Ultrasound guided injection with Collagen-based Medical Device: real-life evaluation of efficacy and safety in hip osteoarthritis.

AIMS: Data regarding the treatment of hip osteoarthritis (OA) with collagen-based extracellular bio-scaffolds are lacking. We evaluated the treatment of hip OA with ultrasound guided intraarticular injections of Collagen-based Medical Device (CMD). MATERIAL AND METHODS: Forty-four patients with Kellgren-Lawrence grade (KLG) I or II were selected, and 20/44 randomly selected patients (CMD group), were treated with 2 weekly consecutive ultrasound guided intraarticular injections of CMD (MD-HIP, Guna S.p.a. Milan, Italy). An additional 24/44 patients were treated with oral non-steroidal anti-inflammatory drugs (NSAIDs) daily (NSAIDs group). Clinical assessment, X-rays and ultrasound evaluation were performed at baseline, and after 1 month in both groups, and after 3 months in the CMD group. Outcome measures were general pain VAS (0-10), the whole WOMAC score, and the WOMAC specific subscores. RESULTS: CMD and NSAIDs group were homogenous for age, gender, VAS pain and WOMAC scores. The CMD group had significant improvement of the VAS pain (p<0.0001), global WOMAC score (p<0.0001) and WOMAC function (p<0.0001) from baseline to the 1st month, with further improvement from the 1st to the 3rd month (p<0,001; p<0.01; p<0.03, respectively). Significant improvement in WOMAC pain (p<0.0001) and WOMAC stiffness (p<0.0001) was detected at 1st month, with no significant change at 3rd month. In the NSAIDs group significant improvement in WOMAC function was detected after 1 month (p=0.021) only. No adverse events were recorded in the CMD and NSAIDs group. CONCLUSION: The ultrasound guided intraarticular hip injections of CMD resulted in significant improvement in VAS pain and WOMAC scores compared to treatment with oral NSAIDs.

Intra-articular injection of monoiodoacetate induces diverse hip osteoarthritis in rats, depending on its dose.

BACKGROUND: Monoiodoacetate (MIA)-induced arthritis models are used widely in osteoarthritis (OA) research to develop effective conservative treatments for hip OA, as an alternative to joint replacement surgery. In joint OA models, such as the MIA-induced knee OA model, various doses of MIA are utilized, depending on the purpose of the research. So far, only 2 mg of MIA has been used for MIA-induced hip OA research. We hypothesized that the amount of MIA should be adjusted according to the osteoarthritis model under investigation. We performed radiographic and histological evaluations in rats for hip OA models induced by different doses of MIA. METHODS: One hundred and eighty right hips of six-week-old, male Sprague-Dawley rats (n = 30 rats per group) were treated with either a single intra-articular injection of various doses of MIA (0.25, 0.5, 1.0, 2.0, and 4.0 mg) dissolved in 25 µl of sterile saline (MIA group), or with 25 µl of sterile saline alone (Sham group). Radiographic and histological evaluations of the hip joint were performed at one, two, four, eight, and 12 weeks after administration (n = 6 rats per group per time point). RESULTS: OA changes progressed from 1 week after administration in the 1.0-mg, 2.0-mg, and 4.0-mg MIA groups. The degree of OA changes increased as the dose of MIA increased. The 0.25-mg and 0.5-mg MIA groups presented fewer OA changes than the 2.0-mg and 4.0-mg MIA groups during the entire study period (up to 12 weeks). The administration of 0.25 mg and 0.5 mg of MIA-induced both radiographic and histological OA changes in a time-dependent manner, whereas more than 2 mg of MIA provoked end-stage OA at 8 weeks after injection. Absolute, dose-dependent histopathological OA changes were observed 4 weeks after MIA administration. CONCLUSIONS: Intra-articular MIA injection to the hip joints of rats induced diverse OA changes dose-dependently. Research for developing novel conservative treatments for hip OA and intractable pain should consider the pathological condition when determining the dose of MIA to be employed.

Analgesic Effect of Duloxetine on an Animal Model of Monosodium Iodoacetate-Induced Hip Osteoarthritis.

