The risk of fragility fracture increases for people with type 2 diabetes mellitus (T2DM), even after controlling for bone mineral density, body mass index, visual impairment, and falls. We hypothesize that progressive glycemic derangement alters micro-scale bone tissue composition. We used Fourier-transform infrared (FTIR) imaging to analyze the composition of iliac crest biopsies from cohorts of post-menopausal women characterized by oral glucose tolerance testing: normal glucose tolerance (NGT; n=35, age=65±7, HbA1c=5.8±0.3%), impaired glucose tolerance (IGT; n=26, age=64±5, HbA1c=6.0±0.4%), and overt T2DM on insulin (n=25, age=64±6, HbA1c=9.13±0.6). The distributions of cortical bone mineral content had greater mean values (+7%) and were narrower (-10%) in T2DM vs. NGT groups (p<0.05). The distributions of acid phosphate, an indicator of new mineral, were narrower in cortical T2DM vs. NGT and IGT groups (-14% and -14%, respectively) and in trabecular NGT and IGT vs. T2DM groups (-11% and -10%, respectively) (all p<0.05). The distributions of crystallinity were wider in cortical NGT vs. T2DM groups (+16%) and in trabecular NGT vs. T2DM groups (+14%) (all p<0.05). Additionally, bone turnover was lower in T2DM vs. NGT groups (P1NP: -25%, CTx: -30%, ucOC: -24%). Serum pentosidine was similar across groups. The FTIR compositional and biochemical marker values of the IGT group typically fell between the NGT and T2DM group values, though the differences were not always statistically significant. In summary, worsening glycemic control was associated with greater mineral content and narrower distributions of acid phosphate, an indicator of new mineral, which together are consistent with observations of lower turnover; however, wider distributions of mineral crystallinity were also observed. A more mineralized, less heterogeneous tissue may affect tissue-level mechanical properties, and in turn degrade macroscale skeletal integrity. In conclusion, these data are the first evidence of progressive alteration of bone tissue composition with worsening glycemic control in humans.

Bone remodelling markers (BRMs) are suppressed following a glucose load and during glucose infusion. As exercise increases indices of bone health and improves glucose handling, we hypothesised that, at rest, hyperinsulinaemic-euglycaemic clamp will suppress BRMs in obese men and that exercise prior to the clamp will prevent this suppression. Eleven obese nondiabetic men (age 58.1±2.2 years, body mass index=33.1±1.4 kg m(-2) mean±s.e.m.) had a hyperinsulinaemic-euglycaemic clamp (HEC) at rest (Control) and 60 min post exercise (four bouts × 4 min cycling at 95% of hazard ratiopeak). Blood samples were analysed for serum insulin, glucose, bone formation markers, total osteocalcin (tOC) and procollagen type 1 N-terminal propeptide (P1NP), and the bone resorption marker, β-isomerised C-terminal telopeptides (β-CTx). In the control trial (no exercise), tOC, P1NP and β-CTx decreased with HEC by >10% compared with baseline (P<0.05). Fasting serum glucose, but not insulin, tended to correlate negatively with the BRMs (β range -0.57 to -0.66, p range 0.051-0.087). β-CTx, but not OC or P1NP, increased within 60 min post exercise (∼16%, P<0.01). During the post-exercise HEC, the glucose infusion rate was ∼30% higher compared with the no exercise trial. Despite this, BRMs were only suppressed to a similar extent as in the control session (10%). HEC suppressed BRMs in obese men. Exercise did not prevent this suppression of BRMs by HEC but improved glucose handling during the trial. It remains to be tested whether an exercise intervention of longer duration may be able to prevent the effect of HEC on bone remodelling.

