Serum Bone Turnover Markers Research Articles

Declining serum bone turnover markers are associated with the short-term positive change of lumbar spine bone mineral density in postmenopausal women.

Objective:While serum bone turnover markers (BTMs) and bone mineral density (BMD) have been confirmed as useable risk assessment tools for postmenopausal osteoporosis, the associations between BTMs and BMD changes are still ambiguous. The aim of this study was to explore the underlying associations between BTMs and BMD changes in postmenopausal women.Methods:Between January 2015 and October 2020, 135 postmenopausal women were retrospectively enrolled. They were divided into two groups according to lumbar spine (LS) 1-4 BMD change (1 y T-score minus baseline T-score, Group 1 [n = 36] < 0 and Group 2 [n = 99] ≥ 0). The changes of BTMs (N-terminal middle segment osteocalcin [N-MID], propeptide of type I procollagen [P1NP], and β-C-terminal telopeptide of type I collagen [β-CTX]) and their associations with LS 1-4 BMD change were analyzed. The biochemical indices and clinical parameters related with LS 1-4 BMD change were also evaluated.Results:The 1 year N-MID, P1NP, β-CTX and Phosphorus in Group 2 were lower than those in Group 1 (P < 0.05), their changes within 1 year were significantly negatively correlated with LS 1-4 BMD change (R2 = –0.200, P < 0.001; R2 = –0.230, P < 0.001; R2 = –0.186, P < 0.001; R2 = –0.044, P = 0.015; respectively). Except for the Phosphorus change (area under the curve [AUC] = 0.623), the changes of N-MID, P1NP, and β-CTX and their 1 year levels had similar AUC to diagnose the short-term LS 1-4 BMD change (AUC > 0.7 for all, with the AUC of 1 y P1NP being the largest at 0.803). Binary logistic regression analysis showed that the physical activity and drug intervention were the determinant factors for the LS 1-4 BMD change (odds ratio = 6.856, 95% confidence interval: 2.058-22.839, P = 0.002; odds ratio = 5.114, 95% confidence interval: 1.551-16.864, P = 0.007; respectively).Conclusions:Declining N-MID, P1NP, β-CTX, and Phosphorus are associated with the short-term increase of LS 1-4 BMD within 1 year. Physical activity and drug intervention are factors significantly influencing the change of LS 1-4 BMD in postmenopausal women.

Prevalence of Vertebral Fractures in Adults With Type 1 Diabetes: DenSiFy Study (Diabetes Spine Fractures).

Vertebral fracture (VF) prevalence up to 24% has been reported among young people with type 1 diabetes (T1D). If this high prevalence is confirmed, individuals with T1D could benefit from preventative VF screening. We compared the prevalence of VFs between adults with T1D and nondiabetic controls. This cross-sectional study included 127 adults with T1D, and 65 controls with a similar age, sex, and BMI distribution, from outpatient clinics of 2 tertiary care centers. Vertebral fracture assessment (VFA) by dual-energy x-ray absorptiometry (DXA) was used for prevalent VFs. The modified algorithm-based qualitative (mABQ) method was applied. Bone mineral density (BMD) and trabecular bone score (TBS) were assessed by DXA. Serum bone turnover markers and sclerostin were measured in a subgroup of participants. Participants with T1D (70 women, 57 men) had a mean age of 42.8 ± 14.8 years, median diabetes duration of 25.8 (15.8-34.4) years, mean BMI of 26.6 ± 5.4 kg/m2 and mean HbA1c over the past 3 years of 7.5 ± 0.9%. Controls (35 women, 30 men) had mean age of 42.2 ± 15.9 years and mean BMI of 26.1 ± 5.1 kg/m2. VF prevalence was comparable between groups (2.4% vs 3.1%, P = 0.99). TBS, BMD at the total hip and femoral neck, and bone formation and resorption markers were lower while sclerostin levels were similar in participants with T1D vs controls. Our VFA results using the mABQ method do not confirm increased prevalence of VFs in men and women with relatively well-controlled T1D.

Bone adaptation to mechanical loading in mice is affected by circadian rhythms.

