Combined electric and magnetic field therapy for bone repair and regeneration: an investigation in a 3-mm and an augmented 17-mm tibia osteotomy model in sheep.

BACKGROUND: Therapies using electromagnetic field technology show evidence of enhanced bone regeneration at the fracture site, potentially preventing delayed or nonunions. METHODS: Combined electric and magnetic field (CEMF) treatment was evaluated in two standardized sheep tibia osteotomy models: a 3-mm non-critical size gap model and a 17-mm critical size defect model augmented with autologous bone grafts, both stabilized with locking compression plates. CEMF treatment was delivered across the fracture gap twice daily for 90 min, starting 4 days postoperatively (post-OP) until sacrifice (9 or 12 weeks post-OP, respectively). Control groups received no CEMF treatment. Bone healing was evaluated radiographically, morphometrically (micro-CT), biomechanically and histologically. RESULTS: In the 3-mm gap model, the CEMF group (n = 6) exhibited higher callus mineral density compared to the Control group (n = 6), two-fold higher biomechanical torsional rigidity and a histologically more advanced callus maturity (no statistically significant differences). In the 17-mm graft model, differences between the Control (n = 6) and CEMF group (n = 6) were more pronounced. The CEMF group showed a radiologically more advanced callus, a higher callus volume (p = 0.003) and a 2.6 × higher biomechanical torsional rigidity (p = 0.024), combined with a histologically more advanced callus maturity and healing. CONCLUSIONS: This study showed that CEMF therapy notably enhanced bone healing resulting in better new bone structure, callus morphology and superior biomechanical properties. This technology could transform a standard inert orthopedic implant into an active device stimulating bone tissue for accelerated healing and regeneration.

Systemic effects of oral tolerance in bone healing.

Bone fractures cause acute inflammation that, despite being important for initial repair, may delay the healing of the damaged bone. Parenteral injection of dietary protein has been shown to decrease inflammation and accelerate the repair of skin wounds and other inflammatory pathologies. Thus, our aim was to evaluate whether the intraperitoneal (i.p.) immunization with zein, an abundant protein in rodent chow, would favor bone healing. Wistar rats received i.p. immunization: saline (SG), adjuvant (AG) and zein associated with adjuvant (ZG). Then, a 2 mm of defect bone was performed on the right tibia, and on days 7, 14, 28 and 45 thereafter, analyses were performed. The results showed that the injection of zein reduced inflammation without impairing bone mineralization. Moreover, biomechanical tests demonstrated higher levels of maximum force (N) in ZG, indicating better mechanical resistance in relation to the others. The computerized tomography also indicated lower levels of medullary content in the ZG than in the SG, suggesting the absence of trabeculae in the medullary region in the ZG. These findings suggest that the injection of zein in previously tolerated animals may improve bone repair, leading to mechanically functional bone formation.

Bone characteristics of autosomal dominant hypophosphatemic rickets patients.

OBJECTIVE: Autosomal dominant hypophosphatemic rickets (ADHR) is a rare disease caused by activating mutations in fibroblast growth factor 23 (FGF23) gene. With FGF23 activation, ADHR is a good model to explore the effects of FGF23 on skeletal development and mineralization. However, the bone microarchitecture of ADHR patients is poorly investigated. This study aims to illustrate the bone properties of ADHR patients and clarify the effect of FGF23 on load bearing and non-load bearing bone. METHODS: Bone microarchitectures of 11 ADHR subjects and sex- and age-matched healthy controls were analyzed by HR-pQCT. The effect of FGF23 mutations on load bearing and non-load bearing bone was explored by comparison of bone microarchitecture in distal radius and distal tibia. The BMD, bone microarchitecture and bone strength were compared between 7 ADHR patients and 7 age- and sex-matched XLH patients. RESULTS: Among 11 subjects with FGF23 mutations, 10 patients presented with obvious symptoms, five of which had received 1-3 years of iron supplement, neutral phosphate, and calcitriol treatments. The symptomatic patients presented with low bone density and fractures in X rays, with decreased Z score of aBMD (L1-L4: -1.3 ± 1.4, femoral neck: -2.1 ± 1.8, total hip: -1.85 ± 1.6). Compared with controls, HR-pQCT analysis of 5 untreated ADHR patients showed increased total area (+61.6 %, p = 0.03) and cortical perimeter (+17.2 %, p = 0.03) in distal radius. No significant differences were found in other parameters in distal radius. In distal tibia, the patients presented obvious defects in cancellous bone, with decreased trabecular vBMD (-62.9 %, p = 0.003), trabecular BV/TV (-48.7 %, p = 0.003) and trabecular number (-42.2 %, p = 0.001). The trabecular separation (+113.3 %, p = 0.007) and trabecular network inhomogeneity (+226.7 %, p = 0.001) were accordingly increased. In addition to another 5 treated patients, the bone microarchitecture changes revealed similar pattern, but the increase of total area and cortical perimeter in distal radius was no longer statistically significant. The non-symptomatic ADHR patient demonstrated slightly decreased total vBMD, trabecular vBMD and trabecular BV/TV in distal tibia. The changing pattern of bone geometry and microarchitecture of ADHR patients were similar to XLH patients but showed less deficit and stronger bone strength. CONCLUSION: ADHR patients presented increased total area and cortical perimeter in distal radius, and obvious defect in cancellous bone in distal tibia. FGF23 have impairment effect on trabecular bone especially in weight bearing site.