Osteoporosis is a major health problem in postmenopausal women and the elderly that leads to fractures associated with substantial morbidity and mortality. Current osteoporosis therapies have significant drawbacks, and the risk of fragility fractures has not yet been eliminated. There remains an unmet need for a broader range of therapeutics. Previous studies have shown that YC-1 has important regulatory functions in the cardiovascular and nervous systems. Many of the YC-1 effector molecules in platelets, smooth muscle cells and neurons, such as cGMP and μ-calpain, also have important functions in osteoclasts. In this study, we explored the effects of YC-1 on bone remodeling and determined the potential of YC-1 as a treatment for postmenopausal osteoporosis. Micro-computed tomography of lumbar vertebrae showed that YC-1 significantly improved trabecular bone microarchitecture in ovariectomized rats compared with sham-operated rats. YC-1 also significantly reversed the increases in serum bone resorption and formation in these rats, as measured by enzyme immunoassays for serum CTX-1 and P1NP, respectively. Actin ring and pit formation assays and TRAP staining analysis showed that YC-1 inhibited osteoclast activity and survival. YC-1 induced extrinsic apoptosis in osteoclasts by activating caspase-3 and caspase-8. In osteoclasts, YC-1 stimulated μ-calpain activity and inhibited Src activity. Our findings provide proof-of-concept for YC-1 as a novel antiresorptive treatment strategy for postmenopausal osteoporosis, confirming an important role of nitric oxide/cGMP/protein kinase G signaling in bone.

Background: Risedronate increases bone mineral density (BMD) and reduces fracture risk, but treatment response may depend on the baseline state of bone turnover. Data regarding the selection of therapeutic drugs or the prediction of therapeutic effects with baseline levels of bone turnover markers (BTMs) as a reference are insufficient. We hypothesized that when the baseline levels of BTMs are higher, baseline BMD might be lower, changes in BMD at 12 months after risedronate treatment might be higher, and the reduction of fracture incidence might be greater. This study aimed to analyze the data of a phase III clinical trial of risedronate from Japan to investigate the relationships between baseline BTM levels and (1) baseline BMD, (2) changes in BMD at 12 months after the start of treatment, and (3) the incidence of new vertebral fractures.

Methods: This post-hoc analysis included 788 postmenopausal women with osteoporosis whose baseline BTM levels as well as baseline and endpoint BMDs were measured. Relationships between baseline BTM levels and BMD at baseline and 12 months after risedronate treatment and new vertebral fractures were examined. One-way analysis of variance, two-tailed Student's t-test, and Fisher's exact test were used to analyze the data.

Results: Baseline BMD showed a significant upward trend when baseline BTM levels were lower in the analysis by tertiles. New vertebral fractures tended to occur in patients with prevalent vertebral fractures, but the relationship between new fractures and BTM levels was not statistically significant. Regardless of BTM types, BMD percentage increments (%) and increments (g/cm²) with the 12-month treatment were high when pretreatment BTM levels were high (P < 0.0001), and a >5.0% increase in BMD was observed even if baseline BTM levels were within the normal range. A new vertebral fracture occurred in only six patients (0.77%), and there was not enough statistical power to clarify the relationship between baseline BTM levels and fracture risk reduction.

Conclusions: When pretreatment BTM levels increased, baseline BMD tended to be lower and the increase in BMD with 12-month risedronate treatment was higher. However, BMD could still be increased even if the baseline BTM levels are within the normal range. Combined with available evidence, baseline BTMs may not have an important role in deciding the optimal therapy. To elucidate the relationship between baseline BTM levels and long-term fracture risk, it will be necessary to conduct more large-scale studies with a longer follow-up period in severe osteoporotic patients with a high fracture risk.

Mini abstract: We evaluated the significance of baseline bone turnover markers in the response to risedronate treatment. The increase in the bone mineral density (BMD) with the 12-month treatment may be higher when the state of bone turnover at baseline is higher, and BMD could still be increased even if the baseline bone turnover is within the normal range.

Keywords: A, anterior; BAP, bone isoforms of alkaline phosphatase; BMD, bone mineral density; BTMs, bone turnover markers; Bone isoforms of alkaline phosphatase; Bone turnover markers; C, central; C-telopeptide of type I collagen; CTX, C-telopeptide of type I collagen; DPD, deoxypyridinoline; LS-BMD, lumbar spine bone mineral density; P, posterior; P1NP, N-propeptide of type I collagen; Risedronate; SD, standard deviation; TRACP-5b, tartrate-resistant acid phosphatase-5b; Tartrate-resistant acid phosphatase-5b; ULN, upper limit of the normal range.

Bone formation/remodeling-associated biomarkers, such as osteocalcin, amino pro-peptide of type 1 collagen (P1NP) and CrossLaps (CTX) have been deregulated in type 2 diabetes mellitus (T2DM) patients. In particular, the T2DM-associated sclerostin markedly inhibits the bone formation, suppresses the osteoblast activity and downregulates the bone turnover.

