Effect of testosterone treatment on bone mineral density in men over 65 years of age.

As men age, their serum testosterone concentrations decrease, as do their bone densities. Because bone density is also low in hypogonadal men, we hypothesized that increasing the serum testosterone concentrations of men over 65 yr to those found in young men would increase their bone densities. We randomized 108 men over 65 yr of age to wear either a testosterone patch or a placebo patch double blindly for 36 months. We measured bone mineral density by dual energy x-ray absorptiometry before and during treatment. Ninety-six men completed the entire 36-month protocol. The mean serum testosterone concentration in the men treated with testosterone increased from 367 +/- 79 ng/dL (+/-SD; 12.7 +/- 2.7 nmol/L) before treatment to 625 +/- 249 ng/dL (21.7 +/- 8.6 nmol/L; P < 0.001) at 6 months of treatment and remained at that level for the duration of the study. The mean bone mineral density of the lumbar spine increased (P < 0.001) in both the placebo-treated (2.5 +/- 0.6%) and testosterone-treated (4.2 +/- 0.8%) groups, but the mean changes did not differ between the groups. Linear regression analysis, however, demonstrated that the lower the pretreatment serum testosterone concentration, the greater the effect of testosterone treatment on lumbar spine bone density from 0-36 months (P = 0.02). This analysis showed a minimal effect (0.9 +/- 1.0%) of testosterone treatment on bone mineral density for a pretreatment serum testosterone concentration of 400 ng/dL (13.9 nmol/L), but an increase of 5.9 +/- 2.2% for a pretreatment testosterone concentration of 200 ng/dL (6.9 nmol/L). Increasing the serum testosterone concentrations of normal men over 65 yr of age to the midnormal range for young men did not increase lumbar spine bone density overall, but did increase it in those men with low pretreatment serum testosterone concentrations.

Effects of isotretinoin on bone mineralization during routine therapy with isotretinoin for acne vulgaris.

OBJECTIVE: To examine the effects of isotretinoin on bone mineralization and other markers of calcium homeostasis in individuals receiving isotretinoin for routine therapy for severe acne vulgaris. DESIGN: Cohort study. SETTING: An academic medical center. PATIENTS: Twenty individuals receiving isotretinoin for severe acne vulgaris. INTERVENTION: None. MAIN OUTCOME MEASURE: The primary outcome was the change in bone mineralization as measured by dual-energy x-ray absorptiometry of the lumbar spine and hip before and after isotretinoin therapy. Additional measurements included serum osteocalcin, calcium, 25-dihydroxyvitamin D, 1,25-dihydroxyvitamin D, and intact parathyroid hormone and urine hydroxyproline or calcium. RESULTS: No changes were noted in bone mineralization of the lumbar spine or hip. Furthermore, no alterations were noted in serum measurements of osteocalcin, calcium, 25-dihydroxyvitamin D, intact parathyroid hormone, or urine measurements of hydroxyproline or calcium. A statistically significant change was noted in 1,25-dihydroxyvitamin D when serum from before and after isotretinoin therapy was compared. CONCLUSION: The use of isotretinoin for 20 weeks for the treatment of severe acne vulgaris does not appear to have any substantial adverse effect on bone mineralization.

Osteoporosis and bone morbidity in cardiac transplant recipients.

PURPOSE: To evaluate the incidence and etiology of osteopenia and pathologic fractures in cardiac transplant recipients. PATIENTS: Thirty-one adult male cardiac transplant recipients and 14 adult men with congestive heart failure (CHF) awaiting cardiac transplantation. METHODS: Assessment of indices of bone and mineral metabolism and of bone mineral density (BMD) by dual-energy x-ray absorptiometry. RESULTS: BMD in the proximal femur was below normal in both groups compared to that in age-matched control subjects, whereas BMD in the lumbar spine was normal. There was no significant difference in BMD at any site between the two groups. No clinical parameter predicted BMD. In all patients, laboratory indices of bone mineral metabolism, except parathyroid hormone (PTH) levels, were normal and not statistically different between the two groups. CHF patients had a trend toward elevations of PTH, 1,25-dihydroxyvitamin D, and urinary calcium excretion compared to transplant patients. Eight of 31 transplant patients and 2 of 14 CHF patients had vertebral compression fractures (c2 = 11.8, p < 0.0006). Transplant recipients with fractures had twice as many rejection episodes as did transplant patients without fractures, but did not differ in cumulative dose of steroids. Two patients developed avascular necrosis of the femoral head following transplantation. CONCLUSIONS: Cardiac transplant recipients and patients with CHF awaiting transplantation had decreased hip BMD, but normal spine BMD. Although immunosuppressive therapy did not appear to influence bone mass, loop diuretics prior to transplantation may have stimulated a mild secondary increase in PTH that could have differentially caused loss of bone density at the hip in both groups. Pulse corticosteroids used in treating rejection may have contributed to the increased incidence of vertebral fractures in transplant patients. These data suggest that severe CHF with its associated diuretic use and decreased activity are primary contributors to osteopenia in these patients.

A longitudinal study of metacarpal bone morphometry in anorexia nervosa.

