The aging process correlates with the accumulation of cellular and tissue damage caused by oxidative stress. Although previous studies have suggested that oxidative stress plays a pathologic role in the development of bone fragility, little direct evidence has been found. In order to investigate the pathologic significance of oxidative stress in bones, we analyzed the bone tissue of mice deficient in cytoplasmic copper/zinc superoxide dismutase (CuZn-SOD, encoded by the Sod1 gene; Sod1 À/À ). In this study, we showed for the first time that in vivo cytoplasmic superoxide caused a distinct weakness in bone stiffness and decreased BMD, aging-like changes in collagen crosslinking, and transcriptional alterations in the genes associated with osteogenesis. We also showed that the surface areas of osteoblasts and osteoclasts were decreased significantly in the lumbar vertebrae of Sod1 À/À mice, indicating the occurrence of low-turnover osteopenia. In vitro experiments demonstrated that intracellular oxidative stress induced cell death and reduced the proliferation in primary osteoblasts but not in osteoclasts, indicating that impaired osteoblast viability caused the decrease in osteoblast number and suppressed RANKL/M-CSF osteoclastogenic signaling in bone. Furthermore, treatment with an antioxidant, vitamin C, effectively improved bone fragility and osteoblastic survival. These results imply that intracellular redox imbalance caused by SOD1 deficiency plays a pivotal role in the development and progression of bone fragility both in vivo and in vitro. We herein present a valuable model for investigating the effects of oxidative stress on bone fragility in order to develop suitable therapeutic interventions. ß

Mechanical stress and aging are major risk factors of cartilage degeneration. Human studies have previously reported that oxidative damage increased, while SOD2 protein was reciprocally downregulated in osteoarthritic degenerated cartilage. However, it remains unclear whether mitochondrial superoxide imbalance in chondrocytes causes cartilage degeneration. We herein demonstrate that mechanical loading promoted mitochondrial superoxide generation and selective Sod2 downregulation in chondrocytes in vivo and that mitochondrial superoxide inducer also downregulated Sod2 expression in chondrocytes in vitro. A genetically manipulated model revealed that Sod2 deficiency in chondrocytes also resulted in mitochondrial superoxide overproduction and dysfunction, thus leading to cartilage degeneration. Intra-articular injection of a permeable antioxidant effectively suppressed the mechanical loading-induced mitochondrial superoxide generation and cartilage degeneration in mice. Our findings demonstrate that mitochondrial superoxide plays a pivotal role in the development and progression of osteoarthritis, and the mitochondrial superoxide balance may therefore be a promising target for the treatment of cartilage degeneration.

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Bone regeneration for the defects in revision surgery of joint replacement is an increasingly important issue. To repair bone defects, bone cell activation by growth factors using synthetic resorbable scaffold is a useful and safe option. We examine the efficiency of nanogel-crosslinking hydrogel as a novel synthetic scaffold for BMP to stimulate osteoblasts and to induce bone formation. Cholesterol-bearing pullulan nanogel-crosslinking hydrogel (CHPA/Hydrogel) was used to deliver BMP. The CHPA hydrogel pellets were implanted in vivo. Single implantation of CHPA/hydrogel containing low amounts of BMP induced osteoblastic activation and new bone formation in vivo. Furthermore, nanogel in a disc shape established recruitment of osteoblastic cells that vigorously formed bone to heal the calvarial defects, which did not heal spontaneously without it. In conclusion, CHPA/hydrogel serves as an efficient and versatile scaffold for the stimulation of osteoblasts to form bone and to repair defects via delivery of BMP.