In the present study, we examined the serum levels of sclerostin, osteocalcin, P1NP and CTX in the T2DM patients. We evaluated the regulation on osteocalcin, P1NP and CTX by sclerostin treatment in osteoblast hFOB 1.19 cells. Finally, we determined the mediation of Wnt signaling in the regulation by sclerostin on osteocalcin, P1NP and CTX in human osteoblast hFOB 1.19 cells.

It was demonstrated that osteocalcin, P1NP and CTX were downregulated in the femur fracture of patients with T2DM, whereas the serum level of the sclerostin was markedly higher in the femur fracture of patients with T2DM. Moreover, the downregulated osteocalcin, P1NP or CTX was negatively associated with the upregulated sclerostin. In vitro results confirmed that sclerostin downregulated the expression of osteocalcin, P1NP and CTX in hFOB 1.19 cells. Also, our results demonstrated that Wnt/β-catenin inhibition was associated with the sclerostin-mediated inhibition of osteocalcin, P1NP and CTX in hFOB 1.19 cells. The Wnt/β-catenin level was markedly inhibited by sclerostin treatment, and the siRNA-mediated downregulation of β-catenin reduced the levels of osteocalcin, P1NP and CTX.

Our study demonstrated that the upregulated serum sclerostin level in the T2DM patients with fracture inhibited the expression of the bone formation/remodeling-associated biomarkers via antagonizing Wnt signaling. It suggests that sclerostin might be an effective target for T2DM-associated bone fracture and delayed fracture healing.

Polycystic ovary syndrome (PCOS) in an intricate disorder characterized by reproductive and metabolic abnormalities that may affect bone quality and strength along with the lifespan. The present study analysed the impact of postnatal androgenization (of a single dose of testosterone propionate 1.25 mg subcutaneously at day 5 of life) on bone development and markers of bone metabolism in adult female Wistar rats. Compared with healthy controls, the results of measurements of micro-computed tomography (microCT) of the distal femur of androgenized rats indicated an increased cortical bone volume voxel bone volume to total volume (VOX BV/TV) and higher trabecular number (Tb.n) with reduced trabecular separation (Tb.sp). A large magnitude effect size was observed in the levels of circulating bone formation Procollagen I N-terminal propeptide (P1NP) at day 60 of life; reabsorption cross-linked C-telopeptide of type I collagen (CTX) markers were similar between the androgenized and control rats at days 60 and 110 of life. The analysis of gene expression in bone indicated elements for an increased bone mass such as the reduction of the Dickkopf-1 factor (Dkk1) a negative regulator of osteoblast differentiation (bone formation) and the reduction of Interleukin 1-b (Il1b), an activator of osteoclast differentiation (bone reabsorption). Results from this study highlight the possible role of the developmental programming on bone microarchitecture with reference to young women with PCOS.

Infusion of the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) suppresses the bone resorption marker carboxy-terminal type 1 collagen crosslinks (CTX). Using separate and combined infusions of the selective GIP receptor (GIPR) antagonist, GIP(3-30)NH₂, and GIP, we investigated how GIPR inhibition affects bone turnover markers. Ten healthy men (median age 22.5 years (range 21-25), BMI 21.3 kg/m² (19.9-24.7)) participated in a randomized, doubled blinded, placebo-controlled, crossover study with four 1 -h 12 mmol/l-hyperglycemic clamps on four separate study days with concomitant infusions of GIP, GIP + GIP(3-30)NH₂, GIP(3-30)NH₂, and placebo, respectively, separated by a period of at least one week. GIP was infused at 1.5 pmol/kg/min and GIP(3-30)NH₂ at 800 pmol/kg/min. Plasma glucose was clamped at 12.0 ± 1.2 mmol/l and plasma levels of GIP and GIP(3-30)NH₂ amounted to ∼80 pmol/l and ∼50 nmol/l, respectively. GIP suppressed CTX more than placebo (baseline-subtracted AUC -6,811 ± 1,260 vs. -3,012 ± 3,018 ng/l × min, P = 0.002) and resulted in CTX values of 53 ± 6.9% (GIP) versus 81 ± 10% of baseline (placebo), respectively (P = 0.0006), at the end of the hyperglycemic clamp. Co-infusion of GIP and GIP(3-30)NH₂ attenuated the GIP-induced CTX suppression by 51 ± 33% (P = 0.01). The peak value of the bone formation marker N-terminal propeptide of type 1 procollagen (P1NP) peaked at higher levels during GIP (109 ± 6.7% of baseline) than during GIP(3-30)NH₂ infusion (101 ± 8.9%) (P = 0.049) and GIP suppressed PTH levels compared to GIP(3-30)NH₂ alone (P = 0.0158). In conclusion, blockade of the GIPR with GIP(3-30)NH₂ diminished GIP-induced CTX and P1NP responses, showing that these effects are GIPR-mediated and that GIPR antagonism might interfere with bone resorption.

