Biochemical Markers Of Bone Metabolism Research Articles

Prophylactic Bisphosphonate Treatment Prevents Bone Fractures After Liver Transplantation

A randomized controlled prospective open-label single center trial was performed. At the time of transplantation patients were randomly assigned to one of two treatment arms: The study group of 47 patients received zoledronic acid (ZOL, 8 infusions at 4 mg during the first 12 months after LT), calcium (1000 mg/d) and vitamin D (800 IE/d). The control group consisted of 49 patients who received calcium and vitamin D at same doses (CON). The incidence of bone fractures or death was predefined as the primary endpoint. Secondary endpoints included bone mineral density (BMD), serum biochemical markers of bone metabolism, parameters of trabecular bone histomorphometry and mineralization density distribution (BMDD). Patients were followed up for 24 months. Analysis was performed on an intention-to-treat basis. The primary endpoint fracture or death was reached in 26% of patients in the ZOL group and 46% in the CON group (p = 0.047, log rank test). Densitometry results were different between the groups at the femoral neck at 6 months after LT (mean+/-SD BMD ZOL: 0.80 +/- 0.19 g/cm2 vs. CON: 0.73 +/- 0.14 g/cm2, p = 0.036). Mixed linear models of biochemical bone markers showed less increase of osteocalcin in the ZOL group and histomorphometry and BMDD indicated a reduction in bone turnover. Prophylactic treatment with the bisphosphonate zoledronic acid reduces bone turnover and fractures after liver transplantation.

Remarkable increase in lumbar spine bone mineral density and amelioration in biochemical markers of bone turnover after parathyroidectomy in elderly patients with primary hyperparathyroidism: a 5-year follow-up study

We evaluated the efficacy of parathyroidectomy (PTX) on bone mineral density (BMD) and hormonal and biochemical markers of bone metabolism in elderly primary hyperparathyroidism (PHPT) patients, and followed these patients for 5 years after PTX. Eleven PHPT patients were enrolled and were followed for 5 years by measuring lumbar spine BMD (LSBMD), femoral BMD (FBMD), radial BMD (RBMD), parathyroid hormone (PTH), 1,25-dihydroxyvitamin D [1,25(OH)(2)D], serum calcium (SCa), inorganic phosphate (iP), bone-specific alkaline phosphatase (BAP), intact osteocalcin (IOC), urinary excretion of type I collagen cross-linked N-telopeptide (NTx), and urinary deoxypyridinoline (DPD). PTX produced significant increases in LSBMD of 12%, 19%, and 29% as compared with pretreatment levels after 1, 3, and 5 years, respectively (P < 0.01, compared to baseline), whereas there was no significant increase in FBMD and a slight decrease in RBMD. SCa and iP levels remained normal over the five years. PTX also resulted in significant decreases in PTH, 1,25(OH)(2)D, BAP, IOC, NTx, and DPD that continued for at least 3 years after PTX. In conclusion, PTX seemed effective to normalize various markers of bone metabolism in elderly PHPT patients and is recommended to patients with low LSBMD to prevent future fractures. On the other hand, the use of PTX for low FBMD or RBMD patients requires further discussion.

Effect of monthly oral ibandronate on anastrozole-induced bone loss during adjuvant treatment for breast cancer: One-year results from the ARIBON study

553 Background: The aromatase inhibitor anastrozole is a highly effective treatment for breast cancer with superior efficacy and tolerability advantages over tamoxifen. However its use is associated with significant declines in bone mineral density (BMD) with an increase in fracture risk. The ARIBON trial is a double blind, randomised, placebo-controlled study designed to evaluate the impact of bisphosphonate treatment on BMD in women taking anastrozole. The study also aims to explore the relationship between levels of biochemical markers of bone metabolism with longer term changes in BMD as measured by Dual energy Xray Absorptiometry (DXA). Methods: 131 postmenopausal, surgically treated breast cancer patients were recruited from oncology clinics in Leeds and Sheffield, UK. Following consent, baseline bone densitometry showed that 68, 50 and 13 patients were found to be normal (T &gt;-1.0), osteopenic (T -1.0 to -2.5) and osteoporotic (T &lt; -2.5) respectively. All patients were treated with anastrozole 1mg once a day and offered calcium and vitamin D supplementation. In addition, osteopenic patients were randomised on a 1:1 basis to receive either treatment with ibandronate 150 mg orally every month or placebo. Osteoporotic patients were treated with open label ibandronate orally 150mg every month. Results: After I year, osteopenic patients treated with ibandronate gained +2.78% (range -3.8, +15.1) and +1.35% (range -4.1, +5.6) at the lumbar spine and hip respectively. Patients treated with placebo however lost -2.61% (range -11.0, +2.2) at the lumbar spine and -2.34% (range -10.4, +5.2) at the hip. The differences between the two treatment arms were statistically significant at both sites (p&lt;0.001, independent samples t-test). Patients with osteoporosis gained +5.05% (range -8.7, +15.2) at the lumbar spine and +2.62% (range -1.0, +8.6) at the hip after 1 year. Conclusions: Ibandronate 150 mg by mouth once a month prevents anastrozole induced bone loss and results in significant increases in BMD at the hip and lumbar spine in osteopenic and osteoporotic patients. Analysis of the biochemical markers of bone metabolism is underway and relationships between biochemical and BMD changes will be presented. No significant financial relationships to disclose.

