Nine month teriparatide (TPTD) monotherapy followed by co-administration of raloxifene (RAL) or alendronate (ALN) for another nine 9 months resulted in incremental bone mineral density (BMD) increase. The aim of this study was to investigate the effects of continued antiresorptive treatments for 12 months in the extension phase. Postmenopausal women (n = 125) with severe osteoporosis on ongoing TPTD treatment for 9 months were randomized into three open-label groups for another 9 months: ALN (70 mg/week, n = 41), RAL (60 mg/d, n = 37) in addition to TPTD or no additional medication (n = 47) except Ca and vitamin D. After discontinuation of TPTD the respective antiresorptives were continued for a further 12 months, while patients in the TPTD monotherapy group received Ca and vitamin D. Amino-terminal propeptide of type I procollagen (P1NP) and cross-linked C-telopeptide (CTX), areal and volumetric BMD at the lumbar spine (LS) and hip were assessed. ALN resulted in continued BMD increase in LS (4.3 ± 1.5%; mean ± SD), femoral neck (4.2 ± 1.6%) and total hip (4 ± 1.6%; p < 0.001 for all), while RAL was only effective at the LS (2.4 ± 1.7%, p < 0.001) but no changes at the femoral neck (0.4 ± 1.4%) or total hip (-0.8 ± 1.5%) were observed. Cortical bone only increased in the ALN group (femoral neck 6.7 ± 2.7% and -1.3 ± 2.5%; total hip 13.8 ± 2.9% and -2.3 ± 2.5% for ALN and RAL, p < 0.001 for all; respectively). Analyzing the entire 30 months of therapy, the ALN group revealed the largest BMD increase in all regions. Our results suggest that the addition of ALN to ongoing TPTD and continuing ALN after TPTD was stopped may be beneficial for patients in terms of areal and volumetric BMD increase. Further research is warranted to determine the optimal timing of the initiation of the combination treatment, the respective antiresorptive medication and the potential benefit of this BMD increase regarding fracture prevention.

Long-term body composition (BC) changes and their determinants have been rarely explored. We aimed to evaluate BC changes in French women from the Os des Femmes de Lyon (OFELY) cohort and to explore several determinants of those changes. At baseline, premenopausal (PreM) women (n = 145) had lower fat body mass (FM) and greater lean body mass (LM), relative skeletal muscle mass index (RASM), and total body bone mineral content (TBBMC) compared with untreated postmenopausal (PostM) women (n = 412). During a 6-year follow-up, LM and RASM did not change, whereas a significant increase of FM and a decrease of TBBMC were observed in PreM (n = 88) and PeriM women (n = 44; women who became PostM during the follow-up). In untreated PostM women, FM increased, whereas LM, RASM, and TBBMC decreased (p < 0.0001). Age was a significant determinant of the changes in BC. After controlling for age, menopausal status was still a significant determinant only for changes in TBBMC. FM, LM, RASM, and TBBMC were higher in women with normal bone mineral density (BMD) compared with women with osteopenia or osteoporosis (p < 0.0001), but after adjusting for age, changes of BC were not significantly different according to the bone status. After controlling for age and menopausal status, levels of P1NP in the highest quartile were associated with a greater decrease of LM and RASM compared with lower levels. In conclusion, BC changes in French women over a 6-year follow-up showed a high interindividual variability. Aging may be the most important determinant of changes in body composition, rather than menopausal and bone status.

BACKGROUND

We have previously found in the chronic SKG mouse model of arthritis that long standing (5 and 8 months) inflammation directly leads to high collagen bone turnover, disorganization of the collagen network, disturbed bone microstructure and degradation of bone biomechanical properties. The main goal of the present work was to study the effects of the first days of the inflammatory process on the microarchitecture and mechanical properties of bone.

METHODS

Twenty eight Wistar adjuvant-induced arthritis (AIA) rats were monitored during 22 days after disease induction for the inflammatory score, ankle perimeter and body weight. Healthy non-arthritic rats were used as controls for compar-ison. After 22 days of disease progression rats were sacrificed and bone samples were collected for histomorphometrical, energy dispersive X-ray spectroscopical analysis and 3-point bending. Blood samples were also collected for bone turnover markers.

RESULTS

AIA rats had an increased bone turnover (as inferred from increased P1NP and CTX1, p = 0.0010 and p = 0.0002, respectively) and this was paralleled by a decreased mineral content (calcium p = 0.0046 and phos-phorus p = 0.0046). Histomorphometry showed a lower trabecular thickness (p = 0.0002) and bone volume (p = 0.0003) and higher trabecular sepa-ration (p = 0.0009) in the arthritic group as compared with controls. In addition, bone mechanical tests showed evidence of fragility as depicted by diminished values of yield stress and ultimate fracture point (p = 0.0061 and p = 0.0279, re-spectively) in the arthritic group.