The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are well known for their insulinotropic effects and they are thought to affect bone homeostasis as mediators in the so-called entero-osseous axis. We examined the contributions of endogenous GIP and GLP-1, respectively, to postprandial bone homeostasis, in healthy subjects in two randomized and double-blind crossover studies. We included healthy men who received either four oral glucose tolerance tests (OGTTs) (n = 18, median age 27 (range 20-70), BMI 27.2 (22.4-37.0) kg/m²) or liquid mixed meal tests (MMTs) (n = 12, .age 23 (19-65), BMI 23.7 (20.3-25.5) kg/m²) with infusions of 1) the GIP receptor antagonist GIP(3-30)NH₂, 2) the GLP-1 receptor antagonist exendin(9-39)NH₂, 3) both GIP(3-30)NH₂ and exendin(9-39)NH₂, or 4) placebo infusions (saline) on four separate visits. Bone resorption was evaluated from levels of circulating carboxy-terminal collagen crosslinks (CTX) and bone formation from levels of procollagen type 1 amino-terminal propeptide (P1NP). During placebo infusions, baseline-subtracted area under the curve values for CTX were -39±5.0 (OGTT) and -57±4.3 ng/ml × min (MMT). When GIP(3-30)NH₂ was administered, CTX suppression was significantly diminished compared to placebo (-30±4.8 (OGTT) and -45±4.6 ng/ml × min (MMT), P=0.0104 and P=0.0288, respectively, compared to placebo. During exendin(9-39)NH₂ infusion, CTX suppression after OGTT/MMT was similar to placebo (P=0.28 (OGTT) and P=0.93 (MMT)). The relative contribution of endogenous GIP to postprandial suppression of bone resorption during both OGTT and MMT was similar and reached 22-25%. There were no differences in P1NP concentrations between interventions. In conclusion, endogenous GIP contributes by up to 25% to postprandial suppression of bone resorption in humans whereas an effect of endogenous GLP-1 could not be demonstrated.

Keywords: Bone metabolism; CTX; Exendin(9-39)NH(2); GIP(3-30)NH(2); Glucagon-like peptide 1; Glucose-dependent insulinotropic polypeptide; Gut-bone axis; Incretin hormones; bone resorption.

Bone quality is probably important for the survival of knee arthroplasty (KA), but little is known about systemic bone mineral density and bone turnover in patients prior to KA surgery. The aim of this study was to explore the prevalence of osteoporosis and bone turnover in relation to knee osteoarthritis (OA) grade in patients scheduled for KA surgery. Prospective preoperative evaluation of 450 patients (259 females) prior to KA between 2014 and 2016 with standing knee radiography, Dual-energy X-ray absorptiometry (DXA), biomarkers for bone turnover (CTX, P1NP), and vitamin D. Grading of knee OA was done with the Altman Atlas and Kellgren Lawrence (KL). Adjustments for age and BMI were made. The mean age was 67.9 years (range 39-94), and mean BMI was 28.8 (SD 4.8). The prevalence of osteoporosis was 9.6% (CI 95% 7.2; 12.7), while the proportion of patients with osteopenia was 36.0%. T score was similar between KL OA grade 3 and 4 (p = 0.06); however, T score was lower (p = 0.02) with the worst knee OA grade (attrition). The median serum Vitamin D level was 78.5 nmol/L (range 10-196), and there was no association between serum vitamin D and the grade of OA (p>> 0.88). P1NP was significantly higher in KL grade 4 compared to KL grade 3 (p = 0.03), but there was no association between KL grade and CTX (p = 0.21). 10% had osteoporosis, which is similar to the age-matched background population. Bone mineral density was lower with severe knee osteoarthritis (attrition), and P1NP was higher with worse osteoarthritis grading.

