The effect of supplementation with alkaline potassium salts on bone metabolism: a meta-analysis.

UNLABELLED: The role of acid-base metabolism in bone health is controversial. In this meta-analysis, potassium bicarbonate and potassium citrate lowered urinary calcium and acid excretion and reduced the excretion of the bone resorption marker NTX. These salts may thus be beneficial to bone health by conserving bone mineral. INTRODUCTION: The role of acid-base homeostasis as a determinant of bone health and the contribution of supplemental alkali in promoting skeletal integrity remain a subject of debate. The objective of this study was, therefore, to conduct a meta-analysis to assess the effects of supplemental potassium bicarbonate (KHCO3) and potassium citrate (KCitr) on urinary calcium and acid excretion, markers of bone turnover and bone mineral density (BMD) and to compare their effects with that of potassium chloride (KCl). METHODS: A total of 14 studies of the effect of alkaline potassium salts on calcium metabolism and bone health, identified by a systematic literature search, were analysed with Review Manager (Version 5; The Cochrane Collaboration) using a random-effects model. Authors were contacted to provide missing data as required. Results are presented as the standardised (SMD) or unstandardized mean difference (MD) (95 % confidence intervals). RESULTS: Urinary calcium excretion was lowered by intervention with both KHCO3 (P = 0.04) and KCitr (P = 0.01), as was net acid excretion (NAE) (P = 0.002 for KHCO3 and P = 0.0008 for KCitr). Both salts significantly lowered the bone resorption marker NTX (P < 0.00001). There was no effect on bone formation markers or BMD. KHCO3 and KCitr lowered calcium excretion to a greater extent than did KCl. CONCLUSIONS: This meta-analysis confirms that supplementation with alkaline potassium salts leads to significant reduction in renal calcium excretion and acid excretion, compatible with the concept of increased buffering of hydrogen ions by raised circulating bicarbonate. The observed reduction in bone resorption indicates a potential benefit to bone health.

Postgraduate Symposium: Positive influence of nutritional alkalinity on bone health.

There is growing evidence that consumption of a Western diet is a risk factor for osteoporosis through excess acid supply, while fruits and vegetables balance the excess acidity, mostly by providing K-rich bicarbonate-rich foods. Western diets consumed by adults generate approximately 50-100 mEq acid/d; therefore, healthy adults consuming such a diet are at risk of chronic low-grade metabolic acidosis, which worsens with age as a result of declining kidney function. Bone buffers the excess acid by delivering cations and it is considered that with time an overstimulation of this process will lead to the dissolution of the bone mineral content and hence to reduced bone mass. Intakes of K, Mg and fruit and vegetables have been associated with a higher alkaline status and a subsequent beneficial effect on bone health. In healthy male volunteers an acid-forming diet increases urinary Ca excretion by 74% and urinary C-terminal telopeptide of type I collagen (C-telopeptide) excretion by 19% when compared with an alkali (base-forming) diet. Cross-sectional studies have shown that there is a correlation between the nutritional acid load and bone health measured by bone ultrasound or dual-energy X-ray absorptiometry. Few studies have been undertaken in very elderly women (>75 years), whose osteoporosis risk is very pertinent. The EVAluation of Nutrients Intakes and Bone Ultra Sound Study has developed and validated (n 51) an FFQ for use in a very elderly Swiss population (mean age 80.4 (sd 2.99) years), which has shown intakes of key nutrients (energy, fat, carbohydrate, Ca, Mg, vitamin C, D and E) to be low in 401 subjects. A subsequent study to assess net endogenous acid production (NEAP) and bone ultrasound results in 256 women aged > or = 75 years has shown that lower NEAP (P=0.023) and higher K intake (P=0.033) are correlated with higher bone ultrasound results. High acid load may be an important additional risk factor that may be particularly relevant in very elderly patients with an already-high fracture risk. The latter study adds to knowledge by confirming a positive link between dietary alkalinity and bone health indices in the very elderly. In a further study to complement these findings it has also been shown in a group of thirty young women that in Ca sufficiency an acid Ca-rich water has no effect on bone resorption, while an alkaline bicarbonate-rich water leads to a decrease in both serum parathyroid hormone and serum C-telopeptide. Further investigations need to be undertaken to study whether these positive effects on bone loss are maintained over long-term treatment. Mineral-water consumption could be an easy and inexpensive way of helping to prevent osteoporosis and could be of major interest for long-term prevention of bone loss.