Association of Vitamin D and Parathyroid Hormone Status With the Aging-Related Decline of Bone Microarchitecture in Older Men: The Prospective Structure of Aging Men's Bones (STRAMBO) Study.

Poor vitamin D status and high parathyroid hormone (PTH) level are associated with impaired bone microarchitecture, but these data are mainly cross-sectional. We studied the association of the baseline PTH and 25-hydroxycholecalciferol (25OHD) levels with the prospectively assessed deterioration of bone microarchitecture and in estimated bone strength in older men. Distal radius and tibia bone microarchitecture was assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline, then after 4 and 8 years in 826 men aged 60-87 years. At distal radius, total bone mineral density (Tt.BMD), cortical thickness (Ct.Thd ), cortical area (Ct.Ar), cortical BMD (Ct.BMD), and trabecular BMD (Tb.BMD) decreased, whereas trabecular area (Tb.Ar) increased more rapidly in men with 25OHD ≤20 ng/mL versus the reference group (>30 ng/mL). Men with 25OHD ≤10 ng/mL had faster decrease in reaction force and failure load than men with 25OHD >30 ng/mL. At the distal tibia, Tt.BMD, Ct.Thd , Ct.Ar, Ct.BMD, failure load, and reaction force decreased, whereas Tb.Ar increased more rapidly in men with 25OHD between 10 and 20 ng/mL versus the reference group. The results were similar when 12 ng/mL was used as a threshold of severe vitamin D deficiency. At distal radius, men with PTH levels above the median (>44 pg/mL) had more rapid decrease in Tt.BMD, Ct.Ar, Ct.BMD, Ct.Thd , reaction force, and failure load, and more rapid increase in Tb.Ar versus the lowest quartile (≤34 pg/mL). At the distal tibia, men in the highest PTH quartile had faster decrease in Tt.BMD, Ct.Thd , Ct.Ar, Ct.BMD, reaction force, and failure load and faster increase in Tb.Ar versus the lowest quartile. The results were similar in men with glomerular filtration rate >60 mL/min. The results were similar in men who took no vitamin D or calcium supplements for 8 years. In summary, vitamin D deficiency and secondary hyperparathyroidism are associated with more rapid prospectively assessed cortical and trabecular bone decline in older men. © 2022 American Society for Bone and Mineral Research (ASBMR).

On the Effect of Electroacupuncture in Promoting Healing after High Tibial Osteotomy.

Purpose: To explore the clinical effect of electroacupuncture in promoting the healing of the osteotomy area after high tibial osteotomy. Methods: 50 patients with knee osteoarthritis who underwent open wedge high tibial osteotomy (OWHTO) were selected and randomly divided into the observation group and control group. The control group got the common postoperative treatment, and the observation group was added electroacupuncture from the 3rd day after the operation on the basis of the control group. The electroacupuncture acupoints were selected SP10, ST34, ST32, EX-LE2, ST40,KI6, KI3, SP6, and ST41, once a day, and 14 days were a course of treatment. And then we contrasted the index of the Lane-Sandhu X-ray score, the skin incision healing time, the swelling subsided time, Visual Analogue Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index Score (WOMAC), and Lysholm in different time. Results: The Lane-Sandhu X-ray score of the observation group was better than that of the control group at all time points (P < 0.05), and the time to achieve bone healing was about 2 weeks earlier than that of the control group. The skin healing and swelling were the subsided time in the osteotomy area. Both were better than the control group, and the difference was statistically significant (P < 0.05). The VAS score, WOMAC score, and Lysholm score of the two groups were significantly improved compared with preoperatively, and the difference was statistically significant (P < 0.05). The improvement of the observation group's VAS score, WOMAC score, and Lysholm score at 1 week, 4 weeks, and 8 weeks after the end of the treatment course was better than that of the control group, and the difference was statistically significant (P < 0.05). Conclusion: Electroacupuncture can quicken the healing of bone tissue and surrounding soft tissues in the osteotomy area after high tibial osteotomy, and at the same time, it can help the relief of knee joint pain and improve knee joint function.

