The Association between Oxytocin and Lower Limb Osteoarthritis: A Prospective Cohort Study.

Oxytocin (OT), a neuropeptide best known for its role in emotional and social behaviors, has been linked to osteoarthritis (OA). This study aimed to investigate the serum OT level in hip and/or knee OA patients and to study its association with disease progression. Patients from the KHOALA cohort with symptomatic hip and/or knee OA (Kellgren and Lawrence (KL) scores of 2 and 3) and follow-up at 5 years were included in this analysis. The primary endpoint was structural radiological progression, which was defined as an increase of at least one KL point at 5 years. Logistic regression models were used to estimate the associations between OT levels and KL progression while controlling for gender, age, BMI, diabetes and leptin levels. Data from 174 hip OA patients and 332 knee OA patients were analyzed independently. No differences in OT levels were found between the 'progressors' and 'non-progressors' groups among the hip OA patients and knee OA patients, respectively. No statistically significant associations were found between the OT levels at baseline and KL progression at 5 years, the KL score at baseline or the clinical outcomes. Higher structural damage at baseline and severe structural progression of hip and knee osteoarthritis did not appear to be associated with a low serum OT level at baseline.

Zoledronate and osteonecrosis of the jaw in osteoporosis: incidence and risk factors. Analysis of the French Pharmacovigilance Database.

INTRODUCTION: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) have been characterized with the use of oral bisphosphonates in osteoporosis and zoledronate in oncology. Uncertainties remain, though, with the occurrence of BRONJ related to the use of zoledronate in osteoporosis. OBJECTIVES: We aimed to estimate the incidence and characterize the risk factors of zoledronate-associated BRONJ in osteoporosis as compared with oral bisphosphonates in real life setting. METHODS: Cases of BRONJ associated with zoledronate, alendronate or risedronate were extracted from the French pharmacovigilance database up to 2020. The incidence of BRONJ was estimated as their respective numbers related to cases of BRONJ in patients treated with bisphosphonates for osteoporosis, over the same period, according to the Medic'AM database. RESULTS: Between 2011 and 2020, BRONJ incidence with zoledronate was 9.6/100,000 patient-year (PY), significantly higher than with alendronate (5.1/100,000 PY, P<0.001), and risedronate (2.0/100,000 PY, P<0.001). The number of patients treated with bisphosphonates has steadily decreased by 44.5% over 10 years. Meanwhile, the incidence of BRONJ decreased (5.8/100,000 PY in 2011; 1.5/100,000 in 2020), although a rebound was observed in 2018, including 47.6% of BRONJ following denosumab. Apart from classical risk factors, recent dental cares stood out in more than 40% of BRONJ, and zoledronate had a shorter exposure time than oral bisphosphonates. CONCLUSIONS: In a real-life setting, our data confirm that zoledronate-associated BRONJ in osteoporosis is scarce, seeming slightly more common compared with oral bisphosphonates. We also raise awareness of dental care guidelines and greater vigilance when using bisphosphonates in patients with previous exposure to denosumab.

Management and outcome of native joint septic arthritis: a nationwide survey in French rheumatology departments, 2016-2017.

OBJECTIVES: To describe current management and outcome of native joint septic arthritis (NJSA) in French rheumatology departments. METHODS: For this retrospective, nationwide multicentric study, 127 French rheumatology departments were contacted to report up to 12 cases of NJSA that occurred between 1 January 2016 and 31 December 2017. Characteristics, diagnosis procedures, therapeutic management and outcome were recorded. RESULTS: Overall, 362 patients were included (mean age 64.0±18.6 years, median Charlson comorbidity index 3.5 (0-14)). Knee was the most frequent site (n=160 (38.9%)), and Staphylococcus sp (n=185 (51.4%)), the most frequent pathogen. All patients received antibiotics for a mean duration of 46.8 (±22.0) days, including intravenous route for a mean of 17.2 (±15.4) days. Management was heterogeneous. Surgical procedure was performed in 171 (48.3%), joint immobilisation in 128 (43.8%). During follow-up, 91 (28.3%) patients have had serious complications and 28 (9.2%) of them died. Factors associated with 1-year mortality were age (OR 1.08, 95% CI 1.04 to 1.13; p<0.001), Charlson's index (OR 1.30, 95% CI 1.06 to 1.58; p=0.012), presence of bacteraemia (OR 4.02, 95% CI 1.35 to 11.99; p=0.008), antibiotic use in the previous 3 months (OR 3.32, 95% CI 1.11 to 9.87; p=0.029) and Staphylococcus aureus NJSA compared with Streptococcus sp. NJSA (OR 7.24, 95% CI 1.26 to 41.68, p=0.027). The complete recovery with no adverse joint outcome at 1 year was observed in n=125/278 patients (55.0%). CONCLUSION: Prognosis of NJSA remained severe with a high rate of morbimortality. Its management was very heterogeneous. This study highlights the importance of the new French recommendations, published after the completion of the study, in order to facilitate NJSA management.

