Bone loss is one of the important extra-intestinal manifestations in patients with inflammatory bowel diseases (IBDs). Compounds derived from natural products have been used to treat IBDs. However, the role of natural products on IBD-induced bone loss is not completely clarified. In the present study, we observed the effects of dihydroartemisinin (DHA), an antimalaria drug, on IBD and IBD-induced bone loss in a rat model. Chronic IBD model was established in Sprague-Dawley rats by giving them 2.5% dextran sodium sulfate in drinking water. DHA was given by intraperitoneal injection. Blood, colon, and bone samples were collected for biomarker assay and histological analysis. There was an obvious increase in tumor necrotic factor (TNF) α and receptor activator of nuclear factor (NF)-kB ligand (RANKL), and decrease in procollagen type 1 N-terminal propeptide (P1NP) level in IBD groups compared with the normal control (p < 0.05). The disease activity score of IBD rats was significantly higher than the control (p < 0.01). Obvious decrease in disease activity score, TNFα, and RANKL level and increase in P1NP were observed in DHA-treated IBD rats. Bone loss, shown as the decrease in bone mineral density, bone volume fraction, and trabecular number and increase in trabecular separation were observed in IBD rats compared with control (p < 0.01). DHA treatment obviously abolished the bone loss, in particular in the high-dose group (p < 0.05). DHA treatment also inhibited the excessive osteoclast formation; RANKL protein expression; and RANK, TRAF6, Fra-1, NFATc1 mRNA expression induced by IBD. Our data indicated that DHA may be a potential therapeutic agent for IBD and IBD-induced bone loss. Impact statement Bone loss is one of the important extra-intestinal manifestations in patients with inflammatory bowel diseases (IBDs). Studies have shown that compounds derived from natural products are useful in the treatment of IBDs. However, few studies have investigated the role of compounds derived from natural products in treatment of osteoporosis in IBDs. The current study aimed to show the effects of dihydroartemisinin (DHA), antimalaria drug, on bone loss in a rat model of IBD. The findings showed that DHA intervention dose dependently protected against bone loss in IBD rats by inhibiting tumor necrotic factor α production and osteoclast formation. These findings highlights that DHA may be beneficial for bone health in those patients with IBD.

Background Whole-body vibration training has recently been proposed as a complementary training modality to improve the bone health of adolescent swimmers. However, there is no longitudinal study regarding the effects of this training combination on bone metabolism. Therefore, the main goal was to analyze the effects of swimming and vibration training on bone turnover markers during adolescence. Methods The present study included 68 adolescent swimmers and 41 normoactive controls (CON). Swimmers were randomly selected to either continue with their regular swimming training (SWI) or participate in an additional vibration protocol (VIB). Anthropometric measurements and serum level determinations of osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide crosslaps (CTX) were performed before and after the 6-month intervention. Results Statistically significant group by time interactions were found for both bone formation markers. VIB showed a decrease over time in OC (baseline: 101.4 μg/mL, follow-up: 82.8 μg/mL, p < 0.05) and P1NP (baseline: 528.4 μg/mL, follow-up: 389.0 μg/mL, p < 0.05) and SWI had analogous reductions in P1NP (baseline: 685.8 μg/mL, follow-up: 542.0 μg/mL, p < 0.05), whereas CON experienced an increase in OC levels (baseline: 94.4 μg/mL, follow-up: 103.4 μg/mL, p < 0.05). After stratifying the sample according to the pubertal status, similar interactions were observed. Conclusions The combination of swimming training and this particular vibration protocol led to a decrease in bone formation markers, especially during early puberty. Whole-body vibration might not induce an osteogenic stimulus in adolescent swimmers.

OBJECTIVE. The aim of this population based study was to compare radiographic changes in the temporomandibular joint (TMJ) with the lumbar spine and femoral neck BMD. To find whether there is any relationship between TMJ radiographic changes, vitamin D (25(OH)D) and bone markers levels and the number of missing teeth. MATERIAL AND METHODS. The study included 95 randomly selected participants. Bilateral TMJ images were obtained using an orthopantomograph (OPTG) and were evaluated for presence of radiographic signs. BMD was measured by dual energy X-ray absorptiometry (DXA). BMD of the lumbar spine (LT score) and femur (FT score) was detected by DXA. The level of type I collagen telopeptide fragments (P1NP), of C-telopeptide crosslaps of type I collagen (CTX-1) and of 25(OH)D were also measured. RESULTS. Subjects with a lower LT score had significantly fewer occluding pairs of teeth (p=0.018) and were more frequent users of removable prostheses (p=0.008). Radiographic changes were negatively correlated with P1NP (p=0.041). CTX-1 correlated positively with P1NP (p<0.001) and negatively with 25(OH)D (p=0.042). Occluding pairs of teeth were positively correlated with the LT score (p=0.012) and FT score (p<0.001). Radiography showed changes in the TMJ of 57% of participants. Out of 95 participants, 60% demonstrated an abnormally low LT value. CONCLUSIONS. This population based study indicates that TMJ radiographic changes and teeth loss seems to be related to the low level of BMD and 25(OH)D level.