[Calcium supplementation in the menopause--unnecessary, advisable, or necessary?]. / Kalzium-Supplementierung in der Menopause: überflüssig, erwünscht oder obligatorisch?

With the menopause, the multiple positive effects of estrogens on bone come to an end, which leads to an increased bone turnover an accelerated bone loss and an increased fracture risk. Although the antifracture effect of calcium alone is questionable, several observations justify the recommendation to avoid calcium deficiency in this age: Very low Calcium intake is related to low BMD and higher hip fracture incidence in several studies; regular Calcium supplementation lowers fracture incidence, when observed over years. Calcium from dairy products, mineral waters and supplements is almost equally well absorbed. But the former contain also other nutrients with positive effects on bone, such as proteins, phosphorus, bicarbonates. The choice goes for the nutrient or supplement with the best acceptance by a given individual.

Effects of usual nutrient intake and vitamin D status on markers of bone turnover in Swiss adolescents.

OBJECTIVE: To evaluate the effects of nutrient intake and vitamin D status on markers of type I collagen formation and degradation in adolescent boys and girls. DESIGN: Cross-sectional study. SETTING: Canton of Vaud, West Switzerland. SUBJECTS: A total of 92 boys and 104 girls, aged 11-16 y. Data were collected on height, weight, pubertal status (self-assessment of Tanner stage), nutrient intake (3-day dietary record) and fasting serum concentration of 25-hydroxyvitamin D (25OHD), and markers of collagen formation (P1NP) and degradation (serum C-terminal telopeptides: S-CTX). RESULTS: Tanner stage was a significant determinant of P1NP in boys and girls and S-CTX in girls. Of the nutrients examined, only the ratio of calcium to phosphorus (Ca/P) was positively associated with P1NP in boys, after adjustment for pubertal status. 25OHD decreased significantly at each Tanner stage in boys. Overall, 15% of boys and 17% of girls were identified as being vitamin D insufficient (serum 25OHD <30 nmol/l), with the highest proportion of insufficiency at Tanner stage 4-5 (29%) in boys and at Tanner stage 3 (24%) in girls. A significant association was not found between 25OHD and either bone turnover marker, nor was 25OHD insufficiency associated with higher concentrations of the bone turnover markers. CONCLUSIONS: The marked effects of puberty on bone metabolism may have obscured any possible effects of diet and vitamin D status on markers of bone metabolism. The mechanistic basis for the positive association between dietary Ca/P ratio and P1NP in boys is not clear and may be attributable to a higher Ca intake per se, a critical balance between Ca and P intake or higher dairy product consumption. A higher incidence of vitamin D insufficiency in older adolescents may reflect a more sedentary lifestyle or increased utilisation of 25OHD, and suggests that further research is needed to define their requirements. SPONSORSHIP: Nestec Ltd and The Swiss Foundation for Research in Osteoporosis.

Intravenous ibandronate in men with osteoporosis: an open pilot study over 2 years.

