Enhanced Outcomes in Femoral Subtrochanteric Fractures Using Long INTERTAN Nails with Titanium Cable Cerclage: A Retrospective Analysis.

BACKGROUND The evidence on use of supplementary titanium cable cerclage (TCC) in treating femoral subtrochanteric fractures (FSF) remains scarce. Therefore, this study aimed to investigate the potential therapeutic effects for FSF patients using TCC. MATERIAL AND METHODS A retrospective study of 68 FSF patients treated by a long intramedullary (IM) nailing with (Observation group, n=41) or without (Control group, n=27) TCC was conducted from January 2020 to December 2021. The primary outcome measure was time to postoperative full weight-bearing. Secondary outcome measures were operation time, intraoperative blood loss, number of blood transfusions needed, varus angle loss, excellent and good rate of fracture reduction, Harris score, and survival rate. RESULTS Patients were followed up for 13 to 36 months. The excellent and good rate of fracture reduction was 100% in the Observation group versus 92.6% in the Control group (P=0.013), and the varus angle loss and time to postoperative full weight-bearing in the Observation group were significantly less than in the Control group (P<0.05). The intraoperative blood loss in the Observation group was significantly higher than in the Control group (P<0.001). No differences were noted between groups for Harris scores and survival rates at last follow-up. CONCLUSIONS TCC fixation combined with IM nailing can improve the excellent and good rate of fracture reduction and reduce varus angle loss, as well as shorten the time to full weight-bearing and promote early functional exercise, which offers an effective treatment option for FSF patients who have failed closed reduction.

[Effects of fine particulate matter on bone mass and osteogenic differentiation of bone marrow mesenchymal stem cells in mice].

OBJECTIVE: To observe the effects of exposure to fine particulate matter(PM_(2.5)) on bone mass, microstructure, biomechanical properties, and osteogenic differentiation ability of bone marrow mesenchymal stem cells(BMSCs) in mice. METHODS: A total of 16 C57BL/6J mice aged 8 weeks were randomly divided into control group(NS group) and PM_(2.5) exposure group(PM group). NS group was given normal saline, PM group was given 14 mg/kg PM_(2.5) suspension, 50 µL, poisoning every 3 day. After 10 weeks, the lungs of mice were taken for HE staining, and the left tibia was taken for Micro CT detection to analyze parameters related to cancellous and cortical bone. The right tibia was taken for HE staining to observe changes in bone trabeculae. Immunohistochemical staining was used to detect type I collagen(Col I), osteoprotegerin(OPG), and nuclear factor-κB receptor activating factor ligand(RANKL) protein expression, tartrate resistant acid phosphatase(TRAP) staining for detection of osteoclasts. Extract primary BMSCs from bilateral femurs, induce osteogenesis, and then perform alkaline phosphatase(ALP) staining to detect ALP activity, alizarin red staining to detect bone mineralization ability, real-time PCR to detect osteocalcin(OCN), ALP, OPG, and RANKL mRNA expression, and biomechanical testing to test the mechanical properties of the femur. RESULTS: Compared with the NS group, the pulmonary alveolar structure of the PM group mice was disrupted and a large number of inflammatory cells gathered. Prompt for successful PM_(2.5) poisoning operation. Micro CT result showed that the bone mineral density(BMD) and bone volume fraction(BV/TV) of the PM group mice were 276.959±15.152 mg/cm~3 and 0.208%±0.009%, respectively. The NS group had 316.709±28.205 mg/cm~3 and 0.236%±0.019%, respectively. The PM group was lower than the NS group(P<0.05), but the trabecular number(Tb. N) There was no statistically significant difference in parameters such as trabecular thickness(Tb. Th) and trabecular separation(Tb. SP)(P>0.05). The HE staining result of the tibia showed that the trabeculae in the NS group were thick, dense, and uniform. The bone trabeculae in the PM group were slender, with a decrease in number, widened spacing, and sparse arrangement. The expression of Col I(0.023±0.009) and OPG(0.036±0.010) in the PM group increased compared to the NS group(0.079±0.007, 0.059±0.012), while the expression of RANKL(0.036±0.006) decreased compared to the NS group(0.022±0.002)(P<0.05); The number of TRAP positive particles increased in the PM group. The experimental result after osteoinduction of BMSCs in mice showed that compared with the NS group, the PM group had a decrease in the number of ALP positive cells and a decrease in the number of calcium nodules. The relative expression of ALP, OCN, and OPG mRNA in the PM group(0.375±0.021, 0.585±0.088, 0.768±0.112) was significantly reduced compared to the NS group(1.001±0.043, 1.006±0.132, 1.002±0.086), while the relative expression of RANKL mRNA(1.278±0.118) was increased compared to the NS group(1.001±0.057)(P<0.05). The biomechanical experimental result showed that the maximum deflection of the NS group was 0.337±0.031 mm, while the maximum deflection of the PM group was 0.258±0.041 mm. Compared with the NS group, the maximum deflection of the PM group decreased significantly(P<0.05), and the maximum stress and maximum load showed a decreasing trend, but the difference was not statistically significant(P>0.05). CONCLUSION: After 10 weeks of exposure to PM_(2.5), it can affect the bone health of mice, and its mechanism may be related to increased osteoclast activity and inhibition of the osteogenic differentiation ability of BMSCs.