The clinical spectrum of hypophosphatasia (HPP) is broad and variable within families. Along severe infantile forms, adult forms with mild manifestations may be incidentally discovered by the presence of low alkaline phosphatase (ALP) activity in serum. However, it is still unclear whether individuals with persistently low levels of ALP, in the absence of overt manifestations of HPP, have subclinical abnormalities of bone remodeling or bone mass. The aim of this study was to obtain a better understanding of the skeletal phenotype of adults with low ALP by analyzing bone mineral density (BMD), bone microarchitecture (trabecular bone score, TBS), and bone turnover markers (P1NP and ß-crosslaps). We studied 42 individuals with persistently low serum ALP. They showed lower levels of P1NP (31.4 ± 13.7 versus 48.9 ± 24.4 ng/ml; p = 0.0002) and ß-crosslaps (0.21 ± 0.17 versus 0.34 ± 0.22 ng/ml, p = 0.0015) than individuals in the control group. There were no significant differences in BMD, bone mineral content, or TBS. These data suggest that individuals with hypophosphatasemia have an overall reduction of bone turnover, even in the absence of overt manifestations of HPP or low BMD. We evaluated bone mineral density (BMD), bone microarchitecture, and bone turnover markers in patients with low serum levels of alkaline phosphatase. Our results show that these patients have low bone remodeling even in the absence of BMD abnormalities, thus supporting the recommendation of avoiding antiresorptives such as bisphosphonates in these subjects.

To assess the effect of testosterone treatment on bone remodelling and density in dieting obese men, 100 obese men aged 53 years (interquartile range 47-60) with a total testosterone level <12 nmol/L receiving 10 weeks of a very low energy diet (VLED) followed by 46 weeks of weight maintenance were randomly assigned at baseline to 56 weeks of intramuscular testosterone undecanoate (n = 49, cases) or matching placebo (n = 51, controls). Pre-specified outcomes were between-group differences (mean adjusted difference, MAD) in serum c-telopeptide (CTx), N-terminal propeptide of type 1 procollagen (P1NP) and bone mineral density (BMD). At trial end, CTx was significantly reduced in men receiving testosterone compared to placebo, MAD -66 ng/L (95% CI -113, -18), p = 0.018, and this was apparent already after the 10 week VLED phase, MAD -63 ng/L (95% CI -108, -18), p = 0.018. P1NP was marginally increased after VLED, MAD +4.2 ug/L (95% CI -0.01, +8.4), p = 0.05 but lower at study end, MAD -5.6 ug/L (95% CI -10.1, -1.1), p = 0.03. No significant changes in sclerostin, lumbar spine BMD or femoral BMD were seen. We conclude that in obese men with low testosterone levels undergoing weight loss, bone remodelling markers are modulated in a way that may have favourable effects on bone mass.

Context: Osteoporosis and anemia are amongst the most common diseases in the aging population with a worldwide increasing prevalence.

Objective: As the bone-derived hormone fibroblast-growth factor-23 (FGF-23) was recently reported to regulate erythropoiesis, we examined age-related associations between hemoglobin levels and bone quality, bone turnover and FGF-23 concentrations.

Design: We used data from more than 5,000 adult subjects who participated in the population-based cohorts of the Study of Health in Pomerania (SHIP and SHIP-Trend). Bone quality was assessed by quantitative ultrasound at the heel, bone turnover by measurement of carboxy-terminal telopeptide of type I collagen (CTX) and intact amino-terminal propeptide of type I procollagen (P1NP) serum concentrations, respectively. Anemia was defined as hemoglobin <13 g/dl in men and <12 g/dl in women. C-terminal FGF-23 levels were measured in plasma in a subset of 852 subjects.

Results: Anemic subjects had poorer bone quality, higher fracture risk, and lower serum levels of P1NP than non-anemic individuals. Linear regression models revealed positive associations between hemoglobin and bone quality in subjects aged 40 or above and inverse associations with CTX in subjects aged 60 or above. Hemoglobin and FGF-23 concentrations were inversely associated, while FGF-23 was not related to bone quality or turnover.