Physical forces are critical for successful function of many organs including bone. Interestingly, the timing of exercise during the day alters physiology and gene expression in many organs due to circadian rhythms. Circadian clocks in tissues, such as bone, express circadian clock genes that target tissue-specific genes, resulting in tissue-specific rhythmic gene expression (clock-controlled genes). We hypothesized that the adaptive response of bone to mechanical loading is regulated by circadian rhythms. First, mice were sham loaded and sacrificed 8h later, which amounted to tissues being collected at zeitgeber time (ZT)2, 6, 10, 14, 18, and 22. Cortical bone of the tibiae collected from these mice displayed diurnal expression of core clock genes and key osteocyte and osteoblast-related genes, such as the Wnt-signaling inhibitors Sost and Dkk1, indicating these are clock-controlled genes. Serum bone turnover markers did not display rhythmicity. Second, mice underwent a single bout of in vivo loading at either ZT2 or ZT14 and were sacrificed 1, 8, or 24h after loading. Loading at ZT2 resulted in Sost upregulation, while loading at ZT14 led to Sost and Dkk1 downregulation. Third, mice underwent daily in vivo tibial loading over 2weeks administered either in the morning, (ZT2, resting phase) or evening (ZT14, active phase). In vivo microCT was performed at days 0, 5, 10, and 15 and conventional histomorphometry was performed at day 15. All outcome measures indicated a robust response to loading, but only microCT-based time-lapse morphometry showed that loading at ZT14 resulted in a greater endocortical bone formation response compared to mice loaded at ZT2. The decreased Sost and Dkk1 expression coincident with the modest, but significant time-of-day specific increase in adaptive bone formation, suggests that circadian clocks influence bone mechanoresponse.

Lack of berberine effect on bone mechanical properties in rats with experimentally induced diabetes

Multidirectional health-promoting activities of some plant-derived substances make them candidates for drugs used in diabetes and its complications such as osteoporosis. Berberine is a compound for which both antidiabetic and antiosteoporotic effects have been documented. The aim of the study was to investigate the effects of berberine on the skeletal disorders induced by experimental type 1 diabetes in rats. The experiments were performed on 3-month-old female rats, divided into three groups: I – healthy control rats, II – diabetic control rats, III – diabetic rats receiving berberine. Diabetes was induced by a single streptozotocin injection. Berberine administration (50 mg/kg/day p.o.) started two weeks later and lasted four weeks. Serum bone turnover markers and other biochemical parameters, bone mass and mineralization, histomorphometric parameters and mechanical properties were studied. Diabetes induced strong disorders of bone turnover, bone microarchitecture, and strength of cancellous bone. Berberine counteracted the effect of diabetes on the bone formation marker (osteocalcin) concentration, the growth plate, and some parameters of cancellous bone microarchitecture, but did not improve bone mineralization and bone mechanical properties in the diabetic rats. The lack of effect of berberine on bone quality does not support its use in the prevention of diabetes-induced bone damage.

Prebiotic to Improve Calcium Absorption in Postmenopausal Women After Gastric Bypass: A Randomized Controlled Trial.

The adverse skeletal effects of Roux-en-Y gastric bypass (RYGB) are partly caused by intestinal calcium absorption decline. Prebiotics, such as soluble corn fiber (SCF), augment colonic calcium absorption in healthy individuals. We tested the effects of SCF on fractional calcium absorption (FCA), biochemical parameters, and the fecal microbiome in a post-RYGB population. Randomized, double-blind, placebo-controlled trial of 20 postmenopausal women with history of RYGB a mean 5 years prior; a 2-month course of 20 g/day SCF or maltodextrin placebo was taken orally. The main outcome measure was between-group difference in absolute change in FCA (primary outcome) and was measured with a gold standard dual stable isotope method. Other measures included tolerability, adherence, serum calciotropic hormones and bone turnover markers, and fecal microbial composition via 16S rRNA gene sequencing. Mean FCA ± SD at baseline was low at 5.5 ± 5.1%. Comparing SCF to placebo, there was no between-group difference in mean (95% CI) change in FCA (+3.4 [-6.7, +13.6]%), nor in calciotropic hormones or bone turnover markers. The SCF group had a wider variation in FCA change than placebo (SD 13.4% vs 7.0%). Those with greater change in microbial composition following SCF treatment had greater increase in FCA (r2 = 0.72, P = 0.05). SCF adherence was high, and gastrointestinal symptoms were similar between groups. No between-group differences were observed in changes in FCA or calciotropic hormones, but wide CIs suggest a variable impact of SCF that may be due to the degree of gut microbiome alteration. Daily SCF consumption was well tolerated. Larger and longer-term studies are warranted.

Bone turnover markers in gingival crevicular fluid and blood serum of patients with fixed orthodontic appliances.

Bone remodelling can be followed through the bone turnover markers (BTMs). Aim of the present study was to record the fluctuation of an osteoclastic and an osteoblastic BTM [C-terminal telopeptide of type I collagen (CTX) and N-terminal pro-peptide of type I pro-collagen (PINP), respectively] in both the gingival crevicular fluid (GCF) and the serum of orthodontic patients before and after the initial application of orthodontic forces. Twenty-one Caucasian patients were prospectively evaluated. GCF and blood samples were collected in order to measure the selected biomarkers by ELISA at three time-points: exactly before, 5 days, and 14 days after bonding of the appliances. Standardized sample handling and patient preparation procedures were adopted in order to reduce pre-analytical variability. GCF and serum CTX levels were found to be independent of age, although higher in the serum of female subjects. PINP levels were found higher in the serum of patients ≥25 years old, as well as in the GCF of males. A positive correlation between serum and GCF baseline PINP levels was observed. The effect of orthodontic treatment on bone remodelling might not be absolutely representative of the local bone microenvironment as the levels of the specific BTMs where measured within the GCF of the lower front teeth. This is the first time PINP and CTX have been evaluated in the GCF and serum of orthodontic patients with fixed appliances. No statistically significant alterations of CTX and PINP levels in the GCF and the serum of patients were recorded over time during the initial stages of orthodontic treatment.