New-onset stroke on the risk of hip fracture: the Kailuan cohort study in China.

PURPOSE: Stroke is a documented risk factor for hip fracture(HF). However, no data is currently available on this issue in mainland China, we therefore assessed the risk of hip fracture after new-onset stroke using a cohort study. METHODS: This study included 165,670 participants without a history of stroke at baseline from the Kailuan study. All participants were followed biennially until December 31, 2021. During follow-up, a total of 8,496 new-onset stroke cases were identified. For each case subject, four control subjects was randomly selected, matched for age (± 1 years) and sex. The final analysis comprised 42,455 pair-matched cases and controls. A multivariate Cox proportional hazard regression model was used to estimate the effect of new-onset stroke on the risk of hip fracture. RESULTS: During an average follow-up of 8.87 (3.94) years, a total of 231 hip fracture cases occurred, 78 cases in the stroke group and 153 cases in the control group, with incidence rates of 1.12 and 0.50 per 1000 person-years, respectively. The cumulative incidence of the stroke group was higher than that of the controls (P < 0.01). The adjusted hazard ratio (95% confidence interval) of hip fractures in the stroke group was 2.35 (1.77 to 3.12) (P < 0.001) to controls. After stratifying by gender, age, and body mass index, the higher risk was revealed in female (HR 3.10, 95 CI: 2.18 to 6.14, P < 0.001), age < 60 years old (HR 4.12, 95% CI: 2.18 to 7.78, P < 0.001), and non-obesity (BMI<28 kg/m2) (HR 1.74, 95% CI:1.31 to 2.31, P < 0.001) subgroup. CONCLUSIONS: Stroke significantly increases the risk of hip fracture, strategy for protecting stroke patients from falls and hip fractures should be emphasized in poststroke long-term management, particularly the female, age < 60 years old, and non-obese patients.

Estrogen deficiency impedes fracture healing despite eliminating the excessive absorption of the posterior callus in a semi-fixed distal tibial fracture mouse model.

BACKGROUND: Treatment of distal tibial fractures is a challenge due to their specific anatomical location. However, there is no appropriate mouse model to simulate a clinical distal tibial fracture for basic research. The aim of this investigation was to evaluate the feasibility of simulating a clinical fracture of the distal tibia of mice and to investigate the effect of ovariectomy (OVX)-induced osteoporosis on fracture healing in this model. METHODS: Sixty female 8-week-old C57BL/6 mice were randomly divided into two groups, either sham or OVX. A semi-fixation distal tibia fracture was established in the right tibia after 8 weeks of OVX. The right tibias were collected at 7, 14, 21, and 28 days post fracture. RESULTS: In the semi-fixation distal tibia fracture model, the posterior callus in the sham group showed excessive bone resorption and lower bone mass phenotype compared with the anterior site; a similar trend was not found in the OVX group. At 28 days post fracture, the posterior callus was more mineralized than the anterior callus in the OVX group. Although the fracture healing of the sham group showed a special phenotype in this mode, the progress and quality of fracture healing were still better than those of the OVX group. CONCLUSION: A semi-fixed distal tibial closed fracture mouse model was successfully established. In this model, excess bone resorption of the posterior callus impaired normal fracture healing, but not in OVX-induced osteoporotic bone. Although the stress shielding effect was not observed in the OVX group, impaired bone healing caused by OVX was still present. Our results suggest that this fracture model may have potential for studies on distal tibial fractures and stress shielding.

