[Effects of weightlessness on phospho-calcium metabolism and its hormonal regulation in man during the 51 G Franco-American space flight]. / Effects de l'apesanteur sur le métabolisme phospho-calcique et sa régulation hormonale chez l'homme au cours du vol spatial Franco-Américain 51 G.

During the 51 G franco-american mission in weightlessness, calcium metabolism and hormonal regulation were analyzed in two astronauts (a male, a female) before (30,7 and 4 days) and after (0,2 and 5 days) the 7-day spaceflight. Calcium, phosphate, alkaline phosphatase, GLA protein, 25 hydro-vitamin D, 1-25 dihydroxyvitamin D, parathyroid hormone, 24 h urinary calcium, total, dialysable and nondialysable hydroxyproline and glycosaminoglycans (GAG) were measured in blood and urine. Only urinary parameters are increased after space flight. Blood parameters, in particular hormone measurements, are unchanged. The data indicate stimulation of resorptive activity which could result in bone matrix atrophy and demineralisation. On the contrary, no bone formation impairment is noted since alkaline phosphatase and GLA protein are unchanged. These changes are not dependent on hormonal variations. They could only reflect the mechanical bone adaptation to weightlessness.

Effects of clodronate on immobilization bone loss.

Clodronate can be used in animals to prevent the effects of immobilization on bone. For this reason we have studied the effects of this agent on immobilisation bone loss in man. We administered clodronate by mouth to 14 paraplegic patients (400 mg/d, n = 7; 1600 mg/day, n = 7), and compared its effect with a placebo (n = 7). Treatment was given for 100 days, 5-29 days after spinal cord injury. Our results suggest that clodronate, given early after immobilization, prevents the acute bone loss observed in immobilization as judged by its effects on serum and urine calcium and hydroxyproline, bone mineral content, trabecular bone volume, and the number of osteoclasts present in bone. No mineralization defect or other side-effects were observed during or after treatment. In addition, a total of 70 patients, with comparable degrees of immobilization, were studied with a variety of antiosteoclastic drugs comprising controls (n = 16), etidronate (n = 20), salmon calcitonin (n = 20) and clodronate 400 mg/d (n = 7) or 1600 mg/d (n = 7). Clodronate, at the dose of 1600 mg/d appeared the most effective drug on bone resorption, together with calcitonin. Unlike calcitonin, clodronate can be administered orally. The mineralisation defects observed during prolonged treatment with etidronate at high doses were not observed with clodronate. We conclude that clodronate 1600 mg/d is a promising agent for the treatment of bone loss and the resorptive hypercalcaemia and hypercalciuria noted in immobilisation.

Urinary elimination of glycosaminoglycans during the immobilization osteoporosis of spinal cord injury patients.

Urinary glycosaminoglycans (GAGs) were measured in 47 paraplegics, six tetraplegics, and ten control subjects. In two paraplegics, the GAG rates were compared with those of hydroxyprolinuria and calciuria during one year. The GAG excretion rate found during the first five months after spinal cord injury increased significantly, up to three or four times the normal rate. No significant differences were found between paraplegics and tetraplegics. This increase in glycosaminoglycanuria parallels the previously reported increase in hydroxyprolinuria. The formation of a neurogenic paraosteoarthropathy showed the highest increase in hydroxyprolinuria. These biochemical assessments reflect the modifications in the bone matrix and cutaneous tissue associated with immobilization osteoporosis in spinal cord injury patients.

[The influence of diet on the urinary excretion of total, free and conjugated non-dialysable hydroxyproline in the normal adult (author's transl)]. / Influence du régime alimentaire sur l'excrétion urinaire de l'hydroxyproline totale, libre et conjuguée non dialysable chez l'adulte normal.

Having established reference values for the different forms of urinary excretion of hydroxyproline on the basis of the results obtained in 12 normal subjects aged from 20 to 43 years, the authors studied the influence of three diets on the excretion of total, free and conjugated hydroxyproline. Urinary levels of total and peptide dialysable hydroxyprolines were found to be highly sensitive to the dietary collagen content, whilst free hydroxyproline increased only when the dietary collagen intake was very high. Peptide non-dialysable hydroxyproline, corresponding to peptides of molecular weight 6000-8000 was not influenced by diet. The ratio dialysable hydroxyproline/non-dialysable hydroxyproline varied from reference values if the diet was loaded with collagen. Only the ratio free hydroxyproline/non-dialysable hydroxyproline seemed to be independent of diet in the subjects studied.