Relationship between Oxytocin and Osteoarthritis: Hope or Despair?

Oxytocin (OT) is involved in breastfeeding and childbirth and appears to play a role in regulating the bone matrix. OT is synthesized in the supraoptic and paraventricular nuclei of the hypothalamus and is released in response to numerous stimuli. It also appears to be produced by osteoblasts in the bone marrow, acting as a paracrine-autocrine regulator of bone formation. Osteoarthritis (OA) is a disease of the whole joint. Different tissues involved in OA express OT receptors (OTRs), such as chondrocytes and osteoblasts. This hormone, which levels are reduced in patients with OA, appears to have a stimulatory effect on chondrogenesis. OT involvement in bone biology could occur at both the osteoblast and chondrocyte levels. The relationships between metabolic syndrome, body weight, and OA are well documented, and the possible effects of OT on different parameters of metabolic syndrome, such as diabetes and body weight, are important. In addition, the effects of OT on adipokines and inflammation are also discussed, especially since recent data have shown that low-grade inflammation is also associated with OA. Furthermore, OT also appears to mediate endogenous analgesia in animal and human studies. These observations provide support for the possible interest of OT in OA and its potential therapeutic treatment.

Impact of smoking on femorotibial and hip osteoarthritis progression: 3-year follow-up data from the KHOALA cohort.

OBJECTIVES: To evaluate the clinical and structural impact of smoking on knee and hip osteoarthritis at baseline and after 3years. METHODS: Observational data on the progressive effects of smoking at baseline and after 3years were collected from The Knee and Hip Osteoarthritis Long-Term Assessment cohort comprising a French population of patients aged 40-75years with symptomatic lower limb osteoarthritis. Clinical (the Western Ontario and McMaster Universities Arthritis Index and Harris scores) and structural (radiography for osteophyte detection and joint-space narrowing assessment) were conducted. The tobacco usage categories were 'never smoker', 'former smoker', and 'current smoker'. RESULTS: Of the 873 subjects included, 215 (25%) were former smokers and 119 (14%) were current smokers. Multivariate analyses revealed that former and current smokers had fewer knee osteophytes in the medial compartment at baseline (odds ratio [OR]=0.64 [0.41-0.99] and 0.63 [0.36-1.11], respectively), lower osteophyte development in the lateral condyle after 3years (OR=011 [0.03-0.45] and 0.15 [0.03-0.97]), and lower osteophyte development in the lateral tibial plateau after 3years (OR=0.22 [0.06-0.75] and 0.68 [0.14-3.35]). Higher tobacco consumption and longer duration of consumption were significantly associated with fewer knee osteophytes at baseline and lower osteophyte development at 3years. CONCLUSION: Although cigarette smoking did not influence knee function, pain, or the need for replacement surgery, current and former smokers developed fewer osteophytes. This relationship may be linked to the quantity and duration of consumption. Our results provide further insight into the smoking-related pathophysiology of osteoarthritis.

Pelvic fractures: epidemiology, consequences, and medical management.

PURPOSE OF REVIEW: Until recently, osteoporotic pelvic fractures have not been specifically studied. This review presents an update on epidemiological data of pelvic fracture, including morbidity, mortality and healthcare costs, the role of surgery and new data on sacroplasty in acute phase management. RECENT FINDINGS: All studies underline the burden of osteoporotic pelvic fractures. Risk factors associated with these fractures are age, sex (women), and previous loss of autonomy. An increased mortality has been reported in all publications, similar to hip fracture for in-patient mortality and at 5 years of follow-up. Pelvic fractures often lead to transient or permanent autonomy loss, reflecting the high costs because of extended hospital stay, combined with nursing home requirement. However, recent studies report a decrease in the length of stay. Sacroplasty displays promising results to control pain and improve functional outcome. Early surgery begins to be discussed to also improve the outcome. SUMMARY: Pelvic fractures display all the features of severe osteoporotic fractures: increased incidence, high morbidity, mortality, and healthcare costs that justify awareness of the practitioner on these fractures. Further studies on sacroplasty and surgery are necessary to improve pain control, functional improvement, thereby reducing the length of hospital stay and cost.

