Serum Bone-specific Alkaline Phosphatase Levels Research Articles

Bone biochemical markers in adolescent girls using either depot medroxyprogesterone acetate or an oral contraceptive

Study objective To examine the relationship between biochemical markers of bone metabolism and hormonal contraception in adolescents. Design A prospective, observational design. Setting The study was conducted in four adolescent health clinics in a large metropolitan area. Participants The study population comprised healthy, postmenarcheal adolescent girls aged 12–18 initiating either medroxyprogesterone acetate (n = 53) or an oral contraceptive (OC) containing 20 μg ethinyl estradiol/100 μg levonorgestrel (n = 165) and those using no hormonal contraception (n = 152). Interventions None. Main outcome measures Serum bone specific alkaline phosphatase (BSAP), urinary deoxypyridinoline (DPD), and bone mineral density (BMD) at baseline and 12 months. Results At 12 month follow-up, serum BSAP levels were significantly higher ( P < 0.05) in the control group (40.4 U/L ± 1.03 SE), than in the DMPA group (35.2 U/L ± 1.05 SE) and the OC group (35.5 U/L ± 1.03 SE). There was a trend in urinary DPD levels to be higher ( P = 0.08) in the control group (9.9 nmol/mmol Cr ± 1.03 SE) than in the DMPA group (9.1 ± 1.05 SE) and the OC group (8.9 ± 1.03 SE). No relationship was found between the biochemical markers and BMD at the lumbar spine or the femoral neck. Conclusions Over 12 months, there was evidence of increased bone formation and resorption in the control group when compared to that in the DMPA and OC groups. This finding may indicate a suppression of bone metabolism in girls using DMPA or an OC containing 20 μg ethinyl estradiol/100 μg levonorgestrel.

Effect of walking exercise on bone metabolism in postmenopausal women with osteopenia/osteoporosis.

The purpose of this prospective study was to determine whether moderate walking exercise in postmenopausal women with osteopenia/osteoporosis would affect bone metabolism. Fifty postmenopausal women, aged 49-75 years, with osteopenia/osteoporosis were recruited: 32 women entered the exercise program (the exercise group) and 18 served as controls (the control group). The exercise consisted of daily outdoor walking, the intensity of which was 50% of maximum oxygen consumption, with a duration of at least 1 h with more than 8000 steps, at a frequency of 4 days a week, over a 12-month period. Lumbar (L2-L4) bone mineral density (BMD) was measured at the baseline and every 6 months with dual-energy X-ray absorptiometry (DXA) in both groups. Serum bone-specific alkaline phosphatase (BAP) and urinary cross-linked N-terminal telopeptides of type I collagen (NTX) levels were measured at baseline and at months 1, 3, 6, 9, and 12 by EIA and ELISA, respectively, in the exercise group, and urinary NTX level was measured at the baseline and every 6 months in the control group. There were no significant differences in baseline characteristics including age, height, body weight, bone mass index, years since menopause, lumbar BMD, and urinary NTX level between the two groups. Although no significant changes were observed in lumbar BMD and the urinary NTX level in the control group, lumbar BMD in the exercise group was increased as compared with the control group, but was sustained from the baseline. In the exercise group, the urinary NTX level rapidly responded to walking exercise from month 3, and this reduction was sustained until month 12, followed by reduction in the serum BAP level. A moderately negative correlation was found between the percent change in the urinary NTX level at month 3 and that in lumbar BMD at month 12 in the exercise group. This study clearly demonstrates that the mechanism for the positive response of lumbar BMD to moderate walking exercise in postmenopausal women with osteopenia/osteoporosis appears to be the suppression of bone turnover, and that an early change in the urinary NTX level may be useful to predict the long-term response of increasing lumbar BMD to exercise, although its efficacy for lumbar BMD may be quite modest.

Osteoporotic vertebral fracture adjacent to a nonsegmented hemivertebra

A combination of osteoporotic vertebral fractures and congenital spinal deformity is theoretically possible, but there have been no reports on this combination in the literature. We describe a rare case of an osteoporotic vertebral fracture adjacent to the nonsegmented hemivertebra. A 60-year-old postmenopausal woman who did not recall any specific trauma presented with severe back pain. She had markedly decreased bone mineral density and significant lumbar kyphoscoliosis with a nonsegmented hemivertebra between L1 and L2 on radiographs of the lumbar spine. Magnetic resonance imaging (MRI) revealed a vertebral fracture adjacent to the nonsegmented hemivertebra. Laboratory studies showed increased serum bone-specific alkaline phosphatase (BAP) and urinary type I collagen crosslinked Ntelopeptide (NTx). A thoracolumbar brace was applied for 3 months. Daily administration of alendronate normalized her serum BAP and urinary NTx levels. MRI scans of the lumbar spine after 6 months also confirmed normalized signal intensities of the fractured vertebra adjacent to the nonsegmented hemivertebra. The vertebral fracture seemed to be induced by spinal malalignment, increased stress on the adjacent level of the fused segment, and its fragility due to osteoporosis.