[Study of Urinary excretion of total, free, and non-dialysable conjugated hydroxyproline in paraplegics]. / Etude de l'excrétion urinaire de l'hydroxyproline totale libre et conjuguée non dialysable chez les sujets paraplégiques.

Eighteen paraplegics with or without neurogenic osteo-arthropathy (POAN) were evaluated for variations in their urinary excretion levels of total (T), and free (L) hydroxyproline and its non-dialysable (ND) and dialysable (D) peptide fractions. Increases in urinary hydroxyproline, moderate rises in free hydroxyproline and more substantial increases in dialysable and non-dialysable peptide fractions could be observed in these patients who all were affected with osteoporosis of disuse. Only variations in dialysable hydroxyproline could be used to differentiate between POAN + and POAN - patients. Of the various ratios which were analyzed (ND/T, L/ND, and D/ND), the D/ND ratio appears to be the most useful for diagnosis and monitoring of patients with POAN.

Effects of disodium dichloromethylene diphosphonate on bone loss in paraplegic patients.

21 paraplegic patients with recent traumatic spinal cord injury were orally administered 400 (n = 7) or 1,600 (n = 7) mg/d of disodium dichloromethylene diphosphonate (Cl2MDP) and compared with a placebo group (n = 7) to test the preventive effects of the drug on acute bone loss and osteoclastic resorption. Cl2MDP therapy was initiated at a mean of 17.6 d after the onset of paraplegia. The study lasted at least 6 mo, consisting of a 3.5-mo treatment period, and a variable follow-up period. The effects of Cl2MDP were assessed by blood and urine biochemistry, bone histomorphometry on transilial samples, photon absorptiometry of the tibia and fibula, and radiomorphometry of the femur. The elevation in serum and urinary calcium and in urine hydroxyproline observed in the placebo group did not appear under treatment. With both doses of Cl2MDP there was no further decrease in the bone mineral content. In the treated groups, a smaller percentage increase in osteoclastic population was also noted when compared with the placebo group, but this difference was not significant. There was no mineralization defect induced by Cl2MDP, as shown by tetracycline double labeling. It thus appears that at doses ranging between 400 and 1,600 mg, given as early as possible, Cl2MDP can prevent or reduce the development of the acute bone loss of paraplegic patients, without adverse side effects, though it does not prevent the development of heterotopic ossification.

[Hyperuricosuria and urinary lithiasis in paraplegic patients (author's transl)]. / Hyperuricosurie et lithiase urinaire chez le paraplégique.

One hundred and thirteen urinary stones fron spinal cord injured patients contain urates in 65,5% of cases. In a prospective study of 21 paraplegic patients, an early increase of uricosuria was found as well as a late and moderate elevation of uricemia. The origin of these changes of the metabolism of uric acid is discussed. Therapeutic consequences from these results are studied.

Neurologic injuries, paraosteoarthropathies, and human leukocyte antigens.

The distribution of human leukocyte antigens (HLA) A and B has been evaluated in the circulatory lymphocytes of 68 patients with spinal cord injury and 32 with severe head injury. Paraosteoarthropathy (POA) was present in 43 spinal cord injury and 23 head injury patients. HLA-B 18 was found in 25.7% of the subjects with POA. Among 341 healthy subjects, the frequency of HLA-B 18 was 7.6%. There is a 0% frequency in patients without POA. The frequency of the HLA-B 18 antigen is significantly raised in POA patients, suggesting relationship between the development of POA and the presence of the HLA-B 18 marker. The presence of HLA-B 18 might be associated with an increased risk of POA in patients with lesion of the central nervous system.

[Value of antibody coated bacteria in the localization and follow-up of chronic urinary tract infections (author's transl)]. / Intérêt de la recherche des anticorps fixés sur les bactéries dans la localisation et la surveillance des infections urinaires chroniques.

Antibody coating of urinary bacteria was performed in order to localize the site of recurrent urinary tract infections in 39 para or tetraplegics. The antibody-coated bacteria test was positive with anti human globulin in 19 out of 39 patients: upper urinary tract infections 7/10, prostatitis 3/3, lower urinary tract infections 9/26. Of the 19 patients with positive antibody-coated bacteria test 14 were tested with monospecific antisera: 13 were IgG positive and 11 were IgA positive; IgM was never present. Among the 11 IgA positive tests, we search for the presence of IgA secretory piece in 8 and all were positive. The immunoglobulins on the bacterial wall result, in part, from local production of urinary antibody. Although positive results with anti human globulins occurred frequently in patients with lower urinary tract infections, this test appears to be a useful screening test for localization of infection in patients with recurrent urinary tract infection.