Parathyroid Hormone (1-34) Attenuates Cartilage Degradation and Preserves Subchondral Bone Micro-architecture in Rats with Patella Baja-Induced-Patellofemoral Joint Osteoarthritis.

Several studies have revealed that PTH1-34 may possess the potential for treating osteoarthritis (OA) and osteoporosis. However, no study has yet determined whether PTH1-34 can be used for the treatment of patella baja-induced patellofemoral joint OA (PFJOA). Thus, this study sought to assess the efficacy of PTH1-34 for the treatment of PFJOA in a rat model. Patella baja was induced in 3-month-old female Sprague-Dawley (SD) rats by patellar ligament shortening (PLS), after which the rats were randomly divided into three groups (n = 12): Sham, PLS, and PTH group (PTH + PLS, PTH1-34, 30 µg/kg/d, 5 days per week for 10 weeks). Thereafter, radiographic imaging, macroscopic and microscopic analyses, immunohistochemistry, and microcomputed tomography (CT) analysis were performed. The appearance of PLS-induced PFJOA promoted obvious changes in the patellar position and structure in the PLS group, which were characterized by cartilage degeneration, subchondral bone microstructure deterioration, patella baja, and increasing patella length. However, these negative characteristics were markedly ameliorated by PTH1-34, which not only inhibited cartilage catabolism by decreasing MMP-13 and ADAMTS-4 but also enhanced anabolism by increasing Col-II and Aggrecan. Furthermore, the micro-CT results showed a marked improvement in subchondral bone microarchitecture. The findings presented herein demonstrated that early treatment with PTH1-34 could improve cartilage metabolism and subchondral bone health in this PFJOA model.

STAT3-mediated osteogenesis and osteoclastogenesis in osteoporosis.

Osteoporosis is a common skeletal disease with marked bone loss, deterioration of the bone microstructure and bone fragility. An abnormal bone remodelling cycle with relatively increased bone resorption is the crucial pathophysiological mechanism. Bone remodelling is predominantly controlled by osteoblasts and osteoclasts, which are specialized cell types that are regulated by a variety of osteogenic and osteoclastic factors, including cytokines expressed within the bone microenvironment under local or systemic inflammatory conditions. Signal transducer and activator of transcription 3 (STAT3) plays a prominent role in the communication between cytokines and kinases by binding downstream gene promotors and is involved in a wide range of biological or pathological processes. Emerging evidence suggests that STAT3 and its network participate in bone remodelling and the development of osteoporosis, and this factor may be a potent target for osteoporosis treatment. This review focuses on the role and molecular mechanism of the STAT3 signalling pathway in osteogenesis, osteoclastogenesis and osteoporosis, particularly the bone-related cytokines that regulate the osteoblastic differentiation of bone marrow stromal cells and the osteoclastic differentiation of bone marrow macrophages by initiating STAT3 signalling. This review also examines the cellular interactions among immune cells, haematopoietic cells and osteoblastic/osteoclastic cells. Video abstract.

Elevated blood purine levels as a biomarker of seizures and epilepsy.

OBJECTIVE: There is a major unmet need for a molecular biomarker of seizures or epilepsy that lends itself to fast, affordable detection in an easy-to-use point-of-care device. Purines such as adenosine triphosphate and adenosine are potent neuromodulators released during excessive neuronal activity that are also present in biofluids. Their biomarker potential for seizures and epilepsy in peripheral blood has, however, not yet been investigated. The aim of the present study was to determine whether blood purine nucleoside measurements can serve as a biomarker for the recent occurrence of seizures and to support the diagnosis of epilepsy. METHODS: Blood purine concentrations were measured via a point-of-care diagnostic technology based on the summated electrochemical detection of adenosine and adenosine breakdown products (inosine, hypoxanthine, and xanthine; SMARTChip). Measurements of blood purine concentrations were carried out using samples from mice subjected to intra-amygdala kainic acid-induced status epilepticus and in video-electroencephalogram (EEG)-monitored adult patients with epilepsy. RESULTS: In mice, blood purine concentrations were rapidly increased approximately two- to threefold after status epilepticus (2.32 ± .40 µmol·L-1 [control] vs. 8.93 ± 1.03 µmol·L-1 [after status epilepticus]), and levels correlated with seizure burden and postseizure neurodegeneration in the hippocampus. Blood purine concentrations were also elevated in patients with video-EEG-diagnosed epilepsy (2.39 ± .34 µmol·L-1 [control, n = 13] vs. 4.35 ± .38 µmol·L-1 [epilepsy, n = 26]). SIGNIFICANCE: Our data provide proof of concept that the measurement of blood purine concentrations may offer a rapid, low-volume bedside test to support the diagnosis of seizures and epilepsy.

