In a prospective, controlled, and randomized clinical trial, we examined the effects of treatment with vitamin D (1,000 IU/d), calcium (1 g/d), and ethane-1-hydroxy-1,1-diphosphonate (EHDP; 7.5 mg/kg body weight) on vertebral bone mass in fourteen asthmatics undergoing long-term treatment with systemically applied corticosteroids. The extent of steroid-induced bone loss was judged by vertebral bone density of the lumbar spine measured by dual-photon absorptiometry as well as by vertebral crush fracture incidence examined by conventional X-ray. Results of the measurements before treatment and after six mo were compared with those of an untreated control group of nineteen asthmatics. Bone density increased during the observation period by 5% in the treated group, compared with a decrease of 4.3% in the untreated control group (p < 0.01). Moreover, in the treated group no radiologically visible new fractures occurred; in the control group new fractures were observed in four patients. There were no serious side effects of the applied drugs during the 6-mo period. Therefore, the combination of EHDP, calcium, and vitamin D appears to be a useful regimen for the management of steroid-induced bone loss in adult asthmatics.
Objectives-Osteocalcin is the major non-coliagenous protein of bone and is regarded as a specific index of bone formation. The aim of this study was to examine the rate of bone formation measured by osteocalcin in 38 patients with ankylosing spondylitis (AS) and its dependence on various parameters of calcium and phosphate metabolism. Methods-Serum osteocalcin, alkaline phosphatase, parathyroid hormone, and 1,25-dihydroxyvitamin D were measured in 38 patients with ankylosing spondylitis and in 52 controls. Results-Mean serum osteocalcin was significantly reduced in patients with AS (men 1*7 (1.1) ng/ml; women 1-2 (1.1) ng/ml) compared with the corresponding control groups (men 3-2 (1.3) ng/ml; women 4-1 (1.7) nglml). Although they have been useful in measuring bone turnover, they also have significant limitations.7 8 y-Carboxyglutamic acid containing protein of bone, the most abundant protein of bone derived from osteoblasts,9 is a specific marker of bone formation. The synthesis of this protein, usually called osteocalcin, is regulated by calciotropic hormones.'01 In particular, 1,25-dihydroxyvitamin D stimulates the production of osteocalcin in osteoblasts.'0 The aim of this study was to examine the rate of bone formation (measured by the amount of osteocalcin) in patients with AS and its dependence on various parameters of calcium phosphate metabolism, especially parathyroid hormone and 1 ,25-dihydroxyvitamin D. Patients and methodsThe study group consisted of an unselected group of 38 consecutive patients with mild to moderate AS (13 women and 25 men, mean ages 37 and 42 years respectively) attending an outpatient clinic for rheumatic disease. The control group (23 women and 29 men aged between 20 and 64 with a mean (SD) age of 37 (14.6) and 41-6 (17) years respectively) had no evidence of calcium or skeletal abnormalities by routine history, physical, and biochemical evaluation. Patients with AS had characteristic physical signs and radiographic features according to New York clinical criteria.'2 None of the patients received glucocorticoids and only two received non-steroidal anti-inflammatory drugs (NSAIDs).For all subjects and patients blood samples were collected in the morning (8 am) after an overnight fast. Serum samples were separated by centrifugation and then frozen at -40'C.Osteocalcin was measured in duplicate by a commercial radioimmunoassay (ImmunoNuclear Corporation, Stillwater, MN, USA) by the method of Price and Nishimoto using purified calf bone GLA protein.'3 The sensitivity of the assay was 0-2 ng/ml and the concentration could be determined in all patients. In all cases the intraassay variation was less than 8% and the interassay variation was less than 12%. Parathyroid hormone was determined by a commercial radioimmunoassay (Fleurus, Belgium) using chicken antibody raised against human parathyroid hormone (c terminal). The interassay variation was less than 13%. 25-Hydroxyvitamin D, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D were determined as described elsewhere. '4
Abstract. The conversion of [1,2,6,7-3H]testosterone2 to [3H]dihydrotestosterone has been assessed in ground spongiosa of normal and osteoporotic bone. The tissue was obtained from 23 patients, 18 women, 3 men and 2 children who were undergoing orthopedic surgery. The formation of dihydrotestosterone was demonstrated in all samples examined. The half maximum rate of dihydrotestosterone formation occurred at a substrate concentration of 0.3 μm a value similar to that reported for dihydrotestosterone formation in other androgen target organs. Under the standardized conditions utilized in this study the rate of dihydrotestosterone formation did not differ significantly in normal as compared to osteoporotic bone. Furthermore, the conversion of testosterone to androstenedione was also similar in osteoporotic and normal bone. Based on these studies it seems reasonable to conclude that dihydrotestosterone rather than testosterone is the active intracellular androgen in human bone since in other androgen target tissues androgen action is mediated by dihydrotestosterone if 5α-reductase is present.
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