A decrease in serum 1,25(OH)2D after elective hip replacement and during bone healing is associated with changes in serum iron and plasma FGF23.

OBJECTIVE: Although calcitriol is essential for bone healing, its serum concentrations are low after hip surgery, and they continue to decline during bone healing. This study aimed to test the hypothesis of an association of changes in calcitriol production with the status of fibroblast growth factor 23 (FGF23) and iron deficiency after elective hip replacement for coxarthrosis. METHODS: In this prospective study, we measured the biomarkers of 17 patients undergoing elective hip replacement on admission, on the first day after surgery, and at the regular check-up after 48 ± 8 days. The serum concentrations of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, transferrin, ferritin, parathyroid hormone, intact plasma FGF23 (iFGF23) and C-terminal FGF23 (cFGF23) were determined. RESULTS: In our patients who underwent elective hip replacement, significant correlations existed between the percent change in the conversion rate of 25(OH)D to 1,25(OH)2D, plasma intact to C-terminal FGF23 ratio, and serum iron. CONCLUSIONS: The production of calcitriol is compromised after elective hip replacement surgery, leading to reduced levels of active vitamin D in the serum. Significant correlations between the percent change in the conversion rate of 25(OH)D to 1,25(OH)2D, plasma intact to C-terminal FGF23 ratio, and serum iron on the first day as well as 7 weeks after surgery could inspire future studies to determine whether and how calcitriol deficiency should be corrected, especially in fracture cases.

Decrease in serum calcitriol (but not free 25-hydroxyvitamin D) concentration in hip fracture healing.

OBJECTIVE: To assess the decrease in serum calcitriol concentrations after hip fracture. METHODS: Serum concentrations of calcitriol, 25(OH)D, parathyroid hormone (PTH), directly measured free 25(OH)D, and indices of bone formation were measured in elderly patients with hip fracture (HF) and patients with elective hip replacement (EHR) at admission and after 7 weeks. RESULTS: A total of 45 patients with HF and 17 patients with EHR completed this prospective study. Baseline serum calcitriol levels were ≤ 60 pmol/l in 26% of the HF patients. After 7 weeks, they significantly decreased (p < 0.001). In patients with EHR, serum calcitriol was within the reference range in all but one patient and did not change during the 7-week recovery phase. Seven weeks after HF, a significant positive relationship was observed between the change in calcitriol and serum 25(OH)D concentration (r = 0.385, p = 0.009) and free 25(OH)D (r = 0.296, p = 0.048), and a decrease in calcitriol during recovery was associated with a decrease in serum PTH (p = 0.038). Seven weeks after HF, changes in both serum PTH and serum 25(OH)D concentrations contributed to the prediction of changes in serum calcitriol (R2 = 0.190, p = 0.012). CONCLUSIONS: Unlike patients with EHR, subjects with HF had low serum 25(OH)D and low free 25(OH)D concentrations at admission, while their serum 1,25D levels were relatively elevated. Decreases in circulating calcitriol levels in the 7 weeks following hip surgery were associated with a resolution of secondary hyperparathyroidism and low availability of free 25(OH)D.

Bone quality of the newest bone formed after two years of teriparatide therapy in patients who were previously treatment-naïve or on long-term alendronate therapy.

