Bone-specific Alkaline Phosphatase Concentrations Research Articles

#1443 Bone and mineral metabolism in patients with nephropathic cystinosis as a function of age and eGFR

Abstract Background and Aims Cystinosis-associated metabolic bone disease (CMBD) is a major challenge in the treatment of patients with infantile nephropathic cystinosis (NC). Study data are limited due to small case numbers, lack of adults or patients on renal replacement therapy and/or inadequate assessment of bone health. Method We investigated markers for CMBD in all age groups (1-44 years; 61% children) and CKD stages 1-5D/T in the largest NC cohort to date with 103 German and Austrian NC patients. Skeletal comorbidity and concentrations of fibroblast growth factor 23 (FGF23), the osteoblast marker bone-specific alkaline phosphatase (BAP), the bone remodeling inhibitor sclerostin, the osteoclast marker tartrate-resistant acid phosphatase 5b (TRAP5b), the soluble receptor activator of nuclear factor kappa B ligand (sRANKL), osteoprotegerin (OPG) and the sRANKL/OPG ratio as surrogates for the regulation of osteoclastogenesis by osteoblasts were determined by ELISA, converted into age- and sex-specific z-scores and compared as a function of eGFR. Multivariable regression analyses were used to identify specific influencing factors associated with biochemical and clinical findings in pre-transplant NC patients. Results Skeletal complications occurred in two-thirds of patients, with the risk being five times higher in adults than in children. Pediatric and adult NC patients with CKD stages 1-4 showed hypophosphatemia and hypocalcemia associated with suppressed FGF23 and PTH levels and elevated BAP concentrations. This was associated with age, eGFR and treatment with phosphate and active vitamin D, suggesting more vigorous treatment of Fanconi syndrome in pre-transplant patients. As indicated by the increased TRAP5b and decreased sRANKL/OPG ratio, osteoclast activity was increased despite counterregulation by osteoblasts, which in conjunction with increased sclerostin activity may have contributed to the progressive bone loss and skeletal comorbidity in our patient cohort. Conclusion Bone health in NC progressively deteriorates with age, largely due to persistent rickets/osteomalacia associated with inadequate treatment of Fanconi syndrome and increased osteoclast activity despite osteoblast counterregulation via OPG/RANKL. Our data suggest that a primary osteoclast defect in NC promotes increased bone resorption, limiting maximal bone mass and leading to progressive bone loss and increased skeletal comorbidity.

Osteoprotegerin and receptor activator of the nuclear factor kappa B ligand (RANKL) in healthy pubertal girls - relationships with physical growth and classical bone turnover markers.

Osteoprotegerin (OPG) is a trap receptor for the receptor activator of the nuclear factor kappa B ligand (RANKL). We aimed to determine the OPG and free soluble RANKL (sRANKL) concentrations in girls during puberty and their relationships with pubertal stage, growth rate and serum concentrations of estradiol, as well as classical bone formation (N-terminal propeptide of type I collagen (PINP), bone-specific alkaline phosphatase (BALP), osteocalcin (OC)) and bone resorption (C-terminal telopeptide of type I collagen (CTX)) markers. The semi-longitudinal study involved 88 healthy girls, aged 11.8-13.2 years. Their weight and height were measured twice at one-year intervals. Pubertal stages were assessed using the Tanner (T) scale. Blood samples were taken at the first examination. Serum concentrations of OPG, sRANKL, CTX and BALP were determined by enzyme-linked immunosorbent assay, estradiol and PINP by radioimmunoassay and osteocalcin by immunoradiometric assay. The one-year increase in height and weight of girls in the T2 and T3 pubertal stages was greater than that of girls in the T4 stage (p=0.000, p<0.03). OPG concentrations (T2: 4.04±0.62; T3: 4.31±0.79; T4: 4.46±0.84 pmol/L) sRANKL concentrations (T2: 0.22 (IQR 0.09-0.54); T3: 0.42 (IQR 0.22-0.79); T4: 0.35 (IQR 0.16-1.04) pmol/L) and sRANKL/OPG ratios (T2: 0.05 (IQR 0.03-0.13); T3: 0.11 (IQR 0.05-0.19); T4: 0.09 (IQR 0.05-0.19) did not differ significantly between pubertal stages. Concentrations of PINP, CTX, BALP and OC were higher in girls at T3 stage than at the T4 stage (p=0.000, p=0.001, p=0.046, p=0.038; respectively). Concentrations of sRANKL and OPG did not correlate with body weight, height, growth rate, or concentrations of estradiol, PINP, CTX, BALP and OC. There were correlations between the increase in height over one year and the concentrations of PINP (r=0.499, p=0.000), CTX (r=0.311, p=0.003) and BALP (r=0.224, p=0.036), as well as of estradiol (r=-0.473, p=0.000). Unlike PINP, OC, BALP, CTX or estradiol concentrations, sRANKL and OPG concentrations do not change in girls during puberty. Neither OPG nor sRANKL concentrations correlate with somatic characteristics and classical bone turnover markers concentrations.