In the treatment of osteoporosis, the tolerance of oral bisphosphonates is often low. The high potency of ibandronate allows iv bolus injections that can be repeated every 2 to 3 months. However, the best dose and time interval of the treatment with iv ibandronate is still debated. Efficacy of 2-mg ibandronate injected every 3 months was tested in men with osteoporosis over 2 yr, in a prospective, open study. Fourteen men with primary osteoporosis, mean age 57 +/- 12 yr (range: 40-73), received 2-mg ibandronate iv every 3 months over 2 yr. All got 1 g/day calcium and 880 UI/day vitamin D for 2 yr. Bone mineral density (BMD) increased after 2 yr by 6.7 +/- 1.5% (mean change +/- SEM) at lumbar spine (p<0.001), by 3.2 +/- 08% at trochanter (p<0.001) and by 1.4 +/- 1.1% at femoral neck (ns). Serum beta-crosslaps and osteocalcin decreased significantly by 30-45 and 30%, respectively, during the 2 yr of treatment. Serum calcium increased from the lower to the middle tertile of the normal range during the 2 yr of the study. The observed decrease of bone remodelling and the increase of BMD are of the same magnitude as those described with oral bisphosphonates. The increase of plasma calcium confirms the positive effect of the supplementation with calcium and vitamin D. These results suggest that 3 months are a good interval between two doses of iv ibandronate, when 2 mg are given.

Diet acids and alkalis influence calcium retention in bone.

The urine-acidifying properties of food constituents depend on their content of non-oxidizable acids or precursors. Acidifying constituents such as animal proteins may negatively affect calcium metabolism and accelerate bone resorption, thus representing an aggravating factor for osteoporosis. This four-period, double-crossover study investigated whether a diet intervention specifically focused on acid load could modify calcium metabolism in humans. Eight healthy volunteers underwent a four-day metabolic preparation with two types of diets, one rich in acid ash-forming nutrients, and one providing base-forming nutrients (including bicarbonate-rich mineral water), both having similar contents of calcium, phosphate, sodium, proteins and calories. On the fourth day, a single oral dose of 1 g calcium was given, either as carbonate or as gluconolactate. Serial blood and urine samples revealed that the diet affected blood pH (average difference 0.014, p=0.002) and urine pH (average difference 1.02, p<0.0001) in the expected direction, but had no influence on the absorption of the calcium supplement. The acid-forming diet increased urinary calcium excretion by 74% when compared with the base-forming diet (p<0.0001), both at baseline and after the oral calcium load, and C-telopeptide excretion by 19% (p=0.01), suggesting a skeletal origin for the excess calcium output. This observation confirms that renally excreted acids derived from food influence calcium metabolism, and that alkalizing nutrients inhibit bone resorption. Further studies are needed to determine the clinical impact of dietary counseling for avoiding diet acids as a preventive measure against osteoporosis.

Effect of supplementation with vitamin D3 and calcium on quantitative ultrasound of bone in elderly institutionalized women: a longitudinal study.

Supplementation of elderly institutionalized women with vitamin D and calcium decreased hip fractures and increased hip bone mineral density. Quantitative ultrasound (QUS) measurements can be performed in nursing homes, and easily repeated for follow-up. However, the effect of the correction of vitamin D deficiency on QUS parameters is not known. Therefore, 248 institutionalized women aged 62-98 years were included in a 2-year open controlled study. They were randomized into a treated group (n = 124), receiving 440 IU of vitamin D3 combined with 500 mg calcium (1250 mg calcium carbonate, Novartis) twice daily, and a control group (n = 124). One hundred and three women (42%), aged 84.5 +/- 7.5 years, completed the study: 50 in the treated group, 53 in the controls. QUS of the calcaneus, which measures BUA (broadband ultrasound attenuation) and SOS (speed of sound), and biochemical analysis were performed before and after 1 and 2 years of treatment. Only the results of the women with a complete follow-up were taken into account. Both groups had low initial mean serum 25-hydroxyvitamin D levels (11.9 +/- 1.2 and 11.7 +/- 1.2 micrograms/l; normal range 6.4-40.2 micrograms/l) and normal mean serum parathyroid hormone (PTH) levels (43.1 +/- 3.2 and 44.6 +/- 3.5 ng/l; normal range 10-70 ng/l, normal mean 31.8 +/- 2.3 ng/l). The treatment led to a correction of the metabolic disturbances, with an increase in 25-hydroxyvitamin D by 123% (p < 0.01) and a decrease in PTH by 18% (p < 0.05) and of alkaline phosphatase by 15% (p < 0.01). In the controls there was a worsening of the hypovitaminosis D, with a decrease of 25-hydroxyvitamin D by 51% (p < 0.01) and an increase in PTH by 51% (p < 0.01), while the serum calcium level decreased by only 2% (p < 0.01). After 2 years of treatment BUA increased significantly by 1.6% in the treated group (p < 0.05), and decreased by 2.3% in the controls (p < 0.01). Therefore, the difference in BUA between the treated subjects and the controls (3.9%) was significant after 2 years (p < 0.01). However, SOS decreased by the same amount in both groups (approximately 0.5%). In conclusion, BUA, but not SOS, reflected the positive effect on bone of supplementation with calcium and vitamin D3 in a population of elderly institutionalized women.