The pathological role of Wnt5a in psoriasis and psoriatic arthritis.

Psoriasis (PsO) is a chronic inflammatory skin disease with both local and systemic components. PsO-associated arthritis, known as psoriatic arthritis (PsA), develops in approximately 13%-25% of PsO patients. Various factors associated with both PsO and PsA indicate that these conditions are part of a single disease. Identification of novel targets for the development of drugs to treat both PsO and PsA is desirable to provide more patient-friendly treatment regimens. Such targets will likely represent 'common checkpoints' of inflammation, for example key components or transduction cascades of the signalling pathways involved. Emerging evidence supports involvement of the non-canonical Wnt signalling pathways in the development of both PsO and PsA, especially the Wnt5a-activated signalling cascades. These, together with interlinked factors, are crucial in the interactions among keratinocytes, immune cells and inflammatory factors in PsO, as well as among chondrocytes, osteoblasts and osteoclasts that trigger both subchondral bone remodelling and cartilage catabolism in PsA. This review focuses on the pathological role of Wnt5a signalling and its interaction with other interlinked pathways in both PsO and PsA, and also on the main challenges for future research, particularly with respect to molecules targeting Wnt signalling pathways for the treatment of PsO and PsA.

Identification of Gli1-interacting proteins during simvastatin-stimulated osteogenic differentiation of bone marrow mesenchymal stem cells.

Simvastatin has been shown to promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Our study aimed to illuminate the underlying mechanism, with a specific focus on the role of Hedgehog signaling in this process. BMSCs cultured with or without 10-7 mol/L simvastatin were subjected to evaluation of osteogenic differentiation capacity. Osteogenic markers such as type 1 collagen (COL1) and osteocalcin (OCN), as well as key molecules of Hedgehog signaling molecules, were examined by Western blot and real-time polymerase chain reaction (PCR). Co-immunoprecipitation and mass spectrometry assays were applied to screen for Gli1-interacting proteins. Cyclopamine (Cpn) was used as a Hedgehog signaling inhibitor. Our results indicated that simvastatin increased alkaline phosphatase (ALP) activity; mineralization of extracellular matrix; mRNA expression of ALP, COL1, and OCN; and expression and nuclear translocation of Gli1. Contrasting effects were observed in Cpn-exposed groups, but were partially rescued by the simvastatin treatment. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that Gli1-interacting proteins were primarily associated with mitogen-activated protein kinase (MAPK) (P = 7.04E-04 ), hippo, insulin, and glucagon signaling. Further, hub genes identified by protein-protein interaction network analysis included Gli1-interacting proteins such as Ppp2r1a, Rac1, Etf1, and XPO1/CRM1. In summary, the current study showed that the mechanism by which simvastatin stimulates osteogenic differentiation of BMSCs involves activation of Hedgehog signaling, as indicated by interactions with Gli1 and, most notably, the MAPK signaling pathway.

Wnt signaling: a promising target for osteoarthritis therapy.

Osteoarthritis (OA) is the most common joint disease worldwide and a leading cause of disability. Characterized by degradation of articular cartilage, synovial inflammation, and changes in periarticular and subchondral bone, OA can negatively impact an individual's physical and mental well-being. Recent studies have reported several critical signaling pathways as key regulators and activators of cellular and molecular processes during OA development. Wnt signaling is one such pathway whose signaling molecules and regulators were shown to be abnormally activated or suppressed. As such, agonists and antagonists of those molecules are potential candidates for OA treatment. Notably, a recent phase I clinical trial (NCT02095548) demonstrated the potential of SM04690, a small-molecule inhibitor of the Wnt signaling pathway, as a disease-modifying oseoarthritis drug (DMOAD). This review summarizes the role and mechanism of Wnt signaling and related molecules in regulating OA progression, with a view to accelerating the translation of such evidence into the development of strategies for OA treatment, particularly with respect to potential applications of molecules targeting the Wnt signaling pathway.

