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Osteointegration of a Biocomposite Suture Anchor After Arthroscopic Shoulder Labral Repair.
Sugaya, H, Suzuki, K, Yoshimura, H, Tanaka, M, Yamazaki, T, Watanabe, M, Iwaso, H, Inaoka, T, Sugimoto, H, Matsuki, K, et al
Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association. 2019;(12):3173-3178
Abstract
PURPOSE To evaluate osteoconductivity of a poly-L-lactide co-glycolide (PLG)-calcium sulfate (CS)-β-tricalcium phosphate (β-TCP) biocomposite suture anchor after arthroscopic shoulder labral repair. METHODS The subjects of this study were patients who participated in a clinical trial for acquisition of marketing approval of a PLG-CS-β-TCP biocomposite anchor in Japan. They underwent arthroscopic labral repair using the anchor, and computed tomographic (CT) images of the glenoid were obtained 2 years after surgery. Osteoconductivity at the anchor sites was evaluated with the CT images using the established ossification quality score. Shoulder function scores including the Rowe score and Japanese Shoulder Society shoulder instability score were also assessed 2 years after surgery. RESULTS CT images and functional scores were obtained from 37 patients, comprising 29 men and 8 women with a mean age of 29 years (range, 25-33 years) at surgery. A total of 148 anchors were implanted in the 37 shoulders. Osteoconductivity was seen in 133 of 148 anchor sites (90.0%) 2 years after implantation. No significant differences in osteoconductivity were found by anchor diameter or position. The Rowe score significantly improved from 39.9 points (95% confidence interval [CI], 33.8-45.9 points) preoperatively to 96.6 points (95% CI, 95.1-98.1 points) at 2 years postoperatively (P < .001). The Japanese Shoulder Society shoulder instability score also significantly improved, from 63.1 points (95% CI, 58.4-67.7 points) preoperatively to 96.3 points (95% CI, 94.7-97.8 points) at 2 years postoperatively (P < .001). CONCLUSIONS Biocomposite suture anchors made of PLG, CS, and β-TCP exhibited some osteoconductivity 2 years after arthroscopic labral repair, as well as good clinical outcomes. LEVEL OF EVIDENCE Level IV, therapeutic case series.
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Bone histomorphometry before and after long-term treatment with cinacalcet in dialysis patients with secondary hyperparathyroidism.
Behets, GJ, Spasovski, G, Sterling, LR, Goodman, WG, Spiegel, DM, De Broe, ME, D'Haese, PC
Kidney international. 2015;(4):846-56
Abstract
The multicenter, single-arm BONAFIDE study characterized the skeletal response to cinacalcet in adult dialysis patients with plasma parathyroid hormone (PTH) levels of 300 pg/ml or more, serum calcium of 8.4 mg/dl or more, bone-specific alkaline phosphatase over 20.9 ng/ml and biopsy-proven high-turnover bone disease. Of 110 enrolled patients, 77 underwent a second bone biopsy with quantitative histomorphometry after 6-12 months of cinacalcet treatment. The median PTH decreased from 985 pg/ml at baseline to 480 pg/ml at the end of study (weeks 44-52). Bone formation rate/tissue area decreased from 728 to 336 μm(2)/mm(2)/day, osteoblast perimeter/osteoid perimeter decreased from 17.4 to 13.9%, and eroded perimeter/bone perimeter decreased from 12.7 to 8.3%. The number of patients with normal bone histology increased from none at baseline to 20 at 12 months. Two patients had adynamic bone at the end of study with a PTH under 150 pg/ml, and one patient with overt hypophosphatemia at baseline that reoccurred during follow-up developed osteomalacia. Thus, long-term treatment with cinacalcet substantially reduced PTH, diminished the elevated bone formation rate/tissue area, lowered several biochemical markers of high-turnover bone disease toward normal, and generally improved bone histology. Twenty patients had normal bone histology at follow-up, whereas most had mild hyperparathyroidism or mixed uremic osteodystrophy.
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Blood perfusion and bone formation before and after minimally invasive periacetabular osteotomy analysed by Positron Emission Tomography combined with Computed Tomography.
