1. A new tracer method is described for the noninvasive measurement of bone formation in the proximal femur. The method is based on our previously described whole-body method using 85 Sr as the tracer (Reeve, J., Hesp, R. & Wootton, R. Calcif. Tissue Res. 1976; 22, 191–206). It allows correction to be made for long-term exchange processes within the skeleton. 2. The method has been applied in a study of regional and whole-body bone formation in 12 rehabilitated patients who had previously suffered a fracture of the proximal femur. Twelve healthy control subjects were studied, who were selected for their good health and continued physical activity. The aim was to explore the relationship between bone formation and physical activity. 3. Bone formation was similar in the two groups, both regionally and in the whole body. Based on analyses of four cadaver specimens, bone formation in the proximal femur was about one and two-thirds times that in the whole skeleton when related to mass of calcium in the region of interest. 4. Whole-body bone resorption, estimated from five measurements per subject of hydroxyproline excretion in relation to creatinine excretion, was significantly higher in the fracture patients ( P <0.01, Wilcoxon's test). 5. Estimates of current physical activity (and immediate pre-fracture physical activity) were made with a newly devised questionnaire. Historical levels of physical activity (at ages 15–45 years) were determined with Astrom's questionnaire. No bone formation index correlated with any index of physical activity. Urinary hydroxyproline excretion correlated inversely both with current physical activity and historical physical activity (for both regression coefficients P <0.01). 6. The results are discussed in the light of our current understanding of the control of bone remodelling by the discrete basic multicellular units of bone. The opportunity to study regional bone resorption by the additional use of serial dual X-ray absorptiometry of the same region will in future allow the direct monitoring of the effects of therapeutic interventions which have been designed to prevent contralateral hip fracture.

1. Four paraplegic men volunteered for an exercise programme in which their paralysed quadriceps muscles were stimulated by means of computer-regulated electrical impulses applied through external electrodes. The first exercise regimen consisted of leg raising against a graded load, and during the second regimen exercise took the form of cycling on a modified bicycle ergometer. Each subject exercised five times weekly for 10 weeks during the first regimen and 32 weeks during the second regimen. 2. Whole-body protein turnover determined by l -[1- 13 C]leucine during feeding remained constant during both exercise regimens, when expressed either in terms of body weight or fat-free mass derived from measurements of total body potassium. 3. Quadriceps muscle protein synthetic rate increased during the study, from 0.0712 to 0.0985%/h ( P < 0.05), as did quadriceps muscle area assessed by computed tomography. 4. Bone mineral content for lumbar vertebrae was normal in all four patients, but for the femoral mid-shaft bone mineral content averaged only 66% of normal for three of the patients. Trabecular bone density in the distal tibia ranged from normal to 2% of normal for the men with the shortest and longest periods of disability, respectively. No changes in bone mineral content or bone density occurred during the exercise period.

1. 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. 2. 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. 3. After separate subcutaneous administrations, a calculated 22-37% of administered hPTH 1-34 was subsequently detected in the plasma, by both assay systems. 4. 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 immunoreactive locus is inactivated by a different reaction from that which destroys bioactivity. 5. To investigate these activity dissociations further will require the application of microfractionation procedures in conjunction with both types of assay system.

1. 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. 2. 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. 3. Daily injections of hPTH 1–34 at 1.7 μg 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. 4. Subcutaneous infusions of hPTH 1–34 at 0.5 μg 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. 5. 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.

1. 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. 2. 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). 3. The scatter in the regressions of the trends of T and TA on calcium balance could be accounted for by known methodological uncertainties.

1. Calcium balances and formation rates of new bone measured with an improved tracer technique using 85 Sr have been determined simultaneously in 21 patients with idiopathic osteoporosis and vertebral crush fractures. 2. A weak positive association was found between calcium balance and the kinetically measured calcium accretion rate, which is the sum of the true rate of bone formation and various long-term exchange processes. 3. The more negative balances were associated with significantly greater early loss of tracer taken up into bone by ‘accretion’, so that long-term (> 200 day) uptake was reduced. 4. This indicates that patients actively losing bone mineral have lower true rates of bone formation and higher rates of long-term exchange than their fellow patients who are more nearly in calcium equilibrium. 5. No statistically significant association was found between measured rates of bone resorption and calcium balance.

1. A comparison of several published methods for analysing plasma protein turnover data has been undertaken, with particular reference to rapidly metabolized proteins such as members of the complement series. 2. With the exception of the equilibrium time method, most methods proved adequate for the determination of overall fractional catabolic rates. A further exception is that the renal clearance method becomes invalid when the fractional catabolic rate approaches the renal iodide clearance, but this may be the method of choice for slowly metabolized proteins if accurate urine collections can be ensured. 3. For the measurement of the ratio of extra-to intra-vascular protein pool size a clear preference emerged for the method of C. M. E. Matthews (1957, Physics in Medicine and Biology , 2 , 36–53). For rapidly metabolized proteins the calculations must be preceded by a correction for the non-protein bound iodide retained in the intra- and extra-vascular spaces. 4. The accurate calculation of fractional catabolic rate in the extravascular pool generally requires more experimental data than are commonly collected as well as an accurate correction for non-protein bound label that remains unexcreted. Only two techniques hold promise of accurate results: Nosslin's rate equations method and a development of Vitek's deconvolution method described herein. Nosslin's integrated rate equations method is particularly affected by systematic errors in renal iodide clearance estimates and should probably not be further used for this purpose.