Iron deficiency and high-intensity running interval training do not impact femoral or tibial bone in young female rats.

In the USA, as many as 20 % of recruits sustain stress fractures during basic training. In addition, approximately one-third of female recruits develop Fe deficiency upon completion of training. Fe is a cofactor in bone collagen formation and vitamin D activation, thus we hypothesised Fe deficiency may be contributing to altered bone microarchitecture and mechanics during 12-weeks of increased mechanical loading. Three-week old female Sprague Dawley rats were assigned to one of four groups: Fe-adequate sedentary, Fe-deficient sedentary, Fe-adequate exercise and Fe-deficient exercise. Exercise consisted of high-intensity treadmill running (54 min 3×/week). After 12-weeks, serum bone turnover markers, femoral geometry and microarchitecture, mechanical properties and fracture toughnessand tibiae mineral composition and morphometry were measured. Fe deficiency increased the bone resorption markers C-terminal telopeptide type I collagen and tartate-resistant acid phosphatase 5b (TRAcP 5b). In exercised rats, Fe deficiency further increased bone TRAcP 5b, while in Fe-adequate rats, exercise increased the bone formation marker procollagen type I N-terminal propeptide. In the femur, exercise increased cortical thickness and maximum load. In the tibia, Fe deficiency increased the rate of bone formation, mineral apposition and Zn content. These data show that the femur and tibia structure and mechanical properties are not negatively impacted by Fe deficiency despite a decrease in tibiae Fe content and increase in serum bone resorption markers during 12-weeks of high-intensity running in young growing female rats.

Increasing Vegetable Intake Decreases Urinary Acidity and Bone Resorption Marker in Overweight and Obese Adults: An 8-Week Randomized Controlled Trial

BackgroundControlled intervention trials are needed to confirm a positive association from epidemiological studies between vegetable consumption and bone health. ObjectiveWe investigated whether providing vegetables at the Dietary Guidelines for Americans (DGA) recommended amount affects excretion of acid and calcium in urine and bone turnover markers in serum in adults with low vegetable intake. MethodsIn total, 102 adults (19 males and 83 females, age 18–65 y, BMI ≥25 kg/m2) consuming ≤1 serving of vegetables (128 g raw leafy or 64 g cooked vegetables) per d were recruited in a 2-arm, parallel, randomized, controlled, and community-based 8-wk feeding intervention trial. The 2 arms included a vegetable intervention (VI) during which participants received extra vegetables (∼270 g/d) and an attention control (CON) group that conducted only the testing visits. Measurements included nutrient intake, plasma carotenoids, and bone-related markers in serum and urine. Differences between CON and VI at week 8 were tested using the ANCOVA with baseline values as a covariate. ResultsCompared with CON, carotenoid intake (mean ± SD) was higher (6.4 ± 3.4 compared with 2.0 ± 1.2 mg/d) (P < 0.01) and dietary potential renal acid load was lower (20 ± 13 compared with 3.4 ± 14 mEq/d) (P < 0.01) in VI. Compared with CON at week 8, urine titratable acid and Mg were 24 and 26% lower, respectively, while urine pH was 3% greater (P < 0.05) and serum C-terminal telopeptide of type I collagen (CTX) was 19% lower in VI. There were no group differences in serum concentrations of propeptide of type 1 procollagen and tartrate-resistant acid phosphatase or urinary excretion of deoxypyridinoline and CTX. ConclusionsConsumption of vegetables at the DGA-recommended amount by adults with low vegetable intake potentially benefits bone health. This trial was registered at http://clinicaltrials.gov as NCT02585102.

The mechanism of Epimedin B in treating osteoporosis as revealed by RNA sequencing-based analysis.

With the ageing of populations, the management of osteoporosis is a priority of society in general. Epimedin B, a major ingredient of Herba Epimedii, which has the advantages of high content and hypotoxicity has been proved to be effective in preventing osteoporosis in vitro. However, the efficacy and mechanism of Epimedin B on osteoporosis in vivo have not been well elucidated yet. This study aimed to investigate the effects and the potential mechanisms of 8-week repeated oral administration of Epimedin B (10 and 20 mg/kg/day) on a mouse osteoporosis model. Effects of Epimedin B were evaluated by examinations of serum bone turnover markers, bone mineral density, bone microstructure parameters and histopathological section. Epimedin B significantly rose N-terminal propeptide of type I procollagen (P1NP) and dropped C-telopeptide of type I collagen (CTX1). Connectivity density (Conn.D) increased significantly while structure model index (DA) decreased significantly after treated by Epimedin B. Meanwhile, Epimedin B administration significantly increased the number of trabecular bones while significantly decreased the gap between them. Overall, Epimedin B showed beneficial effects on osteoporosis. Furthermore, RNA sequencing-based analysis revealed 5 significantly down-regulated transcripts and 107 significantly up-regulated transcripts between the Epimedin B administration group and the model group. These transcripts were mapped to 15 pathways by KEGG enrichment analysis, of which PI3K-Akt signalling pathway, MAPK signalling pathway and PPAR signalling pathway were most connected to osteoporosis. To conclude, Epimedin B is effective in treating osteoporosis in mice via regulating PI3K-Akt, MAPK and PPAR signalling pathway.

