Hip Osteoarthritis (HOA) is the most common joint disorder and a major cause of disability in the adult population, leading to total hip replacement (THR). Recently, evidence has mounted for a prominent etiologic role of femoroacetabular impingement (FAI) in the development of early OA in the non-dysplastic hip. FAI is a pathological mechanical process, caused by abnormalities of the acetabulum and/or femur leading to damage the soft tissue structures. FAI can determine chondro-labral damage and groin pain in young adults and can accelerate HOA progression in middle-aged adults.

The aim of the study was to determine if the presence of calcium crystal in synovial fluid (SF) at the time of FAI surgery affects the clinical outcomes to be used as diagnostic and predictive biomarker.

49 patients with FAI undergoing arthroscopy were enrolled after providing informed consent; 37 SFs were collected by arthrocentesis at the time of surgery and 35 analyzed (66% males), median age 35 years with standard deviation (SD) 9.7 and body mass index (BMI) 23.4 kg/m²; e SD 3.

At the time of surgery, chondral pathology using the Outerbridge score, labral pathology and macroscopic synovial pathology based on direct arthroscopic visualization were evaluated. Physical examination and clinical assessment using the Hip disability & Osteoarthritis Outcome Score (HOOS) were performed at the time of surgery and at 6 months of follow up. As positive controls of OA signs, SF samples were also collected from cohort of 15 patients with HOA undergoing THR and 12 were analysed.

45% FAI patients showed CAM deformity; 88% presented labral lesion or instability and 68% radiographic labral calcification. 4 patients out of 35 showed moderate radiographic signs of OA (Kellegren-Lawrence score = 3). Pre-operative HOOS median value was 61.3% (68.10-40.03) with interquartile range (IQR) of 75-25% and post-operative HOOS median value 90% with IQR 93.8-80.60. In both FAI and OA patients the calcium crystal level in SFs negatively correlated with glycosaminoglycan (component of the extracellular matrix) released, which is a marker of cartilage damage (Spearman rho=-0.601, p<0.001).

In FAI patients a worst articular function after surgery, measured with the HOOS questionnaire, was associated with both acetabular and femoral chondropathy and degenerative labral lesion. Moreover, radiographic labral calcification was also significantly associated with pain, worst articular function and labral lesion. Calcium crystal level in SFs was associated with labral lesions and OA signs.

We concluded that the levels of calcium crystals in FAI patients are correlated with joint damage, OA signs and worst post-operative outcome. The presence of calcium crystals in SF of FAI patients might be a potential new biomarker that might help clinicians to make an early diagnosis, evaluate disease progression and monitor treatment response.

The collagenase of Clostridium Histolyticum enzyme infiltration is a mini-invasive treatment method for Dupuytren's disease which has emerged in recent years as an alternative to traditional surgery (selective aponeurectomy). Although both treatments are effective in the long term, a wider use of the enzyme is spreading worldwide. Indications and protocol of administration of collagenase are strictly regulated by the Italian Drug Administration Agency (AIFA). In the present study an off-label use of this medication has been experienced, in terms of wider indications and more numerous infiltration sites in the same cord (Multipoint technique) and in additional cords affecting other digits (Multicord technique).

All patients suffering from Dupuytren's disease and accessing the Hand Surgery outpatient at Rizzoli Institute were considered for the study, between february 2014 and february 2016. Inclusion criteria were Dupuytren's disease and a positive tabletop test. The collagenase injection was indicated for degrees of passive extension deficit (PED) higher than AIFA regulations (MCPJoints >50° and PIPJoints >45°). These patients were compared with the same PED subgroup of surgical patients who were treated through aponeurectomy. Since the drug is dispensed in vials of 0.90 mg, but according to the protocol only 0.58 mg are to be infiltrated, the injection of the remaining 0.32 mg that would otherwise remain unused was experienced. Therefore, in patients who had only one pathological cord in the hand, the first point of the cord to be treated was inoculated with 0.58 mg, according to standards, while two additional points were selected along the fibrosis and injected with the remaining 0, 32 mg. This group was compared with patients treated with the traditional 0.58 mg only on a single cord.

In patients in whom the presence of more than a single pathological cord was found, the worse lesion was injected with the usual 0.58 mg as by legislation and the second cord was infiltrated with the 0.32 mg residue and the results obtained within the second cord were compared with those achieved with the usual dose of 0.58 mg. The endpoints considered were the perioperative variations of passive extension deficit (PED) and range of motion (ROM), both expressed as degrees. Data were statistically analyzed in order to find any possible significance in the comparison of groups.

Comparing the surgical patients with those treated with collagenase, for the same degrees but higher than AIFA reference, both methods showed a reduction of contracture by at least 50% at 30 days and an improvement of ROM (p>0.05), with fewer complications in those treated enzymatically (p<0.01). Infiltrating the whole dose of collagenase (0.90 mg) through the multipoint mode, has enabled an easier handling of the cord at 24 hours post-injection, a reduction in contracture of at least 50% at 30 days allowing a dowstaging of the disease and a better and faster recovery of hand function, than the classic treatment, although these results are not statistically significant (p>0.05). For degrees of contractures within AIFA indications for collagenase, the 0.32 mg dose is sufficient to cause the lysis of a cord with similar results compared to the greater AIFA-recommended dose of 0.58, in terms of all considered endpoints, with no statistically significant difference (p >0.01).

This study confirms the success of treatment with collagenase compared to surgical treatment, in terms of efficacy, safety, more rapid recovery and less invasiveness. In addition, through further clinical studies, AIFA regulations can be gradually safely and effectively extended in terms of a progressive widening of indications and modalities including:

Indication to collagenase for PED higher than 50° (MCP joints) or 45° (PIP joints)