Effect of Calcium and Vitamin D Supplementation With and Without Collagen Peptides on Volumetric and Areal Bone Mineral Density, Bone Geometry and Bone Turnover in Postmenopausal Women With Osteopenia.

Collagen peptides (CPs) have been shown to potentially have a role as a treatment option in osteopenia. In the present randomized prospective study, we examined the effect of calcium, vitamin D with and without CPs supplementation on changes in volumetric bone mineral density (vBMD) and bone geometry assessed by peripheral quantitative computed tomography at the tibia, areal bone mineral density (aBMD) assessed by dual-energy X-ray absorptiometry at the lumbar spine and the hip and bone turnover markers over 12-mo. Fifty-one postmenopausal women with osteopenia were allocated to Group A who received orally 5 g CPs, 500 mg calcium and 400 IU vitamin D3 and Group B who received the same dose of calcium and vitamin D3 per day. The primary endpoint was the change of trabecular bone mineral content (BMC) and vBMD after 12-mo supplementation in Groups A and B. At the trabecular site (4% of the tibia length), Group A had a significant increase of total BMC by 1.96 ± 2.41% and cross-sectional area by 2.58 ± 3.91%, trabecular BMC by 5.24 ± 6.48%, cross-sectional area by 2.58 ± 3.91% and vBMD by 2.54 ± 3.43% and a higher % change of these parameters at 12 mo in comparison to Group B (p < 0.01, p = 0.04, p < 0.01, p = 0.04, p = 0.02, respectively). At the cortical site (38% of the tibia length), total and cortical vBMD increased by 1.01 ± 2.57% and 0.67 ± 1.71%. Furthermore, the mean aBMD at the spine was higher (p = 0.01), while bone markers decreased in Group A compared to Group B. The present study shows improvement of trabecular and cortical parameters as assessed by peripheral quantitative computed tomography at the tibia, prevention of aBMD decline and decrease of bone turnover after 12-mo supplementation with calcium, vitamin D with CPs.

Once daily calcium (1000 mg) and vitamin D (1000 IU) supplementation during military training prevents increases in biochemical markers of bone resorption but does not affect tibial microarchitecture in Army recruits.

Basic combat training (BCT) is a period of novel physical training including load carriage resulting in higher risk of stress fracture compared to any other time during military service. Prior trials reported a 20% reduction in stress fracture incidence with Ca and vitamin D (Ca + D) supplementation (2000 mg Ca, 800 IU vitamin D), and greater increases in tibia vBMD during BCT compared to placebo. The primary objective of this randomized, double-blind, placebo-controlled trial was to determine the efficacy of a lower dose of Ca (1000 mg/d Ca, 1000 IU vit D) on PTH, bone biomarkers and tibial microarchitecture during BCT. One hundred volunteers (50 males, 50 females; mean age 21.8 ± 3.5 y) were block randomized by race and sex to receive a daily Ca + D fortified food bar or placebo. Anthropometrics, dietary intake, fasted blood draws and high resolution pQCT scans of the distal and mid-shaft tibia were obtained at the start of BCT and 8 wks later at the conclusion of training. As compliance was 98% in both treatment groups, an intent-to-treat analysis was used. At the distal tibia, total vBMD, Tb.vBMD, Tb.N, Th.Th and Tb.BV/TV increased (+1.07 to 2.12% for all, p < 0.05) and Tb.Sp decreased (0.96 to 1.09%, p < 0.05) in both treatment groups. At the mid-shaft, Ct.Pm increased (+0.18 to 0.21%, p = 0.01) and Ct.vBMD decreased (-0.48 to -0.77%, p < 0.001) in both groups. Ca + D prevented increases in CTX and TRAP, which were observed in the placebo group (group-by-time, p < 0.05). Mean circulating 25OHD, BAP, P1NP and iCa increased and PTH decreased in both treatment groups (p < 0.05). These results, in agreement with other studies, suggest that bone microarchitectural changes indicative of bone formation occur during BCT. While Ca + D supplementation at lower doses than those tested in previous studies prevented increases in biochemical markers of bone resorption in this study, there were no significant changes in bone tissue after 8 wks of Army BCT.

Cessation of ambulation results in a dramatic loss of trabecular bone density in boys with Duchenne muscular dystrophy (DMD).

