[Comparison of the effectiveness of 17-beta-estradiol and calcitonin in women with postmenopausal bone loss]. / Porovnání úcinnosti lécby 17 beta-estradiolem a kalcitoninem u zen s úbytkem kostní hmoty po menopauze.

BACKGROUND: The objective of this study was to compare effects of 17 beta-estradiol and intranasal salmon calcitonin on bone mass and biochemical markers of bone turnover in postmenopausal women with an accelerated bone loss and osteopenia or osteoporosis. METHODS AND RESULTS: 72 women with significantly increased bone resorption were evaluated (urinary hydroxyproline/creatinine > or = 21.9 mmol/mol, mean age, 53.7 +/- 6.3 years, time since menopause 6.1 +/- 2.6 years). All patients received daily 500 mg Ca2+ and 400 IU vitamin D supplement. 48 patients with osteopenia and 24 patients with osteoporosis were randomly allocated to treatment with open-label 17 beta-estradiol (50 micrograms transdermally or 2 mg orally) or calcitonin (200 IU every other day). Bone mass was measured by dual-energy x-ray absorptiometry (DPX-L, Lunar, C.V., 1.10 +/- 0.55% and 1.41 +/- 0.55%, lumbar spine and femoral neck, respectively) every six month for 2.5 year, bone stiffness was measured by ultrasound (Achilles, Lunar, C.V., 3.88 +/- 1.95%). Biochemical markers of bone turnover (plasma osteocalcin and tartrate-resistant acid phosphatase, serum bone specific alkaline phosphatase and urinary hydroxyproline) were measured before and after 6, 12 and 24 month of treatment. Patients who received 17 beta-estradiol experienced significant increases (p < 0.05) in bone mass on the first and second year (by 2.6% and 2.1% at lumbar spine, 1.1% and 1.0%, at femoral neck, and 2.3% and 2% at the heel). A significant positive correlation was found between rates of bone mass change in all sites (p < 0.001). No statistically significant bone changes were found in calcitonin treated patients. In 17 beta-estradiol treated patients, biochemical markers of bone turnover decreased by 40-50% to the mean values in premenopausal women. In calcitonin treated patients, biochemical markers reached the upper normal limit. CONCLUSIONS: Estrogen replacement therapy increases bone mass in lumbar spine as well as in femoral neck. It is efficient for both prevention and treatment of postmenopausal osteoporosis. Salmon calcitonin effectively prevents bone loss. Efficacy of both the treatment can be assessed after 6 months using a biochemical marker of bone resorption and after 2 years using dual-energy x-ray densitometry.

Galactosyl hydroxylysine in assessment of Paget's bone disease.

Urinary galactosyl hydroxylysine/creatinine ratio (GHL) was used to assess rates of bone collagen degradation and the activity of the pagetic lesion as well as for monitoring the rate and degree of suppression of bone resorption over 1 year in patients treated with 30 mg of intravenous pamidronate for 3 consecutive days. The clinical utility of GHL was compared with that of urinary hydroxyproline/creatinine and deoxypyridinoline/creatinine and with bone isoenzyme of serum alkaline phosphatase. The results suggest that GHL is a quantitative marker of the activity of Paget's bone disease. GHL is less sensitive than hydroxyproline, deoxypyridinolone and bone alkaline phosphatase in monitoring treatment of Paget's disease. The assay of GHL is easier, faster and less costly than that of hydroxyproline or deoxypyridinoline and it can be easily standardized.

[Transdermal estradiol in the prevention of the menopause-induced increase in osteoresorption]. / Transdermální estradiol v prevenci menopauzou navozeného zvýsení osteoresorpce.

In the introduction of the paper the authors explain that it is essential to adopt effective preventive provisions to prevent the loss of osseous tissue in women after the menopause and to prevent osteoporotic fractures. In Bohemia and Moravia during the last 20 years the incidence of these frequently fatal or invalidating fractures of the proximal femur has increased substantially and in view of the ageing of the population it may be assumed that this trend will proceed further. Among possible preventive provisions, in order to eliminate undesirable metabolic side-effects of long-term hormonal substitution treatment, it seems best to administer by the parenteral route natural oestradiol by using the transdermal therapeutic Estraderm TTS system. Its effectiveness in suppressing menopause-induced enhanced bone resorption was tested in 11 women where on average within three months after bilateral ovariectomy increased bone resorption was found. In all women in the course of four months treatment all biochemical indicators of bone remodelling became normal - urinary excretion of hydroxyproline, acid plasma phosphatase activity, serum alkaline phosphatase isoenzyme, and serum osteocalcin. The dynamics of indicators of osteoresorption were similar as in women treated with oral synthetic oestrogen, which may produce, however, serious metabolic side-effects. Substitution treatment with Estraderm improves significantly also other manifestations of the climacteric oestrogen deficiency syndrome. Its safety is further enhanced by combination with progesterone.

Age and sex dependency of the biochemical indices of bone remodelling.

