Biochemical Markers Of Bone Metabolism Research Articles

Efectos agudos y a largo plazo del tratamiento con zolendronato en pacientes adultos con osteogénesis imperfecta. Estudio español observacional con 5 años de seguimiento

Osteogenesis imperfecta (OI) is an inherited disorder that causes low mineral density and bone fragility. Previous studies have shown the efficacy of bisphosphonates to increase bone mineral density (BMD). This study assessed changes over time in BMD and biochemical markers of bone metabolism in adult patients with osteogenesis imperfecta treated with intravenous zoledronic acid and the safety of this treatment. Patients and methodsA prospective, observational study in patients with OI, osteoporosis or osteopenia (T score <-2) who were administered zoledronic acid infusions (4mg IV) every 6 months for three years and annually thereafter. Densitometry was performed annually. Acute changes in complete blood count and calcium, phosphate, and creatinine levels, as well as side effects of the infusion, were recorded 24 and 48h after treatment. Calcium, phosphate, parathyroid hormone (iPTH), 25OH-vitamin D and bone turnover markers (bone alkaline phosphatase, ß-crosslaps and urinary deoxypyridinoline) were measured at baseline and every 12 months.Adverse events and new fractures were recorded. ResultsTwenty patients (6 men and 14 women) were treated. Median follow-up time was five years. Calcium levels and platelet counts significantly decreased 24 and 48hours after the first infusion, and the red blood cell count decreased at 24hours. These changes were not clinically relevant. Seven patients experienced a flu-like episode after the first dose. Treatment induced significant increases in BMD in the lumbar spine (6.7%) after 12 months of follow-up (0.791±0.178 vs. 0.791±0.140g/cm2, p=.003) and at three (5.7%) and five years (9%) of follow-up. Femoral neck BMD significantly increased after 3 years (11.1%): 0.648±0.148 vs. 0.720±0.138g/cm2; p=.01. In total hip, increase in BMD (10.1%) was significant after three years of treatment (0.706±0.118 vs. 0.720±0.138, p=.01). There were no significant differences in calcium and 25OH-vitamin D levels during follow-up, phosphorus significantly decreased after one year, and iPTH increased at three years. ß-crosslaps decreased after one year of treatment. Only one patient sustained new fractures. ConclusionsZoledronic acid is a convenient, safe, and effective treatment that increases BMD in adult patients with OI.

The influence of thyroid disorders on bone density and biochemical markers of bone metabolism.

Background Thyroid dysfunction, predominantly hyperthyroidism, has been previously linked to impaired bone mass density (BMD) and increased risk of fractures. On the other hand, data in the field of hypothyroidism (HT) are missing. The purpose of the present study was to investigate the impact of thyroid disorders on bone density serum and urine calcium (Ca) and phosphate (P) as well as serum osteocalcin and alkaline phosphatase and urine hydroxyproline in a series of post-menopausal women. Materials and methods The study was conducted in the Reproductive Endocrinology Outpatient Clinic of our hospital. A consecutive series of post-menopausal women was included, after excluding patients under hormone treatment (including levothyroxine supplementation) and those who received raloxifene, tamoxifen or tibolone during the study period as well as those who received treatment during the previous 12 months were excluded from the present study. Results Overall, 188 women were included in the present study. Among them, 143 women had normal thyroid function, 32 women had hyperthyroidism and 13 women had HT. Correlation of thyroid function indices with osteoporosis indices revealed statistically significant correlations between thyroxine (T4) and free triiodothyronine (T3) with T-, Z-scores and BMD. Logistic regression analysis concerning the impact of HT and hyperthyroidism on T-score, Z-score and bone mass density revealed that both pathological entities negatively affect bone health (p < 0.05). Conclusion The findings of our study suggest that not only hyperthyroidism, but also HT negatively affects BMD. Future studies should investigate this association and corroborate our findings.

Does idiopathic hypercalciuria affect bone metabolism during childhood? A prospective case-control study.