Objective In a convenience sample of athletes, we conducted a survey of COVID-19-mediated lockdown (termed ‘lockdown’ from this point forward) effects on: (i) circadian rhythms; (ii) sleep; (iii) eating; and (iv) training behaviors. Methods In total, 3911 athletes [mean age: 25.1 (range 18–61) years, 1764 female (45%), 2427 team-sport (63%) and 1442 elite (37%) athletes] from 49 countries completed a multilingual cross-sectional survey including the Pittsburgh Sleep Quality Index and Insomnia Severity Index questionnaires, alongside bespoke questions about napping, training, and nutrition behaviors. Results Pittsburgh Sleep Quality Index (4.3 ± 2.4 to 5.8 ± 3.1) and Insomnia Severity Index (4.8 ± 4.7 to 7.2 ± 6.4) scores increased from pre- to during lockdown ( p < 0.001). Pittsburgh Sleep Quality Index was predominantly influenced by sleep-onset latency ( p < 0.001; + 29.8%), sleep efficiency ( p < 0.001; − 21.1%), and total sleep time ( p < 0.001; − 20.1%), whilst Insomnia Severity Index was affected by sleep-onset latency ( p < 0.001; + 21.4%), bedtime ( p < 0.001; + 9.4%), and eating after midnight ( p < 0.001; + 9.1%). During lockdown, athletes reported fewer training sessions per week (− 29.1%; d = 0.99). Athletes went to bed (+ 75 min; 5.4%; d = 1.14) and woke up (+ 150 min; 34.5%; d = 1.71) later during lockdown with an increased total sleep time (+ 48 min; 10.6%; d = 0.83). Lockdown-mediated circadian disruption had more deleterious effects on the sleep quality of individual-sport athletes compared with team-sport athletes ( p < 0.001; d = 0.41), elite compared with non-elite athletes ( p = 0.028; d = 0.44) and older compared with younger ( p = 0.008; d = 0.46) athletes. Conclusions These lockdown-induced behavioral changes reduced sleep quality and increased insomnia in athletes. Data-driven and evidence-based recommendations to counter these include, but are not limited to: (i) early outdoor training; (ii) regular meal scheduling (whilst avoiding meals prior to bedtime and caffeine in the evening) with appropriate composition; (iii) regular bedtimes and wake-up times; and (iv) avoidance of long and/or late naps. Supplementary Information The online version contains supplementary material available at 10.1007/s40279-021-01601-y.

Headless compression screw fixation of fifth metatarsal Jones fractures provided excellent results, allowing athletes to return to full activity without both screw insertion site irritation and clinical refracture.

Background:Although anterior cruciate ligament (ACL) reconstruction techniques that preserve remnant tissues have been described, complete preservation may be difficult, with little known about its clinical advantages.Purpose:To compare clinical outcomes in patients undergoing ACL reconstruction with and without ACL remnant preservation.Study Design:Case-control study.Methods:Of 372 patients who underwent surgical treatment of an ACL injury between September 2006 and July 2010, 154 had no remaining identifiable ligament tissue and were excluded from this study. Attempts were made to preserve the ACL remnant as much as possible in the remaining 218 patients. These patients were divided into 2 groups: those in whom the remnant was preserved (group 1, n = 85) and those in whom the remnant was not preserved (group 2, n = 98). Patients were followed for at least 24 months. Outcomes, including graft rupture, were compared in the 2 groups.Results:Time from injury to surgery was significantly shorter (7.3 ± 16.3 vs 16.0 ± 30.3 months; P < .05) and the preinjury Tegner activity was significantly higher (7.6 ± 1.4 vs 7.1 ± 1.2; P < .05; 95% confidence interval, 1.2-13.7) in group 1 than in group 2. The postoperative negative ratio of the pivot-shift test was similar in the 2 groups (87% vs 81%). Anterior stability of the knee, as measured by a KT-2000 arthrometer, was significantly better in group 1 than in group 2 (1.0 ± 0.8 vs 1.3 ± 1.0 mm; P < .05). ACL graft rupture occurred in 1 patient (1.1%) in group 1 and in 7 patients (7.1%) in group 2 (P < .05). Regression analysis showed that preservation of the remnant decreased the likelihood of graft rupture (odds ratio, 11.2; 95% confidence interval, 1.2-101.7).Conclusion:These findings confirmed that preserving the remnant tissue of the ACL may facilitate recovery of function and decrease graft rupture after primary reconstruction.

Osteocytes are major bone cells that play a crucial role in maintaining the quality of and healing damage to bone tissue. The number of living osteocytes and canalicular networks declines in an age-dependent manner. However, the pathological effects of mitochondrial redox imbalances on osteocytes and bone metabolism have not been fully elucidated. We generated mice lacking mitochondrial superoxide dismutase 2 (Sod2) in osteocytes. Like an aged bone, Sod2 depletion in the osteocytes positively enhanced the production of cellular superoxide in vivo. A bone morphological analysis demonstrated that the Sod2-deficient femurs showed remarkable bone loss in an age-dependent manner. Interestingly, Sod2 loss induced markedly disorganized osteocytic canalicular networks and decreased the number of live osteocytes. Furthermore, Sod2 deficiency significantly suppressed bone formation and increased bone resorption concomitant with the upregulation of sclerostin and receptor activator of NF-κB ligand (RANKL). In vitro experiments also revealed that treatment with paraquat, a superoxide inducer in mitochondria, promoted the RANKL expression via, in part, ERK phosphorylation. These findings demonstrate that the mitochondrial superoxide induced in osteocytes by Sod2 ablation causes age-related bone loss due to the impairment of canalicular networks and bone metabolism via the deregulation of the sclerostin and RANKL expression.