Femoro-tibial knee osteoarthritis: One or two X-rays? Results from a population-based study.

OBJECTIVE: Our objective was to compare the use of both anteroposterior (AP) extended-knee X-ray and semi-flexed X-ray (current gold standard) versus the use of semi-flexed X-ray alone to detect femoro-tibial osteoarthritis (OA). METHODS: Individuals 40 to 75 years of age with symptomatic hip and/or knee OA (Kellgren/Lawrence [KL] score≥2) were recruited using a multiregional prevalence survey in France. Both AP and schuss X-rays were performed and read; two years later, the same examiner, blinded to the results of the first reading, performed a second reading of the schuss X-ray. We compared the KL stages of each knee and analyzed osteophyte detection and localization, joint space narrowing (JSN), and the relationship to obesity. RESULTS: The analysis included 350 participants with OA of various stages. Comparing the two readings showed that a higher proportion of patients had KL≥2 when the two X-ray views were combined (right knee: P<0.0001; left knee: P<0.001). There were no differences when using the schuss X-ray alone versus in combination with an AP X-ray in terms of detecting JSN, osteophytes. A comparison of schuss X-ray alone versus AP X-ray alone demonstrated the superiority of the schuss view for evaluating JSN (P=0.0001 and P=0.0001) and no difference in osteophyte detection. CONCLUSION: Our study shows that the schuss view alone was sufficient for detecting knee osteophytes and JSN. Using one X-ray rather than two will reduce medical costs and irradiation burden. Using two views seems preferable for epidemiological studies.

Ultrasound study of entheses in psoriasis patients with or without musculoskeletal symptoms: A prospective study.

OBJECTIVE: To estimate the prevalence of ultrasonographic enthesitis in psoriasis patients with or without musculoskeletal symptoms and to investigate their evolution under systemic treatments given for the cutaneous symptoms. PATIENTS AND METHODS: Prospective bi-centre (rheumatology and dermatology) study over 6months, including psoriasis pts requiring systemic treatment, with or without musculoskeletal symptoms and/or psoriatic arthritis (PsA). Clinical assessment (M0 and M6) included: BASDAI, HAQ, SPARCC, PASI and nail disease. US assessment (M0 and M6) with Grey Scale and PD of 10 entheses was performed by one trained rheumatologist blinded to clinical and biological data, scoring morphological, structural lesions and PD signal. RESULTS: Complete data were obtained on 340 entheses in 34 patients. Twenty-two were asymptomatic (PsO) and 12 symptomatic (PsA). They received conventional treatment and/or biologics. AT BASELINE: US abnormalities were found in 97.1% total population and in 86.4% PsO patients. 95/340 enthesitis were observed, 57/220 in PsO vs 38/120 in PsA (P=0.258). Neither group had PD signal. Presence of 24/90 enthesitis in patients with nail disease vs 33/130 without (P=0.831). AT M6: Twenty-three patients were assessed. US morphological (thickness and hypoechogenicity) abnormalities were improved in PsO (n=13) (P=0.021) and PsA patients (n=10) (P=0.164) with a significant decrease of BASDAI, HAQ, SPARCC. CONCLUSION: We observed a high frequency of US enthesitis in psoriasis patients, with or without musculoskeletal symptoms, requiring systemic treatment. At 6months, US morphological abnormalities were likely to improve. Further studies would be interesting to validate our data and to assess their potential impact on PsA development.

New onset of articular inflammatory manifestations in patients with hidradenitis suppurativa under treatment with infliximab.

OBJECTIVES: Severe hidradenitis suppurativa (HS), under infliximab, can be associated with different forms of arthritis whose mechanism is unclear. Our objective is to establish the frequency and clinical presentation of new-onset arthritis in HS under infliximab. METHODS: Severe HS patients under infliximab were followed up between 2007-2012. New articular inflammatory manifestations were investigated by rheumatologist. RESULTS: Three patients over eleven developed a polyarthritis. Mean duration of arthritis was 3 months. At treatment's stop: 2 patients improved and 1 relieved with adalimumab. CONCLUSION: The inflammatory rheumatism's frequency in HS under infliximab seems underestimated.