The values for the bone isoenzyme of serum alkaline phosphatase peak in the first two years of age, between 6 and 7 years of age, before the end of puberty and in the postmenopause. A population between the ages of 29 and 45 provides a reference population to which all other age groupings can be compared. A significant positive correlation was found between bone isoenzyme of serum alkaline phosphatase and urinary hydroxyproline excretion in children as well as after puberty. However, in the children the urinary hydroxyproline excretion was significantly higher when compared with the bone isoenzyme of alkaline phosphatase. A significant positive correlation was found between the bone isoenzyme of alkaline phosphatase and plasma tartrate-resistant acid phosphatase, irrespective of age and sex. The biochemical indices of bone remodelling correlated significantly with the growth rate in children and adolescents. The results are in good agreement with the concept of the coupling of bone formation to bone resorption.

Biochemical assessment of bone disease in multiple myeloma.

In patients with multiple myeloma, with moderate and severe bone disease, the urinary hydroxyproline excretion was disproportionately elevated with respect to the activity of bone isoenzyme of alkaline phosphatase when compared with the relationship between the variables observed in 58 age- and sex-matched controls and in 50 healthy young subjects. A significant positive correlation was found between urinary hydroxyproline excretion and the clinical variables related to the extent of bone involvement in multiple myeloma (X-rays, patient's performance status, anaemia). In 9 out of 13 patients with moderate and severe bone disease the chemotherapy-induced remission was associated with a significant (p less than 0.05) rise in the activity of bone isoenzyme of alkaline phosphatase and decrease (p less than 0.005) in urinary hydroxyproline excretion. In successfully treated patients, the relationship between the biochemical variables indicated increased but proportionate extents of whole-body rates of bone formation and resorption. This was not the case in patients in whom no chemotherapy-induced remission was noted. The simultaneous evaluation of the activity of bone isoenzyme of serum alkaline phosphatase and urinary excretion of hydroxyproline improves the assessment of bone involvement in multiple myeloma and the efficacy of treatment.

Relationship of plasma tartrate resistant acid phosphatase to the bone isoenzyme of serum alkaline phosphatase in hyperparathyroidism.

In 46 patients with primary hyperparathyroidism, in 21 non-dialysed patients with advanced renal failure, and in 52 patients on hemodialysis, a significant positive correlation was found between bone isoenzyme of serum alkaline phosphatase and plasma tartrate resistant acid phosphatase. In primary hyperparathyroidism, a significant positive correlation was found between the radiological degree of osteodystrophy and the biochemical parameters of bone remodelling. After removal of the parathyroid adenoma, only the tartrate-resistant acid phosphatase decreased to normal limits. Plasma tartrate resistant acid phosphatase was most significantly influenced by serum immunoreactive parathyroid hormone levels. In chronic renal failure, bone isoenzyme of serum alkaline phosphatase was most significantly influenced by serum immunoreactive parathyroid hormone levels, by hypocalcemia and by duration of hemodialysis. The results confirm that in hyperparathyroidism the extent of the whole-body rates of bone resorption and formation are approximately equal. The biochemical parameters can be used for serial assessment of the course of the disease but are not specific for diagnosis.

Plasma 25-hydroxycholecalciferol in oral sulfonylurea treated diabetes mellitus.

In oral sulfonylurea treated diabetics, decreased plasma 25-hydroxycholecalciferol and increased activity of bone isoenzyme of serum alkaline phosphatase and urinary hydroxyproline excretion was found when compared with control subjects. In stepwise regression analysis significant relationships were found between bone isoenzyme, urinary hydroxyproline excretion, serum calcium levels and blood glucose levels. The partial correlation and multivariate regression analysis showed that in oral sulfonylurea treated patients, but not in insulin treated patients, the activity of bone isoenzyme of serum alkaline phosphatase was significantly inverse dependent on the 25-hydroxycholecalciferol levels in plasma. Oral sulfonylurea agents which are known to induce the hepatic microsomal system seem to be an additional factor to poor control of diabetes, leading to osteopathy.

Bone isoenzyme of serum alkaline phosphatase in diabetes mellitus.

Increased activity of bone isoenzyme of serum alkaline phosphatase was found in 52, 82 and 72% of the patients on dietary, oral agents, and insulin regimens, respectively. Significant positive correlations between the activity of bone isoenzyme and urinary hydroxyproline excretion in diabetes are similar to those found in osteoporosis. In stepwise regression analysis, negative correlations were found between the parameters of turnover of bone organic matrix and serum calcium levels; the influence of blood glucose levels in the expression of the biochemical parameters of bone metabolism was most pronounced in patients on oral agents. The results explain moderate hyperphosphatasia, known in diabetes, and support a metabolic etiology for the bone disease in diabetes mellitus.

Relationship of the activity of the bone isoenzyme of serum alkaline phosphatase to urinary hydroxyproline excretion in metabolic and neoplastic bone diseases.

A significant correlation between the activity of the bone isoenzyme or serum alkaline phosphatase and the urinary hydroxyproline excretion in osteomalacia, osteoporosis, primary hyperparathyroidism with osteodystrophy, Paget's disease, secondary bone tumours, and in a control group was found (P less than 0.001). This close correlation was not observed between these variables in patients with active acromegaly. Diagnosis determined from these indices of formation and turnover of bone matrix agreed with that established by histological and histochemical examination of bone, by X-ray investigation of the skeleton, and by the radionuclear 85Sr test. The relationship between the activity of bone isoenzyme and urinary hydroxyproline excretion differed in metabolic bone diseases with a high bone turnover, in patients with osteoporosis and in patients with early osteoclastic bone metastases.