Point-of-care measurements reveal release of purines into venous blood of stroke patients.

Stroke is a leading cause of death and disability. Here, we examine whether point-of-care measurement of the purines, adenosine, inosine and hypoxanthine, which are downstream metabolites of ATP, has potential to assist the diagnosis of stroke. In a prospective observational study, patients who were suspected of having had a stroke, within 4.5 h of symptom onset and still displaying focal neurological symptoms at admission, were recruited. Clinical research staff in the Emergency Departments of two hospitals used a prototype biosensor array, SMARTCap, to measure the purines in the venous blood of stroke patients and healthy controls. In controls, the baseline purines were 7.1 ± (SD) 4.2 µM (n = 52), while in stroke patients, they were 11.6 ± 8.9 µM (n = 76). Using the National Institutes for Stoke Scale (NIHSS) to band the severity of stroke, we found that minor, moderate and severe strokes all gave significant elevation of blood purines above the controls. The purine levels fall over 24 h. This was most marked for patients with haemorrhagic strokes (5.1 ± 3.6 µM, n = 9 after 24 h). The purine levels measured on admission show a significant correlation with the volume of affected brain tissue determined by medical imaging in patients who had not received thrombolysis or mechanical thrombectomy. ClinicalTrials.gov Identifier: NCT02308605.

Protective Effect of Alendronate on Lumbar Facet Degeneration in Ovariectomized Rats.

BACKGROUND Facet joint degeneration (FJD) is a potential source of lower back pain, and estrogen deficiency can accelerate FJD. The present study aimed to investigate the effects of alendronate (ALN) on FJD induced by ovariectomy (OVX) in rats. MATERIAL AND METHODS Thirty female Sprague-Dawley rats underwent either bilateral OVX (n=20) or sham surgery (n=10). The OVX rats subsequently received either subcutaneous ALN (70 µg/kg/week) or vehicle for 12 weeks. Subchondral bone mass and microarchitecture were evaluated by micro-computed tomography. Cartilage degradation was evaluated by toluidine blue staining and histological scoring. RESULTS Compared with the Sham group, the OVX group had significantly decreased bone mineral density, bone volume/trabecular volume, and trabecular thickness, significantly increased trabecular separation in subchondral bone, and significantly higher histological score for cartilage degeneration, particularly loss of cartilage thickness. ALN treatment significantly reversed the changes in subchondral bone, preserved cartilage thickness, and reduced the histological score. Immunohistochemical analyses showed significantly decreased expression of ADAMTS-4, MMP-13, and caspase-3 in the OVX+ALN group compared with the OVX group. CONCLUSIONS Treatment with ALN suppressed bone loss, subchondral bone architecture deterioration, and cartilage degeneration in OVX rats, which can be explained by roles of ALN in preservation of subchondral bone mass and microarchitecture, and counteraction of catabolism and chondrocyte apoptosis in cartilage.

A Novel Rat Model of Patellofemoral Osteoarthritis Due to Patella Baja, or Low-Lying Patella.

BACKGROUND Patella baja, or patella infera, consists of a low-lying patella that results in a limited range of motion, joint pain, and crepitations. Patellofemoral joint osteoarthritis (PFJOA) is a subtype OA of the knee. This study aimed to develop a reproducible and reliable rat model of PFJOA. MATERIAL AND METHODS Three-month-old female Sprague-Dawley rats (n=24) included a baseline group (n=8) that were euthanized at the beginning of the study. The sham group (n=8), and the patella ligament shortening (PLS) group (n=8) were euthanized and evaluated at ten weeks. The PLS model group (n=8) underwent insertion of a Kirschner wire under the patella tendon to induce patella baja. At ten weeks, the sham group and the PLS group were compared using X-ray imaging, macroscopic appearance, histology, immunohistochemistry, TUNEL staining for apoptosis, and micro-computed tomography (micro-CT). The patella height was determined using the modified Insall-Salvati (MIS) ratio. RESULTS The establishment of the rat model of patella baja in the PLS group at ten weeks was confirmed by X-ray. In the PLS group, patella volume, sagittal length, and cross-sectional area were significantly increased compared with the sham group. The PFJ showed typical lesions of OA, confirmed macroscopically and histologically. Compared with the sham group, in the rat model of PFJOA, there was increased cell apoptosis, and immunohistochemistry showed increased expression of biomarkers of osteoarthritis, compared with the sham group. CONCLUSIONS A rat model of PFJOA was developed that was confirmed by changes in cartilage and subchondral bone.