Conclusion: Our data corroborates a close link between FGF-23 and anemia, which is related to poor bone quality in the elderly. Yet, we observed no direct association of FGF-23 with bone parameters. Therefore, further studies are needed clarifying the role of FGF-23 on bone and red blood cell production.

Keywords: Bone quality; FGF-23; anemia; general population study; hemoglobin.

The osteocyte's role in orchestrating diurnal variations in bone turnover markers (BTMs) is unclear. We identified no rhythm in serum sclerostin (osteocyte protein). These results suggest that serum sclerostin can be measured at any time of day and the osteocyte does not direct the rhythmicity of other BTMs in men.

BACKGROUND

The osteocyte exerts important effects on bone remodeling, but its rhythmicity and effect on the rhythms of other bone cells are not fully characterized. The purpose of this study was to determine if serum sclerostin displays rhythmicity over a 24-h interval, similar to that of other bone biomarkers.

METHODS

Serum sclerostin, FGF-23, CTX, and P1NP were measured every 2 h over a 24-h interval in ten healthy men aged 20-65 years. Maximum likelihood estimates of the parameters in a repeated measures model were used to determine if these biomarkers displayed a diurnal, sinusoidal rhythm.

RESULTS

No discernible 24-h rhythm was identified for sclerostin (p = 0.99) or P1NP (p = 0.65). CTX rhythmicity was confirmed (p < 0.001), peaking at 05:30 (range 01:30-07:30). FGF-23 levels were also rhythmic (p < 0.001), but time of peak was variable (range 02:30-11:30). The only significant association identified between these four bone biomarkers was for CTX and P1NP mean 24-h metabolite levels (r = 0.65, p = 0.04).

CONCLUSIONS

Sclerostin levels do not appear to be rhythmic in men. This suggests that in contrast to CTX, serum sclerostin could be measured at any time of day. The 24-h profiles of FGF-23 suggest that a component of osteocyte function is rhythmic, but its timing is variable. Our results do not support the hypothesis that osteocytes direct the rhythmicity of other bone turnover markers (CTX), at least not via a sclerostin-mediated mechanism.

Acromegaly has been associated with calcium-phosphate and bone turnover alterations. Controlled studies of these interactions are sparse.

To evaluate calcium and bone metabolism in active and treated acromegaly.

We conducted a controlled, prospective study at a tertiary referral center. We studied 22 patients with acromegaly referred for surgical or medical therapy (ACM) and 22 with nonfunctioning pituitary adenomas referred for surgery (control).

Calcium (serum and urine), phosphorus, parathyroid hormone (PTH), 25-hydroxy- and 1,25-dihydroxy-vitamin D, bone turnover markers [serum C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP)], and cytokines [receptor activator of nuclear factor κB ligand (RANK-L) and osteoprotegerin (OPG)] at baseline and 3 to 6 months after treatment.

At baseline, the ACM group had lower PTH levels than controls (36.3 ± 13.9 pg/mL vs 56.0 ± 19.9 pg/mL) and higher phosphorus (4.34 ± 0.71 mg/dL vs 3.55 ± 0.50 mg/dL) (P < 0.01). Groups had similar levels of serum and urine calcium and 25-hydroxy- and 1,25-dihydroxy-vitamin D. The ACM group had higher bone turnover markers than control; P1NP and CTX were strongly correlated (r2 = 0.82, P < 0.05). CTX was dependent on age and disease group but not on sex or gonadal status. After treatment of acromegaly, serum calcium (9.52 ± 0.43 mg/dL to 9.26 ± 0.28 mg/dL), phosphorus (4.34 ± 0.71 mg/dL to 3.90 ± 0.80 mg/dL), and CTX (0.91 ± 0.75 ng/mL to 0.63 ± 0.68 ng/mL) decreased, while PTH increased (36.3 ± 13.9 pg/mL to 48.9 ± 16.7 pg/mL) (P < 0.01). 25-hydroxy-vitamin D, P1NP, and RANK-L/OPG ratio did not change significantly.

Acromegaly patients exhibited PTH-independent calcium-phosphate alterations and enhanced coupled bone formation and resorption. Within 6 months of treatment, bone resorption decreased, whereas RANK-L/OPG changes were inconsistent.