We investigated the efficacy of duloxetine on hyperalgesia, histopathological and radiographic findings, pain-related sensory innervation of dorsal-root ganglia (DRG), and spinal changes in a rat model of induced hip osteoarthritis (OA). The right hip joints of male Sprague-Dawley rats (n = 6 rats/group) in the Sham group were injected with 25 µl of sterile saline and 25 µl of sterile saline with 2 mg of monosodium iodoacetate (MIA) were injected to the MIA + Vehicle and MIA + Duloxetine groups. We injected duloxetine 20 mg/kg intraperitoneally in the MIA + Duloxetine group 28 days after injection, whereas rats in the MIA + Vehicle group were injected with 0.5 ml of 20% dimethyl sulfoxide. We assessed hyperalgesia, histopathological changes, immunoreactive (-ir) neurons for calcitonin gene-related peptide and activating transcription factor 3 in DRG, and immunoreactive neurons for ionized-calcium-binding adaptor molecule 1 (Iba1) in the dorsal horn of the spinal cord. MIA administration into the hip joint let to mechanical hyperalgesia of the ipsilateral hind paw (p < 0.05). A single injection of duloxetine significantly attenuated it in induced hip OA (p < 0.05) and suppressed the number of Iba1-ir microglia of the ipsilateral dorsal horn (p < 0.05). These results suggest that a single injection of duloxetine suppressed mechanical hyperalgesia and may influence the expression of Iba1 in the microglia of the ipsilateral dorsal horn in the MIA-induced hip OA. This finding implies the inhibitory effects of duloxetine against neuropathic pain, which may lead to a change of microglial activities. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:422-430, 2020.

Pain-related behavior and the characteristics of dorsal-root ganglia in a rat model of hip osteoarthritis induced by mono-iodoacetate.

The principal aim of this study was to clarify the time course of pain-related behavior and pain-related sensory innervation in a rat model of hip osteoarthritis (OA) induced by intra-articular injection of mono-iodoacetate (MIA). Using 6-week-old male Sprague Dawley rats, 25 µl of sterile saline of 1% Fluoro-Gold solution (FG) (control group; n = 30) and 25 µl of sterile saline of 1% FG with 2 mg of MIA (MIA group; n = 30) was injected into the right hip joints. Gait function was evaluated using a CatWalk system after 7, 14, 28, 42, and 56 days (n = 5, respectively). Neurons in the dorsal root ganglion (DRG) between L1 and L5 were immunostained for calcitonin gene-related peptide (CGRP) and activating transcription factor-3 (ATF3). Gait analysis revealed the mean six parameters of hind paws at all time points were significantly lower in the MIA group (p = 0.05). The number of CGRP-immunoreactive (-IR) DRG neurons was significantly increased on days 7, 14, 28, and 42 peaking at 14 days in the MIA group. By contrast, expression of ATF3-IR in FG-labeled DRG neurons was significantly increased on days 42 and 57. The FG-labeled DRG neurons were distributed between L1 and L5, mainly at the L4 level. Pain-related behavior indicated by gait disturbance was observed in a MIA model of hip OA in rat. Early elevation of CGRP expression and late expression of ATF-3 were demonstrated in DRG neurons, possibly reflecting inflammatory pain and neuropathic pain in hip OA. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1424-1430, 2017.

Intra-articular injection of mono-iodoacetate induces osteoarthritis of the hip in rats.

BACKGROUND: The mechanism for hip pain has been unclear because of a lack of experimental animal models. We aimed to establish an intra-articular injection technique to the rat hip and to document the effect of intra-articular mono-iodoacetate (MIA) injection to the rat hip with radiography and histology. METHODS: Using 60 6-week-old male Sprague Dawley rats, 25 µl of sterile saline (control group; n = 30) and 25 µl of sterile saline with 2 mg of MIA (MIA group; n = 30) was injected into the right hip joints via posterior approach using a 27G needle. The animals were examined with X-ray and histology 7, 14, 28, 42, and 56 days later (MIA group [n = 6] and control group [n = 6], respectively). RESULTS: The MIA group showed progressive radiographic changes to the hip joint during the experimental period, whereas the control group maintained a normal appearance. The microanatomic appearance was consistent with X-ray images of progressive destruction in the MIA group and normal tissue in the control group. Osteoarthritic (OA) changes became apparent at 42 and 56 days in the MIA group. CONCLUSIONS: We established an intra-articular injection technique to the rat hip, creating a hip OA model in the rat by intra-articular injection of MIA.