CONCLUSIONS

We have shown in an AIA rat model that arthritis induc-es early bone high turnover, structural degradation, mineral loss and mechanical weak-ness.

Association between serum bone formation and resorption markers and bone mineral, structural, and strength variables derived from quantitative computed tomography (QCT) in a population-based cohort of 1745 older adults was assessed. The association was weak for lumbar spine and femoral neck areal and volumetric bone mineral density.

BACKGROUND

The aim of this study was to examine the relationship between levels of bone turnover markers (BTMs; osteocalcin (OC), C-terminal cross-linking telopeptide of type I collagen (CTX), and procollagen type 1N propeptide (P1NP)) and quantitative computed tomography (QCT)-derived bone density, geometry, and strength indices in the lumbar spine and femoral neck (FN).

METHODS

A total of 1745 older individuals (773 men and 972 women, aged 66-92 years) from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik cohort were studied. QCT was performed in the lumbar spine and hip to estimate volumetric trabecular, cortical, and integral bone mineral density (BMD), areal BMD, bone geometry, and bone strength indices. Association between BTMs and QCT variables were explored using multivariable linear regression.

RESULTS

Major findings showed that all BMD measures, FN cortical index, and compressive strength had a low negative correlation with the BTM levels in both men and women. Correlations between BTMs and bone size parameters were minimal or not significant. No associations were found between BTMs and vertebral cross-sectional area in women. BTMs alone accounted for only a relatively small percentage of the bone parameter variance (1-10 %).

CONCLUSIONS

Serum CTX, OC, and P1NP were weakly correlated with lumbar spine and FN areal and volumetric BMD and strength measures. Most of the bone size indices were not associated with BTMs; thus, the selected bone remodeling markers do not reflect periosteal bone formation. These results confirmed the limited ability of the most sensitive established BTMs to predict bone structural integrity in older adults.

Bone disease may persist after transplantation. Different approaches aiming to ameliorate this problem have been investigated. The aim of the study was to compare the long-term effect of three medical interventions: (i) two prophylactic oral doses of 50 mg ibandronate; (ii) daily oral dose of 0.25 μg of 1α-OHD3 (both of these regimens in patients receiving steroids), and (iii) steroid minimization immunosuppressive protocol in patients with no other specific prophylaxis.

METHODS

A total of 37 children, at a mean age of 13.33±3.49 yr, dialyzed for 15.93±16.7 months before transplantation, were divided into three groups, depending on medical intervention. Bone mineral content and density (BMC, BMD, DXA), serum markers of bone resorption and formation (CTX, P1NP), calcium, phosphate, 25OHD3/1.25 (OH)2D3 and PTH concentration were evaluated during two yr of follow-up. The mean values of BMD in the whole population and among the three subgroups remained within the age- and gender-matched normal range during follow-up. PATIENTS from groups II (alphacalcidiol) and III (steroid minimization) showed a significant decrease in BMD Z-scores over time, and this effect was determined with increasing age using multivariate analysis. PATIENTS receiving two doses of ibandronate maintained unchanged Z-scores for BMD and BMC over time.

BACKGROUND

Metabolic bone disease and bariatric surgery have long been interconnected. The objective of this study is to better understand the mechanisms of bone mass loss after Roux-en-Y gastric bypass (RYGB) surgery. We evaluated mineral homeostasis and bone mass in diet-induced obese (DIO) rats after RYGB or sham surgery.

METHODS

Twelve DIO male Sprague Dawley rats underwent RYGB (n = 8) or sham (n = 4) surgery at 21 weeks of age. Postoperatively, animals ate an ad libitum 40% fat, normal calcium diet and were euthanized 22 weeks later. Serum and urine chemistries, insulin, leptin, bone turnover markers (BTM), and calciotropic and gut hormones were measured before and 22 weeks after surgery. Femurs were analyzed using microcomputed tomography (µCT).

RESULTS

Compared to sham, RYGB animals had lower serum bicarbonate, calcium, 25-hydroxyvitamin D, insulin, and leptin levels with higher serum parathyroid hormone, peptide YY, and urinary calcium at 43 weeks of age. Sham control rats gained weight and had coupled decreases in formation (P1NP and OC) and unchanged resorption (CTX) BTMs. Comparatively, RYGB animals had higher serum CTX and OC but even lower P1NP levels than controls. µCT revealed lower trabecular bone volume, number, and thickness and lower cortical bone volume, thickness, and moment of inertia relative to controls.