Available studies reported contradictory results about serum levels Dickkopf-1 (DKK1), an inhibitor of Wnt signaling in patients with ankylosing spondylitis (AS). In previous studies, we observed in other conditions that parathyroid hormone (PTH) serum levels were an important determinant of DKK1 serum levels. The aim of the present study was to investigate it in patients with AS. We recruited 71 patients diagnosed with AS. Levels of C-reactive protein (CRP), DKK1, PTH, 25OH-vitamin D, and bone turnover markers (intact N-propeptide of type I collagen, P1NP, and C-terminal telopeptide of type I collagen, CTX) were measured and compared to healthy controls (HC). Dual X-ray absorptiometry at lumbar spine and proximal femoral site was used for bone mineral density (BMD) assessment and spine X-rays were also performed. PTH serum levels were found to be significantly higher in AS patients than in HC (33.8 ± 14.11 vs 24.8 ± 13 pg/ml, p = 0.002), while mean DKK1 serum levels were lower than in HC (23.3 ± 13.1 vs 29.8 ± 15.9 pmol/l, p = 0.009). A positive correlation between DKK1 and PTH (correlation coefficient + 0.25, p = 0.03) was observed; it remained significant in a multivariate analysis. In patients with longer disease duration, DKK1 was also positively correlated with CTX (coefficient 0.42, p = 0.01), and PTH was higher in those patients with low BMD (Z-score ≤ - 1) at any site (p = 0.04). Also in AS, PTH is an important determinant of DKK1 serum levels and should be evaluated in studies on DKK1. PTH might have a role in bone involvement in AS, also through the Wnt pathway.

Fibrous dysplasia is a rare bone disorder, commonly associated with pain, deformity and fractures, which may significantly impact on quality of life. In this study we evaluate quality of life in patients with fibrous dysplasia using the Short Form-36 and the Brief Pain Inventory questionnaires. Data were compared with those of the general Dutch population.

Out of 138 patients from a cohort of 255 patients with fibrous dysplasia that were sent questionnaires assessing quality of life and pain, the response rate was 70.3%, with 97 patients, predominantly female (65%), completing the questionnaires. Monostotic fibrous dysplasia was predominant (n = 62, 64%). Fibrous dysplasia patients had significantly lower quality of life outcome scores than the general Dutch population for all tested domains of the Short Form-36 except for the "Mental health" and the "Role emotional" domains. More severe forms of fibrous dysplasia, had the more severe Short-Form-36 quality of life outcomes, but there was no significant difference in Brief Pain Inventory domains between different subtypes of fibrous dysplasia. Quality of life was lower in patients with higher disease burden, as reflected by high skeletal burden scores (p = 0.003) and high levels of P1NP (p = 0.002).

We demonstrate impairments in all domains of quality of life, except for 'Mental health' and 'Role emotional' domains, across the wide spectrum of fibrous dysplasia including its milder forms. We identified high skeletal burden scores, reflecting disease severity, as the most consistent predictor of impaired quality of life. Our findings hold significant clinical implications as they draw attention to the clinically unmet need to address quality of life issues in the management of patients with all subtypes of fibrous dysplasia, including its milder forms.

OBJECTIVE

We measured the levels of bone turnover markers (BTMs) in patients with early diabetic nephropathy from type 2 diabetes mellitus (T2DM), and investigated the associations of BTMs with adipokines, serum fibroblast growth factor-21 (FGF21) and osteonectin.

METHODS

We included 159 males and 300 females with T2DM in this cross-sectional study. Clinical characteristics, BTMs and adipokines levels were measured.

RESULTS

One-hundred and ninety-two (41.8%) patients presented with albuminuria. Patients with albuminuria had significantly higher levels of serum osteonectin (P<0.0001) and FGF21 (P=0.0125) than those with normoalbuminuria. Serum levels of P1NP were slightly lower among patients with albuminuria (P=0.031), but the difference disappeared after adjusting for FBG, PBG, and HbA1c. Serum FGF21 levels were independently and negatively related to eGFR (overall β=-0.161, P=0.001; albuminuria group β=-0.240, P=0.001) but not related to uACR. While Osteonectin was independently and positively related to uACR (overall β=0.209, P=0.001; albuminuria group β=0.170, P=0.021). The levels of serum FGF21 were independently inversely related with P1NP (overall β=-0.192, P<0.0001; albuminuria group β=-0.195, P=0.031).

