V. Pacovský

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.

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.

Free and peptide hydroxyproline in chronic uremia

Abstract Plasma levels, urinary excretion and renal clearance rates of free and peptide hydroxyproline were estimated in normal subjects, patients with chronic uremia, and in representative cases of generalised bone disease and chronic pyelonephritis without glomerular insufficiency. Chronic uremia was accompanied by an elevation of plasma levels and urinary excretion of free hydroxyproline, whereas the excretion of hydroxyproline peptides was decreased despite increased plasma levels. The changes of free hydroxyproline appeared to be related to the degree of glomerular insufficiency.

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.

Acute effects of calcium infusion on hydroxyproline

Abstract Acute effects of 4-h calcium infusion on plasma levels and urinary excretion of total hydroxyproline have been investigated. During the 3-h postinfusion period a decrease of hydroxyproline excretion was found in 8 normal subjects, 8 cases of primary hyperparathyroidism and in 8 cases of osteomalacia, the average per cent decrease being similar in all three groups, irrespective of high initial values in the latter two. The average excretion and the effect of calcium infusion thereon was lower in 8 cases of chronic uremia. In all four groups studied a slight decrease of plasma hydroxyproline was observed which, in most cases, could not account for the changes in urinary excretion. The acute changes of urinary excretion of total hydroxyproline do not differentiate between primary and secondary hyperparathyroidism in cases without grossly abnormal renal function.

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

Abstract. 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 osteo‐dystrophy, Pagets disease, secondary bone tumours, and in a control group was found (P< 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.

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.