J.J. Štěpán

Bone loss and biochemical indices of bone remodeling in surgically induced postmenopausal women.

In a cross-sectional study in 214 women who had undergone bilateral oophorectomy up to 12 years previously, the maximal rate of bone loss, as judged by radiogrammetry of the metacarpals and by dual-photon absorptiometry of the lumbar spine, coincided with the peak of the dissociation between urinary hydroxyproline excretion and/or plasma tartrate resistant acid phosphatase activity and the activity of bone isoenzyme of serum alkaline phosphatase. A significant negative correlation was found between the prevalence of the biochemical indices of bone resorption relative to bone formation and/or biochemical indices of bone resorption and the change in the metacarpal cortical area per year. The prevalence of bone resorption relative to bone formation was evident even 12 years after oophorectomy, indicating continuous imbalance of bone remodeling in the patients. Accordingly, the rates of 2.8% cortical and 8% trabecular bone loss per year on the first year after oophorectomy decreased exponentially but did not become asymptotic with the slow phase of bone loss in healthy women up to 12 years after oophorectomy.

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.

Cortical Thickness Mapping to Identify Focal Osteoporosis in Patients with Hip Fracture

Background Individuals with osteoporosis are predisposed to hip fracture during trips, stumbles or falls, but half of all hip fractures occur in those without generalised osteoporosis. By analysing ordinary clinical CT scans using a novel cortical thickness mapping technique, we discovered patches of markedly thinner bone at fracture-prone regions in the femurs of women with acute hip fracture compared with controls. Methods We analysed CT scans from 75 female volunteers with acute fracture and 75 age- and sex-matched controls. We classified the fracture location as femoral neck or trochanteric before creating bone thickness maps of the outer ‘cortical’ shell of the intact contra-lateral hip. After registration of each bone to an average femur shape and statistical parametric mapping, we were able to visualise and quantify statistically significant foci of thinner cortical bone associated with each fracture type, assuming good symmetry of bone structure between the intact and fractured hip. The technique allowed us to pinpoint systematic differences and display the results on a 3D average femur shape model. Findings The cortex was generally thinner in femoral neck fracture cases than controls. More striking were several discrete patches of statistically significant thinner bone of up to 30%, which coincided with common sites of fracture initiation (femoral neck or trochanteric). Interpretation Femoral neck fracture patients had a thumbnail-sized patch of focal osteoporosis at the upper head-neck junction. This region coincided with a weak part of the femur, prone to both spontaneous ‘tensile’ fractures of the femoral neck, and as a site of crack initiation when falling sideways. Current hip fracture prevention strategies are based on case finding: they involve clinical risk factor estimation to determine the need for single-plane bone density measurement within a standard region of interest (ROI) of the femoral neck. The precise sites of focal osteoporosis that we have identified are overlooked by current 2D bone densitometry methods.

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.

The application of plasma tartrate-resistant acid phosphatase to assess changes in bone resorption in response to artificial menopause and its treatment with estrogen or norethisterone

SummaryPlasma tartrate-resistant acid phosphatase (TR ACP), urinary hydroxyproline excretion (UH), serum osteocalcin, and bone alkaline phosphatase isoenzyme were determined in a prospective study in 31 women who had undergone bilateral ovariectomy (OOX). Nine patients were followed up for 1 year without treatment and for the following 3 years when on mestranol (M) substitution. On the basis of UH, 22 patients were identified as having increased bone resorption (BR) within 3 months of OOX. Subsequently, 11 patients were treated with transdermal estradiol (E2) and 11 patients with norethisterone (norethindrone, NE). In untreated patients, the biochemical indices of BR peaked 3–6 months following OOX and biochemical indices of bone formation (BF) continued to increase from 3 until 12 months. The substitution with both E2 or M resulted in normalization in serum and urinary calcium, serum phosphate, renal threshold phosphate concentration (TmPO4/GRF), and biochemical indices of BR within 4 months of treatment. Biochemical indices of BF normalized within 6 months of treatment. In the M-treated group, these effects continued for 3 years of the follow-up. The hormonal substitution had a protective effect on cortical and lumbar spine bone mass. A significant decrease, but not to normal values, in biochemical indices of BR and a persistent elevation in indices of BF were found in NE-treated patients. Unlike E2, NE does not depress osteoblastic function. There is strong evidence supporting the utility of measurements of TR ACP in plasma in examination of women who had ovariectomies and in assessment of the efficacy of treatment.

A modified inactivation-inhibition method for determining the serum activity of alkaline phosphatase isoenzymes.

A procedure using heat inactivation and L-phenylalanine inhibition to quantitate the activities of bone, liver and intestinal alkaline phosphatase isoenzymes in human serum was confirmed by alkaline phosphatase isoenzyme analysis using an electrophoretic procedure. The results of this assay were compared with the radionuclear 85Sr test, and gamma-glutamyl transpeptidase activity in a group of patients with hepatobiliary and bone diseases.

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.

Measurement of amylase isoenzymes in human sera and urine using a DEAE-cellulose mini-column method

A DEAE-cellulose mini-column method has been developed which allows for the separation and quantitation in human sera and urine of pancreatic and salivary type isoamylases. Determination of the isoamylases was found to be of value in differentiation of hyperamylasemias due to disorders of the pancreas and parotid gland.

Prospective trial of ossein-hydroxyapatite compound in surgically induced postmenopausal women.

Women with increased bone resorption induced by bilateral oophorectomy 1-5 years previously (of a total of 48 women in the study, 20 were controls, and 28 were the treatment group) were studied during a 3 year follow-up. The ossein-hydroxyapatite compound (OHC) treatment provided 1.6 g calcium, 0.74 g phosphorus and 1.94 g noncollagen peptides a day. Biochemical indices of bone remodeling (urinary hydroxyproline/creatinine and calcium/creatinine ratios, bone alkaline phosphatase isoenzyme in serum and plasma tartrate resistant acid phosphatase) decreased significantly in both treatment and control groups compared with their baseline values. Biochemical indices were significantly lower in the treatment group compared to the controls after the first year, but in only half the patients after three years. By the third year these responders had significantly higher cortical area than controls. In an additional 13 women a transient response to OHC was followed by an accelerated bone loss and a return to the control values of the biochemical indices of bone resorption. In the poor responders an estrogen/progesterone substitution resulted within 6 months in a complete normalization in the biochemical parameters and in no further cortical bone loss. The results confirm a heterogeneous pattern of bone mass loss in menopause and indicate that OHC treatment is of value in preventing cortical bone loss in a portion of at-risk postmenopausal women, provided that the efficacy of the treatment is monitored.

Primary hyperparathyroidism and hyperuricaemia are associated but not correlated with indicators of bone turnover

Urate metabolism was studied in 53 patients with primary hyperparathyroidism. They had compared to controls significantly higher serum urate and reduction of the clearance of urate. In 14 of the tested patients with primary hyperparathyroidism serum urate was increased above normal limits. Six months after parathyroidectomy serum urate fell significantly from 365.3 +/- 75.7 mumol/l to 265.7 +/- 48.3 mumol/l, in 26 patients where urate measurements were available before as well as after surgery. Serum urate levels in our patients with primary hyperparathyroidism did not correlate with clearance of urate. Levels of serum urate cannot be entirely explained by the decrease in renal clearance of urate. Serum urate levels did not correlate with severity of skeletal changes expressed by serum B-ALP and urinary excretion of hydroxyproline. These results suggest that parathormone does not increase the part of the urate pool coming from the nucleic acids of the increased bone metabolism.