CONCLUSIONS

Our results suggest that persistent hyperglycemia may inhibit bone formation. Both osteonectin and FGF21 were associated with early nephropathy in T2DM patients, albeit with different patterns.

Several preclinical and clinical studies show that selective serotonin reuptake inhibitors (SSRI's) are associated with bone loss and an increase in fracture risk, not many reports on their effect on bone turnover markers. This cross-sectional study evaluated the effect of SSRIs treatment on bone turnover markers in Indian population for the first time. Inclusion criteria were subjects of either sex and age 18-45 years undergoing treatment with an SSRI for at least 3 months, regardless of the indication. The results were compared with age-matched healthy controls. A total of 141 subjects were screened out of which 85 were enrolled, 44 in treatment and 41 in the control group. Serum Procollagen Type 1 Amino Terminal Propeptide (P1NP) levels were decreased in patients on SSRI treatment whereas no change was observed in the beta-C-terminal telopeptide (β-CTX) and receptor activator of nuclear factor kappa-Β ligand (RANKL) levels suggesting that these drugs can reduce bone formation but not resorption. Patients on SSRI treatment also showed reduced pCREB levels indicating that reduced bone formation is possibly through the gut mediated pathway. Our study suggests that SSRIs treatment at therapeutic doses may have a deteriorating effect on bone requiring caution in patients with additional risk factors.

Bone loss is one of the emerging extra-articular manifestations of rheumatoid arthritis. TNF-α is the main inflammatory cytokine that can directly increase bone resorption. However, its role in bone formation is still unknown, especially related to secreted frizzled-related protein 1 (SFRP-1), an osteoblast inhibitor. This study examines the correlation between TNF-α and SFRP-1, with a bone turn over marker (CTX and P1NP). This is a cross-sectional study with 38 subjects of premenopausal female patients with RA. This study found that 60.6% of the patients were in remission or low disease activity. The median of TNF-α was 10.6 pg/mL, mean of SFRP-1 was 9.29 ng/mL, mean of CTX was 2.74 ng/mL, and the median of P1NP was 34.04 pg/ml. There is positive correlation between TNF-α and P1NP (r = 0.363, p = 0.026), also between SFRP-1 and P1NP (r = 0.341; p = 0.036). A low level of TNF-𝛼, high level of SFRP-1, high level of CTX, and low level of P1NP in this study indicate a high bone turn over process, with dominant resorption activity in premenopausal female patients with RA.

Purpose: We aimed to determine the relationship between the levels of glycated hemoglobin (HbA1c) and biomarkers of bone metabolism in patients with type 2 diabetes mellitus (T2DM), and whether HbA1c independently influences any of these biomarkers.

Patients and methods: A cohort study of 240 patients with T2DM was performed. Serum was obtained and used to measure HbA1c, total cholesterol (TC), triglycerides, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol (LDL-C), very-low-density lipoprotein-cholesterol, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), total protein, albumin, blood urea nitrogen (BUN), creatinine, serum 25-hydroxyvitamin D (25OHD), osteocalcin (OC), β-C-terminal cross-linked telopeptide of type I collagen (β-CTX), procollagen type 1 N-terminal propeptide (P1NP), or parathyroid hormone (PTH) concentrations. The participants were divided into three study groups according to HbA1c level: <7%, 7-9% and ≥9%. Chi-square testing and one-way analysis of variance were used to compare groups. The relationships between HbA1c and bone metabolism biomarker values were analyzed using linear correlation analysis and multiple linear regression analysis.

Results: Age, duration of T2DM, and the concentrations of TC, LDL-C, apolipoprotein B, albumin, and BUN showed significant difference among the <7%, 7-9% and ≥9% HbA1c groups. Of the bone metabolism biomarkers, there were significant differences in serum 25-hydroxyvitamin D (25OHD) and osteocalcin (OC) among the groups. The correlation coefficients (r) for the relationships of HbA1c with 25OHD and OC were -0.200 and -0.183, respectively (P <0.05). Regardless of adjustment for none, some, or all of the confounding factors (age, sex, and duration of T2DM), the 25OHD and OC concentrations were significantly lower in the HbA1c ≥9% group than in the HbA1c <7% group. HbA1c showed no relationship with β-CTX, PINP, or PTH.