CONCLUSIONS

In rats with DIO, long-term RYGB-associated bone resorption appears to be driven in part by vitamin D malabsorption and secondary hyperparathyroidism. Other mechanisms, such as chronic acidosis, changes in fat-secreted hormones, and persistently elevated gut-derived hormone peptide YY, may also contribute to observed bone mass differences. Further investigation of these potential contributors to bone loss may lead to new targets for skeletal maintenance after RYGB.

Young adults with cystic fibrosis (CF) frequently develop bone disease. One suggested aetiological factor is suboptimal vitamin K status with impaired carboxylation of osteocalcin and abnormal bone formation.

METHODS

We measured bone mineralization and turnover in thirty-two 8-12 year old CF patients (14 boys) using Dual Energy X-ray absorptiometry (whole body (WB) and lumbar spine (LS)), 25-OH Vitamin D, PTH and markers of bone formation (plasma osteocalcin, N-terminal pro-peptide of type 1 collagen (P1NP)), plus an indirect measure of vitamin K status, undercarboxylated osteocalcin (uc-OC).

RESULTS

LS bone mineral density (BMD) standard deviation (SD) scores were < -1.0 in 20% of subjects. Size-adjusted LS and WB bone mass was normal. Compared to reference data, % uc-OC was high and P1NP low. LS bone mass was predicted by % uc-OC but not other markers (0.4% decrease in size-adjusted LSBMC (p=0.05); 0.04 SD decrease in LSBMAD (p=0.04) per 1% increase in uc-OC).

CONCLUSIONS

Markers suggestive of sub-optimal vitamin K status and low bone formation were present despite normal size-adjusted bone mass. The association between LSBMC and % uc-OC is consistent with the hypothesis that sub-optimal vitamin K status is a risk factor for CF bone disease. This should ideally be investigated in an intervention trial.

The objective of this study was to investigate the clinical significance of the Wnt/β-catenin signaling pathway in glucocorticoid-induced osteoporosis. A total of 91 patients with systemic autoimmune diseases who received initial glucocorticoid therapy with prednisolone (30-60 mg daily) were prospectively enrolled. We measured serum levels of N-terminal peptide of type I procollagen (P1NP), bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), N-telopeptide cross-linked type I collagen (NTX), sclerostin, Dickkopf-1 (Dkk-1), and Wnt3a before starting glucocorticoid therapy and every week for 4 weeks after its initiation. The effects of dexamethasone on expression of mRNA and protein of sclerostin and Dkk-1 by cultured normal human osteoblasts (NHOst) were evaluated by RT-PCR and ELISA, respectively. Serum levels of sclerostin and Dkk-1 increased significantly by 1 week of glucocorticoid therapy and then decreased from the second week onward. Serum Wnt3a tended to decrease and serum P1NP showed a significant decrease. However, TRACP-5b was significantly elevated from the first week of treatment onwards. In vitro study, dexamethasone increased Dkk-1 mRNA expression in cultured NHOst, but sclerostin mRNA was not detected. Dexamethasone also increased Dkk-1 protein production by osteoblasts, whereas sclerostin protein was not detected. Bone formation might be impaired at least in the first week of the initiation of glucocorticoid therapy by increase of the serum Wnt signaling inhibitors; however, their reductions in the subsequent weeks were contradictory to the maintained suppression of the bone formation markers after glucocorticoid therapy for patients with systemic autoimmune diseases.

We conducted a randomized control study to compare the effects of pain, QOL, bone metabolism and fracture healing by administering bisphosphonate (BP) or weekly teriparatide preparation (W-TPTD) to 43 patients (5 males and 38 females) with fresh spinal vertebral compression fractures for osteoporosis. The patients were aged between 61 and 93 years old (mean 78.1 years). In principle, a MRI was used for any diagnosis of new vertebral fractures. From this study, lumbar spine bone mineral density (BMD), after 24 weeks of administration, showed a significant increase (p < 0.05) in both the BP group (mean 5.3%) and in the W-TPTD group (mean 4.9%). The W-TPTD group showed a better Roland-Morris disability Questionnaire (RDQ) improvement throughout the whole period of the study compared with the BP group, the difference was statistically significant after 24 weeks of administration (p < 0.05). The EuroQol 5 dimensions (EQ-5D) and visual analogue scale (VAS) score significantly improved over time in both groups (p < 0.05). The fracture-healing rate was observed in 45% of the BP group and 73% of the W-TPTD group at Week 12, and a statistically significant higher fracture-healing rate was obtained in the W-TPTD group compared to the BP group (p < 0.05). The mean time of fracture-healing was 3.9 months for the BP group and 2.8 months in the W-TPTD group. Statistically significant faster fracture-healing was observed in the W-TPTD group (p < 0.05). At Week 12 and Week 24, P1NP was significantly higher in the W-TPTD group compared to that of the BP group (p < 0.05). TRACP-5b showed no major fluctuations during the study period in either group. These results suggest that W-TPTD may promote better fracture healing of any new osteoporotic vertebral compression fractures compared with a BP.