Salmon Calcitonin Attenuates Degenerative Changes in Cartilage and Subchondral Bone in Lumbar Facet Joint in an Experimental Rat Model.

BACKGROUND Facet joint degeneration (FJD) is one of the common causes of low back pain (LBP), and estrogen deficiency is one of the triggers for FJD. Calcitonin may possess the potential for treating osteoarthritis, but to date the hormone has not been studied in the treatment of FJD. Therefore, the aim of this study was to investigate the effects of salmon calcitonin (sCT) on FJD induced by estrogen deficiency after ovariectomy (OVX). MATERIAL AND METHODS Thirty female Sprague-Dawley rats were randomly assigned to 3 groups: the OVX group received bilateral OVX, the OVX + sCT group received subcutaneous administration of sCT (16 IU/kg/2 days) following bilateral OVX, and the Sham group received sham surgery. All rats were euthanized at 12 weeks post-OVX. Serum COMP level, cartilage degradation, and subchondral bone micro-architecture were evaluated. RESULTS sCT relieved cartilage surface lesions, reduced histological score, and significantly increased cartilage thickness. The OVX + sCT group exhibited significantly increased expression of aggrecan, as well as significantly decreased levels of ADAMTS-4, MMP-13, and caspase-3. The results of micro-computed tomography analysis revealed that the OVX + sCT group exhibited higher BMD, BV/TV, and Tb.Th values but a lower Tb.Sp value than that of the OVX group. Serum COMP concentrations were significantly correlated with histological score and cartilage thickness. CONCLUSIONS sCT can inhibit the progression of FJD in OVX rats, which is attributed to its inhibitory effects on cartilage metabolism imbalance, chondrocyte apoptosis, and subchondral bone remodeling. Serum COMP has diagnostic potential for FJD.

Strontium Ranelate Combined with Insulin Is as Beneficial as Insulin Alone in Treatment of Fracture Healing in Ovariectomized Diabetic Rats.

BACKGROUND Type 2 diabetes mellitus (T2DM) and estrogen deficiency both predispose fracture patients to increased risk of delayed union or nonunion. The present study investigated the effects of strontium ranelate (SR) on fracture healing in ovariectomized (OVX) diabetic rats. MATERIAL AND METHODS A mid-shaft fracture was established in female normal control (CF), diabetic (DF), and OVX diabetic (DOF) rats. Treated DOF rats received either insulin alone (DOFI) or combined with SR (DOFIS). All rats were euthanized at 2 or 3 weeks after fracture. Fracture healing was evaluated using radiological, histological, immunohistochemical, and micro-computed tomography analyses. RESULTS At 3 weeks after fracture, radiological and histological evaluations demonstrated delayed fracture healing in the DF group compared with the CF group, which was exacerbated by OVX, as indicated by the significantly lower X-ray score, BMD, BV/TV, and Md.Ar/Ps.Cl.Ar, and the markedly decreased OCN and Col I expression in the DOF group. All these changes were prevented by insulin alone or combined with SR treatment. In comparison with the DOFI group, DOFIS rats displayed markedly higher OCN expression at 2 weeks after fracture and Col I expression at 2 and 3 weeks after fracture. CONCLUSIONS These results demonstrated delayed fracture healing with preexisting estrogen deficiency and T2DM. While insulin alone and combined with SR were both effective in promoting bone fracture healing in this model, their combined treatment showed significant improvement in promoting osteogenic marker expression, but not of the radiological appearance, compared with insulin alone.

Effects of human parathyroid hormone 1-34 on bone loss and lumbar intervertebral disc degeneration in ovariectomized rats.

