but its effects on cortical bone are less well established. This cross-sectional study assessed parameters of cortical bone quality by peripheral quantitative computed tomography (pQCT) in the nondominant distal radius of 101 postmenopausal women with osteoporosis who were randomly allocated to once-daily, self-administered subcutaneous injections of placebo (n = 35) or teriparatide 20 microg (n = 38) or 40 microg (n = 28). We obtained measurements of moments of inertia, bone circumferences, bone mineral content, and bone area after a median of 18 months of treatment. The results were adjusted for age, height, and weight. Compared with placebo, patients treated with teriparatide 40 microg had significantly higher total bone mineral content, total and cortical bone areas, periosteal and endocortical circumferences, and axial and polar cross-sectional moments of inertia. Total bone mineral content, total and cortical bone areas, periosteal circumference, and polar cross-sectional moment of inertia were also significantly higher in the patients treated with teriparatide 20 microg compared with placebo. There were no differences in total bone mineral density, cortical thickness, cortical bone mineral density, or cortical bone mineral content among groups. In summary, once-daily administration of teriparatide induced beneficial changes in the structural architecture of the distal radial diaphysis consistent with increased mechanical strength without adverse effects on total bone mineral density or cortical bone mineral content.

Bone mineral density of competitive male mountain and road cyclists.

The purpose of this study was to compare the bone mineral density (BMD) of two types of trained male cyclists (n = 30) with recreationally active men (n = 15), aged 20-40 years. Sixteen of the cyclists regularly trained for, and competed in, cross-country mountain bike races. The other 14 cyclists trained and raced on the road. The cyclists had trained an average of 11 +/- 3 hours per week for 8 +/- 4 years. Fifteen recreationally active men volunteered as controls. Dual-energy X-ray absorptiometry (DXA) was used to assess BMD of the proximal femur, lumbar spine, and total body. Anthropometric, muscle strength and power, aerobic fitness, and sex hormone data assessments were conducted on all participants. Mountain cyclists were younger and weighed less than road cyclists and controls. BMD at all sites was comparable among the three groups (p > 0.05). When adjusted for body weight and controlled for age, BMD was significantly higher at all sites in the mountain cyclists compared with the road cyclists and controls. Some anthropometric, physical fitness, and sex steroid variables were predictive of BMD, but of these variables, only total body weight, total body fat, and aerobic fitness were different between the groups. In conclusion, endurance road cycling does not appear to be any more beneficial to bone health than recreational activity in apparently healthy men of normal bone mass. Higher BMD in the mountain cyclists suggests that mountain cycling may provide an osteogenic stimulus that is not inherent to road cycling.

Elevated high-density lipoprotein cholesterol levels in older endurance athletes.

To ascertain whether older (masters) athletes exhibit a more favorable plasma lipoprotein/lipid profile than sedentary men of similar age, 14 endurance-trained masters athletes (mean age 60 +/- 2 years [+/- standard error of the mean]), 12 older, untrained-not lean men (mean age 62 +/- 1 years), 9 older untrained-lean men (mean age 61 +/- 2 years), 15 young endurance-trained athletes (mean age 26 +/- 1 years) and 15 young untrained men (mean age 28 +/- 1 years) were studied. The athletes had higher values for maximal oxygen uptake and lower levels of body fatness compared with the untrained men, regardless of age (p less than 0.05). High-density lipoprotein (HDL) cholesterol was markedly higher in the masters athletes than in the other groups (66 vs 42 to 55 mg/dl, p less than 0.05). The total cholesterol (TC) and low-density lipoprotein cholesterol concentrations of the masters athletes generally were higher than those of the younger groups, similar to those of the older lean men, and lower than those of the older-not lean men (p less than 0.05). The TC/HDL cholesterol ratios were similarly low (2.8 to 3.4) for the athletes and the young untrained men compared with the older untrained men (4.0 to 5.6) (p less than 0.05). Thus, some older endurance athletes exhibit markedly higher HDL cholesterol levels and lower TC/HDL cholesterol ratios compared with their sedentary peers. This favorable plasma lipoprotein profile may indicate a reduced risk of developing coronary artery disease for older men who exercise regularly.