Aims To assess the incremental value of biomarkers, including N-terminal prohormone of brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), growth differentiation factor 15 (GDF-15), and procollagen type 1 N-terminal propeptide (P1NP), in predicting incident cardiovascular events and mortality among asymptomatic individuals from the general population, beyond traditional risk factors, including fasting glucose and renal function (cystatin C), medication use, and echocardiographic measures. Methods and results Prospective population-based cohort study of 1324 subjects without a previous cardiovascular event, who underwent baseline echocardiography and biomarker assessment between 2002 and 2006. The clinical endpoint was the composite of myocardial infarction, invasively treated stable/unstable ischemic heart disease, heart failure, stroke, or all-cause mortality. Predictive capabilities were evaluated using Cox proportional-hazards regression, Harrell's concordance index (C-index), and net reclassification improvement. Median age was 66 (interquartile range: 60-70) years, and 413 (31%) were female. During median 8.6 (interquartile range: 8.1-9.2) follow-up years, 368 (28%) composite events occurred. NT-proBNP, hs-TnT, GDF-15, and IL-6 were significantly associated with outcome, independently of traditional risk factors, medications, and echocardiography ( p < 0.05 for all). Separate addition of NT-proBNP and GDF-15 to traditional risk factors, medications, and echocardiographic measurements provided significant improvements in discriminative ability (NT-proBNP: C-index 0.714 vs. 0.703, p = 0.03; GDF-15: C-index 0.721 vs. 0.703, p = 0.02). Both biomarkers remained significant predictors of outcome upon inclusion in the same model ( p < 0.05 for both). Conclusions NT-proBNP and GDF-15 each enhance prognostication beyond traditional risk factors, glucose levels, renal function, and echocardiography in individuals without known cardiovascular disease.

Secondary osteoporosis is the major concern associated with long term intake of antiepileptic drugs (AEDs). Women are the vulnerable targets owing to post-menopausal bone loss. In the present work, we evaluated the effect of 10 weeks of treatment with AED therapy (carbamazepine, CBZ, 75 mg/kg; sodium valproate, SVP, 300 mg/kg; levetiracetam, LTM, 150 mg/kg) on bone mineral density and microarchitecture at femoral epiphysis, lumbar vertebrae and proximal tibia of normal and ovariectomised Wistar rats. In addition, we measured serum levels of vitamin D, receptor activator of nuclear factor kappa β-ligand (RANKL), procollagen type 1 amino-terminal propeptide (P1NP) and wnt inhibitors (sclerostin and DKK-1) following AED therapy. Micro-computed tomography analysis of bones revealed significant reduction in BMD at femur epiphysis and lumbar vertebrae with all the three AEDs evaluated. At proximal tibia, only CBZ showed a significant decline. The reduction in BMD was more pronounced in ovariectomised rats. AEDs also resulted in alteration of micro-CT parameters. These changes were accompanied by an increased serum RANKL with all AEDs while vitamin D levels were reduced only with CBZ treatment and P1NP levels were reduced with SVP and CBZ. Serum sclerostin levels were elevated following all AEDs in normal and ovariectomised rats except with CBZ in normal rats. However, increase in DKK-1 levels was observed with only LTM. Ovariectomy itself resulted in increased RANKL, sclerostin and DKK-1 and reduced vitamin D and P1NP levels. Significant differences were discernible between normal and ovariectomised rats treated with AEDs in all the parameters. However, while sclerostin increased further upon AEDs treatment, P1NP decreased with SVP and CBZ and serum DKK-1 levels showed a declining trend with all the three AEDs studied. We confirm adverse effects on bone following AEDs in female rats. Further, our results demonstrate for the first time that these effects are more pronounced in ovariectomised rats as compared to normal rats and that this could be related to estrogen deficiency which in turn enhances bone resorption via increased RANKL and reduces bone formation via increased sclerostin and reduced P1NP. Finally, our study demonstrated for the first time that AED treatment displayed changes in the serum levels of wnt inhibitors and hence modulation of wnt inhibitors might be partly involved in their adverse effects on bone.