Serum Bone-Specific Alkaline Phosphatase as an indicator of the quantity of callus formation in mandibular fracture patients seen in a Nigerian Teaching Hospital

It is important to evaluate the level of bone-specific alkaline phosphatase as it relates to the quantity of callus formed in mandibular fracture healing. The objective of the present study was to assess Serum Bone-Specific Alkaline Phosphatase (BsALP) as an indicator of callus formation in patients with mandibular fracture and determine the relationship between BsALP and callus formation using two treatment methods. Fifty-five patients with isolated mandibular fractures were enrolled. BsALP was measured at presentation, 3rd and 6th week. The patients were recruited into two treatment groups: Closed Reduction with Mandibulomaxillary Fixation (MMF) and Open Reduction and Internal Fixation (ORIF). The Callus Index was measured at 3rd and 6th week after treatment using digital postero-anterior view of the jaws on DICOM viewer software. The mean value of BsALP was 26.2±9.5 ng/mL. BsALP concentration in patients with double site fractures was higher than those with a single fracture, p=0.102. Peak serum BsALP observed in the 3rd week post-intervention was (28.1±8.2 ng/mL). Statistically significant differences were observed between the BsALP concentration in the 3rd and 6th week, and between BsALP concentration at presentation and 6th week, p&lt;0.001, respectively. There was no significant correlation between the Callus Index and mean serum BsALP at 6 weeks (r=-0.08, p=0.580). MMF treatment group had higher levels of serum BsALP compared with ORIF group in the 3rd week (p=0.14) and in the 6th week (p=0.18). BsALP is an indicator of the amount of callus formed in patients treated for mandibular fractures. Hence, it could be used as an adjunct to monitor the healing of mandibular fractures.

Efficacy and safety of radiofrequency ablation versus parathyroidectomy for secondary hyperparathyroidism in dialysis patients: a single-center retrospective study

We compared the efficacy and safety of ultrasound (US)-guided radiofrequency ablation (RFA) and parathyroidectomy (PTX) for the treatment of secondary hyperparathyroidism (SHPT). In this single-center retrospective study, we divided patients into PTX (n = 53) and RFA (n = 47) groups. The primary outcome was the proportion of patients who achieved the target intact parathyroid hormone (iPTH) concentration range (≤ 300 pg/mL). Secondary outcomes were the differences in the changes in iPTH, calcium, and phosphorus levels over time and prognosis. iPTH concentrations of 82.1% and 64.1% in the PTX and RFA groups, respectively, were within the recommended range at the endpoint (P = 0.07). iPTH concentrations in the PTX and RFA groups dropped sharply after treatment (82 ± 163 pg/mL and 280 ± 307 pg/mL, respectively, P < 0.001). There was no difference in the trends of iPTH, calcium, and phosphorus levels between the two groups (P > 0.05). Survival analysis revealed no differences in all-cause mortality and cumulative response rate between the two groups (P = 0.90, P = 0.14, respectively). Notably, the incidence of infection and length of the hospital stay in the RFA group were significantly lower. The preoperative bone-specific alkaline phosphatase concentration was a risk factor for postoperative hypocalcemia. US-guided RFA is minimally invasive and compared to PTX in terms of long-term efficacy and complications in the treatment of severe SHPT in maintenance dialysis patients. It may be used as an alternative technique to PTX; however, further studies are needed.

Effects of Gastric Bypass and Sleeve Gastrectomy on Bone Mineral Density and Bone Turnover Markers: A Systematic Review and Meta-Analysis.

There is a growing interest in the post-operative bone-related effects of bariatric surgery. However, little is known about the comparative effects of the most commonly performed bariatric procedures, namely Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). To systematically assess the differences in areal bone mineral density (aBMD) and biochemical and hormonal markers of bone metabolism among patients undergoing RYGB and SG. We conducted a systematic review and meta-analysis of studies aBMD at different sites, as well as bone-specific alkaline phosphatase (BALP), 25-OH-vitamin D, calcium and parathyroid hormone (PTH) after RYGB and SG. Fourteen studies were included (717 patients, 50.63% in the RYGB arm). Based on data collected at 1year, 2years and > 2years, there were no significant differences in aBMD measurements at the total hip, lumbar spine, femoral neck, and the whole body with no statistical heterogeneity among different comparisons. Patients in the RYGB group showed significantly higher concentrations of BALP at 1year (SMD = 0.52, 95%CI, 0.23-0.81, p = 0.0004) and PTH at > 2years of follow-up (SMD = 0.68, 95%CI, 0.31-1.05, p = 0.0003) compared to the SG group. There were no significant differences in aBMD measurements at the hip, lumbar spine, femoral neck, and the total body following RYGB and SG procedures. However, BALP and PTH concentrations were significantly higher after RYGB surgeries compared to SG. Attention should be paid to patients undergoing RYGB to prevent the expected skeletal fragility over time.