Oxytocin and bone remodelling: relationships with neuropituitary hormones, bone status and body composition.

PURPOSE: There is growing evidence that oxytocin, which regulates appetite, plays a role in bone remodelling and improves osteoporosis. We previously showed a significant decrease in circulating oxytocin levels in postmenopausal osteoporotic women compared to healthy controls. However, factors involved in the pathophysiology of osteoporosis, such as estrogens and leptin, are known to regulate oxytocin secretion. Herein, we evaluated the relationships between oxytocin and other hormonal factors known to regulate bone remodeling and body composition in postmenopausal osteoporotic women, compared to healthy controls. METHODS: In 20 postmenopausal women with severe osteoporosis compared to 16 healthy controls, we measured serum levels of oxytocin, high sensitive estradiol, testosterone, FSH, LH, SHBG, TSH, osteocalcin, serum type I collagen carboxy-terminal telopeptide, leptin. Bone mineral density and body composition were also measured with DXA. RESULTS: Osteoporotic women had significantly lower oxytocin, leptin and LH serum levels and higher CTX and SHBG; all other biological parameters were similar in both groups. Fat mass and lean mass were significantly decreased in osteoporotic women. Oxytocin serum levels were significantly correlated to bone mineral density but not to any other measured parameter, including leptin, estradiol and age. In a logistic regression analysis, osteoporosis remained significantly correlated to oxytocin, regardless of age. CONCLUSIONS: Low oxytocin serum levels appeared to be associated with severe osteoporosis, independently of other factors associated with osteoporosis or known to regulate oxytocin serum levels, such as estradiol or leptin, reinforcing the concept that oxytocin may be involved in the pathophysiology of postmenopausal osteoporosis.

Effect of discontinuing TNFalpha antagonist therapy in patients with remission of rheumatoid arthritis.

OBJECTIVE: The objective of this study was to determine the time to relapse after tumor necrosis factor alpha (TNFalpha) antagonist discontinuation in patients with remission of rheumatoid arthritis (RA). METHODS: Among 304 patients taking TNFalpha antagonist therapy for RA, 21 achieved a remission and were taken off the TNFalpha antagonist. Remission was defined as DAS28<2.6 for at least 6 months without nonsteroidal inflammatory drugs or more than 5 mg of prednisone per day but with disease-modifying antirheumatic drug (DMARD) therapy if needed. The same TNFalpha antagonist was restarted in the event of a relapse (DAS28>3.2). RESULTS: The 21 patients had a mean age of 61 years, a mean disease duration of 11.3 years, and a mean remission duration at TNFalpha antagonist discontinuation of 19.2 months. The TNFalpha antagonist was infliximab in 2 patients, adalimumab in 5, and etanercept in 14; and 14 patients were taking a concomitant DMARD. The number of patients still in remission after TNFalpha antagonist discontinuation was 9/20 after 6 months and 5/20 after 12 months. Mean time to relapse was 14.7 weeks. While off TNFalpha antagonist therapy, 3 of the 5 relapse-free patients after 12 months were on DMARD therapy, compared to 11 of the 15 patients who relapsed. Compared to the 15 patients who relapsed, the 5 relapse-free patients had a longer time on TNFalpha antagonist therapy (56 months vs. 35 months, P=0.012) and a longer time in remission on TNFalpha antagonist therapy (35 months vs.14.5 months, P=0.04). The 15 patients who relapsed consistently achieved a remission after resuming TNFalpha antagonist therapy; the remission occurred within 2 months in 13 patients. CONCLUSION: TNFalpha antagonist discontinuation in patients in remission of RA was followed by a relapse within 12 months in 75% of cases. Relapsing patients responded well to resumption of the same TNFalpha antagonist.

Outcome of osteoporotic pelvic fractures: an underestimated severity. Survey of 60 cases.