[Osteoporosis and nutrition]. / Osteoporose und Ernährung.

Although nutrition accounts only for a small percentage of bone mass, it is essential for reaching and maintaining peak bone mass and for preventing accelerated bone loss with age. Calcium, proteins, and vitamin D are the best investigated nutrients, protein- and vitamin D-deficiency becoming frequent with advancing age, vitamin K, trace elements, and phosphorus having additional effects. Excessive intake of animal proteins leads to bone loss via acidotic stimulation of osteoclastic bone resorption, and high salt intake enhances negative calcium balance by increasing renal calcium losses. Dairy products offer an equilibrated Calcium and protein intake, but have to be monitored for their fat content. Adequate nutrition in childhood influences positively bone mass in adulthood, while nutritional supplementation in elderlies can even increase bone mass.

Effects of treatment of malignancy-associated hypercalcemia on serum parathyroid hormone-related protein.

Parathyroid hormone-related protein (PTHrP) is the primary mediator of hypercalcemia in patients with malignancy-associated hypercalcemia. We conducted this study to examine the effects of treatment with a bisphosphonate on serum PTHrP. We analyzed 41 episodes of hypercalcemia occurring in 38 patients: 22 patients received alendronate, and 16 were treated with pamidronate. At baseline, 29 patients had an increased serum PTHrP (group I) and 9 had low or undetectable levels (group II). The two groups did not differ significantly in baseline hypercalcemia (3.26 versus 3.41 mM) or the response of serum calcium to therapy. Serum calcium was normalized in 88% of group I and 70% of group II patients. Lowering of the mean calcium level was not associated with a change in the level of PTHrP in group I patients (40.2 versus 36.7 pgEq/ml) or group II patients. We also analyzed data on serum PTH and 1,25-(OH)2D in 20 of the patients. Serum PTH rose with treatment in group I patients (9.7-40.2 pg/ml, p < 0.05), as did the serum 1,25-(OH)2D (19.1-32.4 pg/ml, p < 0.001). Similarly, treatment of group II patients was associated with an increase in serum PTH (9.8-37.2 pg/ml) and serum 1,25-(OH)2D (22.9-40.2 pg/ml). The individual increases in 1,25-(OH)2D levels associated with therapy could not be predicted from the level of PTHrP or the changes in levels of serum calcium or PTH. Our data show that effective treatment of malignancy-associated hypercalcemia is not associated with a consistent change in serum levels of PTHrP. Therapy is associated with a variable increase in the serum levels of PTH and 1,25-(OH)2D.

Treatment of osteoporosis.

No new compounds were tested in 1991, but more results on available therapeutic options were accumulated. Bisphosphonates and calcitonins appeared to increase bone density when used for a period of 1 to 3 years and to decrease vertebral fracture rate. Estrogen replacement therapy is still the most effective prevention of postmenopausal bone loss. Various studies revealed that the risk of inducing breast cancer has not been established and that estrogen has a strong protective effect against cardiovascular mortality. Screening for osteoporosis at menopause to target estrogen replacement therapy to women at increased fracture risk is recommended. Calcium and vitamin D supplements proved to be of significant value, especially in elderly people, in whom they even decreased fracture incidence. Fluoride demonstrated variable bioavailability. This might explain why certain fluoride studies showed fast increases in bone density with heavy side effects but no effect on fracture rate, whereas fluoride preparations of lower bioavailability were better tolerated and decreased fracture incidence. For almost all drugs, some dose dependence was demonstrated and maximally tolerated doses were established, but minimal effective doses are still unknown. Vertebral fracture rate was more often included as the final criterion in therapeutic trials, whereas long-term effects on hip fracture incidence still need more attention.