Effects of strawberries on bone biomarkers in pre- and stage 1-hypertensive postmenopausal women: a secondary analysis.

Postmenopausal women experience an increase in bone remodeling with the rate of bone resorption superseding the rate of bone formation. This results in a net bone loss with a subsequent increased risk for osteoporosis and fractures. High blood pressure (BP) has been associated with loss of bone mineral density and increased propensity to fractures. Strawberries are rich in polyphenols, which have been shown to have anti-hypertensive and bone-protective properties. Thus, we examined whether daily intake of strawberries would positively affect biomarkers of bone metabolism in postmenopausal women with pre- and stage 1-hypertension. Participants (age: 59 ± 6 years; body mass index: 31.5 ± 4.1 kg m-2; systolic BP: 140 ± 13 mmHg) were randomly assigned to consume (1) 50 g of freeze-dried strawberry powder (FDSP), (2) 25 g FDSP + 25 g of placebo powder, or (3) 50 g placebo powder for eight weeks. Results indicate a significant time-by-treatment interaction (P = 0.04) for serum insulin-like growth factor (IGF)-1, a hormone that plays a major role in bone formation. Serum concentrations of bone-specific alkaline phosphatase, a marker of bone formation, and tartrate-resistant acid phosphatase-5b, a specific marker of bone resorption, were not affected by FDSP compared to placebo. Although not statistically significant, after eight weeks, osteocalcin increased in the 50 g FDSP group with a large effect size (d = 0.6) when compared to the placebo-control group. Adiponectin increased by 5% and 6% in the 25 g and 50 g FDSP groups, respectively, while it declined in the placebo-control group by 25% (P = 0.03 for time-by-treatment interaction). Our findings suggest that consumption of 25 g FDSP increases IGF-1 in postmenopausal women with pre- and stage 1-hypertension. However, further studies are needed to assert the effectiveness of a strawberry intervention for bone health.

Zanthoxylum piperitum alleviates the bone loss in osteoporosis via inhibition of RANKL-induced c-fos/NFATc1/NF-κB pathway

BackgroundThe fruit of Zanthoxylum piperitum (ZP) is an herbal medicine as well as a spice agent in Asia to treat carminative, stomachic, anthelmintic and degenerative diseases. Z. piperitum was reported to have anti-oxidant, anti-inflammatory, anti-osteoarthritic and osteosarcoma proliferation-control effects. Purpose and Study designThis study was conducted to determine the anti-osteoporotic effects and mechanisms of action of ZP. MethodsFemale ICR mice underwent ovariectomies (OVX) and were orally administered ZP at 1, 10 and 100 mg/kg for 6 weeks. The femoral and tibial bones were assessed by dual‐energy X‐ray absorptiometry and histology to analyze the bone mineral density (BMD) and the number of osteoclasts. Raw 264.7 cells were stimulated by 100 ng/ml receptor activator of nuclear factor-κB ligand (RANKL) for 7 days in the presence of ZP. RANKL-induced signaling molecules were analyzed in osteoclasts. ResultsThe levels of femoral and tibial BMD were significantly increased by ZP administration. Serum biomarkers such as osteocalcin, calcium, alkaline phosphatase and bone-specific alkaline phosphatase concentrations were markedly recovered to normal levels in ZP-treated osteoporotic mice. In addition, the number of osteoclasts in the head, trochanter and body of the femur was obviously decreased in the ZP treatment groups. Moreover, ZP treated-cells showed a reduction in the number of TRAP-positive multinuclear cells in RANKL-stimulated Raw 264.7 cells. ZP decreased the RANKL-activated NFATc1 and c-fos, transcription factors of osteoclast formation. The nuclear translocation of NF-κB and phosphorylation of ERK42/44 were inhibited by the ZP treatment in RANKL-induced osteoclasts. ConclusionCollectively, ZP exerts its inhibitory effect against bone resorption by regulating RANKL-mediated c-fos/NFATc1/NF-κB in osteoclast. ZP may prove to be a therapeutic agent for osteoporosis.