Osteoporosis is a major health issue. By 2050, a greater than 2-fold increase in patients number with hip fractures will occur in Asia representing 50% of all hip fractures worldwide. For the Asia-Pacific (AP) region, more efforts on controlling osteoporosis and the subsequent fractures are crucial. Bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) is commonly used to diagnose osteoporosis and monitor osteoporosis treatment. However, the inconvenience, cost, limited availability of DXA and the delay in detection of BMD changes after treatment initiation support an important role for bone turnover markers (BTMs), as short-term tools to monitor therapy. With regards to low adherence rates of medical treatment of osteoporosis, the experts reached consensus on the use of BTMs for both raising awareness and short-term monitoring of osteoporosis treatment in the AP region. The experts endorse the use of BTMs, especially serum C-terminal telopeptide of type 1 collagen (CTX) and serum procollagen type 1 N propeptide (P1NP), as short-term monitoring tools to help clinicians assess the responses to osteoporosis therapies and appropriately adjust treatment regimens earlier than BMD. Either the absolute values or the degree of change from baseline in BTMs can be used to monitor the potential efficacy of osteoporosis therapies. The use of BTMs can be incorporated in osteoporosis care programs, such as fracture liaison service (FLS), to improve patient adherence and treatment outcomes. Encouraging sufficient reimbursement from health care systems may facilitate widespread use of BTMs in clinical practice in the AP region.

The objectives of this research were to develop an aerobic step combined with resistance training exercise program, and to compare the effects of A) aerobic step exercise training (STE), B) resistance aerobic exercise training (RES), C) a combined aerobic step with resistance exercise training (COM) on the health-related fitness, balance, and biochemical bone markers. Sixty participants were working female volunteers at the age of 35-45. They were divided into 4 groups by simple random sampling method. Fifteen of the participants were in the STE group, 14 in the RES group, 15 in the COM group, and 16 in the control group (CON). The STE, RES and COM exercise training programs were designed to yield the same intensity and achieve the same range of heart rate during each stage of the program. During the training, music was used to set the tempo of the workouts. At the 8th week, it was found that resting heart rate and systolic blood pressure significantly-increased only in the STE and COM groups. After 16 weeks, the experiment results showed the significant improvement in the COM and STE groups of exercise training for β-CrossLaps, P1NP NMID Osteocalcin and bone formation (PINP/β-CrossLaps x0.31) but not in the RES group. For balance ability, the COM group showed significantly greater change than the RES group after the training intervention (p < 0.05). It can thus be concluded that the STE and COM training were effective in improving bone formation (PINP/β-CrossLaps x 0.31) but not in the RES group. For balance ability, the COM group showed more significant change than the RES group. Therefore, this is not only a good exercise choice for the working-age people but also it can help reduce the risks of osteoporosis and falling in women in particular.

OBJECTIVE

The authors assessed the relationship between implant stability and bone turnover markers in patients with and without a history of bisphosphonate (BP) exposure for treatment of osteopenia/osteoporosis.

METHODS

One dental implant site was evaluated in 58 post-menopausal women with a spectrum of bone health in a "best practice" prospective cohort study. Each site had a previous or simultaneous bone augmentation procedure. BP exposure at enrollment was categorized as "never" or "past/current" exposure. Implant stability was assessed by resonance frequency analysis (RFA ISQ) at surgery and 8 weeks post-implant. Bone turnover markers, C-telopeptide collagen crosslinks (sCTX) and procollagen -1 N-terminal telopeptide (P1NP), were measured pre-treatment, 1, and 8 weeks following implant surgery.

RESULTS

Mean age was 62.4 ± 6.8 years; 66 % were osteopenic/osteoporotic. Average RFA ISQ at placement for all participants was 63.5 ± 11.3, at 8 weeks post-surgery 74.2 ± 9.4 (p < 0.01). Among "past/current" BP users, there was a significant negative correlation between RFA ISQ values at 8 weeks post-implant placement and sCTX and P1NP values at 1 week (ρ = -.65 and ρ = -.55, respectively; p < 0.01) and 8 weeks (ρ = -.64 and ρ = -.52, respectively; p < 0.05).

CONCLUSIONS

RFA ISQ values increased between implant placement and 8 weeks post-surgery demonstrating successful osseointegration. Lower bone turnover was associated with better implant stability among patients with a history of BP exposure.

CONCLUSIONS

Further investigation of the relationship between BP exposure and implant stability is warranted in a larger population, as results may strongly impact on clinical practice decisions.

BACKGROUND

Mechanical loadings by active exercise or passive low amplitude vibration have been demonstrated to enhance bone mass or delay bone loss. Traditional Thai massage can be anabolic to bone due to the application of physical loading on the body in a rhythmic fashion.

OBJECTIVE

To explore the skeletal effect of Thai traditional massage by examining the changes in biochemical markers of bone turnover immediately after the massage.