Mechlenburg, I, Hermansen, F, Thillemann, T, Søballe, K
International orthopaedics. 2013;(5):789-94
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Abstract
PURPOSE Sufficient blood perfusion is essential for successful bone healing after periacetabular osteotomy (PAO). The purpose of this study was to quantify blood perfusion and bone formation before and after PAO analysed by positron emission tomography (PET) combined with computed tomography (CT). METHODS Twelve dysplastic patients (nine women) were included consecutively in the study and all were operated upon by the senior author (KS). Median age was 33 (23-55) years. Initially, two patients were PET scanned in a pilot study to test our models for calculation of the physiological parameters. The following ten patients had their hip joints PET/CT scanned immediately before PAO and three to four weeks after. Oxygen-15-water was used to quantify blood perfusion and Flourine-18-fluoride was used to produce quantitative images interpreted as new bone formation in the acetabular fragment. RESULTS The blood perfusion of the operated acetabulum before surgery was 0.07 ± 0.02 ml/min/ml, and after surgery 0.19 ± 0.03 ml/min/ml (p = 0.0003). Blood perfusion of the non-operated acetabulum was 0.07 ± 0.02 ml/min/ml before PAO and 0.07 ± 0.02 ml/min/ml after surgery (p = 0.47). The fluoride-clearance per volume bone of the operated acetabulum was 0.02 ± 0.01 ml/min/ml preoperatively, and 0.06 ± 0.01 ml/min/ml postoperatively (p = 0.0005). Fluoride-clearance of the non-operated acetabulum was 0.01 ± 0.01 ml/min/ml before PAO and 0.02 ± 0.01 ml/min/ml after PAO (p = 0.49). CONCLUSION Blood perfusion and new bone formation increased significantly in the acetabular fragment. Thus, the results of this study do not support the concern about surgically damaged vascularity after PAO.
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Effect of lyso-phosphatidylcholine and Schnurri-3 on osteogenic transdifferentiation of vascular smooth muscle cells to calcifying vascular cells in 3D culture.
Castro-Chavez, F, Vickers, KC, Lee, JS, Tung, CH, Morrisett, JD
Biochimica et biophysica acta. 2013;(6):3828-34
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Abstract
BACKGROUND In vitro cell culture is a widely used technique for investigating a range of processes such as stem cell behavior, regenerative medicine, tissue engineering, and drug discovery. Conventional cell culture is performed in Petri dishes or flasks where cells typically attach to a flat glass or plastic surface as a cell monolayer. However, 2D cell monolayers do not provide a satisfactory representation of in vivo conditions. A 3D culture could be a much better system for representing the conditions that prevail in vivo. METHODS AND RESULTS To simulate 3D conditions, vascular smooth muscle cells (VSMCs) were loaded with gold-polyvmer-iron oxide hydrogel, enabling levitation of the cells by using spatially varying magnetic fields. These magnetically levitated 3D cultures appeared as freely suspended, clustered cells which proliferated 3-4 times faster than cells in conventional 2D cultures. When the levitated cells were treated with 10nM lysophosphatidylcholine (LPC), for 3days, cell clusters exhibited translucent extensions/rods 60-80μm wide and 200-250μm long. When 0.5μg/μl Schnurri-3 was added to the culture containing LPC, these extensions were smaller or absent. When excited with 590-650nm light, these extensions emitted intrinsic fluorescence at >667nm. When the 3D cultures were treated with a fluorescent probe specific for calcium hydroxyapatite (FITC-HABP-19), the cell extensions/rods emitted intensely at 518nm, the λmax for FITC emission. Pellets of cells treated with LPC were more enriched in calcium, phosphate, and glycosaminoglycans than cells treated with LPC and Schnurri-3. CONCLUSIONS In 3D cultures, VSMCs grow more rapidly and form larger calcification clusters than cells in 2D cultures. Transdifferentiation of VSMC into calcifying vascular cells is enhanced by LPC and attenuated by Schnurri-3. GENERAL SIGNIFICANCE The formation of calcified structures in 3D VSMC cultures suggests that similar structures may be formed in vivo.
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Dose-dependent effects of nicotine on proliferation and differentiation of human bone marrow stromal cells and the antagonistic action of vitamin C.