Age-related bone loss is associated with FGF21 but not IGFBP1 in healthy adults.

What is the central question of this study? Fibroblast growth factor 21 (FGF21) plays important therapeutic roles in metabolic diseases but is associated with bone loss, through insulin-like growth factor binding protein1 (IGFBP1), in animals. However, the effect of the FGF21-IGFBP1 axis on age-related bone loss has not been explored in humans. What is the main finding and its importance? Using 'genetically linked' parent and child family pairs, we show that the FGF21 concentration, but not the IGFBP1 concentration, is higher in older than in younger adults. Our results suggest that age-associated decline in bone mineral density is associated with FGF21 and increased bone turnover but not likely to involve IGFBP1 in healthy humans. ABSTRACT: Bone fragility increases with age. The fibroblast growth factor21 (FGF21)-insulin-like growth factor binding protein1 (IGFBP1) axis regulates bone loss in animals. However, the role of FGF21 in mediating age-associated bone fragility in humans remains unknown. The purpose of this study was to explore the FGF21-regulatory axis in bone turnover and the age-related decline in bone mineral density (BMD). Twenty 'genetically linked' family (parent and child) pairs were recruited. Younger adults were 22-39 years old and older adults 60-71 years old. The BMD and serum concentrations of FGF21, IGFBP1, receptor activator of nuclear factor-κB ligand (RANKL), tartrate-resistant acid phosphatase5b (TRAP5b) and bone-specific alkaline phosphatase (BAP) were measured. Older adults had 10-18% lower BMD at the hip and spine (P<0.008) and a twofold higher FGF21 concentration (P<0.001). The IGFBP1 concentration was similar in younger and older adults (P=0.961). The RANKL concentration was 44% lower (P=0.006), whereas TRAP5b and BAP concentrations were 36 and 31% higher (P=0.01 and P=0.004), respectively, in older adults than in younger adults. Adjusting for sex did not affect these results. The FGF21 concentration was negatively correlated with BMD at the spine (r=-0.460, P=0.003), but not with the IGFBP1 concentration (r=-0.144, P=0.374). The IGFBP1 concentration was not correlated with BMD at the hip or spine (all P>0.05). In humans, FGF21 might be involved in the age-associated decline in BMD, especially at the spine, through increased bone turnover. IGFBP1 is unlikely to be the downstream effector of FGF21 in driving the age-associated decline in BMD and in RANKL-associated osteoclast differentiation.

Correlation of Fgf23 and Balp with Bone Mineral Density in Hemodialysis Patients.

SummaryBackgroundChronic kidney disease (CKD) is associated with numerous complications such as bone mineral disorder. The aim of our study was to analyze the correlation of bone turnover markers with Bone Mineral Density (BMD) measurements in Tunisian end stage renal diseases (ESRD) patients.MethodsThis study included 100 ESRD Tunisian patients. Their estimated glomerular filtration rate (eGFR) was < 15 mL × min-1 × (1.73 m2)-1, which requires hemodialysis. Bone-specific alkaline phosphatase (BALP) serum concentration was determined with a chemiluminescence immunoassay. Fibroblast Growth Factor 23 (FGF23) serum was assessed by Enzyme-Linked Immunosorbent Assay method. The serum levels of 25-Hydroxyvitamin D (25(OH)D), intact parathyroid hormone (iPTH) and Beta cross-laps (CTX) was measured by Electrochemiluminescence Technology. DEXA (dual-energy x-ray absorptiometry) technique was used to evaluate BMD.ResultsWe observed a statistically significant negative correlation between BALP levels and total body BMD (r = -0.268; P = 0.015) particularly in femoral neck (FN) (r = -0.219; P = 0.037). BALP concentrations were negatively associated with total BMD especially in FN for patients with BMI < 30, FGF23 concentrations were also negatively correlated with BMD in lumbar spine site (LS) (r = -0.209; P = 0.046). For osteopenic patients we found an inverse correlation between 25(OH)D concentrations and BMD in LS position (r = -0.336; P = 0.038). In men group, we have also found a negative correlation between iPTH and total BMD (r = -0.326; P = 0.015). However we found a positive correlation between calcium expression and BMD in LS site (r = 0.270; P = 0.031).ConclusionsFGF23 and BALP can predict bone loss in ESRD through their strong correlation with BMD in LS and FN sites respectively.

