The intrinsic pathogenetic mechanisms of tendinopathies are largely unknown and whether inflammation or degeneration has the prominent role is still a matter of debate. Assuming that there is a continuum from physiology to pathology, overuse may be considered as the initial disease factor; in this context, microruptures of tendon fibers occur and several molecules are expressed, some of which promote the healing process, while others, including inflammatory cytokines, act as disease mediators. Neural in-growth that accompanies the neovessels explains the occurrence of pain and triggers neurogenic-mediated inflammation. It is conceivable that inflammation and degeneration are not mutually exclusive, but work together in the pathogenesis of tendinopathies. IntroductionPrimary disorders of tendons are common and account for a high proportion of referrals to rheumatologists and orthopedic surgeons [1]. The most commonly involved tendons are the rotator cuff (particularly supraspinatus) and biceps brachii tendons in the shoulder, the forearm extensor and flexor tendons in the forearm, the patella tendon in the knee, the Achilles tendon in the lower leg, and the tibialis posterior tendon in the ankle and foot.Historically, the term tendinitis was used to describe chronic pain referring to a symptomatic tendon, thus implying inflammation as a central pathological process. However, traditional treatment modalities aimed at modulating inflammation have limited success [2] and histological studies of surgical specimens consistently show the presence of degenerative lesions, with either absent or minimal inflammation [3,4]. As will be clear in this review, we favor the hypothesis that inflammation and degenerative changes often coexist in the course of tendon disorders, and their relative contributions are difficult to dissect. Therefore, the definition of 'tendinitis' has been largely abandoned and the terms 'tendinosis' or, more generically, 'tendinopathy' (TP) are now currently preferred [5].In this review we summarize recent findings useful for understanding the pathogenesis of primary tendon diseases. First, suggestions coming from epidemiology, histopathology and clinics are reported, then we discuss new data on biochemical changes that occur in experimental and human TPs. Finally, we propose a unifying theory, drawn from both experimental and clinical data. Anatomy and physiologyThe tendons are made up of bundles of collagen fibrils (primary, secondary and tertiary fibers), each wrapped in endotenon, which in turn is enveloped by an epitenon, forming the actual tendon. A true synovial sheath is present only in some tendons, such as tibialis posterior, peroneal, and extensor and flexor tendons of the wrist and the hand; other

Background: Viscosupplementation (VS) with hyaluronic acid (HA) is largely used for knee osteoarthritis therapy, but the evidences for its usefulness in hip osteoarthritis (OA) are limited. Methods: In this review, an extensive search of published trials on VS in hip OA was performed. From the selected papers the following data were extracted: sample size, inclusion / exclusion criteria, treatment procedures, evaluation methods, follow-up duration and clinical outcomes. Results: The level of evidence was low in quite all the trials (no placebo controlled groups). A reduction of pain and an improvement of function after 3 months, persistent in the long term (12 -18 months), was observed. Patients with mild morphological alterations responded better to therapy. Side effects were negligible, and were limited to pain and a sensation of heaviness in the injection site. No clear differences among Low (LMW) and High Molecular Weight (HMW) HA preparations were found in the clinical outcomes. However, for HMW-HA preparations, a lower number of injections was, in general, necessary in order to reach the therapeutic effect. Conclusions: Despite the initial promising results, some questions still remain open : 1) the characteristics of responders must be more precisely defined; 2) the treatment schedules, at present mainly based on the individual clinical experience, need a proper and accepted standardization. Finally, larger and placebo controlled trials are necessary to confirm the efficacy of VS in hip OA.

Hip osteoarthritis is very common and costly. The European League Against Rheumatology Committee agenda asks for research to investigate treatments able to slow down the progression of hip osteoarthritis (OA), to delay joint replacement, and to determine the comparative effectiveness and cost-effectiveness of non-surgical and surgical treatment modalities as well as criteria relating to the indications for and timing of total hip replacement (THR). After publishing the results of a randomized controlled trial and a cohort study on the efficacy of Intra-articular sodium hyaluronate (MW 1,500-2,000 kDa) on symptomatic hip OA, we performed this retrospective study in patients suffering from hip OA treated with ultrasound-guided intra-articular injections of HyalOne (Hyalubrix 60 Italian brand name) involving a group of THR expert orthopedic surgeons to appraise whether or not considered eligible for THR and the frequency and timing of THR. Six orthopedists, not routinely performing hip intra-articular injections, each independently assessed whether 176 patients suffering from hip OA and treated with ultrasound-guided intra-articular injections of sodium hyaluronate (MW 1,500-2,000 kDa) were candidates for THR according to the clinical data (age, body mass index, Pain Visual Analog Scale, Lequesne Algofunctional Index, global patient assessment, global physician assessment, nonsteroidal anti-inflammatory drug intake, and hip X-ray) collected at the first intra-articular sodium hyaluronate injection visit and provided as anonymous electronic data. At 24 months, 159 out of 76 (90 %) patients did not undergo to THR. At 48 months, 82 % (N = 144) of the study population treated with intra-articular hyaluronic acid avoided THR. In the group of 93 patients considered candidates for THR (that is, in which 4, 5, or 6 orthopedic surgeons agreed that the patient was a suitable candidate for THR), only 17 had undergone THR, with survival results of 82 % at 24 months. At 48 months, this percentage reduced to 66 % in this group. In the other groups of patients (in which respectively 3, 2, 1 or no surgeons were in agreement that the patient was a candidate for THR) arthroplasty is not recorded. Sodium hyaluronate (MW 1,500-2,000 kDa) given by ultrasound-guided injection seems to delay THR in the real context of actual overall management of symptomatic hip OA patients. Although further studies are necessary to confirm these data and to identify outcome predictors, hip viscosupplementation should be considered as conservative treatment to perform before proposing patients for THR.

Carpometacarpal osteoarthritis (CMC-OA

The tridecapeptide neurotensin (NT) acts in the mammalian brain as a primary neurotransmitter or neuromodulator of classical neurotransmitters. Morphological and functional in vitro and in vivo studies have demonstrated the existence of close interactions between NT and dopamine both in limbic and in striatal brain regions. Additionally, biochemical and neurochemical evidence indicates that in these brain regions NT also plays a crucial role in the regulation of the aminoacidergic signalling. Immune cells, such as lymphocytes, macrophages and mast cells are reported to be activated by neuropeptides, such as neurotensin; this activation leads to cytokine and immunoglobulin production. In addition, neurotensin increases calcium level and the production of nitric oxide. Therefore neurotensin is deeply involved in immunity and inflammation but its real function still remains to be elucidated.