Effects of exercise and lack of exercise on insulin sensitivity and responsiveness.

Insulin action is enhanced in people who exercise regularly and vigorously. In the present study, the hyperinsulinemic, euglycemic clamp procedure was used to determine whether this enhanced insulin action is due to an increased sensitivity and/or an increased responsiveness to insulin. To avoid the variability that exists between individuals and complicates cross-sectional studies, the same subjects were studied in the trained exercising state and again after 10 days of physical inactivity. When the plasma insulin concentration was maintained at approximately 78 microU.ml-1 (a submaximal level), glucose disposal rate averaged 8.7 +/- 0.5 mg.kg-1.min-1 before and 6.7 +/- 0.6 mg.kg-1.min-1 after 10 days of activity (P less than 0.001). When the plasma insulin concentration was maintained at approximately 2,000 microU.ml-1 (a maximally effective concentration), the rate of glucose disposal was not significantly different before (15.3 +/- 0.5 mg.kg-1.min-1) compared with after (14.5 +/- 0.4 mg.kg-1.min-1) 10 days without exercise. These results provide evidence that the reversal of enhanced insulin action that occurs within a few days when exercise-trained individuals stop exercising is due to a decrease in sensitivity to insulin, not to a decrease in insulin responsiveness.

Muscle triglyceride utilization during exercise: effect of training.

The respiratory exchange ratio (RER) is lower during exercise of the same intensity in the trained compared with the untrained state, even though plasma free fatty acids (FFA) and glycerol levels are lower, suggesting reduced availability of plasma FFA. In this context, we evaluated the possibility that lipolysis of muscle triglycerides might be higher in the trained state. Nine adult male subjects performed a prolonged bout of exercise of the same absolute intensity before and after adapting to a strenuous 12-wk program of endurance exercise. The exercise test required 64% of maximum O2 uptake before training. Plasma FFA and glycerol concentrations and RER during the exercise test were lower in the trained than in the untrained state. The proportion of the caloric expenditure derived from fat, calculated from the RER, during the exercise test increased from 35% before training to 57% after training. Muscle glycogen utilization was 41% lower, whereas the decrease in quadriceps muscle triglyceride concentration was roughly twice as great (12.7 +/- 5.5 vs. 26.1 +/- 9.3 mmol/kg dry wt, P less than 0.001) in the trained state. These results suggest that the greater utilization of FFA in the trained state is fueled by increased lipolysis of muscle triglyceride.

Insulin action and secretion in endurance-trained and untrained humans.

To evaluate insulin sensitivity and responsiveness, a two-stage hyperinsulinemic euglycemic clamp procedure (insulin infusions of 40 and 400 mU.m-2.min-1) was performed on 11 endurance-trained and 11 untrained volunteers. A 3-h hyperglycemic clamp procedure (plasma glucose approximately 180 mg/dl) was used to study the insulin response to a fixed glycemic stimulus in 15 trained and 12 untrained subjects. During the 40-mU.m-2.min-1 insulin infusion, the glucose disposal rate was 10.2 +/- 0.5 mg.kg fat-free mass (FFM)-1.min-1 in the trained group compared with 8.0 +/- 0.6 mg.kg FFM-1.min-1 in the untrained group (P less than 0.01). In contrast, there was no significant difference in maximally stimulated glucose disposal: 17.7 +/- 0.6 in the trained vs. 16.7 +/- 0.7 mg.kg FFM-1.min-1 in the untrained group. During the hyperglycemic clamp procedure, the incremental area for plasma insulin was lower in the trained subjects for both early (0-10 min: 140 +/- 18 vs. 223 +/- 23 microU.ml-1.min; P less than 0.005) and late (10-180 min: 4,582 +/- 689 vs. 8,895 +/- 1,316 microU.ml-1.min; P less than 0.005) insulin secretory phases. These data demonstrate that 1) the improved insulin action in healthy trained subjects is due to increased sensitivity to insulin, with no change in responsiveness to insulin, and 2) trained subjects have a smaller plasma insulin response to an identical glucose stimulus than untrained individuals.