[Microbiological findings of 97 cases of acute pyelonephritis]. / Données microbiologiques de 97 cas de pyélonéphrite aiguë.

To optimize the therapeutic approach to acute pyelonephritis (PNA), the medical records of 89 patients (73 women and 16 men) hospitalized with diagnosis of PNA between January 1984 and 1987 have been studied. According to routine bacteriological urinalysis, gram-negatives were found in more than 92% (E. coli in 79%, Proteus in 6%). Gram-positives were found in only 8%. The gram-negatives (n = 82) showed resistance to amoxicillin in 36%, to amoxicillin/clavulanic acid in 17%, to cotrimoxazole in 18%, and to ceftriaxone in 1%. No resistance to netilmicin or norfloxacin was found. These results justify treatment with norfloxacin or ceftriaxone instead of amoxicillin, amoxicillin/clavulanic acid or cotrimoxazole for gram-negatives. Among the 7 cases with gram-positives, resistance was found to amoxicillin/clavulanic acid, cotrimoxazole and also netilmicin, and to norfloxacin, ceftriaxone and amoxicillin. Therefore, an initial therapy using the association amoxicillin-netilmicin is recommended in PNA.

Dose-response in the treatment of hypercalcemia of malignancy by a single infusion of the bisphosphonate AHPrBP.

Fifty-two patients with malignant hypercalcemia were treated with a single dose of 3-amino-1-hydroxypropylidene-1,1- bisphosphonate (AHPrBP, previously APD), a potent inhibitor of osteoclast-mediated bone resorption. In order to establish a dose-response in humans, patients were divided into four groups receiving 30 mg, 45 mg, 60 mg, or 90 mg, respectively, as a 24-hour infusion. Initial plasma calcium was similar in all groups, except in the group receiving 90 mg, of which some patients had higher initial values. All patients responded to AHPrBP with a rapid decrease of plasma calcium concentration from 3.47 +/- 0.10 mmol/L at day 0 to 2.43 +/- 0.06 at day 6 (P less than .001). Plasma calcium became normal within four to six days in 43 patients. Eight of the nine patients whose calcium did not become normal were in the low-dose (30 and 45 mg of AHPrBP) groups. Slight and asymptomatic hypocalcemia occurred in only tow of the 26 patients in the low-dose groups, but in six of the 26 patients in the high-dose groups. A follow-up study in 40 patients showed that hypercalcemia recurred within 1 month in five of ten patients in the group receiving 30 mg, in three of ten patients in the group receiving 45 mg, and in one of 20 patients in the groups receiving 60 and 90 mg, whereas mortality was almost identical in all four groups. In all groups, plasma phosphate, plasma creatinine, urinary calcium, and hydroxyproline excretion decreased significantly. In conclusion, when administered as a single-day infusion in the treatment of tumor hypercalcemia, AHPrBP leads to a dose-dependent decrease in plasma calcium. To prevent transient hypocalcemia and early relapse, the optimal dose should be adapted to the degree of severity of hypercalcemia.

[Treatment of neoplastic hypercalcemia using single-infusion diphosphonate]. / Traitement de l'hypercalcémie tumorale par un diphosphonate en perfusion unique.