METHODS

Subjects consisted of 30 healthy females aged 20-40 years. Each subject received Thai traditional massage for 2 hours by a single masseuse. Bone mineral density (BMD) at baseline was measured by dual-energy X-ray absorptiometry (DEXA). C-terminal telopeptide of type 1 collagen (CTx-I) and total procollagen type 1 amino-terminal propeptide (P1NP) were determined by electrochemiluminescence immunoassay.

RESULTS

There was a 4.8% increase in serum P1NP concentrations after massage (median 43.4 ng/ml vs. 41.3 ng/ml, p < 0.05). Serum CTx-I also decreased after massage (median 2-hour vs. baseline 0.29 ng/ml vs. 0.31 ng/ml, p < 0.05). There was a nearly significant negative correlation between the percentage change in serum P1NP and BMD at the total femur (r = -0.37, p = 0.056) whereas the statistically significant correlation disappeared between percentage change in bone turnover and the other sites of BMD.

CONCLUSIONS

Thai traditional massage induces acute changes in bone formation and resorption markers. Study on the more prolonged effects of Thai traditional massage is warranted to explore its implication in the enhancement of bone health.

In this study, we evaluated the relationships between immune activation, bone turnover, and bone mass in virally suppressed HIV-infected children and HIV-uninfected children in South Africa. We found that decreased bone mass may occur or persist independent of immune activation and altered bone turnover.

OBJECTIVE

HIV-infected children and adolescents have deficits in skeletal growth which include decreases in bone mass and alterations in bone microarchitecture. However, the mechanism by which HIV infection compromises bone accrual in children and adolescents is unclear. The goal of this study was to evaluate the relationships between immune activation, bone turnover, and bone mass in a group of pre-pubertal HIV-infected children randomized to remain on ritonavir-boosted lopinavir (LPV/r)-based antiretroviral therapy (ART) or switch to efavirenz-based ART in South Africa virally suppressed at the time of this study.

METHODS

This cross-sectional analysis included 219 HIV-infected and 180 HIV-uninfected children enrolled in the CHANGES Bone Study conducted in Johannesburg, South Africa. Whole body (WB) bone mineral content (BMC) was assessed by dual x-ray absorptiometry and WB BMC Z-scores adjusted for sex, age, and height were generated. Bone turnover markers, including C-telopeptide of type 1 collagen (CTx) and procollagen type I N-terminal propeptide (P1NP), were analyzed. Markers of immune activation were also measured, including cytokines IL-6 and TNF-alpha, as well as soluble CD14 and high-sensitivity C-reactive protein (CRP).

RESULTS

Compared to uninfected controls, HIV-infected children had lower WB BMC Z-scores, similar IL-6 and TNF-alpha, higher soluble CD14 and high-sensitivity CRP, and lower markers of bone resorption (CTX) and bone formation (P1NP). Bone turnover markers were not different in those remaining on LPV/r or switched to efavirenz.

CONCLUSIONS

Our findings suggest that in HIV-infected children with viral suppression, decreased bone accrual may occur or persist independent of immune activation and altered bone turnover.

Exposure to high-dose radiation results in deleterious effects on skeletal tissue. However, the effects of combined trauma such as radiation and hemorrhage on skeletal properties have yet to be elucidated. The purpose of this study was to evaluate the effects of radiation injury combined with hemorrhage on trabecular bone properties and biomarkers of bone metabolism, and to determine whether hemorrhage enhances radiation-associated bone loss. Male CD2F1 mice (10 weeks old) were exposed to one single dose of gamma radiation ((60)Co): 0 or 7.25 Gy. Two hours after irradiation, animals were bled 0% (n = 8) or 20% (n = 8) of total blood volume via the submandibular vein. Mice were euthanized 30 days after irradiation, and distal femora were analyzed using standard histomorphometry to determine changes in trabecular bone volume (BV/TV), thickness (Tb.Th), spacing (Tb.Sp), number (Tb.N) and marrow adipocyte density. Femurs from mice euthanized 1, 7 and 15 days post injury were flushed and total bone marrow cells were counted. Radiation exposure resulted in deleterious effects on distal femur BV/TV (-63%), Tb.Th (-34%), Tb.N (-45%), Tb.Sp (+125%) and adipocyte density (+286%) compared with the sham-irradiated mice (0 Gy; P < 0.05). Hemorrhage after irradiation resulted in greater deleterious effects on the distal femur with BV/TV (-13%), Tb.Th (-44%), Tb.N (-26%), Tb.Sp (+29%) and marrow adipocyte density (+33%) compared with radiation exposure only (P < 0.05). Analysis of the biomarkers of bone metabolism in serum from irradiated and hemorrhaged mice revealed significantly lower levels of osteocalcin (-60%) and procollagen type 1 amino-terminal propeptide (-36%; P1NP, biomarkers of bone formation activity), as well as elevations in sclerostin (+56%; SOST, an inhibitor of bone formation) compared with serum from irradiated only mice (P < 0.05). Additionally, the onset of bone marrow cell depletion in irradiated and hemorrhaged mice occurred earlier and to a greater extent compared to that in irradiated only mice. This study provides definitive, preliminary evidence that hemorrhage further exacerbates trabecular bone loss associated with nonlethal high-dose gamma radiation.