Levels of bone collagen markers in preterm infants: relation to antenatal glucocorticoid treatment

Although the beneficial effects of antenatally administered glucocorticoids are well documented, data on the potential of adverse consequences are limited. The objective of this study was to determine the effects of antenatally administered glucocorticoids on biochemical markers of bone metabolism of 55 preterm infants with a gestational age of 24-34 weeks who were enrolled in the study. Neonates were divided into two groups according to antenatal exposure to corticosteroids. There were no significant differences between the groups in clinical characteristics and anthropometric variables. We studied blood levels of osteocalcin (OC), carboxy-terminal propeptide of type I procollagen (PICP), and carboxy-terminal telopeptide of type I collagen (ICTP) at the time of delivery, on postnatal day 10, and at 2 and 4 months of life. Comparing the groups, we found statistically significant reduction in PICP levels at birth in corticosteroid-exposed neonates (P < 0.05). The levels of bone markers increased progressively on the first days of life. There were no significant differences between groups in bone markers at 10 days or at 2 and 4 months of life. We found no significant difference for bone markers between groups of infants exposed to single or repeated maternal corticosteroid treatments. In summary, antenatal glucocorticoid treatments are suggested to have a negative impact on fetal bone formation as reflected by low PICP levels at birth. However, this negative effect on bone markers seems to be a temporary effect that subsides on the first days of life and afterward.

Biochemical Markers of Bone Metabolism in Children with Helicobacter pylori Infection

We investigated the biochemical markers of bone metabolism in children with Helicobacter pylori infection. Biochemical markers of bone metabolism and serum levels of vitamin B12, ferritin and estradiol were measured in 41 H. pylori-positive (+) children (23 girls, 18 boys; aged 11.8+/-3 years). Serum levels of intact parathyroid hormone, ss-collagen I carboxy terminal telopeptide, total alkaline phosphatase (ALP), bone-specific ALP, N-terminal cross-links of human procollagen type I, N-mid-osteocalcin, calcium, phosphate, ferritin, and estradiol did not differ significantly between H. pylori(+) and H. pylori negative (-) children. Vitamin B12 levels were significantly decreased in H. pylori(+) compared to H. pylori(-) children. H. pylori infection was not accompanied by significant changes in markers of bone metabolism in children, although vitamin B12 levels were decreased. Further studies are required to clarify whether H. pylori infection causes time-dependent changes in bone turnover markers during the long course of this inflammatory disease.

Effects of Combined Treatment with Alendronate and Alfacalcidol on Bone Mineral Density and Bone Turnover in Postmenopausal Osteoporosis: A two-years, randomized, multiarm, controlled trial