A limited number of studies have evaluated biochemical bone metabolism markers in children with idiopathic hypercalciuria, which in adults has been linked with osteopenia. Our aim was to investigate in children with idiopathic hypercalciuria biochemical markers of bone formation and resorption and the osteoprotegerin (OPG) and soluble receptor activator of nuclear factor kB ligand (sRANKL) system which is involved in the osteoclastogenesis process. A prospective study was conducted on 50 children with idiopathic hypercalciuria and 50 healthy age-, sex-, and Tanner stage-matched control subjects. Following the diagnosis, patients were requested to follow a 3-month dietary recommendation for idiopathic hypercalciuria. In patients, at diagnosis and at 3months of follow-up, and in controls, bone-related hormones and serum/urine biochemical parameters were studied. The bone formation markers (total ALP and osteocalcin) and the bone resorption markers (β-Crosslaps) and the OPG and sRANKL levels were determined. No differences were found in the bone formation markers or OPG and sRANKL between the children with idiopathic hypercalciuria and controls. The β-Crosslaps and the β-Crosslaps/osteocalcin ratio were higher in the patients at diagnosis than in controls (p = 0.019 and p = 0.029, respectively), with a trend to decrease after the 3-month dietary intervention. The initially increased 24-h urinary Ca in the patients decreased after the 3-month dietary intervention (p = 0.002). Children with idiopathic hypercalciuria had biochemical markers compatible with normal bone formation but increased bone resorption. After a 3-month dietary intervention, the trend observed towards decrease in the serum β-Crosslaps may reflect a beneficial response.

The effect of high- and low-impact physical activity on bone mineral density: A literature review

Physical activity is often associated with increased bone mineral density and decreased osteoporosis. Low-impact sports, have been described as having a neutral or negative effect on bone mass. However, the literature is not consensual in this practice. The objective is to identify the effects of high- and low-impact physical exercises on bone remodeling. Research and selection of the most relevant bibliography, published in the electronic database Pubmed (from January 1990 to January 2018), using as keywords “sport”, “bone mass” and “osteoporosis”. Were included 24 articles in this review. In all studies, bone mineral density was calculated by bone densitometry (whole body, femoral neck and lumbar spine) in individuals between 18 and 30 years of age. The review demonstrates that high-impact exercises appear to be important for the prevention of osteoporosis by increasing bone mass. Studies also suggest that regular practitioners of low-impact exercise, particularly swimming, have bone mineral density similar to those who do not exercise, and values lower than those who practice high-impact sports. These data suggest that physicians and other professionals accompanying swimming athletes should implement high-impact exercises before or after training in aquatic environments in order to improve swimmers bone mineral density. The effects described should not discourage the practice of the modality, which undoubtedly also provides positive body effects, but rather encourage a close look of the doctor who recommends regular practice of this modality, given the increased risk of osteoporosis development. Considering that the increase in latitude, with a consequent decrease in the sun exposure of the practitioners of out-door modalities, has reduced the differences found in bone mass among swimmers (in-door) and those with high-impact modalities, it seems fundamental to do more studies in this area to evaluate possible bias and using new evaluation methods as biochemical markers of bone metabolism.

Priorities of the diagnostic search for osteopenic conditions in patients with chronic pancreatitis and hypertensive disease

Objective — to study of the relationship between lactase gene polymorphism (LCT C-13910T) and the determination of the state of biochemical markers of bone metabolism (total and ionized serum calcium, osteocalcin) in the risk of osteopenic conditions in patients with comorbidity of chronic pancreatitis (CP) and hypertensive disease (HD). Materials and methods. The examinations involved 110 patients, from them 70 subjects with CP and HD (main group) and 40 patients with isolated CP (comparison group). The control group consisted of 78 practically healthy persons. All patients were representative by age and sex. Levels of biochemical markers of bone metabolism (total and ionized serum calcium, osteocalcin) and polymorphism of the LCT gene were studied. Results. The study of calcium fractions in the blood serum of patients with CP revealed its decrease, both due to the protein-bound and free pool that became apparent by the value of calcium index. When comparing the content of protein-bound calcium in the alcoholic genesis of the disease and the biliary etiology of CP, a tendency toward an increase in this fraction was noted in the toxic variant (2.36 ± 0.01 mmol/L versus 2.29 ± 0.01 mmol/L). The presence of CP resulted in the quantitative changes in the level of both forms of calcium (free and protein-bound), while practically not changing their relationship between the cell and the intercellular space, as indicated by the POCIC index. The addition of HD leads to a redistribution of this macroelement between biological fluids, which reflects the calcium index. Consequently, the comorbidity of CP and HD can be considered as an unfavorable factor in the formation of osteoporotic conditions. The changes in the blood serum levels of osteocalcin, indicator of bone tissue synthesis, have been established. Changes in the polymorphism of the LCT gene affected the incidence of lesion of the osteoarticular system: in carriers of the C-allele (77 % of patients) the predictors of osteopenic conditions were formed more frequently. Conclusions. The blood serum levels of calcium fraction are decreased in patients with recurrent CP, and it is more significant in case of comorbidity with HD. Violation in the ratio calcium pools in blood serum, which can be considered as one of the pathogenetic links of chronic arterial hypertension. The combined course of CP and HD is accompanied by changes in osteocalcin levels that can be used as a marker of the bone mineral density. The change in the polymorphism of the lactase gene in patients with CP and HD affects the incidence of lesion of the osteoarticular system, with the most unfavorable course observed in carriers of the C allele (77 % of patients) of the LCT gene.