40 patients with malignant hypercalcemia were treated with a single dose of APD, a potent inhibitor of osteoclast-mediated bone resorption. In order to establish a dose response in man, the patients were divided into four groups receiving 30, 45, 60 or 90 mg respectively as 24-hour infusion. Initial plasma calcium was similar in all groups except that receiving 90 mg, some of whose patients had higher initial values. All patients responded to APD with a rapid decrease of plasma calcium concentration from 3.44 +/- 0.10 mmol/l at day 0 to 2.33 +/- 0.06 at day 6, p less than 0.001). Plasma calcium became normal within 4 to 6 days in all patients but 6, all from the group receiving the low doses of APD (30 or 45 mg). Slight and asymptomatic hypocalcemia occurred in only 2 patients of the low dose groups, but in 6 of the high dose groups. A follow-up study in 40 patients showed that hypercalcemia recurred within 2 months in 6 patients of group 30 mg, in 5 patients of group 45 mg, in 1 patient of group 60 mg and in 2 patients of group 90 mg, whereas mortality was almost identical in the 4 groups. When retreated with a single dose of APD, all patients again showed normalization of calcemia. In all groups plasma phosphate, plasma creatinine and urinary calcium excretion decreased significantly. Clinical improvement was observed in all patients, with minimal side effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Paget's disease of bone treated in five days with AHPrBP (APD) per Os.

Amino-hydroxypropylidene bisphosphonic acid (AHPrBP, previously APD) is a potent inhibitor of bone resorption. Since it remains in bone for a long time, and since it was not found to impair bone mineralization, it could be administered at high dose over a short period of time. Therefore, 11 patients with symptomatic Paget's disease received AHPrBP orally at 1200 mg/day over 5 consecutive days. Controls were performed after 1 month in all patients, 6 months in 8 patients, and one year in 4 patients. Clinical improvement and biochemical remission was observed in all patients, except one with severe disease. Side effects were negligible. Disease activity at bone scintigram decreased over 6 months. Plasma alkaline phosphatase activity fell progressively and significantly from 210 +/- 26 U/l (means +/- SEM) to 103 +/- 10 U/l after 6 months (nl less than 120 U/l). Urinary excretion of hydroxyproline decreased immediately and became normal (nl less than 2.3 mumol/lGF) as a mean at day 5 (from 4.6 +/- 0.4 mumol/lGF to 2.1 +/- 0.3 mumol/lGF). Thereafter it remained within the normal range (2.0 +/- 0.2 mumol/l at day 180). Plasma calcium and phosphate concentrations fell transiently between day 4 and 15, whereas plasma PTH levels increased over this period of time. In conclusion, a short course of AHPrBP given per os at high dose induces a rapid decline in activity and remission of moderate Paget's disease, without significant side effects.

[Paget's disease of bone treated per os with APD in 5 days]. / La maladie de Paget de l'os traitée per os par l'APD en cinq jours.

Amino-hydroxy-propylidene bisphosphonic acid (APD) is a potent inhibitor of bone resorption. Its oral use in Paget's disease of bone has proved effective and safe when the drug is administered on a long-term basis. Since APD was found not to impair bone mineralization, it was assumed that a long remission would be obtained by administering a high dose of the compound over a very short period of time. Therefore, 12 patients with symptomatic Paget's disease received 1200 mg/d APD orally over 5 consecutive days. Follow-up is 2 months for all patients, 6 months for 6 patients and one year for one patient. Clinical improvement and biochemical remission were observed in all patients. Side effects were negligible (transient nausea in 2 patients and +1 degree C temperature increment noted for 2 days in 3 patients). Urinary hydroxyproline started decreasing within 2 days and became normal as a mean (+/- SEM) after 5 days (1.9 +/- 0.3 mumol/lGF, nl less than 2.3) and in all cases after 15 days. Thereafter it remained within the normal range (1.9 +/- 0.2 mumol/lGF) for 6 months. Plasma alkaline phosphatase activity fell progressively and significantly, and became normal after 1-3 months in all patients but one, a man with very active disease in whom the parameter remained slightly above normal and stable. At the end of the sixth month, mean plasma alkaline phosphatase activity was 100 +/- 13 U/l (nl less than 120 U/l). Plasma calcium and phosphate fell transiently between days 4 and 15.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcitonin and reflex sympathetic dystrophy syndrome.