Conclusion: T2DM patients with poorer glycemic control had lower concentrations of serum 25OHD and OC, suggesting that HbA1c is an independent risk factor for low 25OHD and OC.

Keywords: bone metabolism; diabetes mellitus type 2; glycated hemoglobin.

Intermittent exercise might be an efficient means of exercise for improving bone strength and quality. The aim of our study was to examine the effect of intermittent running on bone turnover markers using altered exercise-to-rest intervals. Twelve males completed one control (no exercise), and three, 45-min intermittent protocols (5, 20, and 80 s intervals) matched for distance and speed. Fasted venous blood samples were collected at baseline, 1, 2 and 24 h post-exercise. Carboxyterminal crosslinked telopeptide (CTX-I) and procollagen type 1 amino-terminal propeptide (P1NP) were used as markers of bone resorption and formation. After adjustment for baseline, CTX-I concentration at 1 h was higher (very likely to most likely small) for 5 s (30.2%; ±90% confidence limits: 10%), 20 s (2.9.0%; ±10%) and 80 s (32.0%; ±10%) compared to control. The very likely small effect remained for 5 s at 2 h (30.2%; ±15%). The effect for 20 and 80 s was possibly trivial and possibly small/possibly trivial (∼14.5%; ±∼15%). Differences in P1NP concentrations were likely to very likely trivial (∼7.4%; ±∼7.6%). Circulating CTX-I concentration is affected acutely by intermittent running with short-interval (5 s) intermittent loading resulting in a prolonged attenuation in circadian rhythm of CTX-I up to 2 h that was not demonstrated as clearly by longer intervals despite matched internal and external training load.

OBJECTIVE

To investigate the clinical value of serum total procollagen type 1 aminoterminal propeptide (total P1NP), cross-linked C-terminal telopeptide of type I collagen (β-CTX) and 25(OH)D3 detection in evaluating the risks of fragile hip fracture in elderly patients with osteoporosis.

METHODS

Serum levels of total P1NP, β-CTX and 25(OH)D3 was measured in 68 elderly osteoporotic patients with fragile hip fracture and 68 age- and gender-matched osteoporotic controls without fragile hip fracture. In both groups, bone mineral density (BMD) was detected with dual X-ray absorptiometry.

RESULTS

The serum levels of total P1NP and β-CTX were significantly higher and 25(OH)D3 level was significantly lower in fragile hip fracture group than in the control group (P<0.05), but the two groups showed no significant difference in lumbar or total hip BMD. Bivariate correlation analysis suggested that in fragile hip fracture group, serum 25(OH)D3 level was positively, while serum total P1NP and β-CTX levels were inversely correlated with lumbar and total hip BMD (P<0.05). In control group, 25(OH)D3 was not related to lumbar or total hip BMD, and serum total P1NP and β-CTX levels were inversely correlated with total hip BMD (P<0.05) but not related to lumbar BMD.

CONCLUSIONS

In osteoporotic elderly patients with close BMD levels, high serum levels of total P1NP and β-CTX and low serum levels of 25(OH)D3 might independently indicate high fragile hip fracture risk, and detection of the three markers can help identify high-risk individuals.