UNLABELLED: The results of the present study, involving analysis of biopsies from patients who received teriparatide for 2 years and were previously either treatment-naïve or on long-term alendronate therapy, suggest that prior alendronate use does not blunt the favorable effects of teriparatide on bone quality. INTRODUCTION: Examine the effect of 2 years of teriparatide (TPTD) treatment on mineral and organic matrix properties of the newest formed bone in patients who were previously treatment-naïve (TN) or on long-term alendronate (ALN) therapy. METHODS: Raman and Fourier transform infrared microspectroscopic analyses were used to determine the mineral/matrix (M/M) ratio, the relative proteoglycan (PG) content, and the mineral maturity/crystallinity (MMC; determined by three methods: carbonate content, full width at half height of the v 1 PO4 band [FWHH], and wavelength at maxima of the v 1 PO4 band), as well as collagen maturity (ratio of pyridinoline/divalent cross-links), in paired iliac crest biopsies at trabecular, endosteal, and osteonal surfaces of newly formed bone in postmenopausal osteoporotic women who were previously either TN (n = 16) or receiving long-term ALN treatment (n = 24). RESULTS: Trabecular M/M ratio increased and matrix content decreased significantly in the ALN pretreated group. Collagen maturity decreased in both patient groups. Endosteal M/M ratio increased significantly in the TN group. Trabecular M/M ratio was higher at endpoint in the ALN pretreated group than in the TN group. Overall, no changes from baseline were observed in PG content, except that PG content was higher in the ALN pretreated group than in the TN group at endosteal surfaces at endpoint. The ability of TPTD treatment to reduce MMC in both patient groups and at the different bone surfaces depended on the measurement tool (relative carbonate content or wavelength at maxima of the v 1 PO4 band). None of the changes in MMC were different between the two patient groups. CONCLUSIONS: The results suggest some favorable impact of TPTD on bone mineral and organic matrix properties of in situ forming bone in terms of increased initial mineralization and decreased MMC and collagen maturity. Moreover, prior long-term ALN administration may have only limited influence on these properties in bone newly formed after 2 years of TPTD treatment.

Effects of morning vs. evening teriparatide injection on bone mineral density and bone turnover markers in postmenopausal osteoporosis.

UNLABELLED: A 12-month morning teriparatide (TPTD) administration resulted in a larger increase in the lumbar spine bone mineral density (BMD) than the evening application. The results indicate that the response of bone cells to teriparatide treatment depends on dosing time. INTRODUCTION: The aim of this study was to assess the long-term effects of the morning vs. the evening teriparatide administration on BMD and bone turnover markers (BTMs) in postmenopausal osteoporosis. METHODS: Fifty women with established postmenopausal osteoporosis were randomized to 12-month treatment with 20 µg of TPTD, administered daily in the morning or in the evening. The BMD and serum concentrations of C-terminal telopeptide of type I collagen, N-terminal propeptide of type I procollagen (PINP), and tartrate-resistant acid phosphatase isoform 5b (TRAP 5b) were measured at baseline, after 6 and 12 months. General linear model-repeated measurements were used to analyze the data. RESULTS: After 12 months, the lumbar spine BMD grew markedly (p < 0.001) with a significantly greater increase in the morning arm compared to the evening arm (9.1% vs. 4.8%, respectively, p < 0.05). The BMD at the distal radius significantly decreased (p < 0.001), with no differences between the arms. The BMD at proximal femur did not change significantly. After 6 months, the BTMs were significantly increased compared with baseline (p < 0.001). The increases in the evening arm vs. the morning arm, however, were more pronounced in PINP (+358% vs. +215%, respectively) and in TRAP 5b (+70% vs. +37%, respectively) (both p < 0.05). CONCLUSION: 12-month morning administration of TPTD resulted in a larger increase in the lumbar spine BMD than the evening application. The timing of TPTD administration may be important for its efficacy.

Histomorphometric changes by teriparatide in alendronate-pretreated women with osteoporosis.