Impaired secretion of parathyroid hormone, but not refractoriness of osteoblast, is a major mechanism of low bone turnover in hemodialyzed patients with diabetes mellitus

Diabetic bone disease is characterized by low bone turnover resulting from either impaired secretion of parathyroid hormone (PTH) or refractoriness of osteoblasts to PTH. The present study was performed to elucidate which factor contributes more to the reduction in bone turnover by comparison between 64 hemodialyzed patients with diabetes mellitus and 106 hemodialyzed patients without diabetes mellitus. Only men were enrolled to avoid the influence of the menstrual cycle on bone metabolism. Serum intact PTH (iPTH) levels were significantly lower in hemodialyzed patients with diabetes than those without diabetes, although no significant difference existed in age, duration of hemodialysis therapy, or serum calcium or phosphate levels. Of the biochemical markers measured, serum intact osteocalcin (iOC) and deoxypyridinoline levels were significantly lower in patients with diabetes, although serum bone-specific alkaline phosphatase (BAP) and pyridinoline levels did not differ significantly between the two groups of patients. When patients were restricted to those with serum iPTH levels greater than 180 pg/mL, this parameter correlated significantly in a positive manner with both serum iOC and BAP levels and negatively with bone mineral density at distal radius 1/3. Regression slopes between iPTH levels and these parameters were not significantly different between the two groups of patients, indicating the absence of refractoriness of bone to PTH in patients with diabetes. In conclusion, our findings suggest that impaired PTH secretion, but not refractoriness of osteoblasts to PTH, may be responsible for the low bone turnover in hemodialyzed patients with diabetes. © 2002 by the National Kidney Foundation, Inc.

Abnormal Bone Turnover in Cystic Fibrosis Adults

Cystic fibrosis (CF) patients often have low bone mineral density (BMD) and may suffer from fractures and kyphosis. The pathogenesis of low BMD in CF is multifactorial. To study bone metabolism, we collected fasting serum and urine from 50 clinically stable CF adults (mean age 28 years) and 53 matched controls to measure markers of bone formation and bone resorption. The CF subjects had moderate lung disease (FEV1: 46.1 +/- 18.6% predicted) and malnutrition (BMI: 20.0 +/- 3.3 kg/m2). Only 3 subjects had normal BMD. CF subjects had higher urinary N-telopeptides of type I collagen (81.0 +/- 60.0 vs 49.0 +/- 24.2 nm BCE/mmol creatinine, p = 0.0006) and free deoxypyridinoline (7.3 +/- 5.0 vs 5.3 +/- 1.9 nM/mM, p = 0.004) levels than controls. Serum osteocalcin levels were similar in the two groups, a result confirmed by two immunoassays that recognize different epitopes on osteocalcin. Serum bone-specific alkaline phosphatase levels were elevated in CF patients (32.0 +/- 11.3 vs 21.8 +/- 7.0 U/l, p < 0.0001), but were much more closely associated with serum total alkaline phosphatase levels (r = 0.51, p = 0.001) than with age or gender. Parathyroid hormone levels were elevated (p = 0.007) and 25-hydroxyvitamin D levels were depressed (p = 0.0002) in the CF patients in comparison with controls. These results indicate that adults with CF have increased bone resorption with little change in bone formation. Medications that decrease bone resorption or improve calcium homeostasis may be effective therapies for CF bone disease.

A comparison of two techniques for the determination of serum bone-specific alkaline phosphatase activity in dogs

Bone-specific alkaline phosphatase (BALP) shows potential as a marker of bone formation in the dog. Recent studies have indicated that serum BALP may provide a useful, non-invasive indicator of skeletal health in dogs, and as a diagnostic and prognostic marker in the management of dogs with musculoskeletal or metabolic disorders. Two assay techniques (one based on wheatgerm lectin precipitation followed by a simple enzymatic reaction, the second on a specific enzyme-linked immunoassay) were used to measure serum levels of BALP in 35 dogs of different ages.As expected,BALP concentrations decreased with age. For the enzymatic assay, mean (±SD) serum concentrations ofBALP activities were 100·3 (±11·6) U/liter in dogs under 1 year of age, 25·3 (±6·8) U/L in dogs 1 to 2 years of age, 16·5 (±7·3) U/L in dogs 2 to 3 years of age, 14·3 (±5·6) U/L in dogs 3 to 7 years of age, and 12·3 (±4·8) U/L in dogs aged 8 years and older. Corresponding results from the immunoassay were 56·3 (±9·8) U/L, 10·7 (±4·5) U/L, 7·0 (±2·5) U/L, 6·7 (±3·6) U/L and 7·0 (±2·9) U/L. There was excellent correlation between the results from the two assay techniques (r = 0·96; P < 0·0001). The correlation between BALP and total ALP activities was poor (r = 0·20 for enzymatic BALP, r = 0·31 for immunoreactive BALP), indicating that total ALP should be considered unreliable as an indicator of BALP activity in canine serum. The immunoassay demonstrated acceptable (13 per cent) cross-reactivity with the liver isoform ofALP .The commercial immunoassay kit is simple and provides fast results. Although the wheatgerm lectin/enzymatic technique is preferred in situations where the activities of all three isoforms of ALP are required, the immunoassay should be considered whenever the activity of BALP is the focus of interest.