Background and objectives: Para-sports have become increasingly competitive, necessitating greater physical activity; secondary disorder prevention is therefore crucial. Among secondary disorders, the female athlete triad (FAT) is defined as low energy availability (EA), menstrual dysfunction, and low bone mineral density (BMD); although studied in able-bodied athletes, reports on female para-athletes are scarce. We retrospectively investigated the FAT in wheelchair basketball players in the Japanese national team. Materials and Methods: Thirteen female wheelchair basketball players (mean age: 28.9 ± 8.1 years) were enrolled. The medical history (underlying diseases, gynecological disorders, and stress fractures), athletic and sport-specific parameters (wheelchair basketball classification, and wheelchair usage conditions), hematological status (hemoglobin, iron, estradiol, progesterone, total P1NP, and TRACP-5b levels), nutritional status (total energy, protein, calcium, and iron intake), body composition (BMD and lean body mass (LBM)), and EA were assessed. Results: Two (15.4%) had pertinent gynecological histories and six (46.2%) had menstrual cycle disorders. Three (23.1%) experienced excessive menstrual flow and nine (69.2%) had menstrual pain. No stress fractures were reported. All laboratory data were within normal limits. Total energy and iron intakes based on age-specific requirements were 99.8% and 59.8%, respectively. Iron and hemoglobin levels correlated with menstrual flow (ρ = -0.63, p = 0.019 and ρ = -0.56, p = 0.046, respectively). The mean total BMD was 109.2%, and the mean EA (41.4 kcal/kg LBM) was lower than recommended levels. The leg BMD in spinal disorders was significantly lower than that in skeletal disorders (p = 0.003). The arm LBM was higher (150.6%) than that of age-matched controls. Conclusion: Among female wheelchair basketball players with FAT, the total BMD was comparable to that of age-matched controls; however, leg BMD in spinal disorders was significantly lower than that in skeletal disorders. Players with heavy menstrual flow had lower hemoglobin and iron levels. Further research is needed on the FAT to optimize health and sports performance among para-athletes.

Objective: This study aims to investigate the beneficial effects of 17β-estradiol supplementation on the function of osteoblastic cells through the Sirtuin-1/nuclear transcription factor-κB/matrix metalloproteinase-8 (Sirt1/NF-κB/MMP-8) pathway.Methods: Mouse primary osteoblasts were obtained from neonatal mouse calvaria, and the cells were treated with or without 17β-estradiol. We first detected the effect of 17β-estradiol on the function of osteoblastic cells. Then, the changes in estrogen receptor-α (ERα), Sirt1, NF-κB, and MMP-8 were determined after the osteoblasts were treated with 17β-estradiol. During supplementation with 17β-estradiol, knockdown of Sirt1 in osteoblasts was used to further measure the changes of NF-κB and MMP-8 and observe the cell function.Results: In primary osteoblastic cells, exposure to 17β-estradiol improved cell viability and increased the levels of bone formation biomarkers, including osteocalcin, osteoprotegerin (OPG), procollagen type 1 N-terminal propeptide (P1NP), and alkaline phosphatase (ALP). In addition, 17β-estradiol supplement activated ERα and Sirt1 expression and inhibited NF-κB and MMP-8 expression. Moreover, these effects induced by 17β-estradiol were reversed by knockdown of Sirt1 in mouse primary osteoblasts.Conclusion: 17β-Estradiol replacement therapy may treat postmenopausal osteoporosis by improving osteoblastic cell function via the Sirt1/NF-κB/MMP-8 pathway.

Telephone call intervention did not improve alendronate persistence in Fracture Liaison Service (FLS) patients in this study. A bone turnover marker cut-off point for alendronate persistence is proposed for individual FLS patients.

FLS aims to prevent subsequent fractures, which should include improving patients' persistence with prescribed oral bisphosphonates. We studied the influence of telephone calls and the predictive value of changes in bone turnover markers (BTMs) for evaluating persistence with alendronate.

Postmenopausal women with a recent fracture and osteoporosis who started alendronate were randomized to receive three phone calls (PC) (after 1, 4, and 12 months) or no phone calls (no PC). s-CTX and P1NP were measured at baseline and after 3, 6, 9, and 12 months. As a reference group, 30 postmenopausal osteopenic patients with a recent fracture were analyzed as well. Persistence was assessed using the Dutch National Switch Point Pharmacies-GPs database and cross-referenced with PC, no PC, and BTM changes. Cut-off values of BTMs were calculated based on least significant change (LSC) and also on underrunning median values of the untreated osteopenic postmenopausal reference group with a recent fracture.

Out of 119 patients, 93 (78%) completed 12 months follow-up (45 PC and 48 no PC). Mean age was 69 years. Persistence was similar in PC and no PC participants. The cut-off value>> 29% (< 415 ng/L) as LSC of s-CTX and>> 36% (< 53.1 μg/L) as LSC of P1NP was determined optimally showing alendronate persistence after 1 year (being 93 and 88%, respectively).

In this context, telephone calls did not improve persistence. In around 90% of patients, 1-year alendronate persistence was confirmed by achieving LSC of s-CTX and of P1NP at 12 months.