Circulating sclerostin is not suppressed following a single bout of exercise in young men.

The aim of this study was to determine whether an acute bout of exercise reduces serum sclerostin under diet‐controlled conditions that stabilize the parathyroid hormone (PTH)‐1,alpha‐hydroxylase axis. Fourteen male volunteers (age, 22.1 years ± 4.05; BMI, 27.3 kg/m2 ± 3.8) completed a randomized crossover study in which they performed 10 sets of 10 repetitions of plyometric jumps at 40% of their estimated one‐repetition maximum leg press or a nonexercise control period. A calcium‐controlled diet (1000 mg/day) was implemented prior to, and throughout each study period. Blood was drawn for analysis of serum sclerostin, Dickkopf‐1, markers of bone metabolism (PTH, calcium), markers of bone formation (bone alkaline phosphatase, BAP; osteocalcin, OCN), and markers of bone resorption (tartrate‐resistant acid phosphatase 5b, TRAP5b; C‐telopeptide cross‐links of type I collagen, CTX) at baseline and 12, 24, 48, and 72 h following exercise or rest. Changes in serum concentrations were expressed as percentage change from individual baselines. Data were analyzed using a repeated measured linear mixed model to assess effects of time, physical activity status (rest or exercise condition), and the time by activity status interaction. There was a significant effect of exercise on OCN (P = 0.005) and a significant interaction effect for CTX (P = 0.001). There was no effect of exercise on any other biochemical marker of bone metabolism. A single bout of plyometric exercise did not induce demonstrable changes in biochemical markers of bone metabolism under conditions where dietary effects on PTH were controlled.

Changes in tibial bone microarchitecture in female recruits in response to 8 weeks of U.S. Army Basic Combat Training.

U.S. Army Basic Combat Training (BCT) is a physically-demanding program at the start of military service. Whereas animal studies have shown that increased mechanical loading rapidly alters bone structure, there is limited evidence of changes in bone density and structure in humans exposed to a brief period of unaccustomed physical activity. We aimed to characterize changes in tibial bone density and microarchitecture and serum-based biochemical markers of bone metabolism in female recruits as a result of 8 weeks of BCT. We collected high-resolution peripheral quantitative computed tomographic images of the distal tibial metaphysis and diaphysis (4% and 30% of tibia length from the distal growth plate, respectively) and serum markers of bone metabolism before and after BCT. Linear mixed models were used to estimate the mean difference for each outcome from pre- to post-BCT, while controlling for race/ethnicity, age, and body mass index. 91 female BCT recruits volunteered and completed this observational study (age = 21.5 ± 3.3 yrs). At the distal tibial metaphysis, cortical thickness, trabecular thickness, trabecular number, bone volume/total volume, and total and trabecular volumetric bone density (vBMD) increased significantly by 1-2% (all p < 0.05) over the BCT period, whereas trabecular separation, cortical tissue mineral density (TMD), and cortical vBMD decreased significantly by 0.3-1.0% (all p < 0.05). At the tibial diaphysis, cortical vBMD and cortical TMD decreased significantly (both -0.7%, p < 0.001). Bone strength, estimated by micro finite element analysis, increased by 2.5% and 0.7% at the distal tibial metaphysis and diaphysis, respectively (both p < 0.05). Among the biochemical markers of bone metabolism, sclerostin decreased (-5.7%), whereas bone alkaline phosphatase, C-telopeptide cross-links of type 1 collagen, tartrate-resistance acid phosphatase, and 25(OH)D increased by 10-28% (all p < 0.05). BCT leads to improvements in trabecular bone microarchitecture and increases in serum bone formation markers indicative of new bone formation, as well as increases in serum bone resorption markers and decreases in cortical vBMD consistent with intracortical remodeling. Together, these results demonstrate specific changes in trabecular and cortical bone density and microarchitecture following 8 weeks of unaccustomed physical activity in women.