Glucocorticoids are currently used to improve muscle strength and prolong ambulation in boys with DMD although the effect on bone health is still unclear. The aim of this study was to compare bone strength in healthy children and boys with DMD and investigate the interaction between diminished muscle function, loss of ambulation and high dose oral steroids, over a two year time frame. Fifty children were studied, 14 healthy boys (HB), 13 boys with DMD who remained ambulant (DMD-RA) and 23 boys with DMD who lost ambulation (DMD-LA). All boys with DMD had taken oral glucocorticoids. Peripheral quantitative computed tomography was used to measure bone geometry, density, strength and muscle mass of the non-dominant tibia and radius. Measurements were made at baseline, 12 and 24 months at the distal metaphysis and mid diaphysis sites. Differences between the three groups were evaluated using ANOVA and a repeated measures model. There were no significant differences in age between the groups: mean age was 9.4, 8.7 and 8.8 years for HB, DMD-RA and DMD-LA, respectively. There was no significant difference in steroid exposure between the DMD groups. However, boys who lost ambulation had significantly lower muscle function at baseline (North Star Ambulatory Assessment DMD-RA 23.6 vs. DMD-LA 18.8; p < 0.05). At baseline, healthy boys had significantly greater trabecular bone density at the distal radius /ulna (23%/27%) and distal tibia/fibula (30%/46%) than boys with DMD (p < 0.05). They also had significantly larger diaphyseal tibiae/fibulae (74%/36%) and radii/ulnae (49%/31%) with thicker corticies and consequently greater bone strength. In contrast, boys with DMD had greater cortical density (4%). Over time, there were small significant differences in the rate of change of both muscle and bone parameters between healthy boys and boys with DMD. For both ambulant and non-ambulant boys with DMD the greatest changes in cortical bone were evident at the tibia. After two years boys with DMD had on average, 63% less bone strength than healthy boys. However, the most strikingly significant difference was in trabecular bone density for boys who became non-ambulant. By 2 years non-ambulant DMD boys had 53% less trabecular bone density at distal tibia than their healthy age matched peers compared with boys who remained ambulant who had 27% less trabecular bone density. In conclusion, bone and muscle strength is reduced for all boys with DMD even while they remain ambulant. However, tibia trabecular bone density loss is significantly accelerated in DMD boys who lose independent ambulation compared to DMD boys who remain ambulant despite equivalent levels of corticosteroid exposure.

Analysis of type I osteoporosis animal models using synchrotron radiation.

Preclinical experiments to analyze the trabecular space of spongy bones using small animals are required for the evaluation and treatment of patients with osteoporosis (OP). We performed ovariectomy to create OP models. A total of four mice were used. Ovariectomized group (OVX, n = 2) in which both ovaries were resected at random, and the sham operated group (SHAM, n = 2) performed surgery without resecting the ovaries. We propose a study that enables OP analysis by analyzing tibia microstructures of OVX and SHAM using synchrotron radiation (SR). SR imaging is a technology capable of irradiating an extremely small object in the order of several tens of nanometers using a nondestructive method at the microscopic level. Unlike previous imaging diagnoses (staining, micro-CT [Computed Tomography]) it was possible to preserve the real shape and analyze bone microstructures in real-time and analyze and evaluate spongy bones to secure data and increase the reliability of OP analysis. We were able to confirm the possibility of OP diagnosis through experimental animals for spongy bone damage related to bone mineral density. Therefore, we aimed to provide a rehabilitation and medicine therapy intervention method through basic research on the evaluation of OP diagnosis through human-based segmentation of challenging spongy bones while supplementing the limitations of existing imaging methods. RESEARCH HIGHLIGHTS: We present an analysis of osteoporosis through spongy bone using phase-contrast X-ray source. Unlike existing methods, it is possible to analyze the internal microstructure of the tibia with this method. This is an objective mechanism for OP and a basis for rehabilitation.

Microstructure and mechanical behaviors of tibia for collagen-induced arthritic mice treated with gingiva-derived mesenchymal stem cells.

Rheumatoid arthritis (RA) is a systemic polyarticular arthritis that primarily affects the small joints but also causes bone erosion in large joints. None of the currently existing treatment approaches is curable. In this study, the effects of human gingiva-derived mesenchymal stem cells (GMSCs) on collagen-induced arthritis (CIA) mice are examined by experimentally assessing the microstructure and mechanical behaviors of tibia. Bone morphology and mineral density of mouse tibiae were assessed using micro-X-ray computed tomography (micro-CT). Compression testing was performed on mouse tibia to access its stiffness. The deformation and strain localized inside proximal tibia were mapped using mechanical testing coupled with micro-CT and digital volume correlation of micro-CT images. The results show that CIA disease caused bone erosion in epiphyseal cortical bone, which manifested into the adjacent epiphyseal trabecular bone, and also affected the metaphyseal cortical bone. CIA disease also weakened the load-bearing function of proximal tibia. GMSC treatment interfered with the progress of CIA, attenuated the bone erosion in epiphyseal and metaphyseal trabecular bone and resulted in improved load-bearing function of proximal tibia. GMSCs provide a promising potential treatment of autoimmune arthritis.