Effect of exercise on bone: permissive influence of estrogen and calcium.

Estrogen deficiency in postmenopausal women is associated with low lumbar bone mineral density and an increased incidence of fractures of the vertebrae and proximal femur. Estrogen deficiency in premenopausal women with secondary amenorrhea related to athletic training or anorexia nervosa is also associated with decreased lumbar bone mineral density. The purpose of this review is to present four concepts related to the adaptations of bone to physical exercise, as a basis to explain the loss of bone mass in women with athletic amenorrhea. These concepts are based on Lanyon's theory of a Minimum Effective Strain-Related Stimulus. The bone remodeling response to estrogen deficiency is an increase in the rate of bone remodeling activity and in the rate of bone resorption relative to formation, resulting in a net loss of bone mass. In the presence of estrogen deficiency, the stimulus of physical activity is thought first to decrease the rate of turnover and secondly to increase bone formation. Endurance exercise training appears to be an insufficient stimulus to accomplish both tasks, which may explain why these athletes often have low lumbar bone mineral density.

Normalizing strength for body size differences in older adults.

The purpose of this study was to compare the normalization methods of ratio standards, allometry, and ANCOVA with knee extensor strength of older adults. The apparently healthy older volunteers were 71 men (mean +/- SD; age, 71 +/- 4 yr; body mass, 81 +/- 10 kg; height, 174 +/- 7 cm) and 77 women (71 +/- 4 yr, 65 +/- 8 kg, 160 +/- 5 cm. respectively). Strength was defined as peak torque (N.m-1) and measured with a Cybex II isokinetic dynamometer. Body composition was estimated with dual energy x-ray absorptiometry. With allometry, the body mass exponent (0.74) was not statistically different from theory (0.67). Body mass adjusted strengths were 34.7% (allometry), 32.0% (ANCOVA), and 29.4% (ratio standards) greater in older men than women. Allometry revealed that the bone-free lean tissue mass exponent was not different from ratio standard exponent of 1.0. After adjustment by bone-free lean tissue mass, strength in men remained 16.0% (allometry and ratio standards) higher than in women, but, strength differences between genders were eliminated with ANCOVA. The methods used to normalize strength yielded similar results with body mass but conflicting results with bone-free lean tissue mass.

Body composition of healthy sedentary and trained, young and older men and women.

This study examined the effects of age and physical activity on body composition and fat distribution by comparing differences between young and older endurance trained men and women with differences between young and older sedentary people. Although indices of total body adiposity (fat mass, percent body fat) were higher in the older than in the young people in both the trained and the sedentary groups, the magnitude of the difference was markedly less in the trained group (P less than 0.01). The average differences in fat mass between young and old sedentary men and women were 10.1 kg and 12.2 kg, respectively, but only 4.3 kg and 5.5 kg in trained men and women. Skinfold thicknesses were approximately 24% and approximately 47% larger at all sites (triceps, thigh, subscapula, pectoralis, umbilicus, suprailiac) in the older than in the young trained men and women, respectively. Similar differences were found between young and older sedentary people except at central, upper body sites, where the relative differences in skinfold thicknesses between young and older sedentary people were 2- to 6-fold greater than in trained people. Thus, people who exercise regularly appear to accumulate less adipose tissue in upper, central body regions as they get older, potentially reducing the risk for the metabolic disorders associated with upper body obesity.

Comparison of accelerometers with oxygen consumption in older adults during exercise.