There is no way to predict early the growth response to growth hormone (GH) treatment in short children with intrauterine growth retardation (IUGR) or idiopathic short stature (ISS).

OBJECTIVE

To evaluate the capacity of the procollagen type 1 amino-terminal propeptide (P1NP), a new marker of bone formation, to help in this prediction.

METHODS

Longitudinal study of 30 patients treated at 7.7 (range: 2.2-12.5) years for IUGR (n=16) or ISS (n=14) with GH (0.47 and 0.33 or 0.4mg/kg/week respectively). P1NP and insulin-like growth factor I (IGF I) were measured before and after 3-6 months of GH treatment.

RESULTS

Before treatment, IUGR patients were younger and shorter than ISS patients, but their other characteristics were similar. IGF I Z-score (ZS) and P1NP concentrations were positively correlated in the whole population (Rho=0.48; P=0.01). After 3-6 months of treatment, both concentrations increased in IUGR and ISS (P<0.01). They remained correlated only in ISS (Rho=0.54; P<0.05). P1NP before treatment was negatively correlated (Rho=-0.67, P=0.015) with the growth rate (SD) during the first year of treatment in ISS but not in IUGR; IGF I ZS was not. The changes in P1NP for the whole population over 3-6 months, but not the changes in IGF I ZS, were positively correlated with the growth rate (Rho=0.41, P=0.03).

CONCLUSIONS

Lower basal plasma P1NP concentrations predict better growth response to GH treatment during the first year in ISS children. Greater increases in its concentrations after 3-6 months of GH treatment may also predict a better growth response in both ISS and IUGR.

UNASSIGNED

Traditionally, milk proteins have been recommended for skeletal health; recently, soy proteins have emerged as popular alternatives. Excess adiposity appears detrimental to skeletal health, as obese adolescents have increased fracture rates compared with healthy controls. However, soy protein effects on skeletal health during excess adiposity remain unknown.

UNASSIGNED

The study objective was to examine the effects of isocaloric diets containing milk protein isolate (MPI), soy protein isolate (SPI), or a 50/50 combination (MIX) as the sole protein source on metabolic health indicators and bone outcomes in rapidly growing, hyperphagic, male Otsuka Long Evans Tokushima Fatty (OLETF) rats.

UNASSIGNED

OLETF rats, aged 4 wk, were randomly assigned to 3 treatment groups (MPI, SPI, or MIX, n = 20 per group) and provided with access to experimental diets ad libitum for 16 wk.

UNASSIGNED

Body mass did not differ between the groups, but SPI had lower percentage body fat than MPI (P = 0.026). Insulin was lower in MPI than in MIX (P = 0.033) or SPI (P = 0.044), but fasting blood glucose was not different between the groups. SPI significantly reduced serum cholesterol compared with MPI (P = 0.001) and MIX (P = 0.002). N-terminal propeptide of type I collagen (P1NP) was higher in MIX than MPI (P = 0.05); C-terminal telopeptide of type 1 collagen (CTx) was higher in MPI than SPI (P < 0.001) and MIX (P < 0.001); the P1NP to CTx ratio was significantly higher in SPI and MIX than in MPI (P < 0.001). Trabecular separation was reduced in SPI compared with MPI (P = 0.030) and MIX (P = 0.008); trabecular number was increased in SPI compared with MIX (P = 0.038). No differences were seen in cortical geometry and biomechanical properties.

UNASSIGNED

In the context of excess adiposity, soy- and milk-based proteins have comparable effects on cortical bone geometry and biomechanical properties, whereas soy-based proteins favorably affect the trabecular microarchitecture, and the combination of both proteins may offer additional benefits to bone remodeling in rapidly growing male OLETF rats.

Objectives: Chronic obstructive pulmonary disease (COPD) is a risk factor for osteoporosis. Nevertheless, much remains unclear regarding the bone metabolism dynamics associated with COPD. The present study focuses on the associations between the COPD severity and serum bone metabolism biomarkers.