Reflex sympathetic dystrophy syndrome is a difficult condition to treat. Many modalities have been proposed, all of them being clinically effective but whose efficacy is often difficult to assess, and has not been properly compared. A regimen of physical therapy (pressure therapy, antalgic electrotherapy and exercise therapy) with or without calcitonin was investigated in 24 patients randomly assigned to 2 groups, one given physical therapy alone (Group I) and the other physical therapy plus salmon calcitonin 100 MRC units daily for 3 weeks (Group II). Efficacy assessment was based on clinical (pain, oedema and movement in the affected parts), biochemical (blood and urinary phosphorus and calcium levels, plasma 25-OH-D, plasma parathyroid hormone (PTH), creatinin, alkaline phosphatases and urinary hydroxyproline) and scintigraphic parameters, as well as on the patient's ability to resume working. There was significant improvement in pain in the Group II patients after one week of treatment. As a result the authors advocate the use of calcitonin in addition to physical therapy in reflex sympathetic dystrophy syndrome - and even of calcitonin alone where physical therapy is not possible.

[Diagnostic tests in parathyroid diseases]. / Tests de diagnostic des maladies des parathyroïdes.

The diagnosis of primary hyperparathyroidism (PHP) depends increasingly on laboratory tests, since the majority of patients are elderly people without typical symptoms. A mean plasma calcium level close to the upper normal limit serves to diagnose hypercalcemia. To rule out malignant disease, the most common cause of hypercalcemia, measurement of plasma PTH is the most appropriate test. Determination of blood phosphorus, chloride, and alkaline phosphatase, and of urinary calcium and phosphorus, contribute to the investigation of the metabolic effects of the given disease but are not very useful for causal diagnosis. Urinary and nephrogenous cyclic AMP reflect PTH secretion but can be elevated in paraneoplastic hypercalcemia. Diagnosis of subtle forms of PHP by dynamic tests is largely of scientific interest, since they do not necessarily need treatment. The diagnosis of hypoparathyroidism is primarily clinical. PTH measurements rarely distinguish normal from low values. In severe hypocalcemia of non-parathyroid origin, plasma PTH is elevated (except in hypomagnesemia). In borderline cases, measurement of urinary cyclic AMP or of plasma PTH after attempted stimulation by EDTA infusion is helpful, especially in distinguishing between subtle hypoparathyroidism and tetany induced by hyperventilation.

[Simple treatment of tumor-induced hypercalcemia: i.v. aminohydroxypropylidene biphosphonate]. / Un traitement simple de l'hypercalcémie tumorale: l'amino-hydroxypropylidène bisphosphonate (APD) i.v.

The treatment of tumour-induced hypercalcemia (HCa) by diphosphonates appears to be safe and reliable with very mild side effects. We have tested APD as sole treatment in 14 patients with cancer and symptomatic HCa. APD was given i.v. in a dose of 0.38 +/- 0.03 mg/kg BW/day until two subsequent normal plasma calcium (Ca) levels were obtained (Ca determined daily). The mean duration of treatment was 5.56 +/- 1.9 (4 to 11 days). As expected, there was a significant correlation between initial Ca and duration of therapy (p less than 0.001). Mean Ca fell from 3.38 +/- 0.19 mmol/l before APD to 2.43 +/- 0.09 after 4 days of treatment and remained normal four weeks after the start of treatment. Four patients relapsed 11 to 31 days after the end of treatment during a one-month follow-up. This recurrence did not depend on initial Ca, length of treatment and duration of remission. Two of these patients were treated successfully with a second course of APD, while in the other two no further treatment was undertaken. Both mean UCa and UHydroxyproline decreased significantly when measured seven days after the beginning of the treatment. Plasma PTH values remained in the normal range, while NcAMP rose significantly after a week of treatment from low to normal values. Plasma phosphorus decreased significantly (p less than 0.005) during the treatment while TRP % increased, suggesting a positive phosphorus balance. We conclude that short treatments with APD of tumour-induced HCa are effective and sufficiently sustained, even if they are interrupted as soon as normal Ca is obtained.