Annual intravenous administration of 5 mg zoledronate decreases fracture risk, but the optimal dosing regimen for zoledronate has not been determined. We set out to evaluate the antiresorptive effects of a single administration of lower doses of zoledronate. A total of 180 postmenopausal women with osteopenia enrolled in a double-blind, randomized, placebo-controlled trial over 2 years at an academic research center. Participants were randomized to a single baseline administration of intravenous zoledronate in doses of 1 mg, 2.5 mg, or 5 mg, or placebo. The primary endpoint was change in bone mineral density(BMD) at the lumbar spine. Secondary endpoints were change in BMD at the proximal femur and total body, and changes in biochemical markers of bone turnover. After 2 years, the change in spine BMD was greater in each of the zoledronate groups than in the placebo group; values are mean (95% confidence interval [CI]) difference versus placebo: zoledronate 1 mg 4.4% [2.7% to 6.1%]; 2.5 mg 5.5% [3.9% to 7.2%]; 5 mg 5.3% [3.8% to 6.7%], p < 0.001 for each dose). Change in BMD at the total hip was greater in each of the zoledronate groups than the placebo group (mean [95% CI] difference versus placebo: zoledronate 1 mg 2.6% [1.5% to 3.7%]; 2.5 mg 4.4% [3.5% to 5.3%]; 5 mg 4.7% [3.7% to 5.7%], p < 0.001 for each dose). Each of the bone turnover markers, β-C-terminal telopeptide of type I collagen (β-CTX) and procollagen type-I N-terminal propeptide (P1NP), was lower in each of the 2.5-mg and 5-mg zoledronate groups than the placebo group throughout the trial (p < 0.001 versus placebo for each marker for each dose at each time point). For each endpoint, changes were similar in the 2.5-mg and 5-mg zoledronate groups, whereas those in the 1-mg group were smaller than those in the other zoledronate groups. These data demonstrate that single administrations of zoledronate 1 mg or 2.5 mg produce antiresorptive effects that persist for at least 2 years. Trials assessing the antifracture efficacy of intermittent low doses of zoledronate, in particular the 2.5-mg dose, are justified.

BACKGROUND

The concentration of N-terminal propeptide of type I procollagen (PINP) in the serum reflects the rate of type I collagen formation. Intact PINP assay measures the trimeric propeptide while total P1NP assay measures both trimeric and monomeric forms. In this study we compared these two assays emphasizing the possible differences.

METHODS

Intact and total PINP were measured from serum in healthy Finnish blood donors (n = 34) and in the patients with chronic renal failure before and after haemodialysis (n = 39). In addition, the serum of a normal man, pooled hospital serum samples and the serum of a patient with haemodialysis treatment were fractioned by gel filtration and trimeric and monomeric forms were located. Fractions were lyophilized and intact and total PINP were measured in each fraction. Samples from bedridden geriatric patients (n = 173) were also measured using intact and total PINP assays and a degradation marker of type I collagen (ICTP).

RESULTS

The correlation between intact and total PINP in controls was 0.89 and their PINP concentrations were similar. In haemodialysis or bedridden geriatric patients, the PINP methods gave significantly different results. In gel filtration studies, intact PINP hardly measured monomeric form even if its concentration was disproportionately increased in haemodialysis patients. In bedridden geriatric patients, the difference of total and intact PINP correlated significantly to degradation marker ICTP.

CONCLUSIONS

Difference between total and intact assays for PINP seem to reflect degradation of pN-collagen rather than denaturation of intact propeptide.

Roux-en-Y gastric bypass (RYGB) is a profoundly effective treatment for severe obesity, but results in significant bone loss in patients. Developing a murine model that recapitulates this skeletal phenotype will provide a robust tool with which to study the physiologic mechanisms of this bone loss. We studied adult male C57BL/6J mice who underwent either RYGB or sham operation. Twelve weeks after surgery, we characterized biochemical bone markers (parathyroid hormone, PTH; C-telopeptide, CTX; and type 1 procollagen, P1NP) and bone microarchitectural parameters as measured by microcomputed tomography. RYGB-treated mice had significant trabecular and cortical bone deficits compared with sham-operated controls. Although adjustment for final body weight eliminated observed cortical differences, the trabecular bone volume fraction remained significantly lower in RYGB mice even after weight adjustment. PTH levels were similar between groups, but RYGB mice had significantly higher indices of bone turnover than sham controls. These data demonstrate that murine models of RYGB recapitulate patterns of bone loss and turnover that have been observed in human clinical studies. Future studies that exploit this murine model will help delineate the alterations in bone metabolism and mechanisms of bone loss after RYGB.