Shen, Y, Liu, HX, Ying, XZ, Yang, SZ, Nie, PF, Cheng, SW, Wang, W, Cheng, XJ, Peng, L, Xu, HZ
Journal of cellular biochemistry. 2013;(8):1720-8
Abstract
A range of biological and molecular effects caused by nicotine are considered to effect bone metabolism. Vitamin C functions as a biological antioxidant. This study was to evaluate the in vitro effects of nicotine on human bone marrow stromal cells and whether Vitamin C supplementation show the antagonism action to high concentration nicotine. We used CCK-8, alkaline phosphatase (ALP) activity assay, Von Kossa staining, real-time polymerase chain reaction and Western Blot to evaluate the proliferation and osteogenic differentiation. The results indicated that the proliferation of BMSCs increased at the concentration of 50, 100 ng/ml, got inhibited at 1,000 ng/ml. When Vitamin C was added, the OD for proliferation increased. For ALP staining, we found that BMSCs treated with 50 and 100 ng/ml nicotine showed a higher activity compared with the control, and decreased at the 1,000 ng/ml. Bone morphogenetic protein-2 (BMP-2) expression and the calcium depositions decreased at 100 and 1,000 ng/ml nicotine, while the addition of Vitamin C reversed the down regulation. By real-time PCR, we detected that the mRNA expression of collagen type I (COL-I) and ALP were also increased in 50 and 100 ng/ml nicotine groups (P < 0.05), while reduced at 1,000 ng/ml (P < 0.05). When it came to osteocalcin (OCN), the changes were similar. Taken all together, it is found that nicotine has a two-phase effect on human BMSCs, showing that low level of nicotine could promote the proliferation and osteogenic differentiation while the high level display the opposite effect. Vitamin C could antagonize the inhibitory effect of higher concentration of nicotine partly.
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Dapagliflozin has no effect on markers of bone formation and resorption or bone mineral density in patients with inadequately controlled type 2 diabetes mellitus on metformin.
Ljunggren, Ö, Bolinder, J, Johansson, L, Wilding, J, Langkilde, AM, Sjöström, CD, Sugg, J, Parikh, S
Diabetes, obesity & metabolism. 2012;(11):990-9
Abstract
AIMS: Dapagliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, reduces hyperglycaemia in patients with type 2 diabetes (T2DM) by increasing urinary glucose excretion. Owing to its mechanism of action, dapagliflozin could potentially affect the renal tubular transportation of bone minerals. Therefore, markers of bone formation and resorption and bone mineral density (BMD) were evaluated in patients with T2DM after 50 weeks of dapagliflozin treatment. METHODS This international, multi-centre, randomized, parallel-group, double-blind, placebo-controlled study (ClinicalTrials.gov NCT00855166) enrolled patients with T2DM (women 55-75 years and men 30-75 years; HbA1c 6.5-8.5%; BMI ≥ 25 kg/m(2) ; body weight ≤ 120 kg) whose T2DM was inadequately controlled on metformin. One hundred and eighty-two patients were randomly assigned 1:1 to receive dapagliflozin 10 mg/day or placebo added to open-label metformin for a 24-week double-blind treatment period followed by a 78-week site- and patient-blinded extension period. At week 50, serum markers of bone formation (procollagen type 1 N-terminal propeptide; P1NP) and resorption (C-terminal cross-linking telopeptides of type I collagen; CTX), bone mineral density (BMD) as assessed by standardized Dual-Energy X-ray Absorptiometry (DXA) measurements and adverse events of fracture were evaluated as safety objectives. RESULTS One hundred and sixty-five patients (90.7%) completed the first 50 weeks. Compared with placebo, no significant changes from baseline in P1NP, CTX or BMD were identified over 50 weeks of dapagliflozin treatment, with no significant treatment-by-gender interactions. No fractures were reported. CONCLUSIONS Dapagliflozin had no effect on markers of bone formation and resorption or BMD after 50 weeks of treatment in both male and post-menopausal female patients whose T2DM was inadequately controlled on metformin.
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A 7-day continuous infusion of PTH or PTHrP suppresses bone formation and uncouples bone turnover.
Horwitz, MJ, Tedesco, MB, Sereika, SM, Prebehala, L, Gundberg, CM, Hollis, BW, Bisello, A, Garcia-Ocaña, A, Carneiro, RM, Stewart, AF
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2011;(9):2287-97
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Human in vivo models of primary hyperparathyroidism (HPT), humoral hypercalcemia of malignancy (HHM), or lactational bone mobilization for more than 48 hours have not been described previously. We therefore developed 7-day continuous-infusion models using human parathyroid hormone(1-34) [hPTH(1-34)] and human parathyroid hormone-related protein(1-36) [hPTHrP(1-36)] in healthy human adult volunteers. Study subjects developed sustained mild increases in serum calcium (10.0 mg/dL), with marked suppression of endogenous PTH(1-84). The maximal tolerated infused doses over a 7-day period (2 and 4 pmol/kg/h for PTH and PTHrP, respectively) were far lower than in prior, briefer human studies (8 to 28 pmol/kg/h). In contrast to prior reports using higher PTH and PTHrP doses, both 1,25-dihydroxyvitamin D(3) [1,25(OH)(2) D(3) ] and tubular maximum for phosphorus (TmP/GFR) remained unaltered with these low doses despite achievement of hypercalcemia and hypercalciuria. As expected, bone resorption increased rapidly and reversed promptly with cessation of the infusion. However, in contrast to events in primary HPT, bone formation was suppressed by 30% to 40% for the 7 days of the infusions. With cessation of PTH and PTHrP infusion, bone-formation markers abruptly rebounded upward, confirming that bone formation is suppressed by continuous PTH or PTHrP infusion. These studies demonstrate that continuous exposure of the human skeleton to PTH or PTHrP in vivo recruits and activates the bone-resorption program but causes sustained arrest in the osteoblast maturation program. These events would most closely mimic and model events in HHM. Although not a perfect model for lactation, the increase in resorption and the rebound increase in formation with cessation of the infusions are reminiscent of the maternal skeletal calcium mobilization and reversal that occur following lactation. The findings also highlight similarities and differences between the model and HPT.