Total flavonoids of rhizoma drynariae ameliorates bone formation and mineralization in BMP-Smad signaling pathway induced large tibial defect rats.

Osteogenesis and angiogenesis acts as an essential role in repairing large tibial defects (LTDs). Total flavonoids of rhizoma drynariae (TFRD), a traditional Chinese medicinal herb, is reported to show anabolic effects on fracture healing. However, whether TFRD could improve the bone formation and angiogenesis in LTDs remains unknown. The purpose of this study was to evaluate the effect of TFRD on bone formation and angiogenesis in LTDs in distraction osteogenesis (DO). Using a previously established fracture model, LTD rats was established with circular external fixator (CEF). All rats then randomly divided into TFRD low dosage group (with DO), TFRD medium dosage group (with DO), TFRD high dosage group (with DO), model group (with DO) and blank group (without DO). Twelve weeks after treatment, according to X-ray and Micro-CT, TFRD groups (especially in medium dosage group) can significantly promote the formation of a large number of epiphyses and improve new bone mineralization compared with model group, and the results of HE and Masson staining and in vitro ALP level of BMSC also demonstrated the formation of bone matrix and mineralization in the TFRD groups. Also, angiographic imaging suggested that total flavonoids of TFRD was able to promote angiogenesis in the defect area. Consistently, TFRD significantly increased the levels of BMP-2, SMAD1, SMAD4, RUNX-2, OSX and VEGF in LTD rats based on ELISA and Real-Time PCR. In addition, we found that ALP activity of TFRD medium dosage group reached a peak after 10 days of induction through BMSC cell culture in vitro experiment. TFRD promoted bone formation in LTD through activation of BMP-Smad signaling pathway, which provides a promising new strategy for repairing bone defects in DO surgeries.

Effects of green light emitting diode light during incubation and dietary organic macro and trace minerals during rearing on tibia characteristics of broiler chickens at slaughter age.

This study was designed to evaluate the effects of green light emitting diode (LED) light during incubation and dietary organic macro and trace minerals during rearing on tibia morphological, biophysical, and mechanical characteristics of broiler chickens at slaughter age. The experiment was setup as a 2 × 2 × 2 factorial arrangement, with the following treatments: 1) light during incubation (green LED light or darkness), 2) macro mineral source during rearing (organic or inorganic Ca and P), and 3) trace mineral source during rearing (organic or inorganic Fe, Cu, Mn, Zn, and Se). A total of 2,400 eggs (Ross 308) were either incubated under green LED light (16L:8D) or in complete darkness. After hatch, a total of 864 male broiler chickens were reared until slaughter age (day 42) and provided with 1 of 4 diets, differing in macro and/or trace mineral source. During rearing, the experiment had a complete randomized block design with 9 replicate pens per treatment and 12 chickens per pen. At slaughter age (day 42), 2 chickens per replicate were randomly selected and tibia bones were obtained. Tibia weight, length, thickness, osseous volume, pore volume, total volume, mineral content, mineral density, ultimate strength, and stiffness were determined. Green LED light during incubation did not affect any of the tibia characteristics. Dietary organic macro minerals positively affected most of the tibia morphological, biophysical, and mechanical characteristics compared to the inorganic macro minerals, whereas trace mineral sources did not affect tibia characteristics. It can be concluded that dietary organic macro minerals Ca and P stimulated tibia characteristics, whereas green LED light during incubation and dietary trace minerals during rearing did not affect tibia characteristics, locomotion, or leg disorders.

Unprecedented tibial bone lengthening of 33.5 cm by distraction osteogenesis for the reconstruction of a subtotal tibial bone defect. A case report and literature review.