Blood biochemical parameters of bone metabolism in cows and calves kept in a beef suckler system during the early postpartum period

The early lactation and early neonatal period are characterised by intense changes in bone metabolism. The aim of this study was to evaluate blood biochemical parameters of bone metabolism during early lactation in cows and neonatal calves. The study was carried out on 13 Simmental cows and 13 beef suckler calves in cow-calf operations. Blood samples were obtained at 6 time points: 6, 12 and 48 h and 7, 14 and 30 d postpartum (pp). An increase in the concentration of total calcium (tCa) of cows 14 d pp (P = 0.04), an increase in the concentration of inorganic phosphorus (iP) 12 and 48 h pp (P = 0.001, P = 0.002, respectively), an increase in bone specific alkaline phosphatase (BALP) and parathyroid hormone (PTH) concentration 7 d pp (P = 0.02, P = 0.02, respectively) and a decrease of total alkaline phosphatase (TALP) activity during the first 14 d pp (P < 0.05) indicated that the early puerperium in cows is an intense period of change in bone and mineral metabolism. An increase of iP and magnesium (Mg) concentrations in calves at 48 h pp (P < 0.01, P < 0.01, respectively), a decrease in BALP concentration at 48 h pp (P = 0.01), higher TALP activity at 30 d pp (P = 0.02) and decreased PTH at 7 d pp (P = 0.04), indicated bone formation and growth in calves. Our results in cows indicated increased bone resorption and Ca loss through milk production. In neonatal calves we demonstrated high bone turnover during the period of intensive growth and development. The results contribute to a better understanding of bone metabolism in the early postpartum period of cows and neonatal period of calves, and also towards the elucidation of disorders of bone metabolism after calving.

Bone turnover, calcium homeostasis, and vitamin D status in Danish vegans.

A vegan diet has been associated with increased bone fracture risk, but the physiology linking nutritional exposure to bone metabolism has only been partially elucidated. This study investigated whether a vegan diet is associated with increased bone turnover and altered calcium homeostasis due to insufficient intake of calcium and vitamin D. Fractionated and total 25-hydroxyvitamin D (25(OH)-D), parathyroid hormone (PTH), calcium, and four bone turnover markers (osteocalcin, N-terminal propeptide of type I procollagen (PINP), bone-specific alkaline phosphatase (BAP), and C-terminal telopeptide of type I collagen (CTX)) were measured in serum from 78 vegans and 77 omnivores. When adjusting for seasonality and constitutional covariates (age, sex, and body fat percentage) vegans had higher concentrations of PINP (32 [95% CI: 7, 64]%, P = 0.01) and BAP (58 [95% CI: 27, 97]%, P < 0.001) compared to omnivores, whereas CTX (30 [95% CI: -1, 72]%, P = 0.06) and osteocalcin (21.8 [95% CI: -9.3, 63.7]%, P = 0.2) concentrations did not differ between the two groups. Vegans had higher serum PTH concentration (38 [95% CI: 19, 60]%; P < 0.001) and lower 25(OH)-D serum concentration (-33 [95% CI: -45, -19]%; P < 0.001), but similar serum calcium concentration (-1 [95% CI: -3, 1]%, P = 0.18 compared to omnivores. Vegans have higher levels of circulating bone turnover markers compared to omnivores, which may in the long-term lead to poorer bone health. Differences in dietary habits including intake of vitamin D and calcium may, at least partly, explain the observed differences.

Bone health in long-term gastric cancer survivors: A prospective study of high-dose vitamin D supplementation using an easy administration scheme

Bone disease in long-term survivors after gastric cancer resection has received little research attention. This study aimed to investigate bone health after curative resection of gastric cancer and the consequences of high-dose vitamin D supplementation in patients with low levels of 25-(OH)-vitamin D. Disease-free patients at least 24months after gastric cancer resection represented the study cohort. Serum markers of bone metabolism were assessed at baseline and at 3 and 12months. Bone mineral density and presence of fractures were assessed by X-ray at baseline. Patients with 25-(OH)-vitamin D ≤30ng/mL at baseline received 16,000IU of vitamin D3 every 10days during the 1-year follow-up. Forty patients were included in the study. Mean time from surgery was 48.9 (24-109)months. Vitamin D insufficiency and secondary hyperparathyroidism were observed in 38 and 20 patients, respectively. Densitometry showed osteoporosis in 14 women and seven men and prevalent fractures in 12 women and six men at baseline. After 3months of vitamin D supplementation, 35 patients reached values of 25-(OH)-vitamin D over 30ng/mL. After 12months, 38 patients were in the normal range of 25-(OH)-vitamin D. At the same time, iPTH levels and markers of bone turnover (C-terminal cross-linked telopeptide of type-I collagen, serum concentrations of bone-specific alkaline phosphatase and osteocalcin) significantly decreased after vitamin D intervention. Oral administration of high doses of vitamin D is easily implemented and restored 25-(OH)-vitamin D and iPTH values, which are frequently disturbed after gastric cancer resection.