Assessment of Serum sRANKL, sRANKL/OPG Ratio, and Other Bone Turnover Markers with the Estimated 10-Year Risk of Major and Hip Osteoporotic Fractures in Rheumatoid Arthritis: A Cross-Sectional Study.

Background Fracture risk assessment tool (FRAX) index was developed for estimating of the 10-year risk of major or hip osteoporotic fracture. To date, there is insufficient information regarding the correlation between FRAX and serum bone turnover markers (BTMs), such as soluble ligand of receptor activator of nuclear factor-κB (sRANKL), osteoprotegerin (OPG), and other molecules related with secondary osteoporosis in rheumatoid arthritis (RA). Therefore, this study is aimed at assessing the correlation between the FRAX and serum levels of sRANKL, OPG, sRANKL/OPG ratio, Dickkopf-1 (DKK-1), and sclerostin (SOST) in RA. Methods Cross-sectional study included 156 postmenopausal women with RA. Bone mineral density (BMD) was measured at lumbar spine (L1-L4) and total hip using dual-energy X-ray absorptiometry (DXA). RA patients were divided into (A) RA + osteoporosis and (B) RA without osteoporosis. FRAX scores were calculated including the total hip BMD. Serum sRANKL, OPG, DKK-1, and SOST levels were measured by ELISA. Pearson tests were used for assessing the correlation between serum levels of these molecules and FRAX scores in RA. Results The RA + osteoporosis group had elevated sRANKL levels (p = 0.005), higher sRANKL/OPG ratio (p = 0.017), decreased DKK-1 (p = 0.028), and lower SOST levels (p < 0.001). Low total hip BMD correlated with high sRANKL (p = 0.001) and sRANKL/OPG ratio (p = 0.005). Total hip and lumbar spine BMD correlated with DKK-1 (p = 0.009 and p = 0.05, respectively) and SOST levels (p < 0.001 and p < 0.001, respectively). Higher sRANKL levels and sRANKL/OPG ratio correlated with estimated 10-year risk of a major osteoporotic fractures (p = 0.003 and p = 0.003, respectively) and hip fracture (p = 0.002 and p = 0.006, respectively). High serum SOST levels were associated with a low estimated 10-year risk of a major osteoporotic fracture (p = 0.003) and hip fracture (p = 0.009). Conclusion High sRANKL levels and sRANKL/OPG ratio can be useful to detect a subgroup of RA patients who has an increased 10-year risk of major and hip osteoporotic fractures.

Effects of sleeve gastrectomy on bone mass, microstructure of femurs and bone metabolism associated serum factors in obese rats

BackgroundSleeve gastrectomy (SG) is a profoundly effective operation for severe obese patients, but is closely associated with bone mass loss. Previous studies have reported changes of various serum factors which may be associated with bone mass loss after SG. However, those results are contradictory. In this study, we assessed the effects of SG on bone mass, microstructure of femurs, and changes in bone turnover markers (BTMs), serum adipokines, inflammatory factors and gastrointestinal hormones after SG in high-fat diet (HFD) induced obese rats.MethodsEight-week-old male Sprague–Dawley (SD) rats were fed with HFD to induce obesity. Then, SG and sham surgery were performed in anesthetized obese rats. SD rats in control group were fed with standard chow. Microstructure of femurs was scanned and analyzed by micro-computed tomography in control group, HFD sham group and HFD SG group. Serum inflammatory factors, adipokines markers, gastrointestinal hormones and BTMs were also measured.ResultsBone mineral density (BMD) of trabecular bone in both HFD sham group and HFD SG group were remarkably decreased compared with control group. All serum BTMs were significantly higher in HFD SG group than HFD sham group. In the meantime, serum levels of several important inflammatory factors, gastrointestinal hormones and adipokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6, monocyte chemoattractant protein-1(MCP-1), ghrelin, insulin and leptin in HFD SG group were remarkably reduced compared with HFD sham group, whereas glucagon-like peptide-1 (GLP-1), adiponectin, fibroblast growth factor (FGF)-19 and FGF-21 were dramatically increased after SG. Protein tyrosine phosphatase 1B (PTP1B) was significantly increased in the HFD sham group than control group. Spearman’s correlation analysis indicated that serum osteocalcin (OC) and 25-hydroxy vitamin D3 (25(OH)D3) were positively correlated with BMD of trabecular bone, whereas serum PTP1B and TNF-α were negatively related to BMD of trabecular bone.ConclusionsSG aggravates bone mass loss and activates bone remodeling in obese rats. Levels of BTMs, adipokines, inflammatory factors, and gastrointestinal hormones could be affected by SG in obese rats. Serum PTP1B level might be associated with abnormal bone mass in obese rats.