One hundred ninety seven postmenopausal women with osteoporosis were enrolled in a prospective, randomized, single-blind, controlled trial of 24 months' duration to compare the efficacy of Alendronate 10mg + Alfacalcidol 0.5μg + 500 mg calcium (group A), Alendronate 10mg + 500 mg Calcium (group B), Alfacalcidol 0.5 μg + 500mg calcium (group C), or Calcium 500 mg (group D), on bone mineral density and bone metabolism markers. Upon inclusion, the subjects were randomized to groups A, B, C and D according to a 1.5/2/1.5/1 scheme. BMD was measured at the lumbar spine (L2-L4) and the femur neck using dual energy x-ray absorptiometry (LUNAR DPX) at baseline and after 12 and 24 months. Biochemical markers of bone metabolism including osteocalcin, urinary calcium and urinary deoxypyridinoline, were collected at baseline, 6 month, 12 month, and 24 month. Data collection and statistical analyses were performed in a single-blind fashion. SPSS 10.0 and Statistica 7.0 statistical packages were used for data encoding and analysis. The 5% level was used as threshold for statistical significance. Upon inclusion and randomization, patients' characteristics (age, height, weight, time since menopause,) and study outcomes (osteocalcin, urinary calcium, deoxypyridinoline, and BMD values) were homogeneous between the four groups. At 2-years, and at the lumbar level, the highest significant gain in bone mass was seen for group A (+8.4%), followed by group B (+6.4%), and group C (+2.3%), while a significant decrease was seen among subjects from group D (-2.5%). A similar pattern was observed at the femoral neck level, with gains ranging from +5.3% for group A, +3.8% for group B, +1.2% (NS) for group C, and -6.4% for group D. Significant reductions of osteocalcin levels were observed among groups A (-4 %), B (-5.7%), and C (-1.7%). Urinary calcium was significantly increased in group C (+14%), while decreased in group B (-5.6%). Deoxypyridinoline significantly decreased among verum groups (A: -68%, B: -63.3%, C: -45%) and increased in the control group (+18.1%). Intergroup differences revealed a significantly higher gain in bone mass induced by treatments regimen A, B and C compared to D at both the femoral and lumbar levels, a higher decrease of osteocalcin levels in groups A and B versus D, similar variations of urinary calcium among the four groups, and a significantly higher reduction in deoxypyridinoline in group A, followed by B and C, versus D. The incidence of increased 24 h urinary calcaemia was similar between the four groups (p>0.06). No case of clinical hypercalciuria or hypercalcemia has been recorded. Gastrointestinal side effects occurred in 4 patients in Group A, and in 5 patients in Group B, which resulted in the termination of treatment. Data from this randomized controlled trial suggested a higher efficacy in increasing bone mineral density and a similar tolerance of combined therapy with Alendronate and Alfacalcidol compared to Alfacalcidol alone, and to Alendronate as a consistent trend. Importantly, the combined therapy resulted in lower rates of hypercalciuria, hypercalcemia, and hypocalcemia compared to monotherapies.

Zoledronic Acid May Improve Survival Compared to Pamidronate in Patients with MM and High BALP Levels: Univariate and Multivariate Models of Hazard Ratios.

In untreated patients with multiple myeloma, elevated bone-specific alkaline phosphatase (BALP) levels have shown a significant association with bone pain, bone lesions, and pathologic fractures, and have been correlated with reduced survival (Fonseca R, et al. Br J Haemotol. 2000; 109:24–29). Zoledronic acid reduces the risk of skeletal morbidity and levels of biochemical markers of bone metabolism in patients with bone lesions from multiple myeloma. Zoledronic acid has also demonstrated antimyeloma effects in preclinical studies in vitro and in vivo using mice bearing human or mouse myeloma. Therefore, it is possible that zoledronic acid may not only prevent skeletal complications but also increase survival in patients with multiple myeloma. We conducted a retrospective exploratory analysis of patients with multiple myeloma and bone lesions as part of a large, randomized, controlled trial comparing infusions of zoledronic acid 4 mg and pamidronate 90 mg to assess the effect of zoledronic acid on survival based on baseline bone marker levels. In the overall population of patients with multiple myeloma (N=353), survival was comparable between groups. The subset of multiple myeloma patients who had information on baseline BALP levels were examined in these analyses (n=212; 4 mg zoledronic acid [n=109] or 90 mg pamidronate [n=103]). Patients received treatment for up to 24 months with a final assessment at 25 months. Risk of death was assessed in univariate and multivariate models using Cox regression methodology. Factors included in the multivariate analyses were prior skeletal-related events and baseline ECOG performance status. Among patients who had a baseline BALP assessment, zoledronic acid significantly increased the 25-month overall survival compared with pamidronate (76% versus 63%; P=.026). In the univariate and multivariate analyses, zoledronic acid significantly reduced the risk of death by approximately 42% compared with pamidronate (P=.03 for both). The subset of patients was then retrospectively stratified by baseline BALP levels according to the following criteria: low BALP (<146 U/L) and high BALP (≥146 U/L). Among patients who had low baseline BALP (n=123), 25-month survival was similar for both treatment groups. Although zoledronic acid reduced the risk of death in this subset by approximately 30% compared with pamidronate in the univariate and multivariate analyses, the between-group differences were not statistically significant (P>.2 for both). In contrast, among patients with high baseline BALP (n=89), zoledronic acid significantly improved survival compared with pamidronate (82% versus 53%; P=.041). Zoledronic acid significantly reduced the risk of death in this subset by approximately 56% compared with pamidronate in both the univariate and multivariate analyses (P<.05 for both). These exploratory analyses suggest that, in addition to its established benefits in preventing skeletal complications, zoledronic acid may improve survival compared with pamidronate in patients with multiple myeloma who have high BALP levels. Prospective trials are needed to investigate the improved survival in this subset; the high-BALP subset may have higher statistical power to distinguish between the 2 bisphosphonates (higher event rate), or these patients may still have coupled bone metabolism and better recovery after response to antiresorptive therapy.