SUMMARY: The level of increased bone formation after 24 months of treatment with teriparatide (rhPTH (1-34), TPTD) is similar in patients who were either treatment-naïve (TN) or had lower bone turnover initially due to previous alendronate (ALN) therapy. INTRODUCTION: Bone anabolic effects of TPTD in postmenopausal women with osteoporosis may be blunted during the initial phase after switching from ALN to TPTD. To explore the long-term implications, we examined histomorphometric and biochemical markers of bone turnover of patients on TPTD therapy after long-term ALN treatment. METHODS: Paired biopsies were obtained after tetracycline double labeling at baseline and after 24 months of TPTD treatment from 29 ALN-pretreated (64.5 ± 16.4 months) and 16 TN patients. Biochemical markers were measured at baseline, during the treatment, or at study end. RESULTS: Compared with the baseline, after 24-month TPTD, activation frequency (Ac.F.) and osteoid surface (OS) increased in both groups: 0.11-0.34 cycles per year, 3.96-9.8% in the ALN-pretreated group and 0.19-0.33 cycles per year, 6.2-11.3% (p < 0.05) in the TN group, respectively. Biochemical and histomorphometric markers correlated positively both at baseline and endpoint. Serum amino terminal propeptide of type I procollagen (PINP) correlated with Ac.F. (r = 0.57, p < 0.001 and r = 0.48, p < 0.01) and OS (r = 0.51, p < 0.01 and r = 0.56, p < 0.01) at baseline and endpoint, respectively. Following 3 months of treatment, increases in biochemical markers like PINP predicted the increase in Ac.F. (r = 0.52, p < 0.01) and OS (r = 0.54, p < 0.01) after 24 months. CONCLUSIONS: The increased level of formation is similar in patients who were either TN or had lower bone turnover initially due to previous ALN therapy. Elevated bone formation in postmenopausal women with osteoporosis was sustained over a 24-month period by TPTD. Biochemical markers of bone formation are a good surrogate for the assessment of TPTD effects.

Diminished acute response of osteoclasts to calcium load in thyroidectomized patients.

To elucidate the role of endogenous calcitonin (CT) in the regulation of bone resorption, we evaluated the acute effects of an intravenous calcium load in nine patients after total thyroidectomy (aged 29.2 +/- 8 years) compared with nine healthy subjects. After overnight fasting, intravenous infusions of elemental calcium 1.7 mg/kg body weight were given over a 10-minute period. Blood samples for measurements of serum ionized calcium (S-iCa), plasma intact CT, parathyroid hormone (PTH), and plasma type I collagen cross-linked C-terminal telopeptide (beta-CTX) were obtained 3 minutes before and at 13, 30, 60, 90, and 150 minutes after the start of the infusion. At baseline, parameters of calcium and bone metabolism were similar in both groups. A similar increase in S-iCa and decrease in plasma PTH levels were observed in both groups. However, the plasma CT increased significantly by 13 minutes (P < 0.05) and beta-CTX decreased significantly as early as 30 minutes (P < 0.05) (decrease by 36% as compared with the baseline) only in the group consisting of healthy individuals. In the thyroidectomized group, the plasma beta-CTX did not decrease significantly during the first 60 minutes (decrease by only 8% as compared with the baseline) and response to the calcium load was significantly diminished throughout the study period as compared with that of the healthy subjects (P < 0.01). In conclusion, the results indicate that the increased CT secretion is responsible for the rapid initial decrease in the bone resorption following an acute intravenous calcium load.

Intravenous ibandronate injections given every three months: a new treatment option to prevent bone loss in postmenopausal women.

OBJECTIVE: To investigate the efficacy, safety, and dose response of three doses of ibandronate, given intermittently by intravenous (IV) injection every three months, in preventing postmenopausal osteoporosis. PATIENTS AND METHODS: 629 postmenopausal women, categorised according to time since menopause and baseline lumbar spine (L1-4) bone mineral density (BMD), were enrolled into a multicentre, double blind, placebo controlled trial. They were randomly allocated to receive IV ibandronate 0.5 mg, 1 mg or 2 mg, or placebo every three months. All women received daily calcium supplementation. RESULTS: One year's treatment with intermittent IV ibandronate injections produced a dose dependent gain in mean (SD) lumbar spine BMD from baseline of 2.5 (2.5)%, 1.8 (2.6)%, and 1.0 (2.8)% in the groups receiving 2 mg, 1 mg, and 0.5 mg ibandronate, respectively, compared with a loss of BMD of 0.4 (2.4)% in the women in the placebo group; p=0.0001 for each ibandronate dose v placebo. Highest BMD gains occurred in women with osteopenia receiving 2 mg ibandronate. Similarly, at the hip, all three doses of ibandronate produced significantly better gains in BMD than placebo (p<0.05), with the greatest gains in the women with osteopenia receiving the 2 mg dose. Ibandronate concomitantly and dose dependently suppressed markers of bone turnover in comparison with placebo, and injections were well tolerated. CONCLUSION: IV ibandronate injections, given every three months, may be an effective alternative to oral bisphosphonates and hormonal therapy in the prevention of bone loss in postmenopausal women.