BACKGROUND

Fragility fractures are a major public health issue with substantial socioeconomic cost. Vitamin-D deficiency and increased bone turnover are associated with higher rates of bone loss and an increased risk of fracture. We hypothesized that patients with a distal radial fracture would have lower levels of 25-hydroxyvitamin D (25[OH]D) and increased levels of serum bone turnover markers than controls without a fracture.

METHODS

Postmenopausal women with a recent distal radial fracture (fracture group, n = 105) were prospectively recruited and were compared with individuals without a fracture (control group, n = 150). Outcome variables included serum levels of 25(OH)D and markers of bone formation, including N-terminal extension propeptide of type-I collagen (P1NP), parathyroid hormone (PTH), bone-specific alkaline phosphatase (BSAP), and osteocalcin, as well as a marker of resorption (C-terminal telopeptide of type-I collagen [CTX-1]). Bone mineral density was measured with dual x-ray absorptiometry.

RESULTS

The fracture group was slightly older than the control group (mean and standard deviation [SD], 66.8 ± 10.8 years versus 63.3 ± 9.0 years, p = 0.008), had a lower body mass index (26.4 ± 5.9 kg/m(2) versus 28.0 ± 6.2 kg/m(2), p = 0.05), and more commonly had had a prior fracture (52% versus 31%, p < 0.001). Bone mineral density at the hip was lower in the fracture group than in the control group (0.831 ± 0.130 g/cm(2) versus 0.917 ± 0.139 g/cm(2), p < 0.001). The mean 25(OH)D levels were similar in the fracture and control groups (44.4 ± 14.6 ng/mL versus 41.3 ± 14.5 ng/mL, p = 0.08). Levels of serum markers of bone formation were significantly higher in the fracture group than in the control group (P1NP: 70.4 ± 33.2 ng/mL versus 53.2 ± 25.6 ng/mL, p < 0.001; osteocalcin: 22.3 ± 9.9 ng/mL versus 20.2 ± 9.2 ng/mL, p = 0.017). Levels of BSAP, PTH, and CTX-1 were similar in the two groups. Multivariable logistic regression showed independent associations between a distal radial fracture and low total hip bone mineral density (odds ratio [OR] = 2.02 for each decrease of 1 SD, 95% confidence interval [CI] = 1.38 to 3.01, p < 0.001) and a high P1NP level (OR = 2.17 for each 1-SD increase, 95% CI = 1.52 to 3.06, p < 0.001).

CONCLUSIONS

In this cohort, 25(OH)D levels were not associated with distal radial fracture and do not appear to affect the risk assessment for distal radial fracture in postmenopausal women. Patients with a distal radial fracture, however, had increased bone turnover as evidenced by high P1NP and osteocalcin levels. Women with both a high P1NP level and low bone mineral density were at particularly high risk for fracture.

OBJECTIVE

To estimate the discriminative value of serum P1NP/βCTX ratio and albumin levels in hospitalized orthogeriatric patients with and without nonvertebral fractures.

METHODS

In 1,239 orthogeriatric patients (mean age 78.1±9.52 years, 69.1% women) including 854 (68.9%) with osteoporotic nonvertebral fractures (455 [36.7%] with hip fracture [HF]) and 385 (31.1%) without fractures, markers of bone formation (procollagen type 1 N-terminal propeptide [P1NP], osteocalcin [OC], and bone resorption (beta-C-terminal cross-linking telopeptide of type 1 collagen [βCTX]), indices of mineral metabolism, and parameters of liver and renal functions were assessed; data on clinical and laboratory characteristics were collected prospectively.

RESULTS

Both lower serum P1NP/βCTX ratio and albumin concentration (as continuous or categorical variables) were independently associated with fracture presence in multivariate logistic regressions. Compared with the highest P1NP/βCTX tertile, the prevalence of HF, after adjustment for multiple covariates, was 3-fold higher in the lowest tertile and 1.5 times higher in the middle tertile; presence of any fracture was 2.3- and 1.6-fold higher, respectively; patients with albumin levels in the lowest tertile had multivariate odds ratio (OR) of 4.6 for HF and 2.8 for any fracture, in the middle tertile the ORs were 2.2 and 1.3, respectively. The P1NP/βCTX <100.0 (median) and hypoalbuminemia (<33 g/L) demonstrated area under the curve values for HF of 0.802 and 0.806, respectively, and for any fractures of 0.711 and 0.706, respectively. When both characteristics were combined, the ORs for HF or any fracture, compared with the nonfractured group, were 7.8 and 3.2, respectively, with an accuracy of 79.6% and 71.6%, respectively.