0513: Biochemical Markers of Bone Metabolism in Patients with Uterine Cervical Cancer After Treatment

0513: Biochemical Markers of Bone Metabolism in Patients with Uterine Cervical Cancer After Treatment

Effect of treadmill gait on bone markers and bone mineral density of quadriplegic subjects

Quadriplegic subjects present extensive muscle mass paralysis which is responsible for the dramatic decrease in bone mass, increasing the risk of bone fractures. There has been much effort to find an efficient treatment to prevent or reverse this significant bone loss. We used 21 male subjects, mean age 31.95 +/- 8.01 years, with chronic quadriplegia, between C4 and C8, to evaluate the effect of treadmill gait training using neuromuscular electrical stimulation, with 30-50% weight relief, on bone mass, comparing individual dual-energy X-ray absorptiometry responses and biochemical markers of bone metabolism. Subjects were divided into gait (N = 11) and control (N = 10) groups. The gait group underwent gait training for 6 months, twice a week, for 20 min, while the control group did not perform gait. Bone mineral density (BMD) of lumbar spine, femoral neck, trochanteric area, and total femur, and biochemical markers (osteocalcin, bone alkaline phosphatase, pyridinoline, and deoxypyridinoline) were measured at the beginning of the study and 6 months later. In the gait group, 81.8% of the subjects presented a significant increase in bone formation and 66.7% also presented a significant decrease of bone resorption markers, whereas 30% of the controls did not present any change in markers and 20% presented an increase in bone formation. Marker results did not always agree with BMD data. Indeed, many individuals with increased bone formation presented a decrease in BMD. Most individuals in the gait group presented an increase in bone formation markers and a decrease in bone resorption markers, suggesting that gait training, even with 30-50% body weight support, was efficient in improving the bone mass of chronic quadriplegics.

Changes in Serum Biochemical Markers of Bone Cell Activity in Growing Thoroughbred Horses

We studied the changes in biochemical markers of bone metabolism in growing Thoroughbred horses. Serum osteocalcin (OC), as a marker for bone formation, and carboxy-terminal propeptide of type-I collagen (PICP), as a marker for bone formation, carboxy-terminal telopeptide of type-I collagen (ICTP), as a marker for bone resorption, were determined in nine clinically healthy horses from 3 d to 17 mo of age. The BW and withers height (WH) increased during the study. On the other hand, a rapid reduction in body weight gain (BWG) was observed between 1 mo and 9 mo of age and a rapid reduction in withers height gain was observed between 1 mo and 5 mo of age. The serum markers decreased significantly with increasing age. In particular, dramatic changes in serum markers occurred between 3 d to 1 wk and 5 to 7 mo of age in these horses, which suggests that bone turnover rapidly decreased after birth. On the other hand, the ratio of PICP to ICTP decreased through the experiment. This result suggests that the reduction in bone formation exceeded that of bone resorption. There was a significant correlation between markers and growth parameters, except for the correlation between PICP and BWG on single linear regression analysis. Serum OC and ICTP were affected by the WH in multiple linear regression analysis. These results indicated that the age-related variation in serum biochemical markers of bone metabolism reflected bone growth, but neither BW nor BWG. Therefore, we consider that changes in bone modeling are the major factor affecting the levels of serum biochemical markers by 17 mo of age in horses.

Hydroxy-PCBs, PBDEs, and HBCDDs in Serum from an Elderly Population of Swedish Fishermen's Wives and Associations with Bone Density