Effects of a Lifestyle Intervention on Bone Turnover in Persons with Type 2 Diabetes: A Post Hoc Analysis of the U-TURN Trial.

The increased risk of fractures with type 2 diabetes (T2D) is suggested to be caused by decreased bone turnover. Current international guidelines recommend lifestyle modifications, including exercise, as first-line treatment for T2D. The aim of this study was to investigate the effects of an exercise-based lifestyle intervention on bone turnover and bone mineral density (BMD) in persons with T2D. Persons with T2D were randomized to either a 12-month lifestyle intervention (n = 64) or standard care (n = 34). The lifestyle intervention included five to six weekly aerobic training sessions, half of them combined with resistance training. Serum markers of bone turnover (osteocalcin, N-terminal propeptide of type-I procollagen, reflecting bone formation, and carboxyterminal collagen I crosslinks, reflecting bone resorption) and BMD (by DXA) were measured before the intervention and at follow-up. From baseline to follow-up, s-propeptide of type-I procollagen increased by 34% (95% confidence interval [CI], 17%-50%), serum-carboxyterminal collagen I crosslink by 36% (95% CI, 1%-71%), and s-osteocalcin by 31% (95% CI, 11-51%) more in the lifestyle intervention group compared with standard care. Loss of weight and fat mass were the strongest mediators of the increased bone turnover. Bone mineral density was unaffected by the intervention (ΔBMD, 0.1%; 95% CI, -1.1% to 1.2%). A 12-month intensive exercise-based lifestyle intervention led to a substantial but balanced increase in bone turnover in persons with T2D. The increased bone turnover combined with a preserved BMD, despite a considerable weight loss, is likely to reflect improved bone health and warrants further studies addressing the impact of exercise on risk of fractures in persons with T2D.

The Masquelet Technique: Can Disposable Polypropylene Syringes be an Alternative to Standard PMMA Spacers? A Rat Bone Defect Model.

Usually, the two-stage Masquelet induced-membrane technique for extremity reconstruction begins with a polymethylmethacrylate (PMMA) cement spacer-driven membrane, followed by an autologous cancellous bone graft implanted into the membrane cavity to promote healing of large bone defects. In exceptional cases, spacers made of polypropylene disposable syringes were successfully used instead of the usual PMMA spacers because of a PMMA cement shortage caused by a lack of resources. However, this approach lacks clinical evidence and requires experimental validation before being recommended as an alternative to the conventional technique. To (1) develop and (2) validate a critical-sized femoral defect model in rats for two stages of the Masquelet technique and to (3) compare the biological and bone healing properties of polypropylene-induced membranes and PMMA-induced membranes in this model. Fifty male Sprague Dawley rats aged 8 weeks old received a 6-mm femur defect, which was stabilized with an external fixator that was converted into an internal device. In the development phase, the defect was filled with PMMA in 16 rats to determine the most favorable timing for bone grafting. Two rats were excluded since they died of anesthetic complications. The other 14 were successively euthanized after 2 weeks (n = 3), 4 weeks (n = 4), 6 weeks (n = 4), and 8 weeks (n = 3) for induced membrane analyses. In the validation phase, 12 rats underwent both stages of the procedure using a PMMA spacer and were randomly assigned to two groups, whether the induced membrane was preserved or removed before grafting. To address our final objective, we implanted either polypropylene or PMMA spacers into the defect (Masquelet technique Stage 1; n = 11 rats per group) for the period established by the development phase. In each group, 6 of 11 rats were euthanized to compare the biological properties of polypropylene-induced membranes and PMMA-induced membranes using histological qualitative analysis, semiquantitative assessment of the bone morphogenic protein-2 content by immunostaining, and qualitative assessment of the mesenchymal stromal cell (MSC; CD31-, CD45-, CD90+, and CD73+ phenotypes) content by flow cytometry. Quantitative measurements from serum bone turnover markers were also performed. The five remaining rats of each group were used for Masquelet technique Stage 2, in which rat bone allografts were implanted in the induced membrane cavity after the polypropylene or PMMA spacers were removed. These rats recovered for 10 weeks before being euthanized for microCT quantitative measurements and bone histology qualitative assessment to evaluate and compare the extent of bone regeneration between groups. Induced membrane analyses together with serum bone turnover measurements indicated that a 4-week interval time between stages was the most favorable. Removal of the induced membrane before grafting led to almost constant early implant failures with poor bone formation. Four-week-old rats with polypropylene-triggered induced membranes displayed similar histologic organization as rats with PMMA-driven induced membranes, without any difference in the cell density of the extracellular matrix (4933 ± 916 cells per mm2 for polypropylene versus 4923 ± 1284 cells per mm2 for PMMA; p = 0.98). Induced membrane-derived MSCs were found in both groups with no difference (4 of 5 with polypropylene versus 3 of 3 with PMMA; p > 0.99). Induced membrane bone morphogenic protein-2 immunolabeling and serum bone turnover marker levels were comparable between the polypropylene and PMMA groups. MicroCT analysis found that bone regeneration in the polypropylene group seemed comparable with that in the PMMA group (29 ± 26 mm3 for polypropylene versus 24 ± 18 mm3 for PMMA; p > 0.99). Finally, qualitative histological assessment revealed a satisfactory endochondral ossification maturation in both groups. Using a critical-sized femoral defect model in rats, we demonstrated that polypropylene spacers could induce membrane encapsulation with histologic characteristics and bone regenerative capacities that seem like those of PMMA spacers. In a same bone site, polymers with close physical properties seem to lead to similar foreign body reactions and induce encapsulating membranes with comparable bone healing properties. Polypropylene spacers made from disposable syringes could be a valuable alternative to PMMA. These results support the possibility of a cementless Masquelet technique in cases of PMMA shortage caused by a lack of resources.