BACKGROUND: We present a case of an immense unprecedented tibial bone lengthening of 33.5 cm. The management of chronic osteomyelitis of the right tibia with subtotal tibial bone defect, talus defect and equinus ankle deformity. We demonstrate limb reconstruction by distraction osteogenesis and correction of ankle deformity with the Ilizarov technique. Limb salvage was preferred as an alternative to amputation to restore basic limb function. CASE PRESENTATION: A 16-year-old male patient fell and injured his right lower leg. He attempted to treat the symptoms with traditional home remedies. During 15 months of self-treating, he developed osteomyelitis of the right tibia and had lost function in his foot. Radiology revealed immense bone defect of the right tibia, including talus bone defect and equinus deformity of the calcaneus. The patient's right tibia was non weight-bearing, had drainage sinus just below his knee and a large scar anteriorly along the entire length of the tibia. CONCLUSION: Upon completion of treatment, the patient was able to avoid amputation of his leg with partially restored function for weight-bearing. He carried himself without assistance after 3 years of lost function in his right leg. Tibial bone distraction osteogenesis of 33.5 cm was done after 90% of the tibial length was defected. To the best of our best knowledge, this case is one of a kind to achieve distraction of tibial bone to such length.

A predictive model with radiographic signs can be a useful supplementary diagnostic tool for complete discoid lateral meniscus in adults.

PURPOSE: To investigate the diagnostic accuracy of radiographic signs for complete discoid lateral meniscus and whether a predictive model combining the radiographic signs can improve its diagnostic accuracy in adults. METHODS: A total of adult 119 knees with complete discoid lateral meniscus confirmed by arthroscopy and 119 age- and sex-matched knees with normal meniscus were included. The radiographic signs of lateral joint space, fibular head height, lateral tibial spine height, lateral tibial plateau obliquity, lateral femoral condyle squaring, lateral tibial plateau cupping, lateral femoral condyle notching, and the condylar cut-off sign were evaluated. The receiver-operating characteristic (ROC) curves and area under the curve (AUC) were evaluated for best accuracy. A prediction model was developed by multivariable regression with generalized estimating models, and was validated using data from 111 knees of children with complete discoid lateral meniscus and 111 normal controls. RESULTS: The fibular head height, lateral joint space, lateral tibial plateau obliquity, and the condylar cut-off sign were significantly different between the complete discoid lateral meniscus and the normal groups (p < 0.05). Among the four radiographic signs, the fibular head height showed the highest accuracy with 78.9% sensitivity and 57.3% specificity. The prediction models developed by logistic regression showed significantly improved accuracy for complete discoid lateral meniscus compared to the fibular head height (sensitivity: 69.8%, specificity: 82.9%, p = 0.001). For validation, the AUC of children seemed to be larger than that of adults, which indicated that the prediction models could be applied for children to detect complete discoid lateral meniscus. CONCLUSION: Among several radiographic signs, the fibular head height can be used as a screening tool for complete discoid lateral meniscus. The prediction models combined with lateral joint space, fibular head height, lateral tibial plateau obliquity, and/or the condylar cut-off sign yielded a much higher diagnostic value than each radiographic sign. Therefore, fibular head height and prediction models combined with radiographic signs can provide improved diagnostic value for complete discoid lateral meniscus. LEVEL OF EVIDENCE: III.

Computed Tomography Image Analysis of Neuromuscular Electrical Stimulation in the Treatment of Knee Osteoarthritis with Different Radiologic Characteristics Based on Iterative Reconstruction Algorithm.

OBJECTIVE: To use computed tomography image analysis of iterative reconstruction algorithm to understand effect of neuromuscular electrical stimulation of quadriceps on motor function rehabilitation after total knee arthroplasty. METHODS: After total knee arthroplasty, 104 patients were randomly divided into 2 groups. The treatment group comprised 52 patients. The quadriceps femoris was stimulated by neuromuscular electrical stimulation, and patients were required to actively extend the knee along with the current stimulation. In the second group, which received cutaneous nerve electrical stimulation, 2 sets of electrodes were placed on knee pain points. All patients participated in conventional rehabilitation and were discharged from the hospital a mean 14.89 ± 3.65 days after treatment. Visual analog scale, range of motion of knee joint, and Knee Injury and Osteoarthritis Score were evaluated before discharge. The mean interval between follow-up evaluations after discharge was 9.5 months. Knee Society Score and Knee Injury and Osteoarthritis Score were assessed during follow-up. RESULTS: Visual analog scale scores of treatment and control groups at discharge were 18.11 ± 9.66 and 16.13 ± 4.25, and active range of motion of the knee joint was 103.21° ± 15.44° and (99.21° ± 15.19°, respectively. Limitation of active knee extension in the treatment group was 1.93° ± 3.47°, which was significantly smaller than in the control group (6.26° ± 4.28°). CONCLUSIONS: Neuromuscular electrical stimulation of the quadriceps muscle early after total knee arthroplasty helps to improve the function of the knee extension device and accelerate functional rehabilitation. Computed tomography has found that changes in tibial subchondral bone plate and subchondral cancellous bone in patients with knee osteoarthritis are mainly due to destruction of ultrastructural homeostasis. This change may be the cause of knee osteoarthritis.

