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Calcium absorption in rheumatoid arthritis.
Calcium absorption, assessed by a double isotope method, was found to be impaired in postmenopausal women with rheumatoid arthritis of recent onset (mean 14.2 months) compared with controls. Circulating levels of 1,25-dihydroxyvitamin D (calcitriol) were higher than in controls, suggesting a primary malabsorption of calcium in these patients. The reduction in calcium absorption correlated with several measures of disease activity, suggesting that the disease process was responsible for the intestinal defect, but an effect from non-steroidal anti-inflammatory agents cannot be excluded. A primary reduction in calcium absorption may increase the risk of osteoporosis in women with rheumatoid arthritis.
Bone turnover in early rheumatoid arthritis. 2. Longitudinal bone density studies.
Serial measurements of bone mineral in 17 ambulant female patients with rheumatoid arthritis (RA) of recent onset and 19 age matched female controls were made in the radius by computed tomography and in the vertebrae by dual photon absorptiometry. Loss of trabecular bone from the distal radius was more rapid in RA (p = 0.0014), but there was no difference in the rate of loss of bone mineral from the radial midshaft or lumbar spine compared with the controls. This study is consistent with the hypothesis that the predominant form of bone loss early in the disease is the vicinity of affected joints.
Bone turnover in early rheumatoid arthritis. 1. Biochemical and kinetic indexes.
Biochemical, hormonal, and kinetic indexes of bone turnover were measured in 17 ambulant female patients with rheumatoid arthritis (RA) of recent onset (mean disease duration 14.2 months) and 19 controls. Mean serum osteocalcin concentration and 85Sr accretion rates were reduced and mean urinary hydroxyproline-creatinine ratios were increased in RA, but these differences were not significant compared with control values. Mean total body potassium (TBK), an index of skeletal muscle mass, was significantly reduced in RA, and the ratio of observed to predicted TBK correlated with indexes of bone formation. No abnormality of skeletal metabolism could be shown in early RA, but reduced rates of bone formation associated with diminished muscle mass may influence the development of osteopenia later in the disease.
Measurement of lumbar spine bone mineral: a comparison of dual photon absorptiometry and computed tomography.
A comparison of computed tomography (CT) and dual photon absorptiometry (DPA) in the measurement of spinal bone mineral was made in 44 subjects of whom 26 had vertebral crush fractures. Although CT measures only trabecular bone within the vertebral body whilst DPA measures the whole vertebral segment, a good correlation was observed (r = 0.80) when these quantities were expressed in dimensionally similar units. Trabecular bone in the distal radius measured by CT correlated less well with vertebral CT (r = 0.65). Cortical bone in the radius correlated poorly with the spinal DPA measurement (r = 0.38).
Electrochemical detection of depressed circulating levels of vitamin K1 in osteoporosis.
If gamma-carboxylation, by the vitamin K1 - cycle, of glutamate residues of bone-matrix peptides is essential for the formation of bone, the circulating levels of this vitamin might indicate the potential efficiency of this process. Methods involving HPLC with electrochemical detection have very recently been developed for assaying the low levels of vitamin K1 that occur in normal plasma. Using such methods, we found that the circulating levels of vitamin K1 in osteoporotic patients (who had sustained either spinal crush-fractures or fractures of the neck of the femur) were significantly lower than those of age-matched control subjects.
Pharmacokinetics of synthetic human parathyroid hormone 1-34 in man measured by cytochemical bioassay and radioimmunoassay.
Synthetic human parathyroid hormone (hPTH) 1-34 was given by intravenous injection to two healthy men. The time course of its appearance in and disappearance from the plasma was monitored both by cytochemical bioassay and by a specific radioimmunoassay (RIA) system. Immunoreactive N-region parathyroid hormone (iPTH) reached peak concentrations in plasma at 2 min after injection, whereas peak concentrations of biologically active parathyroid hormone (bioPTH) were delayed until 4-6 min. Bioassayable PTH-like activity then disappeared from the plasma (mean transit times 5.8 and 8.6 min), approximately twice as fast as immuno-reactivity. After separate subcutaneous administrations, a calculated 22-37% of administered hPTH 1-34 was subsequently detected in the plasma, by both assay systems. It was not possible to explain fully the non-parallel appearances of bio- and immuno-reactivities in the plasma after intravenous injection nor the non-parallel disappearances after both intravenous and subcutaneous injections on the basis of the present data. It seems likely, however, that in the process of biological degradation the immuno-reactive locus is inactivated by a different reaction from that which destroys bioactivity. To investigate these activity dissociations further will require the application of micro-fractionation procedures in conjunction with both types of assay system.
