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Estimation of whole body bone resorption rate: a comparison of urinary total hydroxyproline excretion with two radioisotopic tracer methods in osteoporosis.
In 37 female patients with primary osteoporosis, urinary hydroxyproline excretion, determined in 18 24-h consecutive complete urine collections was compared with two radioisotopic measurements of bone resorption rate measured simultaneously using 85Sr. A somewhat better fit was obtained when the kinetically determined bone resorption rate was corrected for long-term exchange processes within bone. Regression analysis showed that the intercept of the regression of hydroxyproline excretion on resorption rate, corrected or uncorrected for exchange, was significantly higher than zero at about 100 mumol/day. This is consistent with a substantial fraction of urinary hydroxyproline arising from non-bony sources. Fifteen paired studies were analysed and the results suggested that intra-individual variability in these relationships (when studies were separated by a year or more) were similar to inter-individual variability. We calculated the precision with which an estimate of bone resorption could be determined based on the calculated regressions. As a means of non-invasive quantitation of whole body bone resorption rate, the excretion rate of hydroxyproline, measured over 5 days, for example, appeared competitive with isotopic methods making no correction for exchange and relatively little worse than our exchange corrected method.
Transient hypoparathyroidism induced by synthetic human parathyroid hormone-(1-34) treatment.
Daily injections of low doses of a synthetic fragment of human PTH [hPTH-(1-34) have increased iliac trabecular bone volume when used in the treatment of osteoporosis. In approximately 50 patients no major side-effects had occurred. However, during daily sc 100-micrograms injections of the peptide, one patient repeatedly developed parathyroid hypofunction which resolved each time treatment was stopped. Specific immunoglobulin G (IgG) antibodies binding [125I]hPTH-(1-34) were identified in the patient's serum, and positive immunohistochemical reactions were obtained when bovine parathyroid sections were exposed to the patient's IgG. After adsorption with PTH, the patient's IgG, free of anti-PTH antibodies, reacted with renal cell membranes, as demonstrated by indirect immunofluorescence and blocked renal PTH-dependent adenylate-cyclase activation in vitro. These results support the hypothesis that anti-PTH receptor as well as anti-PTH antibodies were generated during hPTH-(1-34) treatment, which led to the development of hypoparathyroidism when their titers were high.
A stochastic analysis of iliac trabecular bone dynamics.
Published normal histomorphometric data were used to derive distributions of thicknesses of trabecular plates and completed bone remodelling units (the basic multicellular unit carrying out bone remodelling, the BMU, when completed is termed a structural unit BSU). A stochastic model was set up to investigate the predictions of current BMU theory. Each of 100 trabecular "thicknesses" was drawn from the appropriate normal distribution using a pseudorandom number generator. Each day, each of its two surfaces when quiescent was assumed to have a 1:900 chance of initiating a remodelling cycle. Resorption (active, 12 days; reversal phase, 27 days) was followed by formation (94 +/- 35 days) and resulted in BMU balance when resorption depth was 36.8 +/- 9.2 micron. Fenestration (thickness less than 0) was assumed to lead to permanent loss of the trabecula. The original model unrealistically increased its mean trabecular thickness as thin trabeculae were lost. This was corrected by assuming that thin trabeculae had greater osteoblastic stimulation and a consequent tendency to thicken, perhaps due to higher mechanical loading. Over 20 years, 14% of trabeculae were lost when the BMU balance was exact and the distribution of trabecular thicknesses was unchanged. About one-half of fenestrations were due to deeper-than-average resorption cavities developing in thin trabeculae, and the remainder to coincident remodelling on both surfaces. A 10% fall in osteoblast lifespan resulted in an additional 36.7% loss of trabecular bone volume and mean trabecular thickness fell to 83.1 micron, compatible with Courpron's data. Simulating more rapid mechanisms of bone loss, approximately 50% of trabeculae could be lost after ten years by the arrest of bone formation; the doubling of resorption depth with unchanged bone formation; and a doubling in the rate of initiation of new BMUs with unchanged bone formation rate, all three followed by complete recovery of BMU balance after only two years. In each case, mean trabecular thickness fell only transiently but trabeculae continued to be lost after recovery. Prolonged osteoblast life span was the most likely explanation for the increased mean trabecular thicknesses and trabecular bone volumes seen in patients with osteoporosis, when treated with sodium fluoride plus calcium supplements or daily injections of parathyroid peptide hPTH 1-34.
Reduction of skeletal blood flow in Paget's disease with disodium etidronate therapy.
Fourteen patients with Paget's disease of bone were treated with disodium etidronate in doses of 5 to 7 mg/kg per day. Skeletal blood flow (SBF), was measured by the modified 18F clearance technique of Wootton et al. (1976) before treatment and again during treatment. In 10 patients restudied 3-4 months after the start of therapy, SBF had fallen by a mean of 21% of the initial value, and the individual differences correlated well with the individual reductions in serum alkaline phosphatase (r = 0.77, P less than 0.01). The results were similar to those seen in an earlier study in patients treated with calcitonin. However, no early reduction in SBF was seen in six repeat studies performed at the end of the second week of treatment, in contrast with our previous findings with calcitonin.
Triglyceride-lowering effect of marine polyunsaturates in patients with hypertriglyceridemia.
Twenty male patients with primary hypertriglyceridemia were treated for 4 weeks with daily supplements (15 g) of oil, which provided approximately 6 g of polyunsaturated fatty acid (PUFA) either of fish or of vegetable origin. Total plasma cholesterol concentrations were unaffected, but both types of supplement increased high density lipoprotein-3 (HDL3) cholesterol concentrations. The fish, but not the vegetable, oil supplement led to a decrease in plasma triglyceride concentrations. Very low density lipoprotein (VLDL), fatty acid composition, and VLDL triglyceride kinetics were subsequently studied in five patients (four male, one female) before and after 4 weeks of therapy with 15 g of the same fish oil. The fish oil led to increases in the proportion of eicosapentaenoic acid in both the VLDL triglyceride and phospholipid fractions, but the increase was greater in the latter. In contrast, the proportion of docosahexanoic acid was increased only in the VLDL triglycerides. The decrease in plasma triglyceride concentrations that occurred with fish-oil therapy was accompanied by a reduction in the absolute catabolic rate of VLDL triglyceride, implying a concomitant change in synthetic rate; the fractional catabolic rate of VLDL triglyceride was unaltered. It is suggested that polyunsaturated fatty acids of marine origin may be therapeutically useful for hypertriglyceridemia.