Determinants of incident vertebral fracture in men and women: results from the European Prospective Osteoporosis Study (EPOS).

The aim of this analysis was to determine the influence of lifestyle, anthropometric and reproductive factors on the subsequent risk of incident vertebral fracture in men and women aged 50-79 years. Subjects were recruited from population registers from 28 centers across Europe. At baseline, they completed an interviewer-administered questionnaire and had lateral thoraco-lumbar spine radiographs performed. Repeat spinal radiographs were performed a mean of 3.8 years later. Incident vertebral fractures were defined morphometrically and also qualitatively by an experienced radiologist. Poisson regression was used to determine the influence of the baseline risk factor variables on the occurrence of incident vertebral fracture. A total of 3173 men (mean age 63.1 years) and 3402 women (mean age 62.2 years) contributed data to the analysis. In total there were 193 incident morphometric and 224 qualitative fractures. In women, an age at menarche 16 years or older was associated with an increased risk of vertebral fracture (RR = 1.80; 95%CI 1.24, 2.63), whilst use of hormonal replacement was protective (RR = 0.58; 95%CI 0.34, 0.99). None of the lifestyle factors studied including smoking, alcohol intake, physical activity or milk consumption showed any consistent associations with incident vertebral fracture. In men and women, increasing body weight and body mass index were associated with a reduced risk of vertebral fracture though, apart from body mass index in men, the confidence intervals embraced unity. For most variables the strengths of the associations observed were similar using the qualitative and morphometric approaches to fracture definition. In conclusion our data suggest that modification of other lifestyle risk factors is unlikely to have a major impact on the population occurrence of vertebral fractures. The important biological mechanisms underlying vertebral fracture risk need to be explored using new investigational strategies.

Mechanisms of action of antiresorptive therapies of postmenopausal osteoporosis.

In the treatment of osteoporosis, the aim of the antiresorptive therapy is to restore bone density by decreasing bone remodeling. The process of bone remodeling plays a role in plasma calcium homeostasis and serves to modify bone architecture in order to meet changing mechanical needs, to maintain osteocyte viability, and to repair microdamage in bone matrix. Estrogen deficiency results in a number of detrimental effects on bone, including suppression of osteocyte survival as well as impairment of osteoblast response to mechanical stimuli and repair of ageing bone. In this review, effects of available antiresorptive therapies on endocrine regulations of bone metabolism in postmenopausal osteoporosis are compared. The aim of antiresorptive treatment is to ensure adequate bone remodeling, reparation of microdamage of bone, and increased bone strength. Ideally, this effect should be maintained long-term. Several agents are approved for the treatment of osteoporosis. Calcitonin transiently inhibits osteoclast activity without decreasing osteoblast collagen synthesis. Aminobisphosphonates decrease bone remodeling by decreasing osteoclast activity and by inducing osteoclast apoptosis. This allows more time for secondary mineralization to proceed to completion in the existing bone tissue mass, so increasing the mechanical resistance of bone to loading. Estrogens and raloxifene (a selective estrogen receptor modulator that acts as an estrogen agonist in bone) suppress bone remodeling to the premenopausal range, maintaining the function of osteoblasts and osteocytes. In the placebo-controlled osteoporosis treatment trials, all the above treatments reduced the risk of fractures. Raloxifene therapy was also associated with a favorable or neutral effect in the cardiovascular system, and a reduced incidence of breast cancer. Selection of appropriate drug for treatment of postmenopausal osteoporosis should take into account the long-term effect of the antiresorptive agent on bone. Moreover, the effects on other tissues ++should also be considered, and this encompasses both safety concerns, as well as the potentially beneficial effects on other tissues. Further investigation is needed to evaluate the different modes of action of these agents, and their long-term effects on bone and other tissues.

Acute effects in healthy women of oral calcium on the calcium-parathyroid axis and bone resorption as assessed by serum beta-CrossLaps.

The purpose of this investigation was to test the hypothesis that the decrease in bone resorption after the calcium (Ca) load can be assessed by serum type 1 collagen cross-linked C-telopeptide (Elecsys beta-CrossLaps, Roche) (S-CTX). Six young healthy women (23-27 years of age) and six healthy late postmenopausal women (63-69 years of age) with normal bone mineral density (BMD) received, after overnight fasting, 1 g of elemental Ca (in the form of calcium carbonate) dissolved in 250 ml of water or only plain water (fasting period). In addition, the late postmenopausal women were tested with an additional dose of 0.2 g of elemental Ca in 250 ml of water. Serum ionized Ca (S-iCa), S-CTX, plasma immunoreactive intact parathormone (P-PTH) were measured before and during the 5 hours after the oral intake of Ca. Urine was collected at regular intervals, and urinary Ca and creatinine were analyzed. In both the young and late postmenopausal subjects, the load with Ca resulted in a significant increase in S-iCa and urine Ca/creatinine ratio as well and a significant decrease of P-PTH and S-CTX compared with the fasting period. The comparison of the effects of 1 g Ca load between young and late postmenopausal women did not show any statistical significance in any measured parameters. In the late postmenopausal women, a significantly greater increase in S-iCa concentrations and a significantly greater decrease in P-PTH after 1 g were observed compared with those after a 0.2 g dose of Ca. During the first 3 hours, the load of both 1 g and 0.2 g of Ca induced a similar decrease in S-CTX. After 5 hours, however, S-CTX were significantly more suppressed after a 1 g dose than after a 0.2 g dose of Ca. In conclusion, a single oral morning dose of 1 g Ca suppresses bone resorption, as assessed by S-CTX, to a similar degree in both young and late postmenopausal women with normal Ca absorption. In healthy late postmenopausal women the load of 0.2 g of Ca carbonate significantly suppresses bone resorption.

Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: 4-year results from the MORE trial. Multiple outcomes of raloxifene evaluation.

Raloxifene, a selective estrogen receptor modulator approved for the prevention and treatment of postmenopausal osteoporosis, has shown a significant reduction in breast cancer incidence after 3 years in this placebo-controlled, randomized clinical trial in postmenopausal women with osteoporosis. This article includes results from an additional annual mammogram at 4 years and represents 3,004 additional patient-years of follow-up in this trial. Breast cancers were ascertained through annual screening mammograms and adjudicated by an independent oncology review board. A total of 7,705 women were enrolled in the 4-year trial; 2,576 received placebo, 2,557 raloxifene 60 mg/day, and 2,572 raloxifene 120 mg/day. Women were a mean of 66.5-years old at trial entry, 19 years postmenopause, and osteoporotic (low bone mineral density and/or prevalent vertebral fractures). As of 1 November 1999, 61 invasive breast cancers had been reported and were confirmed by the adjudication board, resulting in a 72% risk reduction with raloxifene (relative risk (RR) 0.28, 95% confidence interval (CI) 0.17, 0.46). These data indicate that 93 osteoporotic women would need to be treated with raloxifene for 4 years to prevent one case of invasive breast cancer. Raloxifene reduced the risk of estrogen receptor-positive invasive breast cancer by 84% (RR 0.16, 95% CI 0.09, 0.30). Raloxifene was generally safe and well-tolerated, however, thromboembolic disease occurred more frequently with raloxifene compared with placebo (p=0.003). We conclude that raloxifene continues to reduce the risk of breast cancer in women with osteoporosis after 4 years of treatment, through prevention of new cancers or suppression of subclinical tumors, or both. Additional randomized clinical trials continue to evaluate this effect in postmenopausal women with osteoporosis, at risk for cardiovascular disease, and at high risk for breast cancer.

Immunocytochemical detection of estrogen receptors in bone cells using flow cytometry.

A sensitive method for immunocytochemical detection of estrogen receptors using flow cytometry is reported. Using this method, estrogen receptors were detected in several osteoblastic cell lines with established expression of estrogen receptors, and for the first time, estrogen receptors were also demonstrated in murine fibroblasts and in human primary marrow stromal cells. The distribution of estrogen receptors within all cell lines was unimodal. The method enables for studies of estrogen receptors in the cell types which express low to moderate levels of the receptors, for studies of heterogeneity of the receptors' expression and for simultaneous detection of several parameters on a single-cell level.

Anabolic effects of progestogens in bone remodelling.

The short-term effects of oestrogen deficiency on biochemical indices of bone turnover were studied in 49 women who had undergone hysterectomy with bilateral ovariectomy. In patients treated with norethisterone or tibolone, a significant reduction was observed in urinary hydroxyproline excretion comparable to that observed in estradiol treated patients. Bone isoenzyme of serum alkaline phosphatase activity did not decrease and bone mass remained increased during norethisterone and tibolone treatments. It is concluded that norethisterone and tibolone can act as bone-trophic hormones.

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.

Quantitation of growth factors in ossein-mineral-compound.

Study was undertaken to identify polypeptide factors in the commercially available ossein-mineral-compound and to see if they are present in a biologically relevant quantity. Using the guanidine-EDTA extraction, 35.7 +/- 0.1 mg proteins were obtained from 1 g of the ossein-mineral-compound. At concentration 1 micrograms/ml, guanidine-EDTA-extractable proteins stimulated the incorporation of thymidine into DNA by human bone cells to 581 +/- 122% (p less than 0.001) of that by bovine serum albumin-treated control cells, decreasing thereafter. Similarly, it stimulated the activity of alkaline phosphatase in the human bone cells. Growth factors IGF-I, IGF-II, and TGF-beta were identified in the ossein-mineral-compound. This leads to speculation regarding possible role of growth factors in explaining the beneficial effects of the compound in retarding bone loss in patients with osteoporosis.

Evidence that tartrate-resistant acid phosphatases from osteoclastomas and hairy cell leukemia spleen are members of a multigene family.

1. Osteoclasts and hairy cell leukemia spleen both contain large amounts of a band 5-tartrate-resistant acid phosphatase (TrACP). 2. We have recently purified to homogeneity a band 5 TrACP from human osteoclastomas and two isoforms of band 5 TrACP (5a and 5b) from the spleen of a patient with hairy cell leukemia. 3. Although the N-terminal amino acid sequences and the apparent molecular weights of the osteoclastoma, hairy cell leukemia spleen TrACPs were identical, there were several differences in the physical and biochemical properties between the three isoenzymes. 4. Based on these findings, it is concluded that these isoenzymes are different enzymes, but that they could have originated from a similar ancestral gene. 5. It is proposed that the osteoclastoma and hairy cell leukemia band 5 TrACPs are members of a multigene family.

Purification and N-terminal amino acid sequence of the tartrate-resistant acid phosphatase from human osteoclastoma: evidence for a single structure.

Tartrate-resistant acid phosphatase type-5 was purified to apparent homogeneity from human osteoclastomas by sequential chromatography on CM-Sepharose, Phenyl-Sepharose, concanavalin A-Sepharose, FPLC Superose-12, and FPLC Mono-S. The purification over the original tissue extract was 1167-fold, with a yield of 16%. An identity in the N-terminal amino acid sequence and Mr was found between this enzyme and two type-5 tartrate-resistant acid phosphatases isolated from hairy cell leukemia spleen. However, they appeared to be different as assessed by amino acid composition. In contrast to a previous report, no evidence was found for two subunits of the tartrate-resistant acid phosphatase.

Purification and N-terminal sequence of two tartrate-resistant acid phosphatases type-5 from the hairy cell leukemia spleen.

Tartrate-resistant acid phosphatases types 5a and 5b were purified from human hairy cell leukemia spleen by sequential chromatography on Phenyl-Sepharose, CM-Sepharose, concanavalin A-Sepharose, FPLC Superose-12 and FPLC Mono-S. The purification over the original tissue extract was 1150- and 3300-fold, with a yield of 2.1% and 2.5%, respectively. Gel filtration indicated an Mr of about 30000 for both forms. There was a N-terminal sequence identity between the two enzymes. However, they appeared to be different as assessed by cation exchange chromatography and amino acid composition.

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.

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.