Intestinal absorption of calcium in greyhounds: the response to intermittent and continuous administration of human synthetic parathyroid hormone fragment 1-34 (hPTH 1-34).
Long-term studies of gastrointestinal radio-calcium absorption were undertaken in adult greyhounds before and during two treatment regimes with human parathyroid hormone fragment 1-34 (hPTH 1-34). The results were correlated with plasma vitamin D metabolite levels and kinetic indices related to the balance of fluxes of calcium between plasma and the rapidly exchangeable calcium pools of bone. Compared with adult man, results obtained before treatment started showed lower indices of gastrointestinal calcium absorption and considerably higher concentrations of 24-hydroxycalcidiol in the dogs. Daily injections of hPTH 1-34 at 1.7 microgram day-1 kg-1 significantly increased indices of radiocalcium absorption and plasma calcitriol concentrations, while only causing transient calcaemic responses. The individual magnitudes of the calcaemic response correlated positively with indices of radiocalcium retention in the exchangeable pools of bone which in turn correlated positively with 'late-phase' absorption of radiocalcium from the gut. Subcutaneous infusions of hPTH 1-34 at 0.5 microgram day-1 kg-1 to the same dogs were just insufficient to cause hypercalcaemia, but increased plasma calcitriol concentrations. Indices of radiocalcium absorption were not increased. Continuous parathyroid hormone (PTH) infusion is now known to substantially down-regulate renal PTH receptor density, whereas recovery after a brief exposure to PTH occurs within 24 h. It is possible that the differences in response of the gut to the two regimes may in part be related to their differing effects on some PTH receptors.
Impaired osteoblast function in osteoporosis: comparison between calcium balance and dynamic histomorphometry.
Osteoblast function was investigated in 27 patients with idiopathic osteoporosis. Transiliac bone biopsy specimens were taken after double labelling with tetracycline, and metabolic calcium balance was studied almost simultaneously. Many of the patients showed poor double labelling of their otherwise unremarkable trabecular osteoid, suggesting impaired formation of bone at many of these surfaces. This phenomenon was not accompanied by increased width of osteoid seams (as seen in osteomalacia), indicating that formation of the matrix and its mineralisation were in equilibrium. For the first time, highly significant positive correlations (p less than 0.01) were found between indices of bone formation, determined by labelling with tetracycline, and calcium balance. Thus some patients with osteoporosis who are rapidly losing bone have low rates of formation of trabecular bone both by individual osteoblasts and in relation to available bone surfaces. As histological indices of bone resorption also independently correlated strongly and inversely (p less than 0.01) with calcium balance the rate of initiation of new basic multicellular units by osteoclastic resorption of trabecular surfaces (or the depth of resorption at these surfaces) also appears to be an important determinant of mineral balance. The mechanisms that regulate the effective life span of mature osteoblasts require further investigation, particularly as some promising treatments that can increase trabecular bone volume in osteoporosis, such as parathyroid peptide hPTH (1-34) and sodium fluoride, must work through a reversal of osteoblastic depression.
Trends in trabecular and cortical bone in the radius compared with whole body calcium balance in osteoporosis.
Mean linear attenuation coefficients for trabecular bone (T) in the distal radius and total absorption coefficients (TA) in the radial mid-shafts of 22 patients with crush fracture osteoporosis were measured serially for a year by using computed tomography. After approximately 6 months, each patient was admitted to a metabolic ward for an 18-day calcium balance study. The rate of change (trend) in trabecular bone (T) in the distal radius was a better predictor of calcium balance than the trend in mid-shaft cortical bone (TA). The scatter in the regressions of the trends of T and TA on calcium balance could be accounted for by known methodological uncertainties.