Osteoporosis is a known complication of anorexia nervosa. Although calorie and mineral malnutrition may contribute to changes in bone mass and morphometry, hypoestrogenism is thought to be the most important etiologic factor. In a seven-year longitudinal study of six women aged 19 to 35 years with adolescent-onset anorexia nervosa, the objective was to correlate menstruation and bone morphometry. At the onset of the study, five women were amenorrheic and had abnormal metacarpal bone morphometry. After seven years, three women remained amenorrheic and below 85% of ideal body weight. Anteroposterior roentgenographs of the nondominant second metacarpal taken at the beginning and end of the study revealed an increase in medullary canal diameter (p less than 0.03) and medullary area (p less than 0.04) and a decrease in combined cortical thickness (p less than 0.04) and percent cortical area (p less than 0.02). These findings suggest progressive endosteal resorption in the absence of compensatory periosteal apposition. Such bone remodeling characteristics are distinctly abnormal in this age group. The three women who regained menses showed up to one third less endosteal resorption and less cortical thinning than did the three women who remained amenorrheic. Resumption of menses may be an important milestone in preventing further cortical bone loss in anorexia nervosa.

Trabecular structure: preliminary application of MR interferometry.

A new approach to probe the structure of trabecular bone in the vertebral bodies in humans was evaluated, and preliminary data are presented. The proposed method is based on the hypothesis that the presence of two physical phases--bone and bone marrow--causes a magnetic field distribution across the imaging voxel. The resulting spread in resonance frequency produces line broadening, which is measured as the decay rate of the region of interest signal intensity that has the properties of an interferogram. The interferogram is the result of two principal chemically shifted components of bone marrow--fat and water--getting in and out of phase with one another while being attenuated by T2* processes from the magnetic field distribution within the measuring volume. The time constant for the decay (T2*) can then be obtained by means of curve-fitting techniques. T2* in healthy persons is found to increase slightly with age. However, patients with osteoporosis (low bone mineral density and/or spine compression fractures) have significantly prolonged T2* values, which are interpreted as arising from an increase in the intertrabecular space.

Management of severe hypercalcemia.

Severe hypercalcemia is a medical emergency requiring urgent treatment. It most commonly is caused by malignant tumors, as in the case study, but can also be caused by advanced hyperparathyroidism or high serum levels of vitamin D. The patient described in the case study shows clinical evidence of volume contraction due to hypercalcemia-related anorexia and vomiting. His elevated serum concentrations of urea nitrogen and creatinine reflect intravascular volume depletion and hypercalcemia-induced reduction of renal perfusion. He is also likely to have irreversible renal damage as a result of nephrocalcinosis. His central nervous system depression is most likely a result of hypercalcemia, but other central nervous system disorders such as cerebral metastases should be considered. Appropriate treatment would include intravenous fluids to correct volume depletion, dilute extracellular fluid calcium, and promote renal calcium excretion. Before waiting for the effects of volume expansion, the first dose of an inhibitor of bone resorption should be given. The agent of choice now (this may change when second-generation bisphosphonates become available) is plicamycin. Etidronate is a reasonable second choice. Because both drugs require at least 48 hours before their hypocalcemic action is manifest, calcitonin could be used to accelerate the rate of decline of the serum calcium. As the patient becomes more alert, weight-bearing and ambulation should be encouraged. With this combination of therapeutic modalities, this patient's serum calcium level should be corrected within 3 to 5 days. Intermittent injections of mithramycin or etidronate could be given on an outpatient basis approximately once a week in order to maintain the serum calcium within the normal range. One of the most important aspects of treatment in hypercalcemic patients is eradication of the underlying disease, which usually calls for specific antitumor therapy, including chemotherapy, radiation therapy, or surgery. Most of the agents currently available for the correction of hypercalcemia have cumulative toxicities or are only transiently effective and, therefore, their use should be considered a temporizing measure until specific treatment directed at the primary disease takes effect.

WR-2721 reduces bone loss after hindlimb tenotomy in rats.

WR-2721 is a thiophosphate analog of cysteamine that produces hypocalcemia in vivo. Previous studies suggest that WR-2721 produces hypocalcemia by independent inhibitory effects on parathyroid hormone (PTH) secretion, osteoclastic bone resorption, and tubular reabsorption of calcium. We sought to determine if WR-2721 would decrease bone loss in an animal model of disuse osteoporosis produced by unilateral knee tenotomy in the rat. Tenotomy significantly increased osteoclast number in tibias on the side of the procedure compared with tibias on the opposite side which had not undergone the procedure at 3 and 14 days. Femoral weight of tenotomized limbs were also reduced significantly compared with the contralateral limb at 3 and 14 days. WR-2721 treatment (240 mg/kg daily) prevented 26% of the loss of femoral dry weight and 29% of the loss of femoral ashed weight produced 14 days after tenotomy. In addition, WR-2721 treated (240 mg/kg daily) animals had fewer osteoclasts in tenotomized tibias than control animals at 3 days (6.6 +/- 0.7/mm versus 10.3 +/- 0.9/mm, p less than 0.02) and at 14 days (5.8 +/- 0.3/mm versus 8.7 +/- 0.4/mm, p less than 0.02). These data suggest that WR-2721 decreases bone loss in this model by decreasing osteoclastic bone resorption.