Lack of human exposure data is frequently reported as a critical gap in risk assessments of environmental pollutants, especially regarding "new" pollutants. The objectives of this study were to assess serum levels of the persistent 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153), hydroxylated polychlorinated biphenyl metabolites (OH-PCBs), polybrominated diphenyl ethers (PBDEs), and hexabromocyclodode-canes (HBCDDs) in a group of Swedish middle-aged and elderly women expected to be relatively highly exposed, and to evaluate the impact of potential determinants (e.g., fish intake, age) for the inter-individual variation, as well as to investigate the association between these pollutants and bone density. No associations were found between bone mineral density or biochemical markers of bone metabolism and the analyzed environmental pollutants. Relatively high levels of CB-153 (median 260 ng/g fat) and sigma 3-OH-PCBs (median 1.7 ng/mL serum), and low concentrations of sigma6PBDEs (median 3.6 ng/g fat) were determined. Total level of HBCDDs in serum was quantified by gas chromatography with mass spectrometric detection (median 0.5 ng/g fat). HBCDD diastereomeric and enantiomeric patterns were determined by liquid chromatography with mass spectrometric detection. The dominating stereoisomer was (-)alpha-HBCDD, but 1-3% of gamma-HBCDD was also detected in the serum samples.

Adverse Effects of Antiepileptic Drugs on Bone Mineral Density

The aim of this study is to determine the frequency of changes in biochemical markers of bone metabolism in children who are receiving valproic acid, carbamazepine, and oxcarbazepine. Thirty healthy children and 68 children with idiopathic epilepsy treated with either carbamazepine (n = 23), valproic acid (n = 31), or oxcarbazepine (n = 14) for more than 1 year were enrolled into the study. Blood samples were obtained in order to determine biochemical parameters (calcium, phosphorus, alkaline phosphates, parathormone, and 25-hydroxyvitamin D). Bone mineral density was measured with the dual-energy x-ray absorptiometry method. There were no significant differences in the serum concentrations of calcium, phosphorus, aspartate aminotransferase, alanine aminotransferase, and albumin levels between the four groups. However, serum alkaline phosphatase concentrations were higher in the patient group as compared with the control subjects. In patients receiving antiepileptic drugs, bone mineral density values were significantly lower than the healthy control group. In conclusion, long-term antiepileptic drug treatment either with valproic acid, carbamazepine, or with oxcarbazepine which has unknown effects on skeletal mineralization, induces a state of decreased bone mineral density.

Does the combination of inhaled steroids with long acting beta2 agonists decrease the risk for osteoporosis? A 1-year prospective follow-up study

Combination of inhaled corticosteroids (ICS) with long acting beta2 agonists has been used increasingly in the treatment of moderate-severe asthma, however there is indefinitive data about their effect on bone loss. The aim of this study was to compare the effects of treatment with single ICS and combination of ICS with long acting beta2 agonists (combination therapy) on BMD and biomarkers of bone metabolism in adult patients with asthma over 1 year period. Forty-three patients with asthma were enrolled. Patients were separated into two groups according to their use of asthma drugs: single ICS or combination therapy (ICS plus long-acting inhaled beta2-agonist). Change in bone mineral density (BMD) and biochemical markers of bone metabolism were measured at baseline and at the end of 1 year. Mean ages and basal BMD of patients did not differ between the two groups (P > 0.05). The decrease in BMD was higher in the single ICS group than the combination therapy group, however there was no significant difference between them (P > 0.05). One year change (%) in BMD and biochemical markers of bone metabolism were not different between two groups (P > 0.05). In conclusion, use of ICS-in the range of doses used- does not seem to have an effect on the change of BMD. However, our data indicate a nonsignificant trend towards reducing bone loss with the use of combination therapy. Future studies are needed to provide definitive evidence for this trend to allow us suggesting combination therapy for minimizing bone loss.

Relationship between urinary phytoestrogen levels and Z score of lumbar vertebral bone mineral density in Japanese postmenopausal women

Phytoestrogens are attracting much attention for their anticancer effects, their reduction of menopausal symptoms, and their preventive effects against osteoporosis in the human body, resulting from the consumption of foods that contain phytoestrogens at high concentrations. The effects of 2 phytoestrogens, genistein and daidzein, have been reported, but little data have been published on the effects of equol, coumesterol, and other phytoestrogens. In the present study, using high-performance liquid chromatogaphy, we measured the urinary phytoestrogen levels of 80 postmenopausal Japanese women and simultaneously determined the bone mineral density (BMD) in lumbar vertebrae L2 through L4 (L2-L4BMD), measured the levels of the bone biochemical markers and calciotropic hormones, and also studied the relationships of these with urinary phytoestrogens. Our results showed the following values for phytoestrogens in grams per milligram of creatinine: daidzein, 3.11 ± 3.09; genistein, 2.74 ± 5.02; equol, 6.29 ± 11.44; coumesterol, 0.51 ± 0.77; O-desmethylangolensin (DMA), 1.59 ± 5.19; formononetin, 0.11 ± 0.19; and biochanin A, 0.08 ± 0.19. When these were converted to logarithms, log (genistein) was the only one to show a statistically significant positive correlation ( r = 0.29, P < .05) with the Z score of L2-4BMD. Log (DMA) showed a negative correlation ( r = −0.36, P < .013) with the urinary deoxypyridinoline level. The levels of osteocalcin and the calciotropic hormones showed no correlation with urinary phytoestrogen levels. The fact that there were correlations between the genistein level and Z score of bone density, and between DMA and biochemical markers of bone metabolism, suggested that phytoestrogens may have an effect on bone metabolism in Japanese women. Genistein and DMA might be involved in the inhibition of bone resorption in terms of the correlation between phytoestrogens levels and BMD.

