The metabolic balance technique: a critical reappraisal.

Twenty-six metabolic balance studies (MBS) of Ca, Mg, and P have been conducted in 11 postmenopausal women with osteoporosis and in 4 patients suffering from Paget's disease of bone. Subjects were given a liquid formula diet (LFD) matched as closely as possible to the patient's home diet. Studies lasted for 25 days, separated into 5-day periods by a carmine marker combines with Cr2O3 as continuous fecal marker. The balance studies were combined with a tracer technique using 47Ca to detect a possible loss of Ca by perspiration. The reliability of analytical methods necessary for mineral balances was tested. In 22 of the 26 MBS a steady state (SS) reflecting the patient's regular living conditions was demonstrated, while a non-SS situation possibly due to changes of physical activity was seen in four instances. The overall precision and accuracy of this balance method for Ca and P was found to be better than plus or minus 50 mg/day after four periods and plus or minus 40 mg/day after five periods, as related to an average daily intake of 920 mg Ca and 1230 mg P. For Mg (intake 190 mg/day), a precision of plus or minus 10 mg/day was recorded. The dermal loss of Ca was found to be less than 20 mg/day. As shown for Ca, Mg and P, the precision of a balance study is only little enhanced when the investigation is continued for more than four periods. At the present time is not possible to predict non-SS situations before starting such a study but a simple formula is proposed to detect those which were not performed under SS conditions.

Bone remodeling and calcium metabolism: a correlated histomorphometric, calcium kinetic, and biochemical study in patients with osteoporosis and Paget's Disease.

The extent to which histomorphometric analysis of bone biopsies correlates with Ca kinetic and biochemical parameters to reflect true bone formation and resorption in adult man remains an unsolved issue. Two groups of patients with either low (osteoporosis), (n = 15) or high (Paget's disease, n = 6) bone turnover were studied before and after sodium fluoride (NaF) and diphosphonate (EHDP) treatment, respectively. Histomorphometry of iliac crest biopsies permitted precise quantitation of the osteoblast layers (SVab), osteoid seams (SVos), the number of osteoclasts (NAocl) and the Howship's lacunae (SVhl). These determinations were correlated with serum alkaline phosphatase (aPh), urinary hydroxyproline (HyPro), Ca accretion rate (Vo+), and Ca mobilization rate (Vo-). In both patient groups bone formation indices were significantly correlated: SVob/Vo+, r = 0.85; SVos/Vo+, r = 0.83; and aPh/Vo+, r = 0.97. Provided that bone matrix formation and mineralization progess at the same rate, bone formation may be assessed by measuring either aPh, Vo+, SVob, or SVos. From these correlations it is not possible to draw any conclusions regarding the absolute "true" value of bone formation, be it in terms of Ca kinetics, alkaline phosphatase, or histomorphometry. However, since Vo+ retains its proportionality to all the other bone formation parameters tested, the so-called "slow exchange," which refers to pure physicochemical Ca exchange processes in the bone mineral, does not perturb Vo+ in an unsystematic way. Vo+ as well as aPh and histomorphometric indices are thus reliable, though not absolute indices of bone formation. Bone resorption indices correlated less well than bone formation indices: NAocl/Vo-, r = 0.68 and SVhl/Vo-, r = 0.63 with both groups. In the osteoporotic group, a negative correlation existed between the empty Howship's lacunae SVhe and Vo+, r = -0.62. Consequently, the overall extent of Howship's lacunae SVhl is influenced both by bone resorption and bone formation. On the other hand, the best correlation of HyPro was with the sum of Vo+ and Vo-, r = 0.97, confirming that HyPro is a sensitive index for the change of bone turnover.

[Breath acetone and ketonemia in normal- and overweight subjects during total fasting (author's transl)]. / Aceton in der Atemluft und Ketone im Venenblut bei vollständigem Fasten normal-und übergewichtiger Personen

In subjects of ideal weight (7 males and 7 females) total whole blood ketones and breath acetone were determined during a 6 day fast, and in obese subjects (8 males, 18 females) during 6-28 days of fasting. Development of starvation ketosis was significantly slower in overweight than in normal weight subjects. Breath acetone concentration was up to blood ketone levels of 4 mMol/1 a linear function of the blood ketone concentration, beyond that level, however, an additional exponential component became apparent. The highest acetone elimination found was 4.46 mg/min, corresponding to 6.4 g acetone and 11.2 g acetoacetic acid in 24 hours. Hence the decarboxylation of acetoacetic acid to acetone may be an additional mechanism for the lowering of ketoacidosis in starvation.

Comparison of the effects of vitamin D3, dihydrotachysterol, and parathormone on calcium kinetics in the rat.

Rats were treated with 100 I.U. (= 2.5 mcg) Vit. D3/day during 14 days and submitted to a radio-Calcium assay of Calcium kinetics. The results were compared with those obtained in weight-matched pair-fed controls, and with those obtained in former experiments applying dihydrotachysterol and parathormone. Vit. D3, which is transformed to a hormone, increased the fast exchange compartment, the exchange rate between the compartments, the endogenous fecal Calcium excretion rate, and the bone uptake and release rates. These findings indicate that the Vit. D-hormone is more similar in its action to the other hormone, parathormone, than to its close chemical relative dihydrotachysterol.