PURPOSE: Lumbar intervertebral disc degeneration is a common cause of lower back pain that affects the physical and mental health of patients and increases social burden. Parathyroid hormone has been reported to be effective at inhibiting disc degeneration; however, these effects have not been fully established in vivo in ovariectomized (OVX) rats. Thus, in this study, we aimed to address this issue and examine the effects of parathyroid hormone treatment in OVX rats. METHODS: Thirty female Sprague-Dawley rats, three months-old, were subjected to sham or ovariectomy surgery. Twelve weeks postsurgery, OVX rats were treated with either human parathyroid hormone [hPTH(1-34), 30 µg/kg/day] or vehicle (normal saline (NS)) treatment. The L3-6 spinal segments were harvested after 12 weeks treatment. Bone mineral density (BMD), micro-architectural parameters, and biomechanical assessment were measured at the lumbar vertebral bodies. Histology and immunohistochemistry were performed to analyze the characteristics of the lumbar intervertebral discs. RESULTS: OVX + PTH rats had significantly higher BMD, percentage bone volume density, trabecular thickness, and biomechanical strength compared with those in Sham and OVX + NS rats. Histology and immunostaining revealed that disc degeneration was not significantly different between the OVX + NS rats and the OVX + PTH rats, compared with the Sham group; the structure of nucleus pulposus was disordered, the expression of collagen I was increased, and collagen II and aggrecan were decreased. CONCLUSIONS: These findings confirmed that hPTH(1-34) treatment has substantial anabolic effects on bone mass and trabecular micro-architecture, while the excessively enhanced bone mass and strength were coupled with a non-significant effect on the disc degeneration in ovariectomized rats.

Blood purine measurements as a rapid real-time indicator of reversible brain ischaemia.

To preserve the disequilibrium between ATP and ADP necessary to drive cellular metabolism, enzymatic pathways rapidly convert ADP to adenosine and the downstream purines inosine and hypoxanthine. During ischaemia, these same pathways result in the production of purines. We performed a prospective observational study to test whether purine levels in arterial blood might correlate with brain ischaemia. We made real-time perioperative measurements, via microelectrode biosensors, of the purine levels in untreated arterial blood from 18 patients undergoing regional anaesthetic carotid endarterectomy. Pre-operatively, the median purine level was 2.4 µM (95% CI 1.3-4.0 µM); during the cross-clamp phase, the purines rose to 6.7 µM (95% CI 4.7-11.5 µM) and fell back to 1.9 µM (95% CI 1.4-2.7 µM) in recovery. Three patients became unconscious during carotid clamping, necessitating insertion of a temporary carotid shunt to restore cerebral blood flow. In these, the pre-operative median purine level was 5.4 µM (range 4.7-6.1 µM), on clamping, 9.6 µM (range 9.4-16.1 µM); during shunting, purines fell to below the pre-operative level (1.4 µM, range 0.4-2.9 µM) and in recovery 1.8 µM (range 1.8-2.6 µM). Our results suggest that blood purines may be a sensitive real-time and rapidly produced indicator of brain ischaemia, even when there is no accompanying neurological obtundation.

Strontium ranelate causes osteophytes overgrowth in a model of early phase osteoarthritis.

BACKGROUND: Osteoarthritis (OA) involves cartilage changes as well as modifications of subchondral bone and synovial tissues. Strontium ranelate (SR), an anti-osteoporosis compound, which is currently in phase III clinical trial for treatment of OA. Evidences suggest that SR preferably deposited in osteophyte, other than in subchondral bone in early phase of OA. This phenomenon raises concern about its utility for OA treatment as a disease-modifying drug. To evaluate the effect of SR on cartilage, subchondral bone mass and subchondral trabecular bone structure in medial meniscectomized (MNX) guinea pigs. METHOD: Thirty-six 3-month-old male Dunkin Hartley albino guinea pigs received either sham or medial meniscectomy operations. One week after the procedure, meniscectomized animals began 12 weeks of SR (625 mg/kg, daily) treatment by oral gavage for MNX + SR group, or normal saline for MNX + V group. All animals were euthanized 12 weeks later, cartilage degeneration and subchondral bone micro-architecture was analyzed. RESULTS: Both OARSI scores (P = 0.523 for marcoscopic scores, P = 0.297 for histological scores) and Cartilage thickness (P = 0.335) in MNX + SR group were comparable to MNX + V group. However, osteophyte sizes were larger in MNX + SR group (P = 0.014), and collapsed osteophytes in MNX + SR group (7 by 12) were significantly more than in MNX + V group (1 by 12) (P = 0.027), while immunohistochemistry indicates catabolic changes in osteophyte/plateau junction. Micro-CT analysis showed bone mineral density (BMD) (P = 0.001), bone volume fraction (BV/TV) (P = 0.008), trabecular spacing (Tb.Sp) (P = 0.020), trabecular thickness (Tb.Th) (P = 0.012) and structure model index (SMI) (P = 0.005) levels to be significantly higher in the MNX + SR group than in the MNX + V group. CONCLUSIONS: SR (625 mg/kg/day) did not protect cartilage from degeneration in MNX guinea pigs but subchondral bone was significantly enhanced. In early phase OA, SR administration causes osteophyte overgrowth, which may be related to incorporation into mineralizing osteophytes. This adverse effect is important for future studies of SR in OA.