Treatment of hypercalcemia.

Severe hypercalcemia is a potentially life-threatening complication of several diseases. Most commonly it is caused by cancers that enhance bone resorption. Impaired renal calcium excretion resulting from a combination of volume contraction and calcium-induced renal injury (nephrocalcinosis) plays a critical role in the genesis and aggravation of hypercalcemia. Treatment of hypercalcemia is based on treating the underlying disease, restoring extracellular volume, correcting electrolyte deficiencies (potassium and magnesium), and reducing bone resorption. Several measures are available to reduce bone resorption, of which the most efficacious are the bisphosphonates and plicamycin (mithramycin). One of these agents in combination with volume expansion can reduce serum calcium concentrations to near normal in most patients within 3 to 6 days. Because of the delayed hypocalcemic action of these agents, they should be administered early. Calcitonin has a more modest hypocalcemic action than the bisphosphonates or plicamycin but has a more rapid effect. Combining calcitonin with plicamycin or a bisphosphonate can enhance the rate of decline of the serum calcium level. Bone resorption also can be reduced by getting patients out of bed to stand or walk. Glucocorticoids may be effective in patients with hypercalcemia associated with high levels of vitamin D, such as sarcoidosis, some lymphomas, or vitamin D intoxication. Patients with mild to moderate hypercalcemia may be asymptomatic. Therapy in these patients should be directed at the primary disease as well as at preventing complications that could raise the level of serum calcium. Efforts should be made to prevent volume contraction and prolonged bed rest. Sedatives and narcotic analgesics, by reducing activity and oral intake, can raise serum calcium levels. In the future it may be possible to predict which patients with cancer are likely to develop accelerated local tumor-mediated or humorally mediated osteolysis. For example, high circulating levels of PTH-like peptides in patients with lung cancer might suggest a greater risk of developing hypercalcemia. These patients could be monitored more closely by periodically measuring urinary calcium. Another prophylactic approach would be to treat patients at risk of developing hypercalcemia with drugs, such as the bisphosphonates, that inhibit bone resorption.

Quantitative computed tomography reflects vertebral fracture morbidity in osteopenic patients.

We studied the relationship between spontaneous vertebral compression fractures and lumbar vertebral trabecular bone density in 69 consecutive patients with suspected osteopenia. Seven had biopsy-confirmed osteomalacia. The remaining 62 were divided into three groups: group 1--asymptomatic patients suspected of having osteopenia on plain films, but with no vertebral compression fractures (N = 24); group II--those with one to five vertebral compression fractures (N = 16); and group III--those with six or more vertebral compression fractures (N = 22). A quantitative computed tomographic (QCT) scan of the lumbar spine was performed on all patients. Patients in group I had QCT values of 94 +/- 23 mg/cm3 (mean +/- SE); those in group II had QCT values of 66 +/- 28 mg/cm3; and those in group III had values of 34 +/- 28 mg/cm3. There were significant differences among all groups (P less than .001), although there was considerable overlap of individuals among the groups. There was no significant difference between the mean QCT value of patients with one compression fracture and the value of those with between two and five compression fractures. Patients with biopsy-proven osteomalacia had higher vertebral trabecular bone density than patients with osteoporosis and compression fractures. Our study provides evidence suggesting a strong inverse relationship between QCT-measured vertebral bone density and the presence of vertebral compression fractures in a group of osteopenic patients.

Quantitative autoradiography of parathyroid glands in rats with carbon-14-labeled amino acids.

We have utilized a quantitative autoradiographic method as a means of evaluating amino acid uptake of the rat parathyroid gland for the ultimate purpose of finding agents potentially suitable for position emission tomographic scanning of parathyroid glands. L-[1-14C]leucine and L-[guanido-14C]arginine were evaluated because of their relatively high content in the synthetic products of the parathyroid glands compared with other neck tissues, thyroid gland, and muscle. Carbon-14 leucine disappeared rapidly from plasma following intravenous injection and there was relatively selective uptake of the [14C]leucine and [14C]arginine by the parathyroid glands when compared with uptake by the thyroid gland and neck muscle. These data suggest that both agents warrant further investigation for their potential utility in positron emission tomographic scanning of the parathyroid gland.

[Indirect immunofluorescence in the serodiagnosis of Trichomonas vaginalis infections]. / L'immunofluorescenza indiretta nella sierodiagnosi di infezioni da T. vaginalis.

By using immunofluorescent technique the Authors have observed that high titer circulating antibodies reacting with membrane or cytoplasmic structures of T. vaginalis occur in the majority (42/45) of women presenting because of trichomonas vaginitis. Only exceptionally high titer antibodies have been detected in serum of male subjects affected by urethral trichomoniasis. Low titer antibodies are found in serum of noninfected subjects and are supposed to be induced by cross reacting flagellate group antigens. The contribution of these findings to a better understanding of the natural history of trichomoniasis is briefly discussed.