Development of a model to induce transient synovitis and lameness in the hip joint of dogs.

OBJECTIVE: To develop a model of hip joint synovitis on the basis of intra-articular injection of a sodium urate suspension in dogs and to characterize associated gait changes. ANIMALS: 6 healthy adult dogs. PROCEDURES: Each dog was sedated, and synovitis was induced by injection of 1 mL of a sodium urate suspension (20 mg/mL) into the right hip joint under ultrasonographic guidance. Observational and instrumented gait analyses to determine temporospatial, kinetic, and kinematic variables were performed prior to and 4, 8, and 24 hours after sedation and synovitis induction. RESULTS: Injection of a sodium urate suspension into the hip joint of healthy dogs resulted in lameness of the ipsilateral pelvic limb as determined by observational and instrumented gait analyses. For all dogs, lameness was clinically detectable within 1.5 to 2 hours after injection, reached its maximum intensity at 4 hours after injection, and had subsided by 24 hours after injection. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that injection of a sodium urate suspension into the hip joint of healthy dogs reliably induced synovitis and signs of pain and lameness in the ipsilateral pelvic limb that lasted 24 hours. This model can be used in conjunction with instrumented gait analysis to provide information on gait changes associated with hip joint disease and might be useful for evaluating the efficacy of analgesics or other interventions for the treatment of hip joint disease in dogs.

A novel rat model of hip pain by intra-articular injection of nerve growth factor-characteristics of sensory innervation and inflammatory arthritis.

OBJECTIVES: To determine the direct effects of intra-articular injection of nerve growth factor (NGF) into normal rat hips and the time course of pain-related mediator appearance. METHODS: Using 36 numbers of 8-week-old male Sprague-Dawley rats, 30 µl of 1% Fluoro-Gold solution (FG) (Sham-operated group; n = 12), 30 µl of 1% FG with 50 µg/ml NGF (NGF50 group; n = 12), and 30 µl of 1% FG with 100 µg/ml NGF (NGF100 group; n = 12) were injected into the left hip joints. Neurons in the dorsal root ganglion (DRG) labeled with FG, and FG and calcitonin gene-related peptide-immunoreactivity (CGRP-IR) were counted. The synovia in the left hip joint was examined histologically. RESULTS: The NGF50 and NGF100 groups showed evidence of synovitis without cartilage degeneration compared with the Sham-operated group. At 7 days, the proportions of CGRP-IR FG-labeled to total FG-labeled neurons were 12%, 18%, and 36% in the Sham-operated, NGF50, and NGF100 groups, respectively. At 14 days, the proportions were 13%, 22%, and 35% in the Sham-operated, NGF50, and NGF100 groups, respectively. At 7 and 14 days, the NGF50 and NGF100 groups showed a significantly higher proportion of CGRP-IR FG-labeled neurons than the Sham-operated group. CONCLUSIONS: Intra-articular administration of NGF into the hip joint produces a novel rat model for hip pain.

Association of nitrate use with risk of new radiographic features of hip osteoarthritis in elderly white women: the study of osteoporotic fractures.