The effect of milk basic protein supplementation on bone metabolism during training of young Thoroughbred racehorses

In laboratory animals, man and cell culture experiments, milk basic protein was reported to suppress bone resorption and promote bone formation. However, no studies in horses have previously examined the effect of milk basic protein. To evaluate the effect of milk basic protein supplementation on bone metabolism in young Thoroughbred horses in training. Twenty 2-year-old horses in training were used for 90 days in this study. The treatment group was fed a basal diet with 1 g of milk basic protein and the control group a basal diet only. Blood samples were collected on Days 0, 45 and 90 to determine serum calcium (Ca) and biochemical markers of bone metabolism. Radiographs were taken at the start and end of the study to determine radiographic bone aluminium equivalence (RBAE). Serum osteocalcin (OC) was significantly higher at Day 45 after the beginning of the study in the treatment group compared to that in the control group. The treatment group showed a greater increase in the total RBAE change at the end of this study compared to that in the control group. However, there were no significant differences in serum Ca and carboxy-terminal telopeptide of type I collagen (ICTP) between groups. These findings provide preliminary evidence that milk basic protein has an effect on bone formation in 2-year-old Thoroughbred horses in training. However, further studies in larger groups of horses are now required to substantiate our findings.

Angiogenetic Factors and Biochemical Markers of Bone Metabolism in POEMS Syndrome Treated with High-Dose Therapy and Autologous Stem Cell Support

The cause of the polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder and skin changes (POEMS) syndrome is currently unknown, but increased levels of vascular endothelial growth factor (VEGF) appear to play a pathogenetic role. Osteosclerotic bone lesions are a characteristic finding in POEMS, but there are no data about the specific role of various molecules that control bone remodeling in patients with POEMS. Serum levels of angiogenic cytokines (VEGF, angiogenin, angiopoietin-2, and basic fibroblast growth factor) along with a series of bone remodeling indices (C-telopeptide of type I collagen, bone-alkaline phosphatase [bALP], osteocalcin [OC], soluble receptor activator of nuclear factor–κB ligand [RANKL], osteoprotegerin [OPG], and macrophage inflammatory protein-1α) were measured in 2 patients with POEMS before and after high-dose therapy (HDT) with autologous stem cell transplantation and in age- and sex-matched controls. Increased VEGF levels before HDT were reduced significantly after treatment, although levels of the other angiogenetic factors did not differ from that of controls and were less influenced by HDT. Serum RANKL levels were increased before HDT, whereas OPG levels were within the levels of healthy controls, resulting in an abnormal soluble RANKL to OPG ratio. Levels of bone resorption markers (C-telopeptide of type I collagen) were very low or undetectable before HDT, although bALP and OC levels were similar to that of controls. After HDT, soluble RANKL levels decreased, OPG remained rather stable, bone resorption markers increased to levels of normal individuals, bALP levels were rather unchanged, and OC levels increased. Decreasing VEGF levels parallel clinical improvement, and the restoration of normal bone metabolism follows HDT.

Efficacy of zoledronic acid versus placebo on biochemical markers of bone metabolism in patients with breast cancer metastatic to bone