Comparison of the Effects of Various Antidiabetic Medication on Bone Mineral Density in Patients with Type 2 Diabetes Mellitus.

BackgroundProspective comparative studies on the effects of various antidiabetic agents on bone metabolism are limited. This study aimed to assess changes in bone mass and biochemical bone markers in postmenopausal patients with type 2 diabetes mellitus (T2DM).MethodsThis prospective, multicenter, open-label, comparative trial included 264 patients with T2DM. Patients who had received a metformin, or sulfonylurea/metformin combination (Group 1); a thiazolidinedione combination (Group 2); a dipeptidyl peptidase-4 inhibitor (gemigliptin) combination (Group 3); or an sodium-glucose cotransporter 2 inhibitor (empagliflozin) combination (Group 4) were prospectively treated for 12 months; bone mineral density (BMD) and bone turnover marker (BTM) changes were evaluated.ResultsThe femoral neck BMD percentage changes were −0.79%±2.86% (Group 1), −2.50%±3.08% (Group 2), −1.05%±2.74% (Group 3), and −1.24%±2.91% (Group 4) (P<0.05). The total hip BMD percentage changes were −0.57%±1.79% (Group 1), −1.74%±1.48% (Group 2), −0.75%±1.87% (Group 3), and −1.27%±1.72% (Group 4) (P<0.05). Mean serum BTM (C-terminal type 1 collagen telopeptide and procollagen type 1 amino-terminal propeptide) levels measured during the study period did not change over time or differ between groups.ConclusionSignificant bone loss in the femoral neck and total hip was associated with thiazolidinedione combination regimens. However, bone loss was not significantly associated with combination regimens including gemigliptin or empagliflozin. Caution should be exercised during treatment with antidiabetic medications that adversely affect the bone in patients with diabetes at a high risk of bone loss.

Zoledronic acid and bone health in older adults with cognitive impairment.

Osteoporosis has detrimental consequences for frail older adults. The effects on those with both osteoporosis and cognitive impairment are compounded due to increased risk of falls and changes in mobility, both of which can lead to fracture. However, there are limited data on treatment benefits for osteoporotic individuals with cognitive impairment. This post hoc, secondary analysis of data from a randomized, double-blind, placebo-controlled clinical trial of single-dose zoledronic acid included 179 women age ≥ 65 years residing in assisted living facilities or nursing homes, 43 of whom had mild to severe cognitive impairment. We assessed bone mineral density (BMD) of the total hip, femoral neck, and lumbar spine by dual-energy x-ray absorptiometry and serum bone turnover markers (C-terminal telopeptide of type I collagen and procollagen type I N propeptide) at 6 and 12 months. In participants with cognitive impairment, those who received zoledronic acid had 4.3% greater BMD at the total hip (p=.005) and 5.3% greater BMD at the femoral neck (p<.001) after 12 months compared to those in the placebo group. Bone turnover markers demonstrated significant decreases at 6 months in those with cognitive impairment who received active treatment compared to the placebo group. Improvements in bone health measures with zoledronic acid were similar to those seen in participants without cognitive impairment. Zoledronic acid improves bone health in frail older women with cognitive impairment similar to those without impairment. Further studies are warranted to assess the benefit for fracture reduction in this undertreated population.