Methods: We enrolled 40 patients who visited the orthopedics departments at our institutions and underwent dual-energy X-ray absorptiometry between September 2015 and December 2017. Only male osteoporosis patients over 45 years of age were included, and 5 patients were excluded due to disease or use of internal medicines affecting bone metabolism. All subjects underwent lung function testing, spine radiography, and blood tests. We measured percent forced expiratory volume in 1 second (%FEV₁), which reflects COPD severity, and we examined the relationships between %FEV₁ and serum levels of bone metabolism biomarkers.

Results: All subjects were diagnosed with osteoporosis based on T-scores. %FEV₁ correlated with body weight, body mass index (BMI), and Z-score/T-scores. %FEV₁ moderately correlated with serum levels of alkaline phosphatase (ALP), procollagen type 1 N-terminal propeptide (P1NP), and tartrate-resistant acid phosphatase 5b in the partial correlation analysis adjusted for BMI or T-score in the lumbar vertebrae. We performed a hierarchical multiple regression analysis to identify that serum ALP and P1NP were the independent explanatory variables to %FEV₁ independent of other factors.

Conclusions: The data suggest that the COPD severity in middle-aged and older men with osteoporosis associates with decreased bone formation. COPD patients may exhibit bone metabolism dynamics characterized by low bone turnover with osteogenesis dysfunction as COPD becomes severe.

Keywords: Alkaline phosphatase; Chronic obstructive pulmonary disease; Male osteoporosis; Procollagen type 1 N-Terminal propeptide; Tartrate-resistant acid phosphatase 5b.

OBJECTIVE

To monitor morphological feature and related osteogenic and bone metabolic change during healing of tibia fracture in a rat model.

METHODS

Tibia density and trabecular thickness were evaluated. Histopathology was examined by HE staining. Serous inflammatory factors IL-4, IL-6, TNF-α and metabolic biomarkers ALP, β-CTX, P1NP, were determined by ELISA. The expression of RUNX2, TGF-β1, VEGF-α, BMP-2, BMP-4, and BMP-7 in callus tissue were qualified by RT-PCR.

RESULTS

Bone density decreased until week 4 and then increased post-operation. Trabeculae in callus were thickened over time with active osteogenesis. ELISA indicated the most severe inflammation at week 2, with the highest level of TNF-α, IL-6, and the lowest level of IL-4. After 4 weeks, the inflammation was alleviated accompanying with the decline of TNF-α and IL-6, while there was the elevation of IL-4. Bone metabolism showed active osteogenesis and resorption at week 6 with high P1NP and β-CTX. The expression of RUNX2, TGF-β1, VEGF-α, BMP-2, BMP-4, and BMP-7 increased progressively from week 1 to 6. The major lesions at week 2 in sham were tissue necrosis, periosteal reactive hyperplasia, inflammatory cell infiltration, capillary hyperplasia and slight fibro-blast cytopoiesis. At week 4, proliferation was greatly activated, fibrous callus shaped and chondrogenesis and some osteogenesis occurred at week 8.

CONCLUSIONS

In rat model, bone density started to increase at week 6 after fracture, accompanied with trabeculae thickening, serous inflammatory factors decline, and peaked bone morphogenetic protein/growth factors, which indicated active osteogenesis was conforming to the classical phase of secondary fracture healing.

BACKGROUND

Maternal calcium homeostasis adapts during pregnancy to provide for the needs of the growing fetal skeleton. Wide selections of bone turnover markers are currently available to assess the changes taking place; here, data are presented on two serum-based markers.

METHODS

The use of serum-based biochemical bone turnover markers during pregnancy was assessed in a cohort of 41 women recruited prior to conception. Serum N-terminal extension peptide of procollagen (P1NP) was used to monitor bone formation and serum beta-crosslaps (S-CTX) used to assess resorption. Blood samples were measured at five time points from a pre-conceptual baseline, through pregnancy, to the final sample, which was taken within 1 week of delivery.

RESULTS

An initial decrease from the baseline in both P1NP and S-CTX was observed at 12 weeks; however, it is suggested that this may be due to the haemodilutional effect of pregnancy rather than a true change in bone turnover. Significant increases from the baseline of both analytes were observed by 36 weeks (P1NP, P = 0.013; S-CTX, P = 0.002), when the calcium demands of the fetus are greatest.

CONCLUSIONS

This study illustrates the use of serum-based bone turnover markers to assess turnover during normal pregnancy, a time when ionizing radiation cannot be used to assess bone turnover.