Markov chain based simulation analysis of bone mineral density and changes in the level of biochemical markers of bone transformation in postmenopausal women

The changes in biochemical marker level of bone turnover of women before and after menopause and the relationship between it and bone mineral density (BMD) are analyzed. At the same time, the level of biochemical markers of bone metabolism of women with decreased BMD at premenopause and postmenopause is discussed. In this paper, the lumbar vertebrae (L1–L4) and femoral neck BMD of 225 female outpatients with osteoporosis were measured by dual-energy X ray bone sonometer. Among them, 185 menopause women at age of 45–65 were selected, and they were divided into normal bone mass group (50), decreased bone mass group (35) and osteoporosis group (100) according to BMD; in addition, 45 menopause women with decreased BMD at age of 51–70 were selected as postmenopause decreased-BMD group, and 25 non-menopause decreased-BMD women at age of 42–50 were selected as premenopause decreased-BMD group. Enzyme-linked immunosorbent assay was carried out to measure the level of serum cathespin K (Cathe K), bone alkaline phosphatase (B-ALP) and tartrate-resistant acid phosphatase (TRAP) of all patients; and electrochemiluminescence immunoassay is used to detect the level of osteocalcin, β-crosslaps and type-I procollagen N-terminal propeptide(PINP). The Cathe K, PINP, β-crosslaps, osteocalcin and TRAP level of postmenopausal women with osteoporosis are obviously higher than those of normal bone mass group (P 0.05). The Cathe K and TRAP level of serum in postmenopause decreased-BMD group were significantly lower than those in premenopausal women (P 0.05). Osteoporosis of postmenopausal women is high turnover. The changes in the levels of serum osteocalcin, β-crosslaps, PINP, B-ALP, TRAP and Cathe K could reflect the bone metabolism activity. The joint detection of BMD and bone-turnover biochemical marker is beneficial to the prevention, treatment and efficacy observation of the patients with osteoporosis.

The effect of levetiracetam on rat bone mineral density, bone structure and biochemical markers of bone metabolism

Some data suggest that exposure to levetiracetam (LEV) might be associated with a risk for bone health in the model of orchidectomized rats. The aim of this study was to investigate if there is any significant risk of LEV for bone health in the model of gonadally intact animals.Wistar rats were divided into a control group and a test group, 8 rats in each group. The control rats received standard laboratory diet (SLD) while rats in the test group were fed SLD enriched with LEV for 12 weeks. Dual energy X-ray absorptiometry was used to measure BMD of the whole body, femur and lumbar vertebrae. The concentrations of bone markers were examined in bone homogenate. Both femurs and tibiae were used for biomechanical testing.We found in the LEV group significantly decreased absolute and relative values of adipose tissue, higher whole-body BMD, higher right tibia cortical thickness, and a significantly increased concentration of Bone Alkaline Phosphatase (BALP) and cross-linked C-telopeptide of type I collagen (CTX-I) compared with the control group.The results suggest that the long-term administration of LEV in the model of gonadally intact rats does not have a negative effect on bone. Significant increase in BMD and cortical thickness of the right tibia may indicate even a positive influence on the properties of bone. Further studies will be necessary in animals and humans to confirm these findings.

The Relevance of Osteoclastic and Osteoblastic Activity Markers Follow-Up in Patients on Antiresorptive Osteoporosis Treatment

In general, markers of bone formation and markers of bone resorption are changing synergistically, so the monitoring of any osteoclastic and any osteoblastic marker should reflect the rate of bone transformation. The aim of the study is to monitor the bone metabolism markers in postmenopausal women with osteoporosis and osteopenia along with the variations caused by the effects of bisphosphonate therapy. The study involved 55 women of average age of 57.95 years, with osteopenia or osteoporosis. The patients with osteoporosis were treated with bisphosphonates (75 mg once a week); the laboratory tests were performed before the treatment and 6 months later. Patients with osteopenia were evaluated at the first assessment and 6 months later. The tests included bone densitometry, dual-energy X-ray absorptiometry, osteocalcin, alkaline phosphatase, collagen 1 N-terminal pro-peptide (P1NP), and beta C telopeptide of type I collagen (CTX). The mean T-score was −2.80 ± 0.63 before therapy and −2.64 ± 0.45 6 months later (p < 0.001). Women with osteoporosis had elevated levels of osteocalcin and P1NP at the first assessment, whereas the alkaline phosphatase level did not change with the treatment. After the introduction of antiresorptive therapy, the levels of osteocalcin and P1NP significantly decreased (p < 0.001). In the group with osteopenia, the biochemical markers activity were increased in both assessments. In patients with osteoporosis, Beta-CTX was increased in the first evaluation, and decreased after treatment (p = 0.001). The results indicate that the assessment of biochemical markers of bone metabolism show excellent results in the assessment of prognosis, monitoring the course and the response to various treatment regimens of osteoporosis and evince strong correlation with standard densitometry and dual-energy X-ray absorptiometry procedures. P1NP and CTX show better diagnostic applicability compared with osteocalcin and alkaline phosphatase. The analysis of the activity of biochemical markers may obtain early information on the therapeutic response, before definitive assessment by bone density measurements.