High-intensity Interval Training Elicits Superior Benefits On Bone Metabolism In Sedentary Young Women

PURPOSE: The objective of the present study was to investigate the effects of 8-week high-intensity interval training (HIIT) on bone metabolism in sedentary college women. METHODS: Twenty-six healthy, sedentary female participants were randomly assigned into either HIIT (n = 13, age 23.2 ± 2.9 yr, weight 59.2 ± 7.2 kg, height 162.9 ± 3.3 cm; 90% VO2max run for 3 min interspersed with 40% VO2max run for 2 min, 6 bouts in one session) or moderate-intensity continuous training (MICT) group (n = 13, age 21.9 ± 1.7 yr, weight 59.3 ± 6.6 kg, height 160.9 ± 4.4 cm; 60% VO2max continuous run for 30 min) with 3 sessions per week for 8 weeks. The bone mineral density (BMD), quantitative ultrasound of the calcaneus (CUS), serum bone turnover markers, jump abilities and body composition were measured pre and post HIIT and MICT interventions. RESULTS: After 8-week interventions, 1) The total body BMD (pre vs post: 0.94 ± 0.05 vs 1.01 ± 0.05, p < 0.01 in HIIT; 0.95 ± 0.05 vs 1.00 ± 0.05 g/cm2, p < 0.01 in MICT), lower limb BMD (1.01 ± 0.08 vs 1.06 ± 0.06, p < 0.01 in HIIT; 1.00 ± 0.08 vs 1.04 ± 0.10 g/cm2, p < 0.01 in MICT), pyridinoline (PYD) (29.93 ± 7.00 vs 25.42 ± 6.79, p < 0.01 in HIIT; 31.64 ± 6.22 vs 25.13 ± 5.39 nmol/L, p < 0.01 in MICT) and %body fat (31.43 ± 5.65 vs 28.85 ± 5.52, p < 0.01 in HIIT; 33.15 ± 4.48 vs 31.48 ± 4.73, p < 0.05 in MICT) were significantly changed without differences between two groups. 2) The 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) (12.10 ± 2.59 vs 17.19 ± 3.44, p < 0.01 in HIIT; 12.08 ± 2.11 vs 14.80 ± 2.01 ug/L, p < 0.01 in MICT), standing long jump (1.61 ± 0.78 vs 1.77 ± 0.83, p < 0.01 in HIIT; 1.59 ± 0.13 vs 1.65 ± 0.14 m, p < 0.01 in MICT) and vertical jump (2.30 ± 0.05 vs 2.42 ± 0.05, p < 0.01 in HIIT; 2.33 ± 0.04 vs 2.37 ± 0.04 m, p < 0.01 in MICT) were increased in both groups with significantly higher changes in HIIT group (p < 0.05). 3) The calcaneus stiffness index (CSTI) (108.77 ± 10.47 vs 126.38 ± 11.92 %, p < 0.01 in HIIT), calcaneus broadband ultrasound attenuation (CBUA) (121.70 ± 9.47 vs 140.40 ± 9.17 dB/MHz, p < 0.01 in HIIT) and osteocalcin (OC) only significantly increased after HIIT intervention (p < 0.01). CONCLUSIONS: It suggested that 8-week HIIT and MICT intervention could improve BMD and body composition. Compared with similar workload MICT, HIIT elicited superior benefits on bone formation and related jump abilities.

Biomarkers for Impending Risk of Osteoporosis in Premenopausal Women.

To compare 'cytokines' and 'bone turnover markers' in pre- and post-menopausal women and identify their relationship with bone mineral density (BMD) in both groups. Study Design: A cross-sectional study. Department of Biological & Biomedical Sciences, The Aga Khan University, Karachi, Pakistan, from June 2017 to August 2019. Groups comprised of healthy premenopausal and postmenopausal women from the general population belonging to different ethnic groups and socio-economic status. Serum cytokines and bone turnover markers were assessed by solid-phase immunoassays, BMD (gm /cm2)] measurement was performed by dual-energy X-ray absorptiometry at the hip, lumbar spine, and proximal femur. Results were interpreted as a sum of T scores calculated by BMD of the above-mentioned sites. Cytokines and bone turnover markers were significantly high in post-menopausal women (p<0.001). A negative correlation (r = 0.32) of TNF α with BMD (total T scores) observed in premenopausal women was found to be significant, however, no significant association of BMD was detected in post-menopausal women. There is an increase in the production of cytokines and bone turnover markers after menopause. TNF-α follows this usual pattern of increase in post-menopausal women and can predict impending bone loss and osteopenia in premenopausal females. Therefore, estimation of this cytokine in pre-menopausal women can give a fair indication of a decline in BMD, bone health, and risk of future osteoporosis. Key Words: Bone mineral density, Cytokines, Bone turnover markers, Osteoporosis.