1. Radiocalcium absorption was measured in duplicate in 10 subjects by the double-isotope method, with calcium as the oral carrier (2.5 mmol). Analysis of variance gave 95% confidence limits for a single measurement of fractional absorption and maximum absorption rate in a given individual of ±16.5% of administered dose and ±18.2% of dose/h respectively. 2. The size of these within individual variations suggests that alterations in the rate of calcium absorption-5-contribute to the week-to-week stabilization of some other controlled variable, such as plasma concentration of calcium. 3. In six of the subjects, calcium absorption was also measured with calcium loads at concentrations of 0.5, 5.0 and 20 mmol. Significant falls in fractional absorption, maximum absorption rate and mean transfer rate occurred as the load increased, together with a rise in mean transit time. Although between-individual differences at a given load were considerable, given a single-test result with a known carrier load, it is possible to predict quite accurately the results which would be obtained if a different carrier load were to be given.

1. One-hundred and ten double-tracer ( 47 Ca/ 45 Ca or 47 Ca/ 85 Sr) calcium-absorption studies were performed in patients with a variety of metabolic bone disorders. A computer program was written to fit plasma radioactivity data from both oral and intravenous tracers by spline functions and to deconvolve points interpolated from the fitted curves to obtain the spectrum of *Ca transit times from mouth to plasma. 2. Methodological precision in the estimation of fractional absorption, maximum and mean rates of absorption and mean transit time was not substantially degraded by the normal uncertainties of sample counting. 3. From the results of 35 studies in which 85 Sr was given as an additional intravenous tracer, it is concluded that the use of oral 47 Ca and intravenous 85 Sr is an acceptable alternative to the 47 Ca/ 45 Ca combination and offers considerable practical advantages. 4. The single-tracer whole-body retention and faecal collection methods for estimating calcium absorption were found to be sensitive to variations in endogenous excretion and bone accretion of calcium, making these methods unsuitable for some purposes. 5. The single-tracer method of Marshall and Nordin (1969) provided reasonable estimates of absorption rates, but the simplifications inherent in this model give rise to unpredictable systematic uncertainties in the calculation of mean absorption rates. 6. The double-isotope ( 47 Ca oral, 85 Sr intravenous) calcium-absorption test, in which blood is sampled serially over 6 h, is the method of choice for the detailed investigation in vivo of the physiological mechanisms of radiocalcium absorption by the undisturbed gut.

1. Chromium sesquioxide (Cr 2 O 3 ; 1·5 g/day) and [ 51 Cr]chromic chloride [ 31 CrCl 3 (0·3 μCi/day)] were compared as continuously administered non-absorbed markers for the correction of faecal recoveries in 14 calcium balance studies each lasting at least 18 days. 2. The mean recoveries of each, 98·4% for Cr 2 O 3 and 101·9% for 51 CrCl 3 , were not significantly different from 100. 3. The two markers reduced the uncertainty in a typical 3 × 6 day calcium balance study to a similar extent (sd = 1·4 mmol/day for Cr 2 O 3 and sd = 1·5 mmol/day for 51 CrCl 3 ). 4. 5l CrCl 3 is a convenient and satisfactory alternative to Cr 2 O 3 when the laboratory hazards associated with estimating the latter cannot easily be eliminated.

1. During a 15-month period, 110 elderly patients admitted with fractured neck of femur were studied in comparison with 72 elderly control patients undergoing elective surgery admitted over the same period to the same orthopaedic wards. 2. A striking finding was the marked similarity of all variables measured in the fracture and control groups. The principal differences between the two populations were that the fracture patients had a lower mean forearm bone mineral content, and that their serum concentrations of albumin, globulin and phosphate were reduced. 3. Neither measurements of radioisotopic calcium absorption, nor those of the serum concentrations of calcium, 25-hydroxy-vitamin D 3 nor alkaline phosphatase provided satisfactory discrimination between the groups. 4. Several indices were devised, based on linear combinations of the test results obtained, in an attempt to predict the liability to future fractures of patients being considered for prophylactic therapy with oestrogens or other drugs. However, further work is required to define an index of improved predictive power and to evaluate it prospectively.

1. Renal function has been studied in 312 hypertensive patients by quantitative renography with sodium o -[ 131 I]iodohippurate ( 131 I-labelled Hippuran) and estimation of overall effective renal plasma flow. In 59% of the patients the results were normal. 2. Severe hypertension was associated not only with reduced effective renal plasma flow but also a characteristic abnormality of Hippuran transport in 10% of the patients in which there was a wider than normal variation in transit times of Hippuran through the kidney, which may reflect non-uniformity of reabsorption of filtrate by different groups of nephrons. 3. Plasma renin activity was higher in a group of 14 patients with multimodal transit time spectra than in a matched hypertensive control group, with very substantial overlap between the two groups. 4. The renographic abnormality was usually reversed by treatment.