10559 Background: Zoledronic acid reduces the levels of bone markers and the risk of skeletal complications in patients with bone metastases. Recently, a correlation between the levels of biochemical markers of bone metabolism and the risk of clinical complications (ie, skeletal complications, disease progression, and death) in patients with bone metastases has been reported. The effect of zoledronic acid on bone marker levels was assessed in patients with bone metastases from breast cancer in a multicenter randomized trial conducted in Japan. Methods: Women with bone metastases secondary to breast cancer (N = 228) were randomized to 4 mg zoledronic acid (n = 114) or placebo (n = 114) every 4 weeks for 1 year. Levels of urinary N-telopeptide (NTX), a sensitive marker of bone resorption, were measured at baseline and regularly throughout the study. Results: The table shows that zoledronic acid reduced NTX levels in patients compared with placebo. Patients treated with zoledronic acid had a mean decrease of 61% from baseline NTX levels at week 2. This decrease was maintained throughout the study in this treatment group and was 54% at week 52. In contrast, patients in the placebo group had a mean increase of 27% from baseline NTX levels at week 2, and levels of NTX continued to increase during the study, reaching 146% above baseline at week 52. Conclusions: This analysis shows that treatment with zoledronic acid reduced NTX levels in patients with bone metastases from breast cancer compared with placebo. These results are consistent with published reports in patients with prostate or lung cancer and are consistent with the significant reduction in skeletal morbidity observed in this trial in breast cancer patients. Zoledronic acid demonstrated a 39% reduction in skeletal morbidity in this patient population. [Table: see text] No significant financial relationships to disclose.

Steroid-induced osteonecrosis in severe acute respiratory syndrome: a retrospective analysis of biochemical markers of bone metabolism and corticosteroid therapy

SummaryAimWe investigated the effect of massive doses of corticosteroid therapy on bone metabolism using specific biochemical markers of bone metabolism, and the prevalence of osteonecrosis in severe acute respiratory syndrome (SARS) patients at a university teaching hospital in Hong Kong.MethodsSeventy-one patients with a clinical diagnosis of SARS were studied according to the modified World Health Organization case definition of SARS who were involved in the SARS epidemic between 10 March and 20 June 2003. The clinical diagnosis was confirmed by serological test and/ or molecular analysis. Biochemical markers of bone metabolism were analysed retrospectively using serial clotted blood samples collected from each patient during the course of hospital admission to discharge and subsequent follow-up at out-patient clinic using the arbitrary time periods: (i) Day <10; (ii) Day 28-44; (iii) Day 51-84; and (iv) Day >90 after the onset of fever. Magnetic resonance imaging of the knee and hip joints were performed post-admission to evaluate the prevalence of osteonecrosis amongst these SARS patients. Various risk factors for the development of osteonecrosis were assessed using receiver operating characteristics curve comparison with appropriate test statistics and Spearman’s coefficients of rank correlation with biochemical bone markers.ResultsBiochemical markers of bone metabolism showed significant bone resorption as evidenced by a marked increase in serum C-terminal telopeptide concentration (CTx) from Day 28-44 after the onset of fever. With tapering down of corticosteroid dosage, CTx started to return to previous baseline level from Day 51 onwards, while other bone formation markers, serum osteocalcin and bone- specific alkaline phosphatase concentrations (OC and BALP, respectively), started to increase. The latter effect was even more marked after Day >90. Seven patients developed radiological evidence of osteonecrosis. The prevalence of osteonecrosis in this cohort was 9.9%. A total corticosteroid dosage of >1900mg hydrocortisone, >2000 mg methylprednisolone, >13 340 mg hydrocortisone-equivalent corticosteroid therapy, and >18 days on corticosteroid therapy were found to be significant risk factors for the subsequent development of osteonecrosis. There were also significant positive correlations amongst various biochemical bone markers in this patient cohort.ConclusionBoth bone resorption and formation markers were unable to predict the subsequent development of osteonecrosis. The use of high dose of hydrocortisone or methylprednisolone for an extended duration was shown to be a significant risk factor for osteonecrosis. Its prevalence in this cohort is comparable to those reported in the literature for SARS patients with high-dose corticosteroid therapy. The Day 28–44 increase in the serum CTx coincided with the timing of corticosteroid use. The Day >51 increase in serum OC and BALP coincided with the timing of corticosteroid withdrawal.