Lycopene ameliorates diabetic osteoporosis via anti-inflammatory, anti-oxidation, and increasing Osteoprotegerin/RANKL expression ratio

Diabetic osteoporosis (DOP) is one of the complications of diabetes, with high morbidity, and high disability rate. Here, we established a diabetic rat model and administered lycopene to observe its effect on DOP. Our results showed that ten weeks lycopene treatment lowered blood glucose, improved diabetic induced polydipsia, overeating and body weight loss. Lycopene treatment also enhanced bone mineral density, restored bone mechanical and bone Micro-CT parameters of diabetic rats. Subsequently, lycopene decreased serum inflammatory cytokines levels and increased serum anti-oxidant indicators levels. Moreover, lycopene reduced the number of bone marrow adipocytes, and osteoclasts numbers of diabetic rats. The serum bone turnover markers levels were down-regulated after lycopene treatment. Meanwhile, the bone and serum OPG, RUNX 2 expression levels were up-regulated by lycopene in diabetic rats, and the OPG/RANKL ratio was also up-regulated. This study showed that lycopene could ameliorate diabetic induced bone loss via anti-inflammatory, anti-oxidation, and increasing OPG/RANKL ratio in diabetic rats. Lycopene could be used for nutritional intervention in patients with diabetic osteoporosis.

Effects of prior osteoporosis treatment on 12-month treatment response of romosozumab in patients with postmenopausal osteoporosis.

To investigate the effects of prior treatment and determine the predictors of a 12-month treatment response of romosozumab (ROMO) in 148 patients with postmenopausal osteoporosis. In this prospective, observational, and multicenter study, treatment naïve patients (Naïve; n=50) or patients previously treated with bisphosphonates (BP; n=37) or denosumab (DMAb; n=45) or teriparatide (TPTD; n=16) (mean age, 75.0 years; T-scores of the lumbar spine [LS] -3.2 and total hip [TH] -2.6) were switched to ROMO due to insufficient effects of prior treatment. Bone mineral density (BMD) and serum bone turnover markers were evaluated for 12 months. At 12 months, changes in LS BMD were Naïve (18.2%), BP (10.2%), DMAb (6.4%), and TPTD (11.2%) (P<0.001 between groups) and changes in TH BMD were Naïve (5.6%), BP (3.3%), DMAb (0.6%), and TPTD (4.4%) (P<0.01 between groups), respectively. In all groups, the LS BMD significantly increased from baseline at 6 and 12 months, although only the DMAb group failed to obtain a significant increase in TH BMD during 12-month treatment. Mean values of N-terminal type I procollagen propeptide (PINP; μg/L) from baseline → 1 month → 12 months were Naïve (67.9 → 134.1 → 51.0), BP (32. 2 → 81.7 → 40.9), DMAb (30.4 → 56.2 → 75.3), and TPTD (97.4 → 105.1 → 37.1), and those of isoform 5b of tartrate-resistant acid phosphatase (TRACP-5b; mU/dL) were Naïve (500.4 → 283.8 → 267.1), BP (273.4 → 203.1 → 242.0), DMAb (220.3 → 246.1 → 304.8), and TPTD (446.6 → 305.1 → 235.7), respectively. Multiple regression analysis revealed that the significant predictors of BMD change at 12 months were difference of prior treatment (r=-2.8, P<0.001) and value of PINP at 1 month (r=0.04, P<0.01) for LS, and difference of prior treatment (r=-1.3, P<0.05) and percentage change of TRACP-5b at 1 month (r=-0.06, P<0.05) for TH. The early effects of ROMO on LS and TH BMD increase at 12 months were significantly affected by the difference of prior treatment and are predicted by the early change in bone turnover markers.

Silencing Hoxa2 reverses dexamethasone-induced dysfunction of MC3T3-E1 osteoblasts and osteoporosis in rats

Osteoporosis is damaging the health of women worldwide. Osteoporosis results from the imbalance between bone resorption and formation, which may be regulated by homeobox A2 (Hoxa2). However, the specific role and mechanism of Hoxa2 in osteogenesis and dexamethasone (Dex)-induced osteoporosis remain unknown. The present study investigated the effect of Hoxa2 on differentiation and osteoblastogenesis. Alkaline phosphatase staining and immunofluorescence staining were performed to evaluate the differentiation of MC3T3-E1 cells. Runt-related transcription factor 2 (Runx2), osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa B ligand (RANKL) in Dex stimulated osteoblastic MC3T3-E1 cells, and Dex-induced osteoporotic rats were estimated using western blot and quantitative polymerase chain reaction (qPCR). Serum markers of bone turnover were determined using enzyme-linked immunosorbent assay (ELISA). Trabecular bones of femur tissues were observed using hematoxylin and eosin (H&E) staining. Hoxa2 short hairpin RNA significantly promoted the differentiation of MC3T3-E1 cells and expression of Runx2 and OPG in Dex-treated MC3T3-E1 cells and osteoporotic rats but inhibited the expression of RANKL. Furthermore, silencing Hoxa2 resulted in the upregulation of bone alkaline phosphatase but suppressed the expression of tartrate-resistant acid phosphatase and C-terminal cross-linked telopeptides of type I collagen. Silencing Hoxa2 reversed the Dex-induced inhibition of osteoblastogenesis by modulating Runx2 and RANK-RANKL-OPG axis.