CONCLUSIONS

In orthogeriatric patients, both serum P1NP/βCTX ratio and albumin levels demonstrated an inverse dose-effect relationship with the prevalence of nonvertebral fractures and independently indicated fracture presence with acceptable discriminatory power. Lower P1NP/βCTX (<100) and hypoalbuminemia could be useful simple additive prognostic tools for fracture risk stratification in the elderly.

Bone turnover markers are used for monitoring osteoporosis treatment. Therefore, we evaluated the agreement between different assays for CTX and PINP and established reference intervals in a cohort of 2300 individuals. We found poor agreement between assays and different reference intervals. This highlights the importance of harmonization of the assays.

Two reference markers for bone turnover have been proposed: CTX bone resorption and P1NP for bone formation. The purpose of the current study was to establish reference intervals for the two markers in a Danish cohort and to determine the agreement on the two platforms.

Fasting sera from 2308 individuals (1250 males and 1058 females, age range 24-76 years) participating in the Health2006 study were analyzed for CTX and P1NP using the automated IDS-iSYS analyzer and the automated Cobas e411 analyzer. Participants in anti-osteoporotic treatment were excluded, while subjects on hormonal contraceptives were included.

There was significant disagreement between both the two P1NP assays with a mean difference of -3 μg/L (LoA -19 to 14) (p < 0.001) and the two CTX assays with a mean difference of 13 ng/L (LoA-187 to 214) (p < 0.001). For CTX, there was a systematic bias: at low values, Cobas measured a higher value than iSYS and at higher concentrations, iSYS measured increasingly higher values than Cobas. Based on the results, we propose three reference intervals for each sex: 25-29, 30-39, and 40-80 years for men, and 25-29, >30 (pre-menopausal), and >30 years (post-menopausal) for women.

There is significant disagreement between the IDS-iSYS and Roche Cobas assays for both reference markers. Consequently, the reference intervals for an adult, healthy population are different depending on the analysis method used. Therefore, repeated measurements of patient samples used for monitoring of treatment should be done on the same assay. Moreover, assay-specific reference intervals should be used. Harmonization of assays for BTM is highly warranted.

We explored the effects of PTH(1-84) compared with strontium ranelate on bone remodeling as measured by bone remodeling markers in postmenopausal women with osteoporosis. Biochemical markers of bone formation were significantly increased after treatment with PTH(1-84) but not strontium ranelate, indicating a different mechanism of action between these agents.

BACKGROUND

PTH(1-84) and strontium ranelate (SR) are both known to reduce fracture risk in osteoporosis. Measuring changes in biochemical markers of bone turnover induced by these agents can help in characterizing the action of PTH(1-84) and SR on bone remodeling.

METHODS

A 24-week, randomized, open-label, parallel group, phase IV trial was conducted in 81 postmenopausal women with primary osteoporosis (≥50 years of age, lumbar spine, or total hip T-score ≤-2.5 SD) to assess the effect of SR as compared to PTH(1-84) on bone formation markers P1NP and BSAP. The bone resorption marker CTX was also measured. Subjects were randomly assigned to receive daily either 100 μg PTH(1-84) (n = 41) (subcutaneous injection) or oral 2 g SR (n = 40) for 24 weeks with daily supplements of 800 IU vitamin D(3) and 1,000 mg calcium. Patient-reported outcomes were collected to investigate the effect of treatment on quality of life (QoL).

RESULTS

Percentage changes from baseline in P1NP and BSAP were significantly increased for PTH(1-84) by week 24 compared with SR (p < 0.0001). Significant changes from baseline in P1NP and BSAP were noted for PTH(1-84) from week 4 onwards; no significant changes were noted for SR. A trend towards a positive impact on QoL was seen with PTH(1-84) treatment. Safety profiles concur with previous analyses.

CONCLUSIONS

PTH(1-84) had a more rapid and higher effect on bone formation markers compared to SR, indicating that SR has a different mode of action on bone remodeling than the bone building agent PTH(1-84) in postmenopausal women with osteoporosis.

Progressive bone mineral loss and increasing bone fragility are hallmarks of osteoporosis. A combination of minerals isolated from the red marine algae, Lithothamnion sp. was examined for ability to inhibit bone mineral loss in female mice maintained on either a standard rodent chow (control) diet or a high-fat western diet (HFWD) for 5, 12, and 18 months. At each time point, femora were subjected to μ-CT analysis and biomechanical testing. A subset of caudal vertebrae was also analyzed. Following this, individual elements were assessed in bones. Serum levels of the 5b isoform of tartrate-resistant acid phosphatase (TRAP) and procollagen type I propeptide (P1NP) were also measured. Trabecular bone loss occurred in both diets (evident as early as 5 months). Cortical bone increased through month 5 and then declined. Cortical bone loss was primarily in mice on the HFWD. Inclusion of the minerals in the diet reduced bone mineral loss in both diets and improved bone strength. Bone mineral density was also enhanced by these minerals. Of several cationic minerals known to be important to bone health, only strontium was significantly increased in bone tissue from animals fed the mineral diets, but the increase was large (5-10 fold). Serum levels of TRAP were consistently higher in mice receiving the minerals, but levels of P1NP were not. These data suggest that trace minerals derived from marine red algae may be used to prevent progressive bone mineral loss in conjunction with calcium. Mineral supplementation could find use as part of an osteoporosis-prevention strategy.