The aim is to describe the characteristics of osteoporotic pelvic fractures and their outcome. We recorded clinical and biological characteristics of 60 osteoporotic pelvic fractures hospitalized in our Department of Rheumatology and assessed their outcome in 51 cases, using a questionnaire administrated by phone call. In our population, pelvic fractures mainly affected elderly women (81.6% of women, mean age 79 years), presenting, in more than 50% of the cases, a past medical history of osteoporosis, previous fracture and cardiovascular disease. The fractures were triggered by a fall in 89% of the cases and mainly located at the pubic rami (65%). There was a high rate of vitamin D deficiency (80.6%) associated with a secondary hyperparathyroidism (51.6%). Before the pelvic fracture, all patients lived at their personal home and 84.1% were autonomous. During hospitalization, 52.5% of the patients experienced an adverse event, mostly related to urinary tract infection and bedsore. At time to discharge, only 31% directly returned to their own home. At the final assessment (mean delay from the fracture: 29 months), 11 patients were dead (mean delay: 190 days). Among living patients, 74.5% lived at home, 60% required assistance for at least one daily life activity and 18.6% experienced a new fracture. Only 63.2% were still treated for osteoporosis. Osteoporotic pelvic fractures requiring initial hospitalization share most characteristics of hip fracture: elderly people, women predominance, vitamin D insufficiency, fall triggering the fracture, and also the severity assessed by a high morbidity and mortality and loss of autonomy.

TNFalpha antagonist continuation rates in 442 patients with inflammatory joint disease.

OBJECTIVE: To evaluate TNFalpha antagonist continuation rates in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA). METHODS: We retrospectively reviewed the charts of patients treated with etanercept, infliximab, or adalimumab at our teaching hospital. Drug continuation was evaluated using Kaplan-Meier survival curves. The logrank test was used to compare continuation rates. RESULTS: We identified 442 patients who were prescribed 571 TNFalpha antagonist treatments between August 1999 and June 2005. Among them, 304 had RA, 92 AS, and 46 PsA. In the RA group, continuation rates were high with etanercept (n=157; 87% after 12 months and 68% after 24 months) and adalimumab (n=43, 83% and 66%) but significantly lower with infliximab (n=104, 68% and 46%; P=0.0001 vs. etanercept and P=0.01 vs. adalimumab). In the AS group, in contrast, infliximab (n=53) showed significantly higher continuation rates (89% and 83%) than did etanercept (n=39; 76% after 12 months: P=0.03). Overall continuation rates were higher in AS than in RA (P=0.01). CONCLUSION: Continuation was better with etanercept than with infliximab in patients with RA, whereas the opposite was noted in patients with AS.

New-onset psoriatic palmoplantaris pustulosis following infliximab therapy: a class effect?

Reports of induction or exacerbation of psoriatic palmoplantaris pustulosis (PPPP) after anti-tumor necrosis factor-alpha (TNF-alpha) treatment are few. We describe 2 new cases of PPPP induced by infliximab. In 1999, a total of 442 patients in our department received anti-TNF-alpha treatment for a variety of chronic rheumatic conditions and were regularly followed. Medical records for 166 given infliximab were retrospectively reviewed for disease [rheumatoid arthritis (RA), spondylarthropathies (SpA) including psoriatic arthritis], disease duration, clinical characteristics, skin side-effects, and use of other potentially relevant medications. PPPP was observed in 2 patients treated with infliximab for symmetrical rheumatoid factor-positive RA; the patients had no personal or family history of psoriasis. In both cases, pustulosis appeared after several months of infliximab administration. There was no clinical, biological, or radiological evidence to support a diagnosis of psoriatic SpA. Both patients fulfilled ACR criteria for RA, and there was no reason to suspect previously unidentified psoriasis. Comorbid RA and psoriasis are unusual, and our patients exhibited a clear link between anti-TNF-alpha administration and cutaneous lesions, suggesting a direct effect in both cases. The 28 published cases of PPPP induced by anti-TNF-alpha treatment report lesions that tend towards pustulosis and palmoplantar localization. The mechanisms involved remain elusive. Disappearance of lesions in our second patient when switched to a soluble receptor suggests a molecule-specific side effect, while the literature describing variable reaction to switching anti-TNF agents, and/or their discontinuation and reintroduction, indicates otherwise. Given the rarity of this side effect, its elucidation will require systematic study.

Lumbosacral pain: chordoma--a diagnosis not to forget.

Chordomas are rare tumours (1-4%) whose origin is remnants of the embryonic primitive foetal notochord. Estimated incidence is 0.51 cases per million. They develop at the neuroaxis ends and on vertebral bodies. Clinical manifestations can differ according to different localizations and to insidious and slow evolution. Our case is an illustration of diagnosis and treatment difficulties. Chordomas remain a diagnosis to be reminded.