PURPOSE: The purpose of this study was to compare two commercially available accelerometers with indirect calorimetry in a group of older adults (x +/- SD; 70.6+/-3.7 yr; N = 86, 44 males and 42 females). METHODS: The accelerometers (Caltrac and Tritrac, Hemokinetics, Madison, WI) were worn while performing three submaximal, discontinuous (5 min exercise, 2 min recovery), progressive levels of treadmill walking and bench stepping. The treadmill exercise averaged 3.4 mph, at 0.4% grade, 3.0% grade, and 5.1% grade, while the stepping work rates (24 steps x min(-1)) were performed on 15.2-, 20.3-, and 25.4-cm steps. Estimated energy expenditure (EE) from the two accelerometers was compared with EE as measured by indirect calorimetry. RESULTS: The Caltrac significantly (P < 0.05) overestimated EE at the three treadmill work rates (10-52% difference) and underestimated EE at the three stepping work rates (-19% to -28% difference). When comparing the changes in EE between work rates one, two and three, the Caltrac was not sensitive to the changes (increase in EE) that occurred during graded treadmill walking but did detect some changes in the stepping exercise. The Tritrac significantly (P < 0.05) underestimated EE for the three work rates of both the treadmill and stepping exercise when compared with indirect calorimetry but did detect differences in EE among work rates during stepping exercise (P < 0.05). CONCLUSIONS: These data indicate that the magnitude of the differences between measured and estimated EE is affected by exercise mode and intensity and that caution is warranted when using the accelerometers in an attempt to quantify EE in older adults.

Bone mineral density in elite junior Olympic weightlifters.

The purpose of this study was to examine the relationship of bone mineral density (BMD) to muscular strength in highly trained young male athletes in order to gain insights concerning the influence of heavy resistance training on BMD. Twenty-five elite junior weightlifters (age, 17.4 +/- 1.4 yr) and 11 age-matched controls (16.9 +/- 1.1 yr) volunteered for this investigation. Measurements of BMD (g.cm-2) utilizing dual energy x-ray absorptiometry were obtained for the lumbar spine (L2-4) and the proximal femur (neck; trochanter, Ward's triangle). The BMD values for the junior lifters were found to be significantly greater at all sites for the junior weightlifters compared with their age-matched control group. The BMD values of the spine and femoral neck of the junior weightlifters when compared with adult reference data (i.e., 20-39 yr old men) were found to be significantly greater. Both simple and multiple regression analyses demonstrated significant relationships of BMD with strength accounting for 30-65% of the variance. These data suggest that in elite junior weightlifters, muscle strength, highly specific to the sport of weightlifting, has a major influence on BMD due to the influence of the chronic overloads experienced in training.

Effects of high-intensity strength training on cardiovascular function.

Thirteen healthy, untrained males (age 44 +/- 1 yr, range 40-55 yr) were studied to determine the effects of 16 wk of high-intensity, variable-resistance, Nautilus strength training on cardiovascular function. A control group consisting of 10 untrained males (age 52 +/- 2 yr, range 40-64 yr) underwent the same evaluation procedures as the training group. Maximal oxygen uptake (VO2max), cardiac output during submaximal exercise, and body composition were determined before and after training. In addition, the physiological responses to an acute training session were evaluated. Muscular strength increased markedly, as evidenced by a 44% average increase in the "one-repetition maximum" in the various exercises. Body weight and percent body fat did not change with training, though fat-free weight did increase (66.9 +/- 2.6 vs 68.8 +/- 2.7 kg, P less than 0.05) significantly. Maximal oxygen uptake did not change significantly in either the training or the control group, and there were no changes in the hemodynamic responses to submaximal exercise after training. These findings indicate, therefore, that high-intensity, variable-resistance strength training produces no adaptative improvement in cardiovascular function. The physiological responses measured during a training session provide evidence that this lack of cardiovascular adaptation may be due to the low percentage of VO2max elicited by this form of exercise.

Economy of mobility in older adults.