Effects of long-term oral administration of methimazole on femur and tibia properties in male Wistar rats

Physiological concentrations of thyroid hormones are crucial for skeletal growth and development, physiological bone turnover and bone homeostasis maintenance. Methimazole (1-methyl-2-mercaptoimidazole) is an antithyroid drug used for the treatment of the hyperthyroidism in humans and animals. The aim of the study was to determine effects of long-term oral methimazole treatment in male Wistar rats on biochemical bone metabolism markers, as well as morphological, geometric, densitometric and mechanical properties of femur and tibia. Experimental rats were subjected to 90-day-long oral treatment with 0.05% water solution of methimazole and were kept under identical environmental conditions and received the same diet ad libitum as the control group. Serum concentration of osteocalcin (OC) and C-terminal telopeptides of type I collagen (CTX-I) was determined. Femur and tibia were evaluated using quantitative computed tomography (QCT), peripheral QCT (pQCT) and three-point bending test. Final body weight of the experimental group was significantly decreased by 30% (P=0.01). Methimazole treatment significantly decreased serum OC concentration by 21% (P=0.02) and increased CTX-I concentration by 17% (P=0.06). Methimazole decreased morphological, geometric and densitometric parameters of femur and tibia in rats. Mechanical evaluation of bones has shown significantly decreased maximum elastic strength and ultimate strength of femur in rats treated with methimazole by 36% and 40% when compared to the control group (P<0.05). In conclusion, this study has shown that long-term treatment with methimazole inhibits bone formation and accelerates bone resorption processes. The observed negative effects of methimazole treatment on body weight gain and skeletal properties may be considered as additional possible side effects in living organisms to those reported in the previous studies. It may be suggested that long-term antithyroid treatment should be combined with prevention of the negative effects of methimazole on bone tissue and whole body metabolism.

Bone metabolism markers and angiogenic cytokines as regulators of human hematopoietic stem cell mobilization.

Hematopoietic stem cell (HSC) mobilization involves cleavage of ligands between HSC and niche components. However, there are scarce data regarding the role of bone cells in human HSC mobilization. We studied biochemical markers of bone metabolism and angiogenic cytokines during HSC mobilization in 46 patients' sera with lymphoma and multiple myeloma, by ELISA. Significant changes between pre-mobilization and collection samples were found: (1) Bone alkaline phosphatase (BALP) increased, indicating augmentation of bone formation; (2) Receptor activator of Nf-κB ligand/osteoprotegerin ratio (RANKL/OPG) increased, showing osteoclastic differentiation and survival; however, there was no evidence of increased osteoclastic activity; and (3) Angiopoietin-1/Angiopoietin-2 ratio (ANGP-1/ANGP-2) decreased, consistent with vessel destabilization. Poor mobilizers had significantly higher carboxy-terminal telopeptide of collagen type I (CTX) and lower ANGP-1 at pre-mobilization samples, compared to good ones. CTX, amino-terminal telopeptide of collagen type I (NTX) and ANGP-1 pre-mobilization levels correlated significantly with circulating CD34+ peak cell counts. Our results indicate that bone formation and vessel destabilization are the two major events during human HSC mobilization. Osteoblasts seem to be the orchestrating cells, while osteoclasts are stimulated but not fully active. Moreover, ANGP-1, CTX and NTX may serve as predictors of poor mobilization.

Characteristics of bone metabolism parameters in urban citizens

Aim. To reveal the features of age-dependent changes of bone tissue in urban citizens. &#x0D; Methods. The study of bone metabolism parameters was performed on 629 healthy subjects of middle, elderly and senile age living in Vladivostok for longer than 10 years (55 males and 573 females). Concentration of C-terminal telopeptide of type II collagen, osteocalcin, calcitonin, parathyroid hormone, 1,25(OH)2-vitamin D, and bone isoenzyme of alkaline phosphotase were measured by ELISA. Concentration of C-terminal telopeptide of type I collagen was measured in urine. &#x0D; Results. Biochemical markers of bone metabolism in older age groups are different from the parameters of middle age. In the second period of middle age statistically significant decrease of C-terminal telopeptides level (z=2.88, p

High dose vitamin D supplementation does not affect biochemical bone markers in multiple sclerosis \u2013 a randomized controlled trial