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Differential effects of teriparatide on regional bone formation using (18)F-fluoride positron emission tomography.
Frost, ML, Siddique, M, Blake, GM, Moore, AE, Schleyer, PJ, Dunn, JT, Somer, EJ, Marsden, PK, Eastell, R, Fogelman, I
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2011;(5):1002-11
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Teriparatide increases skeletal mass, bone turnover markers, and bone strength, but local effects on bone tissue may vary between skeletal sites. We used positron emission tomography (PET) to study (18)F-fluoride plasma clearance (K(i)) at the spine and standardized uptake values (SUVs) at the spine, pelvis, total hip, and femoral shaft in 18 postmenopausal women with osteoporosis. Subjects underwent a 1-hour dynamic scan of the lumbar spine and a 10-minute static scan of the pelvis and femurs at baseline and after 6 months of treatment with 20 µg/day teriparatide. Blood samples were taken to derive the arterial input function and lumbar spine K(i) values evaluated using a three-compartment model. SUVs were calculated for the spine, pelvis, total hip, and femoral shaft. After 6 months treatment with teriparatide, spine K(i) values increased by 24% (p = .0003), while other model parameters were unchanged except for the fraction of tracer going to bone mineral (k(3)/[k(2) + k(3)]), which increased by 23% (p = .0006). In contrast to K(i) , spine SUVs increased by only 3% (p = .84). The discrepancy between changes in K(i) and SUVs was explained by a 20% decrease in (18)F(-) plasma concentration. SUVs increased by 37% at the femoral shaft (p = .0019), 20% at the total hip (p = .032), and 11% at the pelvis (p = .070). Changes in bone turnover markers and BMD were consistent with previous trials. We conclude that the changes in bone formation rate during teriparatide treatment as measured by (18)F(-) PET differ at different skeletal sites, with larger increases in cortical bone than at trabecular sites.
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The effect of PTH(1-84) or strontium ranelate on bone formation markers in postmenopausal women with primary osteoporosis: results of a randomized, open-label clinical trial.
Quesada-Gómez, JM, Muschitz, C, Gómez-Reino, J, Greisen, H, Andersen, HS, Dimai, HP
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2011;(9):2529-37
Abstract
UNLABELLED 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. INTRODUCTION 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.
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Effect of acute citrate load on markers of bone metabolism in healthy volunteers.
Chen, Y, Bieglmayer, C, Höcker, P, Dettke, M
Vox sanguinis. 2009;(4):324-9
Abstract
BACKGROUND AND OBJECTIVES This study aims to investigate the possible effects of acute citrate administration on bone metabolism in healthy men. MATERIALS AND METHODS A placebo-controlled, crossover trial was conducted on 10 male volunteers. The volunteers received either a standardized infusion of citrate at 1.5 mg/kg body weight/min or the equal volume of placebo, separated by a washout period of 14 days. Serial blood and urine samples were collected and analysed for bone biochemical markers and electrolytes. RESULTS Infusion of citrate resulted in increased serum levels of the bone formation marker osteocalcin (OC) and bone resorption marker C-telopeptide of type 1 collagen (CTX). Increases in CTX and OC were positively correlated to the surge in the serum concentration of intact parathyroid hormone (iPTH) but only OC showed correlation to changes in ionized calcium. Citrate infusion showed no effect on serum concentrations of bone alkaline phosphatase, osteoprotegerin, and bone tartrate-resistant acid phosphatase 5b, or the expression of receptor activator of nuclear factor kappa B ligand. Variations in OC and CTX were short-term as both bone markers gradually declined within 90 min following citrate exposure. CONCLUSION Acute citrate load resulted in profound alterations of the bone markers OC and CTX. The short-term increase of CTX suggests a temporary shift to a higher bone turnover rate, although the clinical consequence of the observed changes in bone markers remains open.