Putting a Load on Your Bones: Low-Level Cadmium Exposure and Osteoporosis

Vol. 114, No. 6 EnvironewsOpen AccessPutting a Load on Your Bones: Low-Level Cadmium Exposure and Osteoporosisis accompanied byCadmium-Induced Effects on Bone in a Population-Based Study of Women Ernie Hood Ernie Hood Search for more papers by this author Published:1 June 2006https://doi.org/10.1289/ehp.114-a369Cited by:1AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit High-level exposure to cadmium is known to cause bone damage, including osteoporosis, but the effects of low-level exposure have been less clear. A group of Swedish researchers now shows for the first time that low-level exposure to cadmium also can be associated with negative effects on bone in humans [EHP 114:830–834; Åkesson et al.]. Although the impact may be slight, even a limited role for cadmium in the etiology of osteoporosis could be important at the population level, given the prevalence of osteoporosis and our ubiquitous, life-long low-level exposure to the substance through diet.Unlike lead (another contributor to osteoporosis), which is retained in bone tissue, cadmium is retained mainly in the kidneys. Exposure mostly comes from cereals, vegetables, shellfish, and tobacco, all of which absorb cadmium. Some cadmium occurs naturally, and more is released in industrial emissions and vehicle exhaust.To investigate associations between cadmium retention and bone effects, the scientists assessed a cohort of women ranging in age from 53 to 64 years. This segment of the population is the most susceptible to both cadmium retention (which appears to decrease slightly past this point) and osteoporosis. The 820 subjects were recruited from a large (n = 10,766) population-based survey of upper-middle-aged women in the community of Lund, Sweden. The lack of known history of excessive cadmium contamination in this area implied that exposures were fairly constant over time.The team measured cadmium in blood and urine; lead in blood; several biochemical markers of bone metabolism; and forearm bone mineral density (BMD), a test used to assess osteoporosis status. Statistical analysis of the results incorporated a comprehensive array of potential confounders and effect modifiers, including weight, menopausal status, use of hormone replacement therapy, age at menarche, alcohol consumption, smoking history, and physical activity level.Increasing urinary cadmium concentrations were associated with decreasing BMD. Furthermore, urinary cadmium was negatively associated with parathyroid hormone (a bone metabolism hormone) and positively associated with urinary deoxypyridinoline (a bone resorption marker). Those associations were present even in the subgroup with the lowest cadmium exposure—those who had never smoked. The study also showed that the negative bone effects appeared to intensify after menopause.The authors calculated that women in the 99th percentile of urinary cadmium concentration had an average of 5–6% lower BMD than those in the 1st percentile. This difference was similar to what could be expected from a 6-year-greater age or 11-kilogram-lower body weight. Although the researchers acknowledge that this contribution of low-level cadmium exposure to the development of osteoporosis is small, they emphasize that the observed effects should be considered “early signals of potentially more adverse health effects.” The findings thus lend increased urgency to efforts to reduce cadmium pollution of the environment.From cadmium to canes?New data show that even low-level exposure to cadmium may contribute to osteoporosis.FiguresReferencesRelatedDetailsCited by Calvillo S, Williams E and Brooks B (2015) Street Dust: Implications for Stormwater and Air Quality, and Environmental Management Through Street Sweeping Reviews of Environmental Contamination and Toxicology Volume 233, 10.1007/978-3-319-10479-9_3, (71-128), . Related articlesCadmium-Induced Effects on Bone in a Population-Based Study of Women2 February 2006Environmental Health Perspectives Vol. 114, No. 6 June 2006Metrics About Article Metrics Publication History Originally published1 June 2006Published in print1 June 2006 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.

The effect of vitamin K supplementation on biochemical markers of bone formation in children and adolescents with cystic fibrosis

Impaired vitamin K status in cystic fibrosis (CF) has been considered as a newly emerged pathogenetic factor for reduced bone mineral density (BMD). Our aim was to evaluate the effectiveness of vitamin K supplementation in managing bone formation abnormalities in children and adolescents with CF. The statuses of vitamins K and D in relation to biochemical markers of bone metabolism and BMD were examined in 20 CF children receiving vitamin D supplements but not vitamin K supplements. Laboratory tests were carried out at the beginning of the study period and after 1 year of vitamin K supplementation (10 mg single oral dose/week) and the results were compared; the results were also compared with those of 25 healthy controls. Ten of the CF patients had BMD z-score<or=2.5 (n=5) or between -1 and -2.5 (n=5). Biochemical tests on patients before vitamin K supplementation revealed that the levels of osteoblastic activity markers, namely, bone alkaline phosphatase (BAP), serum osteocalcin (Gla-OC), serum carboxy-terminal propeptide of type I procollagen (PICP) and serum amino-terminal propeptide of type I procollagen (PINP), were significantly reduced compared with those of the controls. These patients had also lower 25-hydroxy-vitamin D (25(OH)D) and vitamin K serum levels, higher undercaboxylated osteocalcin (Glu-OC) and parathormone (PTH) levels and a higher calcium to creatinine ratio (Ca/Cr) than the controls. Vitamin K intake was associated with an increase in Gla-OC, PINP, PICP levels and a decrease in Glu-OC levels. PTH levels were lower after vitamin K supplementation without any difference in BMD z-scores. Our data indicate that vitamin K supplementation may have a beneficial role in bone health in CF children.