Effects of Combination Denosumab and High-Dose Teriparatide Administration on Bone Microarchitecture and Estimated Strength: The DATA-HD HR-pQCT Study.

In postmenopausal women at high risk of fracture, we previously reported that combined denosumab and high-dose (HD; 40 µg) teriparatide increased spine and hip bone mineral density (BMD) more than combination with standard-dose teriparatide (SD; 20 µg). To assess the effects of these combinations on bone microarchitecture and estimated bone strength, we performed high-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius and distal tibia in these women, who were randomized to receive either teriparatide 20 µg (n = 39) or 40 µg (n = 37) during months 0 to 9 overlapped with denosumab 60 mg s.c. given at months 3 and 9, for a 15-month study duration. The 69 women who completed at least one study visit after baseline are included in this analysis. Over 15 months, increases in total BMD were higher in the HD-group than the SD-group at the distal tibia (5.3% versus 3.4%, p = 0.01) with a similar trend at the distal radius (2.6% versus 1.0%, p = 0.06). At 15 months, cortical porosity remained similar to baseline, with absolute differences of -0.1% and -0.7% at the distal tibia and -0.4% and -0.1% at the distal radius in the HD-group and SD-group, respectively; p = NS for all comparisons. Tibial cortical tissue mineral density increased similarly in both treatment groups (1.3% [p < 0.0001 versus baseline] and 1.5% [p < 0.0001 versus baseline] in the HD-group and SD-group, respectively; p = 0.75 for overall group difference). Improvements in trabecular microarchitecture at the distal tibia and estimated strength by micro-finite element analysis at both sites were numerically greater in the HD-group compared with SD-group but not significantly so. Together, these findings suggest that short-term treatment combining denosumab with either high- or standard-dose teriparatide improves HR-pQCT measures of bone density, microstructure, and estimated strength, with greater gains in total bone density observed in the HD-group, which may be of benefit in postmenopausal women with severe osteoporosis. © 2020 American Society for Bone and Mineral Research (ASBMR).

Treatment of osteoporosis with a modified zeolite shows beneficial effects in an osteoporotic rat model and a human clinical trial.

The severity of osteoporosis in humans manifests in its high incidence and by its complications that diminish quality of life. A societal consequence of osteoporosis is the substantial burden that it inflicts upon patients and their families. Several bone-modifying drugs have been prescribed to patients with osteoporosis. However, evidence for their anti-fracture efficacy remains inconclusive. To the contrary, long-term use of anti-osteoporotic drugs such as bisphosphonates and Denosumab, an RANKL inhibitor, have resulted in adverse events. We now present an alternative and adjuvant approach for treatment of osteoporosis. The data derive from in vivo studies in an ovariectomized rat model and from a randomized double blind, placebo-controlled human clinical study. Both studies involved treatment with Panaceo Micro Activation (PMA)-zeolite-clinoptilolite, a defined cation exchange clinoptilolite, which clearly improved all bone histomorphometric parameters examined from ovariectomized animals, indicative for increased bone formation. Moreover, intervention with PMA-zeolite-clinoptilolite for one year proved safe in humans. Furthermore, patients treated with PMA-zeolite-clinoptilolite showed an increase in bone mineral density, an elevated level of markers indicative of bone formation, a significant reduction in pain, and significantly improved quality of life compared with patients in the control (placebo) group. These encouraging positive effects of PMA-zeolite-clinoptilolite on bone integrity and on osteoporosis warrant further evaluation of treatment with PMA-zeolite-clinoptilolite as a new alternative adjuvant therapy for osteoporosis.

Medial tibial stress fracture diagnosis and treatment guidelines.

OBJECTIVES: To validate and make evidence based changes to the Israel Defense Forces medial tibial stress fracture diagnosis and treatment protocol. DESIGN: Prospective cohort study. METHODS: 429 Elite infantry recruits were reviewed for signs and symptoms of medial tibial stress fracture during 14 weeks of basic training. Suspicion of medial tibial stress fracture was based on the presence of pain, tenderness <1/3 the length of the tibia and a positive fulcrum and/or hop test. Recruits with suspected medial tibial stress fractures were initially treated with 10-14 days of rest. Bone scan was performed only when recruits failed to respond to the rest regimen or required immediate diagnosis. RESULTS: 31 Out of 49 recruits with a suspicion of medial tibial stress fracture underwent bone scan, including 8/26 recruits whose symptoms did not resolve after being treated clinically as stress fractures. There was a significantly greater incidence of medial tibial stress fractures when a positive hop test was present in addition to tibial pain and tenderness (p=0.0001), odds ratio 52.04 (95% CL, 2.80-967.74). Medial tibial stress fracture was found to occur when the band of tibial tenderness was ≤10cm in length. Tibial pain scores were not predictive of stress fracture. CONCLUSIONS: This validation study provides the clinician with evidence based guidelines for the clinical diagnosis and treatment of medial stress fractures and their differentiation from shin splints. An initial treatment protocol without the use of imaging was found to be effective in more than two-thirds of the cases.