Serum 25-hydroxyvitamin D cutoffs for functional bone measures in postmenopausal osteoporosis.

There is no consensus on the minimal serum 25-hydroxyvitamin D [25(OH)D] concentration required to maintain bone health. The aim of this study was to investigate the relationship between 25(OH)D measured via liquid chromatography-mass spectrometry (LC-MS/MS), which is the current gold standard, and biochemical markers of bone turnover, PTH, and bone mineral densitometry (BMD). The medical records of 750 postmenopausal women newly diagnosed with osteoporosis or osteopenia at Samsung Medical Center from 2009 to 2014 were investigated. Subjects were divided into four groups according to serum 25(OH)D concentration: <10, 10-20, 20-30, and ≥30ng/mL. Serum concentrations of bone-specific alkaline phosphatase (BS-ALP), carboxy-terminal cross-linking telopeptide of type 1 collagen (CTx), intact PTH (iPTH), and BMD were compared among the four groups using analysis of covariance. Thresholds of 25(OH)D were then assessed using spline plots and locally weighted regression smoothing (LOESS) plots. 25(OH)D was negatively correlated with serum BS-ALP, CTx, and iPTH. Only femur neck and total femur BMD had significant positive relationships with 25(OH)D. Cutoff values of 11.9 and 9.7ng/mL were estimated from the spline plots of femur neck and total femur BMD, respectively. For iPTH, the LOESS plot showed a steep decrease to a serum 25(OH)D concentration of about 20ng/mL, followed by a plateau. According to this study, a serum 25(OH)D concentration of 20ng/mL, rather than 30ng/mL, was appropriate for bone health.

Physical activity may be a potent regulator of bone turnover biomarkers in healthy girls during preadolescence.

This study investigated the effects of different levels of habitual physical activity (PA) assessed by pedometry on bone turnover markers of preadolescent girls according to a cross-sectional experimental design. Sixty prepubertal girls of similar chronological age, bone age, maturity level, and nutritional status were assigned to a low PA (LPA; n=25), a moderate PA (MPA; n=17), or a high PA (HPA; n=18) group. Dual-energy X-ray absorptiometry was used to measure areal bone mineral density (BMD) and bone mineral content (BMC) of the lumbar spine (L2-L4) and dominant hip (femoral neck and trochanter). Blood was collected for the measurement of alkaline phosphatase (ALP), bone-specific ALP (BSAP), procollagen typeIN-terminal propeptide (PINP), C-terminal telopeptide of collagen I (CTX), parathyroid hormone (PTH), osteocalcin, thyroid-stimulating hormone, estradiol, testosterone, luteinizing hormone, and follicle-stimulating hormone concentrations. ANOVA revealed that the HPA group (18,695±1244 steps per day) had a lower daily energy intake and body mass than the MPA group (10,774±521steps per day) and the LPA group (7633±1099 steps per day). The HPA group had higher (P<0.05) lumbar and hip BMD and hip BMC than the LPA group and higher (P<0.05) lumbar BMD than the MPA group. The MPA group had higher (P<0.05) hip BMC than the LPA group. The HPA group had greater (P<0.05) values of BSAP, PINP, and ALP and lower (P<0.05) values of PTH and CTX than the LPA group but not the MPA group. A partial correlation analysis (adjusted for body mass index) revealed a positive correlation of steps per day with BMD and BSAP concentration and a negative correlation with PTH and CTX concentration. In conclusion, PA increases BMD and BMC of premenarcheal girls by favoring bone formation over bone resorption.

Preventive effect of zoledronic acid on aromatase inhibitor-associated bone loss for postmenopausal breast cancer patients receiving adjuvant letrozole