Tumoral calcinosis: accumulation of bone-seeking tracers in the calcium deposits.

Rapid and preferential uptake of 47 calcium 87m Strontium by the multinodular calcareous masses was seen in a patient with tumoral calcinosis. Using 87m Strontium, scintigraphic imaging of the tumors was achieved, while the skeleton was barely visible. More intense accumulation of 87m Sr. in one tumor suggested a higher rate of calcium depostion. This was in agreement with the observation that this tumor showed less tendency to decrease in size during calcium and phosphorus deprivation therapy. Quantitative measurements of the uptake of bone seeking tracers by the tumors may be of value in estimating calcium turnover in the calcified masses.

Tumoral calcinosis. Observations during six years.

Findings of a 56 year old woman suffering from tumoral calcinosis, who was treated for 6 years, are presented. Under conditions known to lead to negative calcium-phosphorus balance, a reduction in tumor size was seen. Transient hypercalcemia was attributed to immobilization. The process of tumor reduction was not definitely accelerated by treatment with ethane-hydroxy-diphosphonate (EHDP; 500 mg/day for 20 months). Nephrotic syndrome as a consequence of amyloidosis developed. Amyloidosis seems to have resulted from the aseptic histiocytic inflammatory process in the tumors. The possible importance of high cholesterol in very low density lipoproteins in the serum of the patient is discussed.

[Primary hyperparathyroidism--bone turnover and osteitis fibrosa assessed by x-ray (author's transl)]. / Primärer Hyperparathyreoidismus--Semiquantitative Erfassung der Fibroosteoklasie und des Knochenumsatzes im Handröntgenbild.

1. In primary hyperparathyroidism an increased bone turnover is seen, accompanied by osteitis fibrosa (= fibroosteoclasia, FO) in severe forms of the disease. Both types of bone reaction may be detected by microradioscopy X-rays of the hand, extensive striation of metacarpal cortical bone indicating increased bone turnover and subperiosteal resorption of phalanges pointing to FO. 2. In the present study 65 patients with proven PHPT were evaluated before and 39 after operation. Microradioscopy was combined with biochemical assessment of hyperparathyroidism including alkaline serum phosphatase (aPh) as an index of osteoblastic activity, hydroxyprolin excretion (HyPro) reflecting bone turnover, immunoreactive parathyroid hormone levels (PTH), serum calcium (SCa), urinary calcium (UCa), serum inorganic phosphorus (SP) and clearance of phosphate (Cp). A comparison was made with the incidence of renal stone disease and the degrees of metacarpal striation (StG) and subperiosteal resorption (UG) were followed after operation. 3. Preoperative X-rays of 60% of the PHPT subjects showed increased StG and/or UG, and in 41,5% the diagnosis of PHPT was possible from the X-ray findings only. There existed a significant correlation between StG and UG on one hand and aPh, HyPro and PTH on the other. No correlation, either positive or negative, was seen between FO and the incidence of renal stones. After surgery, subperiosteal bone lesions disappeared in all patients, while intracortical striations persisted in half of the subjects despite the normalised bone turnover. Thus, primary hyperparathyroidism may not only lead to endosteal bone loss but to an irreversible intracortical bone deficit as well.

[Long-term results of fasting. Results from 132 consecutive patients after 1-6 1/2 years]. / Langzeiterfolg von Fastenkuren Resultate von 132 konsekutiven Patienten nach 1-61/2 Jahren

132 consecutive patients were reexamined 1-6.5 years (m = 2.8) after total fasting in hospital. 37 patients had continued to lose weight, 20 patients had maintained their fasting result (+/-2 kg) and 7 patients had slightly regained (less than 1/3 of their weight loss during fast). These 3 groups, totalling 64 patients (48%), were considered successful. Their mean overweight was diminished from 57 to 29%, corresponding to a 60% reduction of mortality in certain age groups. On the other hand, 63 patients (48%) had regained more than 1/3 of their original weight loss. Five patients (4%) were lost to follow-up. Selection of patients and long-term follow-up appeared to have a decisive bearing on long-term results of fasting, whereas factors such as age, sex, degree of overweight, onset of overweight in childhood and sports were without significant effect. From the long-term results presented, it is concluded that under certain conditions fasting in hospital is warranted. Behaviour therapy is a possible alternative in the treatment of obesity.

[Normocalcemic nephrolithiasis and primary hyperparathyroidism]. / Normocalciämische Nephrolithiasis and primärer Hyperparathyreoidismus.

In normocalciuric and in hypercalciuric renal stone formers tubular calcium reabsorption (TRCa) was studied before and during an intravenous calcium infusion. In addition two patients with proven primary hyperparathyroidism (pHPT) were studied. TRCa was decreased in hypercalciuric stone formers whereas an increase was noted both in pHPT and in normocalciuric subjects. It is concluded that normocalciuric nephrolithiasis may be a manifestation of mild and/or early pHPT.