OBJECTIVE: To examine the association between nitrate medication use and the development of new radiographic findings of hip osteoarthritis (OA) in elderly women. METHODS: Pelvic radiographs were obtained at baseline and a mean of 8.3 years later in 5,987 women, age > or =65 years at the baseline examination of the Study of Osteoporotic Fractures. Atlas-standardized individual radiographic features (IRFs) of OA were assessed and minimal joint space was measured on paired films. New radiographic findings of hip OA were defined as the development in hips free of these findings at baseline: 1) joint space narrowing (JSN), which consisted of either a MJS < or =1.5 mm or an IRF score indicating lateral JSN > or =2 or medial JSN > or =3; 2) an IRF score for osteophytes of > or =2 in any location; or 3) a summary grade of 2 or more (at least 2 IRFs present). Nitrate use was recorded by interview at years 6 and 8. Logistic and linear regression analyses were performed to determine the association of nitrate use with new radiographic findings of hip OA, adjusting for age, weight, height, bone mineral density, and estrogen. RESULTS: Compared with no reported use of nitrates, we found significant associations between use of nitrates at 1 clinic visit and new JSN (odds ratio [OR] 1.94, 95% confidence interval [95% CI] 1.18-3.17, P = 0.009), new osteophyte formation (OR 1.70, 95% CI 1.03-2.88, P = 0.04), and any new radiographic finding of hip OA or total hip arthroplasty for OA (OR 1.71, 95% CI 1.16-2.52, P = 0.007). Any nitrate use was associated with an increased risk of developing summary grade 3 or greater hip OA (OR 1.84, 95% CI 1.03-3.31, P = 0.041), but not with any other incident findings of OA. CONCLUSION: Older women using nitrates may have an increased risk of developing new radiographic findings of hip OA.

Postmenopausal estrogen and increased risk of clinical osteoarthritis at the hip, hand, and knee in older women.

OBJECTIVE: We examined postmenopausal estrogen (PME) use and prevalence of clinical osteoarthritis (OA) at the hand, knee, and hip in 1001 community-dwelling postmenopausal women aged 43-97 years (mean age 72). METHODS: OA at the hip, hand, and knee was defined by validated and standardized criteria based on pain history plus a clinical examination performed by a specially trained nurse. RESULTS: PME, validated by examination of pills and prescriptions, had been used for at least 1 year by 638 women (63.4%) for an average duration of 14.6 (+/-10.6) years. OA prevalence was 34.5% among women who had used PME for at least 1 year and 30.9% among women who did not use PME (age adjusted p = 0.02). Knee OA prevalence did not differ by PME use (p > 0.05). A significantly larger proportion of women who used PME for at least 1 year had hip and hand OA compared with women not using PME (4.1% vs. 1.1%, age-adjusted p = 0.002, and 15.8% vs. 13.5%, age-adjusted p = 0.02, respectively). In analyses adjusted for the potential confounding effects of age, body mass index (BMI), smoking, exercise, and type of menopause, women who used PME still were more likely to have hip OA (odds ratio [OR] = 5.03, confidence interval [CI] = 1.70-14.84, p = 0.003) and hand OA ([OR] = 1.57, CI = 1.05-2.33, p = 0.03). Among estrogen users, duration of PME use was longer for women with OA than for women without OA (16 vs. 11 median years, p = 0.01). CONCLUSIONS: PME is associated with a higher prevalence of clinical OA.

[Apropos of 2 rare severe surgical complications from the use of intramuscular and intrarectal quinine]. / A propos de deux complications chirurgicales rares graves de l'usage de la quinine intra-musculaire et intra-rectale.

Quinine by intramuscular or intrarectal injection has been found to be the best treatment for malaria in Niger, particularly in field health centres where the use of solutions can pose problems. There have been several reports of complications following injections, usually due to technical error or to the toxic side effects of quinine. In our hospital, we treated two such rare complications consisting of a case of coxal osteoarthritis induced by intramuscular injection and a case of anorectal necrotising induced by intrarectal injection. The occurrence of such life-threatening events could be reduced in frequency by teaching health personnel about techniques of quinine administration as well as its dangers.

[Diffuse idiopathic skeletal hyperostosis (DISH) and pseudo-coxarthritis following long-term etretinate therapy]. / Diffuse idiopathische skelettale Hyperostose (DISH) und Pseudocoxarthrose nach Langzeit-Etretinat-Therapie.

A 51-year old patient with congenital basal cell naevus syndrome was treated with etretinate (50-100 mg/daily) over a period of 5 years (cumulative dose 110 g). Clinically he developed a stiff back with pronounced disability of both hips. Radiologically, axial involvement of the spine with severe diffuse idiopathic skeletal hyperostosis especially of the lumbar spine, and ossifications of both hips were documented. Rheumatological implications of long-term therapy with etretinate are discussed.