A decline in economy of mobility indicates that more physical work is required for a task (ie., walking) and may suggest an abnormal gait pattern. A normal gait pattern is essential for maintaining independence in older adults. The purpose of this study was to compare economy of mobility between sedentary older men and women. The subjects were 47 men (mean +/- SD; age = 71 +/- 4 years, weight = 83 +/- 8 kg, height = 175 +/- 7 cm) and 51 women (70 +/- 3 years, 65 +/- 8 kg, 161 +/- 5 cm). Men were significantly (p < 0.05) older, heavier, and taller than women. Maximal oxygen uptake (VO2max) was collected while subjects walked on a treadmill until volitional exhaustion. On a separate day, a submaximal test was performed at one speed requiring approximately 60% of VO2max on a level treadmill for 5 minutes. Men had significantly greater absolute and relative VO2max than women. Men walked at a significantly faster speed (92 +/- 8 vs. 86 +/- 7 m/min) than women during the submaximal test. Economy of mobility was the same for older men and women (0.17 +/- 0.02 ml/kg/m) with differences in walking speed controlled. The results indicate that there is not a gender-specific decrement in economy of mobility with aging.

Guidelines for diagnosing osteoporosis.

Women who are estrogen deficient have an increased risk of osteoporosis and future fractures. In recent years, improving technology and a consensus on the definition of osteoporosis have made it easier to measure bone density and assess the risk of osteoporosis. Density should be measured at two sites, the lumbar spine and the femoral neck. If only one measurement is possible, the site should be the lumbar spine in women younger than 65 and the femoral neck in women 65 and older. Treatment is recommended if a woman's bone density is more than one standard deviation below the young adult reference value.

The role of exercise in the prevention of osteoporosis.

The response of an individual's bone mass to exercise training will depend, in part, on their present level of functional activity and on the hormonal and nutritional milieus of bone tissue. For normally active, but not trained persons, an exercise training program may lead to a new bone mass as much as 5% to 10% above baseline. In an individual with a bone mass which is markedly reduced because of inactivity, poor nutrition, or hormonal deficiency (or excess, depending on the hormone), it is possible that exercise will result in even larger gains in bone mass. Training with weight-bearing exercises may serve as an osteogenic stimulus to both young and older individuals. If the training program is limited or restricted, however, older people may not show the same magnitude of change as do younger subjects. In women, low estrogen levels may reduce the apparent benefit from exercise training, as seen from the studies of amenorrheic athletes. Low bone mass may be related to an estrogen withdrawal effect as well as to the basic estrogen deficiency. Exercise training is likely to provide an osteogenic stimulus for the maintenance of bone mass when it is done in an environment of optimal hormonal levels and nutrition. Physical activity, however, may not be an effective substitute for estrogen therapy. Under optimal conditions, exercise training does provide an osteogenic stimulus to bone, resulting in an increase or maintenance of bone mass, when a loss might otherwise be expected. It is not realistic, however, to expect that exercise training will bring about a large increase in bone mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of raloxifene after recombinant teriparatide [hPTH(1-34)] treatment in postmenopausal women with osteoporosis.

UNLABELLED: Loss of bone mineral density occurs after discontinuation of teriparatide, if no subsequent treatment is given. Sequential raloxifene prevented rapid bone loss at lumbar spine and further increased bone mineral density (BMD) at femoral neck, whether raloxifene was started immediately or after a one-year delay following teriparatide treatment. INTRODUCTION: We compared the sequential effects of raloxifene treatment with a placebo on teriparatide-induced increases in bone mineral density (BMD). A year of open-label raloxifene extended the study to assess the response with and without delay after discontinuation of teriparatide. METHODS: Following a year of open-label teriparatide 20 mug/day treatment, postmenopausal women with osteoporosis were randomly assigned to raloxifene 60 mg/day (n = 157) or a placebo (n = 172) for year 2, followed by a year of open-label raloxifene. BMD was measured by dual energy x-ray absorptiometry. RESULTS: The raloxifene and placebo groups showed a decrease in lumbar spine (LS) BMD in year 2 for raloxifene and placebo groups (-1.0 +/- 0.3%, P = 0.004; and -4.0 +/- 0.3%, P < 0.001, respectively); the decrease was less with raloxifene (P < 0.001). Open-label raloxifene treatment reversed the LS BMD decrease with a placebo, resulting in similar decreases 2 years after randomization (-2.6 +/- 0.4% (raloxifene-raloxifene) and -2.7 +/- 0.4% (placebo-placebo). At study end, LS and femoral neck (FN) BMD were higher than pre-teriparatide levels, with no significant differences between the raloxifene-raloxifene and placebo-raloxifene groups, respectively (LS: 6.1 +/- 0.5% vs. 5.1 +/- 0.5%; FN: 3.4 +/- 0.6% vs. 3.0 +/- 0.5%). CONCLUSION: Sequential raloxifene prevented rapid bone loss at the LS and increased FN BMD whether raloxifene was started immediately or after a one-year delay following teriparatide treatment.