BackgroundPeople with multiple sclerosis have high risk of osteoporosis and fractures. A poor vitamin D status is a risk factor for MS, and vitamin D supplementation has been recommended both to prevent MS progression and to maintain bone health.MethodsWe assessed the effect of 20,000 IU vitamin D3 weekly compared to placebo on biochemical markers of bone metabolism in 68 persons with relapsing remitting multiple sclerosis.ResultsSerum levels of 25-hydroxyvitamin D more than doubled in the vitamin D group, and parathyroid hormone decreased in the vitamin D group compared to the placebo group at week 48 and week 96. There was however no effect on bone formation as measured by procollagen type I N propeptide (PINP), or on bone resorption as measured by C-terminal cross-linking telopeptide of type I collagen (CTX1). Neither PINP nor CTX1 predicted bone loss from baseline to week 96.ConclusionsThese findings corroborate the previously reported lack of effect of weekly high dose vitamin D supplementation on bone mass density in the same patients, and suggest that such vitamin D supplementation does not prevent bone loss in persons with MS who are not vitamin D deficient.Trial registrationThe trial was registered at ClinicalTrials.gov on April 4 2008, registration number NCT00785473.

A randomized multicenter clinical trial of 99 Tc-methylene diphosphonate in treatment of rheumatoid arthritis.

To investigate the efficacy and safety of technetium-99 conjugated with methylene diphosphonate (99 Tc-MDP, Yunke Pharmaceutical industry) in the treatment of rheumatoid arthritis (RA). A total of 120 patients with active RA were randomly divided into three groups: Group A (receiving oral meloxicam tablets); Group B (receiving intravenous drip of 99 TC-MDP); Group C (receiving combination treatment of intravenous drip of 99 Tc-MDP and oral meloxicam tablets). The main clinical and laboratory parameters were evaluated at baseline and after 14 days of therapy. After 14 days of treatment, American College of Rheumatology 20 response was 15.62%, 34.04% and 48.78% in the three groups, respectively. The incidence of adverse events in three groups were 3.13%, 8.51% and 9.76% respectly, and has no significant difference. In addition, biochemical markers of bone metabolism including bone alkaline phosphatase (BAP), tartrate resistant acid phosphatase (TRAP) and dickkopf-1 (DKK-1), all improved in the three groups, although more significant in Group B than Group A, and more significant in the combination group than monotherapy groups. 99 Tc-MDP has good efficacy and safety in the treatment of active RA patients; the benefit was more remarkable when 99 Tc-MDP was combined with NSAIDs. 99 Tc-MDP may also have potential to improve bone metabolism.

The effect of low-dose intravenous bisphosphonate treatment on osteoporosis in children with quadriplegic cerebral palsy.

PurposeQuadriplegic children with cerebral palsy are more susceptible to osteoporosis because of various risk factors that interfere with bone metabolism. Pamidronate is effective for pediatric osteoporosis, but there are no guidelines for optimal dosage or duration of treatment in quadriplegic children with osteoporosis. We aimed to evaluate the efficacy of low-dose pamidronate treatment in these patients.MethodsTen quadriplegic patients on antiepileptic drugs (6 male, 4 female patients; mean age, 10.9±5.76 years), with osteoporosis and gross motor function classification system level V, were treated with pamidronate (0.5–1.0 mg/kg/day, 2 consecutive days) every 3–4 months in a single institution. The patients received oral supplements of calcium and vitamin D before and during treatment. The lumbar spine bone mineral density (BMD) z score and biochemical markers of bone metabolism were measured regularly during treatment.ResultsThe main underlying disorder was perinatal hypoxic brain damage (40%, 4 of 10). The mean cumulative dose of pamidronate was 4.49±2.22 mg/kg/yr, and the mean treatment period was 10.8±3.32 months. The BMD z score of the lumbar spine showed a significant increase from −4.22±1.24 before treatment to −2.61±1.69 during treatment (P=0.008). Alkaline phosphatase decreased during treatmentn (P=0.037). Significant adverse drug reactions and new fractures were not reported.ConclusionLow-dose pamidronate treatment for quadriplegic children with cerebral palsy increased lumbar BMD and reduced the incidence of fracture.

Clinical-laboratory findings of bone metabolism in healthy premature and full-term neonates: preliminary results.

