R. Hesp

The Effects of Treatment with Recombinant Human Growth Hormone on Body Composition and Metabolism in Adults with Growth Hormone Deficiency

In a double-blind, placebo-controlled trial, we studied the effects of six months of growth hormone replacement in 24 adults with growth hormone deficiency. Most of the patients had acquired growth hormone deficiency during adulthood as a consequence of treatment for pituitary tumors, and all were receiving appropriate thyroid, adrenal, and gonadal hormone replacement. The daily dose of recombinant human growth hormone (rhGH) was 0.07 U per kilogram of body weight, given subcutaneously at bedtime. The mean (+/- SE) plasma concentration of insulin-like growth factor I increased from 0.41 +/- 0.05 to 1.53 +/- 0.16 U per liter during rhGH treatment. Treatment with rhGH had no effect on body weight. The mean lean body mass, however, increased by 5.5 +/- 1.1 kg (P less than 0.0001), and the fat mass decreased by 5.7 +/- 0.9 kg (P less than 0.0001) in the group treated with growth hormone; neither changed significantly in the placebo group. The basal metabolic rate, measured at base line and after one and six months of rhGH administration, increased significantly; the respective values were 32.4 +/- 1.4, 37.2 +/- 2.2, and 34.4 +/- 1.6 kcal per kilogram of lean body mass per day (P less than 0.001 for both comparisons). Fasting plasma cholesterol levels were lower (P less than 0.05) in the rhGH-treated group than in the placebo group, whereas plasma triglyceride values were similar in the two groups throughout the study. We conclude that growth hormone has a role in the regulation of body composition in adults, probably through its anabolic and lipolytic actions.

The relationship between changes in femoral bone density and calcium balance in patients with involutional osteoporosis treated with human parathyroid hormone fragment (hPTH 1–34)

Abstract The effect of treatment of crush fracture osteoporosis with human parathyroid hormone fragment (hPTH 1–34) in low (normocalcaemic) dosage was monitored by calcium balances and serial measurements of cortical bone density in the distal femur. There was a significant correlation between the results using the two techniques, so that serial densitometry may be used in the estimation of calcium balance although with somewhat less precision than is obtainable with the best balance technique. Further analysis of the data suggested that hPTH therapy was associated with a significant redistribution of bone mineral away from this cortical bone site, presumably towards trabecular bone volume (Reeve et al., 1980).

A new method for calculating the accretion rate of bone calcium and some observations on the suitability of strontium-85 as a tracer for bone calcium.

Abstract1.A new method for calculating the accretion rate (A) of bone calcium is proposed, based on an impulse analysis of47Ca data. The method is free of most of the assumptions inherent in previous methods of analysis and appears to give more accurate estimates.2.In fourteen normal subjects and twelve patients with metabolic bone disease, measurements ofA by the new method gave very similar results to the mineralization rate calculated by the method of Burkinshawet al. (1969). Analysis of twelve studies performed by Neeret al. (1967) gave good agreement with their five compartment model. A close relation betweenA and Marshall’s (1964)A5 was observed, but the latter gave systematically higher results.3.In sixteen studies both47Ca and85Sr were injected simultaneously. Although there were no systematic differences between the values ofA for the two tracers, the differences between individual values were greater than the known experimental errors.

A new tracer method for the calculation of rates of bone formation and breakdown in osteoporosis and other generalised skeletal disorders

Abstract1.Evidence has accumulated that the rate of acceretion (A) of calcium to bone is the sum of two fluxes; apposition involving the laying down of new bone and augmentation which is the result of slow exchange of non-surface bone calcium with plasma calcium pools as the result of solid state diffusion.2.A method has been devised for separating A into its two components. It requires the use of45Ca or, for clinical studies,85Sr as a calcium tracer. Studies which are initiated with a combined accretion rate-calcium balance study, are concluded with an estimate of the exponent of the power function which has been found to describe the whole body retention of tracer from the second month onward.3.The impulse response function of the skeleton for the tracer is then calculated, making the assumption that in any uniform volume of bone, osteoclastic resorption is a first order process. Making in addition certain simplifying assumptions, which are shown to have a modest influence on the final results, a mean rate of bone resorption can be calculated using a development of the well known Stewart-Hamilton formula. The apposition rate is calculated as the sum of the resorption rate and the calcium balance. Augmentation and diminution, defined as equal and opposite exchange processes, are given by the difference between A and the apposition rate.4.The results of our first thirteen studies in normal subjects and patients with metabolic bone disease are presented, together with analyses of some data from the literature. It is concluded that the development of an atraumatic method for measuring rates of bone formation and resorption in the whole body would be an important advance in the study of metabolic bone disease, and this work is presented so that critical comparisons may be initiated between this tracer method and independent histological methods for measuring these parameters.

Measurement of 57Co-vitamin B12 uptake using a static whole-body counter

Abstract Using a whole-body counter which incorporates eight static NaI((Tl) detectors, it has been found possible to measure the absorption of vitamin B12 labelled with 57Co instead of 58Co, with a consequent reduction in absorbed radiation dose to the patient.

Regional bone density measurements compared to total body calcium in osteoporosis.

In 21 women with crush fracture osteoporosis quantities related to trabecular bone density in lumbar vertebrae and in the distal radius were significantly correlated (r = 0.50, P less than 0.05). When the group was enlarged to include data from other patients without osteoporosis, a higher coefficient of correlation was obtained (r = 0.69, P less than 0.001). Total body calcium, measured by in vivo neutron activation analysis, was significantly correlated to quantities related to cortical bone mass in the radius and femur. Thus, these quantities could be used to make estimates of total body calcium in osteoporotic patients. There was no significant correlation between total body calcium and quantities related to trabecular bone density, measured by computed tomography, in vertebrae or in the distal radius.

High indices of remodelling in iliac trabecular bone predict reduced forearm cortical bone mass indices in patients with proximal femoral fractures

To investigate whether high bone turnover could be a predictor of cortical bone loss and a candidate risk factor for fractures of the proximal femur, 33 7.5-mm transiliac biopsies taken at fracture fixation from 48 patients who participated in a study of potential risk factors have been quantitated. Twenty-four of the 33 patients made good recoveries and about 6 weeks postoperatively consented to bone densitometry of the forearm midshaft. Forearm bone density correlated negatively (r = 0.77, P = 0.001) with the surface of trabecular bone covered with osteoid, which in osteoporotic patients with crush fractures of the vertebrae was previously shown to relate both to rates of bone formation and resorption. An important minority of these femoral fracture patients appeared to be suffering from high rates of iliac trabecular bone resorption. Thus, high bone remodelling activity could lead to excessive cortical thinning. This has pathogenetic implications which may be clinically important.

A new tracer method for the estimation of rates of bone formation and breakdown in man.

Tracer or histological techniques are required to study the basic metabolic processes which cause changes in total body calcium. This paper reports results obtained from studies on patients with osteoporosis using an improved tracer method. The method provides results which are more compatible with histological and other estimates of skeletal turnover than those obtained by previous shortterm tracer techniques.