Bilateral Looser zones or pseudofractures in the anteromedial tibia as a component of medial tibial stress syndrome in athletes.

PURPOSE: Medial tibial stress syndrome (MTSS) represents a common diagnosis in individuals exposed to repetitive high-stress loads affecting the lower limb, e.g., high-performance athletes. However, the diagnostic approach and therapeutic regimens are not well established. METHODS: Nine patients, diagnosed as MTSS, were analyzed by a comprehensive skeletal analysis including laboratory bone turnover parameters, dual-energy X-Ray absorptiometry (DXA), and high-resolution peripheral quantitative computed tomography (HR-pQCT). RESULTS: In 4/9 patients, bilateral pseudofractures were detected in the mid-shaft tibia. These patients had significantly lower levels of 25-hydroxycholecalciferol compared to patients with MTSS but similar levels of bone turnover parameters. Interestingly, the skeletal assessment revealed significantly higher bone mineral density (BMD) Z-scores at the hip (1.3 ± 0.6 vs. - 0.7 ± 0.5, p = 0.013) in patients with pseudofractures and a trend towards higher bone microarchitecture parameters measured by HR-pQCT at the distal tibia. Vitamin D supplementation restored the calcium-homeostasis in all patients. Combined with weight-bearing as tolerated, pseudofractures healed in all patients and return to competition was achieved. CONCLUSION: In conclusion, deficient vitamin D levels may lead to pseudofractures due to localized deterioration of mineralization, representing a pivotal component of MTSS in athletes with increased repetitive mechanical loading of the lower limbs. Moreover, the manifestation of pseudofractures is not a consequence of an altered BMD nor microarchitecture but appears in patients with exercise-induced BMD increase in combination with reduced 25-OH-D levels. The screening of MTSS patients for pseudofractures is crucial for the initiation of an appropriate treatment such as vitamin D supplementation to prevent a prolonged course of healing or recurrence. LEVEL OF EVIDENCE: III.

Oral Exposure to ZnO Nanoparticles Disrupt the Structure of Bone in Young Rats via the OPG/RANK/RANKL/IGF-1 Pathway.

PURPOSE: To evaluate the effects of ZnO NPs on bone growth in rats and explore the possible mechanisms of action. MATERIALS AND METHODS: Three-week-old male rats received ultrapure water or 68, 203, and 610 mg/kg zinc oxide nanoparticles (ZnO NPs) for 28 days, orally. RESULTS: The high-dosage groups caused significant differences in weight growth rate, body length, and tibia length (P<0.05), all decreasing with increased ZnO NP dosage. There were no significant differences in body mass index (BMI) (P>0.05). The zinc concentration in liver and bone tissue increased significantly with increased ZnO NP dosage (P<0.05). Clearly increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were observed in the 610 mg/kg ZnO NP group (P>0.05), whereas alkaline phosphatase (ALP) increased in the 610 mg/kg ZnO NP group (P<0.05). Significant differences in insulin-like growth factor type 1 (IGF-1) levels and a decrease in calcium (Ca) levels were observed in 203 and 610 mg/kg ZnO NP groups (P<0.05). Phosphorus (P) levels increased and the Ca/P ratio decreased in the 610 mg/kg ZnO NP group (P<0.05). Micro-computed tomography (micro-CT) of the tibia demonstrated signs of osteoporosis, such as decreased bone density, little trabecular bone structure and reduced cortical bone thickness. Micro-CT data further demonstrated significantly decreased bone mineral density (BMD), trabecular number (Tb.N), and relative bone volume (BV/TV) with increasing dosage of ZnO NPs. Osteoprotegerin (OPG) expression and the ratio of OPG to receptor activator of nuclear factor-κB ligand (RANKL) were statistically lower in the 610 mg/kg ZnO NP group (P<0.05), whereas RANKL expression did not change significantly (P>0.05). CONCLUSION: We infer that ZnO NPs affect bone growth in young rats directly or indirectly by altering IGF-1 levels. Overall, the results indicate that ZnO NPs promote osteoclast activity and increase bone loss through the OPG/RANK/RANKL/IGF-1 pathway.