Premature infants are a major risk group for bone metabolic disorders. The purpose of this study is to clarify certain aspects of bone metabolism in healthy preterm and full-term neonates. Forty neonates (20 preterm and 20 full-term) were the material of the study. For each neonate demographic data (gender, gestational week) and anthropometric data (body weight) were recorded. Blood samples were collected and biochemical markers of bone metabolism (serum ALP, Ca, P, Mg) were immediately estimated. According to the results there is a statistically significant difference in average ALP of preterm neonates compared to full term neonates. Slightly higher values of Ca, P, Mg occurred in premature neonates while there was a statistically significant difference in the weeks of gestation and body weights between the two groups. It is typical in premature neonates the decrease in levels of ALP by the weeks of gestation and the stable levels of Ca. Gestational week seems to positively affect P and Mg levels in preterm neonates. Conclusively from our study's results arises that the week of gestation and not so much the body weight influence the alterations of bone biochemical biomarkers in healthy premature newborns. It seems that very premature neonates have high levels of serum ALP in decompensation of lower levels of Mg and P from all the newborns in this study. Therefore in very premature neonates, it is recommended to estimate serum ALP, Mg and P for assessment of bone turnover.

Low‑molecular weight fucoidan inhibits the differentiation of osteoclasts and reduces osteoporosis in ovariectomized rats.

Fucoidan is a type of sulfated polysaccharide isolated from seaweed. The present study used ovariectomized Sprague‑Dawley rats, which were treated with fucoidan. The effects of fucoidan on bone metabolism, density and microarchitecture were assessed using micro‑computed tomography (CT), histomorphometric analysis, biochemical markers of bone metabolism (Serum procollagen typeI N propeptide and C‑terminal telopeptide‑1) and tests of mechanical competence of the femur. In addition, the effects of low‑molecular weight fucoidan (LMWF) on invitro cultured osteoclasts were examined, in order to determine the mechanisms underlying LMWF‑induced osteoclastic inhibition. In ovariectomized rats, LMWF increased femoral bone density. Micro‑CT scan also revealed that LMWF prevented microarchitectural deterioration and histomorphometric analysis determined that LMWF increased trabecular bone number and reduced the surface of bone resorption. In addition, LMWF reduced the high bone turnover rate, and improved the mechanical properties of the femur in ovariectomized rats. Invitro experiments revealed that LMWF inhibited the receptor activator of nuclear factor κB ligand (RANKL) and macrophage colony‑stimulating factor‑induced differentiation of RAW264.7cells into tartrate‑resistant acid phosphatase (TRAP)‑positive osteoclasts, and reduced the bone resorption surface of the osteoclasts. Reverse transcription‑quantitative polymerase chain reaction demonstrated that LMWF inhibited mRNA expression of TRAP, matrix metallopeptidase‑9, nuclear activator of activated T‑cells1, and osteoclast‑associated immunoglobulin‑like receptor, which are components of the signaling pathway for osteoclast differentiation. LMWF had no effect on RANK mRNA expression. In conclusion, the present study confirmed that LMWF inhibited osteoclast differentiation and bone resorption, and may be a potential treatment for osteoporosis in ovariectomized rats.

Lenalidomide, Adriamycin, and Dexamethasone (RAD) As Induction Therapy for Patients with Newly Diagnosed Multiple Myeloma Who Are Eligible for Autologous Transplantation (ASCT): A Phase 2 Study from the Greek Myeloma Study Group