BackgroundThis study aims to compare the efficacy and safety between zoledronic acid combined with calcium and calcium alone to prevent aromatase inhibitor-associated bone loss for postmenopausal breast cancer patients receiving adjuvant letrozole.MethodsOne hundred twenty patients were randomly divided into two groups, A and B. Patients in group A (n=60) received modified radical mastectomy or breast-conserving surgery + four cycles of AC followed by T regimen (optional) + radiotherapy (optional) + letrozole 2.5 mg daily + calcium 500 mg twice daily + vitamin D 400 international units daily +4 mg of zoledronic acid every 6 months, while patients in group B (n=60) were not given zoledronic acid and the rest of the treatments of group B were the same as group A. All the patients were followed up for 1 year. The primary endpoint was the intrapatient percentage change in lumbar spine (LS) bone mineral density (BMD) from baseline to month 12. Secondary endpoints included the percentage change in total hip (TH) and femoral neck (FN) BMD, the incidence of osteoporosis, the incidence of a clinically meaningful 5% decline in BMD at 1 year, change of serum N-telopeptide of type 1 collagen (NTX) and bone-specific alkaline phosphatase (BSAP) concentrations.ResultsPatients in group A had a statistically significant higher average change and average percent change in LS, FN, and TH than group B. Group A had a statistically significant lower incidence of a clinically meaningful loss of bone density at the LS, FN, or TH than Group B. The incidence of osteoporosis in group A was significantly lower than group B. The decreases in NTX and BSAP concentrations from baseline to month 12 in patients of group A were significant; in contrast, patients in group B were found to have increases in NTX and BSAP concentrations from baseline. The most common adverse reactions in patients are flu-like symptoms (38%), bone pain (28%), and joint pain (20%).ConclusionAI-associated bone loss can be prevented by concurrent zoledronic acid for postmenopausal breast cancer patients.

Vitamin D3 supplementation, bone health and quality of life in adults with diabetes and chronic kidney disease: Results of an open label randomized clinical trial

Adults with diabetes (DM) and chronic kidney disease (CKD) are at risk for vitamin D (vitD) insufficiency, suboptimal bone health and reduced quality of life (QoL) due to limited sunlight exposure, poor vitD intake and CKD. This open-labeled, randomized clinical trial, compared the impact of daily (2000IU/D) verses monthly (40,000IU/month) vitD3 supplementation over six months on markers of vitD status, bone health and QoL in adults with DM and CKD (stages: 1-4). Participants (18-80 years) were randomized to daily (n=60) or monthly (n=60) vitD3 for six months. Primary outcomes included: vitD status (25-hydroxyvitD [25(OH)D], 1, 25-dihydroxyvitD [1,25(OH)2D], bone health (bone mineral density [BMD] and serum concentrations of bone-specific alkaline phosphatase [BSAP], osteocalcin [OC], N-telopeptide-type 1-collagen [NTx]) and Fibroblast Growth Factor-23 (FGF-23). Secondary outcomes included QoL (Short Form-36 questionnaire). Adherence by dose allocation over six months was 95.0±5.7% (daily) and 94.1±4.1% (monthly), respectively (p=0.44); resulting in an overall median [95% CI] increase in serum 25(OH)D of 19 (12-26)nmol/L (p<0.001). Serum 25(OH)D increased at three (p<0.001) and six months (p<0.001) in the daily and monthly groups, respectively. No significant differences over six months between groups were observed in serum concentrations of 1,25(OH)2D, FGF-23, OC and NTx, BMD and QoL measures (p>0.05). Serum 25(OH)D≥75nmol/L was associated with significant reductions in BSAP (p=0.01) and improved physical functioning vs those with concentrations<75nmol/L (62.5±26.8 vs 52.7±26.3; p=0.03) in the monthly and daily groups, respectively. Daily (2000IU/D) and monthly (40,000IU/month) vitD3 supplementation for six months in adults with DM and CKD was safe, and resulted in equivalent adherence and improvements in overall vitD status, but only modest changes in markers of bone health and QoL.

Total and bone-specific alkaline phosphatase are associated with bone mineral density over time in end-stage renal disease patients starting dialysis.

Alkaline phosphatase (ALP) and bone-specific ALP (BALP) are implicated in the abnormal skeletal mineralization and accelerated vascular calcification in chronic kidney disease (CKD) patients. Whereas ALP and BALP may predict mortality in CKD, BALP is reported to have higher sensitivity and specificity than total ALP in reflecting histological alterations in bone; however, results on their associations with bone mineral density (BMD) are inconsistent. Here we evaluated associations of total ALP and BALP with BMD during up to 24months in end-stage renal disease (ESRD) patients. In this longitudinal study, 194 ESRD patients (median age 57years, 66% male, 32% diabetes mellitus, mean body mass index 24.8kg/m2) underwent measurements of total ALP and BALP and total and regional body BMD (by dual-energy X-ray absorptiometry) at dialysis initiation (n=194), and after 12 (n=98) and 24months (n=40) on dialysis. At baseline, patients had median total ALP 65.4 (43.3-126.4)U/l, BALP 13.5 (7.1-27.3)µg/l and BMD 1.14 (0.97-1.31)g/cm2. During the study period, serum concentrations of ALP and BALP increased significantly (p<0.001), whereas total and regional BMD remained stable. BMD correlated inversely with total ALP (rho=-0.20, p=0.005) and BALP (rho=-0.30, p<0.001) at baseline, and correlations were similar also at 12 and 24months. ALP and BALP are equally accurate albeit weak predictors of BMD in ESRD patients, both at baseline and longitudinally. The dissociation between stable BMD and increasing ALP and BALP may possibly reflect increased soft tissue calcifications with time on dialysis.

