Plasma Tartrate-resistant Acid Phosphatase Research Articles

Biochemical markers of bone turnover.

The noninvasive assessment of bone turnover has received increasing attention over the past few years because of the need for sensitive markers in the clinical investigation of osteoporosis. Markers of bone formation include the serum measurement of total and bone-specific alkaline phosphatase, osteocalcin, and type I collagen extension peptides. Assessment of bone resorption can be achieved with measurement of fasting urinary calcium and hydroxyproline, urinary hydroxylysine glycosides, urinary excretion of the pyridinium cross-links (pyridinoline and deoxypyridinoline), and plasma tartrate-resistant acid phosphatase activity. Several studies performed in a variety of metabolic bone diseases have shown these markers to be of unequal sensitivity and specificity. In addition, some of them are not fully characterized. For assessment of the level of bone turnover in women with vertebral osteoporosis, serum osteocalcin and urinary pyridinoline appear to be the most sensitive markers so far. Programs combining bone mass measurement and assessment of bone turnover by several markers in women at the time of menopause are being developed in an attempt to improve the assessment of the risk for osteoporosis. Efforts are being made to develop more convenient assays and to identify other markers of bone turnover. A battery of various specific markers is likely to improve the assessment of the complex and subtle abnormalities of bone metabolism that characterize metabolic bone diseases, especially the various aspects of osteoporosis.

Biochemical markers of bone turnover for the clinical investigation of osteoporosis.

The non-invasive assessment of bone turnover has received increasing attention over the past few years because of the need for sensitive markers in the clinical investigation of osteoporosis. Markers of bone formation include the serum measurement of total and bone-specific alkaline phosphatase, osteocalcin, and type I collagen extension peptides. Assessment of bone resorption can be achieved by measurement of urinary hydroxyproline, urinary excretion of the pyridinium crosslinks (pyridinoline and deoxypyridinoline), and by measurement of plasma tartrate-resistant acid phosphatase activity. For the screening of bone turnover in women at the menopause, and for the assessment of the level of bone turnover in elderly women with vertebral osteoporosis, serum osteocalcin and urinary pyridinoline appear to be the most sensitive markers, so far. Programs combining bone mass measurement and assessment of bone turnover by several markers in women at the time of menopause are being developed in an attempt to improve the assessment of the risk for osteoporosis. Efforts are made to develop more convenient assays and to identify other markers of bone turnover. In future a battery of various specific markers is likely to improve the assessment of the complex and subtle abnormalities of bone metabolism that characterize the various aspects of osteoporosis.

Biochemical assessment of bone loss in patients on long-term thyroid hormone treatment

To test conditions under which thyroid hormone might be deleterious to bone, we studied a group of 58 patients who had undergone thyroidectomy because of thyroid cancer 1 to 21 years previously and were treated with steady doses of exogenous thyroid hormone. Vertebral bone density (BMD Z-score) was significantly reduced and biochemical indices of bone resorption (urinary hydroxyproline and plasma tartrate-resistant acid phosphatase activity) and of osteoblastic activity (plasma osteocalcin and bone isoenzyme of serum alkaline phosphatase) as well as the calculated prevalence of bone resorption relative to osteoblastic activity (HBP) were significantly increased in thyroid hormone-treated post-menopausal women but not in men and premenopausal women. The HBP as well as the biochemical indices of bone remodeling were significantly negatively correlated with serum TSH levels. In treated patients, BMD Z-score was significantly dependent on the HBP, menopausal state, duration of treatment and serum TSH levels. In conclusion, the further increase in bone resorption by thyroid hormone is predisposed by menopausal changes in bone turnover. The simultaneous evaluation of biochemical indices of bone resorption and formation improves the assessment of bone loss in patients treated with thyroid hormone in a suppressive dose.

Hydrochlorothiazide inhibits parathormone-stimulated increase in plasma tartrate-resistant acid phosphatate in mice

The inhibitory effect of hydrochlorothiazide (HTZ) on parathormone-induced bone changes in mice was studied with the aid of the analysis of plasma calcium and tartrate-resistant acid phosphatase. We have found that HTZ alone had no effect on plasma tartrate-resistant acid phosphatase (Tr-ACP), phosphate, and creatinine concentration. Parathormone (PTH) administration increased plasma Tr-ACP from 15.00 +/- 1.50 to 20.62 +/- 2.35 U/liter in intact mice. The increase of plasma Tr-ACP in HTZ-treated mice after PTH administration was not significant. The plasma calcium was affected in a way similar to Tr-ACP. HTZ reduced the sensitivity of bone to resorbing effects of PTH, using Tr-ACP as a useful biomarker of bone resorption.

Castrated men exhibit bone loss: effect of calcitonin treatment on biochemical indices of bone remodeling.

To test the hypothesis that the reduction in gonadal function can lead to bone mass loss, a group of 12 men who had undergone bilateral orchidectomy at the age of 28.2 +/- 6.8 yr was evaluated. A progressive loss of the lumbar bone density was observed as a function of time after orchidectomy. Both the biochemical indices of bone resorption (urinary hydroxyproline/creatinine ratio and plasma tartrate-resistant acid phosphatase) and bone formation (serum osteocalcin and bone isoenzyme of alkaline phosphatase) were significantly increased in the patients compared with healthy controls. A positive correlation was found between urinary hydroxyproline excretion and percent change in spinal bone mineral density per yr. Because of this increase in the biochemically indicated bone resorption, nine of the patients were studied again after 1-3 yr and were thereafter treated with intranasal calcitonin. Urinary hydroxyproline excretion normalized after 3 months of treatment, and a significant decrease, but not to normal levels, was also observed in the mean values for the other biochemical indices of bone remodeling. Thus, testosterone deficiency, like estrogen deficiency, is associated with accelerated bone loss. The increase in osteoresorption was partially corrected by calcitonin treatment.

Bone demineralization, biochemical indices of bone remodeling, and estrogen replacement therapy in adults with Turner's syndrome.

The study centered on a controversy about whether long-term estrogen replacement therapy may ameliorate the osteoporosis seen in patients with Turner's syndrome. This study comprised 26 adult patients with Turner's syndrome (9 treated and 17 untreated or insufficiently treated) and 12 adult women with pure gonadal dysgenesis (8 untreated and 4 treated). A low bone density below -2 standard deviations from the age- and sex-matched predicted normal mean was documented by dual-photon absorptiometry of the lumbar spine in all the untreated and insufficiently treated patients, but only in 6 treated patients. The biochemical indices of bone resorption (urinary hydroxyproline excretion and plasma tartrate-resistant acid phosphatase activity), as well as osteoblastic function (serum osteocalcin and bone alkaline phosphatase isoenzyme), were significantly increased in untreated and insufficiently treated patients compared with treated patients. A significant negative correlation was found between biochemically documented osteoresorption and spinal bone mineral density corrected for age of the patients. Significant positive correlations were found between serum osteocalcin and bone alkaline phosphatase isoenzyme and between biochemical indices of bone resorption and formation. Although in the patients there was an evidence of a high bone remodeling rate, the rate of bone mass loss seemed to be low, comparable with that seen in oophorectomized women who had already passed their accelerated phase of bone loss. The results indicate that long-term hormonal replacement therapy is justified in gonadal dysgenesis, regardless of the karyotype of the patient, to prevent further bone mass loss.

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

Plasma tartrate-resistant acid phosphatase (TR ACP), urinary hydroxyproline excretion (UH), serum osteocalcin, and bone alkaline phosphatase isozyme 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 assessement of the efficacy of treatment.

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 osseinhydroxyapatite 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.

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.

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.

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.