Protective effect of calcitonin on lumbar fusion-induced adjacent-segment disc degeneration in ovariectomized rat.

BACKGROUND: Intervertebral disc (IVD) degeneration and pathological changes in the spinal cord are major causes of back pain. In addition to its well-established anti-resorptive effect on bone, calcitonin (CT) potentially exerts protective effects on IVD degeneration in ovariectomized rats. However, possible therapeutic effects of CT on lumbar fusion-induced adjacent-segment disc degeneration (ASDD) have not been investigated yet. In this study, we examined the effects of CT on IVD degeneration adjacent to a lumbar fusion in ovariectomized rats. METHODS: Posterolateral lumbar fusion (PLF) at L4-5 was performed 4 weeks after ovariectomy (OVX) or sham surgery in female Sprague-Dawley rats. Following PLF + OVX, rats received either salmon CT (OVX + PLF + sCT, 16 IU/Kg/2d) or vehicle (OVX + PLF + V) treatment for 12 weeks; the remaining rats were divided into Sham + V, OVX + V, and PLF + V groups. Fusion status was analyzed by manual palpation and radiography. Adjacent segment disc was assessed by histological, histomorphometric, immunohistochemical analysis. L6 vertebrae microstructures were evaluated by micro-computed tomography. RESULTS: Histological analysis showed more severe ASDD occurred in OVX + PLF + V rats compared with the OVX + V or PLF + V groups. CT treatment suppressed the score for ASDD, increased disc height, and decreased the area of endplate calcification. Immunohistochemical staining demonstrated that CT decreased the expression of collagen type-I, matrix metalloproteinase-13, and a disintegrin and metalloproteinase with thrombospondin motifs-4, whereas it increased the expression of collagen type-II and aggrecan in the disc. Micro-computed tomography indicated that CT increased bone mass and improved the microstructure of the L6 vertebrae. CONCLUSIONS: These results suggest that CT can prevent ASDD, induce beneficial changes in IVD metabolism, and inhibit deterioration of the trabecular microarchitecture of vertebrae in osteoporotic rats with lumbar fusion.

An increase in the incidence of hip fractures in Tangshan, China.

UNLABELLED: We determined the number and incidence of hip fractures in Tangshan, China, in 2010. Compared with data we reported in Tangshan from 1994, the crude and age-specific incidence increased significantly for both sexes, especially in women. Strategies are needed for effective fracture prevention in the future. INTRODUCTION: The aims of the study were to determine the incidence of cervical and trochanteric fractures of the proximal femur in Tangshan, China, in 2010 and to compare the incidence with data from 1994. METHODS: The orthopedic departments of 15 hospitals in Tangshan were visited in 2010; the medical records and radiographs of patients who had sustained cervical and trochanteric fractures were reviewed. The absolute number of admissions was collated and the incidence rate per 100,000 person years was calculated, adjusted by different age ranges, and gender. We then calculated the age-standardized incidence in 2010 as compared with those from 1994. RESULTS: The population of Tangshan in 2010 was determined to be 3,075,382 (1,558,173 males; 1,517,209 females); there were 1,509 cervical and trochanteric fractures (in 745 males and 764 females). The overall incidence was 47.8 and 50.4 fractures per 100,000 per year for men and women, respectively. Females showed a higher fracture incidence than males in those aged 55 years and over. Comparing the 2010 data with the 1994 findings, the incidence increased by 85% in men and by 306% in women; age-specific increases were observed in all female and male groups (except the 55-59 years age group). CONCLUSIONS: Compared with the results in 1994, the incidence of hip fracture has markedly increased in 2010 in Tangshan, China. It is necessary to implement a comprehensive policy for hip fracture prevention in our communities.