Severity of vertebral fracture reflects deterioration of bone microarchitecture.

INTRODUCTION: Bone microarchitecture, a component of bone strength, is generally measured on transiliac bone biopsy samples. The objective of this study was to determine whether assessment of four grades of vertebral fracture severity could serve as a noninvasive surrogate marker for trabecular bone volume and microarchitecture. METHODS: Baseline vertebral fracture severity was determined by semiquantitative assessment of spine radiographs from 190 postmenopausal women with osteoporosis. Bone-structure indices were obtained by 2D histomorphometry and 3D microcomputed tomography (CT) analyses. Significance of differences was determined after adjusting for age, height, and lumbar spine bone mineral density. RESULTS: There were significant (P < 0.05) trends in decreasing bone volume, trabecular number, and connectivity, and increasing trabecular separation with greater vertebral fracture severity. Histomorphometric bone volume was 25 and 36% lower (P < 0.05) in women with moderate and severe fractures than in women with no fractures, respectively. Compared with women without fractures, women with mild, moderate, and severe fractures had lower (P < 0.05) microCT bone volume (23, 30, and 51%, respectively). CONCLUSIONS: Microarchitectural deterioration was progressively worse in women with increasing severity of vertebral fractures. We conclude that assessment of vertebral fracture severity is an important clinical tool to evaluate the severity of postmenopausal osteoporosis.

Teriparatide effects on vertebral fractures and bone mineral density in men with osteoporosis: treatment and discontinuation of therapy.

Teriparatide (rhPTH[1-34]), a bone-forming agent for the treatment of osteoporosis, increases bone mineral density in men and women, and reduces the risk of fractures in women with osteoporosis. However, fracture efficacy has not yet been confirmed in men. Further, there is limited information on the effect of withdrawal of teriparatide. The purpose of this manuscript is to report on bone mineral density and vertebral fracture incidence during a 42-month observation period, from the baseline of the previously reported treatment study in men [1] through 30 months of posttreatment follow-up. Three hundred fifty-five men who were treated with once-daily self-injections of either placebo or 20 or 40 microg of teriparatide participated in the follow-up study. Bone mineral density gradually decreased following discontinuation of teriparatide therapy. However, the lumbar spine and total hip values remained significantly higher than baseline after 30 months of follow-up (p< or =0.001). Antiresorptive treatment prevented the decline and tended to further increase bone mineral density. Lateral thoracic lumbar radiographs obtained at baseline and 18 months after discontinuation of teriparatide were available for 279 men. Of these men, 11.7% assigned to placebo, 5.4% treated with teriparatide 20 microg, and 6.0% treated with teriparatide 40 microg had an incident vertebral fracture. In the combined teriparatide treated groups vs placebo, the risk of vertebral fracture was reduced 51% (nonsignificant, p=0.07). The incidence of moderate or severe fractures was significantly reduced by 83% (p=0.01). In conclusion, men who received teriparatide and who may have received follow-up antiresorptive therapy had a decreased risk of moderate and severe vertebral fractures.