RAD combination is highly effective for patients with relapsed/refractory multiple myeloma (MM), but there is limited data for its efficacy on newly-diagnosed patients (NDMM). Although lenalidomide exerts its function, at least partially, through the inhibition of interactions between myeloma and stromal cells, there is no information for the effect of RAD on bone metabolism and angiogenesis in NDMM. The primary endpoint of this phase 2 study was the assessment of overall response rate (ORR) after 4 cycles of RAD induction in NDMM patients who are eligible for ASCT. Secondary endpoints included toxicity, PFS, TTP, and TtNT. Exploratory endpoints included: i) the yield of stem cell collection after RAD; ii) the effects of RAD on biochemical markers of bone metabolism: CTX, TRACP-5b, bone-alkaline phosphatase (bALP), P1NP, osteocalcin, soluble RANKL, osteoprotegerin (OPG) and dickkopf-1 (Dkk-1) and iii) the effects of RAD on angiogenic cytokines: angiopoietin- (Angp) 1 & -2, angiogenin (Ang), VEGF and bFGF. Main inclusion criteria were: i) NDMM patients eligible for ΑSCT; ii) Κarnofsky performance status ≥ 60; iii) platelet count ≥100x10 9 /L, neutrophil count ≥1.5x10 9 /L. Main exclusion criteria included: i) serum ALT or AST >3-fold or bilirubin >2-fold the upper normal limit; ii) eGFR 2 , on days 1-4 of each cycle. RAD was repeated on day 28 if the neutrophil count was >1.5x10 9 /L and the platelet count was >50x10 9 /L. All patients received anti-coagulation with LMWH and monthly zoledronic acid. Between November 2014 and February 2016, 45 patients were enrolled. Median age was 56 years (range: 37-69 years); 28 (62%) patients had IgG, 12 (27%) IgA, 4 (9%) light chain only and one IgM MM; 18 (40%) patients had ISS-1, 22 (49%) ISS-2 and 5 (11%) ISS-3 disease. Osteolytic lesions were present in 33 (73%) patients. Seven (15.5%) patients had elevated serum LDH (>250 U/l) and 3 (6.6%) had hypercalcemia (>11 mg/dl). All but one patient completed 4 cycles of RAD. Best response included one (2.2%) CR, 8 (17.8%) VGPRs, 21 (46.7%) PRs, for an ORR of 66.7%, while 14 (31%) patients had stable disease and one progressed during the 4 th cycle of treatment. Adverse events of grade 3 or 4 included: anemia (4 patients, 9%), neutropenia (3 patients, 6.6%), febrile neutropenia (one patient), hypocalcemia (one patient), acute renal failure (one patient), pulmonary embolism (one patient), fatigue (one patient) and pathological fracture (one patient). Forty (89%) patients had adequate stem cell collection post-RAD induction (mean±SD: 8.94±6.50 x10 6 /kg CD34+ cells). Three patients failed to collect adequate number of stem cells and two patients refused to proceed to stem cell collection. Patients at baseline had elevated levels of CTX, TRACP-5b, sRANKL/OPG, Dkk-1, Ang, VEGF, VEGF-A, bFGF and reduced levels of Angp-1/Angp-2, bALP and P1NP compared to 30 healthy subjects of similar age and gender (p We conclude that RAD resulted in successful induction for NDMM patients and produced an ORR of approximately 67%. RAD reduced bone resorption and increased bone formation; the latter has not been previously described with lenalidomide-based regimens. Furthermore, RAD reduced angiogenic cytokines and this supports the action of the regimen also through the disruption of the interactions between myeloma and stromal cells. Disclosures Terpos: Celgene: Honoraria; Amgen: Consultancy, Honoraria, Other: Travel expenses, Research Funding; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: Travel expenses, Research Funding; BMS: Consultancy, Honoraria; Novartis: Honoraria; Genesis: Consultancy, Honoraria, Other: Travel expenses, Research Funding. Katodritou: Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Genesis: Honoraria, Research Funding; Takeda: Consultancy, Honoraria. Symeonidis: Amgen: Honoraria; Roche: Honoraria; Takeda: Consultancy, Honoraria; Genesis: Honoraria. Kourakli: Genesis: Consultancy, Honoraria. Kastritis: Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Genesis: Consultancy, Honoraria. Dimopoulos: Genesis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees.

Biochemical markers of bone metabolism during early orthodontic tooth movement with aligners.

To evaluate the expression of receptor activator of nuclear factor-kappa ligand (RANKL), osteoprotegerin (OPG), osteopontin (OPN), interleukin 1β (IL-1β), and transforming growth factor ß1 (TGF-ß1) in the gingival crevicular fluid (GCF) of teeth subjected to orthodontic forces released by aligners. A total of 10 healthy, adult patients were selected to participate in this split-mouth study. The treatment plan was designed to obtain only one movement with the first aligner: distalization of a second molar. GCF samples were obtained from pressure and tension sites of the test tooth and from the mesiobuccal and distobuccal sites of the control tooth. The GCF sample volumes were measured using a Periotron 8000. Levels of TGF-β, IL-1β, RANKL, OPG, and OPN were measured by enzyme-linked immunosorbent assay. IL-1β showed a significant increase at the pressure sites after 1 week and 3 weeks with respect to baseline (P < .05) compared with control sites. The kinetics of TGF-1β and OPN were characterized by a significant increase at the tension sites of the test teeth (P < .05) after 3 weeks from the application of orthodontic force. The RANKL level was significantly increased at pressure and tension sites after 1 hour and after 1 week from the application of the orthodontic forces (P = .023 and P = .043, respectively). An increased concentration of bone modeling and remodeling mediators at the pressure sites (IL-1β, RANKL) and tension sites (TGF-1β, OPN) was observed. These scenarios are compatible with previous in vivo and in vitro studies investigating the biological effects of orthodontic tooth movement.