AB0838 Bone Metabolism Biomarkers in Tunisian Hemodialysis Patients

BackgroundAlthough bone biopsy is a golden standard in the diagnosis of chronic kidney disease mineral and bone disorders (CKD-MBD), this method is invasive and repetitive evaluation of bone status cannot...

Association of Blood Biomarkers of Bone Turnover in HIV-1 Infected Individuals Receiving Anti-Retroviral Therapy (ART).

To evaluate the association of bone turnover biomarkers with blood levels of alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BAP), osteocalcin (OC), tartrate-resistant acid phosphatase (TRAP), parathyroid hormone (PTH), and other blood markers in HIV-1 infected men receiving anti-retroviral therapy (ART). Advances in the treatment of HIV-1 infection have extended the life span of HIV-1 infected individuals. However, these advances may come at the price of metabolic side effects and bone disorders, including premature osteopenia, osteoporosis and osteonecrosis. Analyses of Ostase BAP, osteocalcin, and TRAP in blood were measured in three groups of MACS participants: 35 HIV-1 infected men on ART (A); 35 HIV-1- infected men not on ART (B); and 34 HIV-1 uninfected men (C). The mean and standard deviation results for groups A, B, and C were 19.7 ± 6.56, 17.2 ± 3.96, and 16.9 ± 5.78 for ostase BAP; 7.9 ± 9.53, 8.5 ± 8.30, and 5.5 ± 1.65 for osteocalcin; and 3.9 ± 1.04, 3.1 ± 0.81, and 2.5 ± 0.59 for TRAP, respectively. Simple and multivariate analyses showed significant differences in mean TRAP and BAP concentrations between the three groups. In addition strong correlations between blood levels of Ostase BAP and TRAP (r=0.570, p=0.0004), and between blood levels of Ostase BAP and PTH (r=0.436, P=0.0098) for HIV-1 infected men on ART were observed. New strategies for measurement of blood and urine biochemical markers of bone formation and resorption during bone turnover can be useful for clinical monitoring of treatment of HIV-1 infected patients. Recently developed methods for measuring serum levels of TRAP and Ostase BAP represent superior laboratory tools for assessing the hyperactivity of osteoclasts, osteoblasts and bone loss in HIV-1 infected individuals receiving ART. Measurements of TRAP and BAP as bone turnover biomarkers are economical and are important for monitoring bone metabolism during ART and the need for osteoporosis treatment.

Advanced oxidation protein products accelerate bone deterioration in aged rats

Advanced oxidation protein products (AOPPs) are novel markers of oxidation-mediated protein damage, and accumulation of AOPPs is involved in many pathophysiological conditions. Our previous studies demonstrated that the serum level of AOPPs negatively correlated with the age-related change in bone mineral density (BMD) in rats and that AOPPs inhibited rat osteoblast-like cell proliferation and differentiation in vitro. However, whether AOPPs are involved in senile osteoporosis is still largely unknown. The present study aimed to test the hypothesis that accumulation of AOPPs might accelerate bone deterioration in aged rats. Seventy 18-month-old male Sprague Dawley (SD) rats were randomized to intravenous injection of vehicle, native rat serum albumin (RSA), AOPPs-modified RSA (AOPPs-RSA) with or without oral administration of apocynin (a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor), or apocynin alone. After treatment for 8weeks or 16weeks, seven rats in each group were sacrificed. Bone and blood samples were harvested for BMD measurement, micro-computed tomographic (micro-CT) imaging, and biochemical analysis of circulating bone biomarkers. Compared to RSA- or vehicle-treated rats, AOPPs-RSA-treated animals displayed significantly decreased total vertebral BMD and deteriorated microstructure in both the tibias and the lumbar vertebral bodies, which were associated with down-regulated plasma bone-specific alkaline phosphatase concentration and up-regulated tartrate-resistant acid phosphatase 5b concentration. These AOPPs-induced perturbations in aged rats could be prevented by the oral administration of apocynin. However, no significant differences in BMD were detected in the femurs or the biomechanical parameters tested between the different treatment groups. These data suggest that accumulation of AOPPs accelerates bone deterioration in aged rats, likely via the activation of NADPH oxidase. This study provides new information toward understanding the pathogenic basis of senile osteoporosis and may provide targets for intervention.