This study aimed to investigate the effect of feeding carbohydrate and protein (CHO + PRO), immediately or 2 h after an exhaustive run, on the bone turnover response in endurance runners.

Ten men (age = 28 ± 5 yr, height = 1.74 ± 0.05 m, body mass [BM] = 69.7 ± 6.3 kg) performed treadmill running at 75% V˙O2max, until exhaustion, on three occasions. Blood was collected before and immediately, 1, 2, 3, 4, and 24 h postexercise, for measurement of β-CTX, P1NP, parathyroid hormone, PO4, ACa, and Ca. This was a randomized, counterbalanced, placebo-controlled, and single-blinded crossover study. The three trials were (i) placebo (PLA), where the PLA solution was ingested immediately and 2 h postexercise; (ii) immediate feeding (IF), where CHO + PRO (1.5 g·kg BM dextrose and 0.5 g·kg BM whey) was ingested immediately postexercise and PLA 2 h postexercise; and (iii) delayed feeding (DF), where PLA was ingested immediately postexercise and CHO + PRO solution 2 h postexercise. Data were analyzed using repeated-measures ANOVA and Tukey's HSD post hoc test.

At 1 and 2 h postexercise, β-CTX concentrations were lower in the IF trial compared with the DF and PLA trials (P ≤ 0.001). At 3 h postexercise, β-CTX concentrations were higher in the PLA trial compared with the IF (P ≤ 0.001) and DF trials (P = 0.026). At 4 h postexercise, β-CTX concentrations were lower in the DF trial compared with the IF (P = 0.003) and PLA trials (P ≤ 0.001). At 4 h postexercise, P1NP was higher in the IF trial compared with the DF (P = 0.026) and PLA trials (P = 0.001). At 3 h postexercise, parathyroid hormone was higher in the IF trial compared with the DF trial (P ≤ 0.001).

After exhaustive running, immediate ingestion of CHO + PRO may be beneficial, as it decreases bone resorption marker concentrations and increases bone formation marker concentrations, creating a more positive bone turnover balance.

The gut hormone glucose-dependent insulinotropic polypeptide (GIP) causes postprandial insulin release and inhibits bone resorption assessed by carboxy-terminal collagen crosslinks (CTX).

To study if GIP affects bone homeostasis biomarkers independently of insulin release and glycemic level.

Randomized, double-blinded, crossover study with 5 study days.

Ten male C-peptide-negative patients with type 1 diabetes.

On 3 matched days with "low glycemia" (plasma glucose in the interval 3 to 7 mmol/L for 120 minutes), we administered intravenous (IV) GIP (4 pmol × kg-1 × min-1), glucagon-like peptide 1 (1 pmol × kg-1 × min-1), or placebo (saline), and on 2 matched days with "high glycemia" (plasma glucose 12 mmol/L for 90 minutes), we administered either GIP or saline.

CTX, procollagen type 1 N-terminal propeptide (P1NP), and parathyroid hormone (PTH).

During low glycemia: GIP progressively suppressed CTX from baseline by up to 59 ± 18% compared with 24 ± 10% during saline infusion (P < 0.0001). Absolute values of P1NP and PTH did not differ between days. During high glycemia: GIP suppressed CTX from baseline by up to 59 ± 19% compared with 7 ± 9% during saline infusion (P < 0.0001). P1NP did not differ between days. GIP suppressed PTH after 60 minutes compared with saline (P < 0.01), but this difference disappeared after 90 minutes.

Short-term GIP infusions robustly reduce bone resorption independently of endogenous insulin secretion and during both elevated and low plasma glucose, but have no effect on P1NP or PTH after 90 minutes.

The purpose of this study was to perform a meta-analysis to examine the efficacy and safety of denosumab in postmenopausal women with osteoporosis.Medline, Cochrane Library, EMBASE, and Google Scholar databases were searched until October 30, 2014 using combinations of the following search terms: osteoporosis, postmenopause, postmenopausal, women, denosumab. The primary outcome was bone mineral density (BMD) change, and secondary outcomes were change in the bone turnover markers β-isomerized carboxy-terminal cross-linking telopeptide of type I collagen (CTX) and serum procollagen type I amino-terminal propeptide (P1NP), and adverse events.Patients treated with denosumab had significantly increased BMD of the lumbar spine (7.58%), total hip (4.86%), and distal third of the radius (2.92%) than those treated with placebo (all, P < 0.001). Patients treated with denosumab had a significant decrease of CTX (-66.16%) and P1NP (-64.65%) as compared with those treated with placebo (both, P < 0.001). Adverse events were similar between the 2 groups (pooled odds ratio = 1.04, P = 0.625).Denosumab increases BMD and decreases markers of bone turnover in postmenopausal women with osteoporosis, and is not associated with significant side-effects.