Biochemical bone turnover markers in patients with ankylosing spondylitis.

In this study, bone formation markers [alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP) and osteocalcin (BGP)] and bone resorption markers [pyridinium cross-links: pyridinoline (Pyd) and deoxypyridinoline (Dpyd)] were studied in 44 patients with ankylosing spondylitis (AS) and in a control group of 41 subjects. The AS group was classified according to duration of disease, erythrocyte sedimentation rate (ESR) values and gender. Urinary Pyd and Dpyd concentrations of the patients were higher than in the control group, concomitant with the lower T-score values of the patients in both the anteroposterior lumbar spine and femoral neck. Although a correlation between markers of disease activity [ESR and C-reactive protein (CRP)] and bone turnover markers was not observed, urinary excretion of Dpyd and Pyd was enhanced in the ESR >20 mm/h subgroup compared with the ESR < or =20 mm/h subgroup. A significant elevation of urinary Dpyd was also observed in the female subgroup and long disease duration subgroup. Serum ALP, BALP and BGP levels of the patients and control group were not statistically different (p>0.05). No significant differences were observed between mineral and calcitropic hormone levels in either group, and total testosterone levels of the patients were within the reference range. According to this study, urinary Pyd levels are elevated in patients with AS. Gender, duration of disease and ESR also have an impact on urinary excretion of these collagen compounds. It can be concluded that bone turnover in patients with AS reflects normal osteoblastic activity and high osteoclastic activity.

Changes in Bone Resorption During the Menstrual Cycle

To determine if the cyclic changes of female sex hormones during the menstrual cycle are related to changes in bone formation and resorption, we measured serum bone-specific alkaline phosphatase (BAP) and osteocalcin (OC) and bone resorption markers, serum and urine deoxypyridinoline (Dpyr), three times per week during one menstrual cycle in 20 healthy premenopausal women. Serum estradiol (E2) and progesterone (P) showed characteristic cyclic fluctuations. Serum Dpyr was higher during the follicular phase (FP) than in the luteal phase (p = 0.027). Serum BAP, OC, and urine Dpyr levels did not change substantially across the cycle. Serum Dpyr correlated negatively with serum E2 values measured 6 (p = 0.011) and 8 (p = 0.001) days earlier and with P measured concurrently (p = 0.033) 2 (p = 0.002), 4 (p = 0.003), and 6 (p = 0.014) days earlier. BAP correlated negatively with E2 measured 6 days earlier (p = 0.006). We found no statistically significant correlations of E2 or P with OC or urine Dpyr within women over their cycles. BAP was positively correlated with concurrent serum Dpyr (p = 0.015) during the menstrual cycle. Serum OC levels correlated inversely with age (rs = -0.48, p = 0.036). Women with higher mean urine Dpyr levels had higher mean serum OC levels (rs = 0.49, p = 0.033) and showed a trend toward lower hip bone mineral density (rs = -0.40, p = 0.078). We conclude that the low level of E2 and/or P observed during the FP of the normal menstrual cycle is associated with increased bone resorption. These relationships suggest that normal women experience monthly episodes of increased bone resorption from menarche to menopause.

Changes in bone mass and serum markers of bone metabolism after parathyroidectomy

Background . Primary hyperparathyroidism (PHPT) is associated with an increased bone turnover. The simultaneous use of biochemical and bone mass measurements before and after parathyroidectomy is sparsely reported. This study was carried out to evaluate changes in bone mass and markers of bone metabolism in postmenopausal women with PHPT after parathyroidectomy. Methods . Twelve women, mean age of 63 years, were investigated. Measurements of bone mineral density (total body, spine, hip, and forearm bone mineral density) with dual-energy x-ray absorptiometry were performed before operation and at follow-up at a median of 23 months. Concomitantly, changes in serum intact parathyroid hormone, bone-specific alkaline phosphatase (B-ALP), osteocalcin, carboxyterminal propeptide of type I procollagen, and the immunoactive carboxyterminal telopeptide of type I collagen were recorded. Results . At follow-up a significant increase in bone mineral density of the spine (p < 0.05), femoral neck (p < 0.05), Ward's triangle (p < 0.05), and trochanter (p < 0.01) was observed. No significant changes in the forearm were registered. Levels of parathyroid hormone, B-ALP, and osteocalcin were elevated and intercorrelated before operation. The serum levels of these parameters decreased significantly after operation. Serum levels of carboxyterminal propeptide of type I procollagen and the immunoactive carboxyterminal telopeptide of type I collagen did not significantly differ from a reference population, and no major changes were observed at follow-up. Conclusions . Bone mineral density in the spine and hip is improved after parathyroidectomy in postmenopausal women with primary hyperparathyroidism. Serum levels of B-ALP and osteocalcin are elevated in PHPT and decrease after operation. The clinical usefulness of serum markers of collagen metabolism in investigating bone metabolism in PHPT seems limited.