Bone response to a single bout of exercise can be observed with biochemical markers of bone formation and resorption. The purpose of this study was to examine the response of bone biochemical markers to a single bout of exhaustive high-impact exercise. 15 physically active young subjects volunteered to participate. The subjects performed continuous bilateral jumping with the ankle plantarflexors at 65 % of maximal ground reaction force (GRF) until exhaustion. Loading was characterized by analyzing the GRF recorded for the duration of the exercise. Venous blood samples were taken at baseline, immediately after, 2h and on day 1 and day 2 after the exercise. Procollagen type I amino terminal propeptide (P1NP, marker of bone formation) and carboxyterminal crosslinked telopeptide (CTx, marker of bone resorption) were analyzed from the blood samples. CTx increased significantly (32 %, p = 0.015) two days after the exercise and there was a tendensy towards increase seen in P1NP (p = 0.053) one day after the exercise. A significant positive correlation (r = 0.49 to 0.69, p ≤ 0.038) was observed between change in P1NP from baseline to day 1 and exercise variables (maximal slope of acceleration, body weight (BW) adjusted maximal GRF, BW adjusted GRF exercise intensity and osteogenic index). Based on the two biochemical bone turnover markers, it can be concluded that bone turnover is increased in response to a very strenuous single bout of exhaustive high-impact exercise. Key pointsStudies on bone acute biochemical response to loading have yielded unequivocal results.There is a paucity of research on the biochemical bone response to high impact exercise.An increase in bone turnover was observed one to two days post exercise.

The aim of the study was to investigate a potential role for vitamin D status on bone mineral density (BMD) during weight gain in patients with anorexia nervosa (AN).

Spine and hip BMD assessed by dual-energy X-ray absorptiometry (DXA), serum vitamin D (25-OH-D), N-propeptide of type I collagen (P1NP), C-terminal telopeptide of type I collagen (CTX), and intact parathyroid hormone (PTH) were measured before and after a 20-week intensive weight-restoration program in ninety-one female patients with AN and secondary amenorrhoea.

Ninety-one consecutive female patients (age 13-45 years; weight 39.4 ± 5.6 kg, body mass index [BMI] 15.1 ± 1.6 kg m-2 ) were included in the study. Although weight and BMI significantly increased in all patients during treatment, mean BMD only significantly increased at the spine (1.0% ± 3.6%, p = .009). The increase in spine BMD was significantly higher only above post-treatment 25-OH-D levels of 30 ng mL-1 (2.5% vs. 0.5%, respectively, for 25-OH-D ≥ and < 30 ng mL-1 , p = .026). There was a significant decrease in bone resorption (CTX; p = .043) and increased bone formation (P1NP; p < .001) after weight restoration. Nevertheless, a significant increase in PTH was also found, which was inversely correlated with decreased post-treatment 25-OH-D levels (R2 = .153, p < .001).

Hypovitaminosis D may counteract the efficacy of refeeding in AN through increased bone resorption mediated by secondary hyperparathyroidism, which strongly supports the use of vitamin D supplements for bone health in AN.

Vitamin D is synthesised in the skin during exposure to sunlight and its fundamental roles are the regulation of calcium and phosphate metabolism and bone mineralisation. The aim of our study was to evaluate serum levels of 25-hydroxyvitamin D3, PTH and bone turnover markers (P1NP, OC, beta-CTx, OC/beta-CTx) and the intake of calcium and vitamin D in Polish Professional Football League (Ekstraklasa) players and in young men with a low level of physical activity. Fifty healthy men aged 19 to 34 years were included in the study. We showed that 25(OH)D3 and P1NP levels and OC/beta-CTx were higher in the group of professional football players than in the group of physically inactive men. The daily vitamin D and calcium intake in the group of professional football players was also higher. We showed a significant relationship between 25(OH)D3 levels and body mass, body cell mass, total body water, fat-free mass, muscle mass, vitamin D and calcium intake. Optimum 25(OH)D3 levels were observed in a mere 16.7% of the football players and vitamin D deficiency was observed in the physically inactive men. The level of physical activity, body composition, calcium and vitamin D intake and the duration of